PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND ...

PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND MANAGEMENT 2019

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© 2019 PHILIPPINE COLLEGE OF CHEST PHYSICIANS COUNCIL ON ASTHMA


Preface

Philippine Consensus Report Update Project Committee

Table A. Levels of Evidence (Adapted from GINA guidelines)

Introduction

Chapter 1: Epidemiology, Definition and Diagnosis

Chapter 2: Assessment and Classification of Asthma

Chapter 3: Risk Factors for Asthma Exacerbations

Chapter 4: Asthma Medications

Chapter 5: Management of Asthma Exacerbations

Chapter 6: Chronic Asthma Management

Chapter 7: Patient Education

Chapter 8: Special Considerations

Appendices

TABLE OF CONTENTS


PHILIPPINE CONSENSUS REPORT ON ASTHMA DIAGNOSIS AND

MANAGEMENT 2019 UPDATE PROJECT COMMITTEE

Council Chairman: Ma.Bella R. Siasoco, M.D., FPCCP

Project Chairman: Dina V. Diaz, M.D., FPCCP

Project Secretary: Eloisa S. de Guia, M.D., FPCCP

Members:

Twinkle T. Adiaz, M.D., FPCCP

Johann Paolo D. Almazar, M.D., FPCCP

Gene Philip Louie C. Ambrocio, M.D., FPCCP

Eileen G. Aniceto M.D., FPCCP

Gian Carlo T. Arandia, M.D., FPCCP

Tito C. Atienza, M.D., FPCCP

Glynna O. Cabrera, M.D., FPCCP

Elizabeth V. Cadena, M.D., FPCCP

Maryann Cristy T. Dadulla, M.D., FPCCP

Marie Charisma L. De la Trinidad, M.D., FPCCP

Virginia S. Delos Reyes, M.D., FPCCP

Paul Rilhelm M. Evangelista, M.D., FPCCP

Irene V. Felipe, M.D., FPCCP

Liza L. Garcia, M.D., FPCCP

Renato B. Herradura, M.D., FPCCP

Isaias A. Lanzona, M.D., FPCCP

Lalaine L. Mortera, M.D., FPCCP

Ma. Piedad R. Natividad, M.D., FPCCP

Josephine B. Ramos, M.D., FPCCP

Camilo C. Roa, M.D., FPCCP

Oliver A. Tabag, M.D., FPCCP

Dennis C. Teo, M.D., FPCCP

Esther Fredelyn M. Tomas, M.D., FPCCP

Aileen D. Wang, M.D., FPCCP

Ricardo C. Zotomayor, M.D., FPCCP


Table A. Levels of Evidence (Adapted from GINA guidelines)

EVIDENCE LEVEL DESCRIPTION

A

Evidence is from endpoints of well-designed randomized

controlled trials (RCTs) or meta-analyses of relevant

studies that provide a consistent pattern of findings in the

population for which the recommendation is made.

Category A requires substantial numbers of studies

involving substantial numbers of participants

B

Evidence is from endpoints of intervention studies that

include only a limited number of patients, post hoc or

subgroup analysis of RCTs or meta-analysis of such RCTs.

In general, Category B pertains when few randomized

trials exist, they are small in size, they were undertaken in

a population that differs from the target population of the

recommendation, or the results are somewhat

inconsistent.

C Evidence is from outcomes of non-randomized or

uncontrolled trials or from observational studies.

D

This is a panel consensus judgment based on clinical

experience or knowledge that does not meet the above

listed criteria. This category is used only in cases where

the provision of some guidance was deemed valuable but

the clinical literature addressing the subject was

insufficient to justify placement in one of the other

categories.


Introduction

The Philippine Consensus Report on Asthma Diagnosis and Management (PCRADM)

2019 contains a comprehensive approach to asthma management utilizing updated

information from the previous Philippine Asthma Consensus report published in 2009

as well as content adapted from the recent Global Initiative on Asthma (GINA) 2018

report.

This document is a summarized version and is intended to be used in conjunction

with full PCRADM 2019 report. The appendices included here provide additional

information for use by the clinician.

No portion of this document should be reproduced without the permission of the

Philippine College of Chest Physicians.


Chapter 1: Epidemiology, Definition and Diagnosis

What is the burden of asthma globally and in the Philippines?

Bronchial asthma is now recognized as one of the most important non-communicable

threats to global health, social welfare and economic development in all regions of

the world, especially in low- to-middle income countries.1

Recent estimates by the Global Burden of Disease study report that there are 339.4

million people worldwide affected by asthma representing a 3.6% increase in age-

standardized prevalence since 2006.2

Globally, asthma is ranked 28th among the leading causes of burden of the disease

and 16th among the leading causes of years lived with disability.2

In the Philippines, the over-all prevalence of asthma based on wheezing for the past

12 months, was estimated at 8.7% (SE 0.4%), based on a National Nutrition and

Health Survey.3

According to the latest WHO data published in 2017, asthma deaths in the Philippines

reached 13,186 or 2.13% of total deaths; age-adjusted death rate is 19.47 per

100,000 population, which ranks the Philippines number 15 in the world.4 and number

2 among the low-and middle-income countries.5 These statistics draw attention to

the need for more focused and accelerated efforts to make asthma a lung health

priority.1

How is asthma defined?

Based on a consensus statement considering typical asthma characteristics, asthma

is a heterogeneous disease, usually characterized by chronic airway inflammation,

defined by history of respiratory symptoms such as wheeze, shortness of breath,

chest tightness and cough that vary in intensity over time, together with variable

expiratory airflow limitation.6 Symptoms and airway obstruction are often reversible

either spontaneously or with treatment, usually triggered by factors such as exercise,

allergen or irritant exposure, weather changes or viral respiratory infections.

Although the pathogenesis and underlying mechanisms of asthma remain unclear


mainly because it is affected by significant genetic and environmental factors, the

major pathophysiological feature of asthma is episodic airway obstruction

characterized by expiratory airflow limitation. The dominant pathological feature is

airway inflammation, sometimes associated with airway structural changes.

How is asthma diagnosed?

Making the diagnosis of asthma is based on identifying both a characteristic pattern

of respiratory symptoms such as wheezing, shortness of breath (dyspnea), chest

tightness or cough, and variable expiratory airflow limitation.1 Practical tools for the

diagnosis of asthma are recommended to reduce over- or under-diagnosis of asthma.

A diagnostic flowchart for clinicians in making the initial diagnosis of asthma based

on clinical history and objective assessments to confirm presence of variable and

reversible expiratory airflow limitation is shown in Figure 1.3. 6

• Clinical history.

The clinical probability of asthma increases when:

o when symptoms are more than one, especially in adults,

o the symptoms are worse at night or early morning,

o the symptoms vary in intensity over time,

o symptoms are triggered by certain factors, e.g. viral infections, exercise,

changes in weather, laughter, allergens or irritant exposures

o asthma symptoms present in childhood,

o there is a past history of allergic rhinitis or eczema, or family history of

asthma or allergy

Expiratory wheezing, when appreciated on quiet or forced breathing, is the

most frequent abnormal finding for asthma.

Consider other diagnosis in the following clinical conditions that are not typical

features of asthma and the probability of asthma is less likely:

1) when cough is isolated without other respiratory symptoms;

2) when sputum production is chronic;

3) when shortness of breath is associated with lightheadedness,

paresthesia, dizziness or chest pain;

4) when inspiration becomes noisy during exercise;

5) when there is presence of crackles or inspiratory wheezes


• Objective assessment to confirm variability and reversibility of expiratory airflow

limitation.

o Airflow limitation: confirmed by spirometry as a reduced FEV1/FVC ratio

(normally >0.75-0.80 in adults)6

o Variability: improvement and/or deterioration in lung function within the

day (diurnal variability), from day to day, from visit to visit, or seasonally,

or from reversibility tests defined as any of the following:

▪ diurnal variability in PEF by >10% over 2 weeks;

▪ increase in FEV1 by at least 12% AND 200 mL or increase in PEF by

>20% from baseline after 4 weeks of anti-inflammatory treatment;

▪ fall in FEV1 by >10% AND >200 mL from baseline after exercise;

▪ fall in FEV1 from baseline of at least 20% with standard methacholine or

histamine dose or at least 15% with standard hyperventilation,

hypertonic saline or mannitol challenge;

▪ variations in FEV1 of at least 12% AND >200 mL between visits outside

of respiratory infections.

o Reversibility: increase in FEV1 by at least 12% AND 200 mL from baseline

after 10-15 minutes of albuterol 200-400 mcg or equivalent (following

proper medication wash-out of > 4hours for SABA and > 15 hours for LABA)

Figure 1.3. Diagnostic flowchart for diagnosing asthmaat initial presentation in clinical practice6


What diseases may mimic asthma?

Alternative diagnoses may mimic asthma, or may co-exist with asthma. When

patients fail to respond to asthma therapy, the following alternative diagnoses should

be entertained: 7

• Vocal cord dysfunction (VCD)

• Chronic obstructive pulmonary disease (COPD)

Other differential diagnoses in a patient with suspected asthma varies with age and

are listed below.6

• For young adults 12-39 years old:

• Chronic upper airway cough syndrome

• Hyperventilation dysfunctional breathing

• Bronchiectasis

• Cystic fibrosis

• Congenital heart diseases

• Alpha1-antitrypsin deficiency

• Inhaled foreign body

• For adults 40 years and above:

• Hyperventilation dysfunctional breathing

• Bronchiectasis

• Cardiac failure

• Medication-related cough

• Parenchymal lung disease

• Pulmonary embolism

• Central airway obstruction

References:

1. Global Asthma Report 2014. Auckland, New Zealand: Global Asthma Network, 2014.

2. Global Asthma Report 2018, Auckland, New Zealand: Global Asthma Network, 2018.

3. Varona LL, Alava HA, Abong JA, Castor MA, de Leon JC, Kwong SL, Prevalence of asthma among

Filipino adults based on the National Nutrition and Health Survey (NNHeS), Phil J Int Med

2014;52(4):1-7.

4. World Health Statistics, 2017, https://www.worldlifeexpectancy.com/philippines-asthma

5. WHO Mortality Database updated from http://www.who.int/healthinfo/ statistics/mortality

rawdata/en/(version dated 1 October 2017)

6. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention,

2018.Available from www.ginasthma.org [Accessed: 26 April 2018].

7. Amundson Da, Seda G, Daheshia M, Recognizing asthma mimics and asthma complications, Military

Medicine, 2011;176:11


Chapter 2: Assessment and Classification of Asthma

How should we assess asthma?

Asthma should be assessed according to asthma control. (Evidence Level D)

Asthma control assessment is comprised of two parts: symptom control (previously

“current clinical control”) and future risks for adverse outcome (Table 2.1).1 Both

are important because of the close link between current level of control which is the

immediate concern of the patient and the future risk especially of exacerbation or

flare-ups. Lung function test is now included as an important part in the assessment

of future risk.

Table 2.1 Assessment of asthma in adults, adolescents, and children 6-11 years1

What are the tools for assessing asthma symptom control?

A. Categorical symptom control tools

Questions answerable by yes or no are asked. The consensus-based GINA

symptom control tool is an example (Table 2.2). Together with risk

assessment of adverse outcomes, these may be used to guide treatment

decisions. This classification correlates with assessment using numerical

asthma control scores. 2,3


Table 2.2. GINA assessment of asthma control in adults, adolescents,

and children 6-11 years.1

Well controlled asthma has none of these features, partly controlled has 1-2

of these and poorly controlled asthma has 3-4 of these features.

B. Numerical ‘asthma control’ tools

These tools, validated against healthcare provided assessment, provide scores

and cut-off points to differentiate between levels of symptom control.3 These

are more sensitive to change and therefore may be used to document patient

progress than categorical tools.

Some examples of numerical tools are:

• Asthma Control Questionnaire (ACQ) 4,5

o There are three ACQ versions and may contain 5,6 or 7 items that give

the version its name. All include 5 symptom questions, ACQ 6 adds

reliever use and ACQ 7 includes a pre-bronchodilator score. The lower

the number, the better the level of control. • Asthma Control Test (ACT) 3,6,7

o The ACT includes four symptom/reliever questions plus a patient self-

assessed level of control. In ACT, the range of score is 5-25. The higher

score indicates better control.

Whichever numerical tool is used, it is important to note that respiratory

symptoms may not be specific and, therefore, one needs to ascertain that the

symptoms are due to asthma and are not from other co-morbid conditions.


How do we assess future risk of adverse outcomes?

The second part of asthma control is to assess future risk of adverse asthma

outcomes, particularly exacerbations, fixed airflow limitation and side effects of

medication (Table 2.3).1,8

Table 2.3. Risk factors for poor asthma outcomes1

Assess risk factors at diagnosis and periodically, particularly for patients experiencing exacerbations. Measure FEV1 at start of treatment, after 3-6 months of controller treatment to record the patient’s personal best lung function, then periodically for ongoing risk assessment.

Having uncontrolled asthma symptoms is an important factor for exacerbations*

Additional potentially modifiable risk factors for flare-ups(exacerbations) even in patients

with few asthma symptoms† include:

• High SABA use (with increased mortality if >1 x 200-dose canister/month

• Inadequate ICS; nor prescribed ICS; poor adherence; incorrect inhaler technique

• Low FEV1 especially <60% predicted

• Higher bronchodilator reversibility

• Major psychological or socioeconomic problems

• Exposures: smoking, allergen exposure if sensitized

• Comorbidities: obesity, chronic rhinosinusitis, confirmed food allergy

• Sputum or blood eosinophilia

• Pregnancy

• Elevated FENO (in adults with allergic asthma) Other major independent risk factors for flare-ups (exacerbations):

• Ever intubated or in intensive care unit for asthma

• Having 1 or more severe exacerbations in the last 12 months

Having any of

these risk

factors

increases the

patient’s risk of

exacerbations

even if they

have few

asthma

symptoms

Risk factors for developing fixed airway obstruction • Preterm birth, low birth weight and greater infant weight gain • Lack of ICS treatment • Exposure to tobacco smoke, noxious chemicals, occupational exposures

• Low initial FEV1: chronic mucous hypersecretion; sputum or blood eosinophilia

Risk factors for medication side effects

• Systemic: frequent OCS; long-term, high dose and/or potent ICS; also taking P450

inhibitors

• Local: high dose or potent ICS; poor inhaler technique

What is the role of lung function determination in assessment of future risk

of adverse outcome?

Lung function does not correlate strongly with asthma symptoms in adults.9 When

combined in numerical asthma control tools, symptoms frequency can outweigh

important lung function results.10 However, a low initial FEV1 is a strong independent

predictor of risk of exacerbations, even after adjustment for symptom frequency.

FEV1: forced expiratory volume in 1 second; FENO: fraction of exhaled nitric oxide; ICS: inhaled corticosteroids;

OCS: oral corticosteroids; P450 inhibitors: cytochrome P450 inhibitors such as ritonavir, ketoconazole, itraconazole;

SABA: short-acting beta2-agonist †Independent risk factors are those that are significant after adjustment for the level of symptom control. Poor symptom

and exacerbation risk should not be simply combined numerically, as they have different causes and may need

different treatment strategies


Lung function should be assessed at diagnosis or start of treatment; after 3 to 6

months of controller treatment to assess the patient’s personal FEV1; and periodically

thereafter depending on the on the risk of adverse outcomes. In most adult patients,

lung function can be recorded at least every 1 to 2 years.1 Interval lung function

determinations (spirometry monitoring) are usually indicated in hard-to-control

asthma and are preferably referred for specialist care.

The use of PEFR in asthma, either as part of an initial objective measure of airways

caliber to be followed by a formal spirometry, or part of periodic assessment of control

has long been advocated to be incorporated in an asthma management plan. Its use

has been evaluated in multiple studies that supports better outcome when used as

part of a more comprehensive asthma program and is discussed in the

pharmacological management of stable asthma and in acute asthma exacerbations

or flare-ups.

How do you differentiate poorly controlled asthma and asthma

exacerbations?

Poorly controlled asthma is another label that closely applies to the stable asthma

condition that is characterized by more symptoms, increased use of medications, and

resulting in interference with activities of daily living very much akin to uncontrolled

asthma. Some patients may not achieve the goals of good asthma control even with

maximal therapy.11 There are initial steps recommended to investigate a patient with

poor symptom control and/or exacerbation despite treatment (Figure 2.1).1

Asthma exacerbation, also termed acute asthma deterioration, is defined as a change

in the stable condition that warrants a change in therapy and, for both patient and

the physician, has an element of urgency. The patient experiences mild to severe

deterioration in symptoms and is recognized by the patient’s ability to talk, presence

or absence of distress by physical examination and if available the use of an objective

measure of airway caliber like PEFR. Each level of severity, whether mild-to-

moderate, are used to recommend the necessary steps to control/reverse the

condition and prevent morbidity and/or mortality.

In situations where the line between poorly controlled asthma or actual exacerbation

is hard to distinguish, previous recommendation states to err on the side of treatment

as if it is an exacerbation.


Figure 2.1 Investigating a patient with poor symptom control

and/or exacerbations despite treatment1

References:

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention,

2018.Available from www.ginasthma.org [Accessed: 26 April 2018]

2. Haselkorn T, Fish JE, Zeiger RS, Szefler SJ, Miller DP, Chipps BE, Simons FE, et.al. Consistently very

poorly controlled asthma, as defined by the impairment domain of the Expert Panel Report 3

guidelines, increases the risk for future severe asthma exacerbations in The Epidemiology and

Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. J Allergy Clin

Immunol 2009; 124: 895-902.e1-4

3. Patel M, Pilcher J, Reddel HK, Pritchard A, Corin A, Helm C, Tofield C, et.al. Metrics of salbutamol

use as predictors of future adverse outcomes in asthma. Clin Exp Allergy, 2013;43:1144-51


4. Suissa S, Ernst P, Boivin JF, Horwitz RI, Habbick B, Cockroft D, Blais L, et.al A cohort analysis of

excess mortality in asthma and the use of inhaled beta agonists Am J Respir Crit Care Med

1994;149:604-10

5. Ernst P, Spitzer WO, Suissa S, Cockroft D, Haorwitz RI, Bolvin JF, et.al. Risk of fatal and near-fatal

asthma in relation to inhaled corticosteroid use, JAMA 1992;268:3462-4.

6. Melani AS, Bonavia M, Cilenti V, Cinti C, Lodi M, Martucci P, Serra M, et.al. Inhaler mishandling

remains common in real life and is associated with reduced disease control Repir Med 2011; 105:

930-8.

7. Fuhlbrigge Al, Kitch BT, Paltiel AD, Kuntz K, Neumann PJ, Dockery DW, Weiss ST, FEV1 is associated

with risk of asthma attacks in a pediatric population, J Allergy Clin Immunol 2001;107:61-7.

8. Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, Casale TB, Chanez P, et.al. A new

perspective on concepts of asthma severity and control. Eur Respir J 2008; 32(3):545-54.

9. Moore V, Jakkola M, Burge S, A systematic review of serial peak flow measurements in the diagnosis

of occupational asthma. Eur Respir J 2011;38: Suppl 55, P4941

10. Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ Adcock IM, et.al. International ERS/ATS

Guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014; 43: 343-

73

11. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, Pedersen SE; GOAL

Investigators Group. Can guideline-defined asthma control be achieved? The Gaining Optimal

Asthma Control Study. Am J Respir Crit Care Med 2004; 170: 836-44.


Chapter 3: Risk Factors for Asthma Exacerbations

A variety of risk factors, referred to as “triggers” cause asthma exacerbations. As a

result, there is worsening of asthma symptoms and deterioration of asthma control,

often despite existing maintenance treatment. Each of these factors are postulated

to act through different mechanisms but has a final common pathway that includes

cellular inflammation, heightened bronchial hyperresponsiveness and increased

airflow obstruction.1

For many of these risk factors, such as tobacco smoke, occupational agents, certain

foods, additives, and drugs, reducing or eliminating an affected patient’s exposure

improves asthma control and reduces medication needs. For other known asthma

triggers, such as allergens, respiratory infections and pollutants, avoidance measures

where possible should be taken. However, because many asthma patients react to

multiple factors that are ubiquitous in the environment, complete avoidance of these

factors is usually impractical and very limiting to the patient. Thus, controller

medications have an important role because patients are often less sensitive to these

risk factors when their asthma is under good control.2

AEROALLERGENS

House dust mites are by far the most common aeroallergen implicated in allergic

individuals in Asian countries. Cockroach, followed by mold and animal dander, and

subsequently grass and tree pollen, in descending order of positivity, formed the

remainder of aeroallergens commonly seen in Asia. Pollen sensitization in Asia, apart

from Japan, generally has less medical significance in Asia than in the West.3

Dust mite population and sensitization patterns are heavily influenced not only by

urbanization but by climatic conditions. However, the overall burden of dust mite

sensitization in Asia is much higher than that seen in the United States and Europe,

even in areas of similar climate and/or urbanization, and the question has been posed

as to whether other factors such as genetics may play a role.3


House dust mite (HDM) allergens

Is the association of house dust mite allergen exposure and asthma

established?

Studies have found that exposure to dust mite allergens is associated with dust mite

sensitization and with asthma. House dust mite allergen exposure is involved in

triggers of asthma attacks and asthma outcomes such as asthmatic symptoms and a

frequent requirement for medication in allergic asthmatic patients. The relationship

of HDM exposure with visits to the emergency department has provided conflicting

results.4,5

Are avoidance measures directed to house dust mite (HDM) beneficial to

asthma patients?

Many studies which have examined the efficacy of HDM interventions in HDM

sensitized asthmatics revealed inconsistent results. There are measures that may

show some benefit and a recent review indicated the level of evidence for these

measures as follows:6

• Frequent vacuum cleaning has not proven to be sufficiently effective in

reducing HDM exposure while specific barriers, i.e. pillow and mattress

encasing have been demonstrated to be more useful. (Evidence B) Efforts

should be made to restrict the presence of carpets, upholstered furniture and

drapes in the environment of the dust mite-allergic patients.

• Humidifier use should be avoided while de-humidifiers can be used, although

these do not generally filter the air as air conditioners do. (Evidence B)

• Washing sheets, pillowcases, mattress pads and blankets weekly effectively

reduces mite counts. (Evidence B) Using a heated drier, hot water(>130oF)

is able to kill mites; cold water may reduce HDM concentrations by 90%.

• Chemical products or acaricides, e.g. benzyl benzoate, tannic acid, showed

only modest effects on reducing mite allergen and their use is not

recommended. (Evidence B)

Molds and Fungi

What is the effect of indoor dampness and mold on asthma?

Published epidemiologic studies and meta-analyses show consistently that indoor

dampness or mold or measured dampness was positively associated with

exacerbation or severity of asthma. The causal relationship is established with


sufficient evidence in children, but less so in adults. The evidence, however, does not

suggest that this relationship is restricted to those with specific sensitization to fungi

or dust mites.4,5, 7-12

Specific causal agents for asthma exacerbations that are associated with dampness

has been assumed to be fungal but this has not been confirmed. Other causal agents

in dampness may include biologic exposures such as bacteria, amoebas, dust mites

that thrive in dampness or non-biologic exposures such as chemicals emitted from

damp materials.9 Measures that may help discourage mold expansion are: reducing

humidity by increasing ventilation, covering cold surfaces such as water pipes by

insulation, increasing the air temperature to reduce surface humidity.13

Furry animals

What are the effects of furry animal exposure on asthma?

The health effects of furry animal exposure include development of allergen specific

IgE (defined as sensitization) in susceptible individuals, often leading to

manifestations of allergic diseases, such as asthma and rhinitis, if the exposure

persists. Once a sensitized individual develops an allergic disease, continued

exposure to the allergens is likely to exacerbate symptoms and lead to poorer

outcomes.14

In an updated review, it was stated that there is sufficient evidence of a causal

relationship between cat allergen exposure and asthma exacerbation in cat-sensitized

individuals and an association of dog allergen exposure to exacerbation of asthma in

dog-sensitized children.5,15 An association of dog allergen exposure to asthma

exacerbation was also suggested in non-sensitized adults.5,15

What intervention strategies can be adopted?

Avoidance is the most effective way to manage cat and dog allergy and removal of

the cat or dog from the environment is advised.14 (Evidence A)

Cockroach allergens

Does cockroach allergen exposure cause exacerbation of asthma?

There is sufficient evidence of a causal relationship between cockroach allergen


exposure and asthma exacerbation in individuals specifically sensitized to

cockroaches, especially adults, but there is limited or suggestive evidence of such an

association in children not sensitized to cockroaches.5,16,17

What intervention strategies can be adopted to minimize the effects of

cockroach allergens?

Exposure to cockroach allergen in homes should be minimized to reduce the risk of

sensitization (Evidence B) and asthma morbidity in sensitized subjects.18(Evidence

C). In general, it is necessary to use a combination of interventions to eliminate

exposure to cockroach contaminants that includes initial removal of facilitating

factors, e.g. means of ingress, sources of food and shelter; elimination of the

cockroaches and removal of reservoirs of cockroach-derived contaminants

(Evidence D).18

IRRITANTS AND POLLUTANTS

Outdoor air pollution

What are the effects of air pollution on asthma?

Air pollution that involves changes in gaseous and particulate outdoor air pollutants

are associated with daily asthmatic symptoms, a decrease in lung function,

emergency room visits, and hospitalizations for asthma attacks.4

What avoidance measures reduce the impact of air pollution exposure on

asthma?

For patients with clear association of exposure to air pollutants and increase in

asthma symptoms, it is often advised to stay indoors and to limit physical exertion

when air pollutant levels exceed health-based thresholds. However, there is limited

evidence that these individual actions can reduce health risks. Relative contribution

of indoor- and outdoor-generated pollutants to personal exposures depends on

multiple factors, including the type of pollutants, building structure, indoor sources

and personal activities. These should be considered so that healthcare providers and

their patients may tailor interventions to individual circumstances in order to

maximize the net exposure reduction.19


Indoor fuel exposure

What is the effect of indoor fuel exposure on asthma?

Studies examining biomass and adult asthma are not uniformly positive and the

associations with specific fuel type are inconsistent.20 A population survey study from

India indicates that adult women living in households using biomass and solid fuels

have a significantly higher risk of asthma than those living in households using

cleaner fuels.21 A recent review estimated that solid fuel smoke exposure exacerbates

asthma in children ages 5 to 14 years and in those older than 15 years.22 In adults

with asthma, however, there is no evidence that indoor biomass use contributes to

worse morbidity and exacerbations. Existing evidence from five studies is mixed for

use of other fuels and exacerbations in adults.20

Tobacco smoke

What is the effect of tobacco smoke on asthma?

It has been established by several studies that the risk of developing asthma was

significantly higher among current smokers and among ex-smokers compared with

those who have never smoked.23,24,25

Of all forms of secondhand smoke (SHS), maternal exposure seems to have the

largest impact on asthma by increasing the frequency and severity of the disease and

decreasing lung function during pregnancy. Asthmatic children exposed to multiple

household smokers face an increased risk for respiratory illness-related absences

from school, and these effects persist during adolescence but weaken during

adulthood.26

What are the benefits of smoking cessation and the interventions that are

needed?

Smoking cessation improves asthma outcomes that include significant improvement

in quality of life, decreased hyperreactivity, and a reduction in usage of rescue

medications.27 it has also been shown that asthmatic ex-smokers exhibited significant

improvement in FEV1, asthma control, recovery to corticosteroid response and

decrease in neutrophil counts in sputum.


The management of asthmatic smokers should begin with emphatic

recommendations to stop smoking, including having no contact with environmental

smoke.28 It is recommended that asthmatic smokers may need specific medications

for smoking cessation in a concurrent schema of behavioral techniques.

CLIMATE CHANGE AND GLOBAL WARMING

What is the effect of climate change on asthma?

Climate changes affect allergenic plants and pollen distribution worldwide. There is

evidence that, during pollen season, thunderstorms can be associated with allergic

asthma outbreaks in patients suffering from pollen allergy.29,30 Climate change will

increase the frequency and intensity of floods and cyclones 31 and thus fungal spore

production, a powerful asthma and rhinitis trigger. Both diseases are caused or

aggravated by components of bioaerosol from the natural environment or from indoor

environments in enclosed spaces, workspaces and homes.32 Climate change, coupled

with air pollutant exposures, may have potentially serious adverse consequences for

human health. Rising temperatures will contribute to the elevation of the

concentrations of ozone (due to more sunlight and higher temperature) and

particulate matter (due to wildfire, droughts, desertification, sandstorms and an

increased use of coal-fired power to produce energy for cooling) at ground level.32,33

EXERCISE-INDUCED BRONCHOCONSTRICTION (EIB)

What is the effect of exercise on asthma?

Exercise-induced bronchoconstriction (EIB) is acute airway narrowing that occurs as

a result of exercise. It was suggested to use the terms EIB with asthma (EIBA), the

occurrence of bronchial obstruction after exercise in asthmatic patients, and EIB

without asthma (EIBwA), the occurrence of bronchial obstruction in subjects without

other symptoms and signs of clinical asthma.34,35 The latter may be seen particularly

in children, athletes, and patients with atopy or rhinitis, or following respiratory

infections.36


How is EIB diagnosed?

Symptoms alone are insufficient to identify patients with EIB.34 In order to establish

a secure diagnosis, it is important to perform objective testing to confirm dynamic

changes in airway function by measuring the change in the FEV1 before and after a

standardized exercise challenge test (ECT), in the laboratory or in the field.

What is the treatment and prevention of EIB?

Treatment of both EIBA and EIBwA is essentially based on reversing bronchial

obstruction by using short-acting beta2-agonists (SABA).36 For prevention of EIB, use

of an inhaled SABA, typically administered 15 minutes before exercise, is

recommended.37(Strong recommendation, High-quality evidence) Daily

administration of an ICS or a leukotriene receptor antagonist (LTRA) is recommended

for patients who continue to have symptoms despite inhaled SABA before exercise or

who require an inhaled SABA daily or more frequently. 34 Strong recommendation,

Moderate-quality evidence)

BETA-BLOCKERS

Can beta-blockers be given to asthmatics?

When indicated, cardioselective beta-blockers are preferred over non-cardioselective

beta- blockers. (Strong recommendation, High-quality evidence). In a recent

population-based nested case control study, it was shown that cardio-selective beta-

blocker use was not associated with a significantly increased risk of moderate or

severe asthma exacerbations and, thus, potentially could be used more widely when

strongly indicated.38

RESPIRATORY INFECTIONS

What is the impact of viral respiratory infections on asthma?

In both children and adults, viral infections of the airways may be associated with

the development of chronic asthma, as well as with acute exacerbations for those

with existing asthma.39-48


The most commonly involved viruses associated with asthma exacerbations include

human rhinovirus (HRV), respiratory syncytial virus (RSV), influenza and

parainfluenza viruses, coronavirus, enterovirus, and adenovirus. HRV represents the

most frequent cause of infectious respiratory illnesses affecting adults while influenza

and parainfluenza viruses affect all age groups.42,43

Are there effective treatment and preventive strategies for virus-induced

exacerbations?

Eradication of respiratory viruses would be the ideal approach but is not a realistic,

feasible approach. Optimization of current therapies may be beneficial Treatment

with anti-inflammatory drugs such as ICS can reduce the risk of exacerbations by

40% to 50%, and this suggests that moderating inflammation may reduce the

chances that a cold will precipitate bronchospasm.49,50 Exacerbations have also been

prevented by combined treatment with ICS and long-acting beta2-agonists

(LABAs).51-53

Should antibiotics be routinely used in the treatment of asthma

exacerbations?

Bacterial infections are thought to be responsible for asthma exacerbation, however

evidence show that this is true for only a minority.53,54,55 Current guidelines state that

antibiotics should not be routinely used in the treatment of asthma exacerbations

and should be reserved for cases in which clear signs, symptoms, or laboratory test

results are suggestive of bacterial infection.

References:

1. Singh AM, Busse WW, Asthma exacerbations: aetiology, Thorax 2006;61:809-16

2. Global Initiative for Asthma, Global Strategy for Asthma Management and Prevention, 2006.

Available from:www.ginasthma.org [Accessed: 03 March 2018]

3. Tham EH, Lee AJ, Bever HV Aeroallergen sensitization and allergic phenotypes in Asia, Asian Pac. J

Allergy Immunol 2016;34:181-9.

4. Baxi S, Phipatankul W, The role of allergen exposure and avoidance in asthma. Adolesc Med State

Art Rev 2010 April; 21(1):57-71,viii-ix.

5. Kanchongkittiphon W, Mendell MJ, Gaffin JM, Wang G, Phipatanakul W, Indoor environmental

exposures and exacerbation of asthma: an update to the 2000 review by the Institute of Medicine,

Environ Health Perspect 2015 Jan;123(1):6-20.

6. Cipriani F, Calamelli E, Ricci G, Allergen avoidance in allergic asthma, Front. Pediatr 2017; 5: 103.


7. Baxi SN, Portnoy JM, Larenas-Linnemann D, Phipatanakul W, Environmental Allergens Workgroup,

Exposure and health effects of fungi on humans, J Allergy Clin Immunol Pract 2016; 4(3):396-404.

8. World Health Organization Regional Office for Europe, Dampness and Mould, WHO Guidelines for

Indoor Air Quality 2009.

9. Mendell MJ, Mirer AG, Cheung K, Tong M, Douwes J, Respiratory and allergic health effects of

dampness, mold and dampness-related agents:a review of the epidemiologic evidence. Environ

Health Perspect 2011;119(6):748-56.

10. Fisk WJ, Lei-Gomez Q, Mendell MJ, Meta-analyses of the associations of respiratory health effects

with dampness and mold in homes, Indoor Air 2007;17:284-96

11. Quansah R, Jaakkola, MS, Hugg TT, Heikkinen SA, Jaakkola JJ, Residential dampness and molds and

the risk of developing asthma: a systematic review and meta-analysis. PLoS ONE

2012;7(11):e47526.

12. Cox-Ganser JM, Indoor dampness and mould health effects-ongoing questions on microbial

exposures an allergic versus nonallergic mechanisms. Clin Exp Allergy, 2015;45(10):1478-82

13. Hamilton RG, Assessment of mold in the indoor environment, UpToDate 2017, Available

from:www.uptodate.com/contents/assessment-of-mold-in-the-indoor-environment.

14. Joint Task Force on Practice Parameters, chief eds, Portnoy J, Kennedy K, Sublett J, Environmental

assessment and exposure control: a practice parameter-furry animals. Ann Allergy Asthma Immunol

2012; 108: 223.e1-223e.15.

15. Langley SJ, Goldthorpe S, Craven M, Woodcock A, Custovic A. Relationship between exposure to

domestic allergens and bronchial hyperresponsiveness in non-sensitized, atopic asthmatic subjects.

Thorax 2005; 60: 17-21

16. Do DC, Zhao Y, Gao P, Cockroach allergen exposure and risk of asthma, Allergy 2016;71(4):463-

74.

17. Rabito FA, Carlson J, Holt EW, Iqbal S, James MA, Cockroach exposure independent of sensitization

status and association with hospitalizations for asthma in inner-city children, Ann Allergy Asthma

Immunol 2011;106:103-9

18. Portnoy J, Chew GL, Phipatanakul W, Williams PB, Grimes C, Kennedy K, Matsui EC, et.al.

Environmental assessment and exposure reduction of cockroaches: a practice parameter. J Allergy

Clin Immunol 2013;132(4):802-8.e1-25.

19. Laumbach R, Meng Q, Kipen H What can individuals do to reduce personal health risks from air

pollution? J Thorac Dis 2015;7(1):96-107

20. Diette GB, Accinelli RA, Balmes JR, Buist AS, Checkley W, Garbe P, Hansel NN, Kapil V, Gordon S,

Lagat DK, et.al. Obstructive lung disease and exposure to burning biomass fuel in the indoor

environment. Glob Heart 2012;7(3):265-70.

21. Agarwal S, Effect of indoor air pollution from biomass and solid fuel combustion on prevalence of

self-reported asthma among adult men and women in India: findings from a nationwide large-scale

cross-sectional study, J Asthma 2012;49(4):355-65.

22. Torres-Duque C, Maldonado D, Perez-Padilla R, Ezzati M, Viegi G, Forum of International Respiratory

Studies (FIRS) Task Force on Health Effects of Biomass Exposure, Biomass fuels and respiratory

diseases: a review of evidence, Proc Am Thorac Soc 2008;5(5):577-90.

23. Pipari R, Jaakkola JJK, Jaakkola N, Jaakkola MS, Smokking and asthma in adults, Eur Respir J

2004;24:734-9

24. Polosa R, Knoke JD, Piccillo G, Caponnetto P, Sarva M, Proietti L, Al-Delaimy WK, Cigarette smoking

is associated with a greater risk of incident asthma in allergic rhinitis. J Allergy Clin Immunol

2008;12(6):1428-34.


25. Polosa R, Thomson NC, Smoking and asthma:dangerous liaisons, Eur Respir J, 2013;41(3):716-26.

26. US Department of Health and Human Services. The health consequences of involuntary exposure to

tobacco smoke: a report of the Surgeon General, Atlanta, GA: Centers for Disease Control and

Prevention, Office of Smoking and Health; 2006.

27. Tonnesen P, Pisinger C, Hvidberg S, Wennike P, Bremann L, Westin A, Thomsen C, et.al. Effects of

smoking cessation and reduction in asthmatics. Nicotine Tob Res 2005;7(1):139-48.

28. Chatkin JM, Dullius CR. The management of asthmatic smokers. Asthma Res Pract 2016; 2:10

29. D’Amato G, Liccardi G, Frenguelli G, Thunderstorm-asthma and pollen allergy, Allergy

2007;62(1):11-6.

30. Dabrera G, Murray V, Emberlin J, Ayres JG, Collier C, Clewlow Y, Sachon P, Thunderstorm asthma:

an overview of the evidence base and implications for public health advice. QJM 2013; 106: 207-

17.

31. Schiermeier Q, Climate and weather: extreme measures, Nature 2011;477:148-9.

32. D’Amato G, Cecchi L, D’Amato M, Annesi-Maesano I, Climate change and asthma. Eur Respir Rev

2014; 23: 161-9.

33. Department of Health and Expert Group on Climate Change and Health in the UK, Health effects of

climate change in the UK, London: Department of Health;2001;199-214.

34. Parsons JP, Hallstrand TS, Mastronarde JG, Kaminsky DA, Rundell KW, Hull JH, Storms WW, et.al.

An official American Thoracic Society clinical practice guidelines: exercise-induced bronchoconstric-

tion, Am J Respir Crit Care Med 2013; 187:1016-27.

35. Weller JM, Anderson SD, Randolph C, Bonini S, Craig TJ, Pearlman DS, Rundell KW, et.al.

Pathogenesis, prevalence, diagnosis, and management of exercise-induced bronchoconstriction: a

practice parameter. Ann Allergy Asthma Immunol 2010;105: S1-S47.

36. Bonini M, Palange P, Exercise-induced bronchoconstriction: new evidence in pathogenesis, diagnosis

and treatment. Asthma Res Practice 2015; 1: 2. DOI:10.1186/s40733-015-0004-4.

37. Bonini M, Di Mambro C, Calderon MA, Compalati E, Schunemann H, Durham S, Canonica GW, Beta2-

agonists for exercise-induced asthma. Cochrane Database Syst Rev 2013;10:CD003564.

38. Morales DR, Lipworth BJ, Donnan PT, Jackson C, Guthrie B, Respiratory effect of beta-blockers in

people with asthma and cardiovascular disease: population-based nested case control study, BMC

Medicine 2017;15:18.

39. Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TW, Printz MC, Lee WM, Shult

PA, Residorf E, et.al. Wheezing rhinovirus illnesses in early life predict asthma development in high

risk children, Am J Respir Crit Care Med, 2008; 178(7):667-72.

40. Kusel MM, de Klerk NH, Kebadze T, Vohma V, Holt PG, Johnston Sl, Sly PD, Early-life respiratory

viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. J

Allergy Clin Immunol 2007; 119: 1105-10.

41. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ, Asthma and wheezing in

the first six years of life, The Group Health Medical Associates, N Engl J Med, 1995;332:133-8.

42. Busse WW, Lemanske RF Jr, Gern JE, The role of viral respiratory infections in asthma and asthma

exacerbations, Lancet 2010;376:826-34.

43. Tan WC, Viruses in asthma exacerbations Curr Opin Pulm Med 2005;11:21-6.

44. Johnston NW, Johnston SL, Duncan JM, Greene JM, Kebadze T, Keith PK, Roy M, et.al. The

September epidemic of asthma exacerbations in children: a search for etiology, J Allergy Clin

Immunol 2005;115:132-8

45. Gern JE, The ABCs of rhinoviruses, wheezing, and asthma J Virol 2010; 84(15):7418-26.

46. Nicholson KG, Kent J, Ireland DC, Respiratory viruses and exacerbations of asthma in adults BMJ

1993;307:982-6.


47. Teichtahl H, Buckmaster N, Pertnikovs E, The incidence of respiratory tract infection in adults

requiring hospitalization for asthma. Chest 1997; 112:591-6.

48. Atmar RL, Guy E, Guntupalli KK, Zimmerman JL, Bandi VD, Baxter BD, Greenberg SB, Respiratory

tract viral infections in inner-city asthmatic adults. Arch Intern Med 1998; 158: 2453-9.

49. Oliver BG, Robinson P, Peters M, Black J. Viral infections and asthma: an inflammatory interface?

Eur Respir J 2014;44(6):1666-81.

50. Pauwels RA, Pedersen S, Busse WW, Tan WC, Chen YZ, Ohlsson SV, Ullman A, et.al.: START

Investigators Group, Early intervention with budesonide in mild persistent asthma: a randomized,

double-blind trial. Lancet 2003; 361: 1071-6.

51. Edwards MR, Johnson MW, Johnston SL, Combination therapy: synergistic suppression of virus-

induced chemokines in airway epithelial cells. Am J Respir Cell Mol Biol 2006;34: 616-24.

52. Rosenthal LA, Avila PC, Heymann PW, Martin RJ, Miller Ek, Papadopoulos NG, Peebles RS Jr.

Infections and Asthma Committee, Environmental and Occupational Respiratory Diseases Interest

Section, American Academy of Allergy, Asthma & Immunology, Viral respiratory infections and

asthma: the course ahead, J Allergy Clin Immunol, 2010;125(6):1212-7.

53. Jackson DJ, Sykes A, Malla P, Johnston SL Asthma exacerbations: origin, effect, and prevention J

Allergy Clin Immunol 2011;128:1165-74.

54. Hong SJ, The role of Mycoplasma pneumoniae infection in asthma. Allergy Asthma Immunol Res

2012; 4(2):59-61.

55. Normansell R, Sayer R, Waterson S, Dennett EJ, Del Forno M, Dunleavy A, Antibiotics for

exacerbations of asthma. Cochrane Database Syst rev 2018;(6):CD002741.


Chapter 4: Asthma Medications

The pharmacologic options for treatment of asthma fall into three main categories

namely: controller medications, reliever medications and add-on therapies.

CONTROLLERS

Controller medications reduce airway inflammation, control symptoms and reduce

future risks for exacerbations and decline in lung function and are therefore advised

to be used regularly for maintenance treatment.1

What are the recommended controller medications for asthma?

Inhaled Corticosteroids

Inhaled corticosteroids (ICS) are the cornerstone of therapy and are currently the

most effective anti-inflammatory medications for the treatment of persistent asthma.

Several studies consistently demonstrate that ICS are effective in reducing

symptoms, improving quality of life, decreasing frequency of flare-ups, decreasing

the need for bronchodilator rescue therapy, improving lung function, and reducing

asthma mortality. Additional benefits of inhaled ICS include modification of airway

remodeling and prevention of an accelerated decline in lung function. Studies showed

that ICS are relatively safe. At low to moderate doses, ICS do not frequently exhibit

clinically important side effects and provide asthmatics a good risk-benefit profile.

Table 4.2 shows low, medium, and high daily doses of inhaled corticosteroids for

adults and adolescents (12-years and older).1

Table 4.2. Low, medium, and high daily doses of Inhaled corticosteroids1

Adults and adolescents (12 years and older)

DRUG Daily dose (mcg)

LOW MEDIUM HIGH

Beclometasone dipropionate (CFC) 200-500 >500-1000 >1000

Beclometasone dipropionate (HFA) 100-200 >200-400 >400

Budesonide (DPI) 200-400 >400-800 >800

Ciclesonide (HFA) 80-160 >160-320 >320

Fluticasone furoate (DPI) 100 n.a. 200

Fluticasone propionate (DPI) 100-250 >250-500 >500

Fluticasone propionate (HFA) 100-250 >250-500 >500

Mometasone furoate 110-220 >220-400 >440

Triamcinolone acetonide 400-1000 >1000-2000 >2000


Long-Acting Beta2-agonists

Sustained action bronchodilators such as salmeterol and formoterol are administered

twice daily dosing due to its 12-hours duration of action. They are useful in controlling

nocturnal symptoms and exercise-induced asthma. Formoterol has a rapid onset of

action of about 1-3 minutes after administration and has a wide dose range, hence

its usefulness as reliever. On the other hand, salmeterol is not suitable for acute

relief of asthma since it has a long onset of action and is limited by the ceiling dose

of 50 mcg twice a day. However, it cannot be overemphasized that LABAs should

never be used alone as it has been reported in several studies that monotherapy with

LABA increases asthma related deaths.

There are no studies yet for the role of monotherapy with olodaterol, vilanterol and

indacaterol in the treatment of persistent asthma.

Inhaled corticosteroids - Long-acting Beta2 -agonists (ICS-LABA)

Analysis of several studies clearly show that adding a LABA to ICS is more effective

than increasing the dose of ICS in terms of improving asthma control and reducing

exacerbations.2 Combination treatment of ICS and LABA in clinical studies and

systematic reviews consistently show improvement in symptom scores, decrease in

nocturnal asthma symptoms, improvement in lung function, decrease the use of

rapid-acting inhaled beta2-agonists, reduction in the number of exacerbations, and

achievement of clinical control of asthma in more patients, more rapidly, and at a

lower dose of ICS than ICS given alone.

In the local setting, initial therapy with ICS-LABA in patients with mild persistent

asthma may provide greater improvements in lung function and asthma control,

improve compliance and has comparable safety to ICS alone. The use of ICS-

formoterol has an added advantage of serving both as controller and reliever when

used as a single inhaler therapy in the maintenance and reliever strategy.

Role of systemic corticosteroids

Systemic corticosteroids, if given early in the treatment of asthma exacerbations in

the emergency room setting were shown to be effective in reducing symptoms and

decreasing rate of hospitalization.3 For patients discharged from the ER setting after

effective control of symptoms, prescribing a short course of oral corticosteroids (OCS)

was found to reduce the rate of relapse.4 However, courses longer than 5 days were

not found to provide any additional benefit.5,6,7


RELIEVERS

What are the reliever medications for asthma?

Reliever medications, which relieve acute bronchospasm, are “rescue” medications

provided to all patients for relief in case of breakthrough symptoms including

worsening asthma or exacerbations. These are also recommended for short-term

exercise-induced bronchoconstriction. Reducing and, ideally, eliminating the need for

reliever treatment is both an important goal in asthma management and a measure

of success of asthma treatment.1

Reliever medications are usually bronchodilators that quickly relieve bronchospasm.

These medications generally do not treat the underlying inflammatory process of

asthma. Reliever medications for asthma are mainly Short-Acting Sympathomimetic

Beta2-agonists (SABA) and Short-acting muscarinic antagonists (SAMA).

SABA are quick-acting and usually give immediate relief of asthmatic symptoms due

to bronchospasm. SAMA, such as ipratropium, are anticholinergic bronchodilators

which are also quick acting medications, though generally less potent than beta2-

agonists. For patients with moderate to severe exacerbations seen at the emergency

room, the addition of ipratropium to a SABA was associated with fewer

hospitalizations and greater improvement in PEF and FEV1 compared with SABA

alone.8,9,10Under certain circumstances, high dose IV corticosteroids and oral

corticosteroids may also relieve acute asthma symptoms.

Patients who regularly use SABAs alone without concomitant anti-inflammatory

therapy are at an increased risk for asthma-related death and urgent asthma-related

health care.2,8(Evidence A) As such, in the chronic management of asthma, SABA-

only treatment for as-needed relief of symptoms is no longer a preferred option.

The use of low-dose ICS-formoterol for as-needed symptom relief in mild asthma is

based on a large double-blind study comparing this regimen with SABA-only

treatment.11(Evidence B) At present, the use of as-needed ICS-formoterol for mild

asthma is considered off-label.

ADD ON THERAPIES

Add-on therapies are given for patients already on optimized controller medications

with treatment of modifiable risk factor, who remained uncontrolled, with severe

symptoms or persistent exacerbations.1


Leukotriene Modifiers

Montelukast is a cysteinyl leukotriene receptor antagonist (LTRA) used for the

maintenance treatment of asthma and to relieve symptoms of seasonal allergies.

Inhaled corticosteroids are generally superior to montelukast for asthma

management.2 In adults, montelukast is mainly used as a complementary therapy in

addition to ICS if ICS alone do not bring the desired effect.

Xanthine Derivatives

Theophylline is a relatively poor bronchodilator and adverse effects limit the dose and

make it less effective than inhaled bronchodilators.12 Thus, it is no longer

recommended for routine use in asthma. Doxofylline, a newer generation

methylxanthine differs with the presence of a dioxolane group in position 7 and is

thought to have a wider therapeutic window than theophylline.13

Tiotropium

Tiotropium, a long-acting anti-muscarinic agent (LAMA) has been recommended as

add-on therapy for severe asthma with statistically significant increases in PEF and

FEV1 as add-on to ICS, as well as decreased rate of exacerbations and improved

asthma control.14

Omalizumab

Omalizumab is a recombinant DNA-derived humanized IgG1k monoclonal antibody

against human immunoglobulin E (IgE).15 Its primary use is for patients mostly with

severe, persistent allergic asthma, uncontrollable with oral or injectable

corticosteroids. Omalizumab is currently recommended for the treatment of patients

>12 years in the U.S., administered subcutaneously once every 2 to 4 weeks, and

the dosage is determined according to the serum IgE and body weight of the patient.

There are other U.S.FDA approved biological agents for severe asthma, such as

mepolizumab, reslizumab and benralizumab which are not currently available locally.


INHALER THERAPY

Inhaler or aerosolized therapy delivers medicines directly to the lumen of the airways

and onto their therapeutic sites.16 This enables the delivery of low doses of the

medicine to its site of action for a localized effect, leading to a rapid clinical response

and reducing the risk for systemic side effects.17

The effectiveness of inhaled treatments is influenced by their efficacy, i.e. their

positive effects when used under optimal conditions, directly resulting from their

pharmacological properties; and the way they are used, i.e. the appropriateness of

prescription and the patient’s adherence and ability to use inhalation devices.18

Is there a difference between pressurized metered-dose inhalers (pMDIs)

and dry powder inhalers (DPIs)?

Table 4.6 lists the general advantages and disadvantages between two types of inhalers: pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs).19

Table 4.6. Advantages and disadvantages between pMDIs and DPIs19

Types Advantages Disadvantages

Metered-Dose Inhaler (MDI)

Convenient Generally inexpensive Portable Widely available for most inhaled medicines No drug preparation required

Difficult to contaminate

Patient coordination essential Patient actuation required Large pharyngeal deposition Difficult to deliver high dose

MDI with holding chamber

Less patient coordination required Less patient pharyngeal deposition

More complex for some patients More expensive than MDI alone Less portable than MDI alone

Dry Powder Inhaler (DPI)

Less patient coordination required Convenient

Portable Breath-actuated

Requires moderate to high inspiratory flow Some units are single dose

Large pharyngeal deposition Difficult to deliver high dose

Multiple meta-analyses revealed that there was no significant difference between

pMDIs and DPIs in an efficacy outcome in any patient group that was investigated.


An evidence-based guideline concluded that either device may be used provided that

patients are able to use the correct technique for inhalation.14 Unfortunately, errors

in inhaler technique are common and poor inhaler technique is associated with poor

asthma control.20,21

What patient factors should be considered in in the choice of inhaler device?

Figure 4.2 outlines a general algorithm in the proper selection of inhalers for

particular patients.17,22 A pMDI requires good actuation-inhalation coordination for

optimal lung deposition, whereas a DPI requires sufficient inspiratory flow.

What strategies can ensure effective use of inhaler devices?

Table 4.6 lists strategies to ensure effective use of inhaler devices.23,24,25,26

Figure 4.2 How to choose the right inhaler


Table 4.6 Strategies to ensure effective use of inhaler devices

Although not always feasible, use of a single type of device to deliver all medications

is preferable since using a variety of devices increases the likelihood of error. Using

multiple types of inhalers requires the patient to master (and maintain mastery of)

more than one inhaler technique. Such possibility of errors will need to be considered

during training, retraining and education to avoid loss of disease control and stability. 17

What is the role of nebulizers in asthma management?

The role of nebulizers in asthma management should be limited to patients in severe

respiratory distress or in patients on mechanical ventilation.

Nebulizers offer no distinct advantage over pMDIs with spacers or holding chambers

in acute asthma management. Their use may actually be associated with problems

such as a greater dose of drugs leading to systemic side-effects, and contamination

with bacteria increasing the risk for nosocomial pneumonia.27


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9. Rodrigo GJ, Castro-Rodriguez JA, Anticholinergics in the treatment of children and adults with acute

asthma: a systematic review with meta-analysis. Thorax, 2005;60:740-6.

10. Kirkland SW, Vandenberghe C, Voaklander B, Nikel T, Campbell S, Rowe BH Combined inhaled beta-

agonist and anti-cholinergic agents for emergency management in adults with asthma. Cochrane

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11. O’Byrne PM, Fitzgerald JM, Bateman ED, Barnes, PJ, Zhong N, Keen C, Jorup C, et.al. Inhaled

combined budesonide-formoterol as needed in mild asthma. N Engl J Med, 2018; 378:1865-76.

12. Barnes PJ, Theophylline. Am J Respir Crit Care Med, 2013 Oct;188(8): 901-6.

13. Riffo-Vasquez Y, Venkatasamy R, Page CP Steroid sparing effects of doxofylline. Pulm Pharmacol

Ther 2018; 48: 1-4

14. Rodrigo GJ, Castro-Rodriguea JA. What is the role of tiotropium in asthma? a systematic review with

meta-analysis. Chest 2015;147(2):388-96

15. Belliveau PP, Omalizumab: a monoclonal anti-IgE antibody. Med Gen Med 2005;7(1):27.

16. Dolovich MB, Dhand R, Aerosol drug delivery; developments in device, design and clinical use.

Lancet 2011; 377: 1032-45

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the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011; 37:

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18. Philippine College of Chest Physicians. Philippine Consensus Report on Asthma Diagnosis and

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22. Lavorini, F, Mannini C, Chelini E, Challenges of inhaler use in the treatment of asthma and chronic

obstructive pulmonary disease Eur Respir J 2015;3:98-105

23. Papi A, Haughney J, Virchow JC, Roche N, Palkonen S, Price D, Inhaler device for asthma: a call for

action in a neglected field Eur Respir J 2011;37:982-5.

24. Basheti IA, Reddel HK, Amour CL, Bosnic-Anticevich SZ, Improved asthma outcomes with a simple

inhaler technique intervention by community pharmacists, J Allergy Clin Immunol 2007;119: 1537-

8.

25. Crompton GK, Barnes P, Broeders M, Corrigan C, Corbetta L, Dekhuijzen R, Dubus JC, et.al. The

need to improve inhalation technique in Europe: a report from the Aerosol Drug Management

Improvement Team. Respir Med, 2006;100:1479-94.

26. Amour CL, Reddel HK, LeMay KS, Saini B, Smith LD, Bosnic-Anticevich SZ, Song YJ, et.al. Feasibility

and effectiveness of an evidence-based asthma service in Australian community pharmacists: a

pragmatic cluster randomized trial. J Asthma 2013; 50: 302-9.

27. Haughney J, Price D, Barnes NC, Virchow JC, Roche N, Chrystyn H, Choosing inhaler devices for

people with asthma: current knowledge and outstanding research needs, Respir Med

2010;104:1237-45.


Chapter 5: Management of Asthma Exacerbations

Exacerbations of asthma are defined as episodes characterized by a progressive

increase in symptoms of shortness of breath, cough, wheezing or chest tightness and

progressive decrease in lung function, i.e. they represent a change from the patient’s

usual status that is sufficient to require a change in treatment.1 These exacerbations

may occur in patients as an initial presentation or in those previously diagnosed to

have asthma.

An exacerbation is usually triggered by exposure to an external agent or stimuli but

a few patients may develop an exacerbation without a known trigger. Although

exacerbations are more common in patients with poor adherence to controller

medications, i.e. poorly controlled asthma, it can also occur in patients with mild or

well-controlled asthma.1

The goals of treatment of acute exacerbations are to rapidly relieve airflow

obstruction, relieve the hypoxemia, address the underlying inflammatory

pathophysiology, and prevent relapse.1

How is an asthma exacerbation diagnosed?

In a patient previously diagnosed to have asthma, asthma exacerbation is diagnosed

by getting a history of increase in frequency of symptoms, AND documenting the

change in lung function measurements, either a decrease in peak expiratory flow

rates (PEF) or forced expiratory volume in the first second (FEV1), compared with the

patient’s previous lung function or predicted values.2

Lung function measurements are more reliable indicators of severity of exacerbation,

but the frequency of symptoms may be a more sensitive measure of the onset of

exacerbation than PEF.3

How is the severity of an asthma exacerbation evaluated?

A brief focused history, relevant physical examination and objective measurements

should be conducted concurrently with prompt initiation of therapy. Depending on

the patient’s signs and symptoms, the asthma exacerbation can usually be classified


as shown in Table 5.1.4 After classification of severity of exacerbation, appropriate

treatment may be instituted.

Table 5.1 Classification of severity of exacerbations4

The presence of one or more of these risk factors listed in Table 5.2 should be quickly

identifiable in the clinical notes, and these patients should be encouraged to seek

urgent medical care early in the course of an exacerbation.1

Table 5.2. Risk factors for Asthma-related deaths:4

• A history of near-fatal asthma requiring intubation and mechanical

ventilation

• Hospitalization or emergency care visit for asthma in the past year

• Currently using or having recently stopped using oral corticosteroids (a

marker of event severity)

• Over-use of SABAs, especially use of more than one canister of salbutamol

(or equivalent) monthly

• A history of psychiatric disease or psychosocial problems

• Poor adherence with asthma medications and/or poor adherence (or lack

of) a written asthma action plan

• Food allergy in a patient with asthma


What is the ideal first-line therapy for symptom relief in asthma exacerbations?

The ideal first-line therapy for acute exacerbation of asthma is inhaled SABA therapy.

The delivery of SABA via a pMDI with spacer leads to a similar improvement in lung

function as delivery via nebulizer.5,6(Evidence A)

To administer pMDI doses with spacer, it is recommended to give 4 to 10 puffs every

20 minutes for the first hour. Subsequently, 4 to 10 puffs every 3 to 4 hours OR 6 to

10 puffs every 1 to 2 hours can be given. If there is good response to the initial

treatment (i.e. PEF >60-80% of predicted or personal best for 3 to 4 hours), there is

no need to administer additional treatment.

In the treatment of moderate to severe exacerbations in the ER, the addition of

ipratropium, a short-acting anticholinergic, to SABA was associated with fewer

hospitalizations and greater improvement in PEF and FEV1 compared with SABA alone. 7,8 It is, therefore, reasonable to administer the combination as initial treatment for

moderate to severe exacerbations. There is no evidence to support the routine use

of intravenous beta2-agonist in patients with severe asthma exacerbations.9(10)

(Evidence A)

What is the first-line therapy for control of inflammation in asthma

exacerbations?

Systemic corticosteroids should be utilized in all but the mildest exacerbations in

adults, adolescents and children 6 to 11 years because it has been shown to speed

the resolution of exacerbations and prevent relapse.10,11,12 It is recommended that

systemic corticosteroids should be administered within one hour of presentation.

Oral corticosteroids are as effective as intravenous systemic corticosteroids.11,12

Intravenous corticosteroids can be administered when patients are too dyspneic to

swallow, if the patient is vomiting or when patients require non-invasive ventilation

or intubation.

A treatment regimen consisting of daily doses of OCS equivalent to 50 mg

prednisolone as a single morning dose, or 200 mg hydrocortisone in divided doses

are adequate for most patients. (Evidence B) The duration of treatment may vary

but 5- and 7-day courses have been found to be as effective as 10- and 14-day

courses respectively.13 (Evidence B) There is no benefit in tapering the dose of OCS

either in the short term14 or over several weeks.15(Evidence B)


Intravenous magnesium sulfate can be given to adults and children who fail to

respond to initial treatment and have persistent hypoxemia. When administered as a

single 2 g infusion over 20 minutes, intravenous magnesium sulfate reduces hospital

admission in adults with FEV1 <25-30% predicted at presentation.16,17,18(Evidence

A)

Is there a role of ICS in the management of asthma exacerbations?

In the acute care setting, high-dose ICS given within the first hour after presentation

reduces the need for hospitalization in patients not receiving systemic corticosteroids. 12(Evidence A) However, when given in addition to systemic corticosteroids,

evidence is conflicting.12(Evidence B)

Is there a role for ICS-LABA in the management of asthma exacerbations?

The role of ICS-LABA in the ER or hospital is unclear. For exacerbations of asthma

treated at home, patients already on combination formoterol and low-dose ICS

(budesonide or beclomethasone) in a single inhaler, increasing doses of up to 72 mcg

of formoterol in a day is effective in achieving control of symptoms.19 (Evidence A)

What is the role of methylxanthines in the management of asthma

exacerbations?

There is no role for methylxanthines, whether parenteral or oral, in the management

of acute asthma because of poor efficacy and safety profile.20 The use of intravenous

aminophylline is, in fact, associated with severe and potentially fatal side-effects,

particularly in patients already treated with sustained-release theophylline. Evidence

has shown that add-on treatment with aminophylline does not improve outcomes

compared with SABA alone.20

How should asthma exacerbations be managed at home?

All patients with asthma should be provided with guided self-management education,

including monitoring of symptoms and/or lung function, a written asthma action plan

and regular review by a healthcare professional.8

A written asthma action plan helps patients to recognize and respond appropriately


to worsening asthma. It should include specific instructions for changes in reliever

and controller medications.

Figure 5.1 outlines how to increase reliever medication, how to increase controller

medications and how to add corticosteroids.4

The criteria for initiating an increase in controller medication will vary from patient to

patient. For patients taking conventional maintenance ICS-containing treatment, this

should generally be increased when there is a clinically important change from the

patient’s usual level of asthma control, for example, if asthma symptoms are

interfering with normal activities, or PEF has fallen by >20% for more than 2

consecutive days.21

The patient should be instructed to follow up with their physician within 1 to 2 weeks

following a self-managed exacerbation for assessment of symptom control and

additional risk for exacerbation to identify the potential cause of exacerbation. The

written action plan should be reviewed if it met the patient’s needs. The usual

maintenance doses can usually be resumed after 2 to 4 weeks after the exacerbation,

unless history suggests that the patient has long-term poorly controlled asthma, in

which case a step up in treatment is indicated provided the inhaler technique and

adherence is adequate.


How should asthma exacerbations be managed in the out-patient setting?

After evaluation of the severity of exacerbation, initial therapy may be started

consisting of repetitive administration of short-acting bronchodilators, i.e. SABA,

early introduction of corticosteroids, and controlled-flow oxygen supplementation.

The management of asthma exacerbations in the out-patient setting is shown in

Figure 5.2.4

Figure 5.1 Self-management of worsening asthma in adults4

and adolescents with action plan 4(2)


Severe and life-threatening exacerbations should not be managed in the out-patient

setting. These patients should immediately be transferred to an acute care facility.

While waiting for transfer, a combination of inhaled SABA and ipratropium bromide

through pMDI + spacer or by nebulization, oxygen inhalation and systemic

corticosteroids should be promptly administered.

For mild-to-moderate exacerbations (Figure 5.2)4, an initial treatment at the out-

patient setting should consist of SABA 4 to 10 puffls via pMDI + spacer administered

every 20 minutes for one hour, prednisolone or equivalent at 1 mg/kg/day for adults,

maximum of 50 mg and 1-2 mg/kg/day for children, maximum of 40 mg. Controlled

oxygen, if available, should be given to achieve an oxygen saturation of 93-95% in

adults and 94-95% in children.4

Figure 5.2. Management of asthma exacerbations in the outpatient setting4


The clinical response to initial treatment should be evaluated after one hour. If the

patient’s condition is worsening, with deteriorating vital signs, transfer immediately

to an acute care facility. If partially improved after initial treatment, continue SABA

4 to 10 puffs via pMDI with spacer every four hours or 6 to 10 puffs every 1-2 hours.

If, however, the patient has good response, no need for further SABA, and the patient

is evaluated for discharge.

The patient may be discharged from the out-patient service department if symptoms

have improved and SABA is not needed anymore, PEF is 60-80% of predicted or

personal best, and oxygen saturation is > 94% at room air. Home instructions or a

written action plan should include instructions on reliever and controller medications,

OCS to be given for 5-7 days in adults and 3-5 days in children.

How should asthma exacerbations be managed in the emergency room

(ER)?

Severe exacerbations of asthma are life-threatening medical emergencies and should

be managed in an acute care setting such as an ER. An evaluation based on history,

physical examination, and objective measures should indicate whether the patient is

in mild to moderate, severe or life-threatening exacerbation (Figure 5.3).4

For patients in severe exacerbations, combined SABA (salbutamol 2.5 mcg) and

ipratropium (2.5 mcg) may be administered via nebulization intermittently every 20

minutes for three doses, or continuously every 10-15 minutes back-to-back for one

hour while awaiting transfer to the intensive care unit. SABA and ipratropium can

also be given via pMDI with spacer at 4 to 10 puffs every 20 minutes for one hour.

Low flow oxygen therapy should be administered by nasal cannulae or mask to

achieve oxygen saturation of 93-95% in adults (94-98% in children) and intravenous

corticosteroids (hydrocortisone 200 mg) in divided doses should be given while

preparing for intubation.4

For adults with mild-to-moderate exacerbation, in addition to SABA+ipratropium,

systemic corticosteroids should be given either through intravenous route if patient

is too dyspneic to swallow, or by oral administration. Lung function (PEF) should be

measured after one hour, and patients who deteriorate despite intensive

bronchodilator and corticosteroid treatment should be re-evaluated for transfer to

the intensive care unit.


What are the indications for hospitalization?

Clinical status and lung function after 1 hour of bronchodilator and corticosteroid

treatment are more reliable predictors of the need for hospitalization than the

patient’s status on arrival.22,23

Based on lung function measurements, hospitalization is recommended if pre-

treatment FEV1 or PEF is <25% predicted or personal best, or post-treatment FEV1

or PEF is <40% predicted or personal best.23

Figure 5.3. Management of asthma exacerbations at the emergency room (ER)

(Source GINA 2018)2


Other factors associated with increased likelihood of need for admission include:

24,25,26

• Female sex, older age and non-white race

• Use of more than beta2-agonist puffs in the previous 24 hours

• Severity of the exacerbation (e.g. need for resuscitation or rapid medical

intervention on arrival, respiratory rate >22 breaths/minute, O2 saturation

<95%, final PEF <50% predicted).

• Past history of severe exacerbations (e.g. intubations, asthma admissions)

• Previous unscheduled office and emergency department visits requiring use of

OCS.

When do we discharge patients after being treated in the ER for an asthma

exacerbation?

If post-treatment lung function is 40–60% predicted, discharge may be possible after

considering the patient’s risk factors and availability of follow-up care. If post-

treatment lung function is >60% predicted or personal best, discharge27is

recommended after considering risk factors and availability of follow-up care. Prior

to discharge, instructions should be given on correct medications and inhaler skills,

a written action plan should be provided, and a follow up appointment within one

week from discharge should be arranged. (Table 5.3)4


Table 5.3. Discharge management after hospital or emergency room care

for asthma4

Medications

Oral Corticosteroids (OCS)

Prescribe at least a 5-7 days’ course of OCS for adults (prednisolone or equivalent 1 mg/kg/day to

a maximum of 50 mg/day) and 3-5 days for children (1-2 mg/kg/day to a maximum of 40 mg). For

patients considered at risk of poor adherence, intramuscular corticosteroids may be considered.

(Evidence B)

Reliever medication

Transfer patients back to as-needed rather than regular reliever medication use, based on

symptomatic and objective improvement. If ipratropium bromide was used in the emergency

department or hospital, it may be quickly discontinued, as it is unlikely to provide ongoing benefit.

Inhaled corticosteroids (ICS)

Initiate ICS prior to discharge, if not previously prescribed. Patients currently prescribed ICS-

containing medication should generally have their treatment stepped up for 2-4 weeks and should

be reminded about the importance of adherence with daily use.

Risk factors that contributed to the exacerbation

Identify factors that may have contributed to the exacerbation and implement strategies to reduce

modifiable risk factors. An exacerbation severe enough to require hospitalization may follow irritant

or allergen exposure., inadequate long-term treatment, problems with adherence, and/or lack of

written asthma action plan, as well as unavoidable factors such as viral respiratory infections.

Self-management skills and written asthma action plan

• Review inhaler technique

• Review technique with PEF if used

• Provide a written asthma action plan or review the patient’s existing plan, either at discharge or

as soon as possible afterwards. Patient discharged from the emergency room with an action plan

and PEF meter have better outcomes than patients discharged without these resources.

• Evaluate the patient’s response to exacerbation. If it was inadequate, review the action plan and

provide written guidance to assist if asthma worsens again.

• Review the patient’s use of controller treatment before and during exacerbation. Was it increased

promptly and by how much? Were OCS added and if not, why not? Consider providing short-

course of OCS to be on hand for subsequent exacerbations.

Follow-up appointment

A follow-up appointment within 2-7 days of discharge should be made with the patient’s usual

health care provider, to ensure that treatment is continued, that asthma symptoms are well

controlled, and that the patient’s lung function reaches their personal best (if known).

ICS: inhaled corticosteroids; OCS: oral corticosteroids; PEF: peak expiratory flow


References:

1. Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, Casale TB, Chanez P, Enright

PL, Gibson PG, de Jongste JC, Kerstjens HA, Lazarus SC, Levy ML, O’Byrne PM, Partridge MR, Pavord

ID, Sears MR, Sterk PJ, Stoloff SW, Sullivan SD, Szefler SJ, Thomas MD, Wenzel SE, American

Thoracic Society/European Respiratory Society Task Force on Asthma Control and Exacerbations.

An official American Thoracic Society/European Respiratory Society statement: asthma control and

exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir

Crit Care Med 2009 Jul; 180(1):59-99.

2. FitzGerald JM, Grunfeld A. Status asthmaticus. In: Lichtenstein LM, Fauci AS, eds. Current therapy

in allergy, immunology, and rheumatology. 5th edition. St. Louis, MO: Mosby; 1996:p. 63-7.

3. Chan-Yeung M, Chang JH, Manfreda J, Ferguson A, Becker A. Changes in peak flow, symptom score,

and the use of medications during acute exacerbations of asthma. Am J Respir Crit Care Med 1996

Oct;154(4 Pt1):889-93.

4. Global Strategy for Asthma Management and Prevention Updated 2017. Available from:

http://www.ginasthma.org

5. Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist

treatment of acute asthma. Cochrane Database Syst Rev 2013:9:CD000052.

6. Newman KB, Milne S, Hamilton C, Hall K. A comparison of albuterol administered by metered-dose

inhaler and spacer with albuterol by nebulizer in adults presenting to an urban emergency

department with acute asthma. Chest 2002 Apr;121(4):1036-41.

7. Griffiths B, Ducharme FM, Combined inhaled anticholinergics and short-acting beta2-agonists for

initial treatment of acute asthma in children. Cochrane Database Syst Rev 2013;8:CD010179.

8. Gibson PG, Powell H, Coughlan J, et.al. Self-management education and regular practitioner review

for adults with asthma. Cochrane Database Syst Rev 2003:CD001117.

9. Travers AH, Milan SJ, Jones AP, Camargo CA, Jr., Rowe BH. Addition of intravenous beta2-agonists

to inhaled beta-2 agonists for acute asthma. Cochrane Database Syst Rev 2012;12:CD010179

10. Manser R, Reid D, Abramson MJ. Corticosteroids for acute severe asthma in hospitalised patients.

Cochrane Database Syst Rev 2000;2:CD001740.

11. Rowe BH, Spooner CH, Ducharme FM, Bretzlaff JA, Bota GW. Corticosteroids for preventing relapse

following acute exacerbations of asthma. Cochrane Database Syst Rev 2007:3:CD000195.

12. Edmonds ML, Milan SJ, Camargo CA, Jr., Pollack CV, Rowe BH. Early use of inhaled corticosteroids

in the emergency department treatment of acute asthma. Cochrane Database Syst Rev

2012;12:CD002308.

13. Hasegawa T, Ishihara K, Takakura S, Fujili H, Nishimura T, Okazaki M, Katakami N, Umeda B,

Duration of systemic corticosteroids in the treatment of asthma exacerbation: a randomized study,

Intern Med 2000 Oct; 39(10): 794-7.

14. O'Driscoll BR, Kalra S, Pickering CA, Carroll KB, Woodcock AA, Wilson M, Double-blind trial of steroid

tapering in acute asthma. Lancet 1993 Feb; 341(8841):324-7.

15. Lederle FA, Pluhar RE, Joseph AM, Niewoehner DE, Tapering of corticosteroid therapy following

exacerbation of asthma: a randomized, double-blnd, placebo-controlled trial. Arch Intern Med

1987;147(12):2201-3.

16. Rowe BH, Bretzlaff JA, Bourdon C, Bota GW, Blitz S, Camargo CA, Jr. Magnesium sulfate for treating

exacerbations of acute asthma in the emergency department. Cochrane Database Syst Rev

2000;1:CD0014990.

17. FitzGerald JM. Magnesium sulfate is effective for severe acute asthma treated in the emergency

department. West J Med 2000 Mar;172(2):96.


18. Gallegos-Solorzano MC, Perez-Padilla R, Hernandez-Zenteno RJ. Usefulness of inhaled magnesium

sulfate in the coadjuvant management of severe asthma crisis in an emergency department. Pulm

Pharmacol Ther 2010 Oct;23(5):432-7.

19. Bateman ED, Reddel HK, Eriksson G, Peterson S, Ostlund O, Sears MR, Jenkins C, et.al. Overall

asthma control: the relationship between current control and future risk. J Allergy Clin Immunol

2010 Feb; 125(3):600-8.

20. Nair P, Milan SJ, Rowe BH. Addition of intravenous aminophylline to inhaled beta2-agonists in adults

with acute asthma. Cochrane Database Syst Rev 2012;12:CD002742.

21. Gibson PG, Powell H. Written action plans for asthma: an evidence-based review of the key

components. Thorax 2004 Feb;59(2):94-9.

22. Kelly A-M, Kerr D, Powell C. Is severity assessment after one hour of treatment better for predicting

the need for admission in acute asthma? Respir Med 2004 Aug;98(8):777-81.

23. Wilson MM, Irwin RS, Connolly AE, Linden C, Manno MM. A prospective evaluation of the 1-hour

decision point for admission versus discharge in acute asthma. J Intensive Care Med 2003

Sep;18(5):275-85

24. Pollack CV, Jr, Pollack ES, Baren JM, Smith SR, Woodruff PG, Clark S, Camargo CA, for the

Multicenter Airway Research Collaboration Investigators. A prospective multicenter study of patient

factors associated with hospital admission from the emergency department among children with

acute asthma. Arch Pediatr Adolesc Med 2002 Sep;56:934-40.

25. Rowe BH, Villa-Roel C, Abu-Laban RB, Stenstrom R, Mackey D, Stiell IG, Campbell S, Young B,

Admissions to Canadian hospitals for acute asthma: a prospective multicenter study, Can Respir J

2010 Jan-Feb;17(1):25-30.

26. Weber EJ, Silverman RA, Callaham ML, Pollack CV, Woodruff PG, Clark S, Camargo CA, A prospective

multicenter study of factors associated with hospital admission among adults with acute asthma Am

J Med 2002 Oct;113(5):371-78.

27. Grunfeld A, FitzGerald JM. Discharge considerations for adult asthmatic patients treated in

emergency departments. Can Respir J 1996 Jan;3(5):322 -7.


CHAPTER 6: CHRONIC ASTHMA MANAGEMENT

.

Asthma cannot be cured, but appropriate management can result in control of the

disease and enable those affected to enjoy a good quality of life.1

What are the goals of chronic asthma management?

The aim of asthma management is control of the disease.2 The long-term goals are:3

• To achieve good control of symptoms and maintain normal activity levels

• To minimize future risk of exacerbations, fixed airflow limitation and side-effects.

Complete control of asthma is defined2 as:

• no daytime symptoms

• no night-time awakening due to asthma

• no need for rescue medication

• no asthma attacks

• no limitations on activity including exercise

• normal lung function (in practical terms FEV1 and/or PEF>80% predicted or

best)

• minimal side effects from medication.

Current degree of asthma control has been found to predict future risk of instability

and exacerbations.4 On the other hand, an exacerbation in the past year is a strong

independent predictor of future exacerbations, particularly in patients with severe

or difficult-to-treat asthma.5,6

What is control-based asthma management?

Control based asthma management is a continual process of adjustment of

pharmacological and non-pharmacological strategies and involves a cycle of

assessment, treatment modifications based on current status and review of clinical

response. (Fig. 6.1) 3

Successful asthma management requires a system of regular objective monitoring,

stepwise adjustment of medications based on clinical response and patient

preference, addressing non-pharmacologic interventions and comorbidities,

nurturing an excellent patient-healthcare provider partnership and self-management

education planning.


In low- and middle-income countries such as the Philippines, affordability and

availability7 are additional important considerations in the choice of medications,

aside from efficacy and safety. Physicians should check the accessibility of free

generic inhaled asthma medications in local health units.8

What is the stepwise approach for adjusting asthma treatment in adults?

The approach to asthma treatment in Filipino adults is a 5-step continuum of care

that involves a stepwise escalation or de-escalation of the number and dosing of

asthma controller medications that are required to achieve and maintain control.

(Fig. 6.2)

After a diagnosis of asthma is made, pharmacotherapy is initiated. The choice of

medications is based on the patient’s current level of asthma control, the presence

of future risks of adverse outcomes and the response to current asthma treatment,

if any.3 On subsequent clinic visits, controller therapy is adjusted up or down in a

stepwise fashion depending on whether the goals of asthma management are met or

not.

Figure 6.1 The control-based asthma management cycle. (Source: GINA 20183


Once good asthma control has been maintained for 2-3 months, taking a lower

treatment step is done in order to find the minimum effective drug and dosing that

can maintain control. On the other hand, if a patient has persisting symptoms and/or

exacerbations despite 2-3 months of controller treatment, the following common

problems need to be assessed and corrected before considering any step-up in

treatment:3

• incorrect inhaler technique

• Poor adherence

• Persistent exposure to agents which trigger asthma

• Presence of uncontrolled comorbidities

• Incorrect diagnosis

Figure 6.2 Stepwise approach to asthma treatment in Filipino adults


STEP 1

Preferred option: As-needed combination of low dose ICS-formoterol

Eosinophilic airway inflammation and remodeling have been demonstrated even in

the mildest forms of asthma. 9-11The results of a recent post-hoc analysis of the 3-

year inhaled Steroid Treatment As Regular Therapy (START) study on mild recent-

onset asthma do not support restriction of inhaled corticosteroids to patients with

symptoms on more than 2 days per week and suggest that treatment

recommendations for mild asthma should consider both risk reduction and

symptoms.12 (Evidence B) Indeed, anti-inflammatory treatment with inhaled

corticosteroids has been found to reduce asthma symptoms, increase lung function,

improve quality of life, and reduce the risk of exacerbation and asthma-related

hospitalization or death. 13-17 (Evidence A)

STEP 2

Preferred option: As needed low dose ICS-formoterol or as maintenance

and reliever therapy (MART) OR regular low-dose ICS-

LABA combination plus as-needed SABA

In the local setting, patients often carry the financial burden of the out-of-pocket cost

of treatment and the medical care of a significant number of Filipinos is neither

covered by Health Maintenance Organizations nor subsidized by their employers.

Furthermore, Filipino asthmatics prioritize medications that can provide rapid relief

of symptoms.18 To assure the delivery of anti-inflammatory therapy, while providing

bronchodilator efficacy, for the majority of symptomatic asthmatics, the consensus

is to start at step 2 with either low doses of ICS-formoterol as maintenance and

reliever therapy or low doses of a fixed-dose ICS-LABA combination inhaler.

(Evidence D)

Recent data has shown benefit of as-needed budesonide-formoterol in a 52-week

study for mild asthma in reducing exacerbations by 64% compared with SABA only

treatment.19 This is also in congruence with older studies by Zetterstrom and O’Byrne

showing that budesonide-formoterol single inhaler therapy provided better asthma

control than budesonide alone in patients not previously fully controlled by

glucocorticoids.13,20 Bateman, et.al.21 showed that budesonide-formoterol used as-

needed was noninferior to twice-daily budesonide with respect to the rate of severe

asthma exacerbations during 52 weeks of treatment but was inferior in controlling

symptoms.


Alternatively, the regular use of combination ICS-LABA in adolescents and adults with

sub-optimal asthma control on low-dose ICS monotherapy is more effective than ICS

alone in reducing the risk of exacerbations requiring OCS, provides greater

improvement in lung function, symptoms, use of rescue SABA and leads to fewer

withdrawals due to poor asthma control than a higher dose of ICS.22(Evidence A)

Access to corticosteroid inhalers has become a problem in many parts of the

Philippines. Fixed dose ICS-LABA combination inhalers are more easily available,

including the cheaper generic brands that are freely provided in selected local health

units. Where ICS as monotherapy cannot be obtained, maintenance treatment with

low-dose ICS-LABA is an alternative option. (Evidence D)

STEP 3

Preferred option: Combination medium dose ICS-LABA plus as-needed

SABA OR combination ICS-formoterol as maintenance

and reliever therapy (MART)

If control is suboptimal despite combination low-dose ICS-LABA, maintenance

treatment may be increased to medium-dose ICS-LABA.23(Evidence B)

Low dose ICS-formoterol combination inhalers can be prescribed as both

maintenance and reliever therapy (MART). This approach has been shown to result

in reductions in exacerbations and improvements in patient’s lung function and

asthma symptoms in adults and adolescents at relatively low doses of ICS, compared

with a fixed dose of ICS-LABA as maintenance treatment, or a higher dose of ICS

combined with as-needed SABA.24-28 (Evidence A)

STEP 4

Preferred option: Combination high dose ICS-LABA plus as-needed SABA

OR combination ICS-formoterol as maintenance and

reliever therapy (MART)

Step 4 treatment options depend on prior selections at Step 3. As previously stated,

before stepping up, the presence of common problems such as incorrect asthma

diagnosis, suboptimal inhaler technique, poor adherence, continuing environmental

exposure to triggers, and uncontrolled comorbidities must be reviewed and addressed

accordingly. Where possible, patients who are not controlled on Step 3 treatments

should be referred to an asthma specialist for investigation of alternative diagnoses

and/or causes of difficult-to-treat asthma and further management.


For patients already on combination low dose ICS-formoterol as maintenance and

reliever therapy, the maintenance dose may be increased if necessary. In patients

with moderate to severe asthma, MART strategy was found to be more effective and

less expensive than a strategy of clinician-directed titration of ICS-LABA with

salbutamol as reliever therapy.29 (Evidence A).

Pre-defined total asthma control through stepped-up treatment with ICS-LABA

(maximum of 500 μg ICS twice a day) can be achieved by about a third of

patients.30Combination high-dose ICS-LABA may thus be considered in adult patients

with more severe asthma, but the increase in ICS dose generally provides little

additional benefit 31,32,33 (Evidence A), and there is an increased risk of side-effects,

including adrenal suppression.34 A high dose is recommended only on a trial basis for

3–6 months when good asthma control cannot be achieved with medium dose ICS

plus LABA and/or a third controller (e.g. LTRA).3

STEP 5

Preferred option: Step 4 regimen + specialist referral for add-on

treatment

Patients with persistent symptoms or exacerbations despite correct inhaler technique

and good adherence to Step 4 treatment, and in whom other controller options have

been considered, should be referred to a tertiary level medical center with a severe

asthma clinic or to a specialist with expertise in the management and treatment of

severe asthma.3(Evidence D)

Treatment options which are currently available in the local setting that may be

considered in step 5:

1. Add-on Tiotropium by soft-mist inhaler, if not yet started in step 4

2. Add on Anti-Immunoglobulin E (anti-IgE) treatment with omalizumab for

patients ≥ 6 years with moderate to severe allergic asthma that is uncontrolled

in Step 4 treatment.35(Evidence A)

How often should response to treatment be assessed and monitored?

To achieve asthma control, review of symptoms, risk factors and occurrence of

exacerbations as well as response to treatment adjustments, patients should be

monitored on a regular basis.3 For most controller medications, improvement begins

within days of initiating treatment, but the full benefit may only be evident after 3-4

months.36 In severe and chronically under treated disease, this may take even

longer.37


The frequency of healthcare visits and assessments depends upon the patient’s initial

clinical severity and the patient’s training and confidence in playing a role in the

ongoing control of his or her asthma, including adherence and proficiency to use the

assigned inhaler. Typically, patients are seen one to three months after the initial

visit, and every 3-12 months thereafter.3 After an exacerbation, follow-up should be

scheduled within one week.38 (Evidence D)

GUIDELINES FOR ESCALATION OF TREATMENT

Asthma is a variable condition and patients may have more symptoms during allergen

season. Periodic treatment adjustments by the clinician and/or the patient may be

needed.39

The Philippine consensus has adopted these GINA 2018 recommendations3:

• Sustained step up (for at least 2–3 months): some patients may fail to respond

adequately to initial treatment. A step up in treatment may be recommended if

the symptoms are confirmed to be due to asthma; inhaler technique and

adherence are satisfactory; and modifiable risk factors such as smoking have been

addressed (see Table 6.2). Any step up should be regarded as a therapeutic trial,

and the response reviewed after 2–3 months. If there is no response, treatment

should be reduced to the previous level, and alternative treatment options or

referral considered.

• Short-term step up (for 1–2 weeks): an occasional short-term increase in

maintenance ICS dose for 1–2 weeks may be necessary; for example, during viral

infections or seasonal allergen exposure. This may be initiated by the patient

according to their written asthma action plan or by the health care provider.

• Day-to-day adjustment: for patients prescribed combination budesonide-

formoterol or beclomethasone-formoterol as maintenance and reliever treatment

(MART), the patient adjusts the number of as-needed doses of ICS-formoterol

from day to day according to their symptoms, while continuing the maintenance

dosage.


GUIDELINES FOR DE-ESCALATION OF TREATMENT

When asthma control has been achieved and maintained for at least 3 months and

lung function has reached a plateau, treatment can often be successfully reduced,

without loss of asthma control. The appropriate time to step down therapy is when

the patient currently has no respiratory infection, not travelling, not pregnant or will

have minimal exposure to triggers such as weather/season change. Approach to

stepping down of treatment should also be regarded as a therapeutic trial. Patients

must be provided with enough information and a written action plan and instructions

on how and when to resume their previous treatment if their symptoms worsen. If

the patient has risk factors for exacerbations or fixed airflow limitation, close

supervision by a clinician is necessary.3

The goals of stepping down are as follows:

1. To establish the lowest step and dose of treatment necessary (i.e. minimum

effective treatment), which minimizes the cost and maximizes the safety of

treatment

2. To encourage the patient to continue regular controller treatment.3

The following are some of the GINA 2018 strategies that can be adopted in the local

setting3:

• When asthma is controlled with a combination of ICS and LABA, the preferred

approach is to begin by reducing the dose of inhaled steroid by approximately

50% at 3-month intervals while continuing the inhaled LABA (Evidence B).

• When ICS monotherapy in medium to high-doses is being used, a 50%

reduction in dose should be attempted at 3-month intervals (Evidence B).

• Where control is achieved at a low-dose of ICS alone, in most patients,

treatment may be switched to once-daily dosing (Evidence A).

• If control is maintained, further reductions in the inhaled steroid should be

attempted until a low-dose is reached, at which time, the LABA may be stopped

(Evidence D).

• When asthma is controlled with ICS in combination with controllers other than

LABA, the dose of inhaled steroid should be reduced by 50% until a low-dose

is reached, then the combination treatment can be stopped, as described

above (Evidence D).

• Controller treatment may be stopped if the patient’s asthma remains controlled

on the lowest dose of controller and no recurrence of symptoms occurs for at

least one year (Evidence D).


What is the role of immunotherapy in asthma?

Allergen-specific immunotherapy has a role in patients with allergic asthma and

allergic rhinoconjunctivitis.

What is the role of vaccination among asthmatics?

The U.S. Centers for Disease Control and Prevention (CDC) recommend annual

seasonal influenza vaccination for all persons aged 6 months and older, in general,

and, in particular, for individuals with chronic pulmonary diseases including asthma.

For the latter population, this vaccine aims to limit influenza-related mortality and

decrease transmission of the virus. 40

NON-PHARMACOLOGICAL INTERVENTIONS

Aside from pharmacotherapy, there are other interventions, activities and strategies

that can help in managing asthma. The different advices and their level of evidence

are listed and summarized in GINA 2018 (see Table 6.2).3

Table 6.2. Non-pharmacological interventions for asthma3

Intervention Advice/recommendation Evidence

Cessation of

smoking and ETS

exposure

• At every visit, strongly encourage people with asthma who smoke to

quit. Provide access to counselling and smoking cessation programs (if

available)

• Advise parents/carers of children with asthma not to smoke and not to

allow smoking in rooms or cars that their children use

• Strongly encourage people with asthma to avoid environmental smoke

exposure

• Assess smokers/ex-smokers for COPD or overlapping features of

asthma and COPD (asthma-COPD overlap, ACO) as additional

treatment strategies may be required

A

A

B

D

Physical activity • Encourage people with asthma to engage in regular physical activity for

its general health benefits

• Provide advice about prevention and management of exercise-induced

bronchoconstriction

• Regular physical activity improves cardiopulmonary fitness, but confers

no other specific benefit on lung function or asthma symptoms, with

the exception of swimming in young people with asthma

• There is little evidence to recommend one form of physical activity

over another

A

A

B

D

Avoidance of

occupational

exposures

• Ask all patients with adult-onset asthma about their work history and

other exposures

• In management of occupational asthma, identify and eliminate

occupational sensitizers as soon as possible, and remove sensitized

patients from any further exposure to these agents

• Patients with suspected or confirmed occupational asthma should be

referred for expert assessment and advice, if available

A

A

A


Avoidance of

medications that

may make asthma

worse

• Always ask about asthma before prescribing NSAIDs, and advise

patients to stop using them if asthma worsens

• Always ask people with asthma about concomitant medications

• Aspirin and NSAIDs (non-steroidal anti-inflammatory drugs) are not

generally contraindicated unless there is a history of previous reactions

to these patients

• Decide about prescription of oral or intra-ocular beta-blockers on a

case-by-case basis. Initiate treatment under close medical supervision

by a specialist

• If cardio-selective beta-blockers are indicated for acute coronary

events, asthma is not an absolute contra-indication, but the relative

risks/ benefits should be considered

A

D

A

D

D

Healthy diet • Encourage patients with asthma to consume a diet high in fruit and

vegetables for its general health benefits

A

Avoidance of indoor

allergens

• Allergen avoidance is not recommended as a general strategy in

asthma

• For sensitized patients, there is limited evidence of clinical benefit for

asthma with single-strategy indoor allergen avoidance

• Remediation of dampness or mold in homes reduces asthma symptoms

and medication use in adults

• For patients sensitized to house dust mite &/or pets, there is limited

evidence of clinical benefit for asthma with avoidance strategies (only

in children)

• Allergen avoidance strategies are often complicated and expensive, and

there are no validated methods of identifying those who are likely to

benefit

A

A

A

B

D

Weight reduction • Include weight reduction in the treatment plan for obese patients with

asthma

• For obese adults with asthma a weight reduction program plus twice

weekly aerobic and strength exercises is more effective for symptom

control than weight reduction alone

B

B

Breathing exercises • Breathing exercises may be a useful supplement to asthma

pharmacotherapy

B

Avoidance of indoor

air pollution

• Encourage people with asthma to use non-polluting heating and

cooking sources, and for sources of pollutants to be vented outdoors

where possible

B

Avoidance of

outdoor allergens

• For sensitized patients, when pollen and mold counts are highest,

closing windows and doors, remaining indoors, and using air

conditioning may reduce exposure to outdoor allergens

D

Dealing with

emotional stress

• Encourage patients to identify goals and strategies to deal with

emotional if it makes their asthma worse

• There is insufficient evidence to support one stress-reduction strategy

over another, but relaxation strategies and breathing exercises may be

helpful

• Arrange a mental health assessment for patients with symptoms of

anxiety or depression

D

B

D


Avoidance of

outdoor air

pollutants/weather

conditions

• In general, when asthma is well-controlled, there is no need for

patients to modify their lifestyle to avoid unfavorable outdoor (air

pollutants, weather).

• It may be helpful during unfavorable environmental conditions (very

cold weather, low humidity or high air pollution) to avoid strenuous

outdoor physical activity and stay indoors in a climate-controlled

environment; and during viral infections to avoid polluted environments

D

D

Avoidance of foods

and food chemicals

• Food avoidance should not be recommended unless an allergy or food

chemical sensitivity has been clearly demonstrated, usually by carefully

supervised oral challenges

• For confirmed food allergy, food allergen avoidance may reduce asthma

exacerbations

• If food chemical sensitivity is confirmed, complete avoidance is not

usually necessary, and sensitivity often decreases when asthma control

improves

D

D

D

Allergen

immunotherapy

• For adult patients with allergic rhinitis and sensitized to HDM, with

exacerbations despite low to high dose ICS, consider adding sublingual

immunotherapy (SLIT), provided FEV1 >70% predicted

• As for any treatment, potential benefits of allergen immunotherapy

(SCIT or SLIT) for individual patients should be weighed against the

risk of adverse effects and the cost to the patient and health system,

including for SCIT the minimum half-hour wait required after each

injection

B

D

Vaccinations • People with asthma, particularly the children and the elderly, are at

higher risk of pneumococcal disease, but there is insufficient evidence

to recommend routine pneumococcal vaccination in people with asthma

• Advise patients with moderate-severe asthma to have an influenza

vaccination every year, or at least when vaccination of the general

population is advised

B

D

Bronchial

thermoplasty

• For highly-selected adult patients with uncontrolled asthma despite use

of recommended therapeutic regimens and referral to an asthma

specialist center, bronchial thermoplasty is a potential treatment option

in some countries.

• Caution should be used in selecting patients for this procedure, as the

number of studies is small and people with chronic sinus disease,

frequent chest infections or FEV1 <60% predicted were excluded.

B

D


References:

1. Asthma Fact Sheet. Updated August 31,2017. Retrieved from: http://www.who.int/

mediacentre/factsheets/fs307/en/[Last accessed March 15, 2019].

2. British Guideline on the Management of asthma: A national clinical guideline 2016. Available from:

www.sign.ac.uk

3. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2018.

Available from: www.ginasthma.org

4. Bateman ED. Reddel, HK, Eriksson G, Peterson S, Ostulund, O, Sears MR, Jenkins, C., et.al. Overall

asthma control: the relationship between current control and future risk J Allergy Clin Immunol

2010;125:600-8.

5. Miller MK, Lee JH, Miller DP, Wenzel SE, TENOR Study Group. Recent asthma exacerbations:a key

predictor of future exacerbations. Respir Med 2007;101:481-9.

6. Tanaka A, Uno T, Sato H, Jinno M, Hirai K, Miyata Y, Yamaguchi M, et al. Predicting future risk of

exacerbations in Japanese patients with adult asthma: A prospective 1-year follow up study. Allergol

Int 2017;66:568-73.

7. Beran D, Zar HJ, Perrin C, Burney P, Menezes AM, Forum of International Respiratory Societies

working group collaboration. Burden of asthma and chronic obstructive pulmonary disease and

access to essential medicines in low-income and middle-income countries. Lancet Respir Med

2015;3:159-70

8. DOH relaunches 'Botika ng Bayan'. July 18, 2018. Retrieved from: https://pia.go.ph/

news/articles/1010499 [Last accessed March 15, 2019]

9. Van den Toorn LM. Clinical implications of airway inflammation in mild intermittent asthma. Annals

of Allergy, Asthma & Immunology 2004;92(6):589–95.

10. Wilson SJ, Rigden HM, Ward JA, Laviolette M, Jarjour NN, Djukanovic R. The relationship between

eosinophilia and airway remodeling in mild asthma. Clin Exp Allergy 2013;43:1342–50.

11. Gorska K, Paplinska-Goryca M, Nejman-Gryz P, Goryca K, Krenke R. Eosinophilic and neutrophilic

airway inflammation in the phenotyping of mild-to-moderate asthma and chronic obstructive

pulmonary disease. COPD: J Chr Obst Dis. 2017;14(2):181-9.

12. Reddel, HK, Busse WW, Pedersen S, Tan WC, Chen YZ, Jorup C, Lythgoe, D, O’Byrne, PM, Should

recommendations about starting inhaled corticosteroid treatment for mild asthma be based on

symptom frequency: a post-hoc efficacy analysis of the START study, Lancet,

2015;389(10065):157-166.

13. O’Byrne PM, Barnes PJ, Rodriguez-Roisin R, Runnerstrom E, Sandstrom T, Svensson K, Tattersfield

A. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized

trial. Am J Respir Crit Care Med 2001;164(8 Pt 1):1392-7.

14. Pauwels RA, Pedersen S, Busse WW, Tan WC, Chen YZ, Ohlsson SV, Ullman A, et al. Early

intervention with budesonide in mild persistent asthma: a randomized,double-blind trial. Lancet

2003;361:1071-6.

15. Adams NP, Bestall JB, Malouf R, Lasserson TJ, Jones PW. Inhaled beclomethasone versus placebo

for chronic asthma. Cochrane Database Syst Rev 2005:CD002738.

16. Suissa S, Ernst P, Benayoun S, Baltzan M, Cai B. Low dose inhaled corticosteroids and prevention

of death from asthma. N Engl J Med 2000;343:332-6.

17. Adams NP, Bestall JC, Lasserson TJ, Jones P, Cates CJ. Fluticasone versus placebo for chronic asthma

in adults and children. Cochrane Database of Syst Rev 2008;4:CD003135.

18. Price D, David-Wang A, Cho SH, Ho JC, Jeong JW, Liam CK, Lin J, et al. Time for a new language for

asthma control: Results from REALISE Asia. J Asthma Allergy 2015; 8:93-103.


19. O’Byrne PM, FitzGerald JM, Bateman ED, Barnes PJ, Zhong N, Keen C, Jorup C, et. al. Inhaled

combined budesonide–formoterol as needed in mild asthma. N Engl J Med 2018; 378:1865-76.

20. Zetterstrom O, Buhl R, Mellem H, Perpina M, Hedman J, O’Neill S, Ekstrom T. Improved asthma

control with budesonide/formoterol in a single inhaler, compared with budesonide alone. Eur Respir

J 2001;18:262-8.

21. Bateman ED, Reddel HK, O’Byrne PM, Barnes PJ, Zhong N, Keen C, Jorup C, et al. As-needed

budesonide–formoterol versus maintenance budesonide in mild asthma. N Engl J Med 2018;

378:1877- 87.

22. Ducharme FM, Ni Chroinin M, Greenstone I, Lasserson TJ. Addition of long-acting beta2-agonists to

inhaled steroids versus higher dose inhaled steroids in adults and children with persistent asthma.

Cochrane Database Syst Rev 2010;(5):CD005533.

23. O'Byrne PM, Naya IP, Kallen A, Postma DS, Barnes PJ. Increasing doses of inhaled corticosteroids

compared to adding long-acting inhaled beta2-agonists in achieving asthma control. Chest

2008;134:1192-9.

24. Cates CJ, Karner C. Combination formoterol and budesonide as maintenance and reliever therapy

versus current best practice (including inhaled steroid maintenance), for chronic asthma in adults

and children. Cochrane Database Syst Rev 2013;4:CD007313.

25. Kew KM, Karner C, Mindus SM, Ferrara G. Combination formoterol and budesonide as maintenance

and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and

children. Cochrane Database Syst Rev 2013;12:CD009019.

26. Papi A, Corradi M, Pigeon-Francisco C, Baronio R, Siergiejko Z, Petruzzelli S, Fabri LM et al.

Beclometasone–formoterol as maintenance and reliever treatment in patients with asthma: a

double-blind, randomised controlled trial. Lancet Respir Med 2013;1:23-31.

27. Patel M, Pilcher J, Pritchard A, Perrin K, Travers J, Shaw D, Holt S, et al. Efficacy and safety of

maintenance and reliever combination budesonide/formoterol inhaler in patients with asthma at risk

of severe exacerbations: a randomized controlled trial. Lancet Respir Med 2013;1:32-42.

28. Bateman ED, Harrison TW, Quirce S, Reddel HK, Buhl R, Humbert M, Jenkins CR, et al. Overall

asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients

on different treatment steps. Respir Res 2011;12:38.1028

29. Miller E, Sears MR, McIvor A, Liovas A. Canadian economic evaluation of budesonide- formoterol as

maintenance and reliever treatment in patients with moderate to severe asthma. Can Respir J

2007;14(5):269-75.

30. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, Pedersen SE, et al. Can

guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J

Respir Crit Care Med 2004;170:836-44.

31. Powell H, Gibson PG. Inhaled corticosteroid doses in asthma: an evidence-based approach. Med J

Aust 2003;178:223-5.

32. Pauwels RA, Lofdahl CG, Postma DS, Tattersfield AE, O’Byrne P, Barnes PJ, Ullman A. Effect of

inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids

Establishing Therapy (FACET) International Study Group. N Engl J Med 1997;337:1405-11.

33. Szefler SJ, Martin RJ, King TS, Boushey HA, Cherniack RM, Chinchilli VM, Craig TJ, et al. Significant

variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol

2002;109:410-8.

34. Broersen LH, Pereira AM, Jorgensen JO, Dekkers OM. Adrenal insufficiency in corticosteroids use:

Systematic review and meta-analysis. J Clin Endocrinol Metab 2015;100:2171-80.

35. Normansell R, Walker S, Milan SJ, Walters EH, Nair P. Omalizumab for asthma in adults

and children. Cochrane Database Syst Rev 2014;1:CD003559.

36. Bateman ED, Bousquet J, Keech ML, Busse WW, Clark TJ, Pedersen SE. The correlation between

asthma control and health status: the GOAL study. Eur Respir J 2007;29:56-62.


37. Sont JK. How do we monitor asthma control? Allergy 1999;54(Suppl 49):68-73.

38. Schatz M, Rachelefsky G, Krishnan JA. Follow-up after acute asthma episodes: what improves future

outcomes? Proc Am Thorac Soc 2009;6:386-93.

39. Thomas A, Lemanske RF Jr., Jackson DJ. Approaches to stepping up and stepping down care in

asthmatic patients. J Allergy Clin Immunol 2011;128:915-24.

40. Centers for Disease Control. Asthma and Influenza. Retrieved from from: https://

www.cdc.gov/flu/about/disease/high_risk.htm/[Last accessed March 18, 2019]. schedule by

medical condition and other indications, United States, 2019. Retrieved from

https://www.cdc.gov/vaccines/vpd/pneumo/hcp/who-when-to-vaccinate.html

[Last accessed March 18, 2019]


Chapter 7: Patient Education

Patient education is an equally crucial factor as the other pillars of asthma control

which are: (1) accurate diagnosis, level of severity assessment and asthma control

monitoring; (2) control of environmental triggers and comorbid conditions affecting

asthma; (3) highly effective pharmacologic therapy.1 For the past three decades,

guidelines advocated for the provision of Guided or Supported Asthma Self-

Management Education to patients and their caregivers because of its evidence-based

effectiveness in asthma outcomes. Despite global recommendations, its impact on

asthma care has not been fully realized because of suboptimal use in clinical practice.

Factors identified as barriers for its use or implementation include: time constraints,

lack of training of the asthma education providers, lack of belief of patient’s ability to

self-manage, and lack of confidence completing asthma management plans.2

What is Guided Self-Management Education and its impact on asthma

outcomes?

Guided or Supported Self-Management Education is an individualized, dynamic,

continuous, progressive, sequential and regular educational process that emphasizes

on patient’s involvement to take responsibility in his or her own care. It enhances

self-efficacy in symptom monitoring, treatment and prevention. It is achieved

through physician-caregiver-patient collaboration at all points-of-care. The family

and other caregivers are oriented on the treatment plan designed by the patients

with the guidance of the physician. It is tailored to the literacy level, cultural beliefs

and practices of the patient.1

What are the core components of guided self-management education

program?

An asthma self-management education program integrates the four components of

Guided Asthma Self-Management Education. The following core asthma information

and technical skills will be taught, reviewed, refined and reinforced on every patient’s

clinic visit.1

1. Basic facts about asthma (natural history of disease, signs and symptoms,

triggers)

2. What defines well-controlled asthma and patient’s current level of control

3. Role of medications


4. Skills (e.g., inhaler technique, use of valve holding chamber or spacer; and

self-monitoring (peak flow meter use or based on symptom diaries)

5. When and how to handle signs and symptoms of worsening asthma; when and

where to seek care

6. Environmental exposure control measures

7. Develop an active partnership with the patient

8. Provide a written action plan

What are the components of a written asthma action plan?

The following are included in the action plan:

1. Daily management, which includes:

a. Medicines to take daily (medication names and doses)

b. Actions to take to control and avoid asthma triggers

2. Recognizing and handling worsening asthma

a. Signs, symptoms and peak flow values that indicate worsening asthma

b. Medications and dosages to take in response to worsening symptoms

c. Signs, symptoms and peak flow values that indicate the need for urgent medical

attention

d. Emergency telephone numbers of the physician, emergency department and

service to rapidly transport the patient to medical care

Regular review by a healthcare provider is a vital management skill in asthma

education. Asthmatic patients should collaborate with his/her healthcare provider.

The healthcare provider review includes the following components:1

1. Elicit questions and concerns. Discuss and provide additional educational

messages. Patient may be referred to a trained asthma education provider, if

available.

2. Assess asthma control

a. Review patient’s level of symptom control and risk factors

b. Elicit episodes of flare up and identified contributory factors. Evaluate if the

patient’s response or actions taken were appropriate. Elicit if a written asthma

action plan was used to guide the actions taken.

c. Review symptom and/or peak expiratory flow diary, if the patient keeps one

d. Assess comorbidities

3. Assess treatment issues

a. Watch the patient use their inhaler. Re-checking and correcting inhaler

techniques using a standardized checklist leads to improved asthma control.f

(Evidence A)

b. Assess medication adherence and identify barriers

c. Assess adherence with other interventions e.g., smoking cessation


d. Review the asthma action plan and update it if the level of asthma control or

treatment has changed.

By modifying the patient’s therapy based on home monitoring of disease severity,

patients can improve control of their asthma and avoid visits to acute care facilities.

PEF monitoring has been advocated as useful in detecting asthma exacerbations

especially in those who have difficulty in recognizing changes in their symptoms.

Benefits are greater when the asthma action plans are based on percentage personal

best peak flow than percentage predicted peak flow.1 (Evidence A) The 2-3 action

points action plan (peak flow <80% best: increase inhaled steroids; peak flow <60%

best: commence oral steroids and seek medical advice; and peak flow <40% best:

seek urgent medical advice) is consistently effective in reducing admissions and ER

visits than the use of 1-action point or 4-action points plan.1

Whether in written instructions or paper template or electronic plans, the action

points in the asthma action plan should be agreed upon by the patient, caregiver and

primary care physician. It should be reviewed regularly by the physician and updated

accordingly. The family and caregiver should be oriented to the treatment plan for

home education reinforcement.

Who should deliver asthma education?

Provision of asthma education is usually practiced by the primary care physicians or

subspecialists in a clinic setting during clinic visits or hospital setting during

hospitalization due to exacerbation. Trained and certified asthma educators such as

respiratory therapists, nurse practitioners, clinical pharmacists or community health

workers may be as effective in providing asthma education and improving asthma

actions. 1,3, 4, 5, 6,

What are the effective methods of asthma information delivery?

High-impact learning is always targeted in any information delivery situation.

Effective information delivery also hinges on the asthmatic’s ability to sort out

questions and arrive at answers themselves rather than being told. Asthmatics learn

best when they are able to connect what they know (head) with how they feel (heart)

and the skills they need to do what is needed (hands). Learning should be

experienced, not taught.

What are the effective strategies for asthma adherence management?

Andrew Weinstein7proposed an approach composed of four sequential adherence

management principles to enhance asthma guidelines, which could be adapted in the


local clinical practice:

1. Objective adherence monitoring (e.g., self-reports, caregiver reports, canister

weight, electronic monitoring devices) and asthma control monitoring (e.g.,

Asthma Control Questionnaire and Asthma Control Test)

2. Identification of the reasons for non-adherence

3. Delivery of an individually-tailored strategy to address each specific cause of

non-adherence

4. Use of motivational interviewing (MI)8,9 communication skills to enhance the

delivery of each strategy.

References

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention.2018.

Available from www.ginasthma.org [Accessed:30 April 2018].

2. Roberts, NJ, Younis, I, Kidd, L, Partridge, MR, Barriers to the implementation of self -management

support in long term lung conditions. London J Prim Care. 2012; 5(1): 35-47.

3. Mishra, R, Kashif, M, Venkatram, S, George, T, Luo, K, Diaz-Fuentes, G. Role of adult asthma

education in improving asthma control and reducing emergency room utilization and hospital

admissions in an inner city hospital. Can Respir J 2017;49:1-10.

4. Williams, D, Portnoy, J, Meyerson. K.Strategies for improving asthma outcomes: a case-based

review of successes and pitfalls. J Manag Care Pharm. 2010; 16(1c): S3-S17.

5. Klijn, SL, Hiligsmann, M, Evers, SMAA, Roman-Rodriguez, M, van der Molen,T, van Boven.,JFM.

Effectiveness and success factors of educational inhaler technique interventions in asthma and COPD

patients: a systematic review. NPJ Prim Care Respir Med 2017; 27(24): 1-10.

6. Krieger,J, Song,L, Philby,M. Community health worker home visits for adults with Uncontrolled

asthma: the HomeBASE trial randomized clinical trial. JAMA Intern Med. 2015; 175(1): 109-17.

7. Weinstein,AG. The potential of asthma adherence management to enhance asthma guidelines. Ann

Allergy Asthma Immunol 2011; 106(4): 283-91.

8. Lavoie KL, Moullec G, Lemiere C, Blais, L, Labrecque, M, Beauchesne, MF, Peppin, V, et al. Efficacy

of brief motivational interviewing to improve adherence to inhaled corticosteroids among adult

asthmatics: results from a randomized controlled pilot feasibility trial. Patient Prefer Adherence.

2014; 8:1555-69

9. Román-Rodríguez, M, Ibarrola-Ruiz,L, Mora, F, Plaza, V, Sastre, J, Torrego,A, Vega, JM, et.al.

Motivational interviewing for adherence: post-training attitudes and perceptions of physicians who

treat asthma patients. Patient Prefer Adherence. 2017; 11: 811–20


CHAPTER 8: SPECIAL CONSIDERATIONS

There are certain types of patients with asthma who may be more difficult to manage,

and/or may require closer attention because of coexisting co-morbid conditions such

as sinus disease, obesity, food allergy, anaphylaxis, or during special circumstances

such as pregnancy, menstruation, surgery, work-related asthma, stress, GERD-

related asthma, aspirin-exacerbated asthma, difficult-to-treat asthma.

PREGNANCY AND ASTHMA

It is considered as the most common respiratory condition of pregnancy complicating

4%–8% of pregnancies with increasing healthcare utilization and cost.1, 2, 3, 4 Different

regions of the world have varying data on the incidence of asthma in pregnancy.

Values range from 2 to 13%, which mimics the incidence of asthma in the

community.3, 4, 5 In the Philippines, there is a lack of local data on the incidence of

asthma in pregnant patients.

What is the course of asthma during pregnancy?

The “rule of thirds” has always been cited when the course of asthma in pregnancy

is discussed, that is, one-third of patients will remain stable, one-third will have

symptomatic improvement, and in one-third of pregnant patients, their asthma will

deteriorate.6 Unfortunately, it may not always be easy to predict which patients will

go into which group.

Two factors seem to correlate significantly with the course of asthma during

pregnancy: the severity of a patient’s asthma before she became pregnant, and the

use of asthma medications.7 It should be noted that even patients with “mild” pre-

pregnancy asthma may deteriorate significantly during pregnancy.8

Asthma exacerbations usually occur towards the second half of pregnancy. In a

recent prospective cohort study, 50% of all exacerbations and losses of control were

noted to occur before 20 weeks of gestation.8 The risk appears to be increased in

smokers (or ex-smokers), in those who are obese, and in those who are infected with

respiratory viruses, and whose asthma is uncontrolled before their pregnancy.9


What are the possible adverse maternal and fetal outcomes in

pregnant asthmatics?

Asthma is strongly associated with preeclampsia, placental abruption and placenta

previa, and obstetric hemorrhage.3,10 Pregnant women with asthma are at a

significantly increased risk of a range of adverse perinatal outcomes, including low

birthweight, small for gestational age (SGA), preterm labor and delivery.3,10,11

Evidence pointed to a direct correlation between the severity of the asthma, the

higher occurrence of exacerbations, and the increase in the incidences of these

adverse events on the baby. Evidence also revealed that optimal treatment of the

asthma reduced these risks, including exacerbations, significantly.3,10 12 The risk of

cesarean delivery was higher for patients with severe asthma as compared to those

with mild asthma.12 Published studies were conflicting in terms of congenital

malformations in asthma patients who took OCS in the first trimester of pregnancy. 13,14,15 Exacerbations, use of bronchodilators, or use of ICS were not associated with

congenital malformation.3

Asthma in pregnancy has also been associated with multiple comorbid conditions

such as higher risk of gestational diabetes 12, pulmonary embolism16, and greater

frequency and severity of respiratory viral infections. 17

How is asthma diagnosed in pregnancy?

The usual parameters for the diagnosis of asthma in the general population (as

discussed in an earlier chapter) are, for the most part, applicable to the pregnant

asthmatic patient. A problem may arise in a pregnant patient who was never

previously diagnosed with asthma, and who, during her pregnancy, starts

manifesting with symptoms of shortness of breath. The “breathlessness” associated

with a progressively enlarging abdomen may be difficult to differentiate from dyspnea

caused by obstructive airway disease. Spirometry is still the gold standard for the

diagnosis. Peak flow variability may also be helpful. The use of fraction of exhaled

nitric oxide (FENO) has been proposed in the management.18

What medications can be prescribed for pregnant asthmatics?

The ultimate goal of asthma therapy in pregnant patients is to protect both mother

and baby by achieving asthma control. This can be accomplished by prescribing the

same medications as one would a non-pregnant patient. Although there is a general

concern about any medication use in pregnancy, the advantages of actively treating


asthma in pregnancy markedly outweigh any potential risks of usual controller and

reliever medicaitons.19,20 (Evidence A)

The pregnant asthmatic should be prescribed an inhaled corticosteroid, the mainstay

of controller therapy. Majority of the studies have declared that ICS are safe in

pregnancy, and regular use does not result in complications in either the mother or

the fetus. It has been shown that regular use of ICS as maintenance in achieving

asthma control has led to a lower incidence of complications and adverse outcomes. 14,21,-23 if asthma is well controlled throughout pregnancy, there is little or no

increased risk of adverse maternal or fetal complications. 9,20 Inhaled corticosteroids

reduce the risk of exacerbations of asthma during pregnancy, and cessation of ICS

during pregnancy is a significant risk factor for exacerbations. 19.20.21 (Evidence A)

Budesonide is the ICS with the most published human gestational safety data and is

the preferred ICS for use in pregnant patients. 22 There are no published studies on

safety data for the other ICS preparations and there are no data to show that they

are not safe.22 Therefore, if a patient is well controlled on an ICS other than

budesonide prior to getting pregnant, it may be more beneficial to just continue the

current ICS rather than shift to budesonide especially if changing formulations may

jeopardize asthma control.21,22.

Inhaled SABAs are the rescue medications of choice fot the pregnant asthmatic.

Inhaled albuterol (salbutamol) has been the most extensively studied SABA, and

almost all the researches point to a very good safety profile9, 11, 13.

Patients not fully controlled on ICS alone may be given LABA in combination.23 The

safety profile of salmeterol and formoterol are expected to be the same as albuterol

or salbutamol. LABAs should always be given in combination with ICS and never as

monotherapy.20,22,24

Montelukast and zafirlukast have been found in most studies to be safe although

data on their use in pregnancy are more limited.25 OCS is recommended when

indicated for the management of severe asthma during pregnancy.24

What is the approach to the management of the asthma exacerbation in

pregnancy?

Asthma exacerbations are one of the most common medical problems in pregnant

women and can have the most significant impact on fetal morbidity and mortality.

Treatment of exacerbations is exactly the same in the pregnant and non- pregnant

patients. However, a pregnant patient with an acute exacerbation of asthma will


require more intensive monitoring and management. What is vital is that the airway

obstruction be reversed as quickly as possible so that both mother and fetus will

have adequate oxygenation. The patient should be given systemic steroids and

inhaled beta2-agonists. The cause of the exacerbation also has to be addressed.16, 17

Acute severe asthma in pregnancy is an emergency and should be treated vigorously

in hospital. Patients in the third trimester and who are very symptomatic may have

to be admitted to the hospital for close monitoring. The avoidance of maternal and

fetal hypoxia is of primary importance and this requires aggressive treatment of with

SABA, oxygen and early administration of systemic corticosteroids.20 It is

recommended that high flow oxygen be delivered immediately to maintain saturation

above 95 %.26

Acute exacerbations are uncommon during labor and delivery, perhaps due to

endogenous steroid production. The usual controller medications should be taken,

with reliever if needed. Pregnant asthmatics on oral steroids at a dose exceeding

prednisolone 7.5 mg per day for more than 2 weeks prior to delivery should receive

parenteral hydrocortisone 100 mg 6-8 hourly during labor.24,26,27

Caesarian section should be reserved for the usual obstetric indications. If anesthesia

is required, regional blockade is preferable to general anesthesia.24,26

MENSTRUATION AND ASTHMA

What is the association of menstruation with asthma?

Some females with asthma experience an increase in their symptoms, or worse, an

increased incidence of exacerbations during the peri-menstrual period, a condition

that is known as peri-menstrual asthma. Asthma deterioration has been described in

the periovulatory phase, in the middle of the preovulatory or luteal phase, and more

frequently in the pre-menstrual phase, an entity defined as pre-menstrual asthma

(PMA). There is no clear definition of PMA28, although it is considered to be a cyclical

deterioration of asthma during the premenstrual (luteal) phase, sometimes including

the first few days of the menstrual cycle.29

The reports on the incidence of PMA vary, ranging from 17 % to 44 %, due to the

fact that some studies rely on purely subjective data from the patients, while others


require objective parameters such as lung function studies.28,30 The precise

prevalence is difficult to determine due to the lack of explicit diagnostic criteria and

appropriate epidemiological surveys.31 These patients with PMA represent a certain

asthma phenotype that should be recognized, as there is an increased incidence of

asthma related ER visits, hospitalizations, and intubation in this group.32

What causes pre-menstrual asthma (PMA)?

The etiology of PMA remains unknown.30,31-35,36 There is significant fluctuation in the

levels of many hormones, including luteinizing hormone, follicle stimulating hormone,

estradiol progesterone and testosterone, during the menstrual cycle. The fluctuation

in the levels of these hormones is thought to contribute significantly to the

pathogenesis of PMA.

How is pre-menstrual asthma (PMA) diagnosed?

The cyclical deterioration in PMA is defined as a worsening of asthma symptoms

and/or deterioration of lung function tests, such as a decrease of ≥20-40% in the

PEF.36 Women with PMA are older, have more severe asthma, a higher body mass

index, a longer duration of asthma and a greater likelihood of aspirin-sensitive

asthma.37 They more often have dysmenorrhea, shorter menstrual cycles and longer

menstrual bleeding.37 The patients with PMA had significantly higher depressive

symptoms and water retention than other asthmatic patients.38

How is premenstrual asthma (PMA) treated?

As in any patient with asthma, the mainstay of treatment is still regular ICS-LABA,

with a SABA as rescue medication. However, the hormonal imbalances that have

been proven to precipitate the worsening of the symptoms also have to be evaluated.

Other associated comorbid conditions also have to be addressed.

Can pre-menstrual asthma (PMA) be prevented?

Since PMA is significantly associated with fluctuations in hormones during the

menstrual cycle, stabilizing estradiol and progesterone levels and reducing the

hormone-free intervals with oral contraceptives may be considered.34


SURGERY AND ASTHMA

What are the peri-operative risks of surgery in asthmatic patients?

At present, there is no hard evidence of increased peri-operative risk for the general

asthma population.39 There are asthmatic patients, however, who are at risk for

complications during and after surgery and these complications include

bronchoconstriction, hypoxemia, possible hypercapnia, impaired cough reflex,

possible atelectasis, and respiratory infection.40 While an increased risk for surgery

exists for patients with COPD,39 this may also apply to asthma patients with reduced

FEV1 or an incomplete reversibility of airway obstruction (IRAO) despite optimal

treatment and the absence of a significant smoking history. Therefore, the incidence

of severe peri-operative bronchospasm in people with asthma although admittedly

low, may be significant, even life threatening.41

What is the management of asthmatic patients undergoing surgery?

For elective surgery, patients with asthma should be evaluated at least one week

prior surgery to allow time for modification of treatment, if necessary, especially for

those patients who are scheduled for procedures with a high risk of postoperative

pulmonary complications. Postoperative pulmonary complications are most common

following thoracic surgery, upper abdominal surgery, open aortic aneurysm repair,

neurosurgery, and surgery on the head and neck. Meticulous attention should be paid

pre-operatively to achieving good asthma control, especially for patients with more

severe asthma, uncontrolled symptoms, significant exacerbation history (more than

one exacerbation per year), or fixed airflow limitation.41

The following actions are recommended to reduce the risk of complications during

surgery:40

(1) Before surgery, review the level of asthma control, medication use (especially

oral systemic corticosteroids within the past 6 months), and pulmonary

function.

(2) Provide medications before surgery to improve lung function if lung function is

not well controlled. A short course of oral systemic corticosteroids may be

necessary.

(3) For patients receiving oral systemic corticosteroids during the 6 months prior


(4) to surgery and for selected patients on long-term high-dose ICS, give 100 mg

hydrocortisone every 8 hours intravenously during the surgical period, and

reduce the dose rapidly within 24 hours after surgery

For patients requiring emergency surgery, the risks of proceeding without first

achieving good asthma control should be weighed against the need for immediate

surgery. As stated above, patients taking long-term high-dose ICS, or those who

have received OCS for more than 2 weeks during the previous 6 months, should

receive hydrocortisone peri-operatively as they are at risk of adrenal crisis in the

context of surgery.42 For all patients, maintaining regular controller therapy

throughout the peri-operative period is important.

Vigilant monitoring of the asthmatic patient is of primary importance in preventing

perioperative pulmonary complications. Proper preoperative evaluation of disease

level and medical compliance with prescribed medication regimens, along with

perioperative strategies for prevention of bronchospasm decrease postoperative

pulmonary complications in asthmatics.43

Several guidelines on the management of asthma are available. One can easily refer

to such publications as the Expert Panel Report 3 (EPR-3) on the diagnosis and

management of asthma and the American College of Physicians report on risk

assessment for and strategies to reduce perioperative pulmonary complications for

patients undergoing non-cardiothoracic surgery.44,45 Also, such scoring systems as

ARISCAT can guide one to assess more effectively and systematically an asthmatic

patient undergoing surgery.46

SINUS DISEASE (RHINITIS, SINUSITIS, NASAL POLYPS)

AND ASTHMA

Is there a relationship between asthma and allergic rhinitis, sinusitis, nasal

polyps ?

The ‘united allergic airway’ is a theory that connects sinonasal disease, specifically

allergic rhinitis (AR), chronic rhinosinusitis (CRS), nasal polyps, with asthma in which

seemingly disparate diseases, instead of being thought of separately, are instead

viewed as arising from a common atopic entity.47,48 Literature supports the

relationship but there is no direct evidence of causality.49


Epidemiological evidence suggests a strong relationship between AR and asthma. AR

can occur in more than 75% of patients with asthma, whereas asthma can affect up

to 40% of patients with AR.50 Both diseases, which are IgE mediated, can be triggered

by similar allergens, including mold, animal dander, and house-dust mites.51,52

Temporally, AR often occurs before the onset of asthma.

AR is a risk factor for asthma, and its presence is related to asthma severity.47

Patients with nasal symptoms appear to experience worse asthma control.53. Overall,

studies suggest both children and adults with comorbid rhinitis and asthma have

more frequent physician’s visits, emergency room visits and hospital admissions for

asthma, and higher asthma-related drug expenses.54,55

There is also a common pathophysiological relationship between AR and asthma with

four mechanisms postulated to account for this relationship.56 First, with AR, nasal

function may be partially or completely lost as the congestion forces the patient to

become a mouth breather. This may predispose to bronchospasm caused by cooling

and drying in the airways, as what occurs with obligate mouth breathing during

vigorous activity. Second, during an exacerbation of AR, the inflammatory products

from the upper airways may be aspirated directly into the lower airways. Third, nasal

inflammation may result in local cytokine release into the bloodstream, which

eventually causes bronchoconstriction in the lower airways. Fourth, a nasal–bronchial

reflex may exist, where histamine and bradykinin stimulate the afferent nasal sensory

nerve which sends a neural signal that travels to the central nervous system and

activates the efferent vagus nerve, resulting in bronchial smooth muscle

hyperreactivity.56

A frequent association between BHR and rhinitis has also been noted and patients

suffering from AR frequently, in up to 80% of cases, manifest with bronchial

hyperresponsiveness (BHR).57

The etiology for the connection between asthma and AR is likely multifactorial.

Although nasal blockage and aspiration of nasal contents have long been accepted as

contributing factors, there is a growing body of evidence that suggests that a

systemic response plays an important role in the AR–asthma relationship.47

With respect to CRS, it has been reported that around 90% of patients with mild to

moderate asthma, and almost 100% of those with severe asthma, have radiological

abnormalities of the sinuses.59 There is evidence supporting an association between

rhinosinusitis and asthma, although, it appears less clear whether CRS is a direct

trigger for asthma or the two conditions are simply manifestations of a common


underlying process.57 Possible mechanisms for this relationship include naso-

pharyngo–bronchial reflexes, postnasal drip, abnormal breathing and the local

production of inflammatory mediators that trigger pulmonary inflammation.58

It has been reported that 20%–60% of patients with CRS with nasal polyps have

asthma.60,61 Chronic rhinosinusitis has been associated with both more severe and

more difficult to control asthma.61

What is the impact of treatment of sinonasal disease on asthma outcomes?

Results of a meta-analysis demonstrated that intranasal corticosteroid medications

used to treat AR significantly improve some asthma-specific outcome measures in

patients suffering from both AR and asthma but only in patients not also receiving

ICS.62 There is weak evidence that treatment of CRS may improve asthma outcomes

demonstrating only a small decrease in asthma symptoms after using mometasone

but no difference in asthma-related quality of life, lung function, or episodes of poorly

controlled asthma.63A randomized, prospective trial on patients with CRS with or

without nasal polyps and asthma. found that medical as well as surgical treatments

for CRS showed improvements in asthma status with a good correlation to the

improvement achieved in upper airway symptoms.64,65 Although the promise of

targeted biologic therapies seem encouraging, more research needs to be done to

further characterize the complex relationship between upper and lower airway

disease.49

WORK-RELATED ASTHMA

What is work-related asthma?

Work-related asthma (WRA) is a term that includes occupational asthma (OA), i.e.,

asthma that is caused by work, and work-exacerbated asthma (WEA) or work-

aggravated asthma (WAA), i.e., asthma that is worsened by work but not initially

caused by work.66.67 It has been estimated that at least 15% of adult asthma is work-

related. Some studies have reported that more than 25% of working adults with

asthma have exacerbations of asthma at work.66,67

Occupational asthma is a disease characterized by variable airflow limitation and/or

hyperresponsiveness and/or inflammation due to causes and conditions attributable

to a particular occupational environment and not to stimuli encountered outside the

workplace.68


OA refers to asthma caused by occupational exposures and can be due to sensitizers

or irritants.68 OA caused by workplace sensitizers are immunological and

characterized by WRA appearing after a latency period. It encompasses OA caused

by most high and certain low-molecular weight agents for which an allergic IgE-

mediated mechanism has been proven.68 OA caused by irritants or irritant-induced

asthma occur with or without a latency period. This category includes reactive airways

dysfunction syndrome (RADS) which may occur after single or multiple exposures to

non-specific irritants at high concentrations.69

How is OA diagnosed?

Sensitizer-induced occupational asthma should be suspected in every adult with new-

onset asthma.70 Respiratory symptoms such as dyspnea, wheezing, chest tightness,

cough, and sputum production are similar to those seen with non-work-related

asthma, however, their occurrence is usually modulated by the work-related

exposure. A latency period ranging from weeks to years after the first exposure to

the sensitizer is observed before the initial onset of work-related symptoms.

Sensitizer-induced symptoms begin variably— at the beginning of the work shift,

toward its end, or even in the evening after working hours. Improvement or even

remission typically occurs during weekends and holidays. Rhinitis often accompanies

or precedes lower respiratory symptoms, especially when high-molecular-weight

agents are the inciting factors.70

A thorough clinical and occupational history must be obtained but a compatible

history alone is insufficient for diagnosis and has a low positive predictive value.70,71

Diagnostic tests can be divided into 1) tests that confirm asthma, 2) tests that identify

that the asthma is work-related or that the workplace as the cause of the respiratory

symptoms, and 3)tests that identify the agent causing the occupational asthma.68

The best method of confirming that the asthma is work-related is measuring lung

function in relation to work exposure. This can only be done when the patient is still

exposed to the suspected cause of their symptoms, so it needs to be the first

confirmatory test.

Guidelines recommend serial measurement of PEF on days at and away from work

which is considered the best validated method with good sensitivity and specificity in

the diagnosis of work-related asthma.70 Minimum criteria are 3 weeks of usual work

exposure with measurements at least four times a day, or 8 work days and 3 rest

days with 2-hourly measurements, with treatment being kept constant.


A specific inhalation challenge (SIC) (i.e. the subject inhales the agent of concern) is

the best method of confirming the specific cause of occupational asthma when

workplace measurements are not possible or specific IgE measurements are not

available, as is the case for many low molecular weight agents. But it is not readily

available and false-positive or false-negative responses can occur. 68,70,72,73

A supervised return to work with either a workplace challenge (for those with severe

symptoms) or unsupervised PEF measurement on days at and away from work is

helpful when occupational asthma is likely and SIC is negative.68

How is WRA managed?

In contrast to non-WRA, optimal management of OA consists of primary, secondary

and tertiary prevention. Primary prevention aims to prevent sensitization to

workplace agents, thus preventing disease. This may be done by replacing known

sensitizing agents with non-sensitizers, reducing of exposure to respiratory

sensitizers by instituting occupational hygiene measures such as containment,

improved ventilation, and (as a last option) the use of personal protective equipment,

as well as worker education to enhance adherence to recommended measures.71

Secondary prevention includes early identification of workers with occupational

exposure to asthma-causing agents by means of medical surveillance (periodic

respiratory questionnaires with or without spirometry and immunologic tests) and

further investigations to confirm diagnosis and after diagnosis, removal of the

affected worker from further exposure. 71

Appropriate management after diagnosis, in addition to prevention of further

exposure when possible, involves tertiary prevention with pharmacologic

management that follows clinical-practice guidelines.71

Prevention irritant-induced asthma should include occupational-hygiene measures

that ensure the safety of workers in environments where there is the potential for

accidental exposure to irritants. General measures include containment, good

ventilation, worker education regarding safety practices, and, when other measures

are not sufficient, use of fit-tested respiratory protective devices. 71

How is work-exacerbated asthma (WEA) recognized and how is it managed?

Work-exacerbated asthma (WEA) or work-aggravated asthma (WAA) is a term used

to describe the worsening of pre-existing or coincident (adult new-onset) asthma

because of workplace exposures.74 This can manifest as an increase in frequency


and/or severity of asthma symptoms and/or increase in asthma medication required

to control symptoms on work days.

For any individual, OA and WEA are not mutually exclusive, meaning that someone

with OA can subsequently experience WEA, and vice versa.

WEA should be considered in any patient with asthma that is worsening and/or who

has work-related symptoms. The diagnosis depends on demonstrating a relationship

between work exposures and asthma exacerbations, most commonly documented by

changes in symptoms, e.g. frequency, severity, or medication use temporally related

to work and documented by serial PEF recordings.74

The goal of treatment is to minimize asthma exacerbation by reducing work

exposures and optimizing standard medical management with non-work

environmental control measures and pharmacologic treatment.75

OBESITY AND ASTHMA

Is there a relationship between obesity and asthma?

Numerous studies in the last two decades have revealed that obesity is truly an

independent risk factor for the development of asthma.76-80 There is a 2.3 fold

increased odds of developing asthma in the future in both allergic and non-allergic

obese individual with a dose- response effect: 1.7 fold increased risk for BMI 25 –

29; 2.3 fold increased risk for BMI > 30.76

Most studies have shown that females who are obese have a higher risk for

developing asthma, which suggests that hormones may play a role.81 Other studies

observed that the risk is the same for both males and females.82 There are fewer

studies in obese children citing that boys have higher risks than girls.83

Obese asthmatics (compared to non- obese patients) generally report more

symptoms and limitation of activities due to their symptoms, even if they are already

on the same therapeutic regimens as the non- obese asthmatics.84 This may partly

be due to the respiratory effects of the obesity itself, or, these patients may truly

represent a different asthma phenotype that is less responsive to medications such


as inhaled steroids and LABA.85 The mechanism behind this in not clear, but there

may be a certain phenotype of obese asthmatics who have a different type of

inflammation that is less responsive to glucocorticoids. This was mostly found in

asthma patients who were morbidly obese.

How are obese asthmatics best managed?

Weight loss as part of the management is important and has been documented to

lessen asthma symptoms, improve quality of life, decrease bronchial hyper-reactivity,

reduce markers of systemic inflammation, reduce the need for medications and

improve lung function parameters. 85-88

The mainstay of treatment is still the inhaled corticosteroid combined with a long

acting beta agonist (ICS-LABA), with a SABA as a rescue medication. A higher dosage

of ICS may be necessary, as some obese patients may show a degree of resistance

to corticosteroid treatment.86

GASTROESOPHAGEAL REFLUX DISEASE- RELATED ASTHMA

Is gastroesophageal reflux disease (GERD) more common in patients with

asthma?

There is evidence that GERD is more common in patients with asthma compared to

the general population. 89-90, 91-94

What is GERD-related asthma and what mechanisms are involved?

Because GERD and asthma are often encountered together, complex interactions

occur during which GERD may increase asthmatic symptoms or asthma may trigger

or worsen GERD.92 GERD-related asthma has been defined as asthmatic symptoms

being induced or exacerbated by gastroesophageal reflux.95

Although further research is needed in order to elucidate the mechanisms that link

GERD with asthma, postulated mechanisms on acid reflux-induced asthma include:

(1) vagal mediated reflex;89,92 (2) increased bronchial reactivity92;(3)

bronchoconstriction due to aspiration of gastric acid. 89,90,92


Findings suggest that the main mechanism was the reflex bronchospasm secondary

to acid exposure of the distal esophagus rather than direct effect of micro-aspiration

of the proximal airways.95

Asthma can also result in physiological changes that might predispose to GERD which

may be related to the hyperinflation with in an increased pressure gradient between

thorax and abdominal cavity and flattening of the diaphragm which could impair the

anti-reflux barrier and result in GERD.92 Medications taken for asthma, such as beta2-

agonists, theophylline, and high doses of oral corticosteroids which may reduce lower

esophageal sphincter pressure, may also increase acid reflux. 89,92

How is GERD-related asthma diagnosed?

In patients with confirmed asthma, GERD should be considered as a possible cause

of a dry cough.20 However, the most common classic symptoms of GERD such as

heartburn or regurgitation may not always be manifested in patients with

asthma.20,89-97 In addition, while there are many tests that can be done to work up

patients who are suspected as having GERD, there are no diagnostic gold standards.89

Current available diagnostic tests performed for GERD such as

esophagogastroduodenoscopy and esophageal pH monitoring or ambulatory

esophageal reflux monitoring have uncertain sensitivity and specificity for the

diagnosis of GERD-related asthma.96

For patients with asthma and symptoms suggestive of reflux, an empirical trial of

anti-reflux medication, such as a proton pump inhibitor or motility agent, may be

considered.20 A good response of asthmatic symptoms to PPI treatment may permit

a more confident diagnosis of GERD-related asthma.96 Failure to respond to a course

of PPI should prompt a careful re-assessment of the patient, with consideration for

specific investigations such as 24-hour pH monitoring or endoscopy as well as other

work-up for other causative factors for the persistent asthmatic symptoms.96 There

is no value in routine screening of patients with uncontrolled asthma for GERD

(Evidence A).20 Nevertheless, it is important that GERD should be assessed in

asthmatic patients who also have typical symptoms of GERD, as well as in patients

with non-atopic, refractory or difficult asthma.96

How is GERD-related asthma managed?

Proton pump inhibitors (PPIs) are the main therapeutic regimen for GERD and this is

commonly recommended for suspected GERD-related asthma. Non- pharmacologic

treatment includes: weight loss patients who are overweight or have had recent

weight gain; head of bed elevation and avoidance of meals 2–3 hours before bedtime


for patients with nocturnal GERD; avoidance of food that can trigger reflux such as

alcohol, caffeine.

In general, benefits of proton pump inhibitors in asthma appear to be limited to

patients with both symptomatic reflux and night-time respiratory symptoms.20,98,99

But patients with poorly controlled asthma should not be treated with anti-reflux

therapy unless they also have symptomatic reflux (Evidence A).20 Anti-reflux

surgery is an option for asthmatics with well-defined reflux disease, if indicated and

available, preferably done by a skilled, experienced surgeon.96

FOOD ALLERGY AND ANAPHYLAXIS AND ASTHMA

What is relationship of food allergy and anaphylaxis among asthmatics?

Although it is known that food allergic reactions can trigger lower respiratory

symptoms, food allergy generally does not present with chronic or isolated asthmatic

symptoms.100,101 But asthmatic reactions can be part of the allergic response.102

During food allergic reactions, non-specific BHR may increase.103

Although foods are rarely important triggers of asthma exacerbation, occurring in

<2% of people with asthma, coexisting asthma is a strong risk factor for more severe

food-induced allergic reactions (anaphylaxis) as well as for fatal outcome from food-

induced anaphylaxis. 20,102, 103,104 In addition, findings in some studies on both children

and adults with asthma and concurrent food allergy showed an association with worse

asthma morbidity with increased hospitalizations, ER visits and use of oral steroids

than those with asthma alone.105.106

Although any substance has the potential to cause anaphylaxis, the most common

causes of IgE-mediated anaphylaxis are: foods, particularly, peanuts, tree nuts,

shellfish and fish, cow’s milk, eggs and wheat; medications (most commonly

penicillin), and natural rubber latex. 107,108 Exercise, aspirin, non-steroidal anti-

inflammatory drugs (NSAIDs), opiates, and radiocontrast agents can also cause

anaphylaxis, but anaphylactic reactions to these agents often result from non-IgE-


mediated mechanisms. In other cases, the cause of anaphylactic reactions is

unknown (idiopathic anaphylaxis)107,109-112

How is food allergy, anaphylaxis in asthma managed?

For patients with suspected food allergy, a referral to a specialist for accurate allergy

assessment diagnosis is usually necessary.20 Treatment of food allergy involves strict

avoidance of the trigger food. Currently, there is no cure for food allergy, and

medications only manage the symptoms of disease.20

In addition to education in appropriate food avoidance strategies, patients who have

a confirmed allergy, especially food allergy, that puts them at risk for anaphylaxis

must be trained and have an epinephrine auto-injector available at all times.20,113-115.

It is especially important to ensure that their asthma is well controlled, that they

have a written action plan, and that they understand the difference between asthma

and anaphylaxis, and are assessed and seen on a regular basis.20 A multi-faceted

approach to managing this subset of patients leads to optimal care.

ASPIRIN-EXACERBATED RESPIRATORY DISEASE

What is aspirin-exacerbated respiratory disease?

Aspirin-exacerbated respiratory disease (AERD), also called NSAID-exacerbated

respiratory disease (NERD) and previously referred to as aspirin-induced asthma, is

the combination of asthma, chronic rhinosinusitis (CRS) with nasal polyposis (the

“Samter’s triad”), and acute upper and lower respiratory tract reactions to ingestion

of aspirin (acetylsalicylic acid, ASA) and other cyclooxygenase-1 (COX-1)-inhibiting

nonsteroidal anti-inflammatory drugs (NSAIDs).116

AERD occurs in approximately 7 % of adult asthmatic patients and higher prevalence

among severe asthmatics.117 It is a distinct subtype of asthma and polypoid sinus

disease characterized by greater morbidity and healthcare costs for those affected.118

AERD generally occurs due to abnormalities in mediators and expression of

arachidonic acid biosynthesis.119


How is AERD diagnosed?

The clinical presentation begins with nasal congestion and anosmia, and progresses

to chronic rhinosinusitis with nasal polyps that tend to re-grow rapidly after surgery.

Asthma and hypersensitivity to aspirin inevitably develop.119,120 Following ingestion

of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs), an acute asthma attack

develops within minutes to 1–2 hours. It is usually accompanied by rhinorrhea, nasal

obstruction, conjunctival irritation, and scarlet flush of the head and neck, and may

sometimes progress to severe bronchospasm, shock, loss of consciousness, and

respiratory arrest.121,122 AERD is more likely to be associated with low lung function

and severe asthma.118

The diagnosis of AERD can often be made clinically when all three of the conditions

that characterize AERD are present: asthma, visible nasal polyposis (or even just a

history of nasal polypectomy), and a history of a typical reaction to a nonsteroidal

anti-inflammatory drug (NSAID). Nocturnal nasal obstruction with sleep deprivation

fatigue occurs routinely in these patients. Asthma may precede the upper airway

disease or develop later. Computerized tomography (CT) or plain radiographs of the

sinuses reveal complete opacification in nearly all AERD patients. Normal imaging of

the sinuses essentially rules out the diagnosis of AERD.116

Aspirin challenge (oral, bronchial or nasal) is the gold standard for diagnosis as there

are no reliable in vitro tests.116,123 A history of asthma exacerbation following ingestion

of aspirin or other NSAIDs is highly suggestive and sometimes diagnostic.116

How is AERD managed?

The management of AERD involves guideline-based treatment of the patient's

asthma and chronic rhinosinusitis (CRS), in addition to suppression of the

consequences of abnormal leukotriene metabolism.119 Patients should avoid aspirin

or NSAID-containing products and other medications that inhibit cyclooxygenase-1

(COX-1).119

ICS are the mainstay of asthma therapy in AERD, but OCS are sometimes required;

LTRA may also be useful.124-126 An additional option is desensitization, which may be

conducted under specialist care in a clinic or hospital.119,127 Desensitization to aspirin

followed by daily aspirin treatment can significantly improve overall symptoms and

quality of life, decrease formation of nasal polyps and sinus infections, reduce the

need for OCS and sinus surgery, and improve nasal and asthma scores.124


STRESS AND ASTHMA

Does stress contribute to worsening of asthma symptoms?

There is some evidence that different stressors can worsen asthma. But many factors

have to be taken into consideration: the timing, chronicity, and even the quality of

the stress.128 Acute stress may not be a significant precipitant of asthma attacks129,

however, chronic stress seems to play a more important role128. Included as

significant stressors are the following:

- Quality of life: Studies showed an inverse relationship between the socioeconomic

status ad pulmonary function in children. Immigrant status and poverty also

showed some correlation with increased frequency of emergency room visits

among wheezing infants

- Psychosocial status of patients: Severe psychological stressors were found to

significantly increase the risk of asthma if there was also chronic stress

- Environmental stressors: including noise and violence

- Family or caregiver stressors: Presence of even minor psychiatric disorders in

mothers was significantly associated with increased incidence of asthma in their

children

Several factors have been cited as contributing to the worsening of asthma due to

stress.128,130A dysfunctional HPA axis resulting in less cortisol production in asthmatic

patients and/or cortisol insensitivity, along with the promotion of the number of

eosinophils in blood and sputum and cctivation of mast cells by corticotropin releasing

hormone (CRH), is a proposed mechanism.

Another proposed mechanism is the occurrence of changes in the methylation and

expression of genes that regulate behavioral, autonomic, neuroendocrine and

immunologic responses to stress. There are “susceptibility genes” that predispose

chronically stressed patients to worsening of asthma symptoms.131

It has also been theorized that chronic stress may result in a new “homeostasis” with

a short term parasympathetic rebound or shifts in the balance between the

sympathetic and parasympathetic systems.129

How is asthma worsened by stress managed?

The most important mainstays in the treatment of any asthma patient are:

maintenance inhaled corticosteroid, and short acting beta2- agonists used as rescue


medications. Stress, however, may contribute to persistence of symptoms by

reducing response to these medications. It has been theorized that chronic stress

may result in downregulation of glucocorticoid receptor expression and function.129

Aside from the pharmacologic treatment, other interventions may be attempted to

address the stress, which may be contributing to the persistence/ worsening of

symptoms. Several of these interventions have been studied: written emotional

disclosures132, muscle and mental relaxation133 and relaxation breathing

techniques.134 However, all these interventions should be done in conjunction with

the regular medications for asthma, and not as stand- alone treatments.

DIFFICULT-TO-TREAT ASTHMA

How is difficult-to-treat asthma differentiated from severe asthma?

Difficult-to-treat or simply termed ‘difficult’ asthma is asthma that remains

uncontrolled despite treatment with medium or high-dose inhaled corticosteroids

plus a second controller or those requiring maintenance oral corticosteroids. 20,135

Uncontrolled asthma in this context is defined as at least one of the following: (1)

Poor symptom control : ACQ >1.5, ACT < 20 or not well controlled by GINA

guidelines; (2) Frequent exacerbations : two or more bursts of systemic

corticosteroids (>3 days each) in the previous year; (3) Serious exacerbations : at

least one hospitalization, ICU stay, or mechanical ventilation in the past year; (4)

Airflow limitation : FEV1 < 80% predicted (in the face of reduced FEV1/FVC)

following a withhold of both short- and long-acting bronchodilators.20,135,136 Patients

who do not meet the criteria for uncontrolled asthma, but whose asthma worsens on

tapering of corticosteroids, will also meet the definition of severe asthma.20,135

Individuals with difficult-to-treat asthma often have ongoing modifiable factors such

as poor inhaler technique, poor adherence, ongoing allergen exposure or

comorbidities that interfere with achieving good asthma control.20,135 As such,

difficult asthma patients are those in whom appropriate diagnosis and/or treatment

of contributory factors and comorbidities result in improvement of their current

condition.20,135


Severe asthma, on the other hand, is considered a subset of difficult-to-treat

asthma, and includes individuals with uncontrolled asthma despite adherence with

maximal optimized therapy and treatment of contributory factors, or that worsens

when high-dose treatment is decreased.20,135

What is the approach to the diagnosis of difficult-to treat asthma?

An initial step in the evaluation is to determine whether the diagnosis of asthma has

been confirmed. A careful history and physical examination should be done to

identify whether the pattern of signs and symptoms are typical of asthma or more

likely due to an alternative diagnosis. Confirmation of the asthma diagnosis can be

made through objective measures such as spirometry to assess baseline lung

function and evidence of variable expiratory airflow limitation. There may be

persistent airflow limitation in those with long-standing asthma and a specialist

advice should be obtained if the history is suggestive of asthma but the diagnosis

cannot be confirmed by spirometry.20

The next step is to assess whether modifiable risk factors that contribute to poor

asthma outcomes are present. A review of treatment adherence and inhaler

technique is required because incorrect inhaler use and poor adherence are the most

common reasons for failure to achieve good asthma control. An investigation for

persistent environmental exposure to tobacco smoke, allergens or toxic substances

should also be done. Ongoing triggers, if present at home or at the workplace, should

be addressed and removed whenever possible. The presence of comorbidities that

can contribute to poor asthma control should be investigated according to clinical

suspicion. Medication side-effects, local or systemic, should be evaluated as these

may contribute to poor quality of life and increase the likelihood of poor adherence.20

When should referral to a specialist or severe asthma clinic be considered?

A referral may be done at any stage of the evaluation but it is recommended that

patients presenting with “difficult asthma” have their asthma diagnosis confirmed

and be evaluated and managed by an asthma specialist for more than 3 months.

Referral to a specialized center where patients can undergo a systematic evaluation,

resulted in 30–50% of patients previously called severe asthma being initially classed

as difficult-to-control.135

Indications for early referral to a specialist or severe asthma clinic are20:

• There is difficulty in confirming the diagnosis of asthma

• The patient has frequent urgent healthcare utilization

• The patient needs frequent or maintenance oral corticosteroids


• Occupational asthma is suspected

• Presence of food allergy or anaphylaxis

• Clinical features that suggest coexisting or complication bronchiectasis

• Symptoms suggestive of an infective or cardiac cause

• Presence of multiple comorbidities

What is the approach to the management of difficult-to-treat asthma?

Addressing problems of incorrect inhaler technique and poor treatment adherence

should be prioritized in patients with difficult-to-treat asthma. These factors are also

found in severe asthma but in most difficult-to-treat asthma patients, adherence and

health outcomes may be improved with a comprehensive adherence-promoting

intervention that includes patient education and behavioral modification. It is

important to ensure that the inhaler is suitable for the patient and that the inhaler

technique is checked, corrected and re-checked at each clinic visit. Patient education

is important and clinicians should empower patients to make informed choices about

their medicines and individualized interventions to manage non-adherence should

be developed.20

Comorbidities when present, such as obesity, GERD, chronic rhinosinusitis, OSA,

should be managed appropriately. Non-pharmacologic management strategies

deemed relevant, such as smoking cessation, physical exercise, healthy diet, weight

loss, counseling, breathing exercises, mucus clearance techniques, allergen

avoidance, may be implemented.20

The pharmacologic treatment of difficult-to-treat asthma both in adults and children

still relies heavily on the maximal optimal use of corticosteroids and bronchodilators,

and other controllers recommended for moderate-to-severe asthma. A switch to ICS-

formoterol maintenance and reliever therapy or non-biologic add-on therapy to ICS

such as LABA (if not already using ICS+LABA combination) or anti-muscarinic agents

(i.e.tiotropium)137,138 or other controllers may be options.20

A trial of high-dose ICS may be instituted since some patients may respond to higher

doses of ICS than are routinely recommended for general use (Evidence B).

However, this carries the risk of systemic side-effects so stepping down slowly at 3–

6 month intervals after some months dose optimization is recommended (Evidence

D).136


How is treatment response of difficult-to-treat asthma assessed and

addressed?

The response to treatment includes a review of the following: symptom control

(symptom frequency, reliever us, night waking due to asthma, activity limitation),

exacerbation frequency, medication side-effects, inhaler technique, adherence, lung

function, patient satisfaction and concerns.20

If asthma is well-controlled, consider stepping down treatment. If the symptoms and

exacerbations remain well-controlled despite stepping down treatment, the patient

does not have severe asthma and optimal management should be continued.20

If asthma symptoms become uncontrolled or an exacerbation occurs when high-dose

treatment is stepped down, the diagnosis of severe asthma is confirmed. The

patient’s previous dose should be restored to regain good asthma control and a

referr0al to a specialist and/or to a severe asthma clinic should be done.20

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APPENDIX A

Asthma Control Test


APPENDIX B

How to control things that make your asthma worse Tobacco smoke ▪ Ask medical advice how to quit smoking.

▪ Do not allow smoking in your home, car, or around you.

Dust Mites ▪ Encase your mattress and pillows in a special dust mite-proof

cover.

▪ Wash the pillow, sheets and blankets each week in hot water

(>55C) to kill the mites.

▪ Cooler water with detergent and bleach can also be effective.

▪ Reduce indoor humidity to 30 - 50 % by using air conditioners.

▪ Do not lie or sleep on cloth-covered cushions or furniture.

▪ Remove carpets laid on concrete.

▪ Keep stuffed toys out of bed, or wash the toys weekly in hot

water or in cooler water with detergent and bleach.

▪ Prolonged exposure to dry heat or freezing can kill mites but

does not remove allergen.

Animal Dander ▪ Keep animals with fur or hair out of your bedroom or home, or

keep the bedroom door closed.

Cockroach ▪ Keep all food out of your bedroom.

▪ Keep food and garbage in closed containers.

▪ Use poison baits, powder, gels, or paste or traps.

Vacuum Cleaning ▪ Get someone else to vacuum for you once or twice a week.

Indoor mold ▪ Fix leaking faucets, pipes, or other sources of water.

▪ Clean moldy surfaces.

▪ Dehumidify basements.

Pollen and outdoor

mold

▪ Stay indoors with windows closed during midday and

afternoons.

Smoke, strong odors

and sprays

▪ Do not use wood-burning stove, kerosene heater, unvented gas

stove, or heater.

▪ Stay away from perfumes, sprays, talc powder, paints and

particle board with strong odor.

Exercise or sports ▪ Ask for medical advice if you have asthma symptoms when you

are active or during exercise.

▪ Take your reliever medication before you exercise.

▪ Do warm up before you exercise.

▪ Do not play hard outside when the air pollution or pollen levels

are high.

Sulfites in foods ▪ Do not drink beer or wine or eat shrimp, dried fruit or

processed potatoes.

Cold air ▪ Cover nose and mouth with a scarf on cold or windy days.

Cold medicines,

aspirin and eye drops

▪ Ask for medical advice if you have asthma symptoms when you

take these medications.


APPENDIX C

How to use your peak flow meter

A peak flow meter is a device that measures how well air moves out of your lungs. The peak flow meter may tell you if there is narrowing in the airways hours or days before you have asthma symptoms. The peak flow meter also can be used to help you and your doctor:

✓ Learn what makes your asthma worse ✓ Decide if your treatment plan is working well

✓ Decide when to add or stop medicines

Process 1. How to Use Your Peak Flow Meter

Step 1. Move the indicator to the bottom of the numbered scale.

Step 2. Stand up.

Step 3. Take a deep breath, filling your lungs completely.

Step 4. Place the mouthpiece in your mouth and close your lips around it. Do not put your

tongue inside the hole.

Step 5. Blow out as heard and fast as you can in a single blow.

Process 2. Find Your Personal Best Peak Flow Number

Your personal best peak flow number is the highest peak flow number you can achieve over a

period of 2 weeks when your asthma is controlled. Your treatment plan will be based on your

own personal best peak flow number.

Take and record your peak flow readings in your asthma diary:

✓ At least twice a day for 2 to 3 weeks ✓ When you wake up and in the late afternoon or early evening

✓ 15 to 20 minutes after taking your inhaled ‘quick relief’ medicine ✓ As instructed by your doctor

Process 3. The Peak Flow Zone System

Once you know your personal best peak flow number, your peak flow numbers are put into

zones. This will help you know what to do when your peak flow number changes.

GREEN ZONE (GOOD CONTROL): (more than _____ L/min [80 % of your personal best number]).

Action: Take your maintenance medications.

YELLOW ZONE (CAUTION): (between ___ L/min and ___ L/min [50 % to less than 80 % of your personal

best number]).

Action: If you remain in the yellow zone after several measurements of peak flow, take your inhaled reliever

medicine. If you continue to remain in the yellow zone, ask your doctor if you need to change or increase

your daily controller medication.

When PEF increases 20 % or more when measured before and after taking an inhaled short acting beta2-

agonist: Action: Talk to your doctor about adding medications to control your asthma better.

RED ZONE (MEDICAL ALERT): (below ___ L/min [less than 50 % of your personal best number]).

Action: Take an inhaled short acting beta2-agonist right away. Call your doctor or emergency room or go

directly to the hospital emergency room.


APPENDIX D

SAMPLE OF ASTHMA ACTION PLAN (Filipino translation*)

Petsa: __________

Pangalan: _____________________________________ Kapanganakan: ___________

Doktor: _______________________________________

• Gamot ay hindi nakakatulong o nakakaginhawa

• Lumalalal ang hirap ng paghinga

• Hindi na makatrabaho o makagalaw

• Nahihirapan ng magsalita PEAK FLOW: • Mas mababa sa 50% ng pansariling

pinakamataas na peak flow (personal best): ______________________

RED ZONE

‘STOP’

TIGIL Huming i ng tu long

• Kaagad ng tumawag sa iyong doctor o pumunta na sa ‘emergency room’(ER) ng pinakamalapit na ospital.

• Kung meron oral steroid sa bahay, uminom nito :___________________________

papunta sa ospital

• Ituloy ang paggamit ng ‘quick relief’ na gamot _______________________________

habang papunta sa ER

• Ang mga sintomas ng hika ay maaaring mabilis na lumala. Kung may pagdududa, mabuti nang kumonsulta kaagad sa doktor.

• Madaling huminga • Hindi inuubo • Walang halinghing sa paghinga • Hindi kapos sa paghinga • Walang hirap magtrabaho, maglaro at matulog • Gumagamit ng quick relief na gamot na mas

mababa sa dalawang beses sa isang linggo PEAK FLOW: • 80-100% ng pansariling pinakamataas na peak

flow (personal best):

________ - _________

GREEN ZONE

‘GO’ TULOY

P a n a t i l i i n a n g p a g g a m o t

Iwasan o bawasan ang mga ‘triggers’ ng hika tulad ng: _______________________________ Gumamit ng kontroler na gamot: ____________________________ Gumamit ng mga gamot para sa quick relief: • Bago mag-ehersisyo:

________________________________

• Bago malantad sa mga sanhi na nagpapahika(triggers)

_________________________________

Ihanda ang oral steroids sakaling mapunta sa Step 3 ng yellow zone o red zone

• Gumagamit ng quick relief na gamot na higit sa dalawang beses sa isang lingo

• Inuubo

• May halinghing sa paghinga

• Kinakapos sa paghinga

• Hirap sa pisikal na aktibidad

• Nagigising sa gabi

• Pagsikip ng dibdib PEAK FLOW:

• 50-80% ng pansariling pinakamataas na peak flow (personal best):

________ - _________

YELLOW ZONE

‘CAUTION’

MAG-INGAT

K a ra g d a g an g p a gg a m o t

Step 1: Magdagdag ng quick relief na gamot: ___________________________________ Step 2: Subaybayan ang iyong mga sintomas • Kapag nawala kaagad ang mga sintomas, bumalik

sa GREEN ZONE

• Kung nagpapatuloy ang mga sintomas o bumalik pagkatapos ng ilang oras, magdagdag ng:

__________________________

__________________________ Step 3: Magpatuloy sa pagsubaybay ng iyong mga sintomas • Kapag nagpatuloy ang mga sintomas sa Step 2

• Magdagdag ng: (oral corticosteroid) __________________________________

• Tumawag o magkonsulta sa iyong doktor: __________________________________

*Edited from the Original Translation of Virginia delos Reyes, MD, FPCCP


APPENDIX E

INHALER DEVICES INSTRUCTIONS

1. pMDI Instructions:

2. pMDI with spacer Instructions:

1. Remove the inhaler cap or cover. 2. Shake the inhaler 5-10x before each puff. It the pMDI is being used for the first

time, or has not been used for a week or more, spray the inhaler into the air for a few minutes to prime it, then wait for 30 seconds to 1 minute before continuing so as to allow the canister to re-pressurize.

3. Stand or sit up straight. Hold the pMDI with one finger on top and the thumb on the bottom.

4. Breathe out gently to the end of a normal breath. 5. Place the inhaler in the mouth with your lips wrapped around the mouthpiece. 6. Taking only one puff at a time, press down firmly on the pMDI canister as you

begin to breathe in slowly and deeply. Make certain that you are breathing all the way in.

7. Remove the inhaler from your mouth while continuing to hold your breath. 8. Hold your breath for 10 seconds then breathe out slowly (away from the inhaler). 9. Rinse your mouth with water.

1. Remove the cap from the pMDI. Check if both the inhaler and spacer are clean. Attach the inhaler into the end of the back of the spacer.

2. Shake the pMDI. 3. Stand or sit up straight. Hold the pMDI with one finger on top and the thumb

on the bottom. 4. Breathe out gently to the end of a normal breath. 5. Place the spacer attached to the inhaler in your mouth, closing your lips

tightly around the spacer mouthpiece. 6. Press down the inhaler once, then breathe in slowly and deeply. 7. Remove the spacer with inhaler from your mouth while continuing to hold

your breath for 5- 10 seconds. 8. Then breathe out slowly (away from the inhaler). 9. Rinse your mouth with water.


3. Turbuhaler® (DPI) Instructions:

4. Diskus® Dry powder inhaler Instructions:

1. Unscrew the cap of the turbuhaler and lift it off. 2. Hold the turbuhaler upright with one hand and load it by twisting the

colored base to the right with the other hand as far as it will go. Then twist it back to the left until the click is heard. It is now loaded.

3. Hold the turbuhaler with the mouthpiece pointing upwards. Avoid turning the turbuhaler upside down, shaking or dropping it or breathing into the device to prevent medication loss.

4. Stand or sit up straight. Breathe out gently away from the turbuhaler. 5. Place the mouthpiece between the teeth and wrap around the lips tightly

so that no air can escape. 6. Tilt your head back slightly then breathe in as quickly and deeply as

possible. 7. Remove the turbuhaler from your mouth while continuing to hold your

breath for 5 to 10 seconds. 8. Breathe out gently (away from the turbuhaler). If another dose is required,

repeat steps 2 – 8. 9. When finished, replace the cap and twist until it is tightly closed. 10. Rinse your mouth with water.

1. To open the diskus DPI, hold the inhaler in one hand. Then put the thumb of the other hand on the thumb grip, this is the hollow spot which fits the thumb tightly.

2. Push your thumb away as far as it will go; at this point, the mouthpiece and tab or lever beside it should be visible.

3. To prepare the medication, hold the diskus with the mouthpiece facing you. Slide the tab away from you as far as it will go until you hear and/or feel a click. The inhaler is now ready to use.

4. To take the medication, stand or sit up straight. Begin by breathing out. Be sure to avoid breathing out to the mouthpiece.

5. Wrap your lips tightly around the diskus mouthpiece. 6. Breathe in steadily, quickly and deeply. 7. Remove the inhaler from your mouth while continuing to hold your breath

for 5-10 seconds or as long as possible. 8. Breathe out slowly. 9. To close the diskus, put the thumb back on the thumb grip and slide it

toward the body until a clik is heard. The device is ready to use again. 10. Rinse your mouth with water.


5. HandiHaler® (DPI) Instructions:

1. Remove capsule from the blister pack. Fold and separate the two blister strips. Tear the foil strips straight down to reveal the capsule. Expose 1 capsule at a time right before use. A capsule is ready to be loaded to the handihaler.

2. To load the handihaler: a. Open the device by pulling the lid upwards. Next, lift the

mouthpiece open. Place 1 capsule in the capsule chamber. Close the mouthpiece firmly until a click is heard. Leave the lid open.

b. Hold the handihaler with the mouthpiece upwards. c. Immediately before use, press the pierce the piercing button (on

the side) once and then release. Do not shake. 3. Stand or sit up straight. Breathe out gently (away from inhaler). 4. Put the mouthpiece of the handihaler to your mouth between the teeth

(without biting) and close your lips around the mouthpiece to form a good seal.

5. Breathe in slowly and deeply until you know the lungs are full. As you inhale, you should hear the sound of the capsule inside the chamber vibrate.

6. While holding your breath, remove the handihaler from your mouth and continue holding your breath for 5 to 10 seconds or as long as it is comfortable.

7. Breathe out gently (away from handihaler). 8. Inhale a second time to empty the capsule completely by repeating steps

3 to 7. 9. Close the mouthpiece and cap.

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