REFRACTORY ASTHMA

MOKGWANE EUTLWETSE SPARKS

4TH YEAR MED STUDENT

UWI, BAHAMAS CAMPUS

OUTLINE DEFINITION EPIDEMIOLOGY PHYSIOLOGY PRESENTATION RISK FACTORS DIAGNOSIS MANAGEMENT REFERENCE

DEFINITION Before considering asthma, it is important

to establish the diagnosis of asthma itself, since confounding diseases may result in misdiagnosis.

Patients were found to be actually suffering from bronchiectasis, COPD, anxiety or vocal cord dysfunction, although real asthma may coexist with these diagnosis .

Severe asthma is often accompanied by significant comorbidities such as gastrooesophagel reflux, nasal polyps, obesity and depression.

REFRACTORY ASTHMA The term applies to patients who remain

difficult to control despite extensive re-evaluation of diagnosis and management over an observation period of at least 6 months.

REFRACTORY ASTHMA 2000, American Thoracic Society agreed that RA

should be defined on the basis of medication requirements, asthma symptoms, frequency of asthma exacerbations, and degree of airflow limitation.

Agreed on two major and seven minor criteria, with RA being defined as one or both major criteria and at least two minor criteria.

Definition applicable only to patients in whom;1. Other conditions have been excluded,2. Exacerbating factors have been optimally

treated, and3. Poor adherence does not appear to be a

confounding issue.

REFRACTORY ASTHMA Major Characteristics: In order to achieve

control to a level of mild-moderate persistent asthma:  

1. Treatment with continuous or near continuous ( 50% of year) oral corticosteroids  

2. Requirement for treatment with high-dose inhaled corticosteroids:   

   a. Beclomethasone dipropionate    b. Budesonide  c. Flunisolide   d. Fluticasone propionate   e. Triamcinolone acetonide

REFRACTORY ASTHMA Minor Characteristics  

1. Requirement for daily treatment with a controller medication in addition to inhaled corticosteroids, e.g., long-acting -agonist, theophylline, or leukotriene antagonist  

2. Asthma symptoms requiring short-acting -agonist use on a daily or near daily basis

 3. Persistent airway obstruction (FEV1 < 80% predicted; diurnal PEF variability > 20%)  

4. One or more urgent care visits for asthma per year 5. Three or more oral steroid "bursts" per year  6. Prompt deterioration with  25% reduction in oral or

inhaled corticosteroid dose  7. Near fatal asthma event in the past

EPIDEMIOLOGY Asthma affects 5-10% of the population

or an estimated 23.4 million persons, including 7 million children.

It affects 5-7% of the population of North America and Europe and the prevalence is increasing.

Most asthma is mild or moderate and well controlled.

Subgroup of patients with asthma (likely <5%) have more troublesome disease.

PHYSIOLOGY AIRFLOW LIMITATIONThe fixed airflow of most patients with RA can be

defined as a postbronchodilator FEV1 of <80%pred (in the presence of a reduced FEV1/FVC) after 7-14 day course of oral CS.

Explanations: mucous plugging, smooth muscle hypertrophy/

hyperplasia & edema formation. Unresponsiveness to beta agonists: downregulation of beta receptors, fibrosis that limit

dynamicresponses, unknown elements of the obstructive

process & adifferent disease process altogether.

PHYSIOLOGY AIRWAY HYPERRESPONSIVENESSIt is known that airway responsiveness

varies in a temporal fashion, and this generally thought to reflect changes in disease activity and severity.

In RA, after intensive courses of anti-inflammatory medications, patients will continue to exhibit marked airway hyperresponsiveness, failing to attain a plateau in the dose-response curve occurs.

PHYSIOLOGY VARIABLE AIRFLOW LIMITATIONAsthma is also distinguished by periodic

and/or reversible changes in airflow, such as measured by the variability of PEF. Unlike single measures of airflow, sequential measures of PEF variability correlate with increased airway responsiveness.

Patients with RA will have lower values of peak flow, show less response to therapy, and have wide diurnal swings in peak flow.

PRESENTATION The clinical presentation are basically

both the major and minor criteria used to define Refractory Asthma.

RISK FACTORS1. Tobacco smoke  a. In utero  b. Environmental 2. Allergen sensitization3. Viral infections4. Occupational agents5. Air pollutants6. Stress

DIAGNOSIS In making diagnosis of RA, its important to consider

and exclude other diseases in the differential diagnosis of wheeze, dyspnea, cough and eosinophilia.

Patients should be evaluated for diseases such as COPD, bronchiectasis (including allergic bronchopulmonary aspergillosis and cystic fibrosis), vocal cord dysfunction.

finally, in any person with RA, a thorough evaluation for factors that could contribute to the severity of the disease such as sinus disease, gastroesophageal reflux, and compliance/adherences issues should be performed.

Thoroughly evaluated for their understanding of asthma and their ability to use metered dose inhaler.

DIAGNOSIS The diagnostic workup of patients suspected of having chronic

RA should consist of full pulmonary function tests including: Spirometry with a flow-volume curve Total lung capacity Residual volume Diffusion capacity Daily peak flow monitoring Serum Ig E levels Serum eosinophil levels

Further testing could include: High-resolution CT scans Genetic testing for cystic fibrosis or alpha1 anti-trypsin

deficiency Allergy skin testing Specific IgE antibodies for aspergillus.

MANAGEMENT Patients should be treated, as a starting point, as

outlined in the Expert Panel 2 report. High dose/high potency inhaled CS (budesonide,

fluticasone propionate, mometasone). Oral CS at as low a low dose as possible, and one

to three additional controller agents.o No studies have evaluated the benefits of multiple

combinations of these alternative controllers.o Clinician should carefully monitor clinical

parameters to assess the best combination of medications.

o CS pharmacokinetics can identify patients with incomplete CS absorption, failure to convert inactive form to active form, or rapid elimination.

MANAGEMENT Patients who remain asymptomatic

despite optimal application of conventional therapy and management of concomitant disorders, anti-inflammatory and immunomodulating drugs such as methotrexate, gold, cyclosporine, iv gamma globulin and macrolide antibiotics.

Concurrent improvement in pulmonary function is limited when using them and as such their treatments has not been impressive.

MANAGEMENT IV gamma globulin may be effective in some

patients, its high cost prohibitive. Methotrexate- limited efficacy. SE; liver toxicity

and immunosuppressant Cyclosporine has been utilized only in a limited

study population. SE; risk of HTN. Oral gold, limited efficacy. SE; GI adverse

effects. None of them have demonstrated significant

improvement in airway hyperresponsiveness. More studies still needed to define their benefits

and risks, as well as which patients are mostly likely to respond to the selected treatment.

REFERENCEhttp://ajrccm.atsjournals.org/cgi/content/full/162/6/2341#B108National Asthma Education and

Prevention Program Expert Panel. Report 2: Guidelines for the diagnosis and management of asthma. Washington DC: U.S. Government Printing Office; 1997. NIH- NHLBI Publication No. 97-4051.

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