NICOLA A. HANANIA, FACP - NAMDRC Hanania 3-25-17.pdfMedicine and is Associate Editor of Therapeutic...

THE COPD-ASTHMA OVERLAP SYNDROME NICOLA A. HANANIA, MD, MS, FRCP(C), FCCP, FACP ASSOCIATE PROFESSOR OF MEDICINE DIRECTOR OF ASTHMA & COPD CLINICAL RESEARCH CENTER BAYLOR COLLEGE OF MEDICINE HOUSTON, TX

Nicola A. Hanania, MD, MS is Associate Professor of Medicine in the Section of Pulmonary and Critical Care Medicine and Director of the Asthma and COPD Clinical Research Center at the Baylor College of Medicine in Houston, Texas, USA. He completed his medical training at the University of Jordan followed by residency in internal medicine and a fellowship in pulmonary medicine at the University of Toronto, Canada. He subsequently completed a fellowship in critical care medicine at Baylor College of Medicine, where he later earned a master’s degree in clinical investigation. As a Fellow of the American College of Chest Physicians, Dr. Hanania has served on the Board of Regents and as Chair of the Clinical Pulmonary, Airways Networks and Council of Networks for this organization. He has been on the Board of Trustees of the Chest Foundation since 2012. In addition, he is a current member of the Health Policy Committee of the American Thoracic Society, the European Respiratory Society, the Society of Critical Care Medicine and a fellow of the Royal College of Physicians and Surgeons of Canada. He has served on several guideline and workshop panels including the ACP/ATS/ACCP/ERS Clinical Practice guidelines on COPD and the CTS/ACCP COPD exacerbations guidelines. Dr. Hanania has received multiple awards including the ACCP’s Distinguished Scholar in Respiratory Health, ACCP Humanitarian Award, Career Investigator Award (K23) from the NIH, Fulbright and Jaworski’s Faculty Excellence Award for Teaching and Evaluation and the Award for Excellence in Teaching from the Department of Medicine at Baylor. Baylor also named him to the Academy of Distinguished Educators for 2003-2010. Dr. Hanania is a deputy editor of Respiratory Medicine and is Associate Editor of Therapeutic Advances in Respiratory Disease, Current Opinion in Pulmonary Medicine (Asthma Section) and Pulmonary Pharmacology and Therapeutics. Dr. Hanania’s research interests focus on the pharmacology and management of asthma and COPD. He has published more than 200 peer-reviewed papers, book chapters, editorials and reviews on these topics. He is actively involved in clinical trials investigating novel treatments. He is Principal Investigator for the American Lung Association Airway Clinical Research Center at Baylor College of Medicine, as well as Principal Investigator or Co-Investigator in several clinical trials in asthma and COPD. He has been invited and has lectured widely at local, regional, national and international meetings.

OBJECTIVES: Participants should be better able to:

1. Describe current knowledge about Asthma-COPD Overlap Syndrome (ACOS);

2. Discuss Clinical Scenarios of Patients with ACOS;

3. Compare Impact of Asthma, COPD and ACOS;

4. Review Guidelines and Consensus Definition and Diagnostic and Management Strategies for ACOS;

5. Outline Future Research Needs.

SATURDAY, MARCH 25, 2017 10:30 AM

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Nicola A. Hanania, MD, MS, FCCPAssociate Professor of Medicine

Pulmonary and Critical Care MedicineDirector, Asthma Clinical Research CenterBaylor College of Medicine, Houston, Texas

Asthma COPD Overlap Syndrome (ACOS)

Disclosure Information

Advisor/ Consultant:

- Roche/ Genentech, AstraZeneca, BI, Sanofi/Regeneron, Teva

Member, Board of Trustee, CHEST Foundation

Research grant support (to institution):

- NHLBI, ALA

- GSK, BI, Roche/Genentech, AstraZeneca

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Learning Objectives

Describe current knowledge about Asthma‐COPD Overlap Syndrome (ACOS) Discuss Clinical Scenarios of Patients with ACOS Compare Impact of Asthma, COPD and ACOS Review Guidelines and Consensus Definition and Diagnostic and Management Strategies for ACOS Outline Future Research Needs

Case 56 years old White woman with 20 pack.year smoking history presents with increasing dyspnea, wheezing and cough. History of asthma since childhood which has been stable until recently History of allergic rhinitis, GERD and hypertension P/E: audible wheezing and prolonged expiratory sounded Spirometry:

- Post bronchodilator FEV1: 65% predicted, - FEV1/FVC 0.68, 22% reversibility

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Question 1

A. Significant bronchodilator response (12% and 200 ml change) can distinguish asthma from COPD and ACOS

B. Smoking history of >20 pack.year suggests a diagnosis of COPDC. Presence of allergic rhinitis in this patient suggests a diagnosis of

AsthmaD. A post‐bronchodilator FEV1/FVC ratio <0.7 rules out the diagnosis

of ACOS E. None of the above

A. B. C. D. E.

0%

15% 19%7%

59%

Question 1

A. Significant bronchodilator response (12% and 200 ml change) can distinguish asthma from COPD and ACOS

B. Smoking history of >20 pack.year suggests a diagnosis of COPD

C. Presence of allergic rhinitis in this patient suggests a diagnosis of Asthma

D. A post-bronchodilator FEV1/FVC ratio <0.7 rules out the diagnosis of ACOS

E. None of the above

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Question 2

A. ACOS leads to more significant health status impairment, increased exacerbations and increased hospitalizations than COPD

B. Comorbidities in ACOS can contribute to impairmentC. Patients with ACOS may have increase in eosinophils or neutrophils, or both, in sputum.

D. There is limited evidence for treatment recommendations because ACOS patients are excluded from randomized controlled trials

E. All the above

A. B. C. D. E.

3% 3% 0% 3%

91%

Question 2 A. ACOS leads to more significant health status

impairment, increased exacerbations and increased hospitalizations than COPD

B. Comorbidities in ACOS can contribute to impairment

C. Patients with ACOS may have increase in eosinophils or neutrophils, or both, in sputum

D. There is limited evidence for treatment recommendations because ACOS patients are excluded from randomized controlled trials

E. All of the above

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The “Dutch” Hypothesis

Asthma ……CNSLD……….COPD


Professor Dick OrieGroningen, NL

Common Disea

se?

Common M

echan

isms

Orie et al. Bronchitis II Second International Symposium. Assen, Netherlands: Royal Van Gorcum; 1964:398‐99

Host (Genetic) factors

Asthma

COPD

Environmental factors

(Allergens, infection, smoking, air pollution)

The “Dutch”Hypothesis

Bronchial Inflammation

Orie et al. Bronchitis II Second International Symposium. Assen, Netherlands: Royal Van Gorcum; 1964:398‐99Postma DS, Boezen HM. Chest 2004; 126: 96‐104SPostma DS et al. J Allergy Clin Immunol 2015; 136:521 ‐9

CNSLD

(Atopy, AHR)

Endogenous factors

(Sex, age)

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Common Disea

se?

Common M

echan

isms


The Debate Continues…




Common Disea

se?

Common M

echan

isms


Allergies

The British Hypothesis

Professor Charles Fletcher, London, UK

Different Disea

ses

Different Mechan

isms

Asthma COPD

Irritants/ Smoking

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Am J Respir Crit Care Med. 1995;152(5 pt 2):S77‐S121. Soriano JB, et al. Chest. 2003;124:474‐481.Jeffery PK. Am J Respir Crit Care Med. 2001;152:S28‐S38.

The Overlap Between Asthma and COPD Traditional View

Exacerbations

Bronchiect.

Chronicsputum

Revers.

Eosinophil.

Dyspnea

Hyperinsuf.

Enphysema

CBI

Low weight

BHR

CV comorbidity

Rhinitis PulmonaryHTN

Musclealterations

Osteoporosis

COPD: A Heterogenous Disease

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Exacerbations

Bronchiect.

Chronic sputum

Revers.

Eosinophil.

Dyspnea

Hyperinsuf.

Enphysema

CBI

Low weight

BHR

CV comorbidity

Rhinitis PulmonaryHTP

Musclealterations

Osteoporosis

Asthma‐COPD Overlap Syndrome?

COPD: A Heterogenous Disease

Papi A et al: AJRCCM 2000

eNO & Sputum Eosinophils in “Reversible” COPD

Reversible: >15% in FEV1 after b/d

Exhaled NO

Sputum eos

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Kitaguchi et al, International Journal of COPD 2012:7 283–289

Can Sputum Neutrophils and Eosinophils Differentiate COPD vs. ACOS?

Eur Respir J 2014; 43: 421–429

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Eur Respir J 2014; 43: 421–429

Clinically, ACOS can be Defined as 1 of 2 Phenotypes

Asthma with partially reversible airflow obstruction with or without emphysema or reduced DLCO

COPD accompanied by reversible or partially reversible airflow obstruction with or without environmental allergies (elevated IgE or eosinophils)

Postma DS, Rabe KF. N Engl J Med 2015;373:1241‐9.

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COPD (Post Bronchodilator FEV1/FVC <0.7) with One or More of the Following:

a. Past or Current Diagnosis of Asthmab. Clinical Features of AsthmaEpisodic symptomsAllergic Triggers and comorbidities (Rhinitis, sinusitis)Elevated IgE, Antigen Specific IgE sensitization

c. Variable Airflow ObstructionSignificant acute bronchodilator response, Diurnal variability in PEFRAirway hyperresponsiveness

d. Evidence of Eosinophilic Airway InflammationElevated eNO, elevated blood or sputum eosinophils

Late‐Onset Asthma with Partially Reversible Airway Obstruction

Asthma with Current or Past History of Heavy Smoking

Bujarski S, Parulekar A, Hanania NA. Curr Allergy Asthma Rep (2015) 15: 7

Clinical Scenarios When Asthma and COPD may Overlap

The Overlap Between Asthma and COPD Emerging View: Is this ACOS??

Airflow obstruction

OtherAsthma Phenotypes

Other COPD Phenotypes

Emphysema

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Prevalence of Overlap Syndrome Increases with Age

Gibson P G , and Simpson J L Thorax 2009;64:728‐735 de Marco R et al. PLoS ONE 2013: 8: e62985.

Predictors of Asthma Among Subjects with COPD Multivariate Logistic Regression

Hardin et al. Respiratory Research 2011, 12:127

N = 915

ACOS more likely to be younger, African-American, and have less smoking history

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ACOS vs. COPD in ECLIPSE

Keele E. European Respiratory Journal 2016 47: 1559‐1562

Prevalence of Respiratory Symptoms or Conditions

de Marco R et al. PLoS ONE 2013: 8: e62985.

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More Exacerbations in Patients with ACOS and COPD

Hardin et al. Respiratory Research 2011, 12:127

Exacerbation Rate in Patients with ACOS

International Journal of COPD 2015:10 1443–1454

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Health Care Utilization and Clinical Implications of ACOS

Patients with COPD and asthma use more health care services and incur higher costs than those with COPD without the presence of asthma 1

1 Blanchette CM et al. J Manag Care Pharm. 2008;14(2):176‐85

Menezes AMB et al. CHEST 2014; 145(2):297–304

Marc Miravitlles et al. Respiratory Medicine (2013) 107, 1053‐1060

Impact of ACOS on Physical Activity and Health Status

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Clinical Characteristics of Patients with ACOS vs. COPD


Prevalence of Co‐morbidities in ACOS vs. Asthma and COPD

Postma DS. Clin Chest Med 35 (2014) 143–156

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Prevalence of Comorbidities in Patients with ACOS in Primary Care

Van Boven J, et al. ERS 2015

Adjusted ORACOS (n=5093) vs. COPD (n= 22778)

Allergic Rhinitis 1.81, 95% CI: 1.63‐2.00

Anxiety 1.18, 95% CI: 1.1‐1.27

GERD 1.18, 95% CI: 1.04 – 1.33

Osteoporosis 1.14, 95% CI: 1.04‐1.26

Chronic kidney disease 0.79, 95% CI: 0.66‐0.95

Ischemic heart disease 0.88, 95% CI: 0.79‐0.98

Comorbidities in Patients with ACOS

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Fu J‐J et al. Allergy Asthma Immunol Res. 2014 July;6(4):316‐324

Fu J‐J et al. Allergy Asthma Immunol Res. 2014 July;6(4):316‐324

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2 major criteriaor

1 major + 2 minor

Diagnostic criteria

Maj

orM

inor

- Very positive bronchodilator test(increse in FEV1 ≥ 15% y ≥ 400 ml, over baseline)

- Sputum eosinophilia

- Personal history of asthma (history before the age of 40)

- High total IgE- Personal history of atopy

-Positive bronchodilator test on 2 or more occasions(increase in FEV1 ≥ 12% y ≥ 200 ml, over baseline)

Soler‐Cataluña JJ, et al. Arch Bronconeumol 2012; 48: 331 ‐ 7

Spanish Respiratory Society Criteria for ACOS

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Asthma-COPD overlap syndrome (ACOS) [a description]

Asthma-COPD overlap syndrome (ACOS) is characterized by persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD. ACOS is therefore identified by the features that it shares with both asthma and COPD. A specific definition for ACOS cannot be developed until more evidence is available about its clinical phenotypes and underlying mechanisms.

DIAGNOSE CHRONIC AIRWAYS DISEASEDo symptoms suggest chronic airways disease?

STEP 1

Yes No Consider other diseases first

SYNDROMIC DIAGNOSIS IN ADULTS(i) Assemble the features for asthma and for COPD that best describe the patient.(ii) Compare number of features in favour of each diagnosis and select a diagnosis

STEP 2

Features: if present suggest - ASTHMA COPD

Age of onset Before age 20 years After age 40 years

Pattern of symptoms Variation over minutes, hours or days

Worse during the night or early morning

Triggered by exercise, emotionsincluding laughter, dust or exposureto allergens

Persistent despite treatment

Good and bad days but always dailysymptoms and exertional dyspnea

Chronic cough & sputum preceded onset of dyspnea, unrelated to triggers

Lung function Record of variable airflow limitation(spirometry or peak flow)

Record of persistent airflow limitation(FEV1/FVC < 0.7 post-BD)

Lung function betweensymptoms

Normal Abnormal

Past history or family history Previous doctor diagnosis of asthma

Family history of asthma, and other allergic conditions (allergic rhinitis or eczema)

Previous doctor diagnosis of COPD,chronic bronchitis or emphysema

Heavy exposure to risk factor: tobaccosmoke, biomass fuels

Time course No worsening of symptoms over time.Variation in symptoms either seasonally, or from year to year

May improve spontaneously or have an immediate response to bronchodilators or to ICS over weeks

Symptoms slowly worsening over time(progressive course over years)

Rapid-acting bronchodilator treatmentprovides only limited relief

Chest X-ray Normal Severe hyperinflation

DIAGNOSIS

CONFIDENCE INDIAGNOSIS

Asthma

Asthma

Some featuresof asthma

Asthma

Features of both

Could be ACOS

Some featuresof COPD

Possibly COPD

COPD

COPD

NOTE: • These features best distinguish between asthma and COPD. • Several positive features (3 or more) for either asthma or COPD suggestthat diagnosis. • If there are a similar number for both asthma and COPD, consider diagnosis of ACOS

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QUESTION 3

The following statement is correctA. Post bronchodilator FEV1/FVC <0.7 is compatible with

either COPD or ACOSB. Post bronchodilator increase in FEV1 >12% and 400 mL is

commonly seen in COPD and ACOSC. Sputum eosinophils >2% is diagnostic of ACOSD. FeNO > 25 is diagnostic of ACOS

A. B. C. D.

77%

20%

3% 0%

QUESTION 3

The following is correctA. Post bronchodilator FEV1/FVC <0.7 is

compatible with either COPD or ACOS

B. Post bronchodilator increase in FEV1 >12% and 400 mL is commonly seen in COPD and ACOS

C. Sputum eosinophils >2% is diagnostic of ACOS

D. FeNO > 25 is diagnostic of ACOS

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Markedreversible airflow limitation(pre-post bronchodilator) or otherproof of variable airflow limitation

STEP 3PERFORMSPIROMETRY

FEV1/FVC < 0.7post-BD

Spirometric variable Asthma COPD ACOS

Normal FEV1/FVCpre- or post-BD

Compatible with asthma Not compatible withdiagnosis (GOLD)

Not compatible unlessother evidence of chronicairflow limitation

FEV1 ≥80% predicted Compatible with asthma(good control, or intervalbetween symptoms)

C ompatible with GOLDcategory A or B if post-BD FEV1/FVC <0.7

Compatible with mildACOS

Post-BD increase in FEV1 >12% and 400mLfrom baseline

- High probability ofasthma

Unusual in COPD.Consider ACOS

Compatible withdiagnosis of ACOS

Post-BD FEV1/FVC <0.7- Indicates airflowlimitation; may improve

Required for diagnosisby GOLD criteria

Usual in ACOS

Post-BD increase in FEV1 >12% and 200mLfrom baseline (reversibleairflow limitation)

- Usual at some time incourse of asthma; notalways present

Common in COPD andmore likely when FEV1

is low

Common in ACOS, andmore likely when FEV1 islow

FEV1<80% predicted Compatible with asthma.A risk factor for exacerbations

Indicates severity ofairflow limitation and riskof exacerbations and mortality

Indicates severity ofairflow limitation and riskof exacerbations and mortality

Clinical and Physiological Characteristics of Asthma, Overlap and COPD

Gibson P G , and Simpson J L Thorax 2009;64:728-735

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Pulmonary Function in Patients with COPD and ACOS


Goals of Management

Airflow Limitation

Symptom Burden

Exacerbations

Functional Limitations

Improve Lung FunctionSlow FEV1 Decline

Improve Symptoms

Prevent and Manage Exacerbations

Improve Health Status and Exercise Tolerance

Reduce Hospital Admissions and Mortality

Reducing Impairment

Reducing Risk

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Model of Disease Components and Individualized Treatment Approach to Obstructive Airway Disease

.Gibson PG et al. The Lancet 2010; 376: 803‐813

Therapeutic Targets

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Asthma drugsNo LABA

monotherapy

STEP 4INITIALTREATMENT*

COPD drugsAsthma drugs

No LABAmonotherapy

ICS andconsider LABA

+/or LAMACOPD drugs

QUESTION 4Initial treatment of a patient should include:

A. Inhaled CorticosteroidsB. Long‐acting beta2‐agonistsC. Long‐acting anti‐cholinergicsD. LABA/LAMA Combination

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A. B. C. D.

64%

27%

0%9%

QUESTION 4

Initial treatment of a patient should include:

A. Inhaled CorticosteroidsB. Long-acting beta2-agonistsC. Long-acting anti-cholinergicsD. LABA/LAMA Combination

Therapeutic ImplicationsResponse to Beta2‐Agonists ad iCS


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Therapeutic Implications

The recognition of individuals with shared characteristics of asthma and COPD (ACOS) has important implications for disease management. In these patients, the disease will respond to ICSs irrespective of the severity of airflow obstruction. Conversely, patients with COPD but without any features of asthma will have a poor response to ICSs, and treatment with these drugs should be reassessed.

Targeted Approach to Airway Diseases

Barnes PJ. JACI 2015

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Investigation Asthma COPD

DLCO Normal or slightly elevated Often reduced

Arterial blood gases Normal between exacerbations In severe COPD, may be abnormal between exacerbations

Airway hyperresponsiveness

Not useful on its own in distinguishing asthma and COPD. Higher levels favor asthma

High resolution CT scan Usually normal; may show air trapping and increased airway wall thickness

Air trapping or emphysema; may show bronchial wall thickening and features of pulmonary hypertension

Tests for atopy(sIgE and/or skin prick tests)

Not essential for diagnosis; increases probability of asthma

Conforms to background prevalence; does not rule out COPD

FENO If high (>50ppb) supports eosinophilic inflammation

Usually normal. Low in current smokers

Blood eosinophilia Supports asthma diagnosis May be found during exacerbations

Sputum inflammatory cell analysis

Role in differential diagnosis not established in large populations

GINA 2016, Box 5-5

What do we currently know about ACOS?

B. Ding & A Enstone. Expert Rev Respir Med 2016; 10:3, 363‐371,

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ACOS – Take Home Messages

Asthma‐COPD Overlap syndrome is not a disease entity but a term applied to patients with clinical features of both asthma and COPD ACOS is associated with greater morbidity than Asthma and COPD alone and with relative treatment refractoriness, but information is sparse about its course since most clinical studies have excluded such patients Current recommendations based on consensus suggest that patients with suspected ACOS should be given both a long‐acting bronchodilator; the cornerstone of COPD treatment and an inhaled corticosteroids; the cornerstone of asthma treatment

What do we need to know about ACOS?

Consensus definition and to understand the clinical context , size of the problem and reanalysis of population data Large longitudinal (non‐interventional) studies, or retrospective observational studies to understand the clinical and natural history of ACOS. Understand the molecular mechanisms of ACOS and its related phenotypes; Large longitudinal data are required to discover novel molecular pathways involved in ACOS. Understand the role of inhaled corticosteroids in ACOS; prospective clinical trials are required to validate (or refute) response to ICS and the cost‐effectiveness of this approach. Examine the role of biologic therapy on clinical course and outcomes

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