nicola a. hanania, facp - namdrc hanania 3-25-17.pdfmedicine and is associate editor of therapeutic...
TRANSCRIPT
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
5/14/2018
1
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
5/14/2018
2
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
5/14/2018
3
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
5/14/2018
4
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
5/14/2018
5
The “Dutch” Hypothesis
Asthma ……CNSLD……….COPD
The “Dutch” Hypothesis
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)
5/14/2018
6
The “Dutch” Hypothesis
Asthma ……CNSLD……….COPD
The “Dutch” Hypothesis
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
The Debate Continues…
Asthma ……CNSLD……….COPD
The “Dutch” Hypothesis
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
Allergies
The British Hypothesis
Professor Charles Fletcher, London, UK
Different Disea
ses
Different Mechan
isms
Asthma COPD
Irritants/ Smoking
5/14/2018
7
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
5/14/2018
8
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
5/14/2018
9
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
5/14/2018
10
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.
5/14/2018
11
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
5/14/2018
12
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
5/14/2018
13
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.
5/14/2018
14
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
5/14/2018
15
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
5/14/2018
16
Clinical Characteristics of Patients with ACOS vs. COPD
Kitaguchi et al, International Journal of COPD 2012:7 283–289
Prevalence of Co‐morbidities in ACOS vs. Asthma and COPD
Postma DS. Clin Chest Med 35 (2014) 143–156
5/14/2018
17
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
5/14/2018
18
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
5/14/2018
19
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
5/14/2018
20
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
5/14/2018
21
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
5/14/2018
22
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
5/14/2018
23
Pulmonary Function in Patients with COPD and ACOS
Kitaguchi et al, International Journal of COPD 2012:7 283–289
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
5/14/2018
24
Model of Disease Components and Individualized Treatment Approach to Obstructive Airway Disease
.Gibson PG et al. The Lancet 2010; 376: 803‐813
Therapeutic Targets
5/14/2018
25
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
5/14/2018
26
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
Kitaguchi et al, International Journal of COPD 2012:7 283–289
5/14/2018
27
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
5/14/2018
28
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,
5/14/2018
29
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