Barnes-Jewish Hospital andWashington University Physicians

New Directions in COPD, ACO and the

Chronic Airflow Obstruction Phenotype Mario Castro MD, MPH

Asthma & Airway Translational Research UnitWashington University School of Medicine

St. Louis, Missouri, USA

DISCLOSURES

• Speaker; Honorarium- Boehinger Ingelheim - Genentech- AstraZeneca - Teva- Boston Scientific

•Principal Investigator; Contracted Research- Boehinger Ingelheim - Vectura- Chiesi - ALA- Sanofi-Aventis - NIH

DISCLOSURES (cont.)

• Consultant; Consulting fee - Nuvaira - Sanofi-Aventis- Aviragen - Teva- Genentech - Theravance- Neutronic - Vectura

• Author; Royalties- Elsevier

• Co-Investigator; Contracted Research- NIH - PCORI

LEARNING OBJECTIVES

• Define the current definitions of COPD and ACOS

• Interpret the current GOLD classification and treatment for patients with COPD

• Discuss therapeutic approaches to the chronic airflow obstruction phenotype

COPD Is a Major Public Health Problem and Leading Cause of Disability

• More than 20 million Americans have COPD1

• COPD prevalence is 6% (females > males)- 12.7 million diagnosed and 12 million undiagnosed- Asthma prevalence is 8% (28 million) - NHANES

• Chronic lower respiratory disease (COPD) is now the third leading cause of death (surpassing stroke)

• Second leading cause of disability (first is heart disease)

• 70% of patients are <65 years old

Prevalence - COPD►Estimated 384 million COPD cases in 2010.

►Estimated global prevalence of 11.7% (95% CI 8.4%–15.0%).

►Three million deaths annually.

►With increasing prevalence of smoking in developing countries, and aging populations in high-income countries, the prevalence of COPD is expected to rise over the next 30 years.

►By 2030 predicted 4.5 million COPD related deaths annually.

Cosio M et al. N Engl J Med 2009;360:2445-2454

Specimens from the Small Airways in the Healthy Lung of a Nonsmoker and the Lung of a Smoker

with COPD

Exacerbations Contribute to the Cycle of Decline in COPD

Reduced exercise endurance

Dyspnea

Activity limitation

Poor health-related quality of life

Deconditioning

ExacerbationsAir trapping

Expiratory flow limitation

Hyperinflation

Exacerbations become more frequent and more severe as the severity of underlying COPD increases1-3

8

FEV1=forced expiratory volume in the first second. Figure reproduced with permission. Copyright © 2008 Informa Healthcare.11. Decramer M et al. COPD. 2008;5(4):235-256; 2. Cooper CB. Am J Med. 2006;119(10 suppl 1):21-31; 3. Hurst JR et al; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. N Engl J Med. 2010;363(12):1128-1138.

IRV

FRC=functional residual capacity; IC=inspiratory capacity; IRV=inspiratory reserve volume; RV=residual volume; TLC=total lung capacity; VC=vital capacity; VT =tidal volume.

Ferguson GT. Proc Am Thorac Soc. 2006;3:176-179.Modified with permission of the American Thoracic Society. Copyright © 2016 American Thoracic Society.

The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.

9

Lung Volumes Can Be Altered in COPD Patients Both at Rest and During Exercise

Healthy

Patients

Patients With COPD

FRC

FRC

IRV

IRV

Lung

Vol

ume

Maximum

inspiration

IC

Maximum exhalation

VC

TLCVT

RV

IC

IC

Healthy Patients During

Activity

Patients With COPD During

Activity

140120100806040200

140

4020

80

100

120

60

0

0 020

20

40

40

60

60

80

80

Minute Ventilation (L/min)1

Volu

me

(% p

redi

cted

TLC

)

VT

VT

FRC

Dynamic changes in lung volumes during exercise in

normal lungs and COPD

During exercise (dynamic)

VT

VT

Lung volume measurements

FRC

10

1. Cooper CB. Am J Med. 2006;119(10 suppl 1):S21-S31.

2. Ferguson GT. Proc Am Thorac Soc. 2006;3:176-179.

Dynamic Hyperinflation Links to Dyspnea and Activity Limitations in COPD1,2

Dynamic hyperinflation occurs

when patients commence inhalation before full exhalation has been achieved. Consequently, air is

trapped within the lungs with each successive

breath.2

Adapted with permission from Cooper, Am J Med. 2006 (Figure 3).

COPDAirflow

Obstruction

Air Trapping

Dynamic Hyperinflati

on

Poor Health-Related Quality of Life

Patient-centered Outcome

s

Tachypnea

Dyspnea

↑ Ventilatory Requireme

nt

Activity Limitation

DeconditioningAnxiety

Increased work of

breathing

11

Hyperinflation Explained Physical Inactivity Better Than FEV1

• Study examined the contribution of dynamic hyperinflation to limitations in activities of daily living in COPD patients

• For a given FEV1 range, as characterized by GOLD stage, there was variance in daily physical activity

• Using multiple regression, FEV1did not independently correlate with variance in activity (P=0.939)

• Percent change in inspiratory capacity predicted variance in activity (P=0.046)

VMU=vector magnitude units.Lahaije AJ, et al. Respiratory Medicine.

2013;107:834-840.

P<0.0001 for linear trend (N=57)

46% of variance in physical activity was explained by difference in the

degree of hyperinflation

Daily

Phy

sica

l Act

ivity

(VM

U)

Symptom assessment► COPD Assessment Test (CAT TM )

► Chronic Respiratory Questionnaire (CCQ® )► St George’s Respiratory Questionnaire (SGRQ)

► Chronic Respiratory Questionnaire (CRQ)► Modified Medical Research Council (mMRC) questionnaire

GOLD 2018 Algorithm for Assessingthe Clinical Severity of COPD

13

CAT=COPD Assessment TestTM; mMRC=modified Medical Research Council Dyspnea Scale.International Journal of Chronic Obstructive Pulmonary Disease by DOVE Medical Press. Reproduced with permission of DOVE Medical Press in the format Republish in presentation/slides via Copyright Clearance Center. From the Global Strategy for Diagnosis, Management and Prevention of COPD 2015, © Global Initiative for Chronic Obstructive Lung Disease (GOLD), all rights reserved. Available from http://www.goldcopd.org.

GROUPC-HighRisk,LessSymptoms

GROUPD-HighRisk,MoreSymptoms

GROUPA-LowRisk,LessSymptoms

GROUPB-LowRisk,MoreSymptoms

SymptomsCAT<10 CAT≥10

RISK

GOLD

Classificatio

nof

AirflowLim

itatio

n

RISK

Exacerbatio

nHistory

1notleadingtohospitaladmission

0

(C) (D)

(B)(A)

≥2or≥1leadingtohospitaladmission

mMRC0-1 mMRC≥2

Breathlessness

4

3

2

1

Pharmacologic Therapy

© 2017 Global Initiative for Chronic Obstructive Lung Disease

Pharmacologic Therapy

© 2017 Global Initiative for Chronic Obstructive Lung Disease

Bronchodilators in Stable COPD

© 2017 Global Initiative for Chronic Obstructive Lung Disease

Anti-inflammatory Therapy in Stable COPD

© 2017 Global Initiative for Chronic Obstructive Lung Disease

18

Initial Pharmacological Management of COPD Recommended by GOLD 2018

Question 1

Patient with FEV1 of 55% (FEV1/FVC = 0.62), 2 prior hospitalizations for COPD, mMRC score of 3, on budesonide/formoterol.

Which of the following is the correct GOLD group?A.Group AB.Group BC.Group CD.Group D

Question 2

Patient from Prior Question. Based on their Group, what pharmacologic treatment?

A. Roflumilast onlyB. High dose ICS onlyC. LAMA or LABA monotherapyD. Continue LAMA/LABA combo onlyE. Continue ICS/LABA, add LAMA +/- roflumilast

Patient RecommendedFirst choice

Alternative choice Other PossibleTreatments

D

ICS + LABAand/orLAMA

ICS + LABA and LAMA orICS+LABA and PDE4-inh. or

LAMA and LABA orLAMA and PDE4-inh.

CarbocysteineN-acetylcysteine

SABA and/or SAMATheophylline

Question 2

SVC=slow vital capacity; UPLIFT=Understanding Potential Long-Term Impacts on Function with Tiotropium.Tashkin DP et al; for the UPLIFT Study Investigators. N Engl J Med. 2008;359(15):1543-1554; Data on file, Boehringer Ingelheim Pharmaceuticals, Inc.Please see full Prescribing Information and Important Safety Information available at this presentation.

Follow-up(30 days)

Run-in(2 weeks)

Treatment period(48 months)

SPIRIVA HandiHaler, n=2986

Months 0.5 48 49Randomization

Control, n=3006

Secondary endpoints included:• Yearly rate of decline in pre- and

postbronchodilator FEV1, FVC, and SVC from Day 1 until 1 month after end of study drug administration

• Yearly rate of decline in pre- and postbronchodilator FVC and SVC from Day 30 until completion of study

• Exacerbations and related hospitalizations

Screening

Coprimary endpoints:• Yearly rate of

decline in mean FEV1(prebronchodilator)

• Yearly rate of decline in mean FEV1(postbronchodilator)

UPLIFT Clinical Study Design: 4-Year Efficacy and Safety Trial in Patients With COPD

22

UPLIFT Trial: Tiotropium Improved FEV1 vs Control and Sustained the Difference Over 4 Years

Tashkin DP et al N Engl J Med. 2008;359(15):1543-1554.

* Exacerbations were defined as an increase in or the new onset of more than one respiratory symptom (cough, sputum, sputum purulence, wheezing, or dyspnea) lasting 3 days or more and requiring treatment with an antibiotic and/or a systemic corticosteroid.CI=confidence interval; HR=hazard ratio.Tashkin DP et al; for the UPLIFT Study Investigators. N Engl J Med. 2008;359(15):1543-1554.Please see full Prescribing Information and Important Safety Information available at this presentation.

UPLIFT Trial: Reduction in Exacerbations*

24

Secondary Endpoint SPIRIVA vs Control

Risk of Exacerbations• Reduced the risk of exacerbations versus

control by 14%• Mean number of exacerbations per patient-year was 0.73 vs 0.85, respectively

(HR 0.86; 95% CI, 0.81-0.91, P<.001 )

Median Timeto First Exacerbation

• Delayed median time to first COPD exacerbation versus control by 33% (4.2 months)

• Median time to first COPD exacerbation for SPIRIVA was 16.7 months (95% CI, 14.9-17.9) vs 12.5 months for control (95% CI, 11.5-13.8)

Exacerbations Leading to Hospitalization

• Reduced the risk of hospitalization associated with exacerbations versus control by 14%

• HR 0.86; 95% CI, 0.78-0.95; P=.002

SPIRIVA did not slow the yearly rate of decline in pre- and postbronchodilator FEV1vs control, which were the coprimary endpoints of the study (P=NS).

Nonpharmacologic Therapyto Manage COPD

Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Updated 2008. http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=989. Accessed November 21, 2008.

Patient Education

Oxygen TherapySurgical and Non-

surgical AlternativesPulmonary

Rehabilitation

Smoking Cessation Vaccination

• ¼th of patients with COPD report a history of asthma

• Asthma and COPD have common origins (“Dutch hypothesis”)

• In patients with chronic airways disease, the differential diagnosis differs by age- Children and young adults: most likely to be asthma- Adults >40 years: COPD becomes more common, and

distinguishing asthma from COPD becomes more difficult

• Many patients with symptoms of chronic airways disease have features of both asthma and COPD- This has been called asthma-COPD overlap (ACO)

Asthma COPD Overlap

• Patients with features of both asthma and COPD have worse outcomes than those with asthma or COPD alone- Frequent exacerbations- Poor quality of life- More rapid decline in lung function- Higher mortality- Greater health care utilization

• Rates of overlap between15–55% of patients with chronic airways disease, depending on the definitions and population

Asthma-COPD overlap

Major and Minor CriteriaUsed to Define ACO

Major Criteria Minor CriteriaPrevious history of asthma (before age 40)

IgE > 100 IU, or

Bronchodilator response to salbutamol > 15% and 400 mL

History of atopy,

Sputum eosinophils 2 separated bronchodilator responses to salbutamol > 12% and 200 mL

{Blood eosinophils > 5%}*

Soler-Catalonia et al Archivos Bronconeumologia 2012; *Cosio et al. CHEST 2016 149, 45-52

• Distinguishing asthma from COPD can be problematic- Particularly in smokers and older adults- Some patients may have clinical features of both asthma and COPD

• Most clinical trials and guidelines are about asthma or COPD alone

• The descriptive term asthma-COPD overlap (ACO) is useful - It maintains awareness by clinicians, researchers and regulators of the

needs of these patients• “Asthma-COPD overlap” is not a single disease entity

- As for asthma and COPD, it includes patients with several different forms of airways disease (phenotypes)...

- These features are caused by a range of different underlying mechanisms • To avoid the impression that this is a single disease, the

previous term Asthma COPD Overlap Syndrome (ACOS) is no longer advised.

Asthma-COPD overlap– change in terminology

GINA 2017

• Of 10,192 pts in the COPDGene Study with history of smoking, 385 met criteria for ACOS-bronchodilator responsiveness:- history of asthma or hay fever, - the presence of airway obstruction with significant

bronchodilator responsiveness, and - minimal (<15%) emphysema present on CT

• More likely to be younger, African American, higher BMI, and current smokers

• Majority GOLD grade B• More likely to experience severe & and

frequent exacerbations (adjusted analysis)

Defining Asthma-COPD Overlap (ACO)

Cosentino J, and COPDGene Investigators. Ann Am Thorac Soc 2016;13:1483–1489.

Defining Asthma-COPD Overlap (ACO)

Cosio et al. CHEST 2016 149, 45-52DOI: (10.1378/chest.15-1055)

• 831 patients with COPD at 36 sites in Spain in the COPD History Assessment in Spain (CHAIN) cohort

• assumed that all the patients fulfill 3 or more of the usual features of COPD: age > 40 years, postbronchodilator FEV1/FVC < 0.7, and exposure to cigarette smoke.

• Of 125 (15%) fulfilled the criteria for ACOS, and 98.4% of them sustained these criteria after 1 year.

Definitions

GINA 2017, Box 5-1 (3/3)

AsthmaAsthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation. [GINA 2017]

COPDChronic obstructive pulmonary disease (COPD) is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. [GOLD 2017]

Asthma-COPD overlap [not a definition, but a description for clinical use]Asthma-COPD overlap (ACO) is characterized by persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD. Asthma-COPD overlap is therefore identified in clinical practice by the features that it shares with both asthma and COPD.This is not a definition, but a description for clinical use, as asthma-COPD overlap includes several different clinical phenotypes and there are likely to be several different underlying mechanisms.

• Clinical history: consider chronic airways disease if- Chronic or recurrent cough, sputum, dyspnea or wheezing, or

repeated acute lower respiratory tract infections- Previous doctor diagnosis of asthma and/or COPD- Previous treatment with inhaled medications- History of smoking tobacco and/or other substances- Exposure to environmental hazards, e.g. airborne pollutants

• Physical examination- May be normal- Evidence of hyperinflation or respiratory insufficiency- Wheeze and/or crackles

Step 1 – Does the patient have chronic airways disease?

GINA 2017

• Radiology (CXR or CT scan performed for other reasons)

- May be normal, especially in early stages- Hyperinflation, airway wall thickening,

hyperlucency, bullae- May identify or suggest an alternative or additional

diagnosis, e.g. bronchiectasis, tuberculosis, interstitial lung disease, cardiac failure

• Screening questionnaires- Designed to assist in identification of patients at

risk of chronic airways disease- May not be generalizable to all countries, practice

settings or patients

Step 1 – Does the patient have chronic airways disease?

GINA 2017

• Assemble the features that, when present, most favor a diagnosis of typical asthma or typical COPD

• Compare the number of features on each side- If the patient has ≥3 features of either asthma or COPD,

there is a strong likelihood that this is the correct diagnosis• Consider the level of certainty around the diagnosis

- Diagnoses are made on the weight of evidence- The absence of any of these features does not rule out either

diagnosis, e.g. absence of atopy does not rule out asthma- When a patient has a similar number of features of both

asthma and COPD, consider the diagnosis of asthma-COPD overlap

Step 2 – Syndromic diagnosis of asthma, COPD and asthma-COPD overlap

GINA 2017

© Global Initiative for AsthmaGINA 2014 © Global Initiative for AsthmaGINA 2017, Box 5-4

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 COPDAge of onset q Before age 20 years q After age 40 years

Pattern of symptoms q Variation over minutes, hours or days

q Worse during the night or early morning

q Triggered by exercise, emotionsincluding laughter, dust or exposure

to allergens

q Persistent despite treatment

q Good and bad days but always dailysymptoms and exertional dyspnea

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

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

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

Lung function betweensymptoms

q Normal q Abnormal

Past history or family history q Previous doctor diagnosis of asthma

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

eczema)

q Previous doctor diagnosis of COPD,chronic bronchitis or emphysema

q Heavy exposure to risk factor: tobaccosmoke, biomass fuels

Time course q No worsening of symptoms over time.Variation in symptoms either

seasonally, or from year to yearq May improve spontaneously or have

an immediate response to bronchodilators or to ICS over weeks

q Symptoms slowly worsening over time(progressive course over years)

q Rapid-acting bronchodilator treatmentprovides only limited relief

Chest X-ray q Normal q Severe hyperinflation

DIAGNOSIS

CONFIDENCE INDIAGNOSIS

Asthma

Asthma

Some featuresof asthma

Asthma

Features of both

Could be ACO

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 ACO

• Essential if chronic airways disease is suspected- Confirms chronic airflow limitation- More limited value in distinguishing between asthma with

fixed airflow limitation, COPD and asthma-COPD overlap• Measure at the initial visit or subsequent visit

- If possible measure before and after a trial of treatment- Medications taken before testing may influence results

• Peak expiratory flow (PEF) - Not a substitute for spirometry- Normal PEF does not rule out asthma or COPD- Repeated measurement may confirm excessive variability,

found in asthma or in some patients with asthma-COPD overlap

Step 3 - Spirometry

GINA 2017, Box 5-3

© Global Initiative for Asthma

Step 3 - Spirometry

Spirometric variable Asthma COPD Overlap

Normal FEV1/FVCpre- or post-BD

Compatible with asthma Not compatible withdiagnosis (GOLD)

Not compatible unlessother evidence of chronic

airflow limitation

FEV1 ≥80% predicted Compatible with asthma(good control, or interval

between symptoms)

Compatible with GOLDcategory A or B if post-

BD FEV1/FVC <0.7

Compatible with mildACO

Post-BD increase in FEV1 >12% and 400mL

from baseline

- High probability ofasthma

Unusual in COPD.Consider ACO

Compatible withdiagnosis of ACO

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

Required for diagnosisby GOLD criteria

Usual in asthma-COPD overlap (ACO)

Post-BD increase in FEV1 >12% and 200mLfrom baseline (reversible

airflow limitation)

- Usual at some time incourse of asthma; not

always present

Common in COPD andmore likely when FEV1

is low

Common in ACO, andmore likely when FEV1 is

low

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

Indicates severity ofairflow limitation and risk

of exacerbations and mortality

Indicates severity ofairflow limitation and risk

of exacerbations and mortality

GINA 2017, Box 5-3

• Initial pharmacotherapy choices are based on both efficacy and safety• If syndromic assessment suggests asthma as single diagnosis

- Start with low-dose ICS- Add LABA and/or LAMA if needed for poor control despite good adherence

and correct technique- Do not give LABA alone without ICS

• If syndromic assessment suggests COPD as single diagnosis- Start with bronchodilators or combination therapy- Do not give ICS alone without LABA and/or LAMA

• If differential diagnosis is equally balanced between asthma and COPD, i.e. asthma-COPD overlap- Start treatment as for asthma, pending further investigations- Start with ICS at low or moderate dose- Usually also add LABA and/or LAMA, or continue if already prescribed

Step 4 – Commence initial therapy

• For all patients with chronic airflow limitation: - Treat modifiable risk factors including advice about

smoking cessation- Treat comorbidities- Advise about non-pharmacological strategies

including physical activity, and, for COPD or asthma-COPD overlap, pulmonary rehabilitation and vaccinations

- Provide appropriate self-management strategies- Arrange regular follow-up

Step 4 – Commence initial therapy

© Global Initiative for Asthma

Investigation Asthma COPDDLCO Normal or slightly elevated Often reducedArterial blood gases Normal between

exacerbationsIn 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

Step 5 – Refer for specialized investigations if needed

GINA 2017, Box 5-5

Question 3• A 55 y.o. Caucasian female presents to your office for evaluation of

cough and recurring “bronchitis”. She informs you that over the last 3 winters, she has always needed 2 courses of antibiotics for “bronchitis that settled into my chest and won’t go away”. The last episode has left her a little winded climbing stairs, but she also attributes that to her lack of exercise and weight gain since she quit smoking at age 38 (started age 16 1 ppd). FH pertinent for mother had asthma, and that patient reports that she had asthma as a child with symptoms disappearing at about age 14. Blood work demonstrates a serum IgE of 214 (normal < 100) and a peripheral eosinophil count of 435. Spirometry demonstrates an FEV1 60% pred anc FEV1/FVC ratio of 65%. The best diagnosis is:

A. Severe persistent asthmaB. COPD, category AC. Asthma - COPD overlapD. Eosinophilic bronchitis

Characteristic Associations Specifically-targeted treatmentsSevere allergic asthma

High eosinophilHigh serum IgEHigh FeNO

Anti-IgE (adults & children)Anti-IL4/IL-13IL4 Receptor

Eosinophilic asthma High serum IgERecurrent exacerbationsHigh FeNO

Anti-IL5Anti-IL-4/-13 IL-4R

Non-eosinophilic, neutrophilic asthma

Corticosteroid insensitivityBacterial infections

Anti-IL-8CXCR2 antagonistsAnti-LTB4 (adults and children)Macrolides (adults and children)

Chronic airflow obstruction

Airway wall remodelling as increased airway wall thickness

Anti-IL13Bronchial thermoplasty

Recurrent exacerbations

Eosinophils in sputumReduced response to ICS ±OCS

Anti-IL5Anti-IgE (adults and children)

Corticosteroid insensitivity

High neutrophils in sputum2 p38 MAPK inhibitorsTheophylline (adults and children)Macrolides (adults and children)

Potential phenotype-targeted therapiesin severe asthma

International ERS/ATS GUIDELINES Eur Respir J, 2014; 43(2):343-373

Early onset asthma (EOA); Normal lung function; Atopic≤ 2 Controller (medication use); Minimal Health Care

Utilization (HCU); sputum eosinophils (EOS)

Most common cluster; EOA; Borderline normal FEV1 but reverses to normal; Atopic; ≤ 2 Controllers; Very low HCU,

but some oral steroid bursts (OCS); sputum eosinophils

Older; Late onset (LOA); higher BMI; Less atopic; Moderately low FEV1 with some reversibility; Higher dose ICS; ≥ 3 Controllers, but despite this more OCS bursts; increased sputum eosinophils

EOA; 53% male; Severely decreased FEV1, but very reversible to near normal; Atopic; ”Variable” with need for frequent OCS; High

beta agonist use, HCU and symptoms; increased sputum EOS

Older; long duration; 63% female; higher BMI; GERD; HTN,; Less atopic; Severely decreased FEV1 less reversibility; On OCS; High beta-agonist use, HCU, symptoms; increased sputum PMN, EOS)

2 Mild-Moderate Allergic Asthma

3 More SevereOlder Onset Asthma

4 Severe Variable Allergic Asthma

5 Severe Fixed Airflow Asthma

1 MildAllergic Asthma

Moore et al. AJRCCM 2010;181:315-323.

Asthma Cluster Analysis: 5 Clusters

Multiscale Imaging-based Cluster Analysis (MICA) in Asthmatics

45

248 asthmatics

Choi, Chen, Hoffman, Wenzel, Castro, Fain, Jarjour, Schiebler, Lin, JACI 2017

Major Features of 4 Asthma Clusters

Development of COPD from Childhood Asthma – Results from the CAMP study

McGeachie MJ et al. Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma N Engl J Med 2016;374:1842-1852

Development of COPD from Childhood Asthma – Results from the CAMP study

McGeachie MJ et al. Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma N Engl J Med 2016;374:1842-1852

COPD, ACOS and chronic airflow obstruction phenotype

• Recognition of COPD in allergy or pulmonary practice requires spirometry

• Key to COPD assessment is symptom evaluation, exacerbation risk and spirometry

• Recognize the spectrum of Asthma COPD overlap and treat accordingly

• Chronic airflow obstruction phenotype can occur in asthma and is associated with difficult to control asthma