COPD 2018 Insights into the Early Detection, Diagnosis ... into the Early Detection, Diagnosis, and Management Brian W ... dyspnea out of proportion to age or activity 13 1. ... the

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COPD 2018

Insights into the Early Detection, Diagnosis, and Management

Brian W. Carlin, MD, FCCP, FAARC, MAACVPRFebruary 2018

Disclosures (Brian Carlin, MD)

▪ Speakers bureaus, advisory panels▪ Sunovion

▪ Philips Respironics

▪ Monaghan Medical

▪ Astra Zeneca

▪ Glaxo Smith Kline

▪ Fiduciary positions▪ National Lung Health Education Program

▪ National Board for Respiratory Care

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Educational Objectives

Upon completion of this activity, participants should be able to:

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The Importance of Early Detection and Diagnosis

COPD Definition

© 2017 Global Initiative for Chronic Obstructive Lung Disease

►Chronic 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.

Burden of COPD

►4th leading cause of death in the world.1

►COPD projected to be the 3rd leading cause of death by 2020.2

►More than 3 million people died of COPD in 2012 (6% of all deaths globally)

►Globally, the COPD burden is projected to increase in coming decades because of continued exposure to COPD risk factors and aging of the population.

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1. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380(9859): 2095-128.2. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3(11): e442.

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COPD Costs

Annual costs

▪ Direct: ≈$30 billion1

▪ Indirect ≈$20 billion1

▪ COPD exacerbations account for ≈75% of total costs/y2

▪ ≈13 million office visits/y due to exacerbations3

71. Guarascio AJ, et al. ClinicoEconomics and Outcomes Research: CEOR. 2013;5:235-245. 2. ERS-ATS COPD Guidelines. www.thoracic.org/clinical/copd-guidelines/resources/copddoc.pdf. Accessed 3/29/16. 3. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016. www.goldcopd.org. Accessed 3/29/16.

COPD Hospitalization, Death Rates

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Dea

th R

ate

per

100

,000

Po

pu

lati

on H

osp

italization

Rate p

er 10,000 P

op

ulatio

n

Deaths, men

Deaths, women

Hospitalizations, men

Hospitalizations, women

Year

US Adults (1999-2007)

Akinbai LJ et al. NCHA Data Brief no. 63, June 2011. www.cdc.gov/nchs/data/databriefs/db63.pdf. Accessed 3/29/16.

COPD: Underdiagnosed

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▪ ≈15 million Americans diagnosed1

▪ ≈63% remain undiagnosed2

▪ Diagnosis may not occur until disease progresses3

▪ Lack of serious symptoms

▪ Poor recognition of clinical symptoms in early phase

▪ Underuse of spirometry

Undiagnosed COPD (%) by Age4

30% ≥65 y

70% <65 y

1. Morbidity & Mortality 2012 Chart Book. www.nhlbi.nih.gov/files/docs/research/2012_ChartBook_508.pdf. Accessed 9/17/13. 2. CDC. MMWR Morb Mortal Wkly Rep. 2012;61(46);938-943. 3. ERS-ATS COPD Guidelines. www.thoracic.org/clinical/copd-guidelines/resources/copddoc.pdf. Accessed 9/17/13. 4. Mannino DM et al. MMWR Surveill Summ. 2002;51(SS06):1-16.

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Early Intervention Improves Outcomes

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EARLY INTERVENTION1,2

• Smoking cessation• Symptom management• Treating activity limitations• Preventing, treating

exacerbations

IMPROVED OUTCOMES1,2

• Reduced symptoms• Increased exercise tolerance• Improved QOL• Reduced exacerbations• Improved survival

Important clinical challenges leading to gaps in care1,2:1. Underdiagnosis2. Undertreatment (including early intervention)

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016. www.goldcopd.org. Accessed 3/10/16. 2. Malthais F et al. COPD. 2013;10(1):79-103.

Early Detection Strategies

Case Finding and Screening

Spirometry screening for adults without persistent respiratory symptoms is not recommended.

Spirometry should be available in primary care settings and be used for patients at risk for COPD or asthma

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1. USPSTF et al . Screening for COPD: US Preventative Services Task Force recommendation statement, JAMA 2016;315(13):1372-13772. Ruppel, Carlin, Hart, Doherty. Office spirometry in primary care for the diagnosis and management of COPD: National Lung Health Education Program Update. Respir Care February 2018

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Case Finding and Screening

Spirometry should be used for patients:

> 40 years of age who are current or former smokers and

have one or more of the following

chronic cough

excess sputum production

wheezing

dyspnea out of proportion to age or activity

131. Office spirometry in primary care for the diagnosis and management of COPD: National Lung Health Education Program Update. Ruppel, Carlin, Hart, Doherty, Respir Care February 2018

Other Methods

Questionnaires and PEF measurements to select patients for diagnostic spirometry

COPD-population screener (COPD-PS)

Diagnostic score for COPD (DS-COPD)

International Primary Care Airways Guidelines questionnaire (IPAG)

Cost-effective approach

Reduces number of spirometry studies needed

141. Nelson, LaVange, Nie, Walsh, Enright. Questionnaire and pocket spirometers provide an alternative approach for COPD screening in the general population. Chest 2012;142:358-366.2. Soriano, Molina, Miravittlles. Int J TB and Lung Disease 2018;22:106-111.

Diagnosis

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Diagnosis and Initial Assessment


►COPD should be considered in any patient who has dyspnea, chronic cough or sputum production, and/or a history of exposure to risk factors for the disease.

►Spirometry is required to make the diagnosis

►The goals of COPD assessment are to determine ► the level of airflow limitation► the impact of disease on the patient’s health status,► the risk of future events



►Symptoms of COPD

➢ Chronic and progressive dyspnea➢ Cough➢ Sputum production➢ Wheezing and chest tightness➢ Others – including fatigue, weight

loss, anorexia, syncope, rib fractures, ankle swelling, depression, anxiety.

Medical History


►Patient’s exposure to risk factors

►Past medical history

► Family history of COPD or other chronic respiratory disease.

►Pattern of symptom development

►History of exacerbations or previous hospitalizations for respiratory disorder

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Medical History


►Presence of comorbidities

► Impact of disease on patient’s life

►Social and family support available to the patient.

►Possibilities for reducing risk factors, especially smoking cessation.



Summary


►Early detection strategies should be employed►Spirometry►Questionnaires►Peak flow measures

►Spirometry required for the diagnosis

►Should be available in all primary care settings

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GOLD STANDARDS: WHAT YOU NEED TO KNOW

Gerard J. Criner, M.D.

Professor and Chair, Department of Thoracic

Medicine and Surgery

Temple University

Philadelphia, PA

PRESENTER DISCLOSURES

(1) The following relationships with commercial interests related to this presentation existed during the past 60 months:

Gerard J. Criner, M.D.

Honoraria: None

Grants received: NIH-NHLBI, PA-DOH,GSK, Boehringer- Ingelheim,

Novartis, Astra Zeneca, Respironics, Pearl, PneumRx, Pulmonx,

ResMed, Mereo,Probioterix, Broncus, Spiration

Grants pending: NIH-NHLBI, Fisher Paykel,

Consultation: Amirall, Holaira, Boehringer –Ingelheim, Astra

Zeneca, Respironics, Mereo, Patara

Equity Interest: HGE Health Care Solutions, Inc.

GOLD 2017: Most Significant Changes

➢ Assessment of COPD has been refined to separate the spirometric assessment from symptom evaluation

➢ ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations

➢ For each group A to D, escalation strategies for pharmacological treatments are proposed

➢ The concept of de-escalation of therapy is introduced in the treatment assessment scheme

➢ Non-pharmacologic therapies are comprehensively presented

➢ The importance of comorbid conditions in managing COPD is reviewed.

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COPD Definition


►Chronic 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.

COPD Etiology, Pathobiology & Pathology

Etiology

• Smoking and pollutants

• Host factors

Pathobiology

• Impaired lung growth

• Accelerated decline

• Lung injury

• Lung & systemic inflammation

Pathology

• Small airway disorders

• Emphysema

• Systemic effects

Airflow limitation

• Persistent airflow limitationClinical manifestations

• Symptoms & Exacerbations

• Comorbidities

Keys to the Diagnosis of COPD

Assessment of

Clinical

History and

Respiratory

Symptoms *

Physical

Examination*

Presence of

Airflow

obstruction

* Clinical history and physical examination are compatible with COPD and exclude

competing comorbid conditions as the major cause of current symptoms

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Classification of Airflow Limitation Severity in

COPD

GOLD Class Severity FEV1 % predicted

I Mild FEV1 > 80%

II Moderate 50% < FEV1 < 80%

III Severe 30% < FEV1 < 50%

IV Very Severe FEV1 < 30%

Classifying Symptoms: MRC or CAT

0 I only get breathless with strenuous

exercise

1 I get short of breath when hurrying on

the level or walking up a slight hill

2 I walk slower than people of the same

age on the level because of

breathlessness, or I have to stop for

breath when walking on my own pace on

the level

3 I stop for breath after walking about 100

meters or after a few minutes on the

level

4 I am too breathless to leave the house

or I am breathless when dressing or

undressing

Modified MRC Dyspnea Scale COPD Assessment Test (CAT)

Assessment of Exacerbation Risk

➢ Defined as acute worsening of

respiratory symptoms that

results in additional therapy

➢ Severity of events are

characterized as

Mild- treated with SABDs only

Moderate- treated with steroids +

antibiotics

Severe—ER or hospitalized

➢ Higher prevalence of

Exacerbations

Greater airflow limitation

Hospitalization

Prior exacerbations

Number of Exacerbations

Factor Odds Ratio p

AECOPD

prior yr.

5.72 <0.001

GERD 2.07 <0.001

FEV1 1.11 <0.001

WBC 1.08 0.002

SGRQ 1.07 <0.001

Hurst, NEJM, 2010

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Exa

ce

rba

tio

ns p

er

yea

r

0

CAT < 10

mMRC 0-1

GOLD 4

CAT > 10

mMRC > 2

GOLD 3

GOLD 2

GOLD 1

SAMA prn

or

SABA prn

LABA

or

LAMA

ICS + LABA

or

LAMA

GOLD RECOMMENDATIONS TO MANAGE STABLE COPD:

PHARMACOLOGIC THERAPY RECOMMENDED FIRST CHOICE

A B

DC

ICS + LABA

and/or

LAMA


2 or more or

> 1 leadingto hospitaladmission

1 (not leadingto hospitaladmission)

ABCD classification

➢ Pluses➢ “ABCD” assessment tool

of the 2011 GOLD update was a major advancement from the simple spirometricgrading system of earlier GOLD versions

➢ Incorporated patient-reported symptoms

➢ Highlighted the importance of exacerbation prevention in the management of COPD

➢ Minuses➢ Performed no better than

spirometric grades for mortality prediction or other important health outcomes

➢ Unable to assess the individual contributions of severity of airflow limitation from exacerbation frequency or severity

➢ Hindered initial ABCD assessment in subjects without spirometry (ER, hospitalized patient, initial outpatient assessment)

Diagnosis

C D

A B

mMRC 0-1CAT < 10CCQ < 1

mMRC 2+CAT 10+ CCQ 1+

> 2 or >1 leading

to hospitalization

0 or 1 (not leadingto hospitaladmission)

ExacerbationHistory

Grade FEV1

(% pred.)

1 ≥80

2 50-79

3 30-49

4 <30

FEV1/FVC<0.7

Assessment of airflowlimitation

Assessment ofsymptoms/risk of

exacerbations+=

The GOLD Refined ABCD Assessment Tool

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Example: Consider Two Patients

Both with FEV1 < 30% and CAT scores of 18

• No AECOPDs

• 3 AECOPDs

Both labelled GOLD D in prior

classification scheme

C D

A B

• No AECOPDs

• 3 AECOPDs

Grade FEV1 (% pred.)

1 ≥80

2 50-79

3 30-49

4 <30

A B

C D

• 3 AECOPDs - GOLD 4, Category D

• No AECOPDs- GOLD 4, Category B

Recommended Pharmacological Pathway Treatment

Algorithms by GOLD Grade

Exa

ce

rba

tio

ns

Sxs

Management of Stable COPD


Smoking cessation

r/o AATD

Vaccination (flu, pneumococcal pneumonia)

Exercise

Goal weight

Manage comorbid conditions

Inhaled medications Short acting bronchodilators

Long acting bronchodilators

Inhaled steroids

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Treatment of Stable COPD


Manage and prevent exacerbations

Assess for exacerbation risk

Past history

Presence of Chronic bronchitis

Bronchiectasis

Emphysema

Treat promptly

Increased short acting bronchodilators

Antibiotics

Oral steroids

Hospitalization

Prevent exacerbations

Long acting bronchodilators

Inhaled steroids

Chronic azithromycin

Roflumilast

? N-acetylcysteine

? Theophyline

Non-Pharmacologic Treatment


►Education and self-

management

►Physical activity

►Pulmonary rehabilitation

programs

►Exercise training

►Self-management

education

► Nutritional support

► Vaccination

► Oxygen therapy

► Interventional

procedures

► Comorbidities

► End of life and

palliative care

Summary

➢ The diagnosis and treatments of COPD is changing

➢ New data suggests patients develop COPD along different paths

➢ Ultralong bronchodilators and ICS and their combinations may allow us to refine our current treatment paradigms

➢ Additional Tools (HRCT) now enable us to diagnose patients at an earlier stage

➢ New biological characterization schemes (EOS,PMNs) have promise to personalize treatment with novel therapies (IL-5 antagonists)

➢ GOLD continues to use new data to enhance our understanding of the management of patients with COPD

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Strategies to Relieve Dyspnea

Donald A. Mahler, M.D., FCCP

Emeritus Professor of Medicine

Geisel School of Medicine at Dartmouth

Director of Respiratory Services

Valley Regional Hospital

Claremont, NH

Conflicts of Interest

Advisory Boards – AZ; BI; GSK; Mylan;

Sunovion; Theravance

Royalties

CRC Press – Dyspnea 3rd Edition (2014)

Hillcrest Media – COPD: Answers to

Your Questions (2015)

MAPI and pharma – use of BDI/TDI

Speaker’s Bureau: BI, Grifols, Sunovion

Website: http://www.donaldmahler.com

an educational website for those with COPD and their families

Can you help me breathe easier?

http://www.donaldmahler.com/

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Treatment of COPD

GOLD Strategy

↓

Assess for Oxygen

↓

Pulmonary Rehabilitation

↓

Treat Psychosocial Factors

↓

Persistent Dyspnea

Simple Treatments

That Relieve Dyspnea

► Pursed-lips breathing

Pursed-Lips Breathing

Inhale thru nose Purse Lips Exhale thru mouth

► Creates Pressure At The Mouth To Keep

Airways Open Longer and Prolongs Exhalation

↑ SpO2; altered recruitment of respir muscles;

↓ chest wall volume; sense of breathing control

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Simple Treatments



► Body Position

Leaning Forward Position

► Increases Efficiency of the Diaphragm

Sharp. ARRD 1980;122:201

Leaning Forward Position

► Enables accessory muscles to contribute

to rib cage expansion

Gosselink. Chron Respir Dis 2004;1:163

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Simple Treatments



► Body Position

► Use of a fan

Fans

Benefits of a Fan

Design: 50 patients with dyspnea at rest

were randomized to a handheld fan for

5 min directed to leg or face first; after 10

min crossed over to other treatment.

Findings: ↓ breathlessness ratings on

VAS when fan directed to face

compared with leg (p =0.003).

Galbraith. J Pain Sympt Manage 2010;39: 831

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Simple Treatments



► Body Position

► Use of a fan

► Music (distracting stimulus)

► Activites that promote release

of endorphins

Activities that Promote

Release of Endorphins

► Exercise – “runner’s high”

► Laughter

► Listening to soothing music

► Eating chocolate

► Eating hot peppers – capsaicin

► Alcohol – light to moderate

► Acupuncture and massage

Mahler. Breathe Easy 2017;p.128

Simple and Inexpensive

Specific Patient Characteristics

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Condition Individual Therapy

Weak inspiratory → Inspiratory Muscle

muscles Training

(Need to measure PImax)

Inspiratory Muscle Training

Rationale

► Respiratory muscle weakness

causes dyspnea (URI, neuralgic amyotrophy, generalized muscle

weakness, neuromuscular disease, and COPD)

► Increase in respiratory muscle

strength will relieve dyspnea

Targeted Inspiratory Muscle

Training Device

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Inspiratory Muscle

Training in COPDMeta-analysis of 32 RCTs*

Strength training improved:

Mean Change p value

PImax (n = 32) + 13 cmH2O 0.001

6MW (n = 22) + 32 m 0.001

TDI (n = 4) + 2.8 units 0.001

CRQdyspnea (n = 9) + 1.1 units 0.068

Borg scale (n = 14) - 0.9 units 0.001

Gosselink. ERJ 2011;37:416

*Treatment group: 430 patients

Control group: 400





muscles Training

Large Bulla → Bullectomy

Lung BullaDefinition: an air-filled space at least 1 cm in

diameter located in the lung parenchyma

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muscles Training

Large Bulla → Bullectomy

Upper lobe → Volume Reduction

emphysema (VATS or bronchoscopic)

Bronchoscopic Volume Reduction

Endobronchial Valve

Endobronchial Valve

Treatment in EmphysemaDesign: Multicenter RCT comparing EBV

vs Standard of Care (SoC) in patients with heterogeneous emphysema and

no collateral ventilation

Results EBV (n=65) SoC (n=32) p valve

↑ FEV1 > 12%

3 mos* 55% 7% < 0.001

6 mos 56% 3% < 0.001

∆ RV - 700 ml < 0.05

∆ SGRQ - 6.5 < 0.05

Kemp. AJRCCM 2017;196:1535

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Opioids

Effect of Opioids for

Relief of Dyspnea

In systematic review of 26 studies in

526 patients with a variety of advanced

diseases, “there is some low quality

evidence that shows benefit with

oral or parenteral opioids to

palliate breathlessness.”

(mean ∆ = - 0.28)

Barnes. Cochrane Database Syst Rev 2016 Mar 31:3

Opioid Prescription for Dyspnea

Dyspnea Opioid

Episodic IR or short-acting

Constant Sustained-release

► Start with low dose

► Titrate to achieve lowest effective dose

based on patient ratings of dyspnea

► Discontinue opioid if unsatisfactory response

or if adverse effect develops

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Therapies Receptors

► Inhaled Lung

furosemide (↑ SARs and ↓ RARs;

reflex bronchodilation;

? ↓ mucoasl edema)

► Chest Wall Chest wall

Vibration (muscle spindles in intercostal mm)

► Acupuncture Opioid (↑ β-endorphin in blood and CSF)

Investigational Therapies

Can you help me breathe easier?

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COPD GOLD GuidelinesChallenges for the Future

Sidney S. Braman MD Master FCCPProfessor of Medicine

Disclosures

• Non-promotional lectures on lung inflammation- Genentech

• Non-Promotional educational Video on respiratory compromise- Covidien

• Consultant on research directions-AstraZeneca and Sunovion

Learning Objectives

1. Assess the implications of a new definition of COPD

2. List phenotypes of COPD that will have implications for future care of COPD

3. Discuss new directions in the treatment of COPD patients

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What’s Going to be New ?Outline

• Definition of COPD changed!!

• GOLD Stage 0 and 1-should they be treated?

• “De-escalation” refined Will Inhaled corticosteroid controversy be resolved?

GOLD Definition of COPD-Changed

n COPD, a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients

GOLD 2015

n “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

n

……..an abnormal inflammatory responseof the lungs to noxious particles or gases

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Childhood Asthma

Does Childhood asthma cause COPD?

Progression of Asthma Measured by Lung Function in the Childhood Asthma Management Program

25,7% of cohort

Covar RA et al AJRCCM 2004;170(3)234-41

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Progression of Asthma Measured by Lung Function in theChildhood Asthma Management Program

Strunk R C et al JACI 2006

Poor airway function in early infancy and lung function by

age 22 years: a non-selective longitudinal cohort study

123 babies born in Tucson . Lung function at 2 months and 11, 16, 22

Stern et al AJRCCM 2007;370:758

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Conclusions

• Low lung function “Early” in life is as

important a risk for COPD development

• Asthma at an early age may be associated

with a rapid decline in lung function and a

combination of asthma and starting at low

lung function may lead to severe fixed

airflow obstruction.

No known risk factors and...

1. low lung function starting early in

life resulting in fixed airflow

obstruction later in live.

2. asthma resulting in fixed airflow

obstruction later in live.

Is this COPD?

What’s Going to be New ?Outline

• GOLD Stage “0” and 1-should they be treated?

• “De-escalation” refined Will Inhaled corticosteroid controversy be resolved?

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Case Study• A 55 yo Male has a 40 pack year history

of smoking

• Has a daily “smokers cough” and has needed antibiotics two times in the past year for a winter and spring chest cold

• Has to stop walking because of breathlessness after a few minutes on level ground

Current studies Pre-bronchodilator Post-bronchodilator

FEV1 2.44 L (82% predicted) 2.52 L (85% predicted)

FEV1/FVC (%) 71% 72%

55 yo Male

• COPD risk factor

• Chronic bronchitis by history

• Exacerbation 2 mMRC=Grade 3

• His GOLD Stage=?

Jregan et al JAMA Intern Med 2015;175:1539-1549

C D

A B

4

3

2

1

≥

2

1

0

mMRC 0-

1

CAT <10

Symptoms

mMRC or CAT score

Ris

kE

xacerb

ati

on

his

tory

mMRC

≥2

CAT ≥ 10

Ris

kG

OL

D c

lassif

icati

on

of

air

flo

w

lim

itati

on

NO Airflow Obstruction!No COPD!

FEV1/FVC (%)=73%

Smokers with a normal FEV1

Often Have Symptoms

• Ever- or former smokers compared to never smokers with normal FEV1/FVC,%

• CAT cutoff score of 10 or greater, was observed in 50% of smokers; prevalence of CMH* 33% in symptomatic smokers

• They had significantly less physical activity, slightly lower lung function, more respiratory exacerbations, and HRCT** findings consistent with greater airway wall thickening and low percentage emphysema.

*CMH=chronic mucus hypesecretion **HRCT Hi Resolution CT scan

1. Woodruff PG et al N Eng/ J Med 2016;374: 1811-1821

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C D

A B

4

3

2

1

≥

2

1

0

mMRC 0-

1

CAT <10

Symptoms

mMRC or CAT score

Ris

kE

xacerb

ati

on

his

tory

mMRC

≥2

CAT ≥ 10

Ris

kG

OL

D c

lassif

icati

on

of

air

flo

w

lim

itati

on

mMRC Grade 1 “I get short of breath when walking up stairs and inclinesCAT score less than 10

No exacerbations on the last year

Zhou Y et al. N Engl J Med 2017;377:923-935.

Tiotropium in Early-Stage (I&II) Chronic Obstructive Pulmonary Disease

Annual decline in the FEV1 after bronchodilator use was significantly less in the tiotropiumgroup than in the placebo group (29±5 ml per year vs. 51±6 ml per year; difference, 22 ml

per year [95% CI, 6 to 37]; P=0.006).

What’s Going to be New ??Outline

• Inhaled corticosteroid controversy

De-escalation needed?

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GOLD Therapeutic Recommendations

The Global Initiative for Obstructive Lung Disease – 2017 Report. http://goldcopd.org.

Group D

LAMA + LABA

Consider roflumilast if FEV1 < 50% predicted and patient

has chronic bronchitis

FurtherExacerbation(s)

Consider macrolide

LAMA LABA + ICS

LAMA + LABA + ICS

FurtherExacerbation(s)

Persistent symptoms/further

exacerbations

TherapeuticsCorticosteroids for COPD?

• There is growing uncertainty in the value of high-dose inhaled corticosteroids (ICS), in view of the increasing evidence regarding their side effects.

THE EOSINOPHIL

Numbers Increase as Disease Progresses

120

100

80

60

40

20

0PMNs Macrophages Eosinophils

Acute Inflammatory Cells

67

55

84

100

54

6673

92

2533 29

32

Air

way

s w

ith

Mea

sura

ble

Cel

ls (

%)

120

100

80

60

40

20

0

CD4 cells CD8 cells B Cells

Inflammatory Cells

GOLD Stage 0

GOLD Stages 2and 3

GOLD Stage 1

GOLD Stage 4

63

87

77

94

8580

88

98

7 8

45

37

Air

way

s w

ith

Mea

sura

ble

Cel

ls (

%)

Hogg JC et al. New Engl J Med 2004; 350: 2645–2653.

GOLD Stage 0

GOLD Stages 2 and 3

GOLD Stage 1

GOLD Stage 4

PMN = Polymorphonuclear Cells

Inflammatory Cells in COPD

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Significantly Increased During a COPD Exacerbation

Fujimoto K, et al. Eur Respir J. 2005;25:640-646.

Results of nonsmokers from a stable phase and during an exacerbation in patients who developed an

exacerbation during the study.

*P<0.01 vs nonsmokers.†P<0.05 vs stable phase.

Me

an

Eo

sin

op

hils

x 1

05/g

0

2

4

6

8

10

12

14

16

Stable Phase During

Exacerbation

*

Nonsmokers

(n=11)

(n=30)

*

†

Sputum Eosinophils

Eosinophils and COPD• Some patients have high levels of eosinophils in

blood- no features of asthma and in 20 to 30% elevated in sputum

• Blood eosinophil count has been shown to be a good biomarker.

• Shows good short-term and long-term response to glucocorticoids

• WISDOM trial1 showed withdrawal did not increase exacerbations of COPD

• In WISDOM the chance of exacerbating off ICS greater when eosinophil count >300 cells/mcL

1. Manussen et al N Engl J Med 2014;371:1285-1294

Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD

The “FLAME” Study

• A 52-week, randomized, double-blind, double-dummy, noninferiority trial. (FEV1=25-60%)

• A history of at least one exacerbation

• LABA indacaterol (110 μg) plus the LAMA glycopyrronium (50 μg) QD

VS.LABA salmeterol (50 μg) plus glucocorticoid

fluticasone (500 μg) BID

Wedzicha JA et al, NEJM 2016 374;23

2/5/2018

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Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD

The “FLAME” Study

• Indacaterol–glycopyrronium was more effective than salmeterol–fluticasone in preventing COPD exacerbations in patients with a history of exacerbation during the previous year with 11% lower rate.

• Also greater decrease in the use of rescue medication and the greater improvement in health status (decrease in SGRQ-C score) and lung function.

• No difference in results if blood eosinophil count< 2% or>2%

Wedzicha JA et al, NEJM 2016 374;23

TherapeuticsCorticosteroids for COPD

• Blood eosinophil counts may predict the efficacy of ICS in preventing exacerbations in patients with COPD, but prospective studies are needed.

• In patients with lower blood eosinophil counts (< 2%) there is evidence for a poor response to ICS and an increased risk of pneumonia.

Thanks for your attention.

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