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COPD – A New Paradigm: Diagnosis and Treatment Amen Sergew, MD

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Disclosures

• Nothing to disclose

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IntroductionHigh prevalence of COPD worldwide

Kurmi, O. Breathe 2019; 15

Estimated% prevalence of COPD worldwide ranges between 3% and 21%

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Introduction

Highest prevalence in low income patients

Biener, A. JAMA. 2019. 322; 7

US Data from 2014‐2015 on percent prevalence in adults age > 40Propert

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www.cdc.gov/copd

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Mortality from COPD in the US

Crapo, J. Chronic Obstr Pulm Dis. 2019; 6(4)

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Objectives• Review current and emerging therapeutics in the treatment of COPD

• Discuss best practice approaches for initial assessment and management of COPD to improve symptoms and prevent exacerbations

• Describe patient‐centered strategies for creating personalized treatment plans for COPD

• Other hot topics in COPD

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CASE #1: 69 year old man

HPI– Shortness of breath x 2 years; still able to exercise 30 minutes a day– Wheezing and chest tightness– 2 Exacerbations in the past year– Referred new to you

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Fletcher CM. BMJ 1960; 2: 1662.

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© 2020 Global Initiative for Chronic Obstructive Lung Disease

GOLD Group

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You confirm he has COPD. What would you start:a) ICS/LABA/LAMAb) ICS/LABAc) LABAd) LAMAe) LABA/LAMA

ICS=inhaled corticosteroids; LABA=Long acting beta agonists; LAMA=Long acting anti‐muscarinic

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What would you start:a) ICS/LABA/LAMAb) ICS/LABAc) LABAd) LAMAe) LABA/LAMA


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Initial Pharmacological Treatment = LAMA



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Tiotropium in COPD

Tashkin. N Engl J Med 2008; 359 : 15

UPLIFT TrialN=5993

• Improvements in quality of life scores

• No significant benefit in mortality Prop

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Tiotropium in Gold Stage 1 and 2

Zhou, Y. N Engl J Med 2017; 377

N=841

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Why not a LABA in a patient with exacerbations?

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POET‐COPD• Shorter time to first

exacerbation• Fewer moderate and

severe exacerbations

Vogelmeier. N Engl J Med 2011; 524 : 33

LABALAMA

LAMA

LABA

LABA=Long acting beta agonists; LAMA=Long acting anti‐muscarinic

LAMA > LABA in patients with exacerbations

INVIGORATE• Longer time to first

exacerbation• Decrease rate of

exacerbations

Decramer. Lancer Respir Med 2013; 364 : 12

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Initial Pharmacological Treatment



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LABA/LAMA versus LABA/ICS?


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LABA/LAMA versus LABA/ICSFLAME: Fewer exacerbations in LAMA/LABA

AFFIRM:– No difference in dyspnea, rate of exacerbations– LAMA/LABA higher FEV1 at 4 ‐12 ‐24 weeks

Real World Study: – Similar exacerbation rates: LABA/ICS better if eos >6%– LABA/ICS had more incidence of pneumonia

ICS=inhaled corticosteroids; LABA=Long acting beta agonists; LAMA=Long acting anti‐muscarinic Wedzicha JA. NEJM 2016; 374

Vogelmeier C. Eur Resp J 2016; 48Suissa S. Chest 2019; 155

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When should you consider ICS when initiating therapy for COPD?

ICS=inhaled corticosteroids

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© 2020 Global Initiative for Chronic Obstructive Lung DiseaseICS=inhaled corticosteroids

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Initial Pharmacological Treatment



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When should you consider escalating therapy by adding an ICS?

ICS=inhaled corticosteroids

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Triple vs Dual Therapy: IMPACT Study

Lipson. N Engl J Med 2018; 378 : 18

LAMA/LABAICS/LABAICS/LABA/LAMA


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Eosinophils and Treatment Response: IMPACT

Pascoe S. Lancet Respir Med 2019; 7

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Eosinophils and Treatment Response: IMPACT

Pascoe S. Lancet Respir Med 2019; 7

ICS/LABA/LAMA vs LABA/LAMAICS/LABA vs LAMA/LABA

No difference between triple therapy and with LABA/LAMA at eosinophils counts less than 90

Former smokers were more ICS responsive at any eosinophil count than current smokers.

CS=inhaled corticosteroids; LABA=Long acting beta agonists; LAMA=Long acting anti‐muscarinic Prop

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ICS=Inhaled corticosteroidsLABA=Long acting beta agonists LAMA=Long acting anti‐muscarinic

Take Home Points

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CASE # 2 65 year old woman

Symptoms– Stable dyspnea. – No cough or sputum production. No wheezing. No chest tightness. – History of LLL pneumonia 3 months prior. No other exacerbations for the past 2

years.

Medications– Fluticasone furoate, vilanterol, tiotropium (ICS/LABA/LAMA)

ICS=Inhaled corticosteroids LABA=Long acting beta agonists LAMA=Long acting anti‐muscarinic

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What would you do with her medications?

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Withdrawal of inhaled glucocorticoids and exacerbations of COPD (WISDOM)• Design

– Six week run in : fluticasone propionate, tiotropium, salmeterol

– Continuation Group : No change– Withdrawal Group : Steroid withdrawal over 18 weeks

Magnussen. N Engl J Med 2014; 371

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Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD (WISDOM)

Magnussen. N Engl J Med 2014; 371 : 14ICS=Inhaled corticosteroids

ICS Withdrawal

ICS continuation

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• Discontinuation of steroids is not an inferior strategy

Magnussen. N Engl J Med 2014; 371 : 14

Withdrawal of inhaled glucocorticoids and exacerbations of COPD (WISDOM)

FEV1 was slightly lower

• What is the harm in using inhaled corticosteroids?

ICS Withdrawal

ICS continuation

ICS=Inhaled corticosteroids

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ICS– Pneumonia riskStudy Steroid RiskTORCH Fluticasone 19.6 vs 12.3% (p<0.001)Ernst Multiple RR 1.7 (95% CI 1.63 – 1.77)INSPIRE Fluticasone HR 1.94 (95% CI 1.19 – 3.17)Sin Budesonide HR 1.05 (95% CI 0.81 – 1.37)Kew Fluticasone OR 1.78 (95% CI 1.50 – 2.21)Kew Budesonide OR 1.62 (95% CI 1.00 – 2.62)Drummond Multiple RR 1.34 (95% CI 1.03 – 1.75)IMPACT Fluticasone HR 1.53 (95% CI 1.22 – 1.92)

Ernst. Eur Resp J 2015; 45 : 525Lipson. N Engl J Med 2018; 378 : 18ICS=Inhaled corticosteroids

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Other Potential ICS Concerns

• Osteoporosis and Bone Fracture• Mycobacterial Infection: Tuberculosis and Non Tuberculous

• Diabetes Mellitus• Adrenal Suppression• Myopathy• Dysphonia• Cataracts and Glaucoma


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ICS=Inhaled corticosteroidsLABA=Long acting beta agonists LAMA=Long acting anti‐muscarinic

Take Home Points

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CASE # 3 66 year old womanSymptoms

– Wheezing and chest tightness– No cough or sputum production– Six exacerbations in the last year. All requiring hospitalization.

Other Data– Quit smoking 5 years ago. 30 pack year history.– Salmeterol; Fluticasone; Tiotropium (LABA/ICS/LAMA)– Absolute Eosinophils 90– Spiro (POST) FEV1 / FVC Ratio 61%; FEV1 60%

ICS=Inhaled corticosteroids; LABA=Long acting beta agonists; LAMA=Long acting anti‐muscarinic

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What would you do next? Add:a) Additional ICSb) Roflumilastc) Azithromycind) Chronic Prednisone


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What would you do next? Add:a) Additional ICSb) Roflumilastc) Azithromycind) Chronic Prednisone


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Azithromycin for Prevention of COPD Exacerbations

Albert RK. N Engl J Med 2011; 365 : 689

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Predictors of Response to Daily Azithromycin Exacerbations

• Azithromycin (250 mg daily) or placebo for 12 months • Treatment benefit was greatest in

– Ex‐smokers– Age >65 – GOLD Spirometry Stage II, III

• No effect in smokers

Han, M. AJRCC. 2014 Jun 15;189(12)

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Krishnan JK. Eur Respir J. 2019; 53

Chronic Azithromycin and Readmissions

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Consider in:• GOLD II, III • Exacerbations requiring

hospitalizations• Age >65

Take Home Points

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CASE # 3 66 year old womanSymptoms

– Wheezing and chest tightness– No cough or sputum production– Six exacerbations in the last year. All requiring hospitalization.

Other Data– Quit smoking 5 years ago. 30 pack year history.– Salmeterol; Fluticasone; Tiotropium (LABA/ICS/LAMA)– Absolute Eosinophils 90– Spiro (POST) FEV1 / FVC Ratio 61%; FEV1 60%

ICS=Inhaled corticosteroids; LABA=Long acting beta agonists; LAMA=Long acting anti‐muscarinic

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Avoid in:‐low BMI risk of diarrhea

Take Home Points

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Other Medications for Exacerbations

Calverley, P. Int J of COPD 2019:14

RESTORE Study

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What’s on the Horizon for Management of COPD Exacerbations?

• Following CRP to guide antibiotic therapy

Butler, C. NEJM 2019

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• Following CRP to guide antibiotic therapy• Erdosteine:

• an oral mucoactive agent with antioxidant and anti‐inflammatory properties

Butler, C. NEJM 2019Calverley, P. Int J of COPD 2019:14

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• Following CRP to guide antibiotic therapy• Erdosteine• ?Chitotriosidase activity as a possible a predictor of future exacerbations

• ?PD3/4 inhibitors

Harlander, M. Lung 2020 Jan 25

Butler, C. NEJM 2019Calverley, P. Int J of COPD 2019:14

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Other Hot Topics in COPD• Biologics• Lung volume reduction• Non‐Invasive Ventilation• New nomenclature

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Mepolizumab in Eosinophilic COPD: Study Design

Pavord. N Engl J Med. 2017

blood eosinophil count >150 at screening or at least 300 during previous year

P=0.14P=0.07

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Mepolizumab in Eosinophilic COPD: Study Design


Blood eosinophil count >150 at screening or at least 300 during previous year

P=0.04

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Mepolizumab in Eosinophilic COPD:


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Benralizumab to Prevent COPD Exacerbations

Criner G. NEJM. 2019; 3811120 patients

1545 patients

Eosinophils >220

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One of the following is INCORRECT:

A. Lung volume reduction surgery (LVRS) improves survival

B. LVRS improves quality of life

C. LVRS improves dyspnea

D. LVRS should be consider only in high exercise capacity patients

E. LVRS improves exercise tolerancePropert

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One of the following is INCORRECT:

A. Lung volume reduction surgery (LVRS) improves survival

B. LVRS improves quality of life

C. LVRS improves dyspnea

D. LVRS should be consider only in high exercise capacity patients

E. LVRS improves exercise tolerancePropert

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NETT Trial

N Engl J Med. 2003 May 22; 348

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Lung Volume Reduction Surgery

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Lung Volume Reduction Surgery

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Bronchoscopic (Endoscopic) Lung Volume Reduction can be considered in patients with:

A. Large bullaeB. Heterogeneous disease and RV >175%D. Recurrent exacerbationsE. DLCO <20%

RV=residual volume DLCO=diffusion capacity

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Bronchoscopic lung volume reduction can be considered in:

A. Patients with large bullaeB. Heterogeneous disease and RV >175D. Recurrent exacerbationsE. DLCO <20%P

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Evaluate by CT• Intact fissure

Sciurba FC. NEJM 2010; 36Koster D. Int J of COPD. 13 April 2016 113

• Heterogeneous Emphysema

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Bronchoscopic (Endoscopic) Lung Volume Reduction

Placement of valves does not preclude subsequent LVRS or lung transplant

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Criner G. AJRCC 2019; 200

Change in FEV1 (Liters)

EMPROVE: Bronchoscopic (Endoscopic) lung volume reduction Trial

Bronchoscopic/endoscopic valves

Control

0‐6 months: 12.4%increased incidence of seriousPneumothorax in treatment group

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Criner GJ. AJRCC 2018; 198

Risk of pneumothorax: Day 0‐45: 27% Day 45‐1 year: 7%

LIBERATE: Bronchoscopic (Endoscopic) Lung Volume Reduction Trial

Bronchoscopic/endoscopic valvesControl

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Bronchoscopic (Endoscopic) Lung Volume Reduction

• Valve Placement– Valves placed during 30‐60 min bronchoscopy– 3‐5 valves of varying sizes placed in segmental airways of one lobe

• Post – procedure management– Admitted 3‐5 days to monitor for pneumothorax, exacerbation, infection– Regular follow up at 2 weeks, 6 weeks, then 3, 6, 9, 12 monthsProp

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Non invasive ventilation in stable COPD should: A. be considered based on level of hypoxiaB. be considered based on level of hypercarbia > 45 C. preferentially use VAPS technologyD. be set to IPAP >18cmH2OE. be considered in a patient at the time of discharge from hospitalization due to a severe acute exacerbation

VAPS=Volume Assured Pressure Support IPAP=inspiratory positive airway pressure

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Non invasive ventilation in stable COPD should: A. be considered based on level of hypoxiaB. be considered based on level of hypercarbia > 45 C. preferentially use VAPS technologyD. be set to IPAP >18cmH2OE. be considered in a patient at the time of discharge from hospitalization due to a severe acute exacerbation

VAPS=Volume Assured Pressure Support IPAP=inspiratory positive airway pressure

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Trials in Non Invasive Ventilation (NIV) for Hypercapnic COPD

Positive Results

BURR: back‐up respiratory rate

Modified from Duiverman, ML. ERJ Open Research 4 (2018)

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CLINICAL STATUS

WHO?

STABLE • Baseline PaCO2 > 52mmHg• Preserved exercise capacity

(6MWT >200m)• Low annual emergency

admission rate

Non Invasive Ventilation (NIV) for Stable Hypercapnic Severe COPD

Köhnlein T. Lancet Resp Med 2014; 2

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CLINICAL STATUS

WHO? WHEN? HOW? WHY?

STABLE • Baseline PaCO2 > 52mmHg• Preserved exercise capacity

(6MWT >200m)

• Stable State• Low annual

emergency admission rate

Targeted CO2 reductionusing IPAP > 18 cm H2O

Reduces 1 year all cause mortality

Non Invasive Ventilation (NIV) for Stable Hypercapnic Severe COPD

Köhnlein T. Lancet Resp Med 2014; 2

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CLINICAL STATUS


POST ACUTE

• Following a severe exacerbation of COPD requiring acute NIV

Non Invasive Ventilation (NIV) for Post Acute Hypercapnic Severe COPD

Murphy PB. JAMA 2017; 317

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CLINICAL STATUS


POST ACUTE

• Following a severeexacerbation of COPD requiring acute NIV

• 2‐4 weeks post AECOPD if PaCO2 > 52mmHg

Targeted CO2 reduction using IPAP > 18 cm H2O

Increasesadmission‐free survival

Non Invasive Ventilation (NIV) for Post Acute Hypercapnic Severe COPD

Murphy PB. JAMA 2017; 317

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VAPS vs BIPAP in Stable Hypercarbic COPD

Modified from Shaughnessy G. Curr Op Pul Med 2019; 25

No long term studies. No data on survival.

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What’s on the Horizon for Management of Stable COPD?

• Nasal high‐flow

Braunlich J. Int J COPD 2019; 14

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COPDGene® 2019

https://journal.copdfoundation.org

Special Issue November 2019Free subscription online

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COPDGene® 2019

Lowe K. J COPDF, Nov. 2019

COPDGene 2019 Diagnosis

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COPDGene® 2019


– Exposure: • Cigarette smoking > 10 pack‐years


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COPDGene® 2019



– Symptoms: • mMRC dyspnea > 2 or • chronic bronchitis (ATS)


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COPDGene® 2019




– CT structural disease: • emphysema >5%• gas trapping >15% or airway thickening


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COPDGene® 2019




– CT structural disease: • emphysema >5%• gas trapping >15% or airway thickening

– Airflow obstruction: • FEV1/FVC < 0.70 (“classic”) or • FEV1 < 80% predicted (PRISm)


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Lowe KE et al. Redefining the diagnosis of COPD. J COPDF, submitted 2019

Category Description Disease Features

A Exposure 1B Exposure + CT 2C Exposure + Symptoms 2D Exposure + Spirometry 2E Exposure + Symptoms + CT 3

F Exposure + Spirometry + Symptoms 3

G Exposure + Spirometry + CT 3

H Exposure + Spirometry + Symptoms + CT 4

COPDGene 2019 Subgroups

Possible COPD

Definite COPD

Probable COPD

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• The cost of COPD is ballooning

Take Home Points

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• The cost of COPD is ballooning • Reassess therapies with each visit

Take Home Points

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• The cost of COPD is ballooning • Reassess therapies with each visit• Consider better phenotyping your patients

– Eosinophilia (ICS)– Pneumonia (avoid ICS)– Recurrent exacerbations (if maximized on inhalers consider

roflumilast for chronic bronchitis or azithromycin for former smokers, age>65, hospitalized patient)

– Early stage (tiotropium)– Smokers (ICS and azithromycin less effective)

Take Home Points

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• The cost of COPD is ballooning • Reassess therapies with each visit• Consider better phenotyping your patients• Consider biologics in those with overlapping asthma

Take Home Points

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• The cost of COPD is ballooning • Reassess therapies with each visit• Consider better phenotyping your patients• Consider biologics in those with overlapping asthma• Consider LVRS in patient with upper lobe disease

improves survival

Take Home Points

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• The cost of COPD is ballooning • Reassess therapies with each visit• Consider better phenotyping your patients• Consider biologics in those with overlapping asthma• Consider LVRS in patient with upper lobe disease

improves survival• Consider BLVR in patients though significant risk of

pneumothorax

Take Home Points

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• The cost of COPD is ballooning • Reassess therapies with each visit• Consider better phenotyping your patients• Consider biologics in those with overlapping asthma• Consider LVRS in patient with upper lobe disease improves

survival• Consider BLVR in patients though significant risk of

pneumothorax• Consider NIV if PCO2 >52 in stable or post‐acute COPD

Take Home Points

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• The cost of COPD is ballooning • Reassess therapies with each visit• Consider better phenotyping your patients• Consider biologics in those with overlapping asthma• Consider LVRS in patient with upper lobe disease improves

survival• Consider BLVR in patients though significant risk of

pneumothorax• Consider NIV if PCO2 >52 in stable or post‐acute COPD• COPDGene may be changing the COPD nomenclature

Take Home Points

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THANK YOU

Questions?

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Documents

Reproduction Presenter of Property Not for