Chronic Obstructive Pulmonary Disease for the Primary Care Physician

Andrew Gangemi, MDAssistant Professor of Medicine

Department of Thoracic Medicine & SurgeryLewis Katz School of Medicine at Temple University

Disclosures Consulting fee from Nuvaira Inc. Not relevant to this talk

Learning Objectives Define COPD, its impact, and basics of airflow obstruction Clarify the role of pulmonary function testing in the diagnosis

and management of COPD Discuss the attributes of different inhaler devices Introduce advanced treatment options Discuss management of acute exacerbations

What is COPD?Disease characterized by:Persistent respiratory symptomsAirflow limitation

Preventable and treatable disease related to noxious particle exposure*Disease progression is influenced by genetic,

racial, sex, and developmental factorsCan have a variable presentation and symptom

burden based on other comorbidities

GOLD 2020 Report.

Why care about COPD?Global prevalence 8.4 – 15%Affects estimated 16 million AmericansCurrently 4th leading cause of death in the US –

and risingEconomic costs - $32 billion in direct healthcare

costs and additional $20.4 billion in indirect costsSignificant cause of breathless and loss of

productivity for our patientsSecond leading cause of disability-adjusted life

years behind ischemic heart disease

GOLD 2020 Report.

What causes breathlessness in COPD?

YM Luo. J Appl Physiol. 2020. 128: 586–595.

J West. Adv Physiol Educ.2008. 32:177-84.

RV Radiopaedia.org

Global Initiative for Chronic Obstructive Lung Disease

GOLD is a “strategy document” updated annuallyProvides a framework for

management of stable and exacerbating patients

ASSESSMENT

Basic AssessmentHistory and physical!Symptoms burden: dyspnea, cough, sputum

production, recurrent wheezing, exercise limitationPrior exacerbation history: hospitalizations,

prednisone courses, trips to urgent careRisk factors for airflow obstruction: Smoking (including secondhand exposure) Indoor/outdoor pollution Occupational exposures – organic and inorganic dusts

and fumesComorbidities: ischemic heart disease, diastolic

dysfunction, obesity/deconditioning, anemia, osteoporosis, depression/anxiety, lung cancer

GOLD 2020 Report.

GOLD 2020 Report.

GOLD 2020 Report.

Predicting Mortality - BODE

B Celli. N Engl J Med. 2004; 350:1005-12.

SpirometrySpirometry is a reproducible and

objective determination of airflow obstructionAirflow obstruction is required for

the diagnosis of COPD with symptomsNo role for screening spirometry

Performed during a forced expiration

GOLD 2020 Report.

SpirometryLooks at the volume of air exhaled in 1 second

(FEV1) over the full exhaled volume (FVC)Airflow obstruction can be defined using a fixed

ratio <0.7 or lower limit of normal determination Fixed ratio can over-diagnose elderly patients and

under-diagnose mild disease in patients <45 yoGood effort = 6 secondsCloser FEV1 is to FVC higher ratio

Best values taken of at least three reproducible and acceptable efforts

GOLD 2020 Report.

FEV1/FVC <70%

TLC >100%RV >120%RV/TLC >40

DLCO <80%

Let’s put all of this together…

GOLD 2020 Report.

Other Useful Screening Tests6-minute walk test – simple exercise test that

looks at overall cardiopulmonary and musculoskeletal capacityArterial blood gas – if concern for hypercapnia or

saturation <92% Imaging – CT > CXRRecall difference between high-resolution CT and

low-dose CT

GOLD 2020 Report.

TREATMENT

“I take the red one”

Types of Devices

Gangemi, Kim, Criner. Thorax. 2020;75:711–712.

Metered dose inhaler- Pressurized- Can use

with chamber

Dry powder inhaler- Less

coordination- Usually require

high inspiratory flow

Soft mist inhaler- Low

resistance- Complicated

to use- Only 1

available

Nebulizer- No coordination

necessary- Can be used in

severe cases for controller therapy

- Non-portable

Inhaler Technique Matters!

Melani. Respiratory medicine, 2011, Vol.105 (6), p.930-938

Improper technique reduces symptom control, increases need for OCS and antibiotic usage, and leads to more frequent hospitalizations Consider addition of chamber to help with coordination of MDI’s

Principles of BronchodilatorsBeta-agonist and anti-muscarinic agentsAct on smooth muscle to antagonize

bronchoconstriction improve breathlessness and FEV1, also reduce hospitalization and exacerbationAdverse effects: BAs – tachycardia, tremors AMAs – dry mouth, urinary retention, glaucoma Association with adverse CV events not been consistently

seen

Both are equivalent for acute symptoms; dual short-acting agents is superior to either alone.

GOLD 2020 Report.

Principles of Bronchodilators In patients with persistent symptoms requiring

frequent SABA or SAMA LAMA superior to LABA in preventing AECOPD (POET-COPD and INVIGORATE)

Combination long-acting bronchodilators superior to monotherapy in preventing exacerbations and treating more severe dyspnea

GOLD 2020 Report.

GOLD 2020 Report.

Benefit of ICS? Conflicting evidence but overall – in moderate-severe COPD

with history of frequent >2 exacerbation: Combination with ICS reduces symptoms, exacerbation, mortality

(?) Benefit may be more pronounced with eosinophils >300 Triple therapy with ICS > LABA/ICS or LABA/LAMA or LAMA

Side effects: thrush, dysphonia, bacterial pneumonia

Time to exacerbation (FLAME)Wedzicha. N Engl J Med. 2016. 374:2222-34.

Mortality (IMPACT)Lispon. Am J Resp Crit Care Med. 2020. 201(12):1508–16.

For Frequent Exacerbators Azithromycin 250mg daily

or 500mg MWF FEV <80%, use of O2, or

exacerbation within past year, former smokers Monitor QTC, hearing, and

bacterial resistance Roflumilast (PDE-4

inhibitor) Reduces exacerbations in

severe-very severe COPD and chronic bronchitis phenotype Think caffeine! – Diarrhea,

GI upset, weight loss

GOLD 2020 Report.

Albert. N Engl J Med. 2011. 365(8):689-98.

GOLD 2020 Report.

Oxygen Therapy

Strict indications:Resting O2 sat <88%PaO2 <55mmHgPaO2 <60mmHg + Pulmonary hypertension

Moderate hypoxemia at rest (89-93%) or on exertion (<90% for 10 seconds but >80% for 5 minutes) – no benefit in prolonging time to exacerbation or reducing mortality. Symptom benefit?

LOTT Research Group. N Engl J Med. 2016; 375(17):1617-27

Non-Pharmacologic Treatment

Pulmonary rehabilitation Structured endurance and resistance training program 2-3 times

weekly for 6-8 weeks Most beneficial in post-discharge setting – reduces readmission

Smoking cessation Nicotine replacement products Bupropion Varenicline Classes, 1800-QUIT-NOW

Vaccinations Pneumococcal reduces risk of invasive disease and exacerbation Influenza reduces risk for LRTI and death

Palliative care services

GOLD 2020 Report.

Management Cycle

GOLD 2020 Report.

What about biologics? INFLIXUMAB – safe, but no impact on FEV1, symptoms or

6MWT Rennard SI. Am J Resp Crit Care Med. 2007; 175:926-34

METREX and METREO – 100mg mepolizumab reduced exacerbations among patients with eosinoiphils >300 Pavord ID. N Eng J Med 2017; 377:1613-29

GALATHEA and TERRANOVA study – benralizumab did not reduce exacerbations compared to placebo despite suppression of eosinophils Criner GJ and Celli BR. N Engl J Med. 2019; 381:1023-34.

Surgical Options for Hyperinflation

Lung volume reduction surgeryBronchoscopic lung volume

reductionBullectomy*Lung transplantation*

Zantah, Gangemi, Criner. Ann Transl Med. 2020. ePub.

ACUTE EXACERBATIONS

ApproachWhy worry about exacerbations? Reduced health-

associated QOL, increases risk for readmission, accelerates disease progression, increasing risk of death By 8 weeks, 20% may not fully recover

Divided into 3 levels of severity: Mild = treated with SABA alone Moderate = requires antibiotics +/- OCS Severe = ED or inpatient therapy

Purulence to sputum has good predictive value for bacterial LRTI

GOLD 2020 Report.

Outpatient Therapy Increase frequency of SABA/SAMA - can burst 1-2 puffs

every hour initially then space out to every 2-4 hours based on response Add oral corticosteroids (typically 40mg, no more than 5-7

days) REDUCE Trial

If moderate-severe and concern for LRTI (increased dyspnea, sputum volume, and sputum purulence) – add antibiotics Options – Augmentin, Macrolide, Doxycyline, Fluoroquinolone

Identify and control triggering event – medication noncompliance, smoking, exposures, etc.

GOLD 2020 Report.

When to refer to hospital? Severe symptoms – resting dyspnea, respiratory rate

>30bpms, use of accessory muscles/tripoding Cyanosis or low O2 saturation Delirium or confusion Failure to respond to conservative management Poor social support Presence of other comorbidities or features of alternative

diagnosis

GOLD 2020 Report.

GOLD 2020 Report.

Summary COPD is a highly prevalent disease leading to disability and

risk of death for our patients. A history of typical symptoms and exposure risk factors

should make us consider the diagnosis; airflow obstruction by spirometry is required to make a final diagnosis. Consider alternative causes of dyspnea before closing on a

final diagnosis of COPD. Inhaler technique training can optimize device efficacy.

Consider switching devices if patients remain uncontrolled on current regimen.

Summary In patients who complain mainly of persistent dyspnea and

cough but do not frequently flare, LAMA monotherapy is superior to LABA in reducing risk of exacerbations. For highly symptomatic patients with frequent exacerbations

(requiring steroids or hospitalizations), consider initiation of dual therapy with or without ICS depending on features of eosiniphilic disease. Inhaled steroids alone should not be used for initial

treatment. For up to date information of the treatment of COPD, refer to

the GOLD Strategy documents (2021 update coming soon…)

References Albert RK, et al. Azithromycin for Prevention of Exacerbations of COPD. N

Engl J Med. 2011. 365(8):689-98 Celli BA. The Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise

Capacity Index in Chronic Obstructive Pulmonary Disease. N Engl J Med 2004; 350:1005-12.

Criner GJ and Celli BR, et al. Benralizumab for the Prevention of COPD Exacerbations. N Engl J Med. 2019; 381:1023-34.

Gangemi AJ, Kim V, Criner GJ. Customer is always right: optimising inhaler design to fit patient preferences in obstructive lung disease. Thorax. 2020; 75:711-12.

Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevent of chronic obstructive pulmonary disease. 2020 Report.

Leuppi JD, et al. Short-term vs. conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013; 309(21):2223-31.

Lipson DA, et al. Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease. Am J Resp Crit Care Med. 2020. 201(12):1508–16

References LOTT Research Group. A Randomized Trial of Long-Term Oxygen for

COPD with Moderate Desaturation. N Engl J Med. 2016; 375(17):1617-27 Luo YM, et al. Absence of dynamic hyperinflation during exhaustive

exercise in severe COPD reflects submaximal IC maneuvers rather than a nonhyperinflator phenotype. J Appl Physiol. 2020. 128: 586–595.

Pavord ID, et al. Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease. N Eng J Med 2017; 377:1613-29

Rennard SI, et al. The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Resp Crit Care Med. 2007; 175:926-34

Wedzicha JA, et al. Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD. N Engl J Med. 2016. 374:2222-34.

West J. Challenges in teaching the mechanics of breathing to medical and graduate students. Adv Physiol Educ. 2008; 32: 177–184.

Zantah M, Gangemi AJ, Criner GJ. Bronchoscopic lung volume reduction: status quo. Ann Transl Med. 2020. ePub