A brief refresher with useful tables, figures, and research summaries
Chronic obstructive pulmonary disease (COPD) is characterized by persistent expiratory airflow limitation due to destruction of lung parenchyma and decrease in elastic recoil. COPD is associated with chronic airway and parenchymal inflammation, and the resultant airway obstruction leads to air trapping and hyperinflation. The decline in lung function in COPD is generally progressive.
The most important risk factor for developing COPD is cigarette smoking. An estimated 25% of individuals with a history of cigarette smoking develop COPD. Globally, inhalation of biomass fuel emissions is another important etiologic agent. The principal pathophysiological features of COPD are shown in following image.
(Source: Outpatient Management of Severe COPD. N Engl J Med 2010.)
Although spirometry is needed to make a diagnosis of COPD (see Investigations below), evaluation of symptoms, exacerbation history and risk, and physical examination findings provide important clues.
Presentation: COPD should be considered in anyone with the following symptoms:
chronic sputum production
history of exposure to risk factors
Patient symptoms can be rated using objective scales including:
COPD Assessment Test (CAT): measures COPD symptoms (e.g., cough and shortness of breath) on a 0–40 scale, with a score of ≥10 indicating COPD symptoms that limit quality of life
Modified Medical Research Council (mMRC) Dyspnea Scale: scores the degree of breathlessness from 0–4, with 4 representing the highest degree of exercise intolerance
Exacerbation history: In addition to symptoms, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends using the ABCD assessment tool to document exacerbation history, determine patient level of risk, and guide subsequent pharmacologic management. The following figure describes the GOLD Refined ABCD Assessment Tool.
The numbers represent severity of airflow limitation (spirometric grades 1 to 4), and the letters (ABCD) represent symptom burden and risk of exacerbation.
(Reprinted with permission from the Global Strategy for Diagnosis, Management and Prevention of COPD 2020. © 2020 Global Initiative for Chronic Obstructive Lung Disease, all rights reserved.)
Prognostic factors: The BODE index (Body-mass index, airflow Obstruction, Dyspnea, and Exercise) is a simple, multidimensional grading system that incorporates the patient’s BMI, degree of airflow obstruction (FEV1), subjective dyspnea symptoms (mMRC Dyspnea Scale), and exercise capacity (6-minute walking distance). The BODE index can be used to predict the risk of death from any cause and from respiratory causes in patients with COPD. The score ranges from 0–10; for every 1-point increase in the BODE index, the hazard ratio for all-cause mortality increases by 1.34 and for respiratory-related mortality by 1.62.
Physical exam: A number of physical exam findings can hint at an underlying diagnosis of COPD. These findings are a manifestation of airway obstruction, hyperinflation, and chronic hypoxemia. Patients may present with varying degrees of tachypnea, respiratory muscle use, and pursed-lip breathing.
Hyperinflation: On examination, patients may appear cachectic from increased respiratory efforts. An increased anteroposterior-to-lateral diameter >0.9 is indicative of hyperinflation (barrel-shaped chest).
Wheeze: On auscultation, diminished breath sounds may be heard due to decreased airflow. Auscultated wheeze has a high-positive-likelihood ratio for the diagnosis of COPD.
Cyanosis: Examination of the hands may reveal cyanosis or nicotine staining.
For more information on the value of the physical exam in the diagnosis of airway obstruction, see this review.
Spirometry: A spirometry measurement of the ratio of postbronchodilator forced expiratory volume in 1 second [FEV 1] to forced vital capacity (FEV1/FVC) <0.7 is typically consistent with the diagnosis of COPD. GOLD classifies the severity of COPD based on the following spirometric measurements:
|1||Mild||>80% of predicted|
|2||Moderate||50% to <80% of predicted|
|3||Severe||30% to <50% of predicted|
|4||Very severe||<30% of predicted|
Smoking cessation: The importance of smoking cessation should be a key discussion with COPD patients because it has been associated with mortality reduction. See Smoking Cessation in the Ambulatory Care rotation guide.
Bronchodilators: First-line pharmacologic agents for treatment of COPD are inhaled bronchodilators (beta2-agonist or anticholinergics) alone, in combination, or with the addition of inhaled glucocorticoids, depending on the patient's symptoms. The use of bronchodilators and inhaled glucocorticoids is associated with a reduction in exacerbations and hospitalizations and improvement in FEV1 decline. A growing body of evidence suggests that inhaled glucocorticoids are more effective in patients who have high blood eosinophil levels than in patient who do not.
Abbreviations: LAMA, long-acting muscarinic antagonists; LABA, long-acting beta2-agonists; ICS, inhaled corticosteroids
(Source: Global Strategy for Diagnosis, Management and Prevention of COPD 2020. © 2020 Global Initiative for Chronic Obstructive Lung Disease, all rights reserved).
Supplemental oxygen: The use of supplemental oxygen is associated with reduced mortality but is indicated only if partial pressure of oxygen is ≤55 mm Hg or oxygen saturation is ≤88% while respiring ambient air. Patients with COPD and moderate desaturation (resting oxygen saturation of 89% to 93% or moderate exercise-induced desaturation) do not appear to benefit from supplemental oxygen.
Chronic macrolide therapy: In former smokers, chronic macrolide therapy with azithromycin has been shown to prevent COPD exacerbations and improve symptoms. This treatment can be considered in patients with persistent symptoms despite optimal inhaled therapy.
A simplified algorithm for the initial assessment and management of patients with COPD is provided below:
(Source: Update on Clinical Aspects of Chronic Obstructive Pulmonary Disease. N Engl J Med 2019.)
COPD exacerbation is the acute change in baseline dyspnea, cough, and/or sputum beyond day-to-day variation that necessitates a change in therapy. Exacerbations are associated with reduced lung function and quality of life and increased morbidity and mortality. Exacerbations are typically associated with respiratory infections caused by viral and bacterial triggers, as described in the following table:
(Source: Infection in the Pathogenesis and Course of Chronic Obstructive Pulmonary Disease. N Engl J Med 2008.)
Treatment of COPD Exacerbations:
Glucocorticoids are associated with a reduction in hospitalization and treatment failure in patients with COPD exacerbations.
Antibiotics are also frequently prescribed for management of COPD exacerbations, especially those associated with increased purulence of sputum. Chronic macrolide therapy is associated with a reduction in COPD exacerbations.
See the GOLD Pocket Guide to COPD Diagnosis, Management, and Prevention, 2020 Report for a summary of the diagnosis and outpatient management of COPD.
Landmark clinical trials and other important studies
Rabe KF et al. N Engl J Med 2020.
Triple therapy with twice-daily budesonide (at either the 160-μg or 320-μg dose), glycopyrrolate, and formoterol resulted in a lower rate of moderate or severe COPD exacerbations than glycopyrrolate–formoterol or budesonide–formoterol.
Pavord ID et al. N Engl J Med 2017.
In two phase 3, randomized, controlled trials, targeting the interleukin-5 pathway with monoclonal antibodies reduced COPD exacerbations in patients with an eosinophilic phenotype.
Butler CC et al. N Engl J Med 2019.
In this randomized, controlled trial, the use of point-of-care CRP testing led to decreased prescription of antibiotics with no evidence of harm.
Criner GJ et al. for the GALATHEA and TERRANOVA Study Investigators. N Engl J Med 2019.
In two randomized, controlled trials, targeting the interleukin-5 receptor with the monoclonal antibody benralizumab did not affect the rate of COPD exacerbations.
Dransfield MT et al. for the BLOCK COPD Trial Group. N Engl J Med 2019.
In this study of patients with COPD at risk for exacerbation, treatment with metoprolol did not affect time to first exacerbation, and the trial was stopped early due to futility and a worrisome severe-exacerbation safety signal.
Suissa S et al. Lancet Respir Med 2018.
Initial COPD treatment with LABA-ICS inhalers was only more effective than treatment with LAMAs in patients with high blood eosinophil concentrations.
Vestbo J et al. for the ECLIPSE Investigators. N Engl J Med 2011.
In this study, the rate of change in FEV1 among patients with COPD was highly variable, with increased rates of decline among current smokers, patients with bronchodilator reversibility, and patients with emphysema.
Albert RK et al. for the COPD Clinical Research Network. N Engl J Med 2011.
In this RCT in patients with moderately severe COPD, daily treatment with azithromycin for one year was associated with fewer exacerbations.
Vogelmeier C et al. for the POET-COPD Investigators. N Engl J Med 2011.
In this RCT, tiotropium was more effective than salmeterol in preventing exacerbations in patients with moderate-to-very-severe COPD.
Lange P et al. N Engl J Med 2015.
Most people with COPD were thought to have normal lung function in mid-adult life and then lose it rapidly. In this study, many people with COPD already had low lung function in mid-adult life, before COPD developed.
Magnussen H et al. for the WISDOM Investigators. N Engl J Med 2014.
In this study, patients with severe COPD receiving inhaled glucocorticoids and two classes of long-acting bronchodilators, glucocorticoid withdrawal was noninferior to continuation with respect to exacerbations but was associated with a slight worsening in lung function and symptoms.
Anthonisen NR et al. for the Lung Health Study Research Group. Ann Intern Med 2005.
In this RTC, an intensive smoking-cessation program followed by 5 years of reinforcement led to significant reduction in all-cause mortality in people with mild-to-moderate airway obstruction.
Leuppi JD et al. JAMA 2013.
In this randomized, noninferiority multicenter trial, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment for the outcome of reexacerbation within 6 months but significantly reduced glucocorticoid exposure.
The best overviews of the literature on this topic
Boucher RC. N Engl J Med 2019.
This review article covers the spectrum of muco-obstructive lung diseases including COPD, cystic fibrosis, primary ciliary dyskinesia, and bronchiectasis.
Agusti A and Hogg JC. N Engl J Med 2019.
An updated review of COPD pathogenesis
Celli BR and Wedzicha JA. N Engl J Med 2019.
A comprehensive review of clinical aspects of COPD including diagnosis, management, and follow-up
Casaburi R and ZuWallack R. N Engl J Med 2009.
This article reviews the indications and evidence for pulmonary rehabilitation in patients with COPD. Patients with unstable angina or recent myocardial infarction may not be good candidates for pulmonary rehabilitation.
Cosio MG et al. N Engl J Med 2009.
This article reviews how pulmonary damage caused by cigarette smoke and other environmental toxins can incite inflammatory and immunologic reactions that culminate in COPD. The authors present evidence that autoimmunity has a role in the development of COPD.
Postma DS and Rabe KF. N Engl J Med 2015.
Classically, asthma and COPD are viewed as distinct disorders. This article reviews the asthma–COPD overlap syndrome whereby patients have features of both diseases.
Silverman EK and Sandhaus RA. N Engl J Med 2009.
This article provides a review on alpha1-antitrypsin deficiency, which can lead to symptoms of obstructive lung disease.
Niewoehner DE. N Engl J Med 2010.
This case vignette reviews the outpatient management of severe COPD.
Wenzel RP et al. N Engl J Med 2012.
This case vignette explores whether the daily use of macrolides reduces COPD exacerbations.
Sethi S and Murphy TF. N Engl J Med 2008.
This review examines the role of infections as triggers for COPD exacerbations.
The current guidelines from the major specialty associations in the field
Qaseem A et al. Ann Intern Med 2011.
The official statement of the ACP, ACCP, ATS, and ERS on diagnosis and management of COPD
Global Initiative for Chronic Obstructive Lung Disease 2022.