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. Other risk factors include occupational dusts, vapors, fumes, and genetic factors.

The principal pathophysiological features of COPD are shown in the following image.

Airflow obstruction in COPD is largely due to emphysema, characterized by disruption of the alveolar walls, along with inflammation of lung tissue, fibrosis, and mucus plugging in the distal airways (Panel A, normal distal airway surrounded by intact alveolar walls; Panel B, abnormal distal airway surrounded by disrupted alveolar walls). Alveolar attachments provide a radial tethering effect that is essential for keeping small airways patent in the normal lung. Airways narrow at smaller lung volumes because of decreased lung elasticity and weaker tethering effects. Consequently, maximal expiratory airflow decreases as the lung empties and ceases at 25 to 35% of total lung capacity. The remaining air is termed the residual volume. In patients with COPD who have emphysema, the disruption of alveolar attachments, coupled with distal airway disease, causes a substantial decrease in maximal expiratory airflow (Panel A, normal flow; Panel B, reduced flow). Residual volume may account for as much as 60 to 70% of predicted total lung capacity. Patients with COPD must breathe at larger lung volumes to optimize expiratory airflow, but this requires greater respiratory work because the lungs and chest wall become stiffer at larger volumes. These effects are accentuated with exercise. A normal respiratory system meets the increased ventilatory demands of exercise by increasing both tidal volume and respiratory rate, with little change in the final end-expiratory lung volume. In patients with COPD, the respiratory rate does increase in response to exercise, but with insufficient expiratory time, breaths become increasingly shallow and end-expiratory lung volume progressively enlarges (Panel A, normal response to exercise; Panel B, response with COPD). This phenomenon is called dynamic hyperinflation and is thought to be an important factor in the reduction of exercise capacity and the development of dyspnea.

(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 cough

• chronic sputum production

• dyspnea

• history of risk factors, including exposure to tobacco smoke, occupational dusts, vapors, fumes, and the presence of genetic factors

Patient symptoms can be rated using objective scales such as the following:

• COPD Assessment Test (CAT): measures COPD symptoms (e.g., cough and shortness of breath) on a 0–40 scale; a score of ≥10 indicates COPD symptoms that limit quality of life

• Modified Medical Research Council (mMRC) Dyspnea Scale: scores the degree of breathlessness from 0–4; 4 represents the highest degree of exercise intolerance

Exacerbation history: The 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report replaced the ABCD assessment tool with the ABE Assessment Tool to account for the importance of exacerbations independent of level of symptoms. This new tool classifies patients’ disease severity into three groups (A,B, and E) rather than the previous four groups. Groups A and B remain unchanged, while Group E represents the combination of Groups C and D to highlight the important role of exacerbations.

(Reprinted with permission from the 2023 Global Strategy for Diagnosis, Management, and Prevention of COPD. ©2023 Global Initiative for Chronic Obstructive Lung Disease, all rights reserved.)

Prognostic factors: The BODE Index for COPD Survival (Body mass index, airflow Obstruction, Dyspnea, and Exercise) is a simple, multidimensional grading system that incorporates the patient’s body mass index (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 to 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 and vary with the severity of the disease. 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 one second [FEV₁] 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:

(Reprinted with permission from the 2023 Global Strategy for Diagnosis, Management, and Prevention of COPD. ©2023 Global Initiative for Chronic Obstructive Lung Disease, all rights reserved.)

Smoking cessation: A discussion of the importance of smoking cessation is key with COPD patients to reduce the reduced risk of mortality (see Smoking Cessation in the Ambulatory Care rotation guide).

Vaccination: Influenza vaccination reduces serious illness and death in COPD patients. The Centers for Disease Control and Prevention additionally recommends routine vaccination against pneumonia, pertussis, SARS-CoV-2, and herpes zoster.

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. Commonly used maintenance inhalers are categorized into the following four groups:

• long‐acting beta₂‐agonists (LABAs)

• long‐acting muscarinic antagonists (LAMAs)

• LABA/inhaled glucocorticoid combinations

• LABA/LAMA combinations

The LABA/LAMA combination appears to have an advantage over monotherapy or LABA/inhaled glucocorticoid therapy in reducing COPD exacerbations. Additionally, data show a trend that combined therapies (LABA/LAMA and LABA/inhaled glucocorticoid) lead to a greater improvement in symptom and quality-of-life scores than monotherapies. A growing body of evidence suggests that inhaled glucocorticoids are more effective in patients with high blood eosinophil levels than in patients without high levels.

Abbreviations: LAMA, long-acting muscarinic antagonists; LABA, long-acting beta₂-agonists; ICS, inhaled corticosteroids

(Reprinted with permission from the 2023 Global Strategy for Diagnosis, Management, and Prevention of COPD. ©2023 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.)

• Glucocorticoids are associated with improved oxygenation and shortened recovery time and hospitalization duration. Treatment duration is usually 5–7 days.

• 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.

• Noninvasive mechanical ventilation should be the first mode of ventilation in COPD patients with respiratory failure and no absolute contraindications (e.g., altered mental status or facial trauma that precludes safe wearing of the noninvasive mask).