RESPIRATORY CONDITIONS

Chronic Obstructive Pulmonary Disease

Etiology and Risk Factors

Tobacco smoking is the leading risk factor, but COPD can also develop through:

• Secondhand smoke
• Occupational dusts, chemicals, vapors, or fumes
• Indoor biomass-fuel exposure
• Outdoor air pollution
• Abnormal lung development
• Recurrent or severe respiratory insults
• Chronic asthma or airway hyperresponsiveness
• Genetic susceptibility
• Alpha-1 antitrypsin deficiency

Exposure history should extend beyond cigarette smoking. COPD can occur in people who have never smoked, particularly when occupational, environmental, developmental, or genetic risks are present (Wietholter & Whetsel, 2026).

Pathophysiology

COPD produces persistent airflow limitation through small-airway obstruction, mucus hypersecretion, inflammation, loss of elastic recoil, and destruction of alveolar attachments.

Chronic Bronchitis and Small-Airway Disease

Chronic irritation promotes mucus-gland enlargement, goblet-cell proliferation, impaired mucociliary clearance, airway-wall inflammation, and mucus plugging. Small-airway narrowing increases resistance and limits expiratory flow (Norris, 2020; Sisson et al., 2019).

Chronic bronchitis is defined clinically by productive cough for at least 3 months in each of 2 consecutive years after other causes have been excluded. This definition describes a clinical phenotype rather than the full pathophysiology of COPD (Wietholter & Whetsel, 2026).

Emphysema

Emphysema involves permanent enlargement of distal airspaces with destruction of alveolar walls. Loss of elastic tissue reduces recoil and removes the radial traction that normally holds small airways open.

During expiration, intrathoracic pressure compresses unsupported airways, causing premature closure, airflow limitation, air trapping, and hyperinflation. Alveolar and capillary destruction also reduce the surface area available for gas exchange and lower DLCO (Norris, 2020; Sisson et al., 2019).

Gas-Exchange Abnormalities

Uneven airway obstruction and alveolar destruction create ventilation-perfusion mismatch. Hypoxemia may develop as disease progresses. Severe disease may impair alveolar ventilation, resulting in carbon dioxide retention and respiratory acidosis.

Chronic hypoxemia can produce pulmonary vasoconstriction, pulmonary hypertension, secondary erythrocytosis, and eventually right-sided heart strain or cor pulmonale (Norris, 2020).

Clinical Manifestations

Common manifestations include:

• Progressive exertional dyspnea
• Chronic cough
• Sputum production
• Wheezing
• Chest tightness
• Prolonged expiration
• Reduced exercise tolerance
• Recurrent exacerbations

Advanced findings may include:

• Hyperinflation
• Increased anteroposterior chest diameter
• Diminished breath sounds
• Accessory-muscle use
• Pursed-lip breathing
• Weight loss or muscle wasting
• Hypoxemia
• Hypercapnia
• Peripheral edema from right-sided heart dysfunction

Symptoms may be underreported because patients gradually reduce activity to avoid breathlessness.

Diagnostic Evaluation

History

A dyspnea history should characterize onset, progression, triggers, associated symptoms, exposures, and functional effects before the differential diagnosis is narrowed (Ma & Lucey, 2012).

• Tobacco exposure in pack-years
• Vaping and marijuana exposure
• Occupational and environmental exposures
• Biomass-fuel exposure
• Symptom duration and progression
• Exacerbation frequency
• Prior hospitalizations or respiratory failure
• Functional limitation
• Inhaler use and technique
• Vaccination history
• Comorbid cardiovascular disease, anxiety, depression, osteoporosis, reflux, sleep apnea, and malignancy risk

Spirometry

Persistent post-bronchodilator airflow obstruction is required to confirm COPD. Expected findings include:

• Reduced FEV₁
• Reduced FEV₁/FVC ratio
• Incomplete reversibility after bronchodilation

The degree of FEV₁ reduction describes airflow impairment but does not independently capture symptom burden, exacerbation risk, functional status, or prognosis (Wietholter & Whetsel, 2026).

Additional Testing

Evaluation may include:

• Lung volumes to assess air trapping and hyperinflation
• DLCO to evaluate emphysema or another gas-transfer abnormality
• Chest imaging
• Pulse oximetry
• Arterial blood gas testing in severe disease or suspected ventilatory failure
• Alpha-1 antitrypsin testing
• Exercise assessment
• Evaluation for comorbid cardiac disease or sleep-disordered breathing

Expected Findings

Typical findings include:

• Persistent obstructive spirometry
• Increased residual volume
• Increased total lung capacity in hyperinflation
• Reduced DLCO when emphysema is prominent
• Hyperlucency or flattened diaphragms on imaging
• Bronchial-wall thickening or increased markings with chronic bronchitic disease
• Hypoxemia in advanced disease
• Hypercapnia and compensatory metabolic alkalosis in chronic ventilatory failure

Normal imaging does not exclude early COPD.

Differential Diagnosis

Asthma

Asthma usually demonstrates greater symptom variability and reversible airflow limitation. COPD more often produces progressive symptoms and persistent post-bronchodilator obstruction. Some patients have features of both disorders (Norris, 2020; Sisson et al., 2019).

Heart Failure

Heart failure may cause dyspnea, cough, wheezing, and reduced exercise tolerance. Orthopnea, paroxysmal nocturnal dyspnea, edema, cardiac findings, and pulmonary vascular congestion favor a cardiac contribution.

Bronchiectasis

Bronchiectasis is associated with chronic productive cough, recurrent infections, and airway dilation on imaging. It may coexist with COPD.

Interstitial Lung Disease

Interstitial disease usually produces a restrictive pulmonary-function pattern, reduced compliance, fine inspiratory crackles, and characteristic imaging abnormalities.

Lung Cancer

New hemoptysis, unexplained weight loss, focal findings, chest pain, or a change in a chronic cough requires evaluation for malignancy.

Treatment and Management

Nonpharmacologic Management

Core interventions include:

• Smoking cessation
• Reduction of occupational and environmental exposures
• Recommended immunizations
• Pulmonary rehabilitation
• Regular physical activity as tolerated
• Nutritional assessment
• Inhaler education
• Written exacerbation planning
• Management of comorbidities
• Long-term oxygen therapy when established criteria are met

Smoking cessation has the greatest ability to slow further COPD progression. Behavioral counseling and pharmacotherapy should be offered when appropriate (Wietholter & Whetsel, 2026).

Maintenance Pharmacotherapy

Long-acting bronchodilators form the foundation of maintenance treatment. Selection depends on symptoms, exacerbation history, response, adverse effects, device ability, access, and patient preference.

• A long-acting muscarinic antagonist or long-acting beta₂ agonist may be used.
• Dual long-acting bronchodilation may be appropriate when symptoms remain substantial.
• Inhaled corticosteroid-containing therapy may be considered for selected patients with exacerbations, eosinophilic features, or concurrent asthma.
• Inhaled corticosteroids should not be used as COPD monotherapy.
• Treatment should be reassessed for benefit, adverse effects, adherence, and device technique (Wietholter & Whetsel, 2026).

Acute Exacerbation

An exacerbation is an acute worsening of respiratory symptoms beyond usual day-to-day variation.

Management may include:

• Short-acting inhaled bronchodilators
• Systemic corticosteroid therapy
• Antibiotics when bacterial infection is sufficiently likely
• Controlled oxygen therapy
• Evaluation for pneumonia, heart failure, pulmonary embolism, pneumothorax, or another precipitating condition
• Noninvasive or invasive ventilatory support when respiratory failure develops

Excessive oxygen administration can worsen hypercapnia in susceptible patients through multiple mechanisms. Oxygen should be titrated to an appropriate target while ventilation and acid-base status are reassessed.

Complications and Red Flags

Urgent escalation is required for:

• Marked respiratory distress
• New confusion or somnolence
• Inability to speak in full sentences
• Hemodynamic instability
• Severe or worsening hypoxemia
• Rising PaCO₂ with acidemia
• Diminished respiratory effort
• Failure to respond to initial therapy
• Suspected pneumonia, PE, pneumothorax, or acute cardiac disease

Clinical Reasoning Priorities

Do not diagnose COPD from smoking history or symptoms alone. Confirm persistent airflow obstruction with post-bronchodilator spirometry.

During an apparent exacerbation, consider competing diagnoses. Heart failure, pneumonia, pulmonary embolism, pneumothorax, arrhythmia, and medication effects can produce similar deterioration.

Treatment escalation should follow reassessment of diagnosis, adherence, inhaler technique, device suitability, exposure, comorbidities, and medication access.

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References

Ma, I., & Lucey, C. R. (2012). Dyspnea. In M. C. Henderson, L. M. Tierney Jr., & G. W. Smetana (Eds.), The patient history: An evidence-based approach to differential diagnosis (2nd ed., pp. 286–297). McGraw-Hill Medical.

Norris, T. L. (2020). Porth’s essentials of pathophysiology (5th ed.). Wolters Kluwer.

Sisson, T. H., Claar, D., Chesnutt, M. S., & Prendergast, T. J. (2019). Pulmonary disease. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed.). McGraw-Hill Education.

Wietholter, J. P., & Whetsel, T. R. (2026). Chronic obstructive pulmonary disease. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw-Hill.