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1
Question:

A 66-year-old man with chronic obstructive pulmonary disease is admitted to the hospital due to worsening dyspnea and productive cough for the past 3 days.  He has difficulty sleeping due to the cough.  The patient's sputum volume and thickness are increased compared to baseline; it has a greenish hue and is foul smelling.  His most recent spirometry during an office visit a month ago showed FEV1 of 51% of predicted.  Temperature is 37.2 C (99 F), pulse is 96/min, blood pressure is 143/87 mm Hg, and respirations are 23/min.  Oxygen saturation is 86% on room air.  Lung examination shows bilateral low-pitched wheezing and prolonged expiration.  Chest x-ray reveals hyperinflated lungs and prominent bronchial markings without pulmonary infiltrates.  Initial laboratory studies show blood leukocytes of 7,200/mm3 with normal differential.  Respiratory viral panel is negative.  The patient is given supplemental oxygen, nebulized bronchodilators, and intravenous glucocorticoids.  Which of the following additional therapies is most strongly indicated at this time?

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Explanation:

Acute exacerbation of chronic obstructive pulmonary disease

Precipitants

  • Infectious (70%): respiratory viruses (eg, rhinovirus) & commensal bacteria (eg, nontypable Haemophilus influenzae)
  • Noninfectious (30%): sterile inflammation (underlying disease), pulmonary embolism, inhaled irritants

Pathophysiology & presentation

  • Bronchial inflammation: systemic response (eg, fever, leukocytosis) usually absent
  • Cardinal symptoms: ↑ dyspnea, ↑ sputum volume, ↑ sputum purulence
  • ↑ WOB (hyperinflation) & impaired gas exchange (hypoxemia [↓ V/Q], hypercapnia [↑ VD])

Management

  • Maximize expiratory flow: inhaled bronchodilators
  • Reduce airway inflammation: systemic glucocorticoids
  • Treat underlying triggers: ± antibiotics* &/or antivirals (influenza, COVID-19)
  • Maintain adequate oxygenation: SpO2 target 88%-92%
  • Maintain adequate ventilation: NIPPV or invasive mechanical ventilation

*Antibiotics generally indicated if: (1) increased sputum purulence + ≥1 other cardinal symptoms; or (2) patient requires hospitalization.

NIPPV = noninvasive positive pressure ventilation; VD = alveolar dead space ventilation; V/Q = ventilation/perfusion ratio; WOB = work of breathing.

This patient is experiencing an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), defined as an increase in at least 2 of the following 3 cardinal symptoms: dyspnea, sputum volume, and sputum purulence (ie, greenish, malodorous mucus).

Approximately 70% of AECOPD cases likely stem from an infectious trigger, split roughly evenly between common respiratory viruses (eg, rhinovirus, influenza) and commensal bacteria (eg, nontypable Haemophilus influenzae, Moraxella catarrhalis).  Infection promotes an exuberant neutrophilic inflammatory cascade.  Management of AECOPD addresses the inflammatory and potential infectious processes:

  • Systemic glucocorticoids reduce airway inflammation to decrease bronchial wall edema and secretions, which improves expiratory airflow.
  • Antibiotics reduce bacterial burden to dampen the ensuing inflammatory response and are generally indicated for patients with a moderate or severe AECOPD, defined as that requiring hospitalization or involving increased sputum purulence plus ≥1 other cardinal symptom(s).  Appropriate agents offer coverage of commensal flora, including respiratory fluoroquinolones (eg, moxifloxacin, levofloxacin), third-generation cephalosporins (eg, cefpodoxime), and beta-lactam/beta-lactamase inhibitors (eg, amoxicillin-clavulanate).

Inflammation in COPD is usually out of proportion to the bacterial load such that significant symptoms can develop even with bacterial counts far below the culture threshold.  Therefore, respiratory cultures are of limited diagnostic utility and antibiotic therapy is empiric.

(Choice A)  Fungi are an extremely rare cause of AECOPD.  Azole treatment would be indicated for allergic bronchopulmonary aspergillosis; such patients have a history of refractory asthma and chest x-ray typically shows bronchiectasis with mucus impaction.

(Choice B)  Inhaled corticosteroids are used for long-term control of asthma, and occasionally for severe but stable COPD (eg, GOLD Group D).  They do not have therapeutic efficacy for AECOPD and offer no additional advantage in patients already taking systemic corticosteroids.

(Choice C)  Inhaled mucolytic agents (eg, N-acetylcysteine) can aid in thinning of respiratory secretions.  They may be used adjunctively as part of a good pulmonary hygiene regimen, but they have no impact on recovery or outcomes of AECOPD.

(Choice D)  In the general population without COPD, acute bronchitis (predominantly viral in origin) is treated with reassurance and supportive care; antibiotics or steroids are almost never indicated.

(Choice E)  Roflumilast is a selective phosphodiesterase-4 inhibitor with anti-inflammatory properties.  It is effective for AECOPD prophylaxis in high-risk patients (ie, frequent exacerbations), but it has no role in acute treatment.

Educational objective:
Patients with moderate or severe acute exacerbations of chronic obstructive pulmonary disease (eg, hospitalized) should be treated with empiric antibiotic therapy (eg, fluoroquinolone) targeting commensal respiratory bacteria.