Grand roundCystic fibrosis pulmonary exacerbations
Section snippets
Pathophysiology of pulmonary exacerbations
Given the importance of pulmonary exacerbations in CF, remarkably little is known about their pathophysiology. It is likely that complex interactions between respiratory epithelia, immune cells, and bacteria are central to the process by which pulmonary exacerbations occur, though the precise cellular or molecular mechanisms remain to be elucidated.19, 20 It is commonly accepted that pulmonary exacerbations are the result of an increased bacterial endobronchial burden and the associated host
Clinical characteristics defining a pulmonary exacerbation
Despite the central role that pulmonary exacerbations play in CF clinical research and clinical care, no standardized definition has been published nor accepted, so the presence of an exacerbation remains essentially a clinical diagnosis.4 While not validated nor applicable to the clinical trial setting, a definition in widespread clinical use is that from the Cystic Fibrosis Foundation Clinical Practice Guidelines,6 which defines a pulmonary exacerbation as at least 3 of 11 new findings or
Epidemiology of pulmonary exacerbations
The frequency of pulmonary exacerbation occurrence depends on the population being studied and the definition used. Utilizing data collected from the Epidemiologic Study of Cystic Fibrosis, the percent of patients requiring treatment with antibiotics for an exacerbation increased with age: 23% annually for children under 6 years, 32% for ages 6 to 12 years, 48% for age 13 to 17 years, and 63% for patient older than 18 years.27 In another study of patients older than 6 years of age and colonized
Evaluation of pulmonary exacerbations
The evaluation of a patient presenting with a pulmonary exacerbation includes measures to achieve the following: (1) establish the presence and severity of the exacerbation; (2) determine appropriate antibiotic therapy; (3) permit the monitoring of the response to therapy; and (4) determine resolution of the exacerbation.
Evidence-based management of pulmonary exacerbations
Few well-designed and sufficiently powered studies have been conducted to evaluate the efficacy of different therapeutic interventions for the treatment of pulmonary exacerbations. In spite of this, there is general consensus that antibiotic therapy and airway clearance are key components of the treatment of pulmonary exacerbations.43
In general, the trials of pulmonary exacerbation treatment have evaluated patients chronically infected with P. aeruginosa. In these patients, antibiotic therapy
Prevention of pulmonary exacerbations
Given the significant morbidity associated with exacerbations, identifying strategies that decrease their occurrence is of great importance. Several clinical trials, which used exacerbation rates as an outcome variable for the study, showed significant decreases in the rate of investigator-defined exacerbations compared to control groups. The long-term clinical trials examining inhaled antibiotics, mucolytics, and azithromycin16, 17, 18 each showed significant and clinically important
Conclusions
Various insults, including bacteria, viral illnesses, and airborne irritants, can alter the fragile balance between pathogens and local defenses in the CF airway, leading to escalating respiratory signs and symptoms (typically an increasing, productive cough) related to increased airway secretions, which is termed “pulmonary exacerbation.” Pulmonary exacerbations are cardinal features of CF lung disease and are associated with greater morbidity and mortality. They stand out as an important
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Drs Thomas Ferkol and Carlos Milla are or have been members of a speakers’ bureau sponsored by the Chiron Corporation (Emeryville, CA).