Defining a pulmonary exacerbation in cystic fibrosis

Objectives: Despite the central importance of pulmonary exacerbations (PExs ) as an outcome measure in cystic fibrosis clinical trials, no standardized definition of PEx, exists. We conducted a prospective, multicenter study t o establish a standardized PEx definition and score for use in clinical tri als, based on clinical status rather than on treatment decisions. Study design: Subjects were 246 patients enrolled in the placebo arm of a r andomized, controlled trial of tobramycin for inhalation. Physician-investi gators completed PEx questionnaires on all subjects at scheduled intervals during the 6-month study, indicating new or worsening symptoms, physical ex amination findings, and impression of PEx status (presence or absence and s everity). Logistic regression was used to assess the relative importance of each of the characteristics in predicting a PEx. Results: We developed 2 PEx scores that use easily ascertained symptoms and chest examination Findings; one also includes change in forced expiratory volume in 1 second over the preceding month. Both scores were sensitive and specific for predicting the presence of a PEx (sensitivity, 86%; specifici ty, 86%). The scores were validated in subjects in the intervention arm or the trial. Conclusion: We hope that the proposed PEx score might serve as a standardiz ed outcome measure for future clinical trials in cystic fibrosis, allowing meaningful comparisons of study results.