Defining a pulmonary exacerbation in cystic fibrosis.
OBJECTIVE
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 to establish a standardized PEx definition and score for use in clinical trials, based on clinical status rather than on treatment decisions.


METHODS
Subjects were 246 patients enrolled in the placebo arm of a randomized, controlled trial of tobramycin for inhalation. Physician-investigators completed PEx questionnaires on all subjects at scheduled intervals during the 6-month study, indicating new or worsening symptoms, physical examination findings, and impression of PEx status (presence or absence and severity). 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%; specificity, 86%). The scores were validated in subjects in the intervention arm of the trial.


CONCLUSIONS
We hope that the proposed PEx score might serve as a standardized outcome measure for future clinical trials in cystic fibrosis, allowing meaningful comparisons of study results.
Rosenfeld
M
M
Division of Pulmonary Medicine, Children's Hospital and Regional Medical Center, Seattle, Washington 98105, USA.
Emerson
J
J
Williams-Warren
J
J
Pepe
M
M
Smith
A
A
Montgomery
A B
AB
Ramsey
B
B
D000280:Administration, Inhalation; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000503:physiopathology*; D008297:Male; D008448:Maximal Expiratory Flow Rate; D015337:Multicenter Studies as Topic; D012372:ROC Curve; D016032:Randomized Controlled Trials as Topic; D011795:Surveys and Questionnaires; D014031:Tobramycin / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D014031:Tobramycin