Elsevier

The Journal of Pediatrics

Volume 139, Issue 3, September 2001, Pages 359-365
The Journal of Pediatrics

Original Articles
Defining a pulmonary exacerbation in cystic fibrosis,☆☆

https://doi.org/10.1067/mpd.2001.117288Get rights and content

Abstract

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 to establish a standardized PEx definition and score for use in clinical trials, based on clinical status rather than on treatment decisions. Study design: 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. Conclusion: 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. (J Pediatr 2001;139:359-65)

Section snippets

Study design

Physician-investigators completed a PEx questionnaire at 3 scheduled visits for each subject participating in a multicenter, phase III, randomized, controlled trial of tobramycin for inhalation.6 Subjects enrolled in this trial received inhaled tobramycin or placebo twice daily for 28 days, followed by 28 days without study drug. This cycle was repeated 2 more times during the 6-month study period. Treatment with conventional therapy, including oral and intravenous antibiotics, was not altered

Subject characteristics

A total of 520 subjects were enrolled in the clinical trial (258 in the tobramycin group and 262 in the placebo group). PEx data were available from 246 subjects in the placebo arm at the week 8 study visit (94% of total subjects enrolled in the placebo group) and from 234 subjects at the week 20 visit (89% of subjects in the placebo group). Subjects in the current study had demographic characteristics similar to those of subjects enrolled in the phase III study as a whole (Table I).They were

Discussion

The goal of the current study was to develop a standardized definition of a PEx for CF clinical trials that did not rely on therapeutic decisions. We evaluated the assessments of more than 100 physicians as to whether subjects were experiencing a PEx to determine the key components of their decision-making processes. We found that the features most important in determining the presence of a PEx were symptoms and features of the clinical history. Chest examination findings and pulmonary function

Acknowledgements

We thank the investigators in the Cystic Fibrosis Inhaled Tobramycin Study Group (seeAppendix 2).

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  • Cited by (0)

    Supported by the Cystic Fibrosis Foundation (Bethesda, Md) and PathoGenesis Corporation (Seattle, Wash).

    ☆☆

    Reprint requests: Margaret Rosenfeld, MD, MPH, Division of Pulmonary Medicine, Children's Hospital and Regional Medical Center, 4800 Sandpoint Way, Seattle, WA 98105.

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