Lung function changes before and after pulmonary exacerbation antimicrobial treatment in cystic fibrosis

Background In cystic fibrosis, observation of a lung function drop (as percent predicted forced expiratory volume in 1 s [FEV1]; ppFEV(1)) frequently precedes pulmonary exacerbation (PEx) diagnosis. Recovery of ppFEV(1) to a previous baseline is commonly used to assess antimicrobial treatment response. However, not all diagnosed PEx are associated with a ppFEV(1) drop, and it is unclear whether these are a different type of PEx from those associated with a ppFEV(1) drop. Methods We analyzed pre- and posttreatment ppFEV(1) for PEx recorded in the Epidemiologic Study of Cystic Fibrosis from 2003 through 2005. Baseline, pretreatment, and follow-up ppFEV(1) were the best recorded within 12-months pre-PEx, the lowest recorded -30 to +3 days of treatment, and the best recorded during 6-month follow-up, respectively. Logistic regression models for return of ppFEV(1) to baseline during follow-up were developed separately for PEx with >= 10%, <10%, and no ppFEV(1) drop before treatment. Results Of 15 147 PEx, 10 166 (67.1%), 3479 (23.0%), and 1502 (9.9%) presented with a >= 10%, <10%, or no ppFEV(1) drop at diagnosis, respectively. 19.5%, 35.2%, and 65.6% of PEx, respectively, had follow-up ppFEV(1) equal to or exceeding baseline; overall 27.7% of all PEx treatments resulted in complete recovery of baseline ppFEV(1). Significant predictors of ppFEV(1) recovery at follow-up were younger patient age, absence of Aspergillus, lower baseline ppFEV(1), fewer visits during the baseline, lower frequency of prior-year PEx, shorter elapsed time from baseline measure to treatment, smaller relative ppFEV(1) drop before treatment, and non intravenous (ie, oral or inhaled antibiotic) treatment. PEx with >= 10%, <10%, and no ppFEV(1) drop before treatment had only modest differences in covariate odds ratios associated with complete ppFEV(1) recovery. Conclusions Among the 10% of PEx presenting with no apparent ppFEV(1) drop, more than one-third resulted in a decreased ppFEV(1) during follow-up. Risk factors for this outcome were the same as those associated with lack of ppFEV(1) recovery among PEx with pretreatment ppFEV(1) drops. These results suggest that inherent FEV1 variability, baseline and follow-up sampling methodologies, ppFEV(1) regression to the mean, and underlying lung disease progression complicate this approach for assessing effects of PEx and treatment response.