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

Abstract

Background: In cystic fibrosis, observation of a lung function drop (as percent predicted forced expiratory volume in 1 s [FEV₁ ]; ppFEV₁ ) frequently precedes pulmonary exacerbation (PEx) diagnosis. Recovery of ppFEV₁ to a previous "baseline" is commonly used to assess antimicrobial treatment response. However, not all diagnosed PEx are associated with a ppFEV₁ drop, and it is unclear whether these are a different type of PEx from those associated with a ppFEV₁ drop.

Methods: We analyzed pre- and posttreatment ppFEV₁ for PEx recorded in the Epidemiologic Study of Cystic Fibrosis from 2003 through 2005. Baseline, pretreatment, and follow-up ppFEV₁ 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 ppFEV₁ to baseline during follow-up were developed separately for PEx with ≥10%, <10%, and no ppFEV₁ 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 ppFEV₁ drop at diagnosis, respectively. 19.5%, 35.2%, and 65.6% of PEx, respectively, had follow-up ppFEV₁ equal to or exceeding baseline; overall 27.7% of all PEx treatments resulted in complete recovery of baseline ppFEV₁ . Significant predictors of ppFEV₁ recovery at follow-up were younger patient age, absence of Aspergillus, lower baseline ppFEV₁ , fewer visits during the baseline, lower frequency of prior-year PEx, shorter elapsed time from baseline measure to treatment, smaller relative ppFEV₁ drop before treatment, and non intravenous (ie, oral or inhaled antibiotic) treatment. PEx with ≥10%, <10%, and no ppFEV₁ drop before treatment had only modest differences in covariate odds ratios associated with complete ppFEV₁ recovery.

Conclusions: Among the 10% of PEx presenting with no apparent ppFEV₁ drop, more than one-third resulted in a decreased ppFEV₁ during follow-up. Risk factors for this outcome were the same as those associated with lack of ppFEV₁ recovery among PEx with pretreatment ppFEV₁ drops. These results suggest that inherent FEV₁ variability, baseline and follow-up sampling methodologies, ppFEV₁ regression to the mean, and underlying lung disease progression complicate this approach for assessing effects of PEx and treatment response.

Keywords: cystic fibrosis; lung function; pulmonary exacerbations.