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.

Impulse oscillometry and spirometry measurements relative to personal best values at the time of acute exacerbations of cystic fibrosis in adults

“…At the time of AE, the mean variation of FEV1 relative to the best personal value was −0.26 ± 0.22 L, similar to several studies that reported decrease in FEV1 in a context of AE (McCourt et al., 2015; Sanders et al., 2011). Improvement of FEV1 value after AE treatment is also reported (Hoppe et al., 2018; Ren et al., 2006; Wagener et al., 2020). Interestingly, Cooper et al.…”

Epidemiologic Study of Cystic Fibrosis: 25 years of observational research

“…Evaluation of lung function recovery after exacerbation treatment 56 . Complete ppFEV 1 recovery of baseline at follow‐up during 2003–2005 was dependent on baseline definition, timing of assessment, and the ppFEV 1 difference between baseline and treatment start.…”

“…The Epidemiologic Study of Cystic Fibrosis (ESCF) was an observational study begun in 1993 and ultimately spanning more than 10 years of data collection. There have been 56 peer‐reviewed publications 1–56 that have been cited over 3600 times (mean 65, median 43). ESCF was initiated in response to an FDA request for postmarketing pharmacovigilance on the newly approved therapy dornase alfa (Pulmozyme®) and was sponsored by Genentech, Inc.…”

Dr Jeffrey S. Wagener: An impactful career and life

“…Dr Jeffrey S. Wagener passed away in October of 2018, but he left an indelible mark on the field of Pediatric Pulmonary Medicine, Cystic Fibrosis, colleagues, trainees and patients around the world. Through these comments accompanying his last publication, we hope to recognize Jeff's contributions and inspire others by his example.…”

“…He had a particular interest in characterizing pulmonary exacerbations (PEx) in cystic fibrosis and their impact on patient outcomes. In this issue, Jeff reports an analysis of changes in lung function in ESCF participants before and after pulmonary exacerbations (PEx) treated with antimicrobials. Lung function decline often plays a key role in PEx diagnosis and the recovery of percent predicted FEV 1 (ppFEV 1 ) to a prior “baseline value” is commonly used to assess treatment response.…”