Pulmonary Exacerbations (PEx)
Despite the use of CFTR modulators, PEx still occur, and research related to optimizing outcomes has been published this year. Standard of care for PEx is to treat with two anti- PA antibiotics, however a recent analysis using used both the CFF PR and the Pediatric Health Information System (PHIS), one versus two anti-PA antibiotics, was analyzed in over 2500 exacerbations66. Investigating the year 2007-2018, in PwCF 6-17 years of age, no differences were seen between one or two anti-PA antibiotics in pre or post exacerbation FEV1pp, odds of returning to ≥90% of baseline FEV1pp within three months, or time to next PEx requiring IV antibiotics. Therefore, additional prospective studies are indicated to determine use of only one anti – PA antibiotic would be beneficial by limiting antibiotic exposure while remaining clinically effective.
In addition to using FEV1pp as a marker of PEx improvement, the Chronic Respiratory Infection Symptom Score (CRISS) was evaluated in patients as part of the Standardized Treatment of Pulmonary Exacerbations (STOP)- Observational trial. The median baseline CRISS score was 49, and 93% of patients with PEx had a decline of ≥11 points (the minimal clinical important difference), thus CRISS was felt to be a useful efficacy endpoint67. Further analysis of the STOP cohort found the only difference between males and females was 13% more IV antibiotics treatment days for females68.
Optimal length for PEx was the subject of the STOP-2 trial69. If a participant had at least 8% improvement in FEV1pp and 11-point decrease in CRISS by day 7-10 of exacerbation, then 10 days of IV antibiotics was not inferior to 14 days. For those participants without an improvement at 7-10 days, 21 days of IV antibiotics was not superior to 14 days. As a sub study, the participants in STOP-2 study, C-reactive protein (CR) was assessed at start of antibiotics, 7-10 days into the PEx and two weeks after end of treatment, however levels were found to be variable and thus the authors concluded that the utility of CRP as a biomarker for PEx treatment response is limited70. Continued understanding of ideal methods for PEx treatment will remain of use since modulators have not eliminated PExs for PwCF.