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.