Guidelines
Mogayzel PJ Jr, Naureckas ET, Robinson KA, et al. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2013;187:680-9. This document offers graded recommendations for medication use according to patient age and severity of lung disease. It also summarizes areas of uncertainty.
Flume PA, Mogayzel PJ Jr, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med 2009; 180:802-8. This document offers graded recommendations for management of exacerbations, but is most noteworthy for highlighting the lack of evidence guiding many fundamental aspects of care.
Floto RA, Olivier KN, Saiman L, et al. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis: executive summary. Thorax. 2016;7:88-90.
A summary of evidence-based recommendations regarding screening, diagnosis, therapeutics, and transplant considerations for patients with cystic fibrosis.
Treatment of exacerbations
Goss CH, Heltshe SL, West NE,et al; on behalf of the STOP2 Investigators. A randomized clinical trial of antimicrobial duration for cystic fibrosis pulmonary exacerbation treatment. Am J Respir Crit Care Med 2021; 204: 1295-1305. Noteworthy for being the most robust study of antibiotic duration in CF exacerbation to date. Among the 214 patients with an early robust response to IV antibiotics (defined as > 8% improvement in ppFEV1 and significant improvement in symptoms), completing a total of 10 days of IV antibiotics was non-inferior to 14 days. Among the 705 patients without an early robust response, completing 21 days of IV antibiotics was not superior to a 14-day total course. Of note, the mean ppFEV1 decline from baseline was only 2.5% in those without an early response vs. down 9.3% in the early response group, which raises the possibility the patients assigned to the longer course of treatment were less likely to benefit from IV antibiotics in the first place.
Respiratory Complications of CF
Mingora CM, Flume PA. Pulmonary complications in cystic fibrosis: past, present, and future: adult cystic fibrosis series. Chest. 2021; 160:1232-1240. This review provides an overview of pneumothorax, hemoptysis, pulmonary hypertension, and acute respiratory failure, as well as advanced care planning including consideration of lung transplantation and palliative care.
Therapeutics- CFTR Modulators
Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011;365:1663-72. The first study to show a substantial benefit from a therapy targeting the underlying cause of clinical CF, this trial showed an absolute increase in predicted FEV1 of 10% in patients with at least one G551D-CFTR mutation receiving ivacaftor, a CFTR potentiator, compared to a small FEV1 decline in the placebo group, over a study period of approximately six months.
Middleton PG, Mall MA, Drevinek P, et al. Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med. 2019;381:1809-19. Randomized, double-blind, placebo-controlled trial of 403 patients 12 years or older with single Phe508del allele found elexacaftor-tezacaftor-ivacaftor improved percent predicted FEV1 by 14% at 24 weeks compared to placebo (p<0.001). Rate of exacerbation was 63% lower in the treatment group (p<0.001).
Barry PJ, Mall MA, Alvarez A, et al. Triple therapy for cystic fibrosis phe508del-gating and-residual function genotypes. N Engl J Med. 2021; 385: 815-825. RCT noteworthy for showing triple therapy with elexacaftor–tezacaftor–ivacaftor was superior to monotherapy with ivacaftor in this population, including 3.5% higher FEV1% predicted and clinically important differences in respiratory symptom scores.
