Cystic Fibrosis


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.
PMID: 23540878

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.
PMID: 19729669

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.
PMID: 26678435
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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 exacerbations. 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.
PMID: 34469706

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.
PMID: 34147501

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.
PMID: 22047557
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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).
PMID: 31697873

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.
PMID: 34437784
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