ATS Reading List

Cystic Fibrosis

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.
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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Therapeutics- Inhaled Medications

Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis: the Pulmozyme Study Group. N Engl J Med 1994;331:637-42. Large RCT found patients receiving a 24-week course of Pulmozyme had an improvement in FEV1 of 5% compared to placebo and decreased exacerbation rate (28 vs. 37% in placebo group).
PMID: 7503821
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Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999;340:23-9. Study found use of TOBI on alternating months improved lung function, decreased bacterial burden, and decreased the relative risk of hospitalization. The rate of acquired tobramycin resistance was about 7% over 24 weeks.
PMID: 9878641
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Balfour-Lynn IM, Lees B, Hall P, et al. Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis. Am J Respir Crit Care Med 2006; 173:1356-62. This study of 171 children and adults with mean baseline FEV1 of 76% predicted found no difference in time to 1st exacerbation, or use of rescue bronchodilators and antibiotics over the first 6 months of withdrawing inhaled steroid. These results suggest that many CF patients may be able to safely discontinue inhaled steroids.
PMID: 16556691

Elkins MR, Robinson M, Rose BR, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 2006; 354:229-40. This study of 164 children and adults with CF found the combination of bronchodilator and 7% saline neb bid had only a modest impact on pulmonary function but reduced exacerbations (76% exacerbation free vs. 62% placebo, p = .03). These results may not be applicable to patients on more aggressive baseline regimens than the study population.
PMID: 16421364
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Retsch-Bogart GZ, Quittner AL, Gibson RL, et al. Efficacy and safety of inhaled aztreonam lysine for airway Pseudomonas in cystic fibrosis. Chest 2009;135:1223-32. This, the largest published study of inhaled aztreonam, randomized 164 children and adults with moderate-to-severe CF lung disease and pseudomonas infection to receive inhaled aztreonam (75 mg TID) or placebo for 28 days. The treatment group had no increased adverse events, but had a reduction in productive cough (25% vs 12.5%) as well as significant improvement in multiple CFQ-R scales. No difference in treatment emergent infections was observed. This study demonstrated short term safety and benefits.
PMID: 19420195
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Therapeutics- Azithromycin

Saiman L, Marshall BC, Mayer-Hamblett N, et al. Azithromycin in patients with cystic fibrosis chronically infected with pseudomonas aeruginosa. JAMA 2003;290:1749-56. Large multicenter RCT of 6 months duration found chronic azithromycin resulted in a 4.4% improvement in FEV1% predicted compared to a 1.8% decline in placebo. The azithromycin group had fewer exacerbations and gained more weight.
PMID: 14519709
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Therapeutics- CFTR potentiators

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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Wainwright CE, Elborn JS, Ramsey BW, et al. Lumacaftor–ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med 2015; 373: 220-231. This reports on pooled data from two multi-center, double-blind, placebo-controlled studies, lasting 24 weeks, assessing the effect of ivacaftor in combination with two different doses of lumacaftor in patients with homozygous Phe508del CFTR mutations. The treatment group had a mean improvement in percent predicted FEV1 ranging from 2.4 to 4.0 points (p < .001), as well as a 30% reduction in the risk of exacerbation. There were a similar number of adverse event between groups. It remains to be seen whether these benefit persist or accumulate over time.
PMID: 25981758
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Last Reviewed: June 2017