Kalydeco: New Drug Helps Some with Cystic Fibrosis On January 31, the FDA approved ivacaftor (Kalydeco), the first-ever drug that treats an underlying cause of cystic fibrosis. In about 4% of cystic fibrosis patients, defective chloride ion channel transporters (CFTRs) are trafficked to the cell membrane, but don’t work properly. Kalydeco “unlocks” and improves function [... read more]
(image: Bennett Gamel blog) Inhaled hypertonic saline (7% NaCl) increases clearance of mucus by airway cilia, making it an attractive treatment for cystic fibrosis. Hypertonic saline has been a cornerstone of daily therapy for CF ever since a 2006 NEJM randomized trial showed that ~80 adults and kids older than 6 using hypertonic saline for [... read more]
Cystic Fibrosis 2012 Review (More 2012 Topic Updates) From the excellent summary by Felix Ratjen (U-Toronto) and Susanna McColley (Northwestern) in the May 2012 AJRCCM (Blue Journal), and our own cystic fibrosis literature review. Pulmonary Infection in Cystic Fibrosis The standard practice of early eradication of Pseudomonas aeruginosa in cystic fibrosis patients — giving inhaled [... read more]
A novel combination of fosfomycin/tobramycin produced by Gilead Sciences appeared safe and effective for patients with cystic fibrosis and chronic Pseudomonas infection, in a Phase 2 multicenter randomized trial of 119 patients across the U.S. To control chronic Pseudomonas infection, cystic fibrosis patients alternate between 28 days of inhaled antibiotics and 28 days without. The “without” period [... read more]
Most people with cystic fibrosis have mutations in the CFTR gene that prevent sufficient quantities of the assembled channels from making it to the cell membrane surface. That’s a hard problem to fix. However, a small minority (4-5%) have mutations on the G551D allele that impair the function of the CFTR ion channel once it [... read more]
A general overview of a broad topic that neuro-intensivists spend years learning about and refining their knowledge and skills on. So I won’t suggest my summary of a summary can do it justice. Some high-yield, interesting points I took away: Myocardial “stunning” with depressed ejection fraction and pulmonary edema should be expected, due to a [... read more]
It’s long been known in the pediatric cystic fibrosis population that exacerbations accelerate decline of lung function. de Boer et al show that exacerbations are just as bad or worse in adults. Following 446 adults with CF in Ontario for 3 years, those with >2 exacerbations per year had a hazard ratio of 4.05 for [... read more]
Self-reported adherence is usually overestimated. Most people prescribed chronic daily medication take it ~60% of the time, but say/believe they take it 90% of the time. People with cystic fibrosis are instructed to spend more than an hour a day sitting through up to 7 nebulizer treatments. Daniels et al used a smart nebulizer machine [... read more]
Geller et al randomized 151 cystic fibrosis patients with chronic Pseudomonas infection to receive nebulized levofloxacin (at 1 of 3 dosing levels) or placebo for 28 days. All treated groups had a reduction in sputum Pseudomonas density, the primary outcome, and the highest dose had a 1-log drop. FEV1 was 9% better than placebo in [... read more]
Airway remodeling and its relationship to inflammation in cystic fibrosis. Regamey N et al. Thorax 2011;66:624-629.
Update in cystic fibrosis 2010. Mogayzel PJ, Flume PA. AJRCCM 2011;183:1620-1624. Cystic fibrosis review.
Managing cystic fibrosis: strategies that increase life expectancy and improve quality of life. Cohen-Cymberknoh M et al. AJRCCM 2011;183:1463-1471.
Although universally recommended, there was no evidence that nebulized hypertonic saline actually reduced inflammation in the airways of cystic fibrosis patients. Reeves et al proved that it does (specifically, by disrupting IL-8 from glycosaminoglycan matrices before they can recruit neutrophils by chemotaxis to wreak havoc). AJRCCM 2011;183:1517-1523.
CF patients are instructed to inhale dornase alpha 30 minutes before airway clearance techniques. This has always been based on lore and plausibility. Dentice & Elkins publish their meta-analysis of 5 studies, including a total of 122 patients who were randomized and crossed-over to test the effect of the timing of dornase inhalation on outcomes. [... read more]
Accurso et al report phase 3 results from industry-funded TIGER-1, testing t.i.d. inhaled denufusol (an ion channel regulator that alters sodium/chloride transport to improve mucociliary clearance) vs. placebo in early cystic fibrosis (FEV1>74% predicted). After 24 weeks, FEV1 was 45 mL better in the treated group, most of whom were younger than age 19. There [... read more]