Jon-Emile S. Kenny [@heart_lung] In memory of a kind and gentle soul, I would like to share this brief and basic overview of the genetics of cystic fibrosis [CF]. While CF had been known to be an autosomal recessive gene since 1949 – given its inheritance pattern – it was in 1989 when researchers at [… read more]
More Children Under 12 to Be Considered for Adult Lung Transplants The Organ Procurement and Transplantation Network (OPTN), which is responsible for the life-and-death policies for allocation of lung transplants and other organs, announced it will allow children needing lung transplants to file expedited appeals to be listed for adult lungs. Children under 12 with [… read more]
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]
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]
Intracranial hemorrhage is a subject neuro-intensivists spend years learning about and refining their knowledge and skills on. A few key points: Myocardial “stunning” with depressed ejection fraction and pulmonary edema should be expected, due to a form of tako-tsubo cardiomyopathy, most commonly in subarachnoid hemorrhage. It’s not due to ischemia and gets better over weeks. [… 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]
Airway remodeling and its relationship to inflammation in cystic fibrosis. Regamey N et al. Thorax 2011;66:624-629.
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 showed that it can (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]