Mycobacterium chimaera Pulmonary Disease in Cystic Fibrosis Patients, France, 2010-2017.

We report Mycobacterium chimaera pulmonary disease in 4 patients given a diagnosis of cystic fibrosis in a university hospital in Montpellier, France. All patients had M. chimaera-positive expectorated sputum specimens, clinical symptoms of pulmonary exacerbation, or a decrease in spirometry test results that improved after specific treatment.

Personalized medicine in CF: from modulator development to therapy for cystic fibrosis patients with rare CFTR mutations.

Cystic fibrosis (CF) is the most common life-shortening genetic disease affecting ~1 in 3,500 of the Caucasian population. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. To date, more than 2,000 CFTR mutations have been identified, which produce a wide range of phenotypes. The CFTR protein, a chloride channel, is normally expressed on epithelial cells lining the lung, gut, and exocrine glands. Mutations in CFTR have led to pleiotropic effects in CF patients and have resulted in early morbidity and mortality. Research has focused on identifying small molecules, or modulators, that can restore CFTR function. In recent years, two modulators, ivacaftor (Kalydeco) and lumacaftor/ivacaftor (Orkambi), have been approved by the U.S. Food and Drug Administration to treat CF patients with certain CFTR mutations. The development of these modulators has served as proof-of-concept that targeting CFTR by modulators is a viable therapeutic option. Efforts to discover new modulators that could deliver a wider and greater clinical benefit are still ongoing. However, traditional randomized controlled trials (RCTs) require large numbers of patients and become impracticable to test the modulators' efficacy in CF patients with CFTR mutations at frequencies much lower than 1%, suggesting the need for personalized medicine in these CF patients.

The Mist Tent: An Analysis of Therapeutic Change in the History of Cystic Fibrosis Care.

Mist tent therapy for cystic fibrosis went through a rise and fall in popularity between the 1950s and 1970s, providing an opportunity to explore the nature of therapeutic change in medicine. The therapy "worked" in the context of a particularly grim life expectancy in the early 1950s and in the setting of a comprehensive therapeutic program that began in Cleveland in 1957. Although clinical studies published in the 1970s provided evidence that mist tents were ineffective or even harmful, these later studies were not necessarily more robust than earlier studies that provided evidence of mist tent efficacy, suggesting that other factors may have also contributed to mist tent abandonment. In fact, the unpalatable nature of mist tent therapy, which was described by one doctor as akin to incarceration, and studies that questioned the theoretical underpinnings of the therapy also played important roles in the eventual abandonment of mist tents.

Cystic Fibrosis Diagnostic Challenges over 4 Decades: Historical Perspectives and Lessons Learned.

OBJECTIVE: Because cystic fibrosis (CF) can be difficult to diagnose, and because information about the genetic complexities and pathologic basis of the disease has grown so rapidly over the decades, several consensus conferences have been held by the US CF Foundation, and a variety of other efforts to improve diagnostic practices have been organized by the European CF Society. Despite these efforts, the application of diagnostic criteria has been variable and caused confusion. STUDY DESIGN: To improve diagnosis and achieve standardization in terms and definitions worldwide, the CF Foundation in 2015 convened a committee of 32 experts in the diagnosis of CF from 9 countries. As part of the process, all previous consensus-seeking exercises sponsored by the CF Foundation, along with the important efforts of the European CF Society, were comprehensively and critically reviewed. The goal was to better understand why consensus conferences and their publications have not led to the desired results. RESULTS: Lessons learned from previous diagnosis consensus processes and products were identified. It was decided that participation in developing a consensus was generally not inclusive enough for global impact. It was also found that many efforts to address sweat test issues were valuable but did not always improve clinical practices as CF diagnostic testing evolved. It also became clear from this review that premature applications of potential diagnostic tests such as nasal potential difference and intestinal current measurement should be avoided until validation and standardization occur. Finally, we have learned that due to the significant and growing number of cases that are challenging to diagnose, an associated continuing medical education program is both desirable and necessary. CONCLUSIONS: It is necessary but not sufficient to organize and publish CF diagnosis consensus processes. Follow-up implementation efforts and monitoring practices seem essential.