Background In 2011, the median age of survival in cystic fibrosis (CF) reported in the United States (US) was 36.8 years compared to 48.5 years in Canada; however direct comparison of survival estimates between national registries is challenging because of inherent differences in methodologies used, data processing techniques, and ascertainment bias. Objectives To use a standardized approach to calculate CF survival estimates and to explore differences between Canada and the United States (US). Design Population-based study. Setting 42 Canadian CF clinics and 110 CF care centers in the US. Patients Patients followed in the Canadian CF Registry (CCFR) and the US Cystic Fibrosis Foundation (CFF) Patient Registry (CFFPR) between 1990 and 2013. Measurement Cox proportional hazards models were used to compare survival between patients followed in the CCFR (n=5,941) and CFFPR (n=45,448). Multivariable models were used to adjust for factors known to be associated with survival. Results Median age of survival in patients with CF increased in both countries between 1990 and 2013; however in 1995 and 2005, survival in Canada increased at a faster rate relative to the US (p<0.001). Using contemporary data from 2009-2013, the median age of survival in Canada was ten years greater than the US (50.9 vs. 40.6 years, respectively). The adjusted risk of death was 34% lower in Canada compared to the US (hazard ratio 0.66, 95% CI 0.54-0.81). A greater proportion of patients had transplants in Canada (10.3% vs. 6.5% respectively, SD 13.7). Differences in survival between US and Canadian patients varied according to the US patients' insurance status. Limitations Ascertainment bias as a result of missing data or non-random lost to follow-up could impact the results. Conclusions Differences in CF survival between Canada and the US persisted after adjusting for risk factors associated with survival. Differential access to transplantation, improved post-transplant survival and differences in the healthcare systems may, in part, explain the Canadian survival advantage.

No abstract

Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that affects about 70,000 people worldwide. The clinical manifestations of the disease are caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a sophisticated understanding of how thousands of mutations in the CFTR gene affect the structure and function of the CFTR protein. Much progress has been made over the past decade with the development of orally bioavailable small molecule drugs that target defective CFTR proteins caused by specific mutations. Furthermore, there is considerable optimism about the prospect of gene replacement or editing therapies to correct all mutations in cystic fibrosis. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. This review provides an update on advances in our understanding of the structure and function of the CFTR, with a focus on state of the art targeted drugs that are in development.

Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade.Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilatorassociated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

Although several factors have been found to be associated with the CFQ-R in adolescents and adults with CF, FEV1 % predicted and pulmonary exacerbations have the broadest impact on HRQoL. Further research is required to investigate the impact of age-related comorbidities, psychosocial factors, and treatment-related factors on HRQoL in adolescents/adults with cystic fibrosis.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies target the underlying cause of cystic fibrosis (CF), and are generally well-tolerated; however, real-world studies indicate the frequency of discontinuation and adverse events (AEs) may be higher than what was observed in clinical trials. The objectives of this systematic review were to summarize real-world AEs reported for market-available CFTR modulators (i.e., ivacaftor (IVA), lumacaftor/ivacaftor (LUM/IVA), tezacaftor/ivacaftor (TEZ/IVA), and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA)), and to identify ways in which the pharmacist on CF healthcare teams may contribute to mitigating and managing these AEs. The MEDLINE, EMBASE, CINAHL, and Web of Science Core Collection online databases were searched from 2012 to 1 Aug 2020. Full manuscripts or conference abstracts of observational studies, case series, and case reports were eligible for inclusion. The included full manuscripts and conference abstracts comprised of 54 observational studies, 5 case series, and 9 case reports. The types of AEs reported generally aligned with what have been observed in clinical trials. LUM/IVA was associated with a higher frequency of respiratory-related AE and discontinuation in real-world studies. A signal for mental health and neurocognitive AEs was identified with all 4 CFTR modulators. A systematic approach to monitoring for AEs in people with CF on CFTR modulators in the real-world setting is necessary to help better understand potential AEs, as well as patient characteristics that may be associated with higher risk of certain AEs. Pharmacists play a key role in the safe initiation and monitoring of people with CF on CFTR modulator therapies.

No abstract

No abstract