Unsupervised home spirometry is not equivalent to supervised clinic spirometry in children and young people with cystic fibrosis: Results from the CLIMB-CF study.

BACKGROUND: Handheld spirometry allows monitoring of lung function at home, of particular importance during the COVID-19 pandemic. Pediatric studies are unclear on whether values are interchangeable with traditional, clinic-based spirometry. We aimed to assess differences between contemporaneous, home (unsupervised) and clinic (supervised) spirometry and the variability of the former. The accuracy of the commercially available spirometer used in the study was also tested. METHODS: Data from participants in the Clinical Monitoring and Biomarkers to stratify severity and predict outcomes in children with cystic fibrosisc (CLIMB-CF) Study aged ≥ 6 years who had paired (±1 day) clinic and home forced expiratory volume in 1 s (FEV1 ) readings were analyzed. Variability during clinical stability over 6-months was assessed. Four devices from Vitalograph were tested using 1 and 3 L calibration syringes. RESULTS: Sixty-seven participants (median [interquartile range] age 10.7 [7.6-13.9] years) provided home and clinic FEV1 data pairs. The mean (SD) FEV1 % bias was 6.5% [±8.2%]) with wide limits of agreement (-9.6% to +22.7%); 76.2% of participants recorded lower results at home. Coefficient of variation of home FEV1 % during stable periods was 9.9%. Data from the testing of the handheld device used in CLIMB-CF showed a potential underread. CONCLUSION: In children and adolescents, home spirometry using hand-held equipment cannot be used interchangeably with clinic spirometry. Home spirometry is moderately variable during clinical stability. New handheld devices underread, particularly at lower volumes of potential clinical significance for smaller patients; this suggests that supervision does not account fully for the discrepancy. Opportunities should be taken to obtain dual device measurements in clinic, so that trend data from home can be utilized more accurately.

The Equitable Implementation of Cystic Fibrosis Personalized Medicines in Canada.

This article identifies the potential sources of inequity in three stages of integrating cystic fibrosis personalized medicines into the Canadian healthcare system and proposes mitigating strategies: (1) clinical research and diagnostic testing; (2) regulatory oversight and market authorization; and (3) implementation into the healthcare system. There is concern that differential access will cast a dark shadow over personalized medicine by stratifying the care that groups of patients will receive-not only based on their genetic profiles, but also on the basis of their socioeconomic status. Furthermore, there is a need to re-evaluate regulatory and market approval mechanisms to accommodate the unique nature of personalized medicines. Physical and financial accessibility ought to be remedied before personalized medicines can be equitably delivered to patients. This article identifies the socio-ethical and legal challenges at each stage and recommends mitigating policy solutions.

CFTR modulator theratyping: Current status, gaps and future directions.

BACKGROUND: New drugs that improve the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein with discreet disease-causing variants have been successfully developed for cystic fibrosis (CF) patients. Preclinical model systems have played a critical role in this process, and have the potential to inform researchers and CF healthcare providers regarding the nature of defects in rare CFTR variants, and to potentially support use of modulator therapies in new populations. METHODS: The Cystic Fibrosis Foundation (CFF) assembled a workshop of international experts to discuss the use of preclinical model systems to examine the nature of CF-causing variants in CFTR and the role of in vitro CFTR modulator testing to inform in vivo modulator use. The theme of the workshop was centered on CFTR theratyping, a term that encompasses the use of CFTR modulators to define defects in CFTR in vitro, with application to both common and rare CFTR variants. RESULTS: Several preclinical model systems were identified in various stages of maturity, ranging from the expression of CFTR variant cDNA in stable cell lines to examination of cells derived from CF patients, including the gastrointestinal tract, the respiratory tree, and the blood. Common themes included the ongoing need for standardization, validation, and defining the predictive capacity of data derived from model systems to estimate clinical outcomes from modulator-treated CF patients. CONCLUSIONS: CFTR modulator theratyping is a novel and rapidly evolving field that has the potential to identify rare CFTR variants that are responsive to approved drugs or drugs in development.