CFTR-function and ventilation inhomogeneity in individuals with cystic fibrosis.

Bernasconi, Nadine; Kieninger, Elisabeth; Shaw, Michelle; Kurz, Johanna; Moeller, Alexander; Ratjen, Felix; Rochat, Isabelle; Stanojevic, Sanja; Singer, Florian (2021). CFTR-function and ventilation inhomogeneity in individuals with cystic fibrosis. Journal of cystic fibrosis, 20(4), pp. 641-647. Elsevier 10.1016/j.jcf.2020.12.009

[img] Text
1-s2.0-S1569199320309413-main.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (720kB) | Request a copy

BACKGROUND

Increased (abnormal) ventilation inhomogeneity in individuals with mild Cystic Fibrosis (CF) lung disease may become a treatable trait for small-molecule therapeutics improving Cystic Fibrosis Transmembrane Regulator (CFTR) function. The relationship between CFTR function and ventilation inhomogeneity is unknown. We aimed to identify and quantify increased ventilation inhomogeneity in relation to CFTR function.

METHODS

This was an international, multi-center, cross-sectional study. We collated data from individuals aged 3-25 years with minimal (CFTR-MF) or residual (CFTR-RF) function of a variety of CFTR genotypes and FEV1 ≥ 70% predicted. We measured lung function using nitrogen multiple-breath washout and spirometry. We compared lung clearance index (LCI) and FEV1 between individuals with CFTR-MF vs CFTR-RF using a mixed effects multi-variable linear regression model to account for study differences and a logistic model based on propensity-score matching to adjust for possible confounding.

RESULTS

We included 141 with CFTR-MF and 35 with CFTR-RF. LCI (> 1.96 z-score) was elevated in 71.6% individuals with CFTR-MF and in 40.0% with CFTR-RF. FEV1 (< -1.96 z-score) was reduced in 11.3% individuals with CFTR-MF and in 5.7% with CFTR-RF. The mean difference (95% CI) of LCI and FEV1 between CFTR-MF and CFTR-RF was 3.71 (1.63 to 5.79) and -0.40 (-0.83 to 0.02) z-score. The LCI differences were similar after adjustment for confounders and in individuals with normal FEV1.

CONCLUSION

Increased ventilation inhomogeneity is associated with less CFTR function. In individuals with mild CF lung disease, LCI can identify and quantify increased ventilation inhomogeneity, a candidate treatable trait.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Paediatric Pneumology

Graduate School:

Graduate School for Health Sciences (GHS)

UniBE Contributor:

Kieninger, Elisabeth; Kurz, Johanna Manuela and Singer, Florian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1569-1993

Publisher:

Elsevier

Language:

English

Submitter:

Romy Melanie Rodriguez Del Rio

Date Deposited:

19 Jan 2021 14:30

Last Modified:

30 Aug 2021 01:31

Publisher DOI:

10.1016/j.jcf.2020.12.009

PubMed ID:

33349584

Uncontrolled Keywords:

Child Cystic fibrosis Pulmonary function Treatment

BORIS DOI:

10.48350/150378

URI:

https://boris.unibe.ch/id/eprint/150378

Actions (login required)

Edit item Edit item
Provide Feedback