Mucus Clearance and Lung Function in Cystic Fibrosis With Hypertonic Saline

RationaleA previous analysis found significantly higher lung function in the US paediatric cystic fibrosis (CF) population compared with the UK with this difference apparently decreasing in adolescence and adulthood. However, the cross-sectional nature of the study makes it hard to interpret these results.ObjectivesTo compare longitudinal trajectories of lung function in children with CF between the USA and UK and to explore reasons for any differences.MethodsWe used mixed effects regression analysis to model lung function trajectories in the study populations. Using descriptive statistics, we compared early growth and nutrition (height, weight, body mass index), infections (Pseudomonas aeruginosa, Staphylococcus aureus) and treatments (rhDnase, hypertonic saline, inhaled antibiotics).ResultsWe included 9463 children from the USA and 3055 children from the UK with homozygous F508del genotype. Lung function was higher in the USA than in the UK when first measured at age six and remained higher throughout childhood. We did not find important differences in early growth and nutrition, or P.aeruginosa infection. Prescription of rhDNase and hypertonic saline was more common in the USA. Inhaled antibiotics were prescribed at similar levels in both countries, but Tobramycin was prescribed more in the USA and colistin in the UK. S. aureus infection was more common in the USA than the UK.ConclusionsChildren with CF and homozygous F508del genotype in the USA had better lung function than UK children. These differences do not appear to be explained by early growth or nutrition, but differences in the use of early treatments need further investigation.

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Inhaled hypertonic saline, mechanisms, and improved lung function in cystic fibrosis

Thorax ◽

10.1136/thx.2006.la0199 ◽

2006 ◽

Vol 61 (4) ◽

pp. 283-283

Author(s):

A Gondker

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Hypertonic Saline

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TMEM16A: An Alternative Approach to Restoring Airway Anion Secretion in Cystic Fibrosis?

International Journal of Molecular Sciences ◽

10.3390/ijms21072386 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2386

Author(s):

Henry Danahay ◽

Martin Gosling

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Standard Of Care ◽

Fluid Secretion ◽

Airway Epithelial ◽

Anion Secretion ◽

Positive Effects ◽

Mucus Clearance ◽

Airway Mucosa ◽

Treat All

The concept that increasing airway hydration leads to improvements in mucus clearance and lung function in cystic fibrosis has been clinically validated with osmotic agents such as hypertonic saline and more convincingly with cystic fibrosis transmembrane conductance regulator (CFTR) repair therapies. Although rapidly becoming the standard of care in cystic fibrosis (CF), current CFTR modulators do not treat all patients nor do they restore the rate of decline in lung function to normal levels. As such, novel approaches are still required to ensure all with CF have effective therapies. Although CFTR plays a fundamental role in the regulation of fluid secretion across the airway mucosa, there are other ion channels and transporters that represent viable targets for future therapeutics. In this review article we will summarise the current progress with CFTR-independent approaches to restoring mucosal hydration, including epithelial sodium channel (ENaC) blockade and modulators of SLC26A9. A particular emphasis is given to modulation of the airway epithelial calcium-activated chloride channel (CaCC), TMEM16A, as there is controversy regarding whether it should be positively or negatively modulated. This is discussed in light of a recent report describing for the first time bona fide TMEM16A potentiators and their positive effects upon epithelial fluid secretion and mucus clearance.

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