Proton pump inhibitors (PPI) use has been identified as a risk factor for future exacerbations and accelerated decline in FEV1 in children with cystic fibrosis.
The findings, from a Dutch longitudinal observational study involving 545 children with CF aged 5-18 years of age, add to previous evidence linking PPIs to an increased risk of respiratory infections.
Respiratory researchers from Maastricht Medical Centre in the Netherlands analysed data on annual changes of FEV1 % predicted and pulmonary exacerbations at 1, 2, 3, 4, or 5 years among children in the Dutch CF Registry from 2009-2014.
Published in the European Respiratory Journal, their findings show that PPI use was significantly associated with associated with both annual decline of FEV1% predicted (p=0.017) and future pulmonary exacerbations (p=0.006).
Other risk factors for future pulmonary exacerbations included lower FEV1% predicted at baseline, prophylactic inhaled antibiotics use, and pulmonary exacerbations in the baseline year.
In the cohort of children followed, the mean of best performed FEV1% predicted was 88.5% at baseline, and the mean annual decline of FEV1% predicted of the total cohort was −1.92 % per year.
The analysis also found a dose-response relationship between duration of PPI use and annual decline in FEV1% predicted and exacerbation rate.
The study authors said the findings were of concern given that a PPI is often added to pharmacological treatment of CF in children in order to improve gastrointestinal symptoms, fat absorption, and thereby nutritional status.
They said PPIs may contribute to worsening lung function if pH dysregulation alters the respiratory flora and microbiome in the airways, potentiating respiratory pathogens and infections.
It was unlikely that the link between PPI use and worsening lung function was due to confounding factors and reverse causation, they added, since there were no clinical or statistical significant differences in age, sex, lung function, use of prophylactic antibiotics, and presence of allergic bronchopulmonary aspergillosis between PPI users and no PPI users.
“Taken together, prospective randomised controlled trials are needed to shed more light on the relationship between PPI use and lung disease progression in CF,” they concluded.