Risk factors for lung disease progression in children with cystic fibrosis

Abstract

To identify potential risk factors for lung disease progression in children with cystic fibrosis (CF), we studied the longitudinal data of all children with CF (aged ≥5 years) registered in the Dutch CF Registry (2009-2014).Lung disease progression was expressed as a decline in lung function (forced expiratory volume in 1 s (FEV) % pred) and pulmonary exacerbation rate. Potential risk factors at baseline included sex, age, best FEV % pred, best forced vital capacity % pred, genotype, body mass index z-score, pancreatic insufficiency, medication use (proton pump inhibitors (PPIs), prophylactic antibiotics and inhaled corticosteroids), CF-related diabetes, allergic bronchopulmonary aspergillosis and colonisation with The data of 545 children were analysed. PPI use was associated with both annual decline of FEV % pred (p=0.017) and future pulmonary exacerbation rate (p=0.006). Moreover, lower FEV % pred at baseline (p=0.007), prophylactic inhaled antibiotic use (p=0.006) and pulmonary exacerbations in the baseline year (p=0.002) were related to pulmonary exacerbations in subsequent years.In a cohort of Dutch children with CF followed for 5 years, we were able to identify several risk factors for future exacerbations. In particular, the association between PPI use and lung disease progression definitely requires further investigation.

Risk factors for lung disease progression in children with cystic fibrosis

“…A recent global survey of patients, carers and clinicians has indicated that "relieving gastrointestinal symptoms" and "simplifying treatment" were in the top three of 10 consensus research priorities identified in CF [6]. We therefore agree with the view expressed by VAN HORCK et al [1], that the association between PPI use and lung disease progression in CF requires investigation. We feel that such "aerodigestive" studies may be relevant for other chronic lung diseases where reflux has been implicated [7] and where PPI treatment is common.…”

“…We also documented symptoms of extra-oesophageal, gastroduodenal reflux, a known precursor to aspiration. This indicates the possibility of gut to lung movement of micro-organisms, considered by VAN HORCK et al [1], and a potential mechanism long-recognised in lung disease. Micro-aspiration and potential gut to lung microbial movement has also been shown in radiolabel studies of normal subjects [3,4].…”

“…We read with interest the recent paper by VAN HORCK et al [1], which studied 545 children followed for 5 years with longitudinal data from the Dutch Cystic Fibrosis registry. Data from 2009 to 2014 showed that proton pump inhibitor (PPI) use was associated with annual decline of % predicted forced expiratory volume in 1 s and future pulmonary exacerbation rates.…”

Pulmonary findings in infants with cystic fibrosis during the first year of life: Results from the Baby Observational and Nutrition Study (BONUS) cohort study

“…In a recent retrospective study of 114 adults with CF, PPI use was associated with a higher prevalence of clinically-diagnosed GER and a higher mean number of hospitalizations for pulmonary exacerbations in both univariate and multivariate models; there was no difference in Pa colonization between those on PPI and those who were not 18 . In a Dutch CF registry study of patients aged 5–18 years, use of PPI was associated with an accelerated annual decline in FEV1% predicted (estimated pooled effect −0.69, 95% CI −1.26- −0.12) as well as increased risk of pulmonary exacerbations, adjusted for Pa colonization and other risk factors 19 . Another single site retrospective chart review of 126 CF patients on PPI for ≥ 6 months showed higher rates of at least one pulmonary exacerbation (59.6%) compared to only 24.5% of the 49 CF patients not on PPI 20 .…”

Cystic fibrosis year in review 2018, part 1

“…Use of proton pump inhibitors was found to be a significant risk factor for decline in FEV1pp and pulmonary exacerbations in a study of the Dutch CF Registry. In addition, a longer duration of PPI therapy led to a faster rate of FEV1pp decline …”