Abstract
We call for studies of widespread use of proton pump inhibitor therapy in people with cystic fibrosis and chronic lung disease; these should evaluate patient benefit and potential iatrogenic effects, including dysregulation of aerodigestive homeostasis http://ow.ly/ym6H30lxxZu
To the Editor:
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. In a discussion of potential mechanisms, the authors considered that bacteria are normally killed by acid conditions in the stomach but that gastric pH is raised following PPI use. It was therefore hypothesised that with extra-oesophageal reflux, surviving pathogens could reach the upper airway and be aspirated.
We have described the microbiomes isolated from the gastric juice and sputum of PPI-treated adults with cystic fibrosis (CF) lung disease [2]. This showed that all gastric and sputum cultures grew bacteria and/or fungi. Possible communication between the gut and lung microbiome in CF were indicated by describing identical strains of Pseudomonas aeruginosa in sputum and gastric juice from the same patient.
The swallowing of expectorated sputum is a normal homeostatic mechanism that could explain our observation of identical microorganisms in the gut and lung environments. 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].
In supporting data we have looked at the relationship between pH and the microbiology of gastric juice. We found that microbes, including P. aeruginosa, were detected in gastric juice where pH was ≥4.0 [5]. This supports the concept that PPI use could encourage the survival of micro-organisms in gastric juice, which could be translocated to the lung following reflux and micro-aspiration.
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. For example, non-CF patients with co-existing bronchiectasis and reflux have increased chronic infection, and reduced pulmonary function and quality of life [8], with associated increase in mortality [9].
Footnotes
Conflict of interest: H. Al Momani has nothing to disclose.
Conflict of interest: A. Perry has nothing to disclose.
Conflict of interest: R. Jones has nothing to disclose.
Conflict of interest: M. McDonnell has nothing to disclose.
Conflict of interest: A. Krishnan has nothing to disclose.
Conflict of interest: A. Robertson has nothing to disclose.
Conflict of interest: M. Griffin has nothing to disclose.
Conflict of interest: R. Rutherford has nothing to disclose.
Conflict of interest: M. Brodlie reports grants from Pfizer and Roche Diagnostics, honoraria for talking at educational meetings (paid to Newcastle University) from Novartis, honoraria and travel expenses for talking at educational meetings (paid to Newcastle University) from TEVA and Roche Diagnostics, and travel expenses to attend educational meetings from Boehringer Ingelheim, outside the submitted work.
Conflict of interest: J. Pearson has nothing to disclose.
Conflict of interest: S. Bourke has nothing to disclose.
Conflict of interest: C. Ward has nothing to disclose.
Support statement: This work was funded by Medical Research Foundation (MRF-091-0001-RG-GARNE). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received August 7, 2018.
- Accepted August 14, 2018.
- Copyright ©ERS 2018