Abstract
Alveolar epithelial A549 cells may not be the best model in asthma studies. Proton pump inhibitor use may associate with a dysregulated aerodigestive microbiome, and in obese severe asthmatics obstructive sleep apnoea may be a relevant comorbidity. http://bit.ly/2kMHj7q
To the Editor:
We read with interest the recent article by Perotin et al. [1], which investigated epithelial dysregulation in obese severe asthma patients with gastro-oesophageal reflux. The researchers found that bronchial epithelial gene expression, sampled by airway brushing, identified an endotype defined by epithelial dysregulation associated with obesity, gastro-oesophageal reflux and use of proton pump inhibitors (OGP cluster). Relative to non-asthmatic healthy controls, pathway signature analysis indicated that the wingless tail (WNT)/β-catenin pathway was the top epithelial pathway dysregulated in the OGP cluster. The cluster was also associated with paucigranulocytic sputa, lower numbers of biopsy lymphocytes, but no thickening of the basement membrane.
The reported findings of the Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes (U-BIOPRED) initiative is an encouraging example of research between leading centres, and we congratulate the investigators for coordinating the demanding sampling of different airway compartments. With human airway epithelial brushing samplings taken, we wondered why differentially expressed genes in the epithelium were compared to genes regulated by proton pump inhibitors (PPIs) and bile acids through in vitro studies of alveolar A549 cells. The cancer origin of the A549 cell line might also interact with pathways such as WNT/β-catenin signalling [2]?
Transfer of low levels of micro-organisms has been described in radionuclide studies of normal volunteers at night during sleep [3] and we have previously shown that in gastric juice, with pH >4, that viable micro-organisms, including Pseudomonas aeruginosa, can be cultured [4, 5]. PPI use might be expected to lower gastric juice pH and we therefore wondered if the investigators had any data regarding the sputum microbiome detected in the OGP endotype cluster? In subjects with high body mass index we were also interested whether there were any subjects who had obstructive sleep apnoea (OSA), which can be under-diagnosed? We speculate that OSA and a potentially dysregulated aerodigestive microbiome could also be part of the complex interactome relevant in the OGP endotype very usefully highlighted by J.M. Perotin and the U-BIOPRED investigators.
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Footnotes
Conflict of interest: C. Ward has nothing to disclose.
Conflict of interest: Z.J. Kharaba has nothing to disclose.
- Received July 11, 2019.
- Accepted July 14, 2019.
- Copyright ©ERS 2019