Abstract
OGP phenotype is not characterised by obstructive sleep apnoea http://bit.ly/2kv2CKE
From the authors:
We thank C. Ward and Z.J. Kharaba for their interesting comments on the OGP endotype of severe asthma that we recently described [1].
Regarding their query about the use of the A549 cell line, the impact of proton pump inhibitors (PPI) and bile acids on the airway epithelium transcriptome has not been described previously. Therefore, in order to estimate the potential impact of PPI and bile acids on epithelial dysregulation, we exploited information obtained from a freely accessible database listing the transcriptional responses of different cell lines to more than 27 000 genetic or chemical perturbagens [2]. We chose to analyse the transcriptional responses of A459 lung epithelial cells to PPI and bile acids, as this was the most suitable cell line available in the database. Using these data, we identified high connectivity scores, suggesting a direct impact of bile acids and PPI on immune mechanisms in severe asthma. We agree that caution needs to be taken when interpreting data from the A549 cell line, which was established from a human lung carcinoma, and this is why we stated that our study should be viewed as exploratory. The hypotheses generated from this study are currently being tested in our laboratory, this time using primary bronchial epithelial cells cultured in vitro.
C. Ward and Z.J. Kharaba rightly highlight the potential for modification of the airway microbiome as a mechanism involved in epithelial dysregulation associated with severe asthma, gastro-oesophageal reflux disease (GORD) and obesity. GORD is, indeed, associated with changes in oesophageal microbiota [3]. Furthermore, Goleva et al. [4] recently described a change in the bronchoalveolar lavage microbiome of severe asthmatics treated with PPI, with a unique pattern characterised by expansion in Streptococcus species, including S. mitis and S. pseudopneumoniae which were found to be able to alter epithelial response to corticosteroids in vitro. While the airway microbiome was analysed in a subset of participants in the U-BIOPRED study, unfortunately, not enough participants provided both transcriptomic and microbiome data so we were unable to correlate the microbiome with the effects of GORD, obesity and PPI treatment.
The complexity of severe asthma management includes co-morbidities such as obstructive sleep apnoea syndrome (OSAS), which has been associated with poor asthma control, increased burden of asthma independent of any association with obesity and increased hospitalisation length of stay after exacerbation [5]. The impact of OSAS treatment on asthma outcomes is unclear [6, 7]; the mechanisms might involve nuclear factor-κB-dependent pro-inflammatory cytokine production and hypoxia-inducing factor 1 pathway [8]. OSAS was evaluated in the U-BIOPRED study using the Epworth sleepiness score (ESS). Our analysis shows that the OGP (obesity, gastro-oesophageal reflux and use of proton pump inhibitors) phenotype does not differ from the severe asthma clusters C2 and C3 in terms of total ESS score (9.82±4.13 in OGP versus 8.24±4.28 in C2 and 7.7±5.16 in C3) and number of subjects with ESS >10 (mild excessive daytime sleepiness; 4/21 in OGP, 5/23 in C2, 7/22 in C3).
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Footnotes
Conflict of interest: J-M. Perotin has nothing to disclose.
Conflict of interest: R. Djukanovic reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca and TEVA, consultation for TEVA and Novartis as member of advisory boards, and participation in a scientific discussion about asthma organised by GlaxoSmithKline, and is a co-founder and current consultant, and has shares in Synairgen, a University of Southampton spin out company.
Conflict of interest: D.E. Davies has nothing to disclose.
Support statement: This work was supported by ARAIRCHAR (grant 2017); ANAFORCAL (grant: Bourse anaforcal 2017); European Respiratory Society (grant: ERS long term fellowship 2017). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received September 13, 2019.
- Accepted September 13, 2019.
- Copyright ©ERS 2019