The effect of gastric juice on interleukin-8 production by cystic fibrosis primary bronchial epithelial cells

Pauwels, Ans; Verleden, Stijn E.; Farré, Ricard; Vanaudenaerde, Bart M.; Raemdonck, Dirk Van; Verleden, Geert M.; Sifrim, Daniel; Dupont, Lieven

doi:10.1016/j.jcf.2013.03.006

Cited by 22 publications

(17 citation statements)

References 28 publications

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“…It is notable that we found that expression of eight of the EoE genes failed to normalize to that found in the NL individuals; perhaps these refractory genes may explain the clinically observed relapsing propensity of PPI-REE 17 . Given the ability of PPI to modulate multiple components of the inflammatory axis, such as chemokines 6, 18, 19 , interleukins 20 , and vascular cell adhesion molecules 21 and mucosal barrier function 22 , the effects of high-dose, twice daily PPI may have an anti-inflammatory effect in addition to its effect on acid reduction 19 . Our study supports this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of proton pump inhibitor–responsive esophageal eosinophilia reveals proton pump inhibitor–reversible allergic inflammation

Wen¹,

Dellon²,

Moawad³

et al. 2015

Journal of Allergy and Clinical Immunology

214

180

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Background Esophageal eosinophilia can be proton pump inhibitor (PPI) resistant or responsive, representing two entities known as eosinophilic esophagitis (EoE) and PPI-responsive esophageal eosinophilia (PPI-REE), respectively. Although they present with similar clinical features, EoE is accepted to be an antigen–driven, Th2-associated allergic disorder, whereas the etiology of PPI-REE remains a mystery. Objective In this study, our aim was to investigate the pathogenesis of PPI-REE using a recently described esophageal based EoE diagnostic panel (EDP) composed of a set of 94 esophageal transcripts, and to determine if PPI therapy reverses any esophageal transcriptional abnormalities. Methods We evaluated the EDP signature in biopsy samples obtained from adult and pediatric PPI-REE subjects from four institutions and compared the pre and post PPI therapy expression profiles of these subjects with those of active EoE subjects. Results The EDP identified EoE from control subjects with 100% accuracy amongst the four clinical sites. Bioinformatic analysis revealed largely overlapping transcriptomes between PPI-REE and EoE, including the genes for eosinophil chemotaxis (CCL26), barrier molecules (DSG1), tissue remodeling (POSTN), and mast cells (CPA3). After PPI-mono therapy, PPI treatment alone almost completely reversed the allergic inflammatory transcriptome of PPI-REE. Furthermore, we identified a set of candidate genes to differentiate EoE from PPI-REE before treatment. Conclusion These findings provide definitive evidence that PPI-REE is a disease entity with significant molecular overlap with EoE, suggesting that many subjects with PPI-REE represent a continuum of the same pathogenic allergic mechanisms that underlie EoE and thus may constitute a sub-phenotype of EoE. The ability of PPI therapy to nearly entirely reverse gene expression associated with PPI-REE particularly that associated with classic features of allergic inflammation provides new insight into potential disease etiology and management strategies for patients with significant esophageal eosinophilia.

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Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of proton pump inhibitor–responsive esophageal eosinophilia reveals proton pump inhibitor–reversible allergic inflammation

Wen¹,

Dellon²,

Moawad³

et al. 2015

Journal of Allergy and Clinical Immunology

214

180

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“…Later, in a prospective study of CF patients randomized to placebo or esomeprazole, DiMango et al showed a trend towards earlier and more frequent exacerbations in patients randomized to PPI therapy [ 22 ]. Work by Pauwels et al offers a biological explanation to the above clinical findings; they demonstrated that gastric juice under the effects of PPI had a significantly enhanced inflammatory effect on CF bronchial epithelial cells as compared to gastric juice not affected by PPI [ 26 ]. This leads the authors to believe that PPI therapy in CF patients may result in paradoxically increased inflammatory effects on the airway.…”

Section: Discussionmentioning

confidence: 99%

Proton Pump Inhibitor Use Is Associated With an Increased Frequency of Hospitalization in Patients With Cystic Fibrosis

2017

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BackgroundProton pump inhibitors (PPIs) are among the most commonly prescribed medications in clinical practice. PPI use has been associated with the development of community-acquired pneumonia. With a reported prevalence of gastroesophageal reflux disease (GERD) and PPI use that is higher than the general population, patients with cystic fibrosis (CF) are particularly vulnerable to PPI adverse effects. We sought to explore whether PPI use was associated with a higher number of hospitalizations for CF pulmonary exacerbation.MethodsWe conducted a longitudinal retrospective review in an academic outpatient setting. Patients > 18 years of age with a diagnosis of CF and at least 1 year of follow-up were eligible for inclusion. Baseline characteristics, PPI use, and details of hospitalization through 1 year of follow-up were collected.ResultsOne hundred fourteen patients met inclusion criteria. Fifty-nine patients (51.7%) were hospitalized at least once in the follow-up year, mean number of hospitalizations was 2.17 (± 1.9). At least 6 months of PPI use was observed in 59 patients (51.7%). In univariate analysis, PPI use was associated with a significantly higher mean number of hospitalizations (0.9 vs. 1.4, P = 0.009). In a multi-variable regression model, PPI use remained significantly associated with a higher number of hospitalizations (P = 0.03), while controlling for risk factors traditionally associated with increased pulmonary exacerbations.ConclusionPPI use is highly prevalent in CF patients. Exposure to PPI therapy is independently associated with a higher number of hospitalizations for pulmonary exacerbation in CF patients.

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“…However, it has been shown that the gastric juices of patients treated with PPI can induce interleukin‐8 production by bronchial epithelial cells in culture, and such effect is even more pronounced in cystic fibrosis patients known to have high inflammatory susceptibility. Accordingly, it has been suggested that chronic PPI treatment in cystic fibrosis might result in a paradoxically increased inflammatory effect on the airways . It is, therefore, tempting to speculate that PPI inhibitors could negatively affect airway inflammation in asthma patients through an unknown mechanism, resulting in worse disease control.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, it has been suggested that chronic PPI treatment in cystic fibrosis might result in a paradoxically increased inflammatory effect on the airways. 27 It is, therefore, tempting to speculate that PPI inhibitors could negatively affect airway inflammation in asthma patients through an unknown mechanism, resulting in worse disease control.…”

Section: Discussionmentioning

confidence: 99%

Comorbidities in elderly patients with asthma: Association with control of the disease and concomitant treatment

Wardzyńska

Kubsik²,

Kowalski

2014

Geriatrics Gerontology Int

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Aim:The incidence of concomitant conditions increases with age. In elderly patients, the presence of comorbidities has been related to the course and severity of asthma. The aim of the present study was to assess the impact of comorbidities and concomitant treatment on asthma control and severity in older adults.Methods: A total of 93 elderly (age >65 years) and 78 younger (age 30-50 years) asthmatic patients were randomly selected from a database including 1755 asthmatics. Evaluation consisted of a questionnaire, spirometry and skin prick testing. Results:In elderly asthmatics, a higher incidence of chronic comorbidities (mean 8.4 vs 4.7; P < 0.001) and a higher number of prescribed medicines (7.4 vs 4.5, P < 0.001) were observed, but the severity of asthma and the intensity of anti-asthma treatment were similar to that seen in younger patients. Asthma control was not strikingly different between the groups. There was no correlation between the presence of comorbid conditions and asthma control, severity or frequency of exacerbations in older patients. Elderly patients treated with statins had a lower risk of asthma exacerbation (OR 0.39, 95% CI 0.18-0.84, P = 0.017), whereas treatment with proton pump inhibitors was associated with a higher risk of exacerbations in older adults (OR 1.84, 95% CI 1.07-3.18, P = 0.029) and higher disease severity in younger patients (OR 2.49, 95% CI 1.1-5.67, P = 0.029). Conclusion:The higher prevalence of comorbidities observed in elderly asthmatics under specialist care do not seem to be associated with worsened asthma control or severity. However, concomitant medications can significantly affect asthma control in both elderly and younger asthmatics. Geriatr Gerontol Int 2015; 15: 902-909.

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The effect of gastric juice on interleukin-8 production by cystic fibrosis primary bronchial epithelial cells

Cited by 22 publications

References 28 publications

Transcriptome analysis of proton pump inhibitor–responsive esophageal eosinophilia reveals proton pump inhibitor–reversible allergic inflammation

Transcriptome analysis of proton pump inhibitor–responsive esophageal eosinophilia reveals proton pump inhibitor–reversible allergic inflammation

Proton Pump Inhibitor Use Is Associated With an Increased Frequency of Hospitalization in Patients With Cystic Fibrosis

Comorbidities in elderly patients with asthma: Association with control of the disease and concomitant treatment

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