Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma.

Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied.We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry.Subjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations.PAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma

Acceptance of and adherence with long-term positive airway pressure treatment in adults with chronic obstructive pulmonary disease: A systematic review protocol.

BackgroundLong-term noninvasive positive airway pressure (PAP) treatment is effective treatment for sleep-related breathing disorders and chronic hypercarbic respiratory failure secondary to chronic obstructive pulmonary disease (COPD). PAP treatment may be delivered as continuous positive airway pressure or noninvasive ventilation. Success in initiating PAP treatment and barriers to its use in adult patients with COPD are largely unknown. This systematic review aims to identify the acceptance of and adherence to PAP treatment prescribed for long-term use in adult patients with COPD and to summarize variables associated with these measures.MethodsSeven online electronic databases will be searched by an experienced medical librarian to identify records containing the concepts "obstructive airways disease" and "noninvasive positive airway pressure" and "acceptance" or "adherence". Randomized and non-randomized studies of interventions will be included. Citation lists from relevant articles will be reviewed, and experts will be contacted regarding unpublished studies. Abstracts from key conferences between 2018-2023 and Google Scholar search results will be reviewed for inclusion. Titles, abstracts and full texts will be reviewed independently for inclusion by two reviewers. Data extraction will be completed by one author using a pre-established form and primary outcomes confirmed by a second author. Methodological quality will be evaluated. If sufficient data are available for meta-analysis, a pooled summary statistic for the primary outcome will be calculated using a random-effects generic inverse-variance meta-analysis, weighted proportion or weighted medians-based approach. Subgroup analysis will explore clinically meaningful sources of heterogeneity. Variables that are associated with acceptance and adherence will be described.DiscussionLong-term PAP treatment is a complex intervention prescribed to patients with COPD for several indications. Synthesis of the evidence on success with PAP treatment and variables associated with acceptance or adherence will inform program and policy development for supporting patients with COPD who are prescribed this therapy.Trial registrationSystematic review registration: This protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on July 13, 2021 (registration number CRD42021259262), with revisions submitted on April 17, 2023

ROC curve of “% of CD14⁺⁺CD16⁺PAR-2⁺ monocytes” in peripheral blood used to identify patients with severe asthma.

<p>Sensitivity and specificity were calculated according to the optimal cutoffs using R software and AUC with a 95% confidence interval is shown.</p

Asthma exacerbations and CD14⁺⁺CD16⁺PAR-2⁺ expression.

<p>(A) Proportion of CD14⁺⁺CD16⁺PAR-2⁺ cells in peripheral blood was correlated with the total daily dose of ICS in the whole population. (B) Percentage of CD14⁺⁺CD16⁺PAR-2⁺ monocytes in peripheral blood in asthmatics that did not have recent exacerbations (NAE) (n = 26) compared to asthmatics with recent exacerbations (AE) (n = 10). Correlation of the “% of CD14⁺⁺CD16⁺PAR-2⁺ monocytes in peripheral blood” (C) percentage predicted FEV₁ and (D) “% of CRTh2⁺CD4⁺” in peripheral blood in subjects with asthma exacerbations (n = 10).</p

PAR-2 mRNA expression in whole blood of patients with asthma.

<p>(A) PAR-2 mRNA expression in mild/moderate (n = 16) and severe (n = 6) asthmatics. (B) correlation of PAR-2 mRNA expression with percentage of monocytes in peripheral blood. (C) total ICS dose and (D) percentage of FEV₁ predicted in the whole population (n = 22).</p

PAR-2 expression on monocytes and severe asthma

<p><b>A.</b> Gating strategy to study PAR-2 expression on peripheral blood monocytes. B-C. Percentage of CD14⁺⁺CD16⁺ (B) and CD14⁺⁺CD16^- (C) monocytes in the peripheral blood of severe asthmatics compared to mild/moderate asthmatics. D-E. PAR-2 expression on CD14⁺⁺CD16⁺ (D) and CD14⁺⁺CD16^- (E) monocytes in patients with mild/moderate and severe asthma. F-G. Percentage of CD14⁺⁺CD16⁺PAR-2⁺ (F) and CD14⁺⁺CD16^-PAR-2⁺ (G) monocytes in peripheral blood of patients with mild/moderate and severe asthma. H-I. PAR-2 MFI on CD14⁺⁺CD16⁺ (H) and CD14⁺⁺CD16^- (I) monocytes from patients with mild/moderate and severe asthma. Data is presented as boxplots (n = 24 for mild/moderate and n = 12 for severe asthma). Statistical significance was assessed by Mann-Whitney rank sum test, with <i>P</i><0.05 considered significant.</p