ABSTRACT
BACKGROUND: Proteinase-activated receptor 2 (PAR-2) is a G-protein coupled receptor associated with many inflammatory diseases, including asthma. We have shown an association between PAR-2 expression in peripheral blood monocytes and asthma severity as well as blood PAR-2 mRNA level and lung function. Since F2RL1 (the gene encoding PAR-2) polymorphisms affect PAR-2 expression, we hypothesize they may affect asthma severity. METHODS: We recruited 76 subjects with asthma of varying severity and collected clinical (FEV1 [% predicted], FEV1/FVC, IgE) and immunological (PAR-2 mRNA, blood eosinophils) disease parameters. We also genotyped these individuals for 3 F2RL1 SNPs (-45C/T, -149C/G, c.621C/T). RESULTS: We found that the F2RL1 SNP "C" allele of -45C/T (rs1529505) was associated with PAR-2 mRNA and blood eosinophils. F2RL1 SNP c.621C/T (rs631465) was associated with PAR-2 mRNA. The F2RL1 SNP -149C/G (rs2242991) had no association with any of the parameters studied. This study identified one F2RL1 SNP rs1529505 is associated with parameters of asthma, but not asthma severity. CONCLUSION: Larger studies are needed to further elucidate the role of PAR-2 in the pathophysiology of asthma and the influence of genetic variation.
ABSTRACT
BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects up to 10% of Canadians. Patients with COPD may present with secondary humoral immunodeficiency as a result of chronic disease, poor nutrition or frequent courses of oral corticosteroids; decreased humoral immunity may predispose these patients to mucosal infections. We hypothesized that decreased serum immunoglobulin (Ig) levels was associated with the severity of an acute COPD exacerbations (AECOPD). METHODS: A prospective study to examine cardiovascular risks in patients hospitalized for AECOPD, recruited patients on the day of hospital admission and collected data on length of hospital stay at index admission, subsequent emergency department visits and hospital readmissions. Immunoglobulin levels were measured in serum collected prospectively at recruitment. RESULTS: Among the 51 patients recruited during an admission for AECOPD, 14 (27.5%) had low IgG, 1 (2.0%) low IgA and 16 (31.4%) low IgM; in total, 24 (47.1%) had at least one immunoglobulin below the normal range. Patients with low IgM had longer hospital stay during the index admission compared to patients with normal IgM levels (6.0 vs. 3.0 days, p = 0.003), but no difference in other clinical outcomes. In the whole cohort, there was a negative correlation between serum IgM levels and length of hospital stay (R = - 0.317, p = 0.024). There was no difference in clinical outcomes between subjects with normal and low IgG levels. CONCLUSION: In patients presenting with AECOPD, low IgM is associated with longer hospital stay and may indicate a patient phenotype that would benefit from efforts to prevent respiratory infections. Trial registration statement: Retrospectively registered.
ABSTRACT
BACKGROUND: Myeloid cells, especially dendritic cells and macrophages, play important roles in asthma pathophysiology. Monocytes (Mo) and macrophages express protease-activated receptor-2 (PAR-2), a proinflammatory serine protease receptor implicated in the pathophysiology of allergic airway inflammation. We have revealed that patients with severe asthma and those with a history of frequent asthma exacerbations exhibit increased PAR-2 expression on peripheral blood monocytes. OBJECTIVE: To determine PAR-2 expression on peripheral blood intermediate monocytes (IMMo) in subjects with increased airway inflammation, either as a result of an asthma exacerbation or after an inhalation allergen challenge. METHODS: A total of 16 adults who presented to the emergency department with asthma exacerbations were recruited after giving an informed consent. After 2 weeks, 10 patients returned for follow-up. A total of 11 patients with mild asthma treated only with as-needed bronchodilators were recruited and underwent inhalation allergen challenge after providing an informed consent. Immune cell profiling was performed by whole blood flow cytometry in both groups of patients. RESULTS: PAR-2 expression in peripheral blood IMMo increased in patients with an asthma exacerbation compared with those with stable disease, but this expression decreased after treatment of the asthma exacerbation. Subjects with mild asthma had an increase in percentages of IMMo expressing PAR-2 after an allergen challenge. Patients who presented to the emergency department had lower dendritic cell and dendritic cell subset numbers in peripheral blood during exacerbation compared with after treatment. CONCLUSION: Increased PAR-2 expression on Mo during periods of increased airway inflammation may initiate a positive feedback loop leading to systemic inflammatory changes.
