O bstructive sleep apnea (OSA) is characterized by recurring episodes of cessation (apnea) or reduction (hypopnea) in airflow during sleep caused by obstruction of the upper airway. In recent population-based studies, the estimated prevalence of moderate to severe sleep-disordered breathing ranges from 3% to nearly 50% depending on age group and sex. 1,2 A survey conducted by the Public Health Agency of Canada in 2009 found that 26% of Canadian adults reported symptoms and risk factors that are associated with a high risk of OSA; 3 however, prevalence data in Canada are limited by the absence of studies using objective sleep testing. Obstructive sleep apnea may be underdiagnosed; only 3% of Canadians aged 18 years or older reported a formal diagnosis despite high rates of symptom reporting; 3 yet, high-quality prospective studies have shown clear benefit of treatment for patients with sleepiness, cognitive or psychological dysfunction, or poor quality of life owing to obstructive sleep apnea. 4-6 Large population-based studies have shown that untreated moderate or severe OSA is associated with serious complications. 7-9 We review signs, symptoms and morbidity associated with OSA, along with diagnostic options, treatments and considerations for long-term follow-up, based on evidence and recommendations from clinical guidelines, systematic reviews and primary studies (Box 1). What signs, symptoms and risk factors should prompt consideration of obstructive sleep apnea? About 25% of patients with OSA report daytime sleepiness; a greater proportion report unrefreshing sleep or fatigue. 10 Other symptoms include frequent nocturnal waking due to choking or gasping, nocturia, morning headaches, poor concentration, irritability and erectile dysfunction. 11-13 Bed partners may report snoring or witnessed apneas. Atypical symptoms, which are more frequently reported by women, include insomnia, impaired memory, mood disturbance, reflux and nocturnal enuresis. 14 However, the correlation of symptoms with disease severity is poor, 15 which is why it is important for physicians to be alert to milder symptoms. There are many underlying risk factors, predisposing conditions and associated comorbidities for OSA; they are summarized in Appendix 1, available at www.cmaj.ca/ lookup/suppl/

Elevated levels of circulating CD4(+) CRTh2(+) T cells are a feature of severe asthma, despite high-dose corticosteroids. Tracking the systemic level of these cells may help identify type 2 severe asthmatics at risk of exacerbation.

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease resulting from exposure to cigarette smoke, noxious gases, particulate matter, and air pollutants. COPD is exacerbated by acute inflammatory insults such as lung infections (viral and bacterial) and air pollutants which further accelerate the steady decline in lung function. The chronic inflammatory process in the lung contributes to the extrapulmonary manifestations of COPD which are predominantly cardiovascular in nature. Here we review the significant burden of cardiovascular disease in COPD and discuss the clinical and pathological links between acute exacerbations of COPD and cardiovascular disease.

BackgroundProtease-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.MethodsWe 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.ResultsSubjects 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.ConclusionsPAR-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.

Obstructive sleep apnea (OSA) is a common condition associated with significant morbidity and health-care utilization. We determined the validity of an algorithm derived from administrative data for identifying OSA using the respiratory disturbance index (RDI) as the reference standard. We conducted a retrospective cohort study of adults in Alberta, Canada referred for facility and community-based sleep diagnostic testing between July 2005 and August 2007. Validity indices were estimated for several case definitions of OSA derived from outpatient physician billing claims and hospital discharge codes. For each algorithm, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated against several reference standards for OSA (RDI ≥ 5 h , RDI ≥ 15 h or RDI ≥ 30 h ). For the 2149 patients included in the study, an algorithm requiring one hospital discharge code or two outpatient billing claims identifying OSA in a 2-year period had a sensitivity of 24.1%, specificity of 67.8%, PPV of 74.8% and NPV of 18.3% (reference standard RDI ≥ 5 h ). When comorbidities were included in the case definition, the specificity was 90.5% and PPV was 83.3% (reference standard RDI ≥ 5 h ). Similar findings were observed using RDI ≥ 15 h and ≥30 h as the reference standard. We identify a claims-based algorithm that identifies OSA with a high degree of specificity in patients referred for sleep diagnostic testing. This validated algorithm has a good PPV and may be useful when identifying patients with OSA for population studies within a single-payer health-care system.

The purpose of this workshop was to identify knowledge gaps in the perioperative management of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS). A single-day meeting was held at the American Thoracic Society Conference in May, 2016, with representation from many specialties, including anesthesiology, perioperative medicine, sleep, and respiratory medicine. Further research is urgently needed as we look to improve health outcomes for these patients and reduce health care costs. There is currently insufficient evidence to guide screening and optimization of OSA and OHS in the perioperative setting to achieve these objectives. Patients who are at greatest risk of respiratory or cardiac complications related to OSA and OHS are not well defined, and the effectiveness of monitoring and other interventions remains to be determined. Centers involved in sleep research need to develop collaborative networks to allow multicenter studies to address the knowledge gaps identified below.

Background Asthma is a complex disease with variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not been very successful so far. We have previous suggested that PAR-2 and CRTh2 expression on specific peripheral blood cell subtypes may be biomarkers of asthma severity. We reasoned that parameters that remain stable when asthma symptoms are controlled would be the most appropriate to evaluate for their utility to predict loss of asthma control and/or severity of the disease. Methods Nineteen stable asthmatics were recruited from the University of Alberta Asthma clinic and followed in clinic every 3 months for a total of 4 visits. Patients had spirometry and completed the ACQ questionnaire in every visit. Blood was drawn in every visit and analyzed for a number of immune parameters by flow cytometry. These parameters included PAR-2 and CRTh2 expression on monocyte subgroups and T lymphocytes respectively, as well as numbers of eosinophils, innate lymphoid type-2 cells (ILC2) and dendritic cells. Within person stability of immune and physiological parameters was calculated using the intraclass correlation (ICC) using R version 3.4.0. Results FEV 1 (% predicted), FEV 1 /FVC ratio, ACQ5 and ACQ7 did not differ significantly over the 4 visits, as would be expected for patients with stable asthma. Peripheral blood eosinophil numbers by Kimura stain and by flow cytometry showed ICC scores of 0.44 and 0.52 respectively, indicating moderate stability. The % of ILC2 cells in peripheral blood also showed moderate stability [ICC score of 0.45 (0.14–0.67)]. The stability for all other immune parameters was poor. Conclusion Among the peripheral blood immune parameters we studied, only numbers of eosinophils and ILC2 in peripheral blood were moderately stable over a year in stable asthmatics. Further studies are required to understand the reasons for the variability of the other cell types.

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