Neutrophil extracellular traps and thrombosis in COVID-19

Journal of Thrombosis and Thrombolysis - Studies of patients with COVID-19 have demonstrated markedly dysregulated coagulation and a high risk of morbid arterial and venous thrombotic events....     

Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype

Rationale: Obesity is associated with increased prevalence and severity of asthma. Adipose tissue macrophages can contribute to the systemic proinflammatory state associated with obesity. However, it remains unknown whether alveolar macrophages have a unique phenotype in overweight/obese patients with asthma. Objectives: We hypothesized that leptin levels would be increased in the bronchoalveolar lavage fluid from overweight/obese subjects and, furthermore, that leptin would alter the response of alveolar macrophages to bacterial LPS. Methods: Forty-two subjects with asthma and 46 healthy control subjects underwent research bronchoscopy. Bronchoalveolar lavage fluid from 66 was analyzed for the level of cellular inflammation, cytokines, and soluble leptin. Cultured primary macrophages from 22 subjects were exposed to LPS, leptin, or leptin plus LPS. Cytokines were measured in the supernatants. Measurements and Main Results: Leptin levels were increased in overweight/obese subjects, regardless of asthma status (P = 0.013), but were significantly higher in overweight/obese subjects with asthma. Observed levels of tumor necrosis factor-α were highest in overweight/obese subjects with asthma. Ex vivo studies of primary alveolar macrophages indicated that the response to LPS was most robust in alveolar macrophages from overweight/obese subjects with asthma and that preexposure to high-dose leptin enhanced the proinflammatory response. Leptin alone was sufficient to induce production of proinflammatory cytokines from macrophages derived from overweight/obese subjects with asthma. Conclusions: Ex vivo studies indicate that alveolar macrophages derived from overweight/obese subjects with asthma are uniquely sensitive to leptin. This macrophage phenotype, in the context of higher levels of soluble leptin, may contribute to the pathogenesis of airway disease associated with obesity.     

Epidemiology of asthma

The epidemiology of asthma is complex but essential in enhancing the understanding of a disease that affects millions of patients. Asthma is associated with significant morbidity and mortality. Asthma prevalence rates in the United States reached a plateau after 1998 with an estimated overall prevalence of 3.8% in 2003. Racial disparities exist and there are staggering differences in morbidity and mortality. The analysis of data collected from epidemiologic studies continues to be a critical part of enhancing the understanding of the pathophysiology of asthma, which will lead to improved patient outcomes.     

Real-world patterns and implications of short-acting β2-agonist use in patients with asthma in the United States

BackgroundShort-acting β₂-agonist (SABA) use is one measure reflecting asthma control.ObjectiveTo evaluate the associations between real-world SABA use and severe asthma exacerbations in the United States.MethodsPatients with asthma 12 years of age or older receiving SABA in the IBM MarketScan research databases of US administrative claims from September 30, 2014, to September 30, 2016, were evaluated. Patients with 12 months’ continuous eligibility before and after their first SABA claim (index SABA), an asthma diagnosis before through 60 days postindex, and either one additional SABA or at least 1 maintenance fill(s) were included. SABA claims postindex (including index fill) were grouped as follows: low: index only; medium: 2 to 3 canisters per year; and high: 4 or more canisters per year. Differences in SABA exposure with respect to disease severity groups and severe asthma exacerbations (hospitalizations, emergency visits, or outpatient systemic corticosteroids) were analyzed by analysis of variance and χ² (significance, P ≤ .05).ResultsA total of 135,540 patients were included: 62.8% women; mean (SD) age, 40.9 (18.3) years; SABA fills per 12-months postindex: 3.0 (2.7). Furthermore, 28% of patients filled 1 SABA, 47% 2 to 3, and 25% 4 or more canisters per year. Despite higher maintenance medication possession ratio with increasing SABA (low, 0.53 (0.37); medium, 0.59 (0.35); high, 0.66 (0.32)), annual exacerbation rate per person per year and percent of patients within each SABA group having at least 1 exacerbation rose as SABA fills increased (low, 1.00 (1.45), 45.8%; medium, 1.20 (1.62), 54.3%; high, 1.50 (1.94), 58.7%). Mean SABA fills differed between patients with 0 exacerbation, 2.8 (2.6); 1 exacerbation, 2.9 (2.5); and 2 or more exacerbations, 3.3 (2.9).ConclusionExacerbation risk increased with increasing SABA fills. Management strategies ensuring adequate anti-inflammatory therapy delivered to the airways when symptoms occur may be needed to mitigate asthma morbidity.