Immunomodulatory drugs in sepsis: a systematic review and meta-analysis.

Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta-analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all-cause mortality. Fifty-six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti-inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors. At 1-month follow-up, the use of cytokine inhibitors was associated with a decreased risk of serious adverse events, based on 11 studies involving 7138 patients (RR (95%CI) 0.95 (0.90-1.00), I2 = 0%). The only immunomodulatory drugs associated with an increased risk of serious adverse events were toll-like receptor 4 antagonists (RR (95%CI) 1.18 (1.04-1.34), I2 = 0% (two trials, 567 patients)). Based on 18 randomised controlled trials, involving 11,075 patients, cytokine inhibitors reduced 1-month mortality (RR (95%CI) 0.88 (0.78-0.98), I2 = 57%). Mortality reduction was also shown in the subgroup of 13 randomised controlled trials that evaluated anti-tumour necrosis factor α interventions (RR (95%CI) 0.93 (0.87-0.99), I2 = 0%). Anti-inflammatory drugs had the largest apparent effect on mortality at 2 months at any dose (two trials, 228 patients, RR (95%CI) 0.64 (0.51-0.80), I2 = 0%) and at 3 months at any dose (three trials involving 277 patients, RR (95%CI) 0.67 (0.55-0.81), I2 = 0%). These data indicate that, except for toll-like receptor 4 antagonists, there is no evidence of safety concerns for the use of immunomodulatory drugs in sepsis, and they may show some short-term mortality benefit for selected drugs.

Impact of self-reported environmental mould exposure on COPD outcomes.

BACKGROUND: Indoor and outdoor mould exposure can affect respiratory symptoms, but its contribution to COPD outcomes such as exacerbation rates or antibiotics courses is not well defined. Some patients with COPD develop chronic pulmonary aspergillosis (CPA), but the contribution of environmental exposure is not known. METHODS: We correlated activities or exposures related to mould with COPD outcomes in patients with COPD with or without CPA using a questionnaire. RESULTS: One hundred and forty patients were included and 60 had CPA in addition to COPD. Seventy-six were male and mean age was 66.9 years (range 40-87). Thirty-nine (28%) were active cigarette smokers. On multivariate analysis, occupational contact with agricultural resources (p = 0.017), vacuuming once weekly or more often (p = 0.026) and not asking visitors to remove shoes on home entry (p = 0.035) were significantly more common in participants reporting ≥ 4 office visits for COPD symptoms in the last year. Living within one mile of industrial composting sites (p = 0.013), vacuuming once weekly or more often (p = 0.016) and not asking visitors to remove shoes on home entry (p = 0.028) were significantly more common in participants reporting ≥4 antibiotics courses in the last year. Patients with CPA showed a trend for residence within one mile of farms or agricultural areas (P = 0.088, OR 2, 95% CI 0.9-4.4). CONCLUSION: Activities potentially leading to mould exposure were common in a population with COPD with or without CPA and were associated with adverse COPD outcomes. Environmental mould exposure may play a role in the development of CPA in patients with COPD.