BACKGROUND: The active-treatment comparative safety information for all inhaled medications in patients with chronic obstructive pulmonary disease (COPD) is limited. We aimed to compare the risk of overall and cardiovascular death for inhaled medications in patients with COPD.
METHODS: Through systematic database searching, we identified randomised controlled trials of tiotropium Soft Mist Inhaler, tiotropium HandiHaler, long-acting β2 agonists (LABAs), inhaled corticosteroids (ICS), and LABA-ICS combination with at least a 6-month treatment duration. Direct comparison and mixed treatment comparison (MTC) meta-analyses were conducted to estimate the pooled ORs of death for each comparison.
RESULTS: 42 trials with 52 516 subjects were included. The MTC meta-analysis with the fixed effect model indicated tiotropium Soft Mist Inhaler was associated with an universally increased risk of overall death compared with placebo (OR 1.51; 95% CI 1.06 to 2.19), tiotropium HandiHaler (OR 1.65; 95% CI 1.13 to 2.43), LABA (OR 1.63; 95% CI 1.10 to 2.44) and LABA-ICS (OR 1.90; 95% CI 1.28 to 2.86). The risk was more evident for cardiovascular death, in patients with severe COPD, and at a higher daily dose. LABA-ICS was associated with the lowest risk of death among all treatments. No excess risk was noted for tiotropium HandiHaler or LABA. The results were similar for MTC and direct comparison meta-analyses, with less precision in the random effects model.
CONCLUSION: Our study provided a comparative safety spectrum for each category of inhaled medications. Tiotropium Soft Mist Inhaler had a higher risk of mortality and should be used with caution.
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Current therapy for asthma with inhaled corticosteroids and long-acting inhaled β2-agonists is highly effective, safe, and relatively inexpensive, but many patients remain poorly controlled. Most advances have been through improving these drug classes and a major developmental hurdle is to improve existing drug classes. Major unmet needs include better treatment of severe asthma (which has some similarity to chronic obstructive pulmonary disease), as well as curative therapies for mild to moderate asthma that do not result in the return of symptoms when the treatment is stopped. Several new treatments are in development, but many are specific, targeting a single mediator or receptor, and are unlikely to have a major clinical impact, although they may be effective in specific asthma phenotypes (endotypes). Drugs with more widespread effects, such as kinase inhibitors, may be more effective but have a greater risk of side effects so inhaled delivery may be needed. Several new treatments target the underlying allergic/immune process and would treat concomitant allergic diseases. Improved immunotherapy approaches have the potential for disease modification, although prospects for a cure are currently remote.
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Noninvasive ventilation, both continuous positive airway pressure and noninvasive positive pressure ventilation, has been used increasingly for acute respiratory failure over the past several years. Noninvasive ventilation has been proven to be beneficial for some causes of acute respiratory failure, most clearly for acute exacerbations of chronic obstructive pulmonary disease, while its use in other forms of acute respiratory failure remains more controversial.
In this article, the evidence for the use of noninvasive ventilation in various kinds of acute respiratory failure will be examined. Particular attention will be paid to the clinical situations commonly encountered by emergency medicine and general internal medicine clinicians. The potential dangers of noninvasive ventilation as well as some guidelines for clinical decision making when treating patients with this mode of ventilator support will also be discussed.
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BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the small airways. The effect of inhaled corticosteroids (ICS) on lung inflammation in COPD remains uncertain. We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD.
METHODS: We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment in both intervention and control groups. These values were then converted into standardized mean differences (SMD) to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across the original studies. If significant heterogeneity was present (P < 0.1), then a random effects model was used to pool the original data; otherwise, a fixed effects model was used.
RESULTS: We identified eight original studies that met the inclusion criteria. Four studies used bronchial biopsies (n =102 participants) and showed that ICS were effective in reducing CD4 and CD8 cell counts (SMD, -0.52 units and -0.66 units, 95% confidence interval). The five studies used bronchoalveolar lavage fluid (n =309), which together showed that ICS reduced neutrophil and lymphocyte counts (SMD, -0.64 units and -0.64 units, 95% confidence interval). ICS on the other hand significantly increased macrophage counts (SMD, 0.68 units, 95% confidence interval) in bronchoalveolar lavage fluid.
CONCLUSION: ICS has important immunomodulatory effects in airways with COPD that may explain its beneficial effect on exacerbations and enhanced risk of pneumonia.