Critical inhaler errors in asthma and COPD: a systematic review of impact on health outcomes.

BACKGROUND: Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD). However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment. METHODS: A systematic review was conducted to define 'critical' errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2). RESULTS: Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total). Search-2 identified 9 studies. We observed 299 descriptions of critical error. Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency. A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden. CONCLUSIONS: We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes. Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.

Inhaled long-acting ß2 agonists enhance glucocorticoid receptor nuclear translocation and efficacy in sputum macrophages in COPD.

BACKGROUND: Combination inhaled therapy with long-acting ß2 agonists (LABAs) and corticosteroids is beneficial in treating asthma and chronic obstructive pulmonary disease (COPD). OBJECTIVE: In asthma, LABAs enhance glucocorticoid receptor (GR) nuclear translocation in the presence of corticosteroids. Whether this biological mechanism occurs in COPD, a relatively corticosteroid-resistant disease, is uncertain. METHODS: Eight patients with mild/moderate COPD participated in a double-blind, placebo-controlled, crossover study and inhaled single doses of fluticasone propionate (FP) 100 µg, FP 500 µg, salmeterol xinafoate (SLM) 50 µg, and combination FP 100 µg + SLM 50 µg. One hour postinhalation, sputum was induced, nuclear proteins isolated from purified macrophages, and levels of activated nuclear GR quantified by using a GR-glucocorticoid response element ELISA-based assay. RESULTS: Nuclear GR significantly increased after the inhalation of FP 500 µg (P < .01), but not after the inhalation of FP 100 µg or SLM 50 µg, compared with placebo. Interestingly, SLM in combination with FP 100 µg increased nuclear GR levels equivalent to those of FP 500 µg alone. This was significantly greater than either FP 100 µg (P < .05) or SLM 50 µg (P < .01) alone. In vitro in a human macrophage cell line, SLM (10(-8) mol/L) enhanced FP (10(-9) mol/L)-induced mitogen-activated protein kinase phosphatase-1 mRNA (5.8 ± 0.6 vs 8.4 ± 1.1 × 10(-6) copies, P < .05) and 2 × glucocorticoid response element-luciferase reporter gene activity (250.1 ± 15.6 vs 103.1 ± 23.6-fold induction, P < .001). Addition of SLM (10(-9) mol/L) to FP (10(-11) mol/L) significantly enhanced FP-mediated suppression of IL-1ß-induced CXCL8 (P < .05). CONCLUSIONS: Addition of SLM 50 µg to FP 100 µg enhanced GR nuclear translocation equivalent to that seen with a 5-fold higher dose of FP in sputum macrophages from patients with COPD. This may account for the superior clinical effects of combination LABA/corticosteroid treatment compared with either as monotherapy observed in COPD.