BackgroundSleep problems are common in patients with chronic obstructive pulmonary disease (COPD), but the validity of patient-reported outcome measures (PROMs) that measure sleep dysfunction has not been evaluated. We have reviewed the literature to identify disease-specific and non-disease-specific sleep PROMs that have been validated for use in COPD patients. The review also examined the psychometric properties of identified sleep outcome measures and extracted point and variability estimates of sleep instruments used in COPD studies.MethodsThe online EMBASE, MEDLINE, PsycINFO, and SCOPUS databases for all years to May 2014 were used to source articles for the review. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Criteria from the Medical Outcomes Trust Scientific Advisory Committee guidelines were used to evaluate the psychometric properties of all sleep PROMs identified.ResultsOne COPD-specific and six non-COPD-specific sleep outcome measures were identified and 44 papers met the review selection criteria. We only identified one instrument, the COPD and Asthma Sleep Impact Scale, which was developed specifically for use in COPD populations. Ninety percent of the identified studies used one of two non-disease-specific sleep scales, ie, the Pittsburgh Sleep Quality Index and/or the Epworth Sleep Scale, although neither has been tested for reliability or validity in people with COPD.ConclusionThe results highlight a need for existing non-disease-specific instruments to be validated in COPD populations and also a need for new disease-specific measures to assess the impact of sleep problems in COPD.
Aims
Some asthma patients remain symptomatic despite using high doses of inhaled corticosteroids (ICS). We used alveolar macrophages to identify individual patients with insensitivity to corticosteroids and to evaluate the anti‐inflammatory effects of a p38 mitogen‐activated protein kinase (MAPK) inhibitor combined with a corticosteroid on these cells.
Methods
Alveolar macrophages from 27 asthma patients (classified according to the Global Initiative for Asthma (GINA) treatment stage. Six GINA1, 10 GINA2 and 11 GINA3/4) were stimulated with lipoploysaccharide (LPS) (1 μg ml−1). The effects of dexamethasone (dex 1–1000 nm), the p38 MAPK inhibitor 1‐(5‐tert‐butyl‐2‐p‐tolyl‐2Hpyrazol‐3‐yl)‐3(4‐(2‐morpholin‐4‐yl‐ethoxy)naphthalen‐1‐yl)urea (BIRB‐796 1–1000 nm) and both drugs combined at all concentrations on supernatant TNFα, IL‐6 and CXCL‐8 concentrations were analyzed by ELISA. Dose‐sparing and efficacy enhancing effects of combination treatment were determined.
Results
Dexamethasone reduced LPS‐induced TNFα, IL‐6 and CXCL‐8 in all groups, but maximum inhibition was significantly reduced for GINA3/4 compared with GINA2 and GINA1 (P < 0.01). A subgroup of corticosteroid insensitive patients with a reduced effect of dexamethasone on cytokine secretion were identified. BIRB‐796 in combination with dexamethasone significantly increased cytokine inhibition compared with either drug alone (P < 0.001) in all groups. This effect was greater in corticosteroid insensitive compared with sensitive patients. There were significant synergistic dose‐sparing effects (P < 0.05) for the combination treatment on inhibition of TNFα, IL‐6 and CXCL‐8 in all groups. There was also significant efficacy enhancing benefits (P < 0.05) on TNFα and IL‐6.
Conclusions
p38 MAPK inhibitors synergistically enhance efficacy of corticosteroids in macrophages from asthma patients. This effect is greater in corticosteroid insensitive asthma patients, suggesting that this class of drug should be targeted to this patient phenotype.
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