Efficacy and safety of inhaled alpha-1-antitrypsin in patients with severe alpha-1-antitrypsin deficiency and frequent exacerbations of Chronic Obstructive Pulmonary Disease.

Abstract: Patients with inherited alpha-1-antitrypsin (AAT) deficiency (ZZ-AATD) and severe chronic obstructive pulmonary disease (COPD) frequently suffer from exacerbations. We postulated that inhalation of nebulised AAT would be an effective […]

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Diffusing Capacity of Carbon Monoxide in Assessment of Chronic Obstructive Pulmonary Disease.

Diffusing capacity of the lung for carbon monoxide (DLCO) is inconsistently obtained in patients with chronic obstructive pulmonary disease (COPD) and the added benefit of DLCO testing beyond more common tools is unknown.To determine whether lower DLCO is associated with increased COPD morbidity independent of spirometry and CT emphysema.Data for 1806 COPD participants from the COPDGene 5-year visit were analyzed, including pulmonary function testing, quality of life, symptoms, exercise performance, and exacerbation rates. DLCO % predicted was primarily analyzed as a continuous variable and additionally categorized into four groups: (1) DLCO and FEV1 >50% (reference), (2) only DLCO ?50%, (3) only FEV1 ?50%, and (4) both ?50% predicted. Outcomes were modelled using multivariable linear and negative binomial regression, including emphysema and FEV1 % predicted among other confounders.In multivariable analyses, every 10% predicted decrease in DLCO was associated with symptoms and quality of life (CAT: 0.53 p<0.001, SGRQ: 1.67 p<0.001, SF-36 physical functioning: -0.89 p<0.001), exercise performance (6MWD: -45.35 p<0.001), and severe exacerbation rate (RR 1.14 p<0.001). When categorized, severe impairment in DLCO alone, FEV1 alone, or both DLCO and FEV1 was associated with significantly worse morbidity as compared to the reference group (p<0.05 for all outcomes).Impairment in DLCO was associated with increased COPD symptoms, reduced exercise performance, and severe exacerbation risk even after accounting for spirometry and CT evidence of emphysema. These findings suggest that DLCO should be considered for inclusion in future multidimensional tools assessing COPD.

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Prevalence and risk factors for osteoporosis in individuals with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Osteoporosis is prevalent in individuals with chronic obstructive pulmonary disease (COPD). Updated evidence is required to complement the previous systematic review on this topic in order to provide best practice. The aim of this systematic review and meta-analysis was to quantitatively synthesize data from studies with respect to the prevalence and risk factors for osteoporosis among individuals with COPD.EMBASE, CINAHL MEDLINE, and PubMed databases were searched for articles containing the keywords “COPD”, “osteoporosis”, “prevalence”, and “risk factor”. Eligibility screening, data extraction, and quality assessment of the retrieved articles were conducted independently by two reviewers. Meta-analyses were performed to determine osteoporosis prevalence and risk factors in individuals with COPD. Meta-regression analyses were conducted to explore the sources of heterogeneity.The pooled global prevalence from 58 studies was 38% (95% CI= 34, 43). The presence of COPD increased the likelihood of having osteoporosis (OR= 2.83). Other significant risk factors for osteoporosis in COPD patients were body mass index < 18.5 kg/m2 (OR=4.26) and the presence of sarcopenia (OR= 3.65).Osteoporosis is prevalent in individuals with COPD and the prevalence appears to be high and similar in many countries. COPD patients should be screened for osteoporosis and contributing risk factors.

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Pitfalls and caveats in ?1-antitrypsin deficiency testing: a guide for clinicians.

?1-antitrypsin deficiency (AATD) remains the only readily identified genetic cause of chronic obstructive pulmonary disease (COPD). Furthermore, there is growing evidence that even a moderate deficiency increases the risk of lung disease among smokers. Despite these facts, the uptake of testing for AATD in at-risk populations remains low for many reasons, and a lack of clarity among clinicians regarding the most appropriate diagnostic techniques presents a major deterrent. This Personal View addresses the benefits of diagnosis, the technical basis of the available diagnostic methods, and possible clinical confounders for each test. We include a series of unusual cases encountered at our National Centre of Expertise to provide context. The topics covered should equip clinicians with the core knowledge required to confidently assess patients for AATD.

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Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages.

Increased reactive oxygen species (ROS) have been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD).This study examined the effect of exogenous and endogenous oxidative stress on macrophage phagocytosis in patients with COPD.Monocyte-derived macrophages (MDM) were generated from non-smoker, smoker and COPD subjects, differentiated in either GM-CSF (G-M?) or M-CSF (M-M?). Alveolar macrophages were isolated from lung tissue or bronchoalveolar lavage. Macrophages were incubated +/- 200?µM H2O2 for 24?h, then exposed to fluorescently-labelled H. influenzae or S. pneumoniae for 4?h, after which phagocytosis, mitochondrial ROS (mROS), and mitochondrial membrane potential (??m) were measured.Phagocytosis of bacteria was significantly decreased in both G-M? and M-M? from COPD patients, compared to non-smoker controls. In non-smokers and smokers, bacterial phagocytosis did not alter mROS or ??m, however in COPD, phagocytosis increased early mROS and decreased ??m in both G-M? and M-M?. Exogenous oxidative stress reduced phagocytosis in non-smoker and COPD alveolar macrophages, and non-smoker MDM, associated with reduced mROS production.COPD macrophages show defective phagocytosis, which is associated with altered mitochondrial function and an inability to regulate mROS production. Targeting mitochondrial dysfunction may restore the phagocytic defect in COPD.

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Nanotechnology based therapeutics for lung disease.

Nanomedicine is a multidisciplinary research field with an integration of traditional sciences such as chemistry, physics, biology and materials science. The application of nanomedicine for lung diseases as a relatively new area of interdisciplinary science has grown rapidly over the last 10 years. Promising research outcomes suggest that nanomedicine will revolutionise the practice of medicine, through the development of new approaches in therapeutic agent delivery, vaccine development and nanotechnology-based medical detections. Nano-based approaches in the diagnosis and treatment of lung diseases will, in the not too distant future, change the way we practise medicine. This review will focus on the current trends and developments in the clinical translation of nanomedicine for lung diseases, such as in the areas of lung cancer, cystic fibrosis, asthma, bacterial infections and COPD.

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Air pollution, lung function and COPD: results from the population-based UK Biobank study.

Ambient air pollution increases the risk of respiratory mortality but evidence for impacts on lung function and chronic obstructive pulmonary disease (COPD) is less well established. The aim was to evaluate whether ambient air pollution is associated with lung function and COPD, and explore potential vulnerability factors.We used UK Biobank data on 3?03?887 individuals aged 40-69?years, with complete covariate data and valid lung function measures. Cross-sectional analyses examined associations of Land Use Regression-based estimates of particulate matter (PM2.5, PM10 and PMcoarse) and nitrogen dioxide (NO2) concentrations with forced expiratory volume in 1?s (FEV1), forced vital capacity (FVC), the FEV1/FVC ratio, and COPD (FEV1/FVC » Read more

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