The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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Immune mechanisms and autoimmunity seem to play a significant role in idiopathic pulmonary arterial hypertension (IPAH) pathogenesis and/or progression, but the pathophysiology is still unclear. Recent evidence has demonstrated a detrimental involvement of leptin in promoting various autoimmune diseases by controlling regulatory T-lymphocytes. Despite this knowledge, the role of leptin in IPAH is currently unknown. ⋯ Circulating regulatory T-lymphocyte numbers were comparable in all groups, and the percentage of those expressing leptin receptor was higher in IPAH and SSc-PAH compared with controls, whereas their function was reduced in IPAH and SSc-PAH patients compared with controls, in a leptin-dependent manner. Furthermore, endothelial cells from IPAH patients synthesised more leptin than controls. Our data suggest that endothelial-derived leptin may play a role in the immunopathogenesis of IPAH.
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Stroke volume augmentation during exercise is limited in chronic obstructive pulmonary disease patients because of decreased preload from dynamic hyperinflation (DH). We hypothesised that oxygen pulse and pulse pressure (PP) improve following lung volume reduction surgery (LVRS), and the magnitude of improvement correlates with reduction in DH. We compared 16 emphysema patients undergoing LVRS with six emphysema patients not undergoing LVRS. ⋯ LVRS led to increased oxygen pulse and PP during exercise at metabolic isotimes 6 months following surgery. Reductions in DH correlated with increases in oxygen pulse during exercise. Reducing lung volume may improve stroke volume response to exercise by decreasing DH.
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We reviewed the main epidemiological studies that evaluate the respiratory effects of indoor air pollutants quantitatively in industrialised countries. Consistent results support short-term (aggravation) and, although more rarely, long-term (prevalence augmentation) effects on asthma, chronic bronchitis and chronic obstructive pulmonary disease (COPD) in indoor settings with poor air quality. Environmental tobacco smoke is one of the most important risks for respiratory symptoms and diseases worldwide. ⋯ The role of phthalates, persistent organic pollutants and flame retardants in respiratory diseases remains to be established. Results from rural areas of industrialised countries indicate that exposure to some indoor bio-contaminants might be protective in early life, while it is associated with adverse respiratory adverse effects in adulthood. Studies focusing on indoor air pollutants should be developed to better understand their involvement in the inception and aggravation of respiratory diseases.
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Nitric oxide is continually synthesised in the respiratory epithelium and is upregulated in response to infection or inflammation. Primary ciliary dyskinesia (PCD) is characterised by recurrent sinopulmonary infections due to impaired mucociliary clearance. Despite chronic infections, nasal nitric oxide in such patients is markedly reduced and is used as a screening test for this condition. ⋯ The key hypotheses that have been proposed to explain the low nitric oxide levels in this condition are explored and the potential benefits of augmenting airway nitric oxide levels are considered. Further work in these patients clarifying both whether the respiratory epithelium is able to biosynthesise normal levels of nitric oxide and the role played by abnormalities in the anatomy of the paranasal sinuses is essential. While nitric oxide augmentation is unlikely to be beneficial in common PCD phenotypes, it has potential in the treatment of secondary dyskinesias and may also improve treatment of bacterial infections, particularly where biofilms are implicated.
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Randomized Controlled Trial
Efficacy and safety of twice-daily aclidinium bromide in COPD patients: the ATTAIN study.
The efficacy and safety of two doses of aclidinium bromide were evaluated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). In this 24-week, double-blind trial, patients were randomised to twice-daily aclidinium (200 μg or 400 μg) or placebo. The primary efficacy end-point was change in trough forced expiratory volume in 1 s (FEV(1)) at week 24. ⋯ Aclidinium 200 μg and 400 μg produced significant improvements over placebo in baseline-adjusted mean SGRQ total score (-3.8 and -4.6 units; p<0.001 and p<0.0001) and TDI focal score (0.6 and 1.0 units; p<0.05 and p<0.001) at week 24. With both aclidinium doses, the incidence of anticholinergic adverse events was low, and similar to placebo. Twice-daily aclidinium significantly improved bronchodilation, health status and dyspnoea, and was well tolerated in patients with COPD.