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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Bone marrow-derived mesenchymal stem cells (MSCs) reduce acute lung injury in animals challenged by bleomycin or bacterial lipopolysaccaride. It is not known, however, whether MSCs protect from ventilator-induced lung injury (VILI). This study investigated whether MSCs have a potential role in preventing or modulating VILI in healthy rats subjected to high-volume ventilation. 24 Sprague-Dawley rats (250-300 g) were subjected to high-volume mechanical ventilation (25 mL·kg(-1)). ⋯ Lung oedema, histological lung injury index, concentrations of total protein, interleukin-1β, macrophage inflammatory protein-2 and number of neutrophils in BALF and vascular cell adhesion protein-1 in lung tissue significantly increased in over-ventilated rats. All these indices of VILI moved significantly towards normalisation in the rats treated with MSCs, whether intravenously or intratracheally. Both local and systemic pre-treatment with MSCs reduced VILI in a rat model.
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Randomized Controlled Trial
24-h duration of the novel LABA vilanterol trifenatate in asthma patients treated with inhaled corticosteroids.
Current guidelines recommend adding a long-acting inhaled β(2)-agonist (LABA) to inhaled corticosteroids (ICS) in patients with uncontrolled asthma. This study evaluated the novel, once-daily LABA vilanterol trifenatate (VI) in asthma patients who remained symptomatic despite existing ICS therapy. The study involved a randomised, double-blind, placebo-controlled trial of VI (3, 6.25, 12.5, 25 and 50 μg), administered once daily in the evening by dry powder inhaler for 28 days, in asthma patients aged ≥ 12 yrs symptomatic on current ICS therapy. ⋯ All doses of VI were well tolerated with low incidences of recognised LABA-related adverse events (tremor 0-2%; palpitations 0-2%; glucose effects 0-1%; potassium effects 0-<1%). Once-daily VI 12.5-50 μg resulted in prolonged bronchodilation of at least 24 h with good tolerability in asthma patients receiving ICS. Based on the overall efficacy and adverse event profile from this study, the optimum dose of VI appears to be 25 μg.
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Review
Imaging of sarcoidosis of the airways and lung parenchyma and correlation with lung function.
Imaging has a prominent role in the assessment of sarcoidosis diagnosis and outcome, which are extremely variable. Chest radiography staging helps predict the probability of spontaneous remission, and stage IV is associated with higher mortality. However, the reproducibility of reading is poor and changes in radiography and lung function are inconsistently correlated, which may be problematic for the monitoring of disease and treatment response. ⋯ CT findings may also discriminate between active inflammation and irreversible fibrosis, with occasional influence on therapeutic decisions. Three CT patterns of fibrotic sarcoidosis are identified, with different functional profiles: predominant bronchial distortion is associated with obstruction; honeycombing is associated with restriction and lower diffusing capacity of the lung for carbon monoxide; whereas functional impairment is relatively minor with linear pattern. The clinical impact of correlations between CT severity scores and functional impairment is uncertain, except for its utility elucidating the mechanisms of airflow limitation, which include bronchial distortion, peribronchovascular thickening, air-trapping and bronchial compression by lymphadenopathy.