The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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Bronchiolitis obliterans syndrome (BOS) is the most important cause of late mortality following lung transplantation, resulting in major morbidity and a huge burden on healthcare resources. Treatment options are limited, resulting in a mere stabilisation of the lung function decline. Recent introduction of the macrolide antibiotic azithromycin raised new hope after demonstrating lung function improvement in subsets of patients. ⋯ Recent clinical observations, supported by research findings, have revealed a dichotomy in the clinical spectrum of BOS with neutrophilic (partially) reversible allograft dysfunction (responding to azithromycin) and fibroproliferative BOS (not responding to azithromycin). This concept is reinforced by unique data obtained in BOS patients, consisting of histology specimens, physical and radiological examination, FEV(1 )and BAL examination. The acceptance of this dichotomy can improve understanding of the heterogeneous pathological condition that constitutes bronchiolitis obliterans syndrome, thus encouraging a more accurate diagnosis and, ultimately, better tailored treatment for each bronchiolitis obliterans syndrome patient.
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Alterations of the nitric oxide receptor, soluble guanylate cyclase (sGC) may contribute to the pathophysiology of pulmonary arterial hypertension (PAH). In the present study, the expression of sGC in explanted lung tissue of PAH patients was studied and the effects of the sGC stimulator BAY 63-2521 on enzyme activity, and haemodynamics and vascular remodelling were investigated in two independent animal models of PAH. Strong upregulation of sGC in pulmonary arterial vessels in the idiopathic PAH lungs compared with healthy donor lungs was demonstrated by immunohistochemistry. ⋯ Upregulation of soluble guanylate cyclase in pulmonary arterial smooth muscle cells was noted in human idiopathic pulmonary arterial hypertension lungs and lungs from animal models of pulmonary arterial hypertension. Stimulation of soluble guanylate cyclase reversed right heart hypertrophy and structural lung vascular remodelling. Soluble guanylate cyclase may thus offer a new target for therapeutic intervention in pulmonary arterial hypertension.
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The aim of the present study was to establish the agreement between two recommended definitions of airflow obstruction in symptomatic adults referred for spirometry by their general practitioner, and investigate how rates of airflow obstruction change when pre-bronchodilator instead of post-bronchodilator spirometry is performed. The diagnostic spirometric results of 14,056 adults with respiratory obstruction were analysed. Differences in interpretation between a fixed 0.70 forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) cut-off point and a sex- and age-specific lower limit of normal cut-off point for this ratio were investigated. ⋯ The positive predictive value of pre-bronchodilator airflow obstruction was 74.7% among current or ex-smokers aged > or =50 yrs. The current clinical guideline-recommended fixed 0.70 forced expiratory volume in one second/forced vital capacity cut-off point leads to substantial overdiagnosis of obstruction in middle-aged and elderly patients in primary care. Using pre-bronchodilator spirometry leads to a high rate of false positive interpretations of obstruction in primary care.