This study highlights the influence of age on phenotypes of incident pulmonary arterial hypertension and has shown the changes in demographics and epidemiology over the past decade in a national setting. The results suggest that there may be two subtypes of patients: the younger subtype with more severe hemodynamic impairment but better survival, compared with the older subtype who has more comorbidities.

Activation of the innate immune system plays a key role in exacerbations of chronic lung disease, yet the potential role of lung fibroblasts in innate immunity and the identity of epithelial danger signals (alarmins) that may contribute to this process are unclear. The objective of the study was to identify lung epithelial derived alarmins released during endoplasmic reticulum stress (ER stress) and oxidative stress and evaluate their potential to induce innate immune responses in lung fibroblasts. We found that treatment of primary human lung fibroblasts (PHLF) with conditioned media from damaged lung epithelial cells significantly upregulated IL-6, IL-8, MCP-1 and GM-CSF expression (p<0.05). This effect was reduced with anti-IL-1α or IL-1Ra but not anti-IL-1β antibody. Co-stimulation with a TLR3 ligand, Poly I:C, significantly accentuated the IL-1α induced inflammatory phenotype in PHLF, and this effect was blocked with IKK2 and TAKi inhibitors. Finally, Il1r1−/− and Il1a−/− mice exhibit reduced BAL neutrophilia and collagen deposition in response to bleomycin treatment. We conclude that IL-1α plays pivotal role in triggering proinflammatory responses in fibroblasts and this process is accentuated in the presence of dsRNA. This mechanism may be important in the repeated cycles of injury and exacerbation in chronic lung disease.

No abstract

Background-Bronchus associated lym-

Twenty eight patients with bronchial carcinoma were studied before pneumonectomy. Measurement of spirometric indices, static lung volumes, transfer factor (TLCO), and transfer coefficient (Kco) was undertaken before and four months after pneumonectomy. Fourteen of the patients also performed a symptom limited progressive exercise test on a cycle ergometer before and four months after pneumonectomy. All patients had standard xenon-133 ventilation and technetium-99m perfusion scans performed before operation. Eleven patients had krypton-81m ventilation scans in addition. Significant correlations were seen between changes in FEV1, TLCO and Kco and the preoperative function of the resected lung as determined by percentage preoperative perfusion to that lung (p < 0.001). There were mean decreases in FEV, of 22% and in vital capacity (VC) of 28-7% predicted. Estimation of postoperative FEV, from the preoperative values showed equally good agreement with measured postoperative values whether 99mTc perfusion or 8"mKr ventilation scans were used in the 11 patients in whom both scans were available. Significant correlations were seen between change in maximum exercise ventilation (VEmax) or maximum oxygen uptake (Vo2max) after pneumonectomy and percentage preoperative perfusion to the resected lung (p < 0O001). Estimation of postoperative maximum ventilation and maximum oxygen uptake from the postoperative values on the basis of 99mTc perfusion scans showed good agreement with observed values. Perfusion scans are useful in estimating not only the changes in spirometric indices that follow pneumonectomy for bronchial carcinoma but also changes in carbon monoxide transfer and exercise capacity.