The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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Comparative Study
Influenza pneumonia: a comparison between seasonal influenza virus and the H1N1 pandemic.
We compared clinical presentation, complications and outcome in patients with influenza A (H1N1) and seasonal influenza pneumonia. The group of patients with influenza A (H1N1) pneumonia consisted of 75 patients. 52 patients with pneumonia associated with seasonal influenza were included for comparison. Patients with pneumonia associated with novel H1N1 influenza were younger (mean age 39.7 yrs versus 69.6 yrs) and had fewer chronic comorbidities and less alcoholism. ⋯ Respiratory failure was more frequent (those with an arterial oxygen tension/inspiratory oxygen fraction ratio <200 28% versus 12%, p = 0.042), leading to a higher rate of intensive care unit (ICU) admission and mechanical ventilation (29.3% versus 7.7% (p<0.0030) and 18.7% versus 2% (p<0.0045)). Mortality was twice as high in patients with novel H1N1 (12% versus 5.8%; p = 0.238), although this was not significant, and was attributable to pneumonia in most instances (77.8% versus 0%; p = 0.046). Younger age, fewer comorbidities, more extensive radiographic extension and more severe respiratory compromise, and ICU admissions are key features of the clinical presentation of patients with novel H1N1-associated pneumonia compared with seasonal influenza pneumonia.
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In a subset of patients with cystic fibrosis (CF), nonsense mutations (premature stop codons) disrupt production of full-length, functional CF transmembrane conductance regulator (CFTR). Ataluren (PTC124) allows ribosomal readthrough of premature stop codons in mRNA. We evaluated drug activity and safety in patients with nonsense mutation CF who took ataluren three times daily (morning, midday and evening) for 12 weeks at either a lower dose (4, 4 and 8 mg·kg(-1)) or higher dose (10, 10 and 20 mg·kg(-1)). ⋯ CFTR function was greater with time and was accompanied by trends toward improvements in pulmonary function and CF-related coughing. Adverse clinical and laboratory findings were uncommon and usually mild. Chronic ataluren administration produced time-dependent improvements in CFTR activity and clinical parameters with generally good tolerability.
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The composite physiologic index (CPI) was derived to represent the extent of fibrosis on high-resolution computed tomography (HRCT), adjusting for emphysema in patients with idiopathic pulmonary fibrosis (IPF). We hypothesised that longitudinal change in CPI would better predict mortality than forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) or diffusing capacity of the lung for carbon monoxide (D(L,CO)) in all patients with IPF, and especially in those with combined pulmonary fibrosis and emphysema (CPFE). Cox proportional hazard models were performed on pulmonary function data from IPF patients at baseline (n = 321), 6 months (n = 211) and 12 months (n = 144). ⋯ In patients with moderate/severe emphysema, only a 10% decline in FEV(1) predicted mortality (HR 3.7, p = 0.046). In IPF, a five-point increase in CPI over 12 months predicts mortality similarly to relative declines of 10% in FVC or 15% in D(L,CO). For CPFE patients, change in FEV(1) was the best predictor of mortality.
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The aim of this study was to investigate whether inhaled corticosteroid (ICS) use affects outcome in patients with chronic obstructive pulmonary disease (COPD) admitted with community-acquired pneumonia (CAP). This was a prospective, observational study of patients with spirometry-confirmed COPD presenting with a primary diagnosis of CAP in Lothian, UK. Outcome measures were compared between ICS users and non-ICS users. ⋯ There were no significant differences in pneumonia severity (mean ± sd Pneumonia Severity Index (PSI) 4.2 ± 0.8 versus 4.3 ± 0.8 (p = 0.3); mean ± sd CURB-65 score 2.1 ± 1.3 versus 2.3 ± 1.3 (p = 0.07)) or markers of systemic inflammation (median C-reactive protein 148 (interquartile range 58-268) mg·L(-1) versus 183 (IQR 85-302) mg·L(-1); p = 0.08) between ICS users and non-ICS users. On multivariable analysis, after adjustment for COPD severity and PSI, ICS use was not independently associated with 30-day mortality (OR 1.71, 95% CI 0.75-3.90; p = 0.2), 6-month mortality (OR 1.62, 95% CI 0.82-3.16; p = 0.2), requirement for mechanical ventilation and/or inotropic support (OR 0.73, 95% CI 0.33-1.62; p = 0.4) or development of complicated pneumonia (OR 0.71, 95% CI 0.25-1.99; p = 0.5). Prior ICS use had no impact on outcome in patients with COPD admitted with CAP.
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Strategies to improve pulmonary endothelial barrier function are needed to reverse the devastating effects of vascular leak in acute respiratory distress syndrome. FTY720 is a pharmaceutical analogue of the potent barrier-enhancing phospholipid sphingosine 1-phosphate (S1P). FTY720 decreases vascular permeability by an incompletely characterised mechanism that differs from S1P. ⋯ Inhibition of Src, protein kinase (PK)A, PKG, PKC or protein phosphatase 2A failed to alter FTY720-induced barrier enhancement. FTY720 increased c-Abl tyrosine kinase activity and c-Abl siRNA attenuated peak barrier enhancement after FTY720. FTY720 enhances endothelial barrier function by a novel pathway involving c-Abl signalling.