The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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Asthma is a heterogeneous inflammatory airways disorder where interleukin (IL)-1β is thought to be a key mediator, especially in the neutrophilic subtype of asthma. The generation of active IL-1β requires proteolytic cleavage typically mediated through the formation of a caspase-1-containing inflammasome. This study hypothesised that an IL-1β endotype associated with the nucleotide-binding domain, leucine-rich repeat-containing family protein (NLRP)3/apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)/caspase-1 inflammasome is characteristic of patients with the neutrophilic subtype of asthma. ⋯ Protein levels of IL-1β were significantly higher in those with neutrophilic asthma and correlated with sputum IL-8 levels. Sputum macrophages, as well as sputum neutrophils in neutrophilic asthma, expressed NLRP3 and caspase-1 protein. NLRP3 inflammasome is upregulated in neutrophilic asthma and may regulate the inflammation process observed in this asthma phenotype through production of IL-1β.
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Review Meta Analysis Observational Study
Simplification of the IDSA/ATS criteria for severe CAP using meta-analysis and observational data.
The 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines proposed "minor" criteria to predict intensive care unit (ICU) admission in patients with community-acquired pneumonia. These criteria were based on expert opinion. Consequently, the authors of the guidelines asked investigators to determine whether the score could be simplified by excluding noncontributory variables. ⋯ Additional predictors suggested by the IDSA/ATS were associated with mortality and ICU admission, but only incorporating acidosis (pH <7.35) altered the AUC (0.82 (95% CI 0.78-0.86) (p=0.6) for mortality and 0.86 (95% CI 0.82-0.88) (p=0.8) for ICU admission). No improvements were statistically significant. The IDSA/ATS criteria can be simplified by removing three infrequent variables.
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Randomized Controlled Trial Multicenter Study
Once-daily fluticasone furoate alone or combined with vilanterol in persistent asthma.
The inhaled corticosteroid fluticasone furoate (FF) and the long-acting β₂ agonist vilanterol (VI) are in development as a combined once-daily therapy for asthma and chronic obstructive pulmonary disease. Our study objectives were to compare the efficacy and safety of once-daily FF/VI with FF alone and twice-daily fluticasone propionate (FP) in patients aged ≥12 years with moderate-to-severe persistent asthma. Patients (n=586) received FF/VI 200/25 μg or FF 200 μg once-daily (evening dosing), or FP 500 μg twice-daily for 24 weeks. ⋯ Incidence of adverse events was similar across groups. No clinically significant differences were seen for 24-h urinary cortisol excretion, vital signs or ECG. FF/VI resulted in statistically greater improvements in lung function and symptomatic end-points versus FF, and was well tolerated in this asthma population.
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Observational Study
IDSA/ATS minor criteria aid pre-intensive care unit resuscitation in severe community-acquired pneumonia.
The effect of employing severity scores to identify severe community-acquired pneumonia (SCAP) cases for early aggressive resuscitation is unknown. Optimising pre-intensive care unit (ICU) care may improve outcomes in patients at risk of SCAP. We conducted a before-and-after study of patients classified into control and intervention groups (January 2004 to December 2007 and January 2008 to December 2010, respectively). ⋯ ICU admission rates decreased from 52.9% to 38.6% (p=0.008) and inappropriately delayed ICU admissions decreased from 32.0% to 14.8% (p<0.001). There was increased compliance with the aggressive resuscitation protocol after the intervention. A combined intervention, using a pneumonia score to identify those at risk of SCAP early and an aggressive pre-ICU resuscitation protocol may reduce mortality and ICU admissions.