Objective Community-acquired pneumonia (CAP) remains a major cause of death. No studies have reported the use of rapid influenza diagnostic tests (RIDT) for the etiological diagnosis, and the factors contributing to severity and mortality have not yet been fully investigated. The aim of this study was to review the etiologies of CAP using RIDT and to identify risk factors related to the severity and mortality of the disease. Methods This retrospective study assessed these factors in hospitalized patients, with special emphasis on microbial etiology. Results A total of 1,032 patients aged 63.9±18.3 years were studied, 66.2% of whom were men. Microbial identification was obtained in 57.0% of the cases. The most frequent causative microbial agents were Streptococcus pneumoniae, Mycoplasma pneumoniae and the influenza virus, and the second most frequent pathogens in the patients with severe CAP and the non-survivors were S. pneumoniae and the influenza virus. Age (≥65 years), chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, dementia and Legionella spp. infection and polymicrobial infection were each found to be independent factors related to severity in the multivariate analysis, whereas "unidentified pathogen" was found to be an independent factor for non-severe CAP. Age (≥65 years), chronic pulmonary aspergillosis, post-lung cancer surgery and severe CAP were found to be independent factors for non-survival according to a multivariate analysis. Conclusion In addition to S. pneumoniae, the influenza virus was a frequent cause of CAP overall and a frequent causative pathogen in both severe cases of CAP and non-survivors. Legionella spp. infection and polymicrobial infection were found to be an independent factor for the severity of CAP along with advanced age and certain comorbidities. An advanced age, certain respiratory comorbidities and severe CAP were found to be important independent factors for the mortality of CAP.

Objective The prognostic factors of chronic necrotizing pulmonary aspergillosis remain unclear. We assessed the prognostic factors of all-cause mortality in patients with chronic necrotizing pulmonary aspergillosis, focusing especially on underlying pulmonary disease, first-line treatment and host predisposition. Methods We retrospectively analyzed the medical records of 194 patients negative for HIV who had chronic necrotizing pulmonary aspergillosis treated at our institution in Saitama, Japan. Results The patients (median age, 68.5 years) were followed over a median follow-up time of 2.6 years. The underlying pulmonary diseases consisted of previous pulmonary tuberculosis in 59 (30.4%) patients, emphysema in 39 (20.1%) patients, interstitial lung disease in 32 (16.5%) patients, nontuberculous mycobacteriosis in 29 (14.9%) patients and other diseases in 35 (18%) patients. The first-line treatments included observation in 65 (33.5%) patients, itraconazole in 56 (28.9%) patients, micafungin in 46 (23.7%) patients, voriconazole in 22 (11.3%) patients and amphotericin B (including liposomal amphotericin B) in five (2.6%) patients. The overall cumulative mortality rate was 50.2% at five years and 67.4% at 10 years. Multivariate Cox proportional hazard modeling found an older age, the presence of systemic comorbidities, baseline corticosteroid use, a body mass index of <18.5 kg/m2 and a C-reactive protein level of ≥5.0 mg/dL to be negative prognostic factors for all-cause mortality. Conclusion The 5-year mortality rate of chronic necrotizing pulmonary aspergillosis was 50.2%. When clinical trials are designed and implemented to test effective drug therapies in patients with chronic necrotizing pulmonary aspergillosis, the trial patients should be stratified according to these prognostic factors prior to randomization.

Background: Recent reports have suggested an involvement of neutrophilic inflammation driven by interleukin (IL)-17 from Th17 cells, especially in severe, refractory asthma. It remains unknown about the possible interactions of this cytokine and other proinflammatory cytokines to direct neutrophilic airway inflammation. Materials and Methods: We evaluated the effects of IL-17A, IL-17E, and IL-17F in combination with other stimuli such as tumor necrosis factor (TNF) –α on the production and expression of IL-8 in human bronchial epithelial cells. We also studied their effects on other cytokine production. The possible role of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways was evaluated by specific inhibitors. We examined the effects of anti-asthma drugs, such as steroids or salmeterol. Results: IL-17A alone induced only a minimal effect on IL-8 expression. IL-17A, but not IL-17E or IL-17F, in combination with TNF-α showed a synergistic effect on IL-8 expression. Similar findings were found when combination with IL-1β and IL-17A were used, but such was not the case with lipopolysaccharide (LPS). In addition, we further found such synergy on GM-CSF production. The synergy with TNF-α and IL-17A was significantly inhibited by MAPKs inhibitors. Corticosteroids such as fluticasone propionate and dexamethasone, but not salmeterol, partially suppressed the IL-17A and TNF-α-induced IL-8 production. Conclusions: IL-17A in the combination with TNF-α or IL-1β showed a synergistic augmenting effect on IL-8 and GM-CSF production in human airway epithelial cells.

Neutrophilic inflammation is associated with poorly controlled asthma. Serum levels of sST2, a soluble IL-33 receptor, increase in neutrophilic lung diseases. We hypothesized that high serum sST2 levels in stable asthmatics are a predictor for exacerbation within a short duration. This prospective observational study evaluated the serum sST2 levels of 104 asthmatic patients who were treated by a lung disease specialist with follow-ups for 3 months. High serum sST2 levels (> 18 ng/ml) predicted severe asthma exacerbation within 3 months. Serum sST2 levels correlated positively with asthma severity (treatment step), airway H2O2 levels, and serum IL-8 levels. High serum sST2 levels and blood neutrophilia (> 6000 /μl) were independent predictors of exacerbation. We defined a post-hoc exacerbation-risk score combining high serum sST2 level and blood neutrophilia, which stratified patients into four groups. The score predicted exacerbation-risk with an area under curve of 0.91 in the receiver operating characteristic curve analysis. Patients with the highest scores had the most severe phenotype, with 85.7% showing exacerbation, airflow limitation, and corticosteroid-insensitivity. High serum sST2 levels predicted exacerbation within the general asthmatic population and, when combined with blood neutrophil levels, provided an exacerbation-risk score that was an accurate predictor of exacerbation occurring within 3 months.

Background and purpose of the study: Pseudomonas aeruginosa commonly colonizes the airway of patients with chronic obstructive pulmonary disease (COPD) and exacerbates their symptoms. P. aeruginosa carries flagellin that stimulates toll-like receptor (TLR)-5; however, the role of flagellin in the pathogenesis of COPD remains unclear. The aim of the study was to evaluate the mechanisms of the flagellin-induced innate immune response in bronchial epithelial cells, and to assess the effects of anti-inflammatory agents for treatment. Materials and methods: We stimulated BEAS-2B cells with P. aeruginosa-derived flagellin, and assessed mRNA expression and protein secretion of interleukin (IL)-6 and IL-8. We also used mitogen-activated protein kinases (MAPK) inhibitors to assess the signaling pathways involved in flagellin stimulation, and investigated the effect of clinically available anti-inflammatory agents against flagellin-induced inflammation. Results: Flagellin promoted protein and mRNA expression of IL-6 and IL-8 in BEAS-2B cells and induced phosphorylation of p38, ERK, and JNK; p38 phosphorylation-induced IL-6 production, while IL-8 production resulted from p38 and ERK phosphorylation. Fluticasone propionate (FP) and dexamethasone (DEX) suppressed IL-6 and IL-8 production in BEAS-2B cells, but clarithromycin (CAM) failed to do so. Conclusions: P. aeruginosa-derived flagellin-induced IL-6 and IL-8 production in bronchial epithelial cells, which partially explains the mechanisms of progression and exacerbation of COPD. Corticosteroids are the most effective treatment for the suppression of flagellin-induced IL-6 and IL-8 production in the bronchial epithelial cells.