Background and purposeEarly or primary application of high-frequency oscillatory ventilation (HFOV) has been recently suggested not to offer benefit to patients with acute respiratory distress syndrome (ARDS). However, the rescue effects of HFOV on severe pediatric acute respiratory distress syndrome (PARDS) with hypoxemia refractory to conventional mechanical ventilation (CMV) remain unclear. This study aimed to determine whether severe PARDS children would benefit from HFOV when oxygenation deteriorated on CMV and to identify any potential risk factors related to mortality.Patients and methodsIn a retrospective and observational study, 48 children with severe PARDS between January 2009 and July 2015 were divided into two groups: 26 in HFOV group and 22 in CMV group. Data regarding demographic, underlying conditions, arterial blood gases and clinical outcomes were collected and analyzed.ResultsThe arterial partial pressure of oxygen (PaO2)/fraction of inspiration oxygen (FiO2) ratio and PaO2 improved significantly during HFOV, whereas arterial partial pressure of carbon dioxide (PaCO2) and oxygenation index decreased. There was no statistical difference in the in-hospital mortality between the groups (P=0.367). The odds ratio of survival in HFOV group was 2.74 (95% confidence interval 0.52 to 14.58, P=0.237). The pediatric intensive care unit length of stay and total ventilation duration were longer in HFOV group (P=0.048 and P=0.000, respectively). Vasoactive agents were used more frequently in HFOV group (P=0.007). The incidence of new air leak was similar between the two groups (P=0.674). The presence of multiple organ dysfunction syndrome and heavier body weight were identified as predictors of mortality in the HFOV group (P=0.006 and P=0.020, respectively).ConclusionHFOV as an efficient alternative therapy could significantly improve hypoxemia and promote CO2 removal in severe PARDS children when oxygenation progressively worsens on CMV.

Cellular senescence is a complicated process featured by irreversible cell cycle arrest and senescence-associated secreted phenotype (SASP), resulting in accumulation of senescent cells, and low-grade inflammation. Cellular senescence not only occurs during the natural aging of normal cells, but also can be accelerated by various pathological factors. Cumulative studies have shown the role of cellular senescence in the pathogenesis of chronic lung diseases including chronic obstructive pulmonary diseases (COPD) and idiopathic pulmonary fibrosis (IPF) by promoting airway inflammation and airway remodeling. Recently, great interest has been raised in the involvement of cellular senescence in asthma. Limited but valuable data has indicated accelerating cellular senescence in asthma. This review will compile current findings regarding the underlying relationship between cellular senescence and asthma, mainly through discussing the potential mechanisms of cellular senescence in asthma, the impact of senescent cells on the pathobiology of asthma, and the efficiency and feasibility of using anti-aging therapies in asthmatic patients.

Background: Aberrant epithelial remodeling and/or abnormalities in mucociliary apparatus in airway epithelium contribute to infection and inflammation. It is uncertain if these changes occur in both large and small airways in non-cystic fibrosis bronchiectasis (non-CF bronchiectasis). In this study, we aim to investigate the histopathology and inflammatory profile in the epithelium of bronchi and bronchioles in bronchiectasis.Methods: Excised lung tissue sections from 52 patients with non-CF bronchiectasis were stained with specific cellular markers and analyzed by immunohistochemistry and immunofluorescence to assess the epithelial structures, including ciliated cells and goblet cells morphology. Inflammatory cell counts and ciliary proteins expression levels of centrosomal protein 110 (CP110) and dynein heavy chain 5, axonemal (DNAH5) were assessed.Results: Epithelial hyperplasia is found in both bronchi and bronchioles in all specimens, including hyperplasia and/or hypertrophy of goblet cells. The median cilia length is longer in hyperplastic epithelium [bronchi: 8.16 (7.03-9.14) μm, P<0.0001; bronchioles: 7.46 (6.41-8.48) μm, P<0.0001] as compared to nonhyperplastic epithelium (bronchi: 5.60 μm; bronchioles: 4.89 μm). Hyperplastic epithelium is associated with overexpression of CP110 and decreased intensity of DNAH5 expression in both bronchial and bronchiolar epithelium. Though infiltration of neutrophils is predominant (63.0% in bronchi and 76.7% in bronchioles), eosinophilic infiltration is also present in the mucosa of bronchi (30.8%) and bronchioles (54.8%).Conclusions: Aberrant epithelial remodeling with impaired mucociliary architecture is present in both large and small airways in patients with refractory non-CF bronchiectasis. Future studies should evaluate the interplay between these individual components in driving chronic inflammation and lung damage in patients.

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Airway remodeling is a hallmark of bronchial asthma. Our group has previously reported that the thymic stromal lymphopoietin (TSLP), an airway epithelial-derived cytokine, has a central role in the pathogenesis of airway remodeling, and that toll-like receptor (TLR) 4 signaling in epithelial cells may trigger T-helper 2 (Th2) immune responses by overexpression of TSLP. However, it is currently unclear whether TLR4 is a target in the treatment of airway remodeling in asthma. The present study established a house dust mite (HDM)-induced chronic asthmatic model in female BALB/c mice and treated the HDM-exposed mice with 3 mg/kg TAK242, as a TLR4 antagonist, 30 min prior to HDM challenge for up to 2 weeks. General structural changes in the airways were subsequently evaluated and the levels of TSLP in the bronchoalveolar lavage fluid (BALF) and interleukin (IL)-4, IL-13 and interferon (IFN)-γ in the blood serum were determined. Results indicated that TAK242 treatment markedly reduced pathological changes in the airways of HDM-induced asthmatic mice, as demonstrated by reductions in airway wall thickening, peribronchial collagen deposition and subepithelial fibrosis. Furthermore, airway hyperresponsiveness to inhaled methacholine and the levels of TSLP in the BALF and IL-4, IL-13 and IFN-γ in the peripheral blood were significantly reduced by TAK242 treatment (P<0.05). Furthermore, the shift in the IFN-γ/IL-4 ratio induced by HDM treatment was significantly reversed following TAK242 pretreatment, which indicated that TAK242 modulated Th1/Th2 immune homeostasis in the chronic asthma mouse model. The present findings in a chronic asthma mouse model suggest that TAK242 may be an efficient treatment for airway remodeling, possibly through the inhibition of TSLP overexpression and Th2 airway inflammation.

Background and purposeHospital-acquired pneumonia (HAP) remains an important cause of morbidity and mortality despite advances in antimicrobial therapy. The emergence of multidrug resistant (MDR) Pseudomonas aeruginosa (PA) is of major concern. Our aim was to evaluate the risk factors and prognosis of HAP due to MDR-PA infection.Patients and methodsIn a retrospective observational study, we collected data on all episodes of HAP caused by PA (PA-HAP) occurring from January 2013 to December 2016. Characteristics of patients with drug-sensitive PA were compared with those with MDR-PA. Data of demographic, underlying conditions, peripheral neutrophil-to-lymphocyte ratio (NLR), and clinical outcomes were collected and analyzed.ResultsOne hundred fifty-seven patients with PA-HAP were included, of which 69 (43.9%) patients were diagnosed with MDR-PA infection. There were significant differences between MDR-PA group and non-MDR-PA group on the following variables: initial inappropriate antibiotic therapy (P<0.001, OR 0.103, 95% CI 0.044–0.244), admission in more than two departments in previous 30 days (P<0.001, OR 0.186, 95% CI 0.072–0.476), and NLR level (P=0.020, OR 0.911, 95% CI 0.843–0.985). The effect of antibiotic treatment was significantly different (P<0.001, OR 4.263, 95% CI 2.142–8.483). The 30-day mortality was higher in MDR-PA group than that in non-MDR-PA group (P<0.001).ConclusionWe have shown that lower NLR level was identified as a clinical predictor of MDR-PA infection in HAP patients. Even with goal-directed therapy, MDR-PA infection implicates poor outcomes in patients with HPA.

BackgroundUpper airway inflammatory diseases are associated with abnormal expression of nasal epithelial forkhead-box J1 (FOXJ1) which regulates motile cilia formation. We sought to investigate whether aberrant FOXJ1 localizations correlate with the disease severity and the co-existence of allergic rhinitis (AR) or asthma in patients with nasal polyps (NPs).MethodsWe elucidated localization patterns of FOXJ1 by performing immunofluorescence assays in nasal specimens and cytospin samples from controls and patients with NPs. We also assayed mRNA expression levels of FOXJ1 by using quantitative real-time polymerase chain reaction. Four localization patterns [normal (N), intermediate (I), mislocalization (M), and absence (A)] were defined. A semi-quantitative scoring system was applied for demonstrating FOXJ1 localization in five areas per paraffin section, with individual sections being scored between 0 and 2.ResultsFOXJ1 localization score was significantly higher in samples from NPs than in controls (P < 0.001). Elevated FOXJ1 localization scores and down-regulation of FOXJ1 mRNA levels were observed in NPs with co-existing AR or asthma (all P < 0.05). Moreover, FOXJ1 localization scores positively correlated with Lund–Mackay score (r = 0.362, P = 0.007). Of primary cytospin samples, the mean percentage of patients with FOXJ1 localization patterns N, I, M and A was 15.0%, 3.3%, 53.3% and 28.3% in NPs, and 82.5%, 5.0%, 5.0% and 7.5% in controls, respectively (P < 0.001).ConclusionsAberrant localization of FOXJ1 correlates with the severity and co-existence of AR or asthma in patients with NPs, and might be a novel target for assessment and intervention in NPs.Electronic supplementary materialThe online version of this article (10.1186/s13223-018-0296-z) contains supplementary material, which is available to authorized users.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease attributed to the complex interplay of genetic and environmental risks. The muco-ciliary clearance (MCC) system plays a critical role in maintaining the conduit for air to and from the alveoli, but it remains poorly understood whether the MCC abnormalities in conducting airway are involved in IPF pathogenesis. In this study, we obtained the surgically resected bronchi and peripheral lung tissues from 31 IPF patients and 39 control subjects, and we sought to explore the morphologic characteristics of MCC in conducting airway by using immunostaining and scanning and transmission electron microscopy. In the submucosal regions of the bronchi, we found that the areas of mucus glands (MUC5B+) were significantly larger in IPF patients as compared with control subjects (p &lt; 0.05). In the surface epithelium of three airway regions (bronchi, proximal bronchioles, and distal bronchioles), increased MUC5B and MUC5AC expression of secretory cells, decreased number of ciliated cells, and increased ciliary length were observed in IPF patients than control subjects (all p &lt; 0.05). In addition, the mRNA expression levels of MUC5B were up-regulated in both the bronchi and peripheral lung of IPF patients than those of control subjects (p &lt; 0.05), accompanied with 93.55% IPF subjects who had obvious MUC5B+ mucus plugs in alveolar regions. No MUC5B rs35705950 single-nucleotide polymorphism allele was detected in both IPF patients and control subjects. Our study shows that mucus hypersecretion and ciliary impairment in conducting airway are major causes of mucus plugs in alveolar regions and may be closely related to the alveolar injuries in IPF patients.