Vitamin A-regulated ciliated cells promote airway epithelium repair in an asthma mouse model.

BACKGROUND: Asthma is a chronic inflammatory airway disease that causes damage to and exfoliation of the airway epithelium. The continuous damage to the airway epithelium in asthma cannot be repaired quickly and generates irreversible damage, repeated attacks, and aggravation. Vitamin A (VA) has multifarious biological functions that include maintaining membrane stability and integrity of the structure and function of epithelial cells. Our research explored the role of VA in repairing the airway epithelium and provided a novel treatment strategy for asthma. METHODS: A mouse asthma model was established by house dust mite (HDM) and treated with VA by gavage. Human bronchial epithelial (16HBE) cells were treated with HDM and all-trans retinoic acid (ATRA) in vitro. We analyzed the mRNA and protein expression of characteristic markers, such as acetyl-α-tubulin (Ac-TUB) and FOXJ1 in ciliated cells and MUC5AC in secretory cells, mucus secretion, airway inflammation, the morphology of cilia, and the integrity of the airway epithelium. RESULTS: Findings showed destruction of airway epithelial integrity, damaged cilia, high mucus secretion, increased MUC5AC expression, and decreased Ac-TUB and FOXJ1 expression in asthmatic mice. The VA intervention reversed the effect on Ac-TUB and FOXJ1 and promoted ciliated cells to repair the damage and maintain airway epithelial integrity. In 16HBE cells, we could confirm that ATRA promoted the expression of Ac-TUB and FOXJ1. CONCLUSION: These results demonstrated that VA-regulated ciliated cells to repair the damaged airway epithelium caused by asthma and maintain airway epithelial integrity. VA intervention is a potential adjunct to conventional treatment for asthma.

A prediction model for the efficacy of continuous positive airway pressure on bronchiolitis.

Objectives: Prediction of the efficacy of continuous positive airway pressure (CPAP) on bronchiolitis is necessary for timely treatment. This study aims to establish a nomogram for efficacy of CPAP on bronchiolitis, and compares accuracy with Pediatric Risk of Mortality III (PRISM III), Brighton Pediatric Early Warning Score (Brighton PEWS) and Pediatric Critical Illness Score (PCIS). Methods: From February 2014 to December 2020, data on children diagnosed with bronchiolitis and treated with CPAP in Chongqing was collected. The nomogram was evaluated by using multivariate logistic regression analysis. We compared the predictive value of model with PRISM III, PEWS and PCIS. Results: A total of 510 children were included. The nomogram prediction model including fever, APTT, white blood cells, serum potassium concentration, lactic acid, immunodeficiency, atelectasis, lung consolidation, congenital airway dysplasia and congenital heart disease was established. The AUC of the nomogram was 0.919 in the training set and 0.947 in the validating set. The model fitted well, as evidenced by the calibration curve and Hosmer-Lemeshow goodness-of-fit test. We discovered that the nomogram significantly performed better than PRISM III, PCIS and PEWS. Conclusions: A nomogram including ten factors for predicting the efficacy of CPAP on bronchiolitis was established. It had higher performance than the PRISM III, PCIS, and PEWS in terms of clinical benefits.

The Associations of Caesarean Delivery With Risk of Wheezing Diseases and Changes of T Cells in Children.

Objectives: This study aimed to assess the associations of caesarean delivery (CD) with risk of wheezing diseases and changes of immune cells in children. Design: The cross-sectional study was conducted between May, 2020 and April, 2021. Setting and participants: The study was conducted in Shanghai Children's Medical Center, Shanghai, China. A total of 2079 children with a mean age of 36.97 ± 40.27 months and their guardians were included in the present study via face-to-face inquiry and physical examination by clinicians. Methods: Logistic regression was applied to estimate odds ratio (ORs) and 95% confidence intervals (CIs) for the association between CD and first episode of wheezing (FEW) or asthma. Models were adjusted for premature or full-term delivery, exclusive breastfeeding (at least 4 months) or not. Results: Among the 2079 children, 987 children (47.47%) were born by CD and 1092 (52.53%) by vaginal delivery (VD). Children delivered by caesarean had significantly lower gestational age (P<0.01) compared with those who delivered vaginally. Our results also showed that CD was related to increased risk of FEW by the age of 3(adjusted OR 1.50, 95%CI 1.06, 2.12) and increased tendency to develop asthma by the age of 4 (adjusted OR 3.16, 95%CI 1.25, 9.01). The subgroup analysis revealed that the negative effects of CD on asthma were more obvious in children without exclusive breastfeeding (adjusted OR 4.93, 95%CI 1.53, 21.96) or without postnatal smoking exposure (adjusted OR 3.58, 95%CI 1.20, 13.13). Furthermore, compared with children born through VD, a significant change of the T cells (increased proportion of CD4+ T cells and decreased number and proportion of CD8+ T cells) were observed before the age of one in the CD group. However, the changes were insignificant in children over 1 year old. Conclusions: This study showed age-dependent associations of CD with asthma and FEW in offspring. Moreover, CD appeared to have an effect on the cellular immunity in infants, the disorder of which may contribute to the development of asthma in children.

Establishing a patient registry study database of dust mite allergic asthma in children: design, methodology and preliminary exploration.

BACKGROUND: Asthma is a heterogeneous disease with different phenotypes, endotypes and responses to treatment. Dust mite allergic asthma (DMAA) is the most common type in children. Compared with randomized control trials, a patient registry study (PRS) can reflect the real physical condition and clinical diagnosis more comprehensively. METHODS: Children who visited the asthma clinic of the Children's Hospital of Chongqing Medical University between August 2018 and August 2020, and met the inclusion criteria and also agreed to participate, were enrolled in the registry study. Clinical information, laboratory tests and peripheral blood samples were collected after informed consent was given by guardians. RESULTS: To date, 208 children have been enrolled in the patient registry database of DMAA. They are mainly male, with >50% having a history of allergic rhinitis, cesarean section, positive family history and passive smoking. Eosinophils and total immunoglobulin E levels were all significantly higher than normal. According to results for the childhood asthma control test (c-ACT) and ratio of forced expiratory volume in 1 s to predicted value after inhaled corticosteroid treatment, the uncontrolled group had higher hemoglobin (Hb) levels than the control group. The group exhibiting abnormal pulmonary function was older, and had longer disease duration, higher fractional exhaled nitric oxide and Hb than the group in which pulmonary function was restored. CONCLUSIONS: We have preliminarily established a registered study database of children with DMAA. By cluster analysis and using blood samples, we can further study the different pathophysiological mechanisms in order to provide more individualized and targeted treatments for all children.

Therapeutic effect of nebulized hypertonic saline for muco-obstructive lung diseases: a systematic review and meta-analysis with trial sequential analysis.

Overproduction of mucus and impaired clearance play important roles in the pathogenesis of muco-obstructive lung diseases (MOLDs). This study aims to evaluate the therapeutic effect and safety of nebulized hypertonic saline (HS) on MOLDs. Five electronic databases including PubMed, Excerpt Medica Database (EMBASE), Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and International Standard Randomized Controlled Trial Number Register were searched until June 2019. Randomized controlled trials or randomized controlled crossover trials which investigated the therapeutic effect of HS versus non-HS for MOLDs were included. Twenty-one studies met the eligibility criteria. For cystic fibrosis (CF), although the forced expiratory volume in the first second and forced vital capacity did not improve significantly (mean difference (MD) -0.48, 95% CI -3.72 to 2.76), (MD 1.85, 95% CI -4.31 to 8.01), respectively), the clearance capability of lung and quality of life (QOL) improved significantly in the HS group ((standard mean difference 0.44, 95% CI 0.02 to 0.87), (MD -0.64, 95% CI -)1.14, to 0.13), respectively). However, the results of trial sequential analysis showed the evidence needed more researches to support. The effect of nebulized HS on non-CF bronchiectasis, chronic obstructive pulmonary disease, and primary ciliary dyskinesia also need more evidence to conclude, since current studies are limited and results are inconsistent. Most adverse events of nebulized HS were mild and transient. In summary, the current available evidence suggests that nebulized HS may increase the QOL in CF, but there was no significant improvement in lung function. However, it is not possible to draw firm conclusions for other MOLDs due to limited data.

Effect of human umbilical cord-derived mesenchymal stem cells on murine model of bronchiolitis obliterans like injury.

BACKGROUND: Bronchiolitis obliterans is a fatal respiratory disease characterized by the obliteration of small airways. Mesenchymal stem cells (MSCs) is a promising candidate for cell-based therapy. OBJECTIVE: To evaluate the therapeutic effect of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on a murine model of bronchiolitis obliterans like injury (BOLI). METHOD: The murine model of BOLI was established by administrating of diacetyl (DA) via intratracheal instillation. Treatment of HUC-MSCs or HUC-MSCs culture medium (HUC-MSCs-CM) was conducted in the BOLI model. RESULTS: The pathogenic manifestations, lung function, and the number of neutrophils were similar between the oropharyngeal inhalation DA group (OPI-DA), intratracheal instillation group (ITI-DA); however, less reduction of weight and higher survival rate were observed in ITI-DA groups. Compared with the control groups, the trend of weight loss was significantly reduced (p < .05), and the pulmonary function was significantly improved (p < .05) in HUC-MSCs and HUC-MSCs-CM groups. Masson staining and hematoxylin and eosin staining showed that the deposition of collagen around bronchioles and blood vessels is less and airway epithelial cells and basal cells in lung tissue repaired better in HUC-MSCs and HUC-MSCs-CM groups compared with the control groups. Immunofluorescence shows the expression of E-cadherin and cytokeratin 5 (CK-5) were significantly higher in HUC-MSCs and HUC-MSCs-CM groups compared with control groups, while HUC-MSCs themselves did not express E-cadherin or CK-5. The DiI label showed HUC-MSCs gradually reduced after 2 days in the bronchus and 4 days in bronchiole. CONCLUSION: HUC-MSCs could help to repair airway epithelial cells in a murine model of BOLI. It might be related to paracrine factors of HUC-MSCs.

How should our testing behaviour change with time in children in current COVID-19 pandemic?

BACKGROUNDS: More paediatric-confirmed cases have been reported with the global pandemic of COVID-19. This study aims to summarize the key points and supply suggestions on screening paediatric COVID-19 patients more appropriately. MATERIALS AND METHODS: We retrospectively included paediatric patients who have accepted SARS-CoV-2 RT-PCR testing in Children's Hospital of Chongqing Medical University (30 January 2020 to 13 February 2020) and compared them with paediatric-confirmed COVID-19 cases. Besides, a review was carried out by analysing all current literature about laboratory-confirmed paediatric cases with COVID-19. RESULTS: There were 46 suspected cases included in the descriptive study. The results of SARS-CoV-2 RT-PCR testing were all negative. Compared with paediatric-confirmed cases, the incidence of epidemic history was lower in suspected cases (P < .001). The rate of fever (P < .001), cough (P < .001), headache or dizziness (P < .001), vomiting (P < .001) and abdominal discomfort or distention (P = .01) were more observed in the included suspected children. There were more children having decreased WBC count in the confirmed group. In the literature review, twenty-nine studies were obtained with 488 paediatric COVID-19 cases. 88.6% of them had epidemiological history. Cough and fever were the most common symptoms. Compared with older patients, the incidence of fever, respiratory symptoms, lethargy and headache or dizziness was lower, while gastrointestinal symptoms were reported more. CONCLUSIONS: Children with a history of close contact with confirmed cases, manifested as cough and fever should be paid more attention to after excluding infection of other common pathogens. Atypical symptoms should not be over-emphasized in screening paediatric COVID-19. More studies are needed for guiding efficient recognition in paediatric COVID-19.

Risk factors for the development of bronchiolitis obliterans in children with severe adenovirus pneumonia: A retrospective study with dose-response analysis.

To investigate and analyze the relevant risk factors for bronchiolitis obliterans (BO) in children with severe adenovirus pneumonia, a retrospective study of children with severe adenovirus pneumonia was performed in 34 cases that developing BO and 105 cases not developing BO in Children's hospital of Chongqing Medical University from January 2015 to February 2019. The multivariate logistic regression analysis was used to identify factors which were significantly associated with development of BO after the univariate analysis, and receiver operating characteristic (ROC) curve analysis was performed to find out the cut-off value for the significant relevant factors. A nonlinear dose-response relationship between risk factors and the risk of BO was assessed by restricted cubic spline model. Three factors were independently associated with development of BO, which were length of fever (OR 1.129, 95% CI 1.033-1.234), dyspnea (OR 3.922, 95% CI 1.060-14.514) and invasive mechanical ventilation (OR 6.861, 95% CI 1.854-25.387). The cut-off value of length of fever were 10.5 days. A linear dose-response relationship between length of fever and occurrence of BO was observed (P = .57 for nonlinearity). Children with severe adenovirus pneumonia who have a longer duration of fever (especially more than 10.5 days), have dyspnea or require invasive mechanical ventilation in the acute phase are more likely to develop BO.