Evaluation of the factors affecting lung function in pediatric patients with asthma.

PURPOSE: This study aimed to analyze the risk factors affecting lung function in children with asthma based on clinical data to advice on clinical treatment and prognosis. METHODS: This study included newly diagnosed patients with asthma admitted to the Respiratory Department of Chengdu Women's and Children's Central Hospital in Sichuan from July 2020 to June 2021. The factors associated with lung function were analyzed using univariate and multivariate linear regression with the forward method, while factors affecting lung ventilation function were analyzed using multivariate logistic regression. RESULTS: Sixty percent of the patients had normal lung function. Age was significantly negatively correlated with forced vital capacity (FVC)/FVCpredicted (B = -1.385, p = 0.001), FEV1/FEV1predicted (B = -2.092, p < 0.001), and FEV1%/FEV1%predicted (B = -0.834, p = 0.001). Body mass index (BMI) for age Z score (B = 1.661, p = 0.045) and cesarean delivery (B = 4.471, p = 0.013) were significantly positively correlated with FVC/FVCpredicted. Birth weight was significantly positively correlated with FEV1/FEV1predicted (B = 4.593, p = 0.027). Multivariate logistic regression analysis revealed that age ≥6 years and cough variant asthma (CVA) were risk factors for abnormal lung function. CONCLUSIONS: Age, BMI for age Z score, mode of delivery, and birth weight were significantly correlated with lung function in children with asthma. Furthermore, children with asthma and normal lung function were more likely to be overlooked. More attention should be given to children with asthma and normal lung function, and CVA.

Effectiveness of sublingual immunotherapy with house dust mite drops in asthmatic children at different ages.

Background: Respiratory allergies in children, such as asthma and rhinitis, are becoming progressively common every year. Recent studies found that pediatric patients with asthma receiving regular medication and specific immunotherapy (SIT) had improved therapeutic outcomes in a wide age range. However, there are few studies that have examined the effectiveness of SIT treatment in children with allergic asthma at different ages in terms of the degree of asthma control, improvements in lung function, and changes in exhaled nitric oxide (FeNO). Method: A total of 200 asthmatic pediatric patients who had been receiving regular treatment for at least a year were split into the observation and the control groups, which depended on whether sublingual immunotherapy was added based on conventional treatment medicines. The children who were divided by an age cut-off of 6 years old in these two groups were compared before and after therapy based on the exhaled levels of FeNO, pulmonary function, visual analog scale, medication scores, daytime and nighttime ratings of asthma symptom, and rhinitis symptom scores. Results: Before treatment, there was no significant difference between the observation group and the control group in various indicators of the patients under 6 years old; and in the older children (6-16 years old) group, the scores of FVC, FEV1, and FEF25 in the observation group were significantly lower than those in the control group (P < 0.05). The FEF75, FEF50, FEF25, and MMEF75/MMEF25 indexes in the observation group were significantly higher than those in the control group after treatment (P < 0.05), but there was no statistical significance in other indexes (P > 0.05). The scores of ACT, FEF75, FEF50, MMEF72/MMEF25, and FeNO in the observation group were all higher than those in the control group after treatment (P < 0.05), and the differences in other indexes were not statistically significant (P > 0.05). Between the young-age group and the elder group, there was no significant difference in all indexes in the observation group before and after treatment (P > 0.05). Conclusion: Children with asthma of all ages can considerably benefit from sublingual immunotherapy. Specifically, younger patients showed greater tendency on the improvement of small airway resistance, whereas school-age children with asthma significantly improved their small airway resistance as well as their asthma control and inflammation alleviation.

A pilot study exploring the association of bronchial bacterial microbiota and recurrent wheezing in infants with atopy.

Background: Differences in bronchial microbiota composition have been found to be associated with asthma; however, it is still unclear whether these findings can be applied to recurrent wheezing in infants especially with aeroallergen sensitization. Objectives: To determine the pathogenesis of atopic wheezing in infants and to identify diagnostic biomarkers, we analyzed the bronchial bacterial microbiota of infants with recurrent wheezing and with or without atopic diseases using a systems biology approach. Methods: Bacterial communities in bronchoalveolar lavage samples from 15 atopic wheezing infants, 15 non-atopic wheezing infants, and 18 foreign body aspiration control infants were characterized using 16S rRNA gene sequencing. The bacterial composition and community-level functions inferred from between-group differences from sequence profiles were analyzed. Results: Both α- and ß-diversity differed significantly between the groups. Compared to non-atopic wheezing infants, atopic wheezing infants showed a significantly higher abundance in two phyla (Deinococcota and unidentified bacteria) and one genus (Haemophilus) and a significantly lower abundance in one phylum (Actinobacteria). The random forest predictive model of 10 genera based on OTU-based features suggested that airway microbiota has diagnostic value for distinguishing atopic wheezing infants from non-atopic wheezing infants. PICRUSt2 based on KEGG hierarchy (level 3) revealed that atopic wheezing-associated differences in predicted bacterial functions included cytoskeleton proteins, glutamatergic synapses, and porphyrin and chlorophyll metabolism pathways. Conclusion: The differential candidate biomarkers identified by microbiome analysis in our work may have reference value for the diagnosis of wheezing in infants with atopy. To confirm that, airway microbiome combined with metabolomics analysis should be further investigated in the future.

Bacterial composition and colony structure of the lower respiratory tract in infants and children with recurrent wheezing: a case-control study.

BACKGROUND: The bacterial load of the human lower respiratory tract is at least several times lower than that of the other parts of the body. This study aimed to identify the bacterial composition and colony structure of the lower respiratory tract in infants and children with recurrent wheezing compared with those of children with a bronchial foreign body and clarify whether the length of wheezing in infants can contribute to differences in the lower respiratory tract's bacterial colony structure. METHODS: We collected specimens of alveolar lavage fluid from 48 infants and children who underwent fiberoptic bronchoscopy and were divided into groups: A1 (multiple wheezing: wheezing more than three times in < 1 month), A2 (persistent wheezing: > 1 month), and B (bronchial foreign body; control group). We analyzed the bacterial community structure of alveolar lavage fluid using high-throughput sequencing. The richness and diversity of the microbial communities were assessed by α and ß diversity analyses. RESULTS: A total of 6,644 operational taxonomic units (OTUs) were obtained based on the Illumina Nova sequencing platform and clustered according to those that met the 97% identity threshold, followed by species annotation of the OTU sequences. In the annotation results, 2,608 (39.25%) OTUs were annotated at the genus level. At the genus level, Sphingomonas and Phyllobacterium were significantly higher in group A1 than in group B. There were significantly more Phyllobacterium in group A2 than in group B. Prevotella, Neisseria, and Haemophilus were higher in group B than in groups A1 and A2. The differences in the between-group α and ß diversity analyses were statistically significant. The microbial diversity in groups A1 and A2 was significantly less than that in group B, but there was no statistical difference in bacterial community diversity between groups A1 and A2. CONCLUSION: Recurrent wheezing in infants and children is more likely due to alterations in the overall bacterial microecology and disruption of host respiration and immune homeostasis than the effects of a single bacterium.

Lower airway microbiome of children with recurrent wheezing: a clinical cohort study.

Background: Wheezing is one of the most common respiratory symptoms in childhood especially in infants. In recent years, the incidence of recurrent wheezing is on the rise worldwide. To investigate the lower airway microbiota in patients with recurrent wheezing and provide insights into clinical diagnosis and treatment. Methods: This study initially enrolled 45 hospitalised children with recurrent wheezing symptoms awaiting complete fiberoptic bronchoscopy. Of these, 13 children with tracheobronchomalacia were excluded. The final population included 32 participants (group A). The control group comprised 23 children who inhaled a foreign body and were admitted to the hospital for fiberoptic bronchoscopy within 24 hours (group B). Deoxyribonucleic acid (DNA) was extracted from the bronchoalveolar lavage fluid (BALF) and amplified for the 16S ribosomal Ribonucleic Acid (rRNA) gene, and sequencing of the microbiome was performed using the Illumina Nova Seq 6000 system. Results: There were significant differences in the gestational duration (P=0.0458), mode of delivery (P=0.0261), and allergy status (P=0.0000) between groups A and B, but they had similar richness (P=0.8574). There was also a marked difference in the diversity of flora composition between the two groups (P=0.0095). The three most common phyla of microbiota in the two groups were Proteobacteria, Firmicutes, and Bacteroidetes. Species with notably different phyla included Proteobacteria, Bacteroidota, Fusobacteriota, and Acidobacteriota. There was a significant enrichment in the of Proteobacteria and lower levels of Bacteroidota, Fusobacteriota, and Acidobacteriota in group A compared to that in group B. Conclusions: Significant changes occur in the lower airway microbiota during recurrent wheezing in children. The discovery of beneficial airway bacteria may facilitate the prevention and treatment of recurrent wheezing or asthma in children.

A delayed diagnosis of atypical immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: A case report.

INTRODUCTION: Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome is a rare monogenic autoimmune disease, which is caused by mutations in the forkhead box protein 3 gene, can affect various systems. The typical clinical manifestations of IPEX are enteropathy, type 1 diabetes mellitus, and skin diseases. However, some atypical phenotypes can easily be misdiagnosed clinically. PATIENT CONCERNS: A 9-year-and-7-month old patient suffered from recurrent wheezing, hematochezia, and eczematous dermatitis at the age of six months, but did not have any manifestations of autoimmune endocrinopathy. The patient was treated with glucocorticoids for more than six years, and he developed bronchiectasis. DIAGNOSIS: Whole exome sequencing revealed a hemizygous pathogenic mutation c.1010G>A, p. (Arg337Gln) in Forkhead box protein 3 gene (NM_014009.3). INTERVENTIONS: The patient was treated with oral mycophenolate mofetil combined with inhaled budesonide formoterol for six months after diagnosis. OUTCOMES: The respiratory symptoms of the patient seemed to be controlled but eczematous dermatitis progressed, which led the patient to give up the treatment. CONCLUSION: Early diagnosis and treatment of IPEX are crucial. Lung injury may be a major problem in the later stages of atypical IPEX, and mycophenolate mofetil seems to control the respiratory symptoms, but could induce significant skin side effects.

A multicenter survey of pediatric flexible bronchoscopy in western China.

BACKGROUND: This study aims to investigate the current use of pediatric flexible bronchoscopy (PFB) in western China. METHODS: A cross-sectional survey was conducted in western China between January 1, 2018 to December 30, 2018. Fifty-four centers were invited to answer a questionnaire for seeking information about performance of PFB. The data collected were analyzed to investigate the current status of western China, and hierarchical cluster analysis was conducted to identify developmental level of PFB of cities. RESULTS: Forty-seven centers were included in analysis. A total of 22,585 flexible bronchoscopies were carried out in the participating centers from January 1, 2018 to December 30, 2018. Eight centers (17.0%) performed more than 1,000 pediatric flexible bronchoscopies for children, but 20 centers (42.6%) performed less than 100. The median proportion of systematic and professional trained physicians in a single team was 50%, and the pooled rate was 59% (95% CI, 47-70%). Only 10, 8 and 11 centers performed balloon dilatation, thermal ablation and cryoablation, respectively. Obvious cough was the most frequent complication after the PFB procedure, the pooled rate is 24% (95% CI, 18-29%). No one died during and after the PFB procedure. Hierarchical cluster analysis showed that the development of PBF in western China varies, and Chongqing might be the most developed area in PFB use in western China. CONCLUSIONS: Flexible bronchoscopy in children is now a mature and safe procedure, while the development of PFB varies in western China, especially for the advanced bronchoscopic intervention.

Safety of semi-depot house dust mite allergen extract in children and adolescents with allergic rhinitis and asthma.

Aim: Multicenter study to investigate the safety of mite extract product Novo-Helisen Depot, Strengths 1 to 3 (NHD3), as subcutaneous immunotherapy (SCIT), in Chinese children and adolescents with allergic rhinitis (AR) and allergic asthma (AA). Patients & methods: We evaluated SCIT-related adverse events (AEs) during NHD3 14-week initial therapy in children (5-11 years) and adolescents (12-17 years) with perennial symptomatic AR and AA. Results: Among 3600 injections in 250 patients, 361/3600 (10.0%) injections caused SCIT-related AEs in 96/250 (38.4%) patients, 321/3600 injections (8.9%) caused local reactions in 89/250 (35.6%) and 40/3600 injections (1.1%) caused systemic reactions in 23/250 (9.2%). Conclusion: Initial SCIT treatment using NHD3 was safe and well tolerated in Chinese children and adolescents with AR and AA.

[Findings of electric bronchoscopy in 67 children with recurrent wheezing].

OBJECTIVE: To investigate the common causes of recurrent wheezing in young children. METHODS: Electronic bronchoscopy was performed on 67 children with recurrent wheezing or who did not respond to the conventional treatment. RESULTS: The electronic bronchoscopy showed intimitis in trachea and bronchi in 19 cases, intimitis and inflammatory stricture in 11 cases, foreign bodies in the bronchi in 11 cases, trachea and bronchus softening in 19 cases, and bronchopulmonary dysplasia in 3 cases. The other 4 cases presented endometrial tuberculosis, epiglottic cyst, laryngeal papilloma or compression outside trachea (thymus) under the electronic bronchoscope. CONCLUSIONS: In addition to inflammation, trachea and bronchus softening as well as foreign bodies in the bronchi are also the common causes in children with recurrent wheezing or who do not respond to the conventional treatment. Electronic bronchoscopy appears to be an effective way to determine the cause in these children.

Effects of sublingual-specific immunotherapy on pulmonary function and exhaled nitric oxide levels in asthmatic children with and without allergic rhinitis.

BACKGROUND: Allergic asthma and allergic rhinitis are common chronic respiratory diseases in children. The prevalence rate of disease is increasing year by year. And avoid allergens, drug treatments and special immunotherapy (SIT) is the fundamental treatment for respiratory allergies diseases. But there are few comprehensive studies on the control level of asthma, improvement of lung function, and changes of exhaled nitric oxide (FeNO) after SLIT treatment in children with allergic asthma and rhinitis. METHODS: In all, 71 child asthma patients who received sublingual-specific immune therapy for 1 year or more were divided into an asthmatic rhinitis group (31 cases) and an asthma-alone group (40 cases). The two groups of patients were compared before and after treatment in terms of rhinitis symptom scores, daytime and nighttime asthma symptom scores, visual analog scale (VAS) score, drug score, pulmonary function, and exhaled nitric oxide level (FeNO). RESULTS: After treatment, daytime symptom scores, VAS scores, drug scores, and FeNO levels of the asthma-alone group were all lower than before treatment, and the lung function was significantly improved (P<0.05), while the difference in night symptom scores before and after treatment was not statistically significant (P>0.05). The lung function and FeNO level of children in the asthmatic rhinitis group were lower after treatment than before treatment, with statistically significant differences (P<0.05). The scores of rhinitis and VAS in the asthmatic rhinitis group were higher than those in the asthma-alone group, and the differences were statistically significant. There was no significant difference in other scores between the two groups. There was no significant difference in lung function and FeNO level between the two groups. CONCLUSIONS: SLIT for children with or without allergic asthma or with or without rhinitis has a significant effect, but its effect on children with asthma combined with rhinitis is not superior to that of children with asthma alone.

Effects of Sublingual Duster Mite Drops on Lung Function and Exhaled Nitric Oxide in Children with Multiple and Single Allergic Respiratory Diseases.

Objective: To evaluate the efficiency of sublingual immunotherapy with Dermatophagoides Farinae Drops in children with single and multiple respiratory allergic diseases. Methods: Seventy-one children with allergic respiratory diseases who had been treated with Dermatophagoides Farinae Drops for one year or more were divided into a single allergic group (12 cases) and multiple allergic group (59 cases). The rhinitis score, daytime and night symptom score of asthma, VAS score, drug score, pulmonary function, and FeNO level before and after treatment were evaluated and compared between the two groups. Results: The rhinitis score, night symptom score, VAS score, and drug score in the single allergic group after treatment were significantly lower than those before treatment (p < 0.05), but there was no significant difference in the daytime symptom score before and after treatment (p > 0.05). The rhinitis score, VAS score, and drug score in the multiple allergic group after treatment were significantly lower than those before treatment (p < 0.05), but there was no significant difference in the scores of daytime symptoms and nighttime symptoms before and after treatment (p > 0.05). In both the single allergic group and multiple allergic group, the pulmonary function indexes of the patients were significantly improved after treatment, and the FeNO after treatment was significantly lower than that before treatment (p < 0.05). There was no significant difference in scores, pulmonary function, and FeNO between the two groups (p > 0.05). Conclusion: Sublingual specific immunotherapy is effective in treating multiple and single allergic respiratory diseases in children.

Genes involved in leukotriene synthesis pathway are dynamically regulated during lung development in Rhesus monkeys.

BACKGROUND: Leukotrienes play critical roles in many inflammatory lung diseases and several antagonists of their receptors have been used in the clinical settings. However, the physiological functions of leukotrienes in lung development are still unclear. METHOD: The expression levels of 34 genes involved in leukotriene synthesis and function pathway in the lungs of Rhesus monkey during different developmental time points were determined on a MiSeq platform and analyzed by the reads per kilobase of transcript per million mapped reads (RPKM) method. RESULTS: The results showed that the expression levels of PLA2G1B, PLA2G10, PLA2G2D, ALOX5, and ALOX5AP increased dramatically in the lung of Rhesus monkey, reflecting the changes in the pulmonary environment after delivery. Additionally, the different expression patterns between molecules related to LTB4 and LTC4 synthesis suggested distinct roles of LTB4 and LTC4 in lung development. Finally, the constant expression of CysLT1 during the development process provided new information to the pharmaceutical basis of the use of leukotriene receptor antagonists in the clinical setting. CONCLUSION: The expression levels of several key genes involved in leukotriene synthesis changed dramatically during lung development in Rhesus monkeys, suggesting the potential roles of leukotrienes in lung development in this animal model.