The impact of perinatal and at birth risk factors on the progression from preschool wheezing to adolescent asthma.

Asthma is a global health concern affecting millions of children and adolescents. This review focuses on the possible factors that are associated with the transition from preschool wheezing to childhood asthma and highlights the significance of early-life environmental exposures during pregnancy and the first 6 months of life in shaping allergies and asthma. We observed a scarcity of studies investigating this subgroup, with most focusing on wheezing trajectories. We undertook a thorough investigation of diverse perinatal exposures that have the potential to impact this transition. These factors include maternal asthma, smoking during pregnancy, diet, prepregnancy weight, infant birthweight, gestational age, and breastfeeding. Although limited, studies do suggest that maternal asthma increases the likelihood of preschool wheeze in offspring that persists through childhood with potential asthma progression. Findings concerning other perinatal exposures remain inconsistent. Further research is needed to identify asthma progression risk factors and assess perinatal exposure effects.

Metabolomics of bronchoalveolar lavage in children with persistent wheezing.

BACKGROUND: Recent studies have demonstrated the important role of metabolomics in the pathogenesis of asthma. However, the role of lung metabolomics in childhood persistent wheezing (PW) or wheezing recurrence remains poorly understood. METHODS: In this prospective observational study, we performed a liquid chromatography/mass spectrometry-based metabolomic survey on bronchoalveolar lavage samples collected from 30 children with PW and 30 age-matched infants (control group). A 2-year follow-up study on these PW children was conducted. RESULTS: Children with PW showed a distinct characterization of respiratory metabolome compared with control group. Children with PW had higher abundances of choline, oleamide, nepetalactam, butyrylcarnitine, L-palmitoylcarnitine, palmitoylethanolamide, and various phosphatidylcholines. The glycerophospholipid metabolism pathway was the most relevant pathway involving in PW pathophysiologic process. Additionally, different gender, prematurity, and systemic corticoids use demonstrated a greater impact in airway metabolite compositions. Furthermore, for PW children with recurrence during the follow-up period, children who were born prematurely had an increased abundance of butyrylcarnitine relative to those who were carried to term. CONCLUSIONS: This study suggests that the alterations of lung metabolites could be associated with the development of wheezing, and this early alteration could also be correlated with wheezing recurrence later in life.

Mycoplasma Pneumoniae Infection and Persistent Wheezing in Young Children: A Retrospective Case-Control Study.

Background: To investigate the clinical characteristics of children with persistent wheezing (PW) with Mycoplasma pneumoniae (MP) DNA in bronchoalveolar lavage fluid (BALF). Methods: This retrospective case-control study included consecutive admitted children under 3 years of age who were diagnosed with PW and had MP DNA detected in BALF. Patients with mycoplasma pneumoniae pneumonia (MPP) and foreign-body aspiration (FBA) were enrolled as controls. The clinical characteristics of the groups were compared. Results: During the study period, there were 89 patients diagnosed with PW without structural anomalies of the conductive airways, and 30 of these patients (33.7%, 30/89) with MP DNA detected in the BALF were selected as the study group. We included 44 patients with MPP and 44 patients with FBA as controls. Patients with MPP were older and had a higher occurrence of fever and C-reactive protein (CRP) than patients with PW (all P < 0.001). The median MP DNA copy number in patients with MPP was higher than that of patients with PW (P = 0.004). The median level of MP IgG in patients with PW was lower than that of patients with MPP and higher than that of patients with FBA (all P < 0.001). MP DNA copy number positively correlated with age (r = 0.392, P = 0.001) and CRP (r = 0.235, P = 0.048). Conclusions: Our study reveals that MP was highly detected in the BALF of PW patients. In addition, young patients with a low load of MP infection showed lower amounts of antibody, and a weak inflammatory response might be associated with PW.

Follow-up study of airway microbiota in children with persistent wheezing.

BACKGROUND: Increasing evidence revealed that airway microbial dysbiosis was associated with increased risk of asthma, or persistent wheezing (PW). However, the role of lung microbiota in PW or wheezing recurrence remains poorly understood. METHODS: In this prospective observational study, we performed a longitudinal 16S rRNA-based microbiome survey on bronchoalveolar lavage (BAL) samples collected from 35 infants with PW and 28 age-matched infants (control group). A 2-year follow-up study on these PW patients was conducted. The compositions of lower airway microbiota were analyzed at the phylum and genus levels. RESULTS: Our study showed a clear difference in lower airway microbiota between PW children and the control group. Children with PW had a higher abundance of Elizabethkingia and Rothia, and lower abundance of Fusobacterium compared with the control group. At the end of the 2-year follow-up, 20 children with PW (57.1%) experienced at least one episode of wheezing, and 15 (42.9%) did not suffer from wheezing episodes. Furthermore, PW children with recurrence also had increased abundances of Elizabethkingia and Rothia relative to those who had no recurrence. Additionally, wheezing history, different gender, and caesarean section demonstrated a greater impact in airway microbiota compositions. CONCLUSION: This study suggests that the alterations of lower airway microbiota could be strongly associated with the development of wheezing, and early airway microbial changes could also be associated with wheezing recurrence later in life.

Persistent wheezing along with apparent stridor caused by a rare anomaly: double aortic arch.

Vascular rings are rare anomalies that occur as a result of abnormal development of the aortic arch complex, often manifested by signs of tracheo-oesophageal compression during the infant period. A double aortic arch anomaly is the most common type of vascular ring pathology. Here we report a case presenting with wheezing and stridor in a 10-month-old child.

Flexible Bronchoscopy in Evaluation of Persistent Wheezing in Children-Experiences from National Pediatric Center.

Background and objectives: Persistent wheezing (PW) is defined as prolonged or recurrent episodes of wheezing despite regular treatment. Flexible bronchoscopy (FB) is recommended to determine the etiology of PW in children. This study aimed to determine the etiology of PW based on FB findings in a national pediatric center. Materials and Methods: Children presenting with PW that underwent flexible bronchoscopy from April 2016 to August 2019 at the Mother and Child Health Institute of Serbia were included in this observational study. After endoscopic evaluation, bronchoalveolar lavage fluid (BALF) samples were taken and further analyzed. Quantitative microbiology, cytological analysis and oil-red staining of specimens were performed to determine cellular constituents and presence of lipid laden macrophages (LLM). Upper gastrointestinal series were performed to exclude gastroesophageal reflux disease, swallowing dysfunction and vascular ring. Results: Pathological findings were revealed in 151 of 172 study participants, with bacterial lower airway infection (BLAI) (48.3%) and primary bronchomalacia (20.4%) as the most common. Younger participants were hospitalized for significantly longer periods (ρ = -0.366, p < 0.001). Study participants with BLAI and associated mucus plugging were notably younger (p < 0.001). Presence of LLM in BALF was not associated with findings of upper gastrointestinal series. All patients with confirmed BLAI were treated with oral antibiotics. Although FB is considered to be invasive, there were no complications associated with the procedure. Conclusions: Flexible bronchoscopy has an exceptional diagnostic value in evaluation of PW. In younger patients with BLAI, presence of mucus plugs may complicate the clinical course, so significant benefits can be achieved with therapeutic lavage during bronchoscopy.

A Pediatric Asthma Risk Score to better predict asthma development in young children.

BACKGROUND: Asthma phenotypes are currently not amenable to primary prevention or early intervention because their natural history cannot be reliably predicted. Clinicians remain reliant on poorly predictive asthma outcome tools because of a lack of better alternatives. OBJECTIVE: We sought to develop a quantitative personalized tool to predict asthma development in young children. METHODS: Data from the Cincinnati Childhood Allergy and Air Pollution Study (n = 762) birth cohort were used to identify factors that predicted asthma development. The Pediatric Asthma Risk Score (PARS) was constructed by integrating demographic and clinical data. The sensitivity and specificity of PARS were compared with those of the Asthma Predictive Index (API) and replicated in the Isle of Wight birth cohort. RESULTS: PARS reliably predicted asthma development in the Cincinnati Childhood Allergy and Air Pollution Study (sensitivity = 0.68, specificity = 0.77). Although both the PARS and API predicted asthma in high-risk children, the PARS had improved ability to predict asthma in children with mild-to-moderate asthma risk. In addition to parental asthma, eczema, and wheezing apart from colds, variables that predicted asthma in the PARS included early wheezing (odds ratio [OR], 2.88; 95% CI, 1.52-5.37), sensitization to 2 or more food allergens and/or aeroallergens (OR, 2.44; 95% CI, 1.49-4.05), and African American race (OR, 2.04; 95% CI, 1.19-3.47). The PARS was replicated in the Isle of Wight birth cohort (sensitivity = 0.67, specificity = 0.79), demonstrating that it is a robust, valid, and generalizable asthma predictive tool. CONCLUSIONS: The PARS performed better than the API in children with mild-to-moderate asthma. This is significant because these children are the most common and most difficult to predict and might be the most amenable to prevention strategies.

Optimum predictors of childhood asthma: persistent wheeze or the Asthma Predictive Index?

BACKGROUND: The Asthma Predictive Index (API) and persistent wheezing phenotypes are associated with childhood asthma, but previous studies have not assessed their ability to predict objectively confirmed asthma. OBJECTIVE: To determine whether the University of Cincinnati API Index (ucAPI) and/or persistent wheezing at age 3 can accurately predict objectively confirmed asthma at age 7. METHODS: Data from the Cincinnati Childhood Allergy and Air Pollution Study, a high-risk prospective birth cohort, was used. Asthma was defined as parent-reported or physician-diagnosed asthma objectively confirmed by a change in FEV1 of ≥12% after bronchodilator or a positive methacholine challenge (PC20 ≤ 4 mg/mL); or as prior treatment with daily asthma controller medication(s). Multivariate logistic regression was used to investigate the relationship between confirmed asthma at age 7 and a positive ucAPI (adapted and modified from prior published API definitions) and persistent wheezing at age 3. RESULTS: At age 7, 103 of 589 children (17.5%) satisfied the criteria for asthma. Confirmed asthma at age 7 was significantly associated with a positive ucAPI (adjusted odds ratio [aOR] 13.3 [95% CI, 7.0-25.2]; P < .01) and the persistent wheezing phenotype (aOR 9.8 [95% CI, 4.9-19.5]; P < .01) at age 3. Allergic persistent wheezing was associated with a significantly higher risk of asthma (aOR 10.4 [95% CI, 4.1-26.0]; P < .01) than nonallergic persistent wheezing (aOR 5.4 [95% CI, 2.04-14.06]; P < .01). CONCLUSION: Both a positive ucAPI and persistent wheeze at age 3 were associated with objectively confirmed asthma at age 7; however, the highest risk was associated with ucAPI. These results demonstrate the ucAPI as a clinically useful tool for predicting future asthma in school-age children.

Elevated level of serum osteopontin in school-age children with asthma.

BACKGROUND: The role of osteopontin (OPN) has not been elucidated in childhood asthma. OBJECTIVE: Our purpose was to investigate whether OPN levels change due to allergic inflammation in pre-school and school-age children. METHODS: In this prospective, cross-sectional study, 42 healthy children and a total of 51 children with asthma were recruited. OPN levels and its association with clinical and laboratory parameters were investigated in the study population. The asthma group were divided into two groups with respect to age, ≤ 5-years (n = 23) and >5-years (n = 28), and labelled Asthma Group 1 and Asthma Group 2, respectively. OPN levels were compared between subgroups. RESULTS: Serum OPN levels were significantly higher in the asthma group when compared to the control group (p = 0.004). OPN levels were similar in Asthma Group 1 and control groups, whereas it was found to be higher in Asthma Group 2 (p>0.025, p = 0.001, respectively). In the >5-years age asthmatic group, OPN levels of the patients with allergic rhinitis (n = 15) were higher than those of the patients (n=13) without allergic rhinitis (p = 0.021). CONCLUSION: The study underscores the relationship between childhood asthma and OPN as the first study in the literature. In this study we found that OPN, which plays a role in Th2 mediated inflammation, may also play a role in childhood asthma. The fact that OPN levels do not increase in preschool-age children with asthma might be due to the transient wheezing in this group.

Application of fiberoptic bronchoscopy in diagnosis and treatment of refractory and persistent wheezing in infants / 临床儿科杂志

Objective To investigate the roles of fiberoptic bronchoscopy in diagnosis and treatment for infants with refractory and persistent wheezing. Methods From Jun. 2012 to Dec. 2013, 52 hospitalized children with age between four 4 months and 1 year old were recruited for ifberoptic bronchoscopy, who had been wheezing for at least four weeks and treated ineffectively with conventional anti-inlfammatory agents:budesonide and compound ipratropium bromide solution. Then, the pathogenesis of refractory and persistent wheezing was summarized based on clinical features, detection of CT imaging of three-dimensional airway reconstruction and cardiac CT, results of bronchoscopy inspection, and bronchoalveolar lavage lfuid culture. Results Among the 52 cases, 40 were with ground glass-like changes (76.92%) in pulmonary spiral CT testing, 4 with mosaic perfusion syndrome (7.69%), 8 with segmental pulmonary consolidation (15.38%), 8 with obstructive pulmonary emphysema (15.38%), and 1 with left primary bronchial foreign body. In addition, through bronchofibroscopy, there were 52 cases with imlfammation (100%),3 with tracheal stenosis (5.77%), 3 with left and/or right main bronchus stenosis of the external pressure, 18 with bronchomalacia(34.62%), 2 cases with foreign body (3.84%), one in trachea (1.92%), the other in left main bronchus (1.92%), 10 with bronchial mucus plug (19.23%), and 8 (15.38%) with congenital airway malformations (including 3 at tracheal bronchus, 1 at left upper lobe bronchial stenosis and 1 at bronchial Bridge). The culture of bronchoalveolar lavage lfuid were conducted for all patients. The positive rate of bronchoalveolar lavage lfuid was 9.62%(5/52 cases), including 2 cases with tip Escherichia coli, 2 with Haemophilus inlfuenzae, and 1 with Acinetobacter baumannii. Conclusions First, infection is the primary cause of refractory and persistent wheezing, which is persistent in airway resulted from multi-drug resistant bacteriua. Second, refractory and persistent wheezing is often caused by multi-factors including infection, congenital airway malformations, the endogenous and exogenous foreign body, cardiovascular malformation, etc. These factors often lead to dififcult wheezing control. The last, the diagnosis rate of the refractory and persistent wheezing can be improved by combination of ifberoptic bronchoscopy and lung spiral CT.