Functional analysis of airway remodeling is related with fibrotic mediators in asthmatic children.

BACKGROUND: Asthmatic children present variable degrees of airway inflammation, remodeling, and resistance, which correlate with disease control and severity. The chronic inflammatory process of the airway triggers airway remodeling, which reflects the degree of airway resistance. Pro-inflammatory and pro-fibrotic mediators are centrally involved in this process. OBJECTIVE: To investigate whether the levels of pulmonary and systemic pro-inflammatory and pro-fibrotic mediators present a correlation with the resistance of the respiratory system and of the proximal and distal airways. METHODS: 39 Asthmatic children (persistent mild and moderate) and 39 non-asthmatic children (both between 6 and 13 years old) were evaluated for anthropometric characteristics, lung function and mechanics, and pulmonary and systemic immune responses. RESULTS: Asthmatic children showed an increased number of blood eosinophils (p < 0.04), basophils (p < 0.04), monocytes (p < 0.002) and lymphocytes (p < 0.03). In addition, asthmatic children showed impaired lung function, as demonstrated by FEV1 (p < 0.0005) and FEV1/FVC (p < 0.004), decreased total resistance of the respiratory system (R5Hz; p < 0.009), increased resistance of the proximal airways (R20Hz; p < 0.02), increased elastance (Z5Hz; p < 0.02) and increased reactance (X5Hz; p < 0.002) compared to non-asthmatic children. Moreover, the following inflammatory factors were significantly higher in asthmatic than non-asthmatic children: GM-CSF in the breath condensate (BC) (p < 0.0001) and in the serum (p < 0.0001); TGF-beta in the BC (p < 0.0001) and in the serum (p < 0.004); IL-5 in the BC (p < 0.02) and in the serum (p < 0.01); IL-4 in the serum (p < 0.0002). CONCLUSIONS: Impulse oscillometry is a sensitive method to detect airway resistance in persistent mild and moderate asthmatic children, an event followed by increased levels of pro-inflammatory and pro-fibrotic mediators.

The relationship between changes in peak expiratory flow and asthma exacerbations in asthmatic children.

BACKGROUND: Asthma is one of the most common chronic airway diseases in children. Preventing asthma exacerbation is one of the objectives of all asthma action plans. In patients with poor perception, it is difficult to identify acute asthma exacerbations by clinical asthma score, asthma control test or asthma control questionnaire. The aim of this study is to analyze whether children with asthma have changes in peak expiratory flow(PEF)before an acute asthma exacerbation and to evaluate the relationship between PEF and asthma exacerbation. METHODS: Basic information (including sex, age, atopy, etc.) and clinical information of asthmatic children who registered in the Electronic China Children's Asthma Action Plan (e-CCAAP) from 1 September 2017 to 31 August 2021 were collected. Subjects with 14 consecutive days of PEF measurements were eligible. Subjects in this study were divided into an exacerbation group and a control group. We analyzed the relationship between changes in PEF% pred and the presence of asthma symptoms. RESULT: A total of 194 children with asthma who met the inclusion criteria were included, including 144 males (74.2%) and 50 females (25.8%), with a male-to-female ratio of 2.88:1. The mean age of the subjects was 9.51 ± 2.5 years. There were no significant differences in sex, age, allergy history or baseline PEF between the two groups. In children with and without a history of allergy, there was no significant difference between the variation in PEF at 14 days. Patients who only had a reduced in PEF but no symptoms of asthma exacerbation had the greatest reduction in PEF compared to the other groups. The most common cause of acute exacerbations of asthma is upper respiratory tract infection. Among the causes of acute exacerbations of asthma, the variation in PEF caused by air pollution was significantly higher than that of other causes (P < 0.05). In acute exacerbations, the decrease in PEF was significantly greater in the exacerbation group than in the control group. In children with asthma symptoms, there was a decrease in PEF approximately 1.34 days before the onset of symptoms. CONCLUSION: Children with asthma show a decrease in PEF 1.34 days before the onset of asthma symptoms. We recommend that asthmatic children who show a decrease in PEF should step-up asthma therapy. The most common cause of acute exacerbations of asthma was upper respiratory tract infections, and the variation in PEF caused by air pollution was significantly higher than that caused by other factors.

The frequency of sleep-disordered breathing in preschool children with asthma and its effects on control of asthma.

CONCLUSION: The frequency and score of SDB were higher in patients with uncontrolled asthma. Frequency and score of SDB were significantly affected by the severity of asthma. SDB must be evaluated in preschool children with uncontrolled asthma. CONCLUSION: Sleep-disordered breathing (SDB) is more common in asthmatic patients than in non-asthmatic persons, and SDB affects negatively to control asthma. A limited number of studies are discovered on the effect of SDB in preschool asthmatic children. In this study, we aimed to investigate the prevalence of SDB and its effect on control and severity of asthma in preschool children. A pediatric sleep questionnaire was completed by parents of asthmatic children. Patients who received a score of 0.33 or higher were diagnosed with SDB. Control and severity of asthma was assessed by a pediatric allergy specialist based on the Global Initiative for Asthma (GINA) criteria. The study included 249 patients, with a mean±SD age of 4.37±1.04 (range: 2-5.9) years; 69% were boys; 56.6% children had uncontrolled asthma and 28.7% had SDB. The SDB score was significantly different between controlled and uncontrolled asthma (0.19 vs 0.28; P < 0.001). The frequency of uncontrolled asthma in patients with and without SDB was 74.3% and 49.4%, respectively (P < 0.010). Based on the severity of asthma, the frequency of SDB among patients with mild, moderate, and severe asthma was 23.4%, 35.2%, and 47.4%, respectively (P = 0.010).

Residential greenness and air pollution's association with nasal microbiota among asthmatic children.

Both greenness and air pollution have widely been linked with asthma. However, the potential mechanism has rarely been investigated. This study aimed to identify the association between residential greenness and air pollution (fine particulate matter [PM2.5]; nitrogen dioxide [NO2]; ozone [O3]) with nasal microbiota among asthmatic children during the recovery phase. The normalized difference vegetation index was used to assess the extent of residential greenness. Spatiotemporal air pollution variation was estimated using an integrated hybrid kriging-LUR with the XG-Boost algorithm. These exposures were measured in 250-m intervals for four incremental buffer ranges. Nasal microbiota was collected from 47 children during the recovery phase. A generalized additive model controlled for various covariates was applied to evaluate the exposure-outcome association. The lag-time effect of greenness and air pollution related to the nasal microbiota also was examined. A significant negative association was observed between short-term exposure to air pollution and nasal bacterial diversity, as a one-unit increment in PM2.5 or O3 significantly decreased the observed species (PM2.5: -0.59, 95%CI -1.13, -0.05 and O3: -0.93, 95%CI -1.54, -0.32) and species richness (PM2.5: -0.64, 95%CI -1.25, -0.02 and O3: -0.68, 95%CI -1.43, -0.07). Considering the lag-time effect, we found a significant positive association between greenness and both the observed species and species richness. In addition, we identified a significant negative association for all pollutants with the observed species richness. These findings add to the evidence base of the links between nasal microbiota and air pollution and greenness. This study establishes a foundation for future studies of how environmental exposure plays a role in nasal microbiota, which in turn may affect the development of asthma.

Effect of using acoustic flo-tone training device and its smartphone application on enhancing inhalation technique from metered-dose inhaler with spacer in asthmatic children.

Aim of study: This research study aims to compare between two different counseling approaches; traditional verbal counseling vs. advanced counseling (in which we used the acoustic Flo-tone training device and its smartphone application combined with traditional verbal counseling) to determine the most beneficial counseling approach for asthmatic children who use metered-dose inhaler (MDI) with spacers concerning inhalation duration and inhalation technique mistakes. Methods: A total of 100 asthmatic children (8-18) years old were randomized into two groups (a control group, and an advanced group). Each group included 50 subjects. Every subject received 3 counseling meetings, one each month. Asthmatic children in the control group were trained on inhalation technique from MDI + spacer verbally (traditional counseling), while asthmatic children in advanced group were trained on inhalation technique from MDI + spacer verbally and by advanced counseling (whistling Flo-tone + smartphone application). At each visit mistakes in inhalation technique steps were; detected, corrected, and recorded and the inhalation duration was measured for every child in each group. Results: In both study groups, the total mean number of inhalation technique mistakes decreased significantly (p < 0.05) from visit 2, also the total mean inhalation durations in seconds showed a significant increase (p < 0.05) from visit 2. A significant (p < 0.05) reduction in the total mean number of mistakes and a significant (p < 0.05) increase in total mean inhalation durations were observed from visit 2 in advanced group compared to control group. Conclusion: Combination between traditional verbal and advanced counseling methods resulted in significant (P < 0.05) improvements in the number of inhalation technique mistakes and inhalation durations from MDI with spacer in children compared to using traditional verbal counseling alone.

Parental decision and intent towards COVID-19 vaccination in children with asthma: an econometric analysis.

OBJECTIVE: Vaccination will be instrumental in controlling the COVID-19 pandemic, and vaccination of children will be necessary to achieve herd immunity. Given that children with chronic health conditions may be at increased risk of COVID-19, it is crucial to understand factors influencing parental decisions about whether to have their child vaccinated. The study objectives were to measure parental intent to have their child with asthma vaccinated against COVID-19 and identify the determinants of their vaccination decision. STUDY DESIGN: This study is based on a cross-sectional exploratory observational online survey assessing parents' risk perception in the context of COVID-19. METHODS: In this study conducted in August 2020, the primary outcome was parent's answer to the question on their intention to get their child vaccinated if a vaccine against COVID-19 was available. Participants were also asked about their intention to get vaccinated themselves. Independent variables studied included sociodemographic, clinical data (e.g. presence of other chronic diseases), psychological, cognitive and risk perception related to COVID-19. Simultaneous equations models (3SLS) and seemingly unrelated regressions model (SUR) were carried out to identify factors associated with intention to have the child vaccinated and participants' intention to get vaccinated themselves against COVID-19. RESULTS: A total of 305 participants completed the survey. Overall, 19.1% of participants reported being unlikely or very unlikely to vaccinate their child against COVID-19 if a vaccine was available. Similarly, 21.0% were unlikely or very unlikely to get vaccinated themselves. The following factors were significantly associated with parents' decision to have their child vaccinated: parental level of education (p = 0.003), employment status (p < 0.001), sex of the child (p = 0.019), presence of other chronic diseases (p = 0.028), whether or not the child had been vaccinated against influenza in the past (p < 0.001), parental anxiety (p = 0.046), and consultation with a health professional since the beginning of the pandemic (p = 0.009). There was a strong relationship between likelihood of not intending to have one's child vaccinated and personal intent not to get vaccinated. CONCLUSION: These findings are essential in planning for the communication and dissemination of COVID-19 vaccination information to parents, especially for children with asthma or other chronic medical conditions.

Serum dual-specificity phosphatase 1 reflects decreased exacerbation risk, correlates with less advanced exacerbation severity and lower inflammatory cytokines in children with asthma.

BACKGROUND: It is as fact that dual-specificity phosphatase 1 (DUSP1) regulates the T cell activation, pro-allergic response, and inflammation to engage with the pathogenesis of asthma, but its clinical role in children with asthma is unclear. The present study aimed to explore the expression of DUSP1, its association with exacerbation risk, severity, and inflammatory cytokines in children with asthma. METHOD: Around 52 children with asthma-exacerbation, 50 children in asthma-remission, and 50 healthy children were chosen for the study. The serum levels of DUSP1, as well as tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-17 were detected by the enzyme-linked immunosorbent assay. RESULTS: The levels of DUSP1 was the highest in healthy children (median (IQR)=34.305 (25.892- 43.693) ng/mL), the second highest in children in asthma-remission (median (IQR)=21.471 (18.581-27.934) ng/mL), and the lowest in children with asthma-exacerbation (median (IQR)=13.982 (7.901-21.624) ng/mL) (P<0.001). At the same time, DUSP1 was also related to decreased asthma risk with area under curve (AUC) (95%CI) of 0.847 (0.780-0.914), and correlated with its lower exacerbation risk with AUC (95%CI) of 0.755 (0.661-0.849). Besides, DUSP1 was negatively linked with exacerbation severity (rs =-0.338, P=0.014), immunoglobulin E (rs =-0.277, P=0.047), TNF-α (rs =-0.423, P=0.002), IL-1ß (rs =-0.389, P=0.004), and IL-17 (rs =-0.293, P=0.035), but not related with other disease features in children with asthma-exacerbation. Meanwhile, DUSP1 was only negatively associated with TNF-α (rs=-0.300, P=0.034) and IL-1ß (rs =-0.309, P=0.029) in children in asthma-remission. However, no correlation was found in DUSP1 with inflammatory cytokines or other disease features in healthy children (all P>0.05). CONCLUSION: DUSP1 reflects the reduced exacerbation risk, and associates with lower exacerbation severity and inflammatory cytokines in children with asthma-exacerbation; it also associates with inflammatory cytokines in children in asthma-remission. These findings suggest that DUSP1 may help to improve the management of asthmatic children.

Personal Exposure to PM2.5 Oxidative Potential in Association with Pulmonary Pathophysiologic Outcomes in Children with Asthma.

Fine particulate matter (PM2.5) with a higher oxidative potential has been thought to be more detrimental to pulmonary health. We aim to investigate the associations between personal exposure to PM2.5 oxidative potential and pulmonary outcomes in asthmatic children. We measured each of the 43 asthmatic children 4 times for airway mechanics, lung function, airway inflammation, and asthma symptom scores. Coupling measured indoor and outdoor concentrations of PM2.5 mass, constituents, and oxidative potential with individual time-activity data, we calculated 24 h average personal exposures 0-3 days prior to a health outcome measurement. We found that increases in daily personal exposure to PM2.5 oxidative potential were significantly associated with increased small, large, and total airway resistance, increased airway impedance, decreased lung function, and worsened scores of individual asthma symptoms and the total symptom score. Among the PM2.5 constituents, organic matters largely of indoor origin contributed the greatest to PM2.5 oxidative potential. Given that the variability in PM2.5 oxidative potential was a stronger driver than PM2.5 mass for the variability in the respiratory health outcomes, it is suggested to reduce PM2.5 oxidative potential, particularly by reducing the organic matter constituent of indoor PM2.5, as a targeted source control strategy in asthma management.

Reduction in mouse allergen exposure is associated with greater lung function growth.

BACKGROUND: Current childhood asthma therapies have little effect on lung function trajectory. OBJECTIVE: We sought to determine whether mouse allergen exposure reduction is associated with lung function growth in mouse-sensitized/exposed asthmatic children. METHODS: Three hundred fifty mouse-sensitized/exposed asthmatic children (5-17 years old) were enrolled in a 1-year randomized trial of integrated pest management plus education versus education alone. Prebronchodilator/postbronchodilator spirometry was performed at baseline and 6 and 12 months, and bedroom floor mouse allergen levels were measured every 3 months. Mouse allergen reduction was defined as a 75% or greater decrease in mouse allergen levels from baseline. Treatment groups were combined for analyses because there were no differences in outcomes between groups. Changes in lung function over time were modeled, adjusting for age, sex, race, atopy, group, and bronchodilator reversibility and including an interaction term (allergen reduction*time). RESULTS: The study population was predominantly black (79.4%) and low income (66.3% [<$30,000]). At baseline, the median mouse allergen level was 5.7 µg/g (interquartile range, 1.5-22.8 µg/g), and the mean (SD) prebronchodilator FEV1/forced vital capacity ratio was 80.2% (9.0%). Ninety-two (26.3%) participants had 75% or greater reduction in mouse allergen levels. For a 10-year-old black boy, 75% or greater allergen reduction was associated with an increase in prebronchodilator FEV1 of 238 mL/y (95% CI, 177-299 mL/y), whereas less than 75% allergen reduction was associated with an increase in prebronchodilator FEV1 of 131 mL/y (95% CI, 97-166 mL/y). Estimated differences in prebronchodilator and postbronchodilator FEV1 growth were as follows: 107 mL/y (95% CI, 37-177 mL/y; Pint = .003) and 48 mL/y (95% CI, -17 to 113 mL/y; Pint = .15), respectively. Estimated differences in prebronchodilator and postbronchodilator forced expiratory flow at 25% to 75% of vital capacity growth were as follows: 182 mL/y (95% CI, 61-304 mL/y; Pint = .003) and 181 mL/y (95% CI, 48-314 mL/y; Pint = .008), respectively. CONCLUSION: Mouse allergen reduction is associated with greater increases in prebronchodilator FEV1 and prebronchodilator/postbronchodilator forced expiratory flow at 25% to 75% of vital capacity over 1 year among sensitized/exposed asthmatic children.

Evaluation of miR-196a2 expression and Annexin A1 level in children with bronchial asthmaEvaluation of miR-196a2 expression and Annexin A1 level in children.

BACKGROUND: Annexin A1 (ANXA1) is an important anti-inflammatory mediator that may play a significant role in bronchial asthma. MiR-196a2 can target ANXA1 and therefore may play a role in the pathogenesis of asthma. AIM OF STUDY: This is the first study which aimed to evaluate the expression of miR-196a2 in the serum of asthmatic children and correlate its expression with ANXA1 serum level and asthma severity. SUBJECTS AND METHODS: The study included 100 asthma patients who were subdivided into three groups (mild, moderate and severe) and 50 healthy control subjects. Assessment of miR-196a2 expression and ANXA1 serum level were done using quantitative reverse transcriptase PCR (RT qPCR) and Elisa techniques, respectively. RESULTS: Compared to the control group, asthmatic children showed an increased ANXA1 serum level and decreased expression of miR-196a2 (p=0.001). However, ANXA1 serum level was lower and miR-196a2 expression was higher in severe asthmatic patients compared to moderate asthmatic ones (p=0.01, 0.03). Pearson's correlation coefficient revealed no significant correlations between ANXA1 serum level and miR-196a2 expression in the patient group (p=0.9). CONCLUSIONS: Altered miR-196a2 expression and serum ANXA1 concentration may play a role in the pathogenesis of asthma. In addition, ANXA1 and miR-196a2 may represent potential diagnostic biomarkers for asthma and future targets for therapy.

Reduced Akkermansia muciniphila and Faecalibacterium prausnitzii levels in the gut microbiota of children with allergic asthma.

INTRODUCTION AND OBJECTIVES: The amounts of Akkermansia muciniphila and Faecalibacterium prausnitzii in gut microbiota are reduced in patients with allergic diseases compared to healthy controls. We aimed to quantify levels of A. muciniphila and F. prausnitzii amounts using real-time quantitative PCR (qPCR) in the gut microbiota of children with allergic asthma and in healthy controls. MATERIALS AND METHODS: In total, 92 children between the ages of three and eight who were diagnosed with asthma and 88 healthy children were included in the study and bacterial DNA was isolated from the stool samples using the stool DNA isolation Kit. qPCR assays were studied with the microbial DNA qPCR Kit for A. muciniphila and microbial DNA qPCR Kit for F. prausnitzii. RESULTS: Both bacterial species showed a reduction in the patient group compared to healthy controls. A. muciniphila and F. prausnitzii were found to be 5.45±0.004, 6.74±0.01 and 5.71±0.002, 7.28±0.009 in the stool samples of the asthma and healthy control groups, respectively. CONCLUSIONS: F. prausnitzii and A. muciniphila may have induced anti-inflammatory cytokine IL-10 and prevented the secretion of pro-inflammatory cytokines like IL-12. These findings suggest that A. muciniphila and F. prausnitzii may suppress inflammation through its secreted metabolites.

Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA methylation and lung function decrements among urban children.

BACKGROUND: Both short and long-term exposure to traffic-related air pollutants have been associated with asthma and reduced lung function. We hypothesized that short-term indoor exposure to fine particulate matter <2.5 µm (PM2.5) and vanadium (V) would be associated with altered buccal cell DNA methylation of targeted asthma genes and decreased lung function among urban children in a nested subcohort of African American and Dominican children. METHODS: Six day integrated levels of air pollutants were measured from children's homes (age 9-14; n = 163), repeated 6 months later (n = 98). Buccal samples were collected repeatedly during visits. CpG promoter loci of asthma genes (i.e., interleukin 4 (IL4), interferon gamma (IFNγ), inducible nitric oxide synthase (NOS2A), arginase 2 (ARG2)) were pyrosequenced and lung function was assessed. RESULTS: Exposure to V, but not PM2.5, was associated with lower DNA methylation of IL4 and IFNγ. In exploratory analyses, V levels were associated with lower methylation of the proinflammatory NOS2A-CpG+5099 among asthmatic overweight or obese children but not nonasthmatics. Short-term exposure to PM2.5, but not V, appeared associated with lower lung function (i.e., reduced z-scores for forced expiratory volume in one second (FEV1, FEV1/ forced vital capacity [FEV1/FVC] and forced expiratory flow at 25-75% of FVC [FEF25-75]). CONCLUSIONS: Exposure to V was associated with altered DNA methylation of allergic and proinflammatory asthma genes implicated in air pollution related asthma. However, short-term exposure to PM2.5, but not V, appeared associated with decrements in lung function among urban children.

The protective role of Helicobacter pylori neutrophil-activating protein in childhood asthma.

BACKGROUND: Helicobacter pylori quantity and HP-NAP gene expression were evaluated in the faeces of healthy and asthmatic children. METHODS: H. pylori DNAs and RNAs were isolated from the stool samples of 92 asthmatic children (AC; 3-8 years) and 88 healthy controls (HC). Quantitative PCR was used to determine the quantity of H. pylori and HP-NAP expression relative to the 16S rRNA (reference gene). Gene expression was analysed using the delta delta-Ct method. RESULTS: H. pylori DNA was detected in the stool samples of 18 (20.4%) of the 88 HC (p<0.0001, OR=0.79) and none of AC. No meaningful statistical differences were found between individuals with positive and negative family histories for asthma in AC and HC (p>0.05). H. pylori quantity was higher in seven of 18 H. pylori-positive samples, but HP-NAP expression levels were low in four of these seven samples. Based on a multivariate logistic regression analysis of these three variables together, only males displayed a significant difference based on gender differences (p<0.02) and it was determined that, based on the OR value of 0.46 and the 95% CI range of 0.241-0.888, male gender was an independent protective factor in asthma. CONCLUSIONS: HP-NAP levels vary to the relative concentrations of bacteria in the stationary or late logarithmic phases. Different napA expression levels may be caused by different endogenous napA gene expression or different environmental conditions.

The lipid profile in obese asthmatic children compared to non-obese asthmatic children.

BACKGROUND: A relationship between asthma and obesity has been documented in children and adolescents. An alternate day calorie restriction diet has been reported to improve asthma symptoms by decreasing levels of serum cholesterol and triglycerides, reducing markers of oxidative stress and increasing levels of the antioxidant uric acid. Therefore, to investigate the lipid profile in asthmatic children may be important in asthma control treatment. MATERIALS AND METHODS: One hundred and sixty newly diagnosed persistent asthmatic children were selected to participate in the study. They were divided into four groups based on their body mass index (BMI): Group I normal weight (BMI=20-24.9kg/m(2), n=30); Group II under-weight (BMI<20kg/m(2), n=30); Group III overweight (BMI=25-30kg/m(2), n=25); and Group IV obese (BMI>30kg/m(2), n=25). Fasting blood sugar, fasting insulin, and HbA1c were measured to exclude the possibility of pre-diabetes. Lipid profile measurements included total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apo-A1, apo-B and triglycerides. RESULTS: There were no significant differences in the levels of apo-A1, apo-B, triglycerides, cholesterol and LDL in all four groups. Only the level of HDL was higher in GIV>GIII>GII>GI (75.84±13.95, 68.56±15.28, 64.17±13.93, 63.17±14.34mg/dl, respectively). There were no cases of pre-diabetes in any of the four groups. CONCLUSION: Hypercholesterolaemia and hypertriglyceridaemia were not found in any of the persistent asthmatic children, and thus they are not high risk factors for asthma. Similarly, there were no differences in apo-A1 and apo-B between any of the BMI groups. No differences were found in LDL levels, however HDL levels were increased in all four groups, indicating that allergic sensitisation may have occurred. Controlling body weight and restricting calorie intake may be as important as appropriate pharmacological management in controlling asthma.

Usefulness of modified Pulmonary Index Score (mPIS) as a quantitative tool for the evaluation of severe acute exacerbation in asthmatic children.

BACKGROUND: Acute exacerbation of asthma is divided qualitatively into mild, moderate, and severe attacks and respiratory failure. This system is, however, not suitable for estimating small changes in respiratory condition with time and for determining the efficacy of treatments, because it has a qualitative, but not quantitative nature. METHODS: To evaluate the usefulness of quantitative estimation of asthma exacerbation, modified Pulmonary Index Score (mPIS) values were measured in 87 asthmatic children (mean age, 5.0 ± 0.4 years) during hospitalization. mPIS was calculated by adding the sum of scores for 6 items (scores of 0-3 were given for each item). These consisted of heart rate, respiratory rate, accessory muscle use, inspiratory-to-expiratory flow ratio, degree of wheezing, and oxygen saturation in room air. Measurements were made at visits and at hospitalization and were then made twice a day until discharge. RESULTS: mPIS values were highly correlated among raters. mPIS values at visits were 9.1 ± 0.1 and 12.6 ± 0.4 in subjects with moderate and severe attacks, respectively (p < 0.001). mPIS values of subjects requiring continuous inhalation therapy (CIT) with isoproterenol in addition to systemic steroids were significantly higher than the values of those without CIT (12.0 ± 0.5 and 9.3 ± 0.2, respectively, p < 0.001). A score of 10 was suggested to be the optimal cutoff for distinguishing between subjects requiring and not requiring CIT, from the perspectives of both sensitivity and specificity. mPIS at hospitalization correlated well with the period until discharge, suggesting that this score was a useful predictor for the clinical course after hospitalization. CONCLUSIONS: mPIS could be a useful tool for several aspects during acute asthma attacks, including the determination of a treatment plan, and prediction of the period of hospitalization in admitted patients, although prospective studies would be required to establish our hypothesis.

Serum CDC42 reflects the exacerbation risk and severity, Th1/2 cell imbalance and inflammation in asthmatic children.

Aim: To explore the clinical implication of serum CDC42 in asthmatic children. Materials & methods: Serum CDC42 from 80 asthmatic children experiencing exacerbation, 80 asthmatic children in remission and 40 healthy controls was detected by ELISA. Results: CDC42 was highest in asthmatic children experiencing exacerbation followed by asthmatic children in remission and healthy controls (p < 0.001). Among asthmatic children experiencing exacerbation, CDC42 positively correlated with exacerbation severity (p = 0.011), Th2 (p = 0.017), TNF-α (p < 0.001), IL-6 (p = 0.009) and IL-8 (p = 0.008) and negatively correlated with Th1/Th2 ratio (p = 0.028). In asthmatic children in remission, CDC42 correlated with lower Th1/Th2 ratio (p = 0.028) and higher TNF-α (p = 0.026). In healthy controls, CDC42 showed no correlation with Th1/2 or inflammatory cytokines. Conclusion: Circulating CDC42 reflects exacerbation risk, Th1/2 imbalance and inflammation in asthmatic children.

Responses of schoolchildren with asthma to recommendations to reduce desert dust exposure: Results from the LIFE-MEDEA intervention project using wearable technology.

Current public health recommendations for desert dust storms (DDS) events focus on vulnerable population groups, such as children with asthma, and include advice to stay indoors and limit outdoor physical activity. To date, no scientific evidence exists on the efficacy of these recommendations in reducing DDS exposure. We aimed to objectively assess the behavioral responses of children with asthma to recommendations for reduction of DDS exposure. In two heavily affected by DDS Mediterranean regions (Cyprus & Crete, Greece), schoolchildren with asthma (6-11 years) were recruited from primary schools and were randomized to control (business as usual scenario) and intervention groups. All children were equipped with pedometer and GPS sensors embedded in smartwatches for objective real-time data collection from inside and outside their classroom and household settings. Interventions included the timely communication of personal DDS alerts accompanied by exposure reduction recommendations to both the parents and school-teachers of children in the intervention group. A mixed effect model was used to assess changes in daily levels of time spent, and steps performed outside classrooms and households, between non-DDS and DDS days across the study groups. The change in the time spent outside classrooms and homes, between non-DDS and DDS days, was 37.2 min (pvalue = 0.098) in the control group and -62.4 min (pvalue < 0.001) in the intervention group. The difference in the effects between the two groups was statistically significant (interaction pvalue < 0.001). The change in daily steps performed outside classrooms and homes, was -495.1 steps (pvalue = 0.350) in the control group and -1039.5 (pvalue = 0.003) in the intervention group (interaction pvalue = 0.575). The effects on both the time and steps performed outside were more profound during after-school hours. To summarize, among children with asthma, we demonstrated that timely personal DDS alerts and detailed recommendations lead to significant behavioral changes in contrast to the usual public health recommendations.

Clinical-functional characteristics of children with asthma and obstructive sleep apnea overlap associated with attention deficit hyperactivity disorder: A cross-sectional study.

Background: Asthma and obstructive sleep apnea (OSA) are common chronic respiratory disorders in children. The relationship between asthma and OSA is bidirectional; these conditions share multiple epidemiological risk factors. Untreated OSA may cause attention deficit hyperactivity disorder (ADHD) symptoms. This study aimed to assess the prevalence of ADHD in asthmatic children with OSA and the link between asthma control and lung function of children with asthma and OSA. Methods: A total of 96 children aged 6-15 years diagnosed with asthma, according to the Global Initiative for Asthma (GINA) 2020, were enrolled in this study. All demographic data, including age, gender, body mass index, asthma control status, therapy, the Vanderbilt ADHD Diagnostic Parent Rating Scale, lung function, and exhaled nitric oxide, were collected. In addition, home respiratory polygraphy was used to identify OSA in study subjects. Results: A total of 96 patients (8.4 ± 2.4 years) were included in the present study. OSA was identified in 60.4% of asthmatic children with a mean apnea-hypopnea index (AHI) of 3.5 ± 3.0 event/h. The inattentive ADHD subtype was significantly lower in the non-OSA asthmatic group than in the OSA asthmatic group (7.9 vs. 34.5%, p < 0.05). ADHD had a higher probability of presence (OR: 3.355; 95% CI: 1.271-8.859; p < 0.05) in the OSA group (AHI >1 event/h). Children with poorly controlled asthma had a significantly high risk of OSA (83.0 vs. 17.0%, p < 0.001) than children with well-controlled asthma. Allergic rhinitis increased the odds of having OSA in patients with asthma [OR: 8.217 (95% CI: 3.216-20.996); p < 0.05]. Conclusion: The prevalence of OSA is increased among poorly controlled asthma. ADHD may have a higher prevalence in children with OSA. Therefore, prompt diagnosis of OSA will lead to an accurate asthma control strategy in patients with asthma.

Clinical and functional characteristics of OSA in children with comorbid asthma treated by leukotriene receptor antagonist: A descriptive study.

Background: Obstructive sleep apnea (OSA) is the most common form of respiratory disorders during sleep in children, especially those with severe asthma. However, optimal treatment of asthma might significantly improve OSA severity. Methods: It was a cohort study including children aged >5 years old and diagnosed with asthma according to GINA (Global Initiative for Asthma). The data related to age, gender, height, weight, body mass index (BMI), clinical symptoms and medical history of asthma, spirometry (FEV1: forced expiratory in 1 s), and exhaled nitric oxide (FENO) were recorded for analysis. Respiratory polygraphy (RPG) was done for each study subject to diagnose OSA and its severity. Results: Among 139 asthmatic children, 99 patients with OSA (71.2%) were included in the present study (9.3 ± 0.2 years): 58.6% with uncontrolled asthma and 32.3% with partial controlled asthma. The mean ACT (asthma control testing) score was 19.0 ± 3.4. The most frequent night-time symptoms were restless sleep (76.8%), snoring (61.6%), sweating (52.5%), and trouble breathing during sleep (48.5%). The common daytime symptoms were irritable status (46.5%) and abnormal behavior (30.3%). The mean AHI (apnea-hypopnea index) was 3.5 ± 4.0 events/h. There was a significant correlation between BMI and snoring index (R = 0.189 and P = 0.027), bronchial and nasal FENO with AHI (R = 0.046 and P < 0.001; R = 0.037 and P < 0.001; respectively). There was no significant correlation between asthma level, FEV1 and AHI. The severity of asthma and respiratory function were improved significantly after 3 months and 6 months of asthma treatment in combination with leukotriene receptor antagonist (LRA) treatment. The symptoms related to OSA were significantly improved after treatment with LRA. The severity of OSA was decreased significantly after 3 months and 6 months of treatment. Conclusion: The treatment of asthmatic children with comorbid OSA by LRA in combination with standard therapy for asthma could improve the control of asthma and the symptoms and severity of OSA.

Reduced JKAP correlates with advanced disease features, inflammation, as well as increased exacerbation risk and severity in asthmatic children.

BACKGROUND: This study aimed to investigate the correlation of JNK pathway-associated phosphatase (JKAP) with clinical features, inflammation, exacerbation risk, and severity in asthmatic children. METHODS: Asthmatic exacerbation children (N = 90), asthmatic remission children (N = 90), and healthy controls (N = 90) were enrolled in this case-control study, whose venous blood samples were collected after enrollment for routine blood test, JKAP, and inflammatory cytokines detection by enzyme-linked immune sorbent assay. The clinical features included demographic data, family history of asthma, and pulmonary ventilation function. RESULTS: JKAP level was the lowest in asthmatic exacerbation children, followed by asthmatic remission children and healthy controls. ROC curve revealed good ability of JKAP in distinguishing three groups from each other, especially in telling asthmatic exacerbation children from healthy controls (AUC: 0.926; 95%CI: 0.887-0.965). In addition, JKAP was negatively correlated with eosinophil count, immunoglobulin E (IgE), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and interleukin-17 (IL-17), positively correlated with forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC) and FEV1 (%predicted) in asthmatic exacerbation children. Whereas in asthmatic remission children, JKAP was negatively correlated with eosinophil count, TNF-α, IL-1ß, IL-6, and IL-17 and positively correlated with FEV1 (%predicted), but not with IgE or FEV1/FVC. In healthy controls, the correlation of JKAP with clinical features and inflammatory cytokines was non-obvious. For exacerbation severity, JKAP was the highest in mild exacerbation children, followed by moderate exacerbation children, and severe exacerbation children. CONCLUSION: JKAP serves as a potential biomarker for asthmatic susceptibility, inflammation, exacerbation risk, and severity in children.