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The static charge on the plastic body of spacers attracts drug aerosols, reducing the drug available for inhalation from plastic spacers. Some instructions exist to decrease the electric charge on plastic spacers, such as priming them with salbutamol (20 puffs) before use. This study investigates whether priming plastic spacer devices with this method can improve the bronchodilator test result. This study included children with stable mild to moderate asthma. All subjects underwent two pulmonary function tests to evaluate their bronchodilator response on separate days at 24-48 hours intervals. On each day, spirometry was performed at the baseline and 15 min after inhalation of four puffs of salbutamol (100 μg/puff) through either a primed or a new spacer. The change in forced expiratory volume in the first second (FEV1) after inhaling salbutamol was the primary outcome measure. When the patients used a new spacer, the mean baseline FEV1 (% predicted) and FEV1/FVC (forced vital capacity) were 89.56±11.95 and 86.17±6.87, respectively. However, the mean increase in FEV1 from the baseline was 10.87±8.99 in this group. On the other hand, with the primed spacer, the respective mean baseline FEV1 and FEV1/FVC values were 89.41±12.14 and 85.49±6.76, while it increased by 12.1±11.01 after salbutamol inhalation. There were no significant differences between the techniques regarding the variation in FEV1 before and after bronchodilator use via a new spacer or primed spacer. Priming new plastic spacers with 20 puffs of salbutamol did not cause additional bronchodilation in asthmatic children, suggesting this practice is inefficient in clinics. [ABSTRACT FROM AUTHOR]

Abstract Background Asthma is a common respiratory disease. In asthma, the small airways have more intensive inflammation and prominent airway remodelling, compared to the central airways. We aimed to investigate the predictive value of risk factors and the fractional concentration of exhaled nitric oxide (FeNO) for persistent small airway dysfunction (p-SAD), and compare the effects of different treatment modalities. Methods This retrospective cohort study included 248 children with asthma (aged 4–11 years). Binary logistic regression was used to analyse the risk factors for p-SAD. Correlations among FEV1/FVC, small airway function parameters, and FeNO levels in patients with asthma were analysed using Spearman’s rank correlation. The receiver operating characteristic curve and the Delong test were used to analyse the predictive value of FeNO for p-SAD. Differences in the treatment effects of inhaled corticosteroids (ICS) and ICS with a long-acting beta-agonist (ICS/LABA) on p-SAD were analysed using Fisher’s exact test. Results Asthmatic children with older age of receiving the regular treatment (OR 1.782, 95% CI 1.082–2.935), with younger age at the time of onset of suspected asthma symptoms (OR 0.602, 95% CI 0.365–0.993), with longer duration of using ICS or ICS/LABA (OR 1.642, 95% CI 1.170–2.305) and with worse asthma control (OR 3.893, 95% CI 1.699–8.922) had increased risk for p-SAD. Significant negative correlations of small airway function parameters with FeNO at a 200 mL/s flow rate (FeNO200), and the concentration of nitric oxide in the alveolar or acinar region (CaNO) were observed. The areas under the curve of FeNO200 (cut-off:10.5ppb), CaNO (cut-off:5.1ppb), and FeNO200 combined with CaNO were 0.743, 0.697, and 0.750, respectively, for asthma with p-SAD. After using ICS or ICS/LABA, switching to ICS/LABA was easier than continuing with ICS to improve small airway dysfunction (SAD) in the 8th month. Conclusions Paediatric asthma with p-SAD is associated with older age at receiving regular treatment, younger age at the time of onset of suspected asthma symptoms, longer duration of using ICS or ICS/LABA, worse asthma control, and higher FeNO200 and CaNO levels, all of which can be combined with small airway function indicators to distinguish p-SAD from asthma. ICS/LABA improves SAD better than ICS alone.

Background: Asthma is a common respiratory disease. In asthma, the small airways have more intensive inflammation and prominent airway remodelling, compared to the central airways. We aimed to investigate the predictive value of risk factors and the fractional concentration of exhaled nitric oxide (FeNO) for persistent small airway dysfunction (p-SAD), and compare the effects of different treatment modalities. Methods: This retrospective cohort study included 248 children with asthma (aged 4–11 years). Binary logistic regression was used to analyse the risk factors for p-SAD. Correlations among FEV1/FVC, small airway function parameters, and FeNO levels in patients with asthma were analysed using Spearman's rank correlation. The receiver operating characteristic curve and the Delong test were used to analyse the predictive value of FeNO for p-SAD. Differences in the treatment effects of inhaled corticosteroids (ICS) and ICS with a long-acting beta-agonist (ICS/LABA) on p-SAD were analysed using Fisher's exact test. Results: Asthmatic children with older age of receiving the regular treatment (OR 1.782, 95% CI 1.082–2.935), with younger age at the time of onset of suspected asthma symptoms (OR 0.602, 95% CI 0.365–0.993), with longer duration of using ICS or ICS/LABA (OR 1.642, 95% CI 1.170–2.305) and with worse asthma control (OR 3.893, 95% CI 1.699–8.922) had increased risk for p-SAD. Significant negative correlations of small airway function parameters with FeNO at a 200 mL/s flow rate (FeNO200), and the concentration of nitric oxide in the alveolar or acinar region (CaNO) were observed. The areas under the curve of FeNO200 (cut-off:10.5ppb), CaNO (cut-off:5.1ppb), and FeNO200 combined with CaNO were 0.743, 0.697, and 0.750, respectively, for asthma with p-SAD. After using ICS or ICS/LABA, switching to ICS/LABA was easier than continuing with ICS to improve small airway dysfunction (SAD) in the 8th month. Conclusions: Paediatric asthma with p-SAD is associated with older age at receiving regular treatment, younger age at the time of onset of suspected asthma symptoms, longer duration of using ICS or ICS/LABA, worse asthma control, and higher FeNO200 and CaNO levels, all of which can be combined with small airway function indicators to distinguish p-SAD from asthma. ICS/LABA improves SAD better than ICS alone. [ABSTRACT FROM AUTHOR]

Background: Asthma is a common childhood disease that leads to impairment of quality of life (QOL) of both the children affected by the disease and their caregivers. Management of asthma includes pharmacotherapy along with education about asthma and its self-management, which is most often given verbally. There is limited evidence regarding the benefits of using a written asthma action plan (WAAP) that has been improved using pictorial representation. Objective: The study aimed to assess the effectiveness of a WAAP in improving the QOL of children with bronchial asthma and also of their caregivers. It also educates the patients and families about various triggers and danger signs of an acute attack of asthma. Methods: This was an interventional study with the aim of improving the quality of asthma management. Children of age group 7–17 years in whom the diagnosis of asthma was made and those parents and children who could read and answer the questionnaire (mini-PAQLQ and PACQLQ) were included in the study. Subjects were randomized into Case and Control groups. The intervention was to give the randomly selected patients (Case group) an individualized WAAP along with standard asthma care to both groups. Both groups were followed up to assess and record variations in the quality of life. Results: The P value was highly significant in the following parameters post-intervention: missed doses of controller medication (P value = 0.001), need for rescue medication (

Abstract Background Asthma is a common disease in childhood and adolescence with lifelong consequences particularly among those at risk of severe disease, poor control and/or frequent exacerbations. Specialist care is recommended for at-risk children and adolescents, yet access to specialist management in free-to-access healthcare settings remains poorly understood. Methods A Danish nationwide cohort of children and adolescents aged 2–17 years with persistent asthma, defined as repeated redemption of inhaled corticosteroids (ICS) during 2015, were followed for two years, to identify at-risk children and adolescents comprising those with severe asthma (classified according to GINA 2020 guidelines), poor control (defined as use of 400/600 (ages 2–11/12 +) annual doses of short-acting bronchodilators), or frequent exacerbations (defined as use of oral steroids or hospitalization), and access to specialist care. The population is chosen due to detailed medical records in the setting of universal health care. Results The cohort comprised of 29,851 children and adolescents (59% boys), with a median age of 9 years. While 17% of children were on high dose ICS, 22% were on daily ICS below GINA low dose cut-off. Prevalence of severe asthma (3.0–6.5%) was lower than poor asthma control (6.4–25%); both declined from childhood to adolescence. Exacerbations occurred in 7.1–9.0% of children, with median number of exacerbations being 1 (IQR 1–1). Despite being classified as having mild-to-moderate asthma, 15% had poor asthma control and 3.8% experienced exacerbation(s), respectively. While 61% of children with severe asthma and 58% with exacerbation-prone disease were in specialist care, only 24% with uncontrolled disease were receiving specialist care. Of children and adolescents using high-dose ICS, 71% were managed in primary care, while the use of additional controllers was more common in specialist care. Conclusions Throughout childhood and adolescence, there was a high prevalence of severe asthma and poor control, although their prevalence declined with age. We demonstrate a large unmet need for specialist care among children with at-risk asthma, particularly among those with poorly controlled asthma, even in a system with free-to-access, tax-funded healthcare.

Background: Asthma is a common childhood disease that leads to impairment of quality of life (QOL) of both the children affected by the disease and their caregivers. Management of asthma includes pharmacotherapy along with education about asthma and its self-management, which is most often given verbally. There is limited evidence regarding the benefits of using a written asthma action plan (WAAP) that has been improved using pictorial representation. Objective: The study aimed to assess the effectiveness of a WAAP in improving the QOL of children with bronchial asthma and also of their caregivers. It also educates the patients and families about various triggers and danger signs of an acute attack of asthma. Methods: This was an interventional study with the aim of improving the quality of asthma management. Children of age group 7-17 years in whom the diagnosis of asthma was made and those parents and children who could read and answer the questionnaire (mini-PAQLQ and PACQLQ) were included in the study. Subjects were randomized into Case and Control groups. The intervention was to give the randomly selected patients (Case group) an individualized WAAP along with standard asthma care to both groups. Both groups were followed up to assess and record variations in the quality of life. Results: The P value was highly significant in the following parameters post-intervention: missed doses of controller medication (P value = 0.001), need for rescue medication (<0.001), ACT score (0.001), total PAQLQ (<0.001), and PACQLQ (<0.001) score. Though statistical significance was not established, improvement was also observed in the number of unscheduled OPD visits (P value = 0.082) and hospitalization events (P value = 0.554). Conclusion: On being provided with the WAAP, the frequency of acute asthma events, treatment compliance, and QOL improved. There was a significant increase in the primary outcomes-PAQLQ and PACQLQ scores. Significant improvement in the secondary outcomes-number of missed school days, missed doses of controller medication, need for rescue medication, and ACT score was also observed. [ABSTRACT FROM AUTHOR]

Background: Asthma is a common disease in childhood and adolescence with lifelong consequences particularly among those at risk of severe disease, poor control and/or frequent exacerbations. Specialist care is recommended for at-risk children and adolescents, yet access to specialist management in free-to-access healthcare settings remains poorly understood. Methods: A Danish nationwide cohort of children and adolescents aged 2–17 years with persistent asthma, defined as repeated redemption of inhaled corticosteroids (ICS) during 2015, were followed for two years, to identify at-risk children and adolescents comprising those with severe asthma (classified according to GINA 2020 guidelines), poor control (defined as use of 400/600 (ages 2–11/12 +) annual doses of short-acting bronchodilators), or frequent exacerbations (defined as use of oral steroids or hospitalization), and access to specialist care. The population is chosen due to detailed medical records in the setting of universal health care. Results: The cohort comprised of 29,851 children and adolescents (59% boys), with a median age of 9 years. While 17% of children were on high dose ICS, 22% were on daily ICS below GINA low dose cut-off. Prevalence of severe asthma (3.0–6.5%) was lower than poor asthma control (6.4–25%); both declined from childhood to adolescence. Exacerbations occurred in 7.1–9.0% of children, with median number of exacerbations being 1 (IQR 1–1). Despite being classified as having mild-to-moderate asthma, 15% had poor asthma control and 3.8% experienced exacerbation(s), respectively. While 61% of children with severe asthma and 58% with exacerbation-prone disease were in specialist care, only 24% with uncontrolled disease were receiving specialist care. Of children and adolescents using high-dose ICS, 71% were managed in primary care, while the use of additional controllers was more common in specialist care. Conclusions: Throughout childhood and adolescence, there was a high prevalence of severe asthma and poor control, although their prevalence declined with age. We demonstrate a large unmet need for specialist care among children with at-risk asthma, particularly among those with poorly controlled asthma, even in a system with free-to-access, tax-funded healthcare. [ABSTRACT FROM AUTHOR]

Background: In the USA, genetically admixed populations have the highest asthma prevalence and severe asthma exacerbations rates. This could be explained not only by environmental factors but also by genetic variants that exert ethnic-specific effects. However, no admixture mapping has been performed for severe asthma exacerbations.Objective: We sought to identify genetic variants associated with severe asthma exacerbations in Hispanic/Latino subgroups by means of admixture mapping analyses and fine mapping, and to assess their transferability to other populations and potential functional roles.Methods: We performed an admixture mapping in 1124 Puerto Rican and 625 Mexican American children with asthma. Fine-mapping of the significant peaks was performed via allelic testing of common and rare variants. We performed replication across Hispanic/Latino subgroups, and the transferability to non-Hispanic/Latino populations was assessed in 1001 African Americans, 1250 Singaporeans and 941 Europeans with asthma. The effects of the variants on gene expression and DNA methylation from whole blood were also evaluated in participants with asthma and in silico with data obtained through public databases.Results: Genomewide significant associations of Indigenous American ancestry with severe asthma exacerbations were found at 5q32 in Mexican Americans as well as at 13q13-q13.2 and 3p13 in Puerto Ricans. The single nucleotide polymorphism (SNP) rs1144986 (C5orf46) showed consistent effects for severe asthma exacerbations across Hispanic/Latino subgroups, but it was not validated in non-Hispanics/Latinos. This SNP was associated with DPYSL3 DNA methylation and SCGB3A2 gene expression levels.Conclusions: Admixture mapping study of asthma exacerbations revealed a novel locus that exhibited Hispanic/Latino-specific effects and regulated DPYSL3 and SCGB3A2. [ABSTRACT FROM AUTHOR]

BackgroundNon-communicable lung disease and exposure to air pollution are major problems in sub-Saharan Africa. A high burden of chronic respiratory symptoms, spirometric abnormalities and air pollution exposures has been found in Malawian adults; whether the same would be true in children is unknown.MethodsThis cross-sectional study of children aged 6-8 years, in rural Malawi, included households from communities participating in the Cooking and Pneumonia Study (CAPS), a trial of cleaner-burning biomass-fuelled cookstoves. We assessed; chronic respiratory symptoms, anthropometry, spirometric abnormalities (using Global Lung Initiative equations) and personal carbon monoxide (CO) exposure. Prevalence estimates were calculated, and multivariable analyses were done.ResultsWe recruited 804 children (mean age 7.1 years, 51.9% female), including 476 (260 intervention; 216 control) from CAPS households. Chronic respiratory symptoms (mainly cough (8.0%) and wheeze (7.1%)) were reported by 16.6% of children. Average height-for-age and weight-for-age z-scores were -1.04 and -1.10, respectively. Spirometric abnormalities (7.1% low forced vital capacity (FVC); 6.3% obstruction) were seen in 13.0% of children. Maximum CO exposure and carboxyhaemoglobin levels (COHb) exceeded WHO guidelines in 50.1% and 68.5% of children, respectively. Children from CAPS intervention households had lower COHb (median 3.50% vs 4.85%, p=0.006) and higher FVC z-scores (-0.22 vs -0.44, p=0.05) than controls.ConclusionThe substantial burden of chronic respiratory symptoms, abnormal spirometry and air pollution exposures in children in rural Malawi is concerning; effective prevention and control strategies are needed. Our finding of potential benefit in CAPS intervention households calls for further research into clean-air interventions to maximise healthy lung development in children.

Abstract Public health measures to mitigate the COVID-19 pandemic have altered health care for chronic conditions. The impact of the COVID-19 pandemic on paediatric asthma, the most common chronic respiratory cause of childhood hospitalisation, in Australia, remains unknown. In a multicentre study, we examined the impact of three waves of COVID-19 on paediatric asthma in New South Wales Australia. Time series analysis was performed to determine trends in asthma hospital presentations in children aged 2–17 years before (2015–2019) and during the COVID-19 pandemic (2020–2021) using emergency department and hospital admission datasets from two large tertiary paediatric hospitals. In this first report from Australia, we observed a significant decrease in asthma hospital presentations during lockdown periods including April (68.85%), May (69.46%), December (49.00%) of 2020 and August (66.59%) of 2021 compared to pre-pandemic predictions. The decrease in asthma hospital presentations coincided with the lockdown periods during first, second and third waves of the COVID-19 pandemic and was potentially due to reduced transmission of other common respiratory viruses from restricted movement.

Very few studies have been carried out on asthma and allergies in pre-schoolchildren. This is the first study of pre-school children with asthma and allergies in the United Arab Emirates. We studied 4,000 pre-schoolchildren from the United Arab Emirates: Dubai, Sharjah, Abu Dhabi, and Al-Ain. The ages of the study group were between 1-5 years, and were 2,000 boys and 2,000 girls; they were randomly selected from kindergartens and nurseries. We used the standardised International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The mean (SD) age, height, weight and BMI were 3.3 (1.4) years, 92.0 (1.3) cm, 17.3 (5.2) kg, and 23.4 (9.3). The prevalence rates of “wheeze ever”, “current wheeze”, “speech limitation”, “asthma” , “dry night cough”, and “exercise-induced asthma” were 40.4%, 43.8%, 37.6%, 26.5%, 36.1, and 37.6%, respectively. Boys had a significantly higher prevalence of wheeze ever and current wheeze than girls. Girls had a significantly higher prevalence of speech limitation than boys. The prevalence rates of “rhinitis ever”, “current rhinitis”, “itchy watery eyes” and “hay fever” were 42%, 40.5%, 39.1% and 46.9%, respectively. Boys had significantly higher prevalence rates of “rhinitis ever”, “current rhinitis”, and “itchy watery eyes” than girls. The prevalence rates of “rash ever”, “current rash” and “eczema ever” were 38.9%, 33.7% and 58.0%, respectively. Boys had significantly higher prevalence rates of rash ever, current rash, and eczema ever than girls. Children who were exposed to parental smoking have significantly higher prevalence rates of asthma, wheezing, and cough than those whom were not exposed. Children who breastfed more than 10 months had a significantly lower prevalence rates of “wheeze ever”, “current wheeze”, “speech limitation”, and “asthma”, than those whom breastfed less than 10 months. The prevalence rates of asthma, rhinitis and eczema were very high. Breastfeeding was found to be protective for asthma. The study can be used as a baseline intervention project to reduce incidents of asthma and allergies in these children and to establish atopic march in order to implement strategies to improve the respiratory health and allergies in these children.

Background: Preschool-aged children have among the highest burden of acute wheeze. We investigated differences in healthcare use, treatment and outcomes for recurrent wheeze/asthma in preschoolers from different ethno-socioeconomic backgrounds., Methods: Retrospective cohort study using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics in England. We reported number of acute presentations and hospitalisations stratified by index of multiple deprivation (IMD) and ethnicity; and factors associated with treatment non-escalation, and hospitalisation rates using multivariable logistic and Poisson regression models., Results: 194 291 preschool children were included. In children not trialled on asthma preventer medications, children from the most deprived IMD quintile (adjusted OR 1.67; 95% CI 1.53 to 1.83) and South Asian (1.77; 1.64 to 1.91) children were more likely to have high reliever usage and where specialist referral had not occurred, the odds of referral being indicated was higher in the most deprived quintile (1.39; 1.28 to 1.52) and South Asian (1.86; 1.72 to 2.01) children compared with the least deprived quintile and white children, respectively.Hospitalisation rates for wheeze/asthma were significantly higher in children from the most deprived quintile (adjusted IRR 1.20; 95% CI 1.13 to 1.27) compared with the least, and in South Asian (1.57; 1.44 to 1.70) and black (1.32; 1.22 to 1.42) compared with white children., Conclusions: We identified inequalities in wheeze/asthma treatment and morbidity in preschool children from more deprived, and non-white backgrounds. A multifaceted approach to tackle health inequality at both the national and local levels, which includes a more integrated and standardised approach to treatment, is needed to improve health outcomes in children with preschool wheeze/asthma., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare the following: DL and CL receive support from the National Institute for Health and Care Research (NIHR). DL has also received an institutional research grant from the Midlands Asthma and Allergy Research Association (MAARA). HP holds institutional research grants from NIHR and Asthma UK unrelated to this publication and has received personal fees from Teva Pharmaceuticals and Sandoz UK. Additionally, HP has received travel expense payments from the European Respiratory Society (ERS). JKQ has received institutional grants from the Industrial Strategy Challenge Fund, the Medical Research Council, Health Data Research, GlaxoSmithKline (GSK), Boehringer Ingelheim (BI), Asthma+Lung UK, and Astra Zeneca (AZ); and personal fees from GSK, Evidera, Chiesi, AZ, and Insmed. EAG has received institutional grants from Gilead, Circassia, Chiesi, Propellar Health, Helicon Health, Adherium Ltd, and AZ; and personal fees from Circassia and Sanofi. SS and CG had no competing interests to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Spirometry is used by many clinicians to monitor asthma in children but relatively little is understood about its variability over time. The aim of this study was to determine the variability of forced expiratory volume in 1 s (FEV 1 ) in children with symptomatically well-controlled asthma by applying three different methods of expressing change in FEV 1 over 3-month intervals., Methods: Data from five longitudinal studies of children with asthma which measured FEV 1 at 3-month intervals over 6 or 12 months were used. We analysed paired FEV 1 measurements when asthma symptoms were controlled. The variability of FEV 1 % predicted (FEV 1 %), FEV 1 z-score (FEV 1 z) and conditional z score for change (Zc) in FEV 1 was expressed as limits of agreement., Results: A total of 881 children had 3338 FEV 1 measurements on occasions when asthma was controlled; 5184 pairs of FEV 1 measurements made at 3-month intervals were available. Each unit change in FEV 1 z score was equivalent to a Zc 1.45 and an absolute change in FEV 1 % of 11.6%. The limits of agreement for change in FEV 1 % were -20 and +21, absolute change in FEV 1 z were -1.7 and +1.7 and Zc were -2.6 and +2.1. Regression to the mean and increased variability in younger children were present for change in FEV 1 % and FEV 1 z comparisons, but not Zc., Conclusion: Given the wide limits of agreement of paired FEV 1 measurements in symptomatically well-controlled children, asthma treatment should primarily be guided by symptoms and not by a change in spirometry., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Infants and young children might be particularly susceptible to the potential side effects from inhaled corticosteroid (ICS) on height and bone mineral content (BMC), but this has rarely been studied in long-term prospective studies.Methods: Children from two Copenhagen Prospective Studies on Asthma in Childhood cohorts were included. ICS use was registered prospectively from birth to age 6 and the cumulative dose was calculated. Primary outcomes were height and BMC from dual-energy X-ray absorptiometry (DXA) scans at age 6.Results: At age 6, a total of 930 children (84%) from the cohorts had a valid height measurement and 792 (71%) had a DXA scan. 291 children (31%) received a cumulated ICS dose equivalent to or above 10 weeks of standard treatment before age 6. We found an inverse association between ICS use and height, -0.26 cm (95% CI: -0.45 to -0.07) per 1 year standard treatment from 0 to 6 years of age, p=0.006. This effect was mainly driven by children with ongoing treatment between age 5 and 6 years (-0.31 cm (95% CI: -0.52 to -0.1), p=0.004), while there was no significant association in children who stopped treatment at least 1 year before age 6 (-0.09 cm (95% CI: -0.46 to 0.28), p=0.64). There was no association between ICS use and BMC at age 6.Conclusions: ICS use in early childhood was associated with reduced height at age 6 years but only in children with continued treatment in the sixth year of life. [ABSTRACT FROM AUTHOR]

Public health measures to mitigate the COVID-19 pandemic have altered health care for chronic conditions. The impact of the COVID-19 pandemic on paediatric asthma, the most common chronic respiratory cause of childhood hospitalisation, in Australia, remains unknown. In a multicentre study, we examined the impact of three waves of COVID-19 on paediatric asthma in New South Wales Australia. Time series analysis was performed to determine trends in asthma hospital presentations in children aged 2–17 years before (2015–2019) and during the COVID-19 pandemic (2020–2021) using emergency department and hospital admission datasets from two large tertiary paediatric hospitals. In this first report from Australia, we observed a significant decrease in asthma hospital presentations during lockdown periods including April (68.85%), May (69.46%), December (49.00%) of 2020 and August (66.59%) of 2021 compared to pre-pandemic predictions. The decrease in asthma hospital presentations coincided with the lockdown periods during first, second and third waves of the COVID-19 pandemic and was potentially due to reduced transmission of other common respiratory viruses from restricted movement. [ABSTRACT FROM AUTHOR]

Background: International asthma guidelines recommend against epinephrine (adrenaline) administration in acute asthma unless associated with anaphylaxis or angio-oedema. However, administration of intramuscular epinephrine in addition to nebulised selective β2-agonist is recommended for acute severe or life-threatening asthma in many prehospital guidelines. We conducted a systematic review to determine the efficacy of epinephrine in comparison to selective β2-agonist in acute asthma.Methods: We included peer-reviewed publications of randomised controlled trials (RCTs) that enrolled children or adults in any healthcare setting and compared epinephrine by any route to selective β2-agonist by any route for an acute asthma exacerbation. The primary outcome was treatment failure, including hospitalisation, need for intubation or death.Results: Thirty-eight of 1140 studies were included. Overall quality of evidence was low. Seventeen studies contributed data on 1299 participants to the meta-analysis. There was significant statistical heterogeneity, I2=56%. The pooled Peto's OR for treatment failure with epinephrine versus selective β2-agonist was 0.99 (0.75 to 1.32), p=0.95. There was strong evidence that recruitment age group was associated with different estimates of the odds of treatment failure; with studies recruiting adults-only having lower odds of treatment failure with epinephrine. It was not possible to determine whether epinephrine in addition to selective β2-agonist improved outcomes.Conclusion: The low-quality evidence available suggests that epinephrine and selective β2-agonists have similar efficacy in acute asthma. There is a need for high-quality double-blind RCTs to determine whether addition of intramuscular epinephrine to inhaled or nebulised selective β2-agonist improves outcome.Prospero Registration Number: CRD42017079472. [ABSTRACT FROM AUTHOR]

In the current study, efforts are being made to formulate transdermal salbutamol-cubosomal gel to manage paediatric asthma. Salbutamol-loaded cubosomal gels were prepared by melt emulsification and sonication. The cubosomal gels were characterised by morphology, particle size, zeta potential, entrapment efficacy, assay, viscosity, and texture profiles. Ex vivo permeation and pharmacokinetic studies were performed using rats. The mean cubosomal particle size (208–361 ± 12.5–32.5 nm), PDI (0.06–0.11 ± 0.01–0.02), viscosity (8527–9019 cp), and entrapment efficacy (76.3–91.0% w/w) increase with the level of monoolein. The ex vivo permeation study showed a biphasic release pattern, with salbutamol cleared from control gel within 8 h, while cubosomal gels showed sustained release up to 72 h. The pharmacokinetic profiles in the rat model showed 8.62-fold higher bioavailability with cubosomal gel. The study demonstrated the potential of cubosomal nanoparticle-laden gel to sustain the release of salbutamol to treat paediatric asthma. [ABSTRACT FROM AUTHOR]

Most genome-wide association studies of obesity and body mass index (BMI) have so far assumed an additive mode of inheritance in their analysis, although association testing supports a recessive effect for some of the established loci, for example, rs1421085 in FTO In two whole-genome sequencing (WGS) studies of children with asthma and their parents (892 Costa Rican trios and 286 North American trios), we discovered an association between a locus (rs9292139) in LOC102724122 and BMI that reaches genome-wide significance under a recessive model in the combined analysis. As the association does not achieve significance under an additive model, our finding illustrates the benefits of the recessive model in WGS analyses. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study., Design: Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined., Setting: Children aged 0-18 years from 26 European birth cohorts., Participants: 136 071 individual children from 26 cohorts, with information on PA and/or sedentary behaviour in early childhood and asthma assessment in later childhood., Main Outcome Measure: Questionnaire-based current asthma and lung function measured by spirometry (forced expiratory volume in 1 s (FEV 1 ), FEV 1 /forced vital capacity) at age 6-18 years., Results: Questionnaire-based and accelerometry-based PA and sedentary behaviour at age 3-5 years was not associated with asthma at age 6-18 years (PA in hours/day adjusted OR 1.01, 95% CI 0.98 to 1.04; sedentary behaviour in hours/day adjusted OR 1.03, 95% CI 0.99 to 1.07). PA was not associated with lung function at any age. Analyses of sedentary behaviour and lung function showed inconsistent results., Conclusions: Reduced PA and increased sedentary behaviour before 6 years of age were not associated with the presence of asthma later in childhood., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Early infant diet might influence the risk of subsequent allergic disease.Methods: The Merthyr Allergy Prevention Study (MAPS) was a randomised controlled trial in infants at high risk of allergic disease. The trial determined whether a cow's milk exclusion diet for the first 4 months of life decreased the risk of allergic disease including asthma compared with a normal diet. A soya milk preparation was offered to those in the intervention group. A standardised questionnaire for allergic disease was completed at ages 1, 7, 15 and 23 years, with clinical assessment at 1, 7 and 23 years. The effect of the intervention on the risk of atopy, asthma and wheeze at age 23 years was determined.Findings: 487 subjects entered the study; at age 23 years 299 completed the questionnaire, of which 119 attended clinical assessment. Subjects randomised to the intervention group had a significantly increased risk of atopy (adjusted OR 2.97, 95% CI 1.30 to 6.80; p=0.01) and asthma (OR 2.07, 95%CI 1.09 to 3.91; p=0.03) at age 23 years, but not wheeze (OR 1.43, 95%CI 0.87 to 2.37; p=0.16). Earlier exposure to cow's milk was associated with a decreased risk of wheeze and asthma at age 23 years, while earlier exposure to soya milk was associated with an increased risk of atopy and asthma.Interpretation: In infants at high risk of allergic disease, either cow's milk exclusion or early soya milk introduction for the first 4 months of life increases the risk of atopy, wheeze and asthma in adulthood. [ABSTRACT FROM AUTHOR]

Introduction: The influence of mometasone furoate for paediatric asthma remains controversial. Aim: We conducted a systematic review and meta-analysis to explore the efficacy and safety of mometasone furoate for paediatric asthma. Material and methods: We have searched PubMed, Embase, Web of science, EBSCO, and Cochrane library databases through October 2019 for randomized controlled trials assessing the effect of mometasone furoate versus placebo for paediatric asthma. This meta-analysis was performed using the random-effects model. Results: Four RCTs were included in the meta-analysis. Overall, as compared to placebo for paediatric asthma, mometasone furoate is associated with substantially increased predicted forced expiratory volume in 1 s (FEV1) (mean difference (MD) = 7.53; 95% CI: 7.02-8.04; p < 0.00001), FEV1 (MD = 0.11; 95% CI: 0.10-0.12; p < 0.00001), and morning peak expiratory flow (AM PEF) (MD = 17.70; 95% CI: 9.91-25.49; p < 0.00001), but demonstrates no obvious effect on pharyngitis (RR = 0.96; 95% CI: 0.59-1.58; p = 0.89), upper respiratory tract infections (RR = 0.73; 95% CI: 0.50-1.05; p = 0.09), or adverse events (RR = 1.05; 95% CI: 0.84-1.31; p = 0.69). Conclusions: Mometasone furoate may be effective and safe for paediatric asthma. [ABSTRACT FROM AUTHOR]

Airway inflammation plays a key role in asthma pathogenesis but is heterogeneous in nature. There has been significant scientific discovery with regard to type 2-driven, eosinophil-dominated asthma, with effective therapies ranging from inhaled corticosteroids to novel biologics. However, studies suggest that approximately 1 in 5 adults with asthma have an increased proportion of neutrophils in their airways. These patients tend to be older, have potentially pathogenic airway bacteria and do not respond well to classical therapies. Currently, there are no specific therapeutic options for these patients, such as neutrophil-targeting biologics.Neutrophils comprise 70% of the total circulatory white cells and play a critical defence role during inflammatory and infective challenges. This makes them a problematic target for therapeutics. Furthermore, neutrophil functions change with age, with reduced microbial killing, increased reactive oxygen species release and reduced production of extracellular traps with advancing age. Therefore, different therapeutic strategies may be required for different age groups of patients.The pathogenesis of neutrophil-dominated airway inflammation in adults with asthma may reflect a counterproductive response to the defective neutrophil microbial killing seen with age, resulting in bystander damage to host airway cells and subsequent mucus hypersecretion and airway remodelling. However, in children with asthma, neutrophils are less associated with adverse features of disease, and it is possible that in children, neutrophils are less pathogenic.In this review, we explore the mechanisms of neutrophil recruitment, changes in cellular function across the life course and the implications this may have for asthma management now and in the future. We also describe the prevalence of neutrophilic asthma globally, with a focus on First Nations people of Australia, New Zealand and North America. [ABSTRACT FROM AUTHOR]

Background: Several childhood asthma risk loci that relate to immune function have been identified by genome‐wide association studies (GWAS), but the underlying mechanisms remain unknown. Objective: Here, we examined whether perturbed innate immune responses mediate the association between known genetic risk variants and development of childhood asthma. Methods: Peripheral blood mononuclear cells from 336 six‐month‐old infants from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) cohort were stimulated in vitro with six different innate ligands (LPS, CpG, poly(I:C), R848, HDMAPP and aluminium hydroxide together with low levels of LPS) followed by quantification of 18 released cytokines and chemokines 40 h after the stimulations. The innate immune response profiles were decomposed by principal component (PC) analysis, and PC1‐5 were used in mediation analyses of the effect of 25 known genetic risk variants on childhood asthma until age 7. Results: The effects of two variants from the 17q21 locus (rs7216389, rs2305480) on asthma and exacerbation risk were significantly mediated by immune parameters induced in response to ligands mimicking intracellular colonization; bacterial DNA (CpG) and double‐stranded viral RNA (poly(I:C)). The Th17 and innate lymphoid cell type 3‐amplifying cytokine IL‐23 was the most prominent cytokine involved. Conclusion: The 17q21 effect on childhood asthma and exacerbations was partly mediated by deregulation of IL‐23 in response to intracellular microbial ligands, which may suggest ineffective clearance of intracellular pathogens in the lungs. [ABSTRACT FROM AUTHOR]

Background: Australia has one of the highest rates of asthma worldwide. Indigenous children have a particularly high burden of risk determinants for asthma, yet little is known about the asthma risk profile in this population.Aim: To identify and quantify potentially preventable risk factors for hospitalised asthma in Australian Aboriginal children (1-4 years of age).Methods: Birth, hospital and emergency data for all Aboriginal children born 2003-2012 in Western Australia were linked (n=32 333). Asthma was identified from hospitalisation codes. ORs and population attributable fractions were calculated for maternal age at birth, remoteness, area-level disadvantage, prematurity, low birth weight, maternal smoking in pregnancy, mode of delivery, maternal trauma and hospitalisations for acute respiratory tract infection (ARTI) in the first year of life.Results: There were 705 (2.7%) children hospitalised at least once for asthma. Risk factors associated with asthma included: being hospitalised for an ARTI (OR 4.06, 95% CI 3.44 to 4.78), area-level disadvantage (OR 1.58, 95% CI 1.28 to 1.94), being born at <33 weeks' gestation (OR 3.30, 95% CI 2.52 to 4.32) or birth weight <1500 g (OR 2.35, 95% CI 1.39 to 3.99). The proportion of asthma attributable to an ARTI was 31%, area-level disadvantage 18%, maternal smoking 5%, and low gestational age and birth weight were 3%-7%. We did not observe a higher risk of asthma in those children who were from remote areas.Conclusion: Improving care for pregnant Aboriginal women as well as for Aboriginal infants with ARTI may help reduce the burden of asthma in the Indigenous population. [ABSTRACT FROM AUTHOR]

Objective: Research has linked early adverse childhood experiences (ACEs) with asthma development; however, existing studies have generally relied on parent report of exposure and outcome. We aimed to examine the association of early life ACEs with empirically determined trajectories of childhood asthma risk, using independent register information on both exposures and outcome.Methods: Based on nationwide registries, we established a study cohort of 466 556 children born in Denmark (1997-2004). We obtained information on ACEs during the first 2 years of life (bereavement, parental chronic somatic and/or mental illness) and childhood asthma diagnosis or medication use from birth through age 10 years from the Danish National Patient and Prescription Registries, respectively. We identified asthma phenotypes using group-based trajectory modelling. We then used multinomial logistic regression to examine the association between early ACEs and asthma phenotypes.Results: We identified four asthma phenotypes: non-asthmatic, early-onset transient, early-onset persistent and late-onset asthma. Girls with early-onset transient asthma (OR 1.13, 95% CI 1.04 to 1.24), early-onset persistent asthma (1.27, 95% CI 1.08 to 1.48) or late-onset asthma (OR 1.28, 95% CI 1.11 to 1.48) vs no asthma were more likely to have early life ACE exposure compared with girls without ACE exposure. Results were similar for boys who also had experienced early life ACEs with ORs of 1.16 (95% CI 1.08 to 1.25), 1.34 (95% CI 1.20 to 1.51) and 1.11 (95% CI 0.98 to 1.25), respectively.Conclusion: In a nationwide-population study, we identified three childhood onset asthma phenotypes and found that ACEs early in life were associated with increased odds for each of these asthma phenotypes among both girls and boys. [ABSTRACT FROM AUTHOR]

Childhood asthma has been with us for many years, and prevalence has been increasing. Asthma is the fifth most common killer in our country, and although it may not kill as many people as infectious diseases, the quality of life of an asthmatic may be seriously impaired, leaving a child or adult with compromised lung health that never goes away. The diagnosis of asthma, which is characterised by variable expiratory airflow limitation, is primarily based on recurrent cough and wheeze. Asthma management should be personalised, and long-term asthma management involves assessing, adjusting and reviewing treatment response. Medication should be titrated up or down for individual patient needs. [ABSTRACT FROM AUTHOR]

Asthma is one of the most common chronic diseases. Epidemiological studies show that asthma will develop among around 40% of children under six years old with symptoms of bronchial obstruction.Diagnosis of asthma is complicated, especially in the paediatric population. As a result, a lot of research is being carried out to establish the pathophysiology and to find new biomarkers of this disease. Progranulin (PGRN) is a recently discovered growth factor with many biological functions. PGRN has anti-inflammatory properties because it inhibits neutrophil degranulation and blocks tumor necrosis factor α (TNF-α) transmission. The underlying mechanisms are still being researched, but TNF-α is considered to be a cytokine responsible for neutrophilic inflammation in the airways and bronchial hyperresponsiveness. Therefore, PGRN, by lowering TNF-α concentration and stimulating regulatory T-cell (Treg) prolifera­tion, relieves symptoms of bronchial inflammatory diseases. This article attempts to verify the current knowledge about basic pathophysiological mechanisms in asthma. We also summarise the most recent research advances in the role of PGRN in the respiratory system.

Introduction: The comparison of fluticasone propionate/ formoterol (FP/FORM) with fluticasone propionate/salmeterol(FP/SAL) for paediatric asthma remains controversial. Aim: We conduct a systematic review and meta-analysis to explore the efficacy and safety of FP/FORM versus FP/SAL for paediatric asthma. Material and methods: We have searched PubMed, Embase, Web of science, EBSCO, and Cochrane library databases through August 2019 for randomized controlled trials (RCTs) assessing the effect of FP/FORM versus FP/SAL for paediatric asthma. This meta-analysis is performed using the random-effects model. Results: Three RCTs are included in the meta-analysis. Overall for paediatric asthma, FP/FORM and FP/SAL demonstrate a comparable influence on FEV, (Std. MD = -0.01; 95% CI: -0.04 to 0.03; p = 0.62), FVC (Std. MD = 0; 95% CI: -0.07 to 0.06; p = 0.87), FEF25 (Std. MD = -1.69; 95% CI: -6.69 to 3.31; p = 0.51), FEF50 (Std. MD = 0.10; 95% CI: -0.12 to 0.33; p = 0.37), FEF75 (Std. MD = 0.01; 95% CI: -0.21 to 0.24; p = 0.91), asthma symptom scores (Std. MD = -0.03; 95% CI: -0.11 to 0.04; p = 0.43), sleep disturbance scores (Std. MD = 0.03; 95% CI: -0.19 to 0.24; p = 0.81) and adverse events (RR = 1.07; 95% CI: 0.83 to 1.38; p = 0.61). Conclusions: FP/FORM and FP/SAL show a comparable efficacy for paediatric asthma. [ABSTRACT FROM AUTHOR]

Background: Shortages of clinical staff make chronic asthma care challenging in low-income countries. We evaluated an outpatient asthma care package for children, including task-shifting of asthma management roles.Methods: We conducted a non-blinded individually randomised controlled trial at a tertiary-level government hospital in Blantyre, Malawi. Children aged 6-15 years diagnosed with asthma were recruited from outpatient clinic, stratified by Childhood Asthma Control Test (cACT) score and allocated 1:1 from a concealed file, accessed during electronic questionnaire completion. The intervention, delivered by non-physicians, comprised clinical assessment, optimisation of inhaled treatment, individualised asthma education. The control group received standard care from outpatient physicians. Primary outcome for intention-to-treat analysis was change in cACT score at 3 months. Secondary outcomes included asthma exacerbations requiring emergency healthcare and school absence.Findings: Between September 2018 and December 2019, 120 children (59 intervention; 61 control) were recruited; 65.8% males, with mean (SD) age 9.8 (2.8) years, mean (SD) baseline cACT 20.3 (2.6). At 3 months, intervention children (n=56) had a greater mean (SD) change in cACT score from baseline (2.7 (2.8) vs 0.6 (2.8)) compared with standard care participants (n=59); a difference of 2.1 points (95% CI: 1.1 to 3.1, p<0.001). Fewer intervention children attended emergency healthcare (7.3% vs 25.4%, p=0.02) and missed school (20.0% vs 62.7%, p<0.001) compared with standard care children.Interpretation: The intervention resulted in decreased asthma symptoms and exacerbations. Wider scale-up could present substantial benefits for asthmatic patients in resource-limited settings.Trial Registration Number: PACTR201807211617031. [ABSTRACT FROM AUTHOR]

Background/objective: Limited research exists regarding the association between grandmaternal smoking during pregnancy and the risk for asthma and altered lung function in grandchildren. This study aimed to investigate this association in a three-generation design.Methods: 37 291 participants (25 747 adults and 11 544 children) were included from the Lifelines study, a prospective longitudinal three generation cohort study in The Netherlands. Spirometry was available in 69.5% and 61.1% of the included adults and children. Logistic and linear regression were used to analyse the association between grandmaternal smoking during pregnancy and (1) asthma, (2) early childhood asthma (ie, onset before 6 years) and (3) lung function level. Maternal and paternal grandmaternal smoking were studied separately and the analyses were stratified by adult/child and by gender. The analyses were adjusted for gender, current smoking, birth variables and socioeconomic status.Results: In the adult population, maternal grandmaternal smoking during pregnancy was associated with a higher risk for asthma (OR (95% CI): 1.38 (1.06 to 1.79)), early childhood asthma (1.49 (95% CI 1.06 to 2.11)) and a lower FEV1/FVC% predicted (B (95% CI): -1.04 (-1.91 to -0.16) in men. These findings were not observed in a separate analysis of children that participated in this study. There was also no significant association between paternal grandmaternal smoking and asthma/lung function.Conclusion: Maternal grandmaternal smoking during pregnancy is associated with higher asthma risk and lower lung function in male grandchildren and a reverse effect in male grandchildren of subsequent generations. Our study highlights the deep-rooted effects of tobacco smoking across generations. [ABSTRACT FROM AUTHOR]

Background: There is conflicting research about the association between asthma and poor educational attainment that may be due to asthma definitions. Our study creates seven categories of current chronic and acute asthma to investigate if there is an association for poorer educational attainment at age 6-7 years, and the role of respiratory infections and school absence.Methods: This study used a population-based electronic cross-sectional birth cohort 1998-2005, in Wales, UK, using health and education administrative datasets. Current asthma or wheeze categories were developed using clinical management guidelines in general practice (GP) data, acute asthma was inpatient hospital admissions and respiratory infections were the count of GP visits, from birth to age 6-7 years. We used multilevel logistic regression grouped by schools to ascertain if asthma or wheeze was associated with not attaining the expected level in teacher assessment at Key Stage 1 (KS1) adjusting for sociodemographics, perinatal, other respiratory illness and school characteristics. We tested if absence from school was a mediator in this relationship using the difference method.Results: There were 85 906 children in this population representative cohort with 7-year follow-up. In adjusted multilevel logistic regression, only asthma inpatient hospital admission was associated with increased risk for not attaining the expected level at KS1 (adjusted OR 1.14 95% CI (1.02 to 1.27)). Lower respiratory tract infection (LRTI) GP contacts remained an independent predictor for not attaining the expected level of education. Absence from school was a potential mediator of the association between hospital admission and educational attainment.Conclusions: Clinicians and educators need to be aware that children who have inpatient hospital admissions for asthma or wheeze, or repeated LRTI, may require additional educational support for their educational outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Elevated particulate matter (PM) concentrations of anthropogenic and/or desert dust origin are associated with increased morbidity among children with asthma., Objective: The Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches randomised controlled trial assessed the impact of exposure reduction recommendations, including indoor air filtration, on childhood asthma control during high desert dust storms (DDS) season in Cyprus and Greece., Design, Participants, Interventions and Setting: Primary school children with asthma were randomised into three parallel groups: (a) no intervention (controls); (b) outdoor intervention (early alerts notifications, recommendations to stay indoors and limit outdoor physical activity during DDS) and (c) combined intervention (same as (b) combined with indoor air purification with high efficiency particulate air filters in children's homes and school classrooms. Asthma symptom control was assessed using the childhood Asthma Control Test (c-ACT), spirometry (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC)) and fractional exhaled nitric oxide (FeNO)., Results: In total, 182 children with asthma (age; mean=9.5, SD=1.63) were evaluated during 2019 and 2021. After three follow-up months, the combined intervention group demonstrated a significant improvement in c-ACT in comparison to controls (β=2.63, 95% CI 0.72 to 4.54, p=0.007), which was more profound among atopic children (β=3.56, 95% CI 0.04 to 7.07, p=0.047). Similarly, FEV1% predicted (β=4.26, 95% CI 0.54 to 7.99, p=0.025), the need for any asthma medication and unscheduled clinician visits, but not FVC% and FeNO, were significantly improved in the combined intervention compared with controls., Conclusion: Recommendations to reduce exposure and use of indoor air filtration in areas with high PM pollution may improve symptom control and lung function in children with asthma., Trial Registration Number: NCT03503812., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Airway obstruction is defined by spirometry as a low forced expiratory volume in 1 s (FEV 1 ) to forced vital capacity (FVC) ratio. This impaired ratio may originate from a low FEV 1 (classic) or a normal FEV 1 in combination with a large FVC (dysanaptic). The clinical implications of dysanaptic obstruction during childhood and adolescence in the general population remain unclear., Aims: To investigate the association between airway obstruction with a low or normal FEV 1 in childhood and adolescence, and asthma, wheezing and bronchial hyperresponsiveness (BHR)., Methods: In the BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology; Sweden) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy; the Netherlands) birth cohorts, obstruction (FEV 1 :FVC ratio less than the lower limit of normal, LLN) at ages 8, 12 (PIAMA only) or 16 years was classified as classic (FEV 1 1 ≥LLN) obstruction. Cross-sectional and longitudinal associations between these two types of obstruction and respiratory health outcomes were estimated by cohort-adjusted logistic regression on pooled data., Results: The prevalence of classic obstruction at ages 8, 12 and 16 in the two cohorts was 1.5%, 1.1% and 1.5%, respectively. Dysanaptic obstruction was slightly more prevalent: 3.9%, 2.5% and 4.6%, respectively. Obstruction, regardless of FEV 1 , was consistently associated with higher odds of asthma (dysanaptic obstruction: OR 2.29, 95% CI 1.40 to 3.74), wheezing, asthma medication use and BHR compared with the normal lung function group. Approximately one-third of the subjects with dysanaptic obstruction in childhood remained dysanaptic during adolescence., Clinical Implications: Children and adolescents with airway obstruction had, regardless of their FEV 1 level, a higher prevalence of asthma and wheezing. Follow-up and treatment at these ages should be guided by the presence of airway obstruction., Competing Interests: Competing interests: GHK reports grant support from the Netherlands Lung Foundation, TEVA the Netherlands, GSK, Vertex, Ubbo Emmius Foundation, European Union (H2020) and ZonMW outside the submitted work. GHK reports lecture and/or advisory fees from GSK, AstraZeneca and PureIMS (money to institution). EM reports lecture and/or advisory board fees from ALK, Airsonett, AstraZeneca, Chiesi, Novartis and Sanofi outside the submitted work. GW reports lecture fees from Sanofi outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In spite of the substantial impact of pediatric asthma on healthcare resources, there is a notable dearth of research focusing on allergen sensitization specifically in children and adolescents with asthma in Cameroon, with existing studies primarily concentrating on adult populations. We, therefore, set out to determine factors associated with sensitization to selected aero-allergens in children and adolescents with asthma followed up at Laquintinie Hospital Douala, Cameroon., Methodology: We conducted a cross-sectional analytical study on patients aged 2-17 years followed up for pediatric asthma at Laquintinie Hospital Douala for 8 months (January to August 2023). Skin prick tests were performed using selected standardized aeroallergens extracts. Factors associated with sensitization were determined using multivariable logistic regression analysis. The threshold for significance was set at p < .05., Results: In total, 126 children and adolescents with asthma were recruited, 50.79% of whom were male with an average age of 8.00 ± 3.99 years. Eight out of 10 patients (83.52%) were sensitized to common aero-allergens (20.59% monosensitized and 79.41% polysensitized). The most common aero-allergens found were the dust mites Dermatophagoïdes pteronyssinus (81.37%), Blomia tropicalis (67.64%) and Dermatophagoïdes farinae (52.94%) followed by Blatella species (25.49%). The factors independently associated with sensitization in our population were the personal history of allergic rhinitis in the patient [adjusted odds ratio, aOR: 4.07 (95% confidence interval, CI: 1.41-11.76), b = 0.54, p = .009], chest tightness at rest [aOR: 5.92 (95% CI: 1.08-32.38), b = 0.87, p = .040), and age above 5 years [aOR: 4.65 (95% CI: 1.47-14.69), b = 0.59, p = .009)., Conclusion: Sensitization to multiple aeroallergens is common in children and adolescents with asthma, especially for dust mites and cockroaches. Factors associated with sensitization are patients aged >5 years, chest tightness at rest, and a personal history of allergic rhinitis., (© 2024 Wiley Periodicals LLC.)

Background: Body composition might influence lung function and asthma in children, but its longitudinal relations are unclear. We aimed to identify critical periods for body composition changes during childhood and adolescence in relation to respiratory outcomes in adolescents., Methods: In a population-based prospective cohort study, we measured body mass index, fat mass index (FMI), lean mass index (LMI) and the ratio of android fat mass divided by gynoid fat mass (A/G ratio) by dual-energy X-ray absorptiometry at 6, 10 and 13 years. At 13 years, lung function was measured by spirometry, and current asthma was assessed by questionnaire., Results: Most prominently and consistently, higher FMI and A/G ratio at age 13 years were associated with lower forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) and forced expiratory flow after exhaling 75% of FVC (FEF 75 ) (range Z-score difference -0.13 (95% CI -0.16 to -0.10) to -0.08 (95% CI -0.11 to -0.05) per SD score increase), and higher LMI at all ages was associated with higher FEF 75 (range Z-score difference 0.05 (95% CI 0.01 to 0.08) to 0.09 (95% CI 0.06 to 0.13)). Between the ages of 6 and 13 years, normal to high FMI and A/G ratio were associated with lower FEV 1 /FVC and FEF 75 (range Z-score difference -0.20 (95% CI -0.30 to -0.10) to -0.17 (95% CI -0.28 to -0.06)) and high to high LMI with higher FEF 75 (range Z-score difference0.32 (95% CI 0.23 to 0.41)). Body composition changes were not associated with asthma., Conclusion: Adolescents with higher total and abdominal fat indices may have impaired lung function, while those with a higher lean mass during childhood and adolescence may have better small airway function. Public health measures should focus on a healthy body composition in adolescents to minimise respiratory morbidity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The potential association between the use of inhaled corticosteroids (ICS) and the risk of pneumonia among adults is disputed and paediatric-specific evidence is scarce., Aim: To assess the potential association between ICS, use and the risk of hospitalisation for pneumonia among children (age 2-17 years) with asthma., Methods: This was a cohort study based on nationwide data from routine clinical practice in Sweden (January 2007 to November 2021). From 425 965 children with confirmed asthma, episodes of new ICS use and no use were identified using records of dispensed drugs. We adjusted for potential confounders with propensity score overlap weighting and the risk of a hospitalisation with pneumonia as primary diagnosis was estimated. Multiple subgroup and sensitivity analyses were also performed., Results: We identified 249 351 ICS (mean follow-up of 0.9 years) and 214 840 no-use (mean follow-up of 0.7 years) episodes. During follow-up, 369 and 181 events of hospitalisation for pneumonia were observed in the ICS and no-use episodes, respectively. The weighted incidence rates of hospitalisation for pneumonia was 14.5 per 10 000 patient-years for ICS use episodes and 14.6 for no-use episodes. The weighted HR for hospitalisation for pneumonia associated with ICS use was 1.06 (95% CI 0.88 to 1.28) and the absolute rate difference was -0.06 (95% CI -2.83 to 2.72) events per 10 000 patient-years, compared with no use., Conclusions: In this nationwide cohort study, we found no evidence of an association between ICS use and the risk of hospitalisation for pneumonia among children with asthma, as compared with no use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Respiratory syncytial virus (RSV) causes exacerbations of asthma and preschool wheeze (PSW). However, the anti‐viral and repair responses of the bronchial epithelium in children with severe therapy‐resistant asthma (STRA) and PSW are poorly understood. Methods: Children with STRA (age 12 [6‐16] years), PSW (age 2 [1‐5] years) and non‐asthmatic controls (age 7 [2‐14] years) underwent bronchoscopy with endobronchial brushings and biopsies. Anti‐viral, wound injury responses were quantified in biopsies and primary bronchial epithelial cells (PBECs) in response to RSV, poly(I:C), house dust mite (HDM) or IL‐33 using RT‐qPCR, Luminex and live cell imaging. Collagen deposition and tissue expression of epithelial growth factor receptor (EGFR), IL‐33 and receptor ST2 were investigated in bronchial biopsies. Results: PBECs from STRA and PSW had increased TLR3 gene expression and increased secretion of anti‐viral and pro‐inflammatory cytokines (IFN‐γ, IL‐6 and IL‐13) in response to RSV compared to controls. Exposure of PBECs to concomitant TLR3 agonist poly(I:C) and HDM resulted in a significant reduction in epithelial cell proliferation in PSW compared to controls. Wound‐healing was also impaired in PSW compared to controls at baseline and following IL‐33 stimulation. In addition, tissue EGFR expression was significantly reduced in PSW and correlated with collagen deposition in endobronchial biopsies. Conclusions: Despite increased anti‐viral responses, preschool children with severe wheeze had impaired airway epithelial proliferative responses following damage. This might be connected to the low expression of EGFR in PSW which may affect epithelial function and contribute to asthma pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Studies suggest an increased all-cause mortality among adults with asthma. We aimed to study the relationship between asthma in children and young adults and all-cause mortality, and investigate differences in mortality rate by also having a life-limiting condition (LLC) or by parental socioeconomic status (SES).Methods: Included in this register-based study are 2 775 430 individuals born in Sweden between January 1986 and December 2012. We identified asthma cases using the National Patient Register (NPR) and the Prescribed Drug Register. Those with LLC were identified using the NPR. Parental SES at birth (income and education) was retrieved from Statistics Sweden. We estimated the association between asthma and all-cause mortality using a Cox proportional hazards regression model. Effect modification by LLC or parental SES was studied using interaction terms in the adjusted model.Results: The adjusted hazard rate (adjHR) for all-cause mortality in asthma cases versus non-asthma cases was 1.46 (95% CI 1.33 to 1.62). The highest increased rate appeared to be for those aged 5-15 years. In persons with asthma and without LLC, the adjHR remained increased at 1.33 (95% CI 1.18 to 1.50), but differed (p=0.002) from those with asthma and LLC, with an adjHR of 1.87 (95% CI 1.57 to 2.22). Parental SES did not alter the association (income, p=0.55; education, p=0.83).Conclusion: This study shows that asthma is associated with an increased mortality in children and young adults regardless of LLC or parental SES. Further research is warranted to investigate the possible mechanisms for this association. [ABSTRACT FROM AUTHOR]

Background: Although maternal psychological distress during pregnancy is associated with increased risks of respiratory morbidity in preschool children, it is unknown whether this association persists into later childhood.Objective: To examine the association between parental psychological distress during pregnancy and lung function and asthma in children of school age.Methods: This study of 4231 children was embedded in a population-based prospective cohort. Parental psychological distress was assessed by the Brief Symptom Inventory during and 3 years after pregnancy, and in mothers also at 2 and 6 months after pregnancy. At age 10 years, lung function was obtained by spirometry and asthma by questionnaire.Results: The prevalence of asthma was 5.9%. Maternal overall psychological distress during pregnancy was associated with a lower forced vital capacity (FVC) (z-score difference -0.10 (95% CI -0.20 to -0.01) per 1-unit increase), maternal depressive symptoms during pregnancy with a lower forced expiratory volume in the first second (FEV1) and FVC (-0.13 (95% CI -0.24 to -0.01) and -0.13 (95% CI -0.24 to -0.02) when using clinical cut-offs) in their children. All maternal psychological distress measures during pregnancy were associated with an increased risk of asthma (range OR: 1.46 (95% CI 1.12 to 1.90) to 1.91 (95% CI 1.26 to 2.91)). Additional adjustment for paternal psychological distress during pregnancy and parental psychological distress after pregnancy did not materially change the associations. Paternal psychological distress during pregnancy was not associated with childhood respiratory morbidity.Conclusion: Maternal, but not paternal, psychological distress during pregnancy is associated with an increased risk of asthma and partly lower lung function in children. This suggests intrauterine programming for the risk of later-life respiratory disease. [ABSTRACT FROM AUTHOR]

ObjectivesAssociations of emergency department (ED) visits and hospital admissions for asthma in children with demographics and area socio-economic status (SES) were examined to evaluate long-term trends and identify vulnerable populations.Study designRetrospective population-based trend and cross-sectional analyses.MethodsAsthma hospital admissions (2000-2007) and ED visits (2005-2007) for children aged 0-14 years living in Orange County, California were linked with zip-code-level SES data (2000 US Census). Annual population estimates were obtained to calculate age-specific admissions and ED visit rates. Average annual percentage changes (AAPC) were calculated with joinpoint analyses. The risks of ED visits and hospital admissions were estimated from SES indicators with negative binomial regression.ResultsRates of asthma hospital admissions and ED visits were highest among children aged 0-4 years, males and African Americans, and lowest among Asian/Pacific Islanders. African Americans and Hispanics/Latinos were more likely to be uninsured. Asthma admissions decreased significantly for all age groups over the study period. The greatest declines per 100,000 were among children aged 0-4 years (AAPC: -15.3%, 95% confidence interval -17.0% to -13.4%). Rates of hospital admissions and ED visits were significantly higher in low-SES groups. Hospital admission rates were 30-60% higher and ED visits were 80-90% higher in zip codes in the lowest tertile of median household income compared with the highest tertile of median household income.ConclusionsPaediatric asthma hospitalizations and ED visit rates are declining in Orange County. However, certain groups are disproportionately affected, including those living in areas with low SES. This information will help in targeting intervention strategies to children at highest risk for severe asthma episodes.

Background: Respiratory syncytial virus (RSV) is associated with childhood asthma. Nevertheless, not all children exposed to RSV develop asthma symptoms, possibly because genes modulate the effects of RSV on asthma exacerbations.Objective: The purpose of this study was to identify genes that modulate the effect of RSV latent infection on asthma exacerbations.Methods: We performed a meta-analysis to investigate differentially expressed genes (DEGs) of RSV infection from Gene Expression Omnibus datasets. Expression quantitative trait loci (eQTL) methods were applied to select single nucleotide polymorphisms (SNPs) that were associated with DEGs. Gene-based analysis was used to identify SNPs that were significantly associated with asthma exacerbations in the Taiwanese Consortium of Childhood Asthma Study (TCCAS), and validation was attempted in an independent cohort, the Childhood Asthma Management Program (CAMP). Gene-RSV interaction analyses were performed to investigate the association between the interaction of SNPs and RSV latent infection on asthma exacerbations.Results: A total of 352 significant DEGs were found by meta-analysis of RSV-related genes. We used 38 123 SNPs related to DEGs to investigate the genetic main effects on asthma exacerbations. We found that eight RSV-related genes (GADD45A, GYPB, MS4A3, NFE2, RNASE3, EPB41L3, CEACAM6 and CEACAM3) were significantly associated with asthma exacerbations in TCCAS and also validated in CAMP. In TCCAS, rs7251960 (CEACAM3) significantly modulated the effect of RSV latent infection on asthma exacerbations (false-discovery rate <0.05). The rs7251960 variant was associated with CEACAM3 mRNA expression in lung tissue (p for trend=1.2×10-7). CEACAM3 mRNA was reduced in nasal mucosa from subjects with asthma exacerbations in two independent datasets.Conclusions: rs7251960 is an eQTL for CEACAM3, and CEACAM3 mRNA expression is reduced in subjects experiencing asthma exacerbations. CEACAM3 may be a modulator of RSV latent infection on asthma exacerbations. [ABSTRACT FROM AUTHOR]

Paediatric asthma is a common inflammatory disease in children. Atractylenolide III is an active component of the Atractylodes rhizome, an herbal medicine that has been used as an asthma treatment. This study aimed to explore the effects and underlying mechanisms of atractylenolide III in IL‐4‐induced 16HBE cells and ovalbumin‐induced asthmatic mice. The results showed that IL‐4 stimulation significantly decreased, and atractylenolide III treatment increased, growth and apoptosis of 16HBE cells. In 16HBE cells, administration of atractylenolide III also significantly suppressed the IL‐4‐induced increases in the expression of cleaved caspase‐1; apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC); and nucleotide‐binding domain and leucine‐rich repeat protein 3 (NLRP3). Moreover, the numbers of total leukocytes, neutrophils, eosinophils, and macrophages significantly increased in ovalbumin‐induced mice, and then decreased after atractylenolide III treatment. In ovalbumin‐induced asthmatic mice, atractylenolide III treatment also significantly inhibited NLRP3 inflammasome activation and restored the Th1/Th2 balance. These results indicate that atractylenolide III reduced NLRP3 inflammasome activation and regulated the Th1/Th2 balance in IL‐4 induced 16HBE cells and ovalbumin‐induced asthmatic mice, suggesting it has a protective effect that may be useful in the treatment of paediatric asthma. [ABSTRACT FROM AUTHOR]

Background: Spirometry and fraction of exhaled nitric oxide (FeNO) are commonly used in specialist centres to monitor children with asthma. The National Institute for Health and Care Excellence recommends spirometry for asthma monitoring from 5 years in all healthcare settings. There is little spirometry and FeNO data in children managed for asthma in UK primary care to support their use.Objectives: To study the prevalence of abnormal spirometry and FeNO in children with asthma managed in primary care and to explore their relationship with asthma control and unplanned healthcare attendances (UHA).Methods: Prospective observational cohort study in children aged 5-16 years with suspected or doctor-diagnosed asthma attending an asthma review in UK general practice. Spirometry, FeNO, asthma control test (ACT) scores and number of UHAs were studied.Results: Of 612 children from 10 general practices, 23.5% had abnormal spirometry, 36.0% had raised FeNO ≥35 parts per billion and 41.8% reported poor control. Fifty-four per cent of children reporting good asthma control had abnormal spirometry and/or raised FeNO. At follow-up, the mean number of UHAs fell from 0.31/child in the 6 months preceding review to 0.20/child over the 6 months following review (p=0.0004). Median ACT scores improved from 20 to 22 (p=0.032), and children's ACT from 21 to 23 (p<0.0001).Conclusions: Abnormal lung function and FeNO are common in children attending for asthma review in primary care and relate poorly to symptom scores. A symptoms-based approach to asthma monitoring without objective testing is likely to miss children at high risk of future severe asthma attacks. [ABSTRACT FROM AUTHOR]

Background and objective: We conducted a comprehensive assessment of guideline adherence in paediatric asthma care, including inpatient and ambulatory services, in Australia. Methods: National and international clinical practice guidelines (CPG) relating to asthma in children were searched and 39 medical record audit indicator questions were developed. Retrospective medical record review was conducted across hospital inpatient admissions, emergency department (ED) presentations, general practice (GP) and paediatrician consultations in three Australian states for children aged ≤15 years receiving care in 2012 and 2013. Eligibility of, and adherence to, indicators was assessed from medical records by nine experienced and purpose‐trained paediatric nurses (surveyors). Results: Surveyors conducted 18 453 asthma indicator assessments across 1600 visits for 881 children in 129 locations. Overall, the adherence for asthma care across the 39 indicators was 58.1%, with 54.4% adherence at GP (95% CI: 46.0–62.5), 77.7% by paediatricians (95% CI: 40.5–97.0), 79.9% in ED (95% CI: 70.6–87.3) and 85.1% for inpatient care (95% CI: 76.7–91.5). For 14 acute asthma indicators, overall adherence was 56.3% (95% CI: 47.6–64.7). Lowest adherences were for recording all four types of vital signs in children aged >2 years presenting with asthma attack (15.1%, 95% CI: 8.7–23.7), and reviewing patients' compliance, inhaler technique and triggers prior to commencing a new drug therapy (20.5%, 95% CI: 10.1–34.8). Conclusion: The study demonstrated differences between existing care and CPG recommendations for paediatric asthma care in Australia. Evidence‐based interventions to improve adherence to CPG may help to standardize quality of paediatric asthma care and reduce variation of care. [ABSTRACT FROM AUTHOR]