Pediatric Pulmonology

Aims of the studyRoutinely collected health data are increasingly used for research, however important history items may be incomplete in medical records. We assessed clinical documentation of exercise-induced respiratory symptoms (EIS) by treating physicians and compared with parent-reported EIS for the same children. MethodsWe analysed data from the Swiss Paediatric Airway Cohort (SPAC), a multicentre observational study of children treated in Swiss outpatient pulmonology clinics. We included children 6 to 17 years of age who were referred to a paediatric pulmonologist for evaluation of EIS. Features of EIS recorded by physicians were extracted from outpatient clinical letters transmitted to the referring physician, while parent-reported EIS data were collected from a standardized questionnaire completed at SPAC enrolment. We calculated agreement between physician-documented and parent-reported EIS characteristics using Cohens and Fleisss kappa. ResultsOf 1669 children participating in SPAC (2017-2019), 193 (12%) met the inclusion criteria, of whom 48% were girls. Physicians provided detailed information on EIS in 186 (96%) outpatient clinical letters. Documented characteristics included: type of physical activity triggering EIS (69%), localisation of EIS in chest or throat (48%), respiratory phase of EIS (45%), and timing of EIS during or after exercise (37%). Previous bronchodilator use (94%) and its effect on EIS (88%) were consistently documented by physicians. The clinical letters of children diagnosed with dysfunctional breathing more often contained detailed EIS characteristics than for children diagnosed with asthma. The agreement between physician-documented and parent-reported EIS was moderate for use of bronchodilators (k=0.53) and poor to fair for all other features (k=0.01-0.36). ConclusionThis study highlights that outpatient clinical letters may lack some details on EIS characteristics, information which parents could provide. A standardized and detailed method for documenting paediatric respiratory symptoms in the coordinated data infrastructure may enhance future analyses of routinely collected health data.

ObjectiveThis systematic review aims to identify social risk factors that influence pediatric asthma exacerbations. MethodsCohort studies published between 2010 and 2020 were systematically searched on the OVID Medline, Embase, and PsycInfo databases. Using our established phased inclusion and exclusion criteria, studies that did not address a pediatric population, social risk factors, and asthma exacerbations were excluded. Out of a total of 707 initially retrieved articles, 3 prospective cohort and 6 retrospective cohort studies were included. ResultsUpon analysis of our retrieved studies, two overarching domains of social determinants, as defined by Healthy People 2030, were identified as major risk factors for pediatric asthma exacerbations: Social/Community Context and Neighborhood/Built Environment. Social/Community factors including African American race and inadequate caregiver perceptions were associated with increased risk for asthma exacerbations. Patients in high-risk neighborhoods, defined by lower levels of education, housing, and employment, had higher rates of emergency department readmissions and extended duration of stay. Additionally, a synergistic interaction between the two domains was found such that patients with public or no health insurance and residence in high-risk neighborhoods were associated with excess hospital utilization attributable to pediatric asthma exacerbations. ConclusionSocial risk factors play a significant role in influencing the frequency and severity of pediatric asthma exacerbations. 3-Question Summary BoxO_ST_ABS1. What is the current understanding of this subject?C_ST_ABSThe individual impact of social factors such as insurance, neighborhood, and ethnicity on pediatric asthma exacerbations has previously been explored. 2. What does this report add to the literature?This review systematically identifies the relative importance of individual sociodemographic factors and interactions between them. Race, neighborhood risk, insurance status, caregiver perceptions, and a synergistic interaction between health insurance status and neighborhood risk were found to be contributary. 3. What are the implications for public health practice?It is important for providers to educate patients on how their surroundings impact their respiratory health and advocate for increased healthcare access for at-risk populations.

Prediction models for asthma remission in school-age are lacking, limiting clinicians' ability to tailor follow-up. Most prediction tools focus on pre-school diagnosis or require lung function testing. We developed and validated a simple, history-based clinical prediction tool for asthma remission. We analyzed prospective data from the Swiss Paediatric Airway Cohort (SPAC), including 1860 children (aged 5-16 years) with physician-diagnosed asthma. We derived asthma remission predictors from parental questionnaires capturing demographics, symptoms, triggers, and family history. We defined clinical remission at 2-3 years following asthma diagnosis, as absence of wheeze and inhaler use during the past 12 months. We developed the model using LASSO regression with multiple imputations for missing data, and assessed its performance by area under the curve (AUC), Hosmer-Lemeshow (HL) test, and calibration plots. We then derived a simplified score and validated it in the German All-Age Asthma Cohort (ALLIANCE). From 12 candidate variables, the final score retained: sex, wheeze frequency, night-time awakening, exercise-induced wheeze, pollen-triggered wheeze, animal-triggered wheeze, maternal asthma, and paternal asthma. The score demonstrated moderate discrimination in the development cohort (AUC 0.71) and maintained discriminative ability in the external validation (AUC 0.71). This practical, prognostic tool for asthma remission based only on clinical history, allows clinicians to identify children who have lower chances for remission, enabling their closer monitoring.

Population-based studies of children presenting with dry night cough alone compared with those who also wheeze are few and inconclusive. Luftibus in the school is a population-based study of schoolchildren conducted between 2013-2016 in Zurich, Switzerland. We divided children into four mutually exclusive groups based on reported dry night cough ( cough) and wheeze and compared parent-reported symptoms, comorbidities and exposures using multinomial regression, FeNO using quantile regression, spirometry using linear regression and healthcare use and treatments using descriptive statistics. Among 3457 schoolchildren aged 6-17 years, 294 (9%) reported cough, 181 (5%) reported wheeze, 100 (3%) reported wheeze and cough and 2882 (83%) were asymptomatic. Adjusting for confounders in a multinomial regression, children with cough reported more frequent colds, rhinitis and snoring than asymptomatic children; children with wheeze or wheeze and cough more often reported hay fever, eczema and parental histories of asthma. FeNO and spirometry were similar among asymptomatic and children with cough, while children with wheeze or wheeze and cough had higher FeNO and evidence of bronchial obstruction. Children with cough used healthcare less often than those with wheeze, and they attended mainly primary care. Twenty-two children (7% of those with cough) reported a physician diagnosis of asthma and used inhalers. These had similar characteristics as children with wheeze. Our representative population-based study suggests only a small subgroup (7%) of schoolchildren reporting dry night cough without wheeze have features typical of asthma, yet the majority (93%) should be investigated for alternative aetiologies, particularly upper airway disease. Take home messageOur population-based study found children with night cough alone clearly differ from those with wheeze, suggesting different aetiologies and pathophysiology. Yet, a small subgroup (7%) has features of asthma and may benefit from specific work-up.

Background: Clinical guidelines recommend objective tests to diagnose asthma in school-age children, but their availability and use in routine practice remain uncertain. We evaluated asthma diagnostic practices in Switzerland, focusing on first-line tests (spirometry, bronchodilator reversibility testing, and fractional exhaled nitric oxide [FeNO]). Methods: Cross-sectional, nationwide online survey of primary care paediatricians (PCPs) and respiratory specialists. We assessed access to and use of diagnostic tests, focusing on first-line tests, and examined reasons for non-use, referral practices, and guideline consultation. We used multivariable logistic regression to identified factors associated with spirometry access among PCPs. Results: Of 1,055 respondents, 625 diagnosed asthma in children, including 419 PCPs. Among PCPs, 50% (95% confidence interval [CI] 45-55) reported no access to spirometry and 95% (95% CI 92-97) no access to FeNO, whereas all paediatric respiratory specialists and almost all adult respiratory specialists had access to both tests. Barriers to first-line testing among PCPs included economic constraints and difficulties interpreting test results. Spirometry access was lower in French- and Italian-speaking regions than in German-speaking regions (adjusted odds ratio [aOR] 0.09, 95% CI 0.05-0.15), but higher among PCPs working full-time (aOR 2.04, 95% CI 1.11-3.82) and those using Swiss asthma guidelines (aOR 1.71, 95% CI 1.01-2.92). PCPs without spirometry access more frequently referred children to specialists for diagnostic confirmation (89% versus 80%; p=0.019). Conclusion: Many PCPs in Switzerland lack access to guideline-recommended tests. Improving access, reimbursement, and training in test interpretation may help reduce the gap between guidelines and clinical practice.

BackgroundClinical practice guidelines for asthma diagnosis are rarely evaluated in real-life practice. Within the Swiss Paediatric Airway Cohort (SPAC), we initiated the SPAC-asthma project to develop a standardised diagnostic approach for school-aged asthma, based on the algorithm recommended by the European Respiratory Society (ERS) guideline. Here, we report the development and feasibility of this approach after implementation across multiple paediatric pulmonology clinics. MethodWe used a modified Delphi process with paediatric pulmonologists from participating clinics to tailor the ERS algorithm for feasible implementation in children aged 5-17 years with suspected asthma. Key adaptations included selection of initial tests, criteria for further testing, test cutoffs, the role of medication trial and follow-up procedures. One year after implementation, we evaluated adherence to the adapted approach at four clinics and explored the reasons for any deviations. ResultsThe final SPAC-asthma approach included spirometry, fractional exhaled nitric oxide and allergy testing as initial tests, followed by either bronchodilator reversibility testing, bronchial challenge test or medication trial. Overall adherence after one year was 77% (182/236 patients). Deviations were due to practice-related (e.g., different criteria for bronchial obstruction), patient-related (e.g., inability to perform spirometry), and logistical reasons (e.g., scheduling difficulties). ConclusionThe diagnostic approach was well implemented, but the observed deviations highlighted the need for flexibility when applying guidelines in real-world settings. As a next step, we will assess whether implementing the ERS asthma guidelines in school-aged children improves diagnostic accuracy. Take home messageWe tested a standardised ERS guideline-based approach to diagnose school-age asthma across Swiss paediatric pulmonology clinics. After expert adaptation and a year, adherence was good and we identified areas to improve guideline implementation.

BackgroundRecent guidelines differ in how fractional exhaled nitric oxide (FeNO) is used to diagnose school-age asthma, either as one of several tests with a cut-off at 25 ppb or as a single rule-in test at 35 ppb. Evidence on its diagnostic performance and clinical utility in subgroups remain limited. MethodsWe analysed data from 1,979 school-age children in the Swiss Paediatric Airway Cohort referred for suspected asthma. We investigated FeNO performance with diagnosis by paediatric pulmonologists as reference standard using receiver operating characteristics curves, selected cut-offs and simulated predictive values across different prevalence. Subgroup analyses considered allergic sensitisation with allergic rhinitis and current inhaled corticosteroid (ICS) use. ResultsIn the overall cohort (asthma diagnosis 70%), FeNO showed poor discrimination for asthma (AUC 0.66; 95% CI 0.64-0.68) with an optimal cut-off at 22 ppb. At 25 and 35 ppb, sensitivity was low (43%, 95% CI 40-46; 31%, 95% CI 29-34) and specificity moderate to high (84%, 95% CI 77-84; 90%, 95% CI 87-92). Positive predictive value at 35 ppb was 88% and was 57% when simulated at a prevalence of 30%. FeNO had no diagnostic value in non-sensitised children and lower performance in sensitised children with allergic rhinitis than in those without (AUC 0.59 vs 0.68). Current ICS use did not influence performance. ConclusionFeNO has limited diagnostic performance as a stand-alone test for school-age asthma, and underlying asthma prevalence and allergic characteristics should be considered in the interpretation.

BackgroundLongitudinal measurements of intra-breath respiratory impedance (Zrs) in preschool-aged children may be able to distinguish abnormal lung function trajectories in children with a history of wheezing compared to healthy ones. MethodsChildren from a prospective, longitudinal community-based cohort performed annual intra-breath oscillometry (IB-OSC) measurements from age 3-years to 7-years. IB-OSC was performed using a single 10 Hz sinusoid while clinically asymptomatic. Linear mixed-effects models were developed to explore the effects of wheezing phenotypes, growth, and sex on seven IB-OSC outcome variables over time: resistance at end-expiration (ReE), resistance at end-inspiration (ReI), the tidal change in resistance ({Delta}R=ReE-ReI), reactance at end-expiration (XeE), reactance at end-inspiration (XeI), the tidal change in reactance ({Delta}X=XeE-XeI), and {Delta}X normalised by tidal volume ({Delta}X/VT). ResultsEighty-five children produced 375 acceptable IB-OSC measurements. Subjects were classified into one of three wheeze groups: never (n=36), transient (n=35), or persistent (n=14). After adjusting for height, children with persistent wheezing, compared to those who never wheezed, had -0.669 hPa{middle dot}s{middle dot}L -1 XeE (95% confidence interval [CI] -1.102 to -0.237, p<0.01), -0.465 hPa{middle dot}s{middle dot}L -1 {Delta}X (95%CI -0.772 to -0.159, p<0.01) and +1.433 hPa{middle dot}s{middle dot}L -1 {Delta}X/VT (95%CI +0.492 to +2.374, p<0.01). Increasing subject height had a significant effect on all IB-OSC resistance and reactance variables when adjusted for the effect of preschool wheezing. ConclusionsIB-OSC is feasible for tracking lung function in preschool-aged children, and intra-breath reactance outcomes may allow abnormal lung function to be identified early in asymptomatic children with a history of persistent wheeze.

Background Upper airway disease is common in primary ciliary dyskinesia (PCD), but management evidence is limited. We aimed to describe management practices and identify factors influencing management decisions. Methods Using data from the Ear-Nose-Throat (ENT) Prospective International Cohort of patients with PCD (EPIC-PCD) and an ENT-specialist survey across participating centres, we described management practices recorded at routine follow-up. We assessed clinical factors associated with practices via mixed-effects logistic regression models. In a subgroup of patients, we assessed factors associated with initiation or discontinuation of practices. Results We included 579 patients: median age 15 years, 46% female. Nasal rinsing (54%) and nasal corticosteroids (22%) were most frequently prescribed. Among 466 patients with available data, 47 had grommets (10%) and 42 hearing aids (9%). Nasal corticosteroids and rinsing were more frequently prescribed in patients with polyps (odds ratio [OR] 3.74, 95% confidence interval [CI] 1.80-7.76; OR 3.39, 95% CI 1.37-8.37) or turbinate hypertrophy (OR 1.89, 95% CI 1.03-3.47; OR 2.89, 95% CI 1.55-5.38), and upper airway nebulisation in patients with frequent nasal symptoms (OR 2.86, 95% CI 1.11-7.39). Management practices differed between centres, as seen also by the specialists survey responses. In 177 patients with multiple visits, initiation of nasal rinsing was associated with frequent nasal symptoms (OR 3.18, 95% CI 1.24-8.18) and turbinate hypertrophy (OR 3.21, 95% CI 1.20-8.59). Conclusion Upper airway disease management in PCD varies and is partly guided by symptom burden and clinical findings. This variation across centres highlights the need for care standardisation and PCD-specific management guidelines.

BackgroundIt is well established that there are different asthma phenotypes, but whereas determinants of atopic asthma are well studied, little is known about non-atopic asthma. We compared risk factors for atopy, atopic asthma (AA) in atopics, and non-atopic asthma (NAA) in non-atopics, in children in a wide variety of countries. MethodsUsing four studies, across 23 countries, we assessed asthma status and atopy (skin prick tests) for children aged 6-17, plus risk factors from housing, heating, pets, family, diet, and air-quality categories. Using mixed effects logistic regression models we assessed risk factors over 4 pathways: Pathway 1: non-atopic non-asthma to NAA; Pathway 2: non-atopic non-asthma to atopy (no asthma); Pathway 3: atopic non-asthma to AA; Pathway 4: non-atopic non-asthma to AA. We compared the log odds of risk factors between pathways using Pearsons correlation coefficient. ResultsOur final sample of 32741 children comprised 67% with neither atopy nor asthma, 15% with atopy but without asthma, 8% with AA and 10% with NAA. Risk factors were similar between Pathway 1 and Pathway 3 (Pearsons correlation = 0.81, 95% confidence interval = [0.68, 0.94]). In contrast, risk factors differed between Pathway 2 and Pathway 3 (-0.06, [-0.29, 0.17]). DiscussionThese findings indicate that although atopy increases the risk of asthma, the risk factors for subsequently developing asthma are generally the same in those with and without atopy. This raises important questions about the role of atopy in asthma, particularly whether it is an inherent part of the aetiological process or is coincidental. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSIt is well established that there are different phenotypes of asthma but little is known about risk factors for non-atopic asthma. What this study addsUsing a novel approach, we found that lifestyle and environmental risk factors for developing asthma are generally similar in atopic children and non-atopic children but the risk factors for atopy are quite different. How this study might affect research, practice or policyOur findings suggest that atopy and asthma may be coincidental in a large proportion of children who are defined as having atopic asthma. This has important implications for our understanding of the causes and mechanisms of different asthma phenotypes, and therefore prevention and treatment of asthma.

Objective: Upper respiratory infections (URI) are the major trigger of asthma exacerbations in children with asthma and are more likely to be reported by Black and Mexican American children compared to White children in the US. We aimed to evaluate the extent to which obesity, nicotine exposure, household size, and socioeconomic status (SES) explained this excess URI risk among all children and among children with asthma. Study Design: Data collected on children aged 6-17 years from the National Health and Nutritional Examination Survey (2007-2012) were analyzed using survey weights and a mediation approach. Household SES was analyzed as a cumulative score reflecting income poverty ratio, education, and rental housing. URI was defined as cough, cold, phlegm, runny nose, or other respiratory illness (excluding hay fever and allergies) in the past 7 days. Results: Obesity and serum cotinine, a marker of nicotine exposure, explained little to none of the excess risk of URI while SES explained 36.4% (95% CI=34.1, 38.6) in Black and 28.5% (95% CI=26.7, 30.5) in Mexican American children. Living in rental housing and income poverty ratio<2, explained half (49.6%, 95% CI=46.9-52.3) and 20% (19.7%, 95% CI=18.9-20.5) of the excess URI risk among Black children, respectively. In Mexican American children, rental housing and low educational attainment each explained approximately 15-17% of the excess URI risk. Results were comparable among children with asthma. Conclusions: Markers of poverty, such as rental housing, contributed substantially to the excess risk of URI among Black and Mexican American children, including among those with asthma.

ObjectiveTo examine whether the use of gas stoves in the home is associated with increased asthma severity among children and adolescents ages 0-17 in the US. MethodsUsing the 2020 CDC Asthma Call-Back Survey for children, the association between gas stove usage and childhood asthma symptoms, asthma attack or episode, and emergency department visit for asthma was assessed. With a cross-sectional study design, bivariate analyses and multivariable logistic regression were conducted. Survey weights were used in the analyses for US population-based estimates. ResultsChildren who live in a household that uses gas for cooking or has a gas stove had 1.133 (95% CI: 0.48, 2.68)) times the odds of having an asthma attack or episode within the past 12 months, 9.141 (95% CI: 1.99, 42.06) times the odds of having visited the emergency department or urgent care within the past 12 months, and 1.739 (95% CI: 1.02, 2.95) times the odds of recent symptoms of asthma compared to children who live in a household that does not use gas for cooking or does not have a gas stove, controlling for all confounders. There is an association between the usage of gas stoves and asthma symptoms, asthma attacks/episodes, and ED visits among asthmatic children. Reducing the exposure of gas stove usage should be a consideration in regards to existing and future interventions to prevent childhood asthma and reduce exacerbation of underlying childhood asthma.

We assessed how prevalence estimates of cough in 6-17-year-olds vary depending on the question asked in the population-based Luftibus in the school (LUIS) study. 3427 parents answered three different questions on cough. The prevalence of parent-reported cough varied substantially depending on the question: 25% of parents reported cough without a cold, 11% dry night cough and 5% that their child coughs more than other children. There was only partial overlap with 3% answering yes to all questions. This suggests that the exact question used to assess cough strongly affects prevalence estimates and must be taken into account when comparing studies.

BackgroundEffective initial asthma treatment in primary care requires a comprehensive assessment of airway inflammation and lung function impairment, including small airway dysfunction (SAD). We investigated the prevalence of type 2 (T2) inflammation and SAD in treatment-naive patients with uncontrolled asthma who received primary care, and assessed the utility of the Asthma Control Questionnaire-5 (ACQ-5) as a potential indicator of these factors. MethodsThis single-center retrospective study enrolled treatment-naive adults who presented with uncontrolled asthma (ACQ-5 score [&ge;] 1.5) between April 2020 and March 2022. T2 inflammation was assessed using blood eosinophil count (bEOS), fractional exhaled nitric oxide (FeNO), and total immunoglobulin E (IgE) levels. Patients with bEOS [&ge;] 300 cells/L and FeNO [&ge;] 50 ppb were designated "T2-high." SAD was defined as a forced expiratory flow between 25% and 75% of the vital capacity percentage predicted value (FEF25-75%pred) < 65%. ResultsAmong 192 patients, 87% exhibited an elevation in at least one T2 biomarker, with 47% meeting the T2-high criteria. An ACQ-5 score [&ge;] 3.0 significantly predicted T2-high status (odds ratio: 2.62, 95% confidence interval: 1.46-4.69, p = 0.00127). SAD was identified in 52% of patients, with ACQ-5 scores showing a strong negative correlation with FEF25-75%pred ({rho} = -0.583, p < 0.0001), particularly for nocturnal awakening score ({rho} = -0.728, p < 0.0001). ConclusionsOur findings revealed a high prevalence of T2 inflammation and SAD in treatment-naive patients with uncontrolled asthma who received primary care. The ACQ-5 demonstrates potential as a practical screening tool for these pathophysiological features, offering valuable guidance for initial treatment decisions where advanced diagnostic capabilities may be limited. Data availability statementData are available upon reasonable request. The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed in accordance with the Creative Commons Attribution Noncommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work noncommercially, and license their derivative works on different terms, provided that the original work is properly cited, appropriate credit is given, any changes are indicated, and the use is noncommercial. See: http://creativecommons.org/licenses/by-nc/4.0/. https://doi.org/10.5061/dryad.j6q573np9 What is already known on this topicDespite therapeutic advances, optimal asthma control remains elusive in many adult patients, particularly in primary care settings, where most treatments occur. Our understanding of type 2 inflammation and small airway dysfunction in treatment-naive patients with uncontrolled asthma remains limited. This knowledge gap hinders the development of enhanced management strategies among primary care practitioners. What this study addsThis study revealed high prevalence rates of type 2 inflammation (87%) and small airway dysfunction (52%) in treatment-naive patients with uncontrolled asthma receiving primary care, with 47% showing high-grade type 2 inflammation. An Asthma Control Questionnaire-5 (ACQ-5) score [&ge;] 3.0, predicted high-grade type 2 inflammation, while nocturnal symptoms correlated with small airway dysfunction. How this study might affect research, practice, or policyThese findings underscore the importance of considering type 2 inflammation and small airway dysfunction when initiating asthma treatment in primary care. ACQ-5 could serve as a practical tool for more targeted treatment decisions, while future research should focus on developing primary care-specific algorithms that combine ACQ-5 scores with biomarker profiles.

IntroductionThe burden of comorbidities in asthma patients significantly affects management strategies and outcomes. This study aimed to analyze the prevalence and trends of comorbidities among adults with asthma and to investigate their association with persistent asthma. MethodsThe study employed data from the Asthma Call-Back Survey (ACBS) to ascertain the prevalence and trends of comorbidities in adults with asthma. Comorbidities were self-reported binary responses. Asthma severity was categorized as intermittent or persistent based on established methodologies to derive asthma severity in the ACBS. Intermittent asthma includes those with current asthma who are well-controlled without being on long-term control medication (LTCM). Persistent asthma includes those on LTCM, regardless of asthma control status, and those not on LTCM whose asthma is not well controlled or is very poorly controlled. Weighted logistic regression controlling for confounders was used to determine the association of comorbidities and asthma severity. ResultsPrevalence of comorbidities in adults with asthma were as follows: hypertension (38.4%), major depressive disorder (35.2%), diabetes (17.2%), MI (5.3%), Angina/CHD (6.0%), Stroke (5.0%), and Emphysema/Chronic bronchitis/COPD (19.0%). Prevalence of all comorbidities were higher among adults with persistent asthma compared to intermittent asthma. MI, Angina/CHD, obesity, depression, COPD/emphysema/chronic bronchitis, and hypertension were associated with increased odds of persistent asthma. No association was found between diabetes, stroke, and persistent asthma. ConclusionComorbidities are associated with persistent asthma. These findings suggest a need for comprehensive healthcare strategy that address these intertwined health conditions along asthma.

BackgroundAsthma is a frequent comorbidity in children with sickle cell disease and has been associated with an increased risk of acute complications, particularly vaso-occlusive crises and acute chest syndrome. However, determinants of clinical severity among children with sickle cell disease and confirmed asthma remain poorly characterized, especially in tropical settings. This study aimed to identify factors associated with clinical severity in this population. MethodsWe conducted an observational study among children with sickle cell disease followed in French Guiana. The analysis was restricted to children with confirmed asthma. Clinical severity was defined as the occurrence of at least two hospitalizations during the 12 months preceding evaluation for vaso-occlusive crises and/or acute chest syndrome. Factors associated with severity were assessed using univariate and multivariate logistic regression analyses. ResultsA total of 138 children with sickle cell disease and confirmed asthma were included, of whom 49 (35.5%) presented a severe clinical form. In multivariate analysis, no variable was independently associated with clinical severity. However, a trend toward an increased risk of severe disease was observed among children living in rural areas (adjusted OR = 1.94; 95% CI: 0.77-4.86), while a trend toward a protective effect was observed for Strongyloides stercoralis infection (adjusted OR = 0.18; 95% CI: 0.02-1.51). Allergic sensitization, although frequent (64.5%), was not associated with clinical severity after adjustment (adjusted OR = 0.66; 95% CI: 0.31-1.44). ConclusionAmong children with sickle cell disease and confirmed asthma, more than one third experience severe clinical disease. Severity does not appear to be driven by allergy but may be influenced by environmental and contextual factors specific to tropical settings. These findings support a stratified approach to sickle cell-associated asthma to identify high-risk children and prevent avoidable acute complications.

BackgroundThe associations between maternal complications during pregnancy and childhood asthma have rarely been investigated in low and middle-income countries. We aimed to investigate the associations among the southern Chinese population, and to determine whether the associations were mediated through preterm birth, cesarean delivery, low birth weight and non-breasting feeding in the first 6 months or modified by childs lifestyles (smoking, body mass index(BMI), and sleep duration). MethodsWe conducted a retrospective cohort study of 208,190 children in Guangzhou, China. Information on maternal gestational hypertension, gestational diabetes, gestational anemia, and hepatitis B during pregnancy was extracted from medical records. Ever diagnosis of asthma of the children was obtained by questionnaire. We used binomial logistic regression models to estimate the adjusted odds ratios (aORs) and 95% confidential interval (CI) for childhood asthma. We conducted mediation analyses to estimate the indirect effects of gestational complications on childhood asthma mediated through preterm birth, cesarean delivery, low birth weight, and non-breastfeeding in the first 6 months. FindingsThe overall prevalence of ever diagnosed asthma was 1.3%. Gestational hypertension, gestational diabetes, gestational anemia, or hepatitis B during pregnancy was positively associated with ever diagnosed childhood asthma, with the aOR of 1.66(95%CI 1.31-2.10), 1.68(95%CI 1.40-2.02), 1.69(95%CI 1.49-1.91) and 1.54(95%CI 1.13-2.08), respectively. A stronger association was observed for 2 or more gestational complications (aOR= 2.34, 95%CI 1.71-3.23) than 1 gestational complication (aOR=1.80, 95%CI 1.62-1.99). The associations between maternal complications and childhood asthma did not differ by childs smoking, BMI, or sleep duration, except that the aOR for maternal gestational hypertension was significantly higher in children who were active smoker (aOR=5.68, 95%CI 2.09-15.42) than those who were non-smoker (aOR=1.56, 95%CI 1.21-2.00). A small proportion of the associations were mediated through preterm birth, cesarean delivery, low birth weight, and non-breastfeeding in the first 6 months. InterpretationGestational hypertension, diabetes, anemia, or hepatitis B during pregnancy was significantly associated with childhood asthma in the southern Chinese population, and the associations were partially explained by the mediation effects of cesarean delivery, preterm birth, low birthweight and non-breastfeeding in the first 6 months. Author summaryO_ST_ABSWhy was this study done?C_ST_ABSO_LIEarly stage of life is a sensitive period for the development of respiratory health, but there is rarely study investigated the associations between maternal complications during pregnancy and childhood asthma in low and middle income countries. C_LIO_LIBirth outcomes, breastdfeeding and childrens lifestyles are associated with athma, but it remain unclear whether the effects of maternal complications during the pregnancy on childhood asthma could be moderated by lifestyles of children or mediated through birth outcomes and breastfeeding. C_LI What did the researchers do and find?O_LIIn this large cohort study of more than 220,000 participants, we found gestational hypertension, diabetes, anemia, or hepatitis B during pregnancy was significantly associated with childhood ever diagnosed asthma. C_LIO_LIA stronger association was observed for 2 or more gestational complications than 1 gestational complication. C_LIO_LIThe associations between maternal complications and childhood asthma did not differ by childs smoking, body mass index, or sleep duration, but a small proportion of the associations were mediated through preterm birth, cesarean delivery, low birth weight, and non-breastfeeding in the first 6 months. C_LI What do these findings mean?O_LIThe findings suggest that interventions to address childhood asthma should consider potential associations with maternal complications. C_LIO_LITo avoid cesarean delivery, preterm birth, low birthweight and non-breastfeeding in the first 6 months may reduce the effects of maternal complication during pregnancy on childhood asthma. C_LI

ObjectivesA current diagnosis of asthma cannot be objectively confirmed in many patients with physician-diagnosed asthma. Estimates of resource use in overdiagnosed cases of asthma are necessary to measure the burden of overdiagnosis and evaluate strategies to reduce this burden. We assessed the difference in asthma-related healthcare resource use between patients with a confirmed asthma diagnosis and those with asthma ruled out.\n\nDesignPopulation-based prospective cohort study.\n\nSettingParticipants were recruited through random-digit dialling of both landlines and mobile phones in BC, Canada.\n\nParticipantsWe included 345 individuals [&ge;]12 years of age with a self-reported physician diagnosis of asthma which was confirmed by a bronchodilator reversibility or methacholine challenge test at the end of the 12-month follow-up.\n\nPrimary and secondary outcome measuresSelf-reported annual asthma-related direct healthcare costs (2017 Canadian dollars), outpatient physician visits, and medication use from the Canadian healthcare system perspective.\n\nResultsAsthma was ruled out in 86 (24.9%) participants. Average annual asthma-related direct healthcare costs for participants with confirmed asthma were $497.9 (SD $677.9), and $307.7 (SD $424.1) for participants with asthma ruled out. In the adjusted analyses, a confirmed diagnosis was associated with higher direct healthcare costs (Relative Ratio [RR]=1.60, 95%CI 1.14-2.22), increased rate of specialist visits (RR=2.41, 95%CI 1.05-5.40) and reliever medication use (RR=1.62, 95%CI 1.09-2.35), but not primary care physician visits (p=0.10) or controller medication use (p=0.11).\n\nConclusionsA quarter of individuals with a physician diagnosis of asthma did not have asthma after objective re-evaluation. These participants still consumed a significant amount of asthma-related healthcare resources. The population-level economic burden of asthma overdiagnosis could be substantial.\n\nStrengths and limitations of this studyO_LIParticipants were recruited through random sampling of the general population in the province of British Columbia.\nC_LIO_LIAsthma diagnosis was confirmed or ruled out using sequential guideline-recommended objective airway tests.\nC_LIO_LIHealthcare resource use was self-reported, potential recall bias may have led to reduced accuracy.\nC_LIO_LIThe study was unable to evaluate the indirect costs of overdiagnosis or the cost-savings from correcting the diagnosis.\nC_LIO_LIThe generalizability of the results may be limited by regional differences in medical costs and practices.\nC_LI

Pediatric asthma exacerbations are a frequent cause of emergency department (ED) visits and hospitalizations, yet accurate risk prediction remains limited and no consensus risk scores exist. Using UF Health electronic health records (EHRs) from 2011-2023, we evaluated two computable phenotypes (i.e., CAPriCORN and COMPAC) to predict exacerbations over 6-, 12-, and 24-month horizons. Exacerbations were defined using a validated composite of diagnosis codes from ED, inpatient, or outpatient encounters combined with systemic corticosteroids prescriptions. Several commonly used machine learning (ML) models were trained with stratified five-fold cross-validation, Bayesian hyperparameter optimization, and Youdens J thresholding. XGBoost achieved the best performance, with SHapley Additive exPlanations (SHAP) highlighting note-derived symptom terms and rescue-medication use as dominant predictors. Future work will focus on external validation and assessment of generalizability. This interpretable, text-integrated framework may support child-specific risk stratification and inform EHR-based decision support for timely pediatric asthma management.

Asthma is a long-term inflammatory disease affecting airways and lungs with usual onset in childhood. Its cause is not fully understood up to now. Here, using single-cell RNA sequencing, we profile peripheral blood mononuclear cells (PBMCs) from three pediatric patients with onset asthma and four age-matched healthy controls to investigate the cellular etiology of childhood asthma. The overall expression features among three asthma patients PBMCs demonstrate that innate immunity is commonly upregulated while adaptive immunity is commonly downregulated in childhood asthma, but each patient has different molecular phenotypes. The analyses of the expression profiles of hematopoietic stem and progenitor cells (HSPCs) further show that the HSPCs of asthma patients have heterogeneous expression backgrounds with more specific differentially expressed genes (DEGs) in each patient than common DEGs and a common feature of low S100 protein binding gene expression. S100A8, S100A9, S100A12, and RETN are universally upregulated in various cell types of asthma patients. The cell developmental trajectories in three asthma cases exhibit an abnormal immune cell development pattern compared to that in health control. The dysregulated lymphoid lineage development is observed in all 3 patients, but there is no identical abnormal pattern for each patient. The pseudo-time analyses of gene expression show that the expression dynamics of two proto-oncogenes, JUN and SPI1, and six inflammatory response related genes (S100A8, S100A9, S100A12, IL7R, IL32, CCL5) are relevant to abnormal immune cell development in asthma patients. The cell-cell communication analyses reveal the contribution of incoming annexin signal towards dendritic cells and the outgoing resistin signal from dendritic cells to asthma heterogeneity. Interestingly, the plasma blast cells of asthma patient 3 with severe symptoms exhibit dual cell identities of both plasma blast cells and T cells. Our scRNA-Seq analyses for three asthma patients reveal a complex cellular etiology for childhood asthma and provide a new research direction for the comprehensive and systematic understanding of key molecular mechanisms of childhood asthma.