Pediatric Pulmonology

BackgroundExercise-induced breathing problems with similar clinical presentations can have different aetiologies. This makes distinguishing common diagnoses such as asthma, extrathoracic and thoracic dysfunctional breathing (DB), insufficient fitness, and chronic cough difficult. ObjectiveWe studied which parent-reported, exercise-induced symptoms (EIS) can help distinguish diagnoses of EIS in children seen in respiratory outpatient clinics. MethodsThis study was nested in the Swiss Paediatric Airway Cohort (SPAC), an observational study of children aged 0-17 years referred to paediatric respiratory outpatient clinics in Switzerland. We studied children aged 6-17 years and compared information on EIS from parent-completed questionnaires between children with different diagnoses. We used multinomial regression to analyse whether parent-reported symptoms differed between diagnoses (asthma as base). ResultsAmong 1109 children, EIS were reported for 732 (66%) (mean age 11 years, 318 of 732 [43%] female). Among the symptoms, dyspnoea best distinguished thoracic DB (relative risk ratio [RRR] 5.4, 95%CI 1.3-22) from asthma. Among exercise triggers, swimming best distinguished thoracic DB (RRR 2.4, 95%CI 1.3-6.2) and asthma plus DB (RRR 1.8, 95%CI 0.9-3.4) from asthma only. Late onset of EIS was less common for extrathoracic DB (RRR 0.1, 95%CI 0.03-0.5) and thoracic DB (RRR 0.4, 95%CI 0.1-1.2) compared with asthma. Localisation of dyspnoea (throat vs. chest) differed between extrathoracic DB (RRR 2.3, 95%CI 0.9-5.8) and asthma. Reported respiration phase (inspiration or expiration) did not help distinguish diagnoses. ConclusionParent-reported symptoms help distinguish different diagnoses in children with EIS. This highlights the importance of physicians obtaining detailed patient histories. Highlights boxO_LIWhat is already known about this topic? Experts suggest that information about the symptoms and their onset and duration can assist accurate diagnosis of children with exercise-induced respiratory problems, but no original studies have tested this. (29/35 words) C_LIO_LIWhat does this article add to our knowledge? Exercise-induced symptoms reported by parents and further information about their onset, triggers, and effects of treatment help differentiate diagnoses in children with exercise-induced respiratory problems. (25/35 words) C_LIO_LIHow does this study impact current management guidelines? Our results emphasize the importance of taking detailed symptom histories of children with exercise-induced problems, and suggest which questions are most helpful. C_LI

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.

INTRODUCTIONBronchial asthma (BA) is a heterogeneous pulmonary disease with various phenotypes based on detection of multiple biomarkers. However, most of the biomarkers are still experimental and present limitations for clinical practice. OBJECTIVEThe purpose of this study was to investigate the relationship between the level of the available T2-inflammatory biomarkers in childhood with poor asthma control and features of asthma management. MATERIAL AND METHODSThe study comprised 100 patients aged 5-17 years (median age 13 years) with an established bronchial asthma diagnosis. The level of asthma control of each patient was assessed by the Asthma Control Test (ACT and C-ACT) and the Composite Asthma Severity Index (CASI). T2-inflammatory biomarkers of the mucous membranes of the respiratory tract include total immunoglobulin E (IgE total) levels, peripheral blood eosinophil levels, fractional exhaled nitric oxide (FeNO) and a nasal smear eosinophil count. A measure of association was determined by standard statistical methods for data analysis. RESULTSDespite the prescribed basic therapy, the majority of children do not achieve adequate asthma symptom control. This research revealed that 43% of patients had at least one or more elevated markers of T2-inflammation. High levels of IgE total, increased levels of blood eosinophils ([≥]400 cells/{micro}L), as well as high FeNO values ([≥] 20 ppb) prevail in children with partially controlled and uncontrolled asthma. The most significant biomarker of poor asthma control in children is the total serum IgE concentration [≥] 100 IU/ml. In addition, a significant positive correlation was found between peripheral blood eosinophil levels and the ACT/C-ACT scores (r=0.287, p=0.0039). CONCLUSIONAllergic asthma in children is typically associated with Th2-lymphocytes predominance and eosinophilic airway inflammation. T2-inflammatory biomarkers may be useful in assessing airway inflammation activity and asthma-control assessment in children.

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.

ObjectiveExercise-induced respiratory symptoms (EIS) are common in childhood and reflect different diseases that can be difficult to diagnose. In children referred to respiratory outpatient clinics for EIS, we compared the diagnosis proposed by the referring primary care physician with the final diagnosis from the outpatient clinic and described diagnostic tests performed and treatment prescribed after the diagnostic evaluation. DesignObservational study nested in the Swiss Paediatric Airway Cohort (SPAC), which includes respiratory outpatients aged 0-16 years. PatientsWe included children with EIS as main reason for referral. Information about diagnostic investigations, final diagnosis, and treatment prescribed came from outpatient records. Results214 were referred for EIS (mean age 12 years, 99 (46%) female). The final diagnosis was asthma in 115 (54%), extrathoracic dysfunctional breathing (DB) in 35 (16%), thoracic DB in 22 (10%), asthma plus DB in 23 (11%), insufficient fitness in 10 (5%), chronic cough in 6 (3%), and other diagnoses in 3 (1%). Final diagnosis differed from referral diagnosis in 115 (54%). Spirometry, body plethysmography and measurements of exhaled nitric oxide were performed in almost all; exercise-challenge tests in a third. 91% of the children with a final diagnosis of asthma were prescribed inhaled medication and 50% of children with DB were referred to physiotherapy. ConclusionsDiagnosis given at the outpatient clinic often differed from the diagnosis suspected by the referring physician. Diagnostic evaluation, management and follow-up were inconsistent between clinics and diagnostic groups, highlighting the need for diagnostic guidelines in children seen for EIS. Mandatory statements for Archives of Disease in ChildhoodO_ST_ABSWhat is already known on this topic (2-3 statements of max 25 words)C_ST_ABSO_LIExercise-induced symptoms are common in childhood but not easy to diagnose because different diagnoses share similar clinical presentations C_LIO_LIOnly few studies focused on children with exercise-induced symptoms and all have included selected groups of patients with difficult-to-diagnose problems C_LI What this study adds (2-3 statements of max 25 words)O_LIExercise-induced respiratory symptoms was the main reason for referral in one fifth of the children referred to paediatric respiratory outpatient clinics. C_LIO_LIDysfunctional breathing is an under-recognised diagnosis; it was frequently diagnosed in the outpatient clinic (in 37%) but rarely suspected by the referring physician (6%) C_LIO_LIDiagnostic evaluation, management, and follow-up were inconsistent between clinics highlighting the need for diagnostic guidelines in children seen for EIS. C_LI

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.

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.

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.

Background and ObjectivesThe COVID-19 pandemic has had a profound impact on healthcare access and utilization, which could have important implications for children with chronic diseases, including asthma. We sought to evaluate changes in healthcare utilization and outcomes in children with asthma during the COVID-19 pandemic. MethodsWe used electronic health records data to evaluate healthcare use and asthma outcomes in 3,959 children and adolescents, 5-17 years of age, with a prior diagnosis of asthma who had a history of well child visits and encounters within the healthcare system. We assessed all-cause healthcare encounters and asthma exacerbations in the 12-months preceding the start of the COVID-19 pandemic (March 1, 2019 - February 29, 2020) and the first 12-months of the pandemic (March 1, 2020 - February 28, 2021). ResultsAll-cause healthcare encounters decreased significantly during the pandemic compared to the preceding year, including well child visits (48.1% during the pandemic vs. 66.6% in the prior year; p < 0.01), emergency department visits (9.7% vs. 21.0%; p < 0.01), and inpatient admissions (1.6% vs. 2.5%; p < 0.01), though there was over a 100-fold increase in telehealth encounters. Asthma exacerbations that required treatment with systemic steroids also decreased (127 vs. 504 exacerbations; p < 0.01). Race/ethnicity was not associated with changes in healthcare utilization or asthma outcomes. ConclusionThe COVID-19 pandemic corresponded to dramatic shifts in healthcare utilization, including increased telehealth use and improved outcomes among children with asthma. Social distancing measures may have also reduced asthma trigger exposure.

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.

ObjectivesTo investigate the clinical efficacy of long-term of low-dose inhaled glucocorticoid (ICS) in the treatment on children with bronchial asthma, and to evaluate its effects on the height, weight and expression of serum insulin-like growth factor of children with bronchial asthma. Methods91 children with bronchial asthma treated in our hospital from January 2017 to December 2017 were chosen, and 31 healthy children without asthma history in our hospital were selected as the control group (Group C); For the different treatment methods comparison, 91 children with bronchial asthma were divided into treatment group A (48 children) and treatment group B (43 children) randomly. In treatment group A, children were treated with low-dose ICS for more than 1 year; in treatment group B, children were treated with low-dose ICS for less than 1 year or received low-dose ICS for less than 2 months/year. For treatment evaluation, the asthma control test (C-ACT) were scored at 0 months, 12 months and 24 months in three groups, and the height and weight of children, the levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in serum in each group were also measured. ResultsIn the control group, the C-ACT scores were increased with time (P<0.01); the C-ACT scores of treatment group A at 12 months and at 24 months was significantly higher than that of treatment group B (P<0.05); there was no significant difference in height and weight between the treatment group and the control group at months, 12 months and 24 months after treatment (P>0.05); there was no significant difference in the expression levels of IGF-1 and IGFBP-3 in serum between treatment group and control group (P>0.05). Compared with the C-ACT scores in treatment group A and treatment group B at 0 month, the C-ACT scores were significantly higher at 12 months and at 24 months, and there was a statistical difference among 0 month, 12 months and at 24 months in treatment group A and treatment group B (P<0.01); The C-ACT score of treatment group A at the 12 month was significantly higher than that in treatment group B at the 12 months(P<0.05), and the C-ACT score in treatment group A at the 24 months was significantly higher than that of treatment group B (P<0.001). ConclusionsTreatment for children with bronchial asthma by long-term use of low-dose ICS is safe and effective, it does not affect health and development of children with bronchial asthma; children with bronchial asthma were treated with low-dose ICS for more than 1 year had a better effective than children were treated with low-dose ICS for less than 1 year or received low-dose ICS for less than 2 months/year.

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.

IntroductionWe aimed to evaluate the longitudinal relationships, both at between- and within-person levels, that adherence to inhaled corticosteroids-based maintenance treatment and inhalation technique present with symptom control, exacerbations, and health-related quality of life (HRQoL) in children and adolescents with asthma. MethodsParticipants (6-14 years old) from the ARCA (Asthma Research in Children and Adolescents) cohort - a prospective, multicenter, observational study (NCT04480242) - were followed for a period from 6 months to 5 years, via computer-assisted telephone interviews and a smartphone application. The Medication Intake Survey-Asthma (MIS-A) was administered to assess the implementation stage of adherence; and the Inhalation Technique Questionnaire (InTeQ) to assess the five key steps when using an inhaler. Symptoms control was measured with the Asthma Control Questionnaire (ACQ), and HRQL with the EQ-5D and the PROMIS-Pediatric Asthma Impact Scale (PROMIS-PAIS). Multilevel longitudinal mixed models were constructed separately with symptom control, exacerbation occurrence, EQ-5D, and PROMIS-PAIS as dependent variables. ResultsOf 360 participants enrolled, 303 (1203 interviews) were included in the symptom control and exacerbation analyses, 265 (732) in the EQ-5D, and 215 (619) in the PROMIS-PAIS. Around 60% of participants were male and most underwent maintenance treatment with inhaled corticosteroids plus long-acting {beta}-agonists in a fixed dose (68-74%). Within-person variability was 83.6% for asthma control, 98.6% for exacerbations, 36.4% for EQ-5D and 49.1% for PROMIS-PAIS. At within-person level, patients with higher adherence had better symptom control (p=0.002) and HRQoL over time (p=0.016). Patients with better inhalation technique reported worse HRQoL simultaneously (p=0.012), but better HRQoL in future assessments (p=0.012). Frequency of reliever use was associated with symptom control (p<0.001), exacerbation occurrence (p<0.001), and HRQoL (p=0.042); and boys were more likely to present better symptom control and HRQoL than girls. ConclusionOur results confirm longitudinal associations at within-person level of the two indicators of quality use of inhalers: for adherence to maintenance treatment with symptom control and HRQoL, and for inhalation technique with HRQoL. Although treatment adherence showed to be excellent, a third part of participants reported a suboptimal inhalation technique, highlighting the need of actions for improving asthma management of pediatric population.

RationaleWhether asthma constitutes a risk factor for COVID-19 is unclear. MethodsWe performed a systematic literature search in three stages: First, we reviewed PubMed, EMBASE and CINAHL for systematic reviews of SARS-CoC-2 and COVID-19 in pediatric populations, and reviewed their primary articles; next, we searched PubMed for studies on COVID-19 or SARS-CoV-2 and asthma/wheeze, and evaluated whether the resulting studies included pediatric populations; lastly, we repeated the second search in BioRxiv.org and MedRxiv.org to find pre-prints that may have information on pediatric asthma. ResultsIn the first search, eight systematic reviews were found, of which five were done in pediatric population; after reviewing 67 primary studies we found no data on pediatric asthma as a comorbidity for COVID-19. In the second search, we found 25 results in PubMed, of which five reported asthma in adults, but none included data on children. In the third search, 14 pre-prints in MedRxiv were identified with data on asthma, but again none with pediatric data. We found only one report by the U.S. CDC stating that 40/345 (~11.5%) children with data on chronic conditions had "chronic lung diseases including asthma". ConclusionThere is scarcely any data on whether childhood asthma (or other pediatric respiratory diseases) constitute risk factors for SARS-CoV-2 infection or COVID-19 severity. Studies are needed that go beyond counting the number of cases in the pediatric age range.

BackgroundOscillometry may be a feasible and sensitive tool for objective remote monitoring of paediatric asthma. MethodsSchool-aged cohorts of healthy, well controlled and poorly controlled asthma (defined as [&ge;]2 exacerbations within the preceding 12m) performed daily home-based oscillometry for 3-4 months (C-100 tremoflo, Thorasys Ltd), alongside objective measures of asthma control (ACQ weekly, ACT monthly), medication use (Hailie(R)) and exacerbations. Day-to-day variability was calculated as coefficient of variation (CV) for resistance at 5Hz (R5), reactance (X5) and Area under reactance curve (AX). We examined the ability to differentiate asthma from health and correlations with asthma control and exacerbation burden. Clinical exacerbation phenotypes were examined using principal component analysis and k-means clustering of oscillometry, symptoms, breathing parameters and symptoms. ResultsFeasibility was 74.9 {+/-} 16.0% in health (n=13, over 93.7 {+/-} 16.2 days) and 80.6 {+/-} 12.9% in asthma (n=42, over 101.6 {+/-} 24.9 days; 17 well controlled 27 poor asthma control). Significantly higher day-to-day variability in all oscillometry indices occurred in asthma, vs. health, and with worsening asthma control. CV R5 when clinically stable (CV R5 stable) was the best discriminator of asthma from health (AUC 0.87, p=0.00001). CV R5 correlated with all measures of asthma control and asthma exacerbation burden, r 0.41-0.52 (all p<0.01). Two exacerbation phenotypes were found based on oscillometry data in the pre- exacerbation period, characterised by severity of impairment of R5, X5, AX and CV R5 (n=12 more severe). Findings were similar using post-exacerbation period oscillometry data (n=8 more severe). Symptoms did not differ across clusters. ConclusionsHome-based oscillometry monitoring was highly feasible over extended periods in school-aged asthmatics. Utility was evidenced by improved ability to differentiate asthma from health, reflect asthma control and exacerbation burden and phenotype exacerbations. TAKE HOME MESSAGES- It is highly feasible to perform daily parent-supervised FOT monitoring for extended periods up to 4 months duration in school-aged children - In contrast to single-session based oscillometry indices, day-to-day variability in oscillometry indices were significantly higher in children with asthma compared to healthy controls, and differentiated levels of asthma control. The best performing parameter was CV R5. - All day-to-day variability indices correlated with measures of asthma control, with the best performing parameter CV R5 during stable periods (i.e., not including exacerbation periods). - Amongst asthmatics, day-to-day variability was greater during exacerbation periods than during non-exacerbation periods. Day-to-day variability correlated with measures of exacerbation burden, with the strongest correlations observed with CV R5 during stable periods - Day-to-day variability identified two distinct clusters of exacerbation, which were not identified by conventional measures or symptom based assessment. AUTHOR CONTRIBUTIONSO_LIConception and design: PDR, CT, GGK C_LIO_LIRecruitment, acquisition, analysis and/or interpretation of data: JH, AW, KH, SP, EdQA, AB, PF, DF, GJ, CP, CT, GGK, PDR C_LIO_LIWriting the manuscript or revising it critically: JH, AW, KH, SP, EdQA, AB, PF, DF, GJ, CP, HS, GGK, CT, PDR C_LI

BackgroundLung oscillometry is an emerging lung function test for assessing obstructive airway disease. Comparisons of oscillometry parameters and their bronchodilator responsiveness (BDR) between bronchial asthma and chronic obstructive pulmonary disease (COPD) patients are limited. Research QuestionDo oscillometry parameters and their BDR differ between stable asthma and COPD patients with similar severity of airflow obstruction? Study Design and MethodsWe included 467 consecutive adult patients with a clinical history of asthma (n=187) or COPD (n=280). Oscillometry, spirometry, and body plethysmography were performed before and after inhaling 400 g of salbutamol. Patients were stratified based on the severity of airflow obstruction in spirometry. The z scores of the oscillometry parameters were used for the comparison. The BDR of oscillometry parameters with other lung function parameters was also compared. ResultsThe average age of the study population was 54.9 years, and 76.4% were male. COPD patients were older, had a greater number of smokers, and had poorer lung function. The magnitude of oscillometry parameters worsened with increasing severity of airflow obstruction, regardless of the underlying disease. Asthma patients, particularly those with moderate and severe airway obstruction, had significantly higher R5 and R19 than COPD patients. The within- and whole-breath X5 of asthma were not different from those of COPD patients with similar severities of airflow obstruction. Expiratory flow limitation at tidal breaths ({Delta}X5 > 0.28 kPa/L/s) was observed in both asthma and COPD patients across all severities of airflow obstruction. The proportion of BDR in oscillometry was significantly lower than that in spirometry for both asthma (35.3% vs. 57.1%; p<0.01) and COPD patients (19.3% vs. 47.1%; p=0.02). InterpretationOscillometry parameters except for R5 and R19 did not differ between asthma and COPD patients with similar severities of airflow obstruction. Similar to spirometry, COPD patients had lower BDR in oscillometry than asthma patients. Take-home PointsO_ST_ABSStudy QuestionC_ST_ABSAre oscillometry parameters and their bronchodilator responsiveness different between bronchial asthma and COPD patients with similar severities of airflow obstruction? ResultsWe compared the FOT between 187 bronchial asthma and 280 COPD patients. Except for R5 and R19, the severity and distribution of high oscillometry parameters did not differ between asthma and COPD patients. InterpretationThe severity of oscillometry abnormalities is primarily determined by the severity of airflow obstruction, not the underlying disease.

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.

BackgroundChildren with night cough but no wheeze might have a mild form of asthma (cough variant asthma), sharing risk factors with children who wheeze, and possibly developing wheeze later. MethodsWe compared risk factors of children with isolated night cough and children with wheeze in the Leicester Respiratory Cohort study at ages 1, 4, 6, and 9 years. We also compared prognoses of children with isolated night cough, children with wheeze, and asymptomatic children. ResultsAmong 4,101 children at age 1 year, 2,854 at 4, 2,369 at 6, and 1,688 at 9 years, the prevalence of isolated night cough was 10% at age 1 and 18% in older children, while prevalence of wheeze decreased from 35% at 1 year to 13% at age 9. Although many risk factors were the same for cough and wheeze, day care, reflux, and family history of bronchitis were more strongly associated with cough, and male sex and family history of asthma with wheeze. Over one-third of pre-schoolers with cough continued to cough at school age, but their risk of developing wheeze was similar to that of children asymptomatic at earlier surveys. Wheeze tracked more strongly throughout childhood than cough. ConclusionsSome risk factors for cough and wheeze were shared and some were not; there was little evidence that children with isolated night cough have an increased risk of future wheeze. This suggests that only a fraction of children with isolated night cough might have a variant of asthma, if at all.

IntroductionAsthma poses a diagnostic challenge due to its intermittent symptoms and variable airflow obstruction. Diagnostic assessments such as spirometry and bronchodilator response are frequently non-diagnostic, necessitating confirmatory bronchial provocation testing. Biomarkers of type-2 inflammation --exhaled nitric oxide (FeNO) and blood eosinophil counts (BEC)-- are useful in asthma, but their diagnostic values in children and in combination (FeNO+BEC) are unclear. This systematic review will evaluate the diagnostic accuracy of FeNO alone or in combination with BEC in paediatric and adult asthma. Methods and AnalysisThis protocol is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. The review will include studies of any design on the diagnostic accuracy of FeNO with or without BEC in asthma compared to the reference standards bronchodilator response and provocation testing in patients [&ge;] 5 years old selected from MEDLINE, Embase, and Cochrane CENTRAL databases. Screening, study selection, and data extraction will be independently performed by two reviewers. Risk of bias will be assessed using QUADAS-2 and QUADAS-C. Meta-analysis will be carried out by pooling the sensitivity and specificity of FeNO alone or in combination with BEC in a bivariate random effects model allowing the generation of summarised operating characteristic curves and summary points. Further analysis utilising a multiple thresholds model will enable the computation of diagnostic thresholds for FeNO. Ethics and DisseminationNo patient data will be stored without prior approval from ethics committee. The findings will be submitted in a peer-reviewed publication. RegistrationPROSPERO CRD42023489738 SOCIAL MEDIA MESSAGEDiagnosing asthma is challenging. Spirometry and bronchodilator reversibility are often non-diagnostic, calling for provocation testing. Our systematic review will explore complementary approaches using FeNO with and without the blood eosinophil count.

BackgroundWheezing and asthma exacerbations are leading causes of pediatric hospital admissions. Predicting which children will experience persistent exacerbations remains challenging. Prior research has identified immune endotypes in the nasal epithelium of children with acute asthma and wheezing, characterized by varying balances of interferons and inflammatory markers. Notably, children exhibiting low interferon responses coupled with high inflammation are at an increased risk for recurrent respiratory exacerbations. ObjectiveThis study aims to determine if blood-based gene network biomarkers can detect immune endotypes in children presenting with acute wheeze and asthma, potentially serving as predictive tools for future exacerbations. MethodsWe conducted gene expression analysis using microarrays of peripheral blood mononuclear cell (PBMC) samples from pediatric patients who presented to hospital for acute wheeze and asthma. Personal network inference was employed to discern gene expression patterns, facilitating the classification of patients into distinct immune endotypes. ResultsThree immune endotypes were identified. One endotype, characterized by low interferon responses and elevated expression of both innate and adaptive immune pathways, was significantly associated with an increased risk of subsequent hospital respiratory presentations and a persistent pattern of respiratory exacerbations over time. ConclusionPBMC-based personal gene network biomarkers can effectively identify immune endotypes correlating with clinical outcomes in pediatric asthma. The high-risk endotype represents a potential treatable trait in acute wheezing episodes. Therapeutic strategies aimed at enhancing interferon responses and/or reducing inflammation may benefit this subgroup. Clinical ImplicationsWe have identified a potential treatable trait of paediatric asthma and wheezing. Classifying children based on their immune profiles may enable tailored management strategies aligned with their future exacerbation risk. Capsule SummaryPersonal gene network biomarkers effectively identifies immune endotypes correlating with clinical outcomes in pediatric asthma. The high-risk endotype, marked by low interferon responses and high innate and adaptive inflammation represents a potential treatable trait in acute wheezing episodes.