Phenotypes of cough in children: A latent class analysis.

INTRODUCTION: Distinguishing phenotypes among children with cough helps understand underlying causes. Using a statistical data-driven approach, we aimed to identify and validate cough phenotypes based on measurable traits, physician diagnoses, and prognosis. METHODS: We used data from the Swiss Paediatric Airway Cohort and included 531 children aged 5-16 years seen in outpatient clinics since 2017. We included children with any parent-reported cough (i.e. cough without a cold, cough at night, cough more than other children, or cough longer than 4 weeks) without current wheeze. We applied latent class analysis to identify phenotypes using nine symptoms and characteristics and selected the best model using the Akaike information criterion. We assigned children to the most likely phenotype and compared the resulting groups for parental atopy history, comorbidities, spirometry, fractional exhaled nitric oxide (FeNO), skin prick tests and specific IgE, physician diagnoses, and 1-year prognosis. RESULTS: We identified four cough phenotypes: non-specific cough (26%); non-allergic infectious and night cough with snoring and otitis (4%); chronic allergic dry night cough with snoring (9%); and allergic non-infectious cough with rhino-conjunctivitis (61%). Children with the allergic phenotype often had family or personal history of atopy and asthma diagnosis. FeNO was highest for the allergic phenotype [median 17.9 parts per billion (ppb)] and lowest for the non-allergic infectious phenotype [median 7.0 parts per billion (ppb)]. Positive allergy test results differed across phenotypes (p < .001) and were most common among the allergic (70%) and least common among the non-specific cough (31%) phenotypes. Subsequent wheeze was more common among the allergic than the non-specific phenotype. CONCLUSION: We identified four clinically relevant cough phenotypes with different prognoses. Although we excluded children with current wheeze, most children with cough belonged to allergy-related phenotypes.

Predictors of asthma control differ from predictors of asthma attacks in children: The Swiss Paediatric Airway Cohort.

BACKGROUND: It is unclear if predictors of asthma attacks are the same as those of asthma symptom control in children. OBJECTIVE: We evaluated predictors for these two outcomes in a clinical cohort study. METHODS: The Swiss Paediatric Airway Cohort (SPAC) is a multicentre prospective clinical cohort of children referred to paediatric pulmonologists. This analysis included 516 children (5-16 years old) diagnosed with asthma. At baseline, we collected sociodemographic information, symptoms, personal and family history and environmental exposures from a parental baseline questionnaire, and treatment and test results from hospital records. Outcomes were assessed 1 year later by parental questionnaire: asthma control in the last 4 weeks as defined by GINA guidelines, and asthma attacks defined as any unscheduled visit for asthma in the past year. We used logistic regression to identify and compare predictors for suboptimal asthma control and asthma attacks. RESULTS: At follow-up, 114/516 children (22%), reported suboptimal asthma control, and 114 (22%) an incident asthma attack. Only 37 (7%) reported both. Suboptimal asthma control was associated with poor symptom control at baseline (e.g. ≥1 night wheeze/week OR: 3.2; 95% CI: 1.7-6), wheeze triggered by allergens (2.2; 1.4-3.3), colds (2.3; 1.4-3.6) and exercise (3.2; 2-5), a more intense treatment at baseline (2.4; 1.3-4.4 for Step 3 vs. 1), history of preschool (2.6; 1.5-4.4) and persistent wheeze (2; 1.4-3.2), and exposure to tobacco smoke (1.7; 1-2.6). Incident asthma attacks were associated with previous episodes of severe wheeze (2; 1.2-3.3) and asthma attacks (2.8; 1.6-5 for emergency care visits), younger age (0.8; 0.8-0.9 per 1 year) and non-Swiss origin (0.3; 0.2-0.5 for Swiss origin). Lung function, exhaled nitric oxide (FeNO) and allergic sensitization at baseline were not associated with control or attacks. CONCLUSION: Children at risk of long-term suboptimal asthma control differ from those at risk of attacks. Prediction tools and preventive efforts should differentiate these two asthma outcomes.

ERS International Congress 2022: highlights from the Paediatrics Assembly.

This review has been prepared by the Early Career Members and Chairs of the European Respiratory Society (ERS) Assembly 7: Paediatrics. We here summarise the highlights of the advances in paediatric respiratory research presented at the ERS International Congress 2022. The eight scientific groups of this Assembly cover a wide range of research areas, including respiratory physiology and sleep, asthma and allergy, cystic fibrosis (CF), respiratory infection and immunology, neonatology and intensive care, respiratory epidemiology, bronchology, and lung and airway developmental biology. Specifically, we report on abstracts presented at the congress on the effect of high altitude on sleep, sleep disorders, the hypoxic challenge test, and measurements of ventilation inhomogeneity. We discuss prevention of preschool wheeze and asthma, and new asthma medications. In children with CF, we describe how to monitor the effect of CF transmembrane conductance regulator modulator therapy. We present respiratory manifestations and chronic lung disease associated with common variable immunodeficiency. Furthermore, we discuss how to monitor respiratory function in neonatal and paediatric intensive care units. In respiratory epidemiology, we present the latest news from population-based and clinical cohort studies. We also focus on innovative and interventional procedures for the paediatric airway, such as cryotherapy. Finally, we stress the importance of better understanding the molecular mechanisms underlying normal and abnormal lung development.

Prevalence of childhood cough in epidemiological studies depends on the question used: findings from two population-based studies.

BACKGROUND: Epidemiological studies use different questions to assess recurrent cough in children. In two independent population-based studies, we assessed how prevalence estimates of cough vary depending on the questions parents are asked about their child's cough and how answers to the different questions overlap. METHODS: We analysed cross-sectional data from two population-based studies on respiratory health: LuftiBus in the School (LUIS), conducted in 2013-2016 among 6- to 17-year-school children in the Canton of Zurich, Switzerland, and the 1998 Leicester Respiratory Cohort (LRC) study, UK where we used data from 6- to 8-year-old children from the 2003 follow-up survey. Both studies used parental questionnaires that included the same three questions on the child's cough, namely cough without a cold, dry cough at night and coughing more than others. We assessed how the prevalence of cough varied depending on the question and how answers to the different questions on cough overlapped. We also assessed how results were influenced by age, sex, presence of wheeze and parental education. RESULTS: We included 3457 children aged 6-17 years from LUIS and 2100 children aged 6-8 years from LRC. All respiratory outcomes - cough, wheeze and physician-diagnosed asthma - were reported twice as often in the LRC as in LUIS. We found large differences in the prevalence of parent-reported cough between the three cough questions. In LUIS, 880 (25%) parents reported cough without a cold, 394 (11%) dry night cough, and 159 (5%) reported that their child coughed more than other children. In the LRC, these numbers were 1003 (48%), 527 (25%) and 227 (11%). There was only partial overlap of answers, with 89 (3%) answering yes to all questions in LUIS and 168 (8%) in LRC. Prevalence of all types of cough and overlap between the cough questions was higher in children with current wheeze. CONCLUSION: In both population-based studies prevalence estimates of cough depended strongly on the question used to assess cough with only partial overlap of responses to different questions. Epidemiological studies on cough can only be compared if they used exactly the same questions for cough.

Standardization of Reporting Obstructive Airway Disease in Children: A National Delphi Process.

BACKGROUND: Pediatric pulmonologists report asthma and obstructive bronchitis in medical records in a variety of ways, and there is no consensus for standardized reporting. OBJECTIVE: We investigated which diagnostic labels and features pediatric pulmonologists use to describe obstructive airway disease in children and aimed to reach consensus for standardized reporting. METHODS: We obtained electronic health records from 562 children participating in the Swiss Pediatric Airway Cohort from 2017 to 2018. We reviewed the diagnosis section of the letters written by pediatric pulmonologists to referring physicians and extracted the terms used to describe the diagnosis. We grouped these terms into diagnostic labels (eg, asthma) and features (eg, triggers) using qualitative thematic framework analysis. We also assessed how frequently the different terms were used. Results were fed into a modified Delphi process to reach consensus on standardized reporting. RESULTS: Pediatric pulmonologists used 123 different terms to describe the diagnosis, which we grouped into 6 diagnostic labels and 17 features. Consensus from the Delphi process resulted in the following recommendations: (i) to use the diagnostic label "asthma" for children older than 5 years and "obstructive bronchitis" or "suspected asthma" for children younger than 5 years; (ii) to accompany the diagnosis with relevant features: diagnostic certainty, triggers, symptom control, risk of exacerbation, atopy, treatment adherence, and symptom perception. CONCLUSION: We found great heterogeneity in the reporting of obstructive airway disease among pediatric pulmonologists. The proposed standardized reporting will simplify communication among physicians and improve quality of research based on electronic health records.

Facemasks do not lead to abnormal gas exchange during treadmill exercise testing in children.

No episodes of oxygen desaturation or carbon dioxide retention were observed in this cross-sectional study assessing children with exercise-induced symptoms wearing a surgical facemask during a submaximal treadmill exercise test https://bit.ly/3GuxhvO.

Treatment Decisions in Children With Asthma in a Real-Life Clinical Setting: The Swiss Paediatric Airway Cohort.

BACKGROUND: Asthma treatment should be modified according to symptom control and future risk, but there are scarce data on what drives treatment adjustments in routine tertiary care. OBJECTIVE: We studied factors that drive asthma treatment adjustment in pediatric outpatient clinics. METHODS: We performed a cross-sectional analysis of the Swiss Paediatric Airway Cohort, a clinical cohort of 0- to 16-year-old children seen by pediatric pulmonologists. We collected information on diagnosis, treatment, lung function, and FeNO from hospital records; and on symptoms, sociodemographic, and environmental factors from a parental questionnaire. We used reported symptoms to classify asthma control and categorized treatment according to the 2020 Global Initiative for Asthma guidelines. We used multivariable logistic regression to study factors associated with treatment adjustment (step-up or down vs no change). RESULTS: We included 551 children diagnosed with asthma (mean age, 10 years; 37% female). At the clinical visit, most children were prescribed Global Initiative for Asthma step 3 (35%). Compared with previsit treatment, 252 children remained on the same step (47%), 227 were stepped up (42%), and 58 were stepped down (11%). Female sex (adjusted odds ratio [aOR] = 1.61; 95% confidence interval [CI], 1.05-2.47), poor asthma control (aOR = 3.08; 95% CI, 1.72-5.54), and lower FEV1 Z-score (aOR = 0.70; 95% CI, 0.56-0.86 per one Z-score increase) were independently associated with treatment step-up, and low FeNO (aOR = 2.34; 95% CI, 1.23-4.45) was associated with treatment step-down, with marked heterogeneity between clinics. CONCLUSIONS: In this tertiary care real-life study, we identified main drivers for asthma treatment adjustment. These findings may help improve both asthma management guidelines and clinical practice.

COVID-19 Vaccinations: Perceptions and Behaviours in People with Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare genetic disease that causes recurrent respiratory infections. People with PCD may be at higher risk of severe coronavirus disease 2019 (COVID-19), and therefore vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important. We studied vaccination willingness, speed of vaccination uptake, side effects, and changes in social contact behaviour after vaccination in people with PCD. We used data from COVID-PCD, an international participatory cohort study. A COVID-19 vaccination questionnaire was emailed to participants in May 2021 and 423 participants from 31 countries replied (median age: 30 years, range 1-85 years; 261 (62%) female). Vaccination uptake and willingness were high, with 273 of 287 adults (96%) being vaccinated or willing to be in June 2021; only 4% were hesitant. The most common reason for hesitancy was fear of side effects, reported by 88%. Mild side effects were common, but no participant reported severe side effects. Half of the participants changed their social behaviour after vaccination by seeing friends and family more often. The high vaccination willingness in the study population might reflect the extraordinary effort taken by PCD support groups to inform people about COVID-19 vaccination. Clear and specific information and involvement of representatives is important for high vaccine uptake.

Rotavirus disease and health care utilisation among children under 5 years of age in highly developed countries: A systematic review and meta-analysis.

BACKGROUND: Rotavirus (RV) infection is the leading cause of diarrhoea-associated morbidity and mortality globally among children under 5 years of age. RV vaccination is available, but has not been implemented in many national immunisation plans, especially in highly developed countries. This systematic review aimed to estimate the prevalence and incidence of health care use for RV gastroenteritis (RVGE) among children aged under 5 years in highly developed countries without routine RV vaccination. METHODS: We searched MEDLINE and Embase databases from January 1st 2000 to December 17th 2018 for publications reporting on incidence or prevalence of RVGE-related health care use in children below 5 years of age: primary care and emergency department (ED) visits, hospitalisations, nosocomial infections and deaths. We included only studies with laboratory-confirmed RV infection, undertaken in highly developed countries with no RV routine vaccination plans. We used random effects meta-analysis to generate summary estimates with 95% confidence intervals (CI) and prediction intervals. RESULTS: We screened 4033 abstracts and included 74 studies from 21 countries. Average incidence rates of RVGE per 100 000 person-years were: 2484 (95% CI 697-5366) primary care visits, 1890 (1597-2207) ED visits, 500 (422-584) hospitalisations, 34 (20-51) nosocomial infections and 0.04 (0.02-0.07) deaths. Average proportions of cases of acute gastroenteritis caused by RV were: 21% (95% CI 16-26%) for primary care visits; 32% (25-38%) for ED visits; 41% (36-47%) for hospitalisations, 29% (25-34%) for nosocomial infections and 12% (8-18%) for deaths. Results varied widely between and within countries, and heterogeneity was high (I2 > 90%) in most models. CONCLUSION: RV in children under 5 years causes many healthcare visits and hospitalisations, with low mortality, in highly developed countries without routine RV vaccination. The health care use estimates for RVGE obtained by this study can be used to model RV vaccine cost-effectiveness in highly developed countries.

Reported Symptoms Differentiate Diagnoses in Children with Exercise-Induced Respiratory Problems: Findings from the Swiss Paediatric Airway Cohort (SPAC).

BACKGROUND: Exercise-induced breathing problems with similar clinical presentations can have different etiologies. This makes distinguishing common diagnoses such as asthma, extrathoracic and thoracic dysfunctional breathing (DB), insufficient fitness, and chronic cough difficult. OBJECTIVE: We studied which parent-reported, exercise-induced symptoms can help distinguish diagnoses in children seen in respiratory outpatient clinics. METHODS: This study was nested in the Swiss Paediatric Airway Cohort, an observational study of children aged 0 to 17 years referred to pediatric respiratory outpatient clinics in Switzerland. We studied children aged 6 to 17 years and compared information on exercise-induced symptoms from parent-completed questionnaires between children with different diagnoses. We used multinomial regression to analyze whether parent-reported symptoms differed between diagnoses (asthma as base). RESULTS: Among 1109 children, exercise-induced symptoms were reported for 732 (66%) (mean age: 11 years, 318 of 732 [43%] female). Among the symptoms, dyspnea best distinguished thoracic DB (relative risk ratio [RRR]: 5.4, 95% confidence interval [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 symptoms 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. Localization of dyspnea (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. CONCLUSION: Parent-reported symptoms help distinguish different diagnoses in children with exercise-induced symptoms. This highlights the importance of physicians obtaining detailed patient histories.

Paediatric cohort studies on lower respiratory diseases and their reporting quality: systematic review of the year 2018.

The paediatric respiratory research community uses cohort studies extensively. However, the landscape of these studies and their quality of reporting has not been assessed.We performed a systematic review of publications on cohort studies reporting on paediatric lower respiratory problems published in 2018. We searched MEDLINE and Embase and extracted data on study and journal characteristics. We assessed the number of items of the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) checklist that a random sample (100 papers) reported. We analysed factors associated with the STROBE score and with the most poorly reported items, using Poisson and logistic regression.Of the 21 319 records identified, 369 full-text articles met our inclusion criteria. Most papers studied asthma aetiology through birth cohorts and were based in Europe or North America. The reporting quality was insufficient: 15% reported the 22 STROBE items; median (interquartile range) score 18 (16-21). The most poorly reported items were sources of bias, sample size, statistical methods, descriptive results and generalisability. None of the study or journal factors were associated with the STROBE score.We need a joint effort of editors, reviewers and authors to improve the reporting quality of paediatric cohort studies on respiratory problems.

Factors influencing harmonized health data collection, sharing and linkage in Denmark and Switzerland: A systematic review.

INTRODUCTION: The digitalization of medicine has led to a considerable growth of heterogeneous health datasets, which could improve healthcare research if integrated into the clinical life cycle. This process requires, amongst other things, the harmonization of these datasets, which is a prerequisite to improve their quality, re-usability and interoperability. However, there is a wide range of factors that either hinder or favor the harmonized collection, sharing and linkage of health data. OBJECTIVE: This systematic review aims to identify barriers and facilitators to health data harmonization-including data sharing and linkage-by a comparative analysis of studies from Denmark and Switzerland. METHODS: Publications from PubMed, Web of Science, EMBASE and CINAHL involving cross-institutional or cross-border collection, sharing or linkage of health data from Denmark or Switzerland were searched to identify the reported barriers and facilitators to data harmonization. RESULTS: Of the 345 projects included, 240 were single-country and 105 were multinational studies. Regarding national projects, a Swiss study reported on average more barriers and facilitators than a Danish study. Barriers and facilitators of a technical nature were most frequently reported. CONCLUSION: This systematic review gathered evidence from Denmark and Switzerland on barriers and facilitators concerning data harmonization, sharing and linkage. Barriers and facilitators were strictly interrelated with the national context where projects were carried out. Structural changes, such as legislation implemented at the national level, were mirrored in the projects. This underlines the impact of national strategies in the field of health data. Our findings also suggest that more openness and clarity in the reporting of both barriers and facilitators to data harmonization constitute a key element to promote the successful management of new projects using health data and the implementation of proper policies in this field. Our study findings are thus meaningful beyond these two countries.