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

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

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

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

Evaluation of the Double-Tracer Gas Single-Breath Washout Test in a Pediatric Field Study

BACKGROUND: The early life origins of chronic pulmonary diseases are thought to arise in peripheral small airways. Predictors of ventilation inhomogeneity, a proxy of peripheral airway function, are understudied in schoolchildren. RESEARCH QUESTION: Is the double-tracer gas single-breath washout (DTG-SBW) measurement feasible in a pediatric field study setting? What are the predictors of the DTG-SBWderived ventilation inhomogeneity estimate in unselected schoolchildren? STUDY DESIGN AND METHODS: In this prospective cross-sectional field study, a mobile lung function testing unit visited participating schools in Switzerland. We applied DTG-SBW, fraction of exhaled nitric oxide (FENO), and spirometry measurements. The DTG-SBW is based on tidal inhalation of helium and sulfur-hexafluoride, and the phase III slope (SIIIHeSF6) is derived. We assessed feasibility, repeatability, and associations of SIIIHe-SF6 with the potential predictors of anthropometrics, presence of wheeze (ie, parental report of one or more episode of wheeze in the prior year), FENO, FEV1, and FEV1/FVC. RESULTS: In 1,782 children, 5,223 DTG-SBW trials were obtained. The DTG-SBW was acceptable in 1,449 children (81.3%); the coefficient of variation was 39.8%. SIIIHe-SF6 was independently but weakly positively associated with age and BMI. In 276 children (21.2%), wheeze was reported. SIIIHe-SF6 was higher by 0.049 g.mol.L-1 in children with wheeze compared with those without and remained associated with wheeze after adjusting for age and BMI in a multivariable linear regression model. SIIIHe-SF6 was not associated with FENO, FEV1, and FEV1/FVC. INTERPRETATION: The DTG-SBW is feasible in a pediatric field study setting. On the population level, age, body composition, and wheeze are independent predictors of peripheral airway function in unselected schoolchildren. The variation of the DTG-SBW possibly constrains its current applicability on the individual level

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Epidemiology of childhood cough in Switzerland.

Background: Cough has not only a protective role for the respiratory tract but it also serves as a warning sign of disease. However, cough significantly impacts the quality of life of children and their families, especially when it is persistent. It is thus fundamental to identify the underlying cause of cough and manage it accordingly. Even if cough is one of the most common respiratory symptoms in children, research on cough remains scarce and challenging. For instance, several cough questions exist, such as cough without a cold, dry night cough, and coughing more than other children, to identify children with cough exceeding the expected physiological occurrence. However, epidemiological studies usually include only one of these cough questions to assess cough prevalence. This makes it difficult to determine if differences in prevalence of cough between studies is due to differences in wording of the question or other factors such as environmental exposures. In addition, many children cough in the absence of wheeze and it is disputed whether these children may have a variant form of asthma. Only few population-based studies have compared whether children who have dry night cough without wheeze differ from those who wheeze, using both parent-reported information and measurable asthma traits. Furthermore, chronic cough has different underlying causes which vary across settings and age groups. Only few studies have assessed causes of chronic cough in children visiting healthcare settings. These studies had a small sample size or restricted age group, and most were single centre studies with limited generalisability of their findings. To classify cough into aetiologies, physicians often rely on clinical guidelines—these are usually based on expert opinions with some degree of overlap between diagnoses. Latent class analysis (LCA), a more objective statistical data-driven method, is increasingly used to distinguish phenotypes of respiratory problems such as wheeze and asthma. However, only few studies have applied LCA to children who cough, and these studies were population-based and mostly focused on asthma and wheeze with little emphasis on cough. Aims: The overall aim of my PhD thesis was to fill these research gaps and contribute to the epidemiological knowledge of childhood cough in Switzerland. More specifically, my aims were 1) to assess how the prevalence of cough varies depending on the cough question asked to parents and how answers to different cough questions overlap, 2) to compare how children who report dry night cough without wheeze differ from children who wheeze, 3) to assess the diagnostic evaluation and final diagnoses given to children referred to respiratory outpatient clinics for prolonged or recurrent cough, 4) to apply LCA to identify phenotypes of cough in a clinical population of children who cough without wheeze and lastly, 5) to assess whether the wearing of surgical facemasks during submaximal physical exercise affects gas exchange in children with exercise-induced symptoms. Methods: For aims 1 and 2, I used data from LuftiBus in the school (LUIS), a Swiss population-based study on respiratory health conducted among schoolchildren in the canton of Zurich. For aim 1, I compared the prevalence of three cough questions namely cough without a cold, dry night cough and coughing more than other children, and assessed how answers to these different questions overlap, and which factors affected the prevalence and overlap. I replicated the analysis in the Leicester Respiratory Cohort (LRC), a UK population-based study on respiratory health of children. For aim 2, I defined four mutually exclusive groups— ‘dry night cough alone’, ‘wheeze alone’, ‘wheeze and dry night cough’ and ‘neither wheeze nor dry night cough’. I assessed how these groups differed with respect to parent-reported symptoms, physiological measurements namely fractional exhaled nitric oxide (FeNO) and spirometry, healthcare use, and parent-reported physician asthma diagnosis and treatment. For aims 3, 4 and 5, I used data from the Swiss Paediatric Airway cohort, an observational multicentre study of children referred to respiratory outpatient clinics for the evaluation of common respiratory problems such as cough, wheeze, and exercise-induced symptoms. For aim 3, I extracted information on diagnostic investigations, final diagnoses proposed by paediatric pulmonologists, and treatment prescribed from outpatient records. For aim 4, I applied LCA to nine cough-related symptoms and characteristics reported by parents, to identify and describe cough phenotypes. I validated the identified cough phenotypes with respect to parental history, comorbidities, paediatric pulmonologists diagnoses, and respiratory prognosis after 1 year. For aim 5, I assessed oxygen saturation (SpO2) before and after exercise and results of capillary blood gas analysis measured immediately after exercise. Results: This thesis consists of five manuscripts (2 published, 1 under review, 1 submitted and 1 to be submitted). The main findings of each manuscript are summarised below: Manuscript 1: There were large differences of up to five-fold in the prevalence estimates of cough based on the three questions, with only a partial overlap of positive answers to all three questions, in both LUIS and LRC. Prevalence estimates of all types of cough, as well as the overlap of positive answers between the cough questions was higher when the children reported wheeze

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 the studies' and journals' 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 regressionOf 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 score: 18 (IQR: 16-21). The most poorly reported items were: sources of bias, sample size, statistical methods, descriptive results and generalisability. None of the studies' or journals' factors were associated with the STROBE score.We need a joined effort of editors, reviewers and authors to improve the reporting quality of paediatric cohort studies on respiratory problems