Exercise-induced respiratory symptoms in childhood.

Background Exercise-induced symptoms (EIS) are common in childhood and can lead to physical activity avoidance, reduced quality of life, and overtreatment with inhaled corticosteroids if mistakenly diagnosed as asthma. Diagnosis of EIS can be difficult because different aetiologies share similar clinical presentations. Reported symptoms can be helpful to identify the correct diagnosis, as certain symptoms are typically associated with specific diagnoses (e.g. expiratory wheeze for exercise-induced bronchoconstriction, and throat tightness for inducible laryngeal obstruction (ILO)). Only few studies have investigated diagnosis, diagnostic evaluations, and reported symptoms in children with EIS. Aims: The overall aim of this PhD thesis were to gain epidemiological knowledge about diagnosis, diagnostic investigations, and reported symptoms in children with EIS. Specifically, I aimed to 1) set up a prospective study including children referred to paediatric respiratory outpatient clinics with respiratory symptoms 2) study diagnosis, diagnostic investigations and management in children referred for EIS 3) study if parent reported EIS are helpful to distinguish different diagnoses and 4) study EIS reported by physicians in the clinical history and assess agreement with parent-reported symptoms. 5) Additionally, I aimed to validate a model to predict asthma in preschool children. Methods To address the aims of this PhD thesis, I used data from the Swiss Paediatric Airway Cohort (SPAC), a longitudinal observational clinical study of children referred with respiratory symptoms to paediatric respiratory outpatient clinics in Switzerland. I used data from medical records to get information on referral diagnosis, final diagnosis, diagnostic investigations and proposed management from the outpatient clinics. I used data from parental questionnaires to get information about symptoms. For publication 5, I used data from the Leicestershire Respiratory Cohort (LRC) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Results The main body of this thesis consists of 5 articles (2 published, 1 in review, and 2 to be submitted). These are the main findings in summary: Publication 1: The SPAC study is a novel longitudinal observational cohort study of children with respiratory symptoms. By January 7, 2020, the SPAC study includes 1893 children 5 recruited from 10 pulmonology clinics. The SPAC study will provide real-life data from paediatric pulmonology clinics in Switzerland and will serve as a platform for nested studies. Publication 2: Diagnosis given at the paediatric respiratory outpatient clinic differed from suspected referral diagnosis in half of the children referred primarily for EIS. Dysfunctional breathing was a common diagnosis at the outpatient clinic but rarely suspected at time of referral. Diagnostic evaluation, management, and follow-up were inconsistent between clinics and diagnostic groups. Publication 3: Parent reported EIS (including information on type of symptoms, activities triggering EIS, and characteristics of symptoms) can help to distinguish different diagnoses in children seen with EIS. Publication 4: Physicians reported EIS in the medical records in almost all children referred for EIS. Activities triggering EIS and characteristics of EIS (e.g. localisation of symptoms, respiratory phase, and onset and duration of symptoms) were reported only in around half of the children. Agreement with parent questionnaire reported EIS ranged from poor to moderate. Publication 5: PARC predicted asthma at school age equally well in the validation cohort, ALSPAC (AUC 0.77), compared with the development cohort, LRC (AUC 0.78). Apart from severity of wheeze and cough, family history of symptoms, age, and sex, also exercise as trigger for respiratory symptoms predicted asthma at school age in the development and validation cohort. The discriminative ability of the PARC appeared to be robust to changes in inclusion criteria, scoring variables, and outcome definitions. PARC may need recalibration when applied in other populations. Additionally, I contributed to further publications, which are included in this PhD thesis as related publications. Conclusion In summary, diagnosis, diagnostic investigations, and management in children with EIS differed between outpatient clinics and diagnosis groups, indicating a need for diagnostic guidelines. Parental reported symptoms can help to distinguish diagnoses in children with EIS. Future studies should focus on developing an algorithm for diagnosing children seen with EIS including both reported symptoms and objective diagnostic tests.

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

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Estimated impact of replacing sitting with standing at work on indicators of body composition: Cross-sectional and longitudinal findings using isotemporal substitution analysis on data from the Take a Stand! study.

The purpose was to examine and compare the effects of replacing time spent sitting with standing at work on fat-free mass, fat mass and waist circumference using isotemporal substitution. Analyses were conducted on work hours on both cross-sectional and longitudinal data. The study included 223 persons from an intervention study aimed at reducing sitting time at work among office employees. Sitting, standing and anthropometry were measured objectively. Cross-sectional isotemporal substitution analyses were modelled on baseline data, while longitudinal analyses were modelled based on differences in sitting and standing time at work between baseline and 1-month follow-up in relation to differences in anthropometric measures between baseline and 3-months follow-up. Replacing one hour of sitting time with one hour of standing was associated with a 0.21 kg higher fat-free mass in the longitudinal analysis and 0.95 kg in the cross-sectional analysis. Fat mass was 0.32 kg lower in the longitudinal analysis and 0.61 kg lower in the cross-sectional analysis. Waist circumference decreased by 0.38 cm in the longitudinal analysis and 0.81 cm in the cross-sectional analysis. Both cross-sectional and longitudinal analyses showed an effect on body composition measures by replacing one hour of sitting with standing however, this effect was largest in the cross-sectional analyses. Trial registration ClinicalTrials.gov NCT01996176

Immunoreactive trypsinogen in healthy newborns and infants with cystic fibrosis.

OBJECTIVE Newborn screening (NBS) for cystic fibrosis (CF) was introduced in Switzerland in 2011 based on an immunoreactive trypsinogen (IRT)-DNA-IRT protocol. CF diagnosis was confirmed by sweat test and/or genetics but remained inconclusive for some newborns (cystic fibrosis transmembrane conductance regulator related metabolic syndrome (CRMS)/CF screen positive, inconclusive diagnosis (CFSPID)). We aimed to (1) Describe IRT levels in healthy newborns in the first year of life and by gestational age (GA), and (2) Compare IRT at two time points between healthy newborns and newborns with CF and CRMS/CFSPID. DESIGN Retrospective study. SETTING National NBS database. PATIENTS All children with an IRT measurement by heel prick test from 2011 to 2019. INTERVENTIONS None. MAIN OUTCOME MEASURES IRT values were extracted from the National NBS Laboratory, and clinical characteristics of positively screened children from the CF-NBS database. Second IRT assessment in positively screened children was usually performed after 18-24 days. We calculated internal IRT Z-Scores and multiples of the median to compare our results across different laboratory tools. RESULTS Among 815 899 children; 232 were diagnosed with CF, of whom 36 had meconium ileus (MI); 27 had CRMS/CFSPID. Among all samples analysed, mean IRT Z-Scores were higher for newborns with GA 0.11) compared with term babies (all Z-Scores ≤0.06). Repeated IRT Z-Scores after a median (IQR) of 19 (17-22) days remained high for infants with CF with or without MI but decreased for infants with CRMS/CFSPID. CONCLUSIONS Measurement of a second IRT value can help distinguish between children with CRMS/CFSPID and CF, early in life

Isotemporal substitution models showing effect of replacing 1 hour of sitting with 1 hour of standing on changes in fat-free mass, fat mass and waist circumference from longitudinal and cross-sectional analyses.

<p>Isotemporal substitution models showing effect of replacing 1 hour of sitting with 1 hour of standing on changes in fat-free mass, fat mass and waist circumference from longitudinal and cross-sectional analyses.</p

Baseline characteristics of participants.

<p>N = 223.</p

COVID-PCD patient advisory group; Kuehni CE. Diagnostic testing in people with primary ciliary dyskinesia: an international participatory study

Diagnostic tests are important in primary ciliary dyskinesia (PCD), a rare disease, to confirm the diagnosis and characterize the disease. We compared diagnostic tests for PCD between countries worldwide, assessed whether people with PCD recall their tests, and identified factors associated with the use of tests. We used cross-sectional data from COVID-PCD—an international participatory cohort study collecting information directly from people with PCD. The baseline questionnaire inquired about tests used for PCD diagnosis. Using logistic regression, we investigated factors associated with measurement of nasal nitric oxide (nNO), biopsy for electron or video microscopy, and genetic testing. We included data from 747 participants (60% females) from 49 countries worldwide with median age 27 (interquartile range 12–44). Most (92%) reported diagnostic tests for PCD. Participants reported measurements of nNO (342; 49%), biopsy samples (561; 75%), and genetic tests (435; 58%). The reported use of individual tests, such as genetics, varied between countries from 38% in Switzerland to 68% in North America. Participant recall of test type also differed between countries with lowest recall in Switzerland. One-third (232; 36%) of participants reported all three tests (nNO, biopsy, and genetics). Recently diagnosed people reported more tests [nNO odds ratio (OR) 2.2, 95% Confidence Interval (CI) 1.5–3.2; biopsy OR 3.2, 95%CI 2.1–4.9; genetics OR 4.7, 95%CI 3.2–6.9] and those with situs abnormalities fewer tests (nNO OR 0.5, 95%CI 0.4–0.7; biopsy OR 0.5, 95%CI 0.4–0.8; genetics OR 0.7, 95%CI 0.5–0.94). Our results indicate PCD diagnostic testing differed widely around the world and many patients received incomplete diagnostic work-up based only on clinical features or single tests. People diagnosed long ago and those with situs abnormalities possibly benefit from supplementary testing to refine their diagnosis as a prerequisite for personalized medicine