Cohort profile: pulmonary early assessment of the lung in paediatric cancer patients (SWISS-PEARL Study).

Background: Due to the limited sensitivity of conventional lung function tests in detecting small airway abnormalities, cancer treatment-related pulmonary toxicity may be underdiagnosed. It has been suggested that the nitrogen multiple-breath washout test (N2MBW) might be more sensitive in detecting small airway abnormalities in childhood cancer survivors.

Objective: The Pulmonary Early Assessment of the Lung in Paediatric Cancer Patients (SWISS-PEARL) study aims to assess the prevalence and development of early pulmonary toxicity at baseline and longitudinally in paediatric cancer patients using spirometry, body plethysmography, diffusing capacity for carbon monoxide (DLCO), N2MBW and magnetic resonance imaging (MRI) and to identify treatment-related pulmotoxic risk factors.

Urinary marker of oxidative stress in children correlates with molecules in exhaled breath.

Real-time breath analysis has shown potential as a non-invasive method for detecting oxidative stress and airway inflammation. However, there is a lack of data on the association of full-breath profiles with established urinary biomarkers of oxidative stress and respiratory inflammation, which could help advance the implementation of this method in clinical practice. We analyzed breath profiles of 25 tobacco smoke-exposed and 103 non-exposed children via real-time secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) and determined in parallel the urinary concentrations of biomarkers of oxidative stress and respiratory inflammation.

Assessing Pulmonary Function in Children and Adolescents After Cancer Treatment: Protocol for a Multicenter Cohort Study (Swiss Childhood Cancer Survivor Study FollowUp-Pulmo).

Background: Childhood cancer survivors (CCS) are at risk of pulmonary dysfunction due to cancer treatments, but evidence on prevalence and risk factors remains limited. Most previous studies had small sample sizes or retrospective study designs, little information about treatments, or a lack of standardization of pulmonary function tests (PFTs) or limited their investigation to certain PFTs. Since spirometry mainly assesses the large airways but cancer therapy also affects peripheral airways, additional functional tests are needed.

Lung Density Measurement in Fontan Patients Using Zero Echo Time Sequences.

Pulmonary complications are known to occur in patients after Fontan palliation. Cardiac MRI is performed in the follow-up of Fontan patients to assess single ventricular function, hemodynamics and potential collateral flow. To date, pulmonary function tests have been used to detect functional lung impairment, but lung MRI has not been integrated into imaging follow-up.

Diagnosis in Children With Prolonged or Recurrent Cough: Findings From the Swiss Paediatric Airway Cohort.

Introduction: Prolonged or recurrent cough is a common reason for referral to pediatric pulmonologists, yet few studies have assessed its causes. We examined records of children visiting respiratory outpatient clinics in Switzerland and assessed how diagnoses vary by age.

Methods: We analyzed data from the multicenter Swiss Paediatric Airway Cohort study.

Nitrogen single and multiple breath washout test and lung imaging to detect treatment-related pulmonary toxicity in paediatric cancer patients and survivors: a systematic review.

Background: Spirometry-based assessment of pulmonary function has limitations in detecting pulmonary toxicity following cancer treatment with chemotherapy, haematopoietic stem cell transplantation, radiotherapy or thoracic surgery. Nitrogen single and multiple breath washout tests are sensitive in assessing peripheral airway function, and lung imaging detects structural abnormalities, but little is known about their use in paediatric cancer patients and survivors. We aimed to 1) identify studies using nitrogen single or multiple breath washout tests and/or lung imaging to assess pulmonary toxicity in paediatric cancer patients and survivors, and 2) describe reported abnormalities.

Pharmacometabolomics via real-time breath analysis captures metabotypes of asthmatic children associated with salbutamol responsiveness.

Asthma is a widespread respiratory disease affecting millions of children. Salbutamol is a well-established bronchodilator available to treat asthma. However, response to bronchodilators is very heterogeneous, particularly in children.

Comparison of nasal microbiota between preterm and full-term infants in early life.

Background: The respiratory microbiota influences infant immune system maturation. Little is known about how perinatal, physiological, and environmental exposures impact the nasal microbiota in preterm infants after discharge, or nasal microbiota differences between preterm and healthy full-term infants.

Methods: Nasal swabs (from 136 preterm and 299 full-term infants at mean postmenstrual age of 45 weeks from the prospective Basel-Bern Infant Lung Development cohort) were analyzed by 16S-rRNA gene amplification and sequencing (Illumina MiSeq).

Early nasal microbiota and subsequent respiratory tract infections in infants with cystic fibrosis.

Background: Respiratory tract infections (RTIs) drive lung function decline in children with cystic fibrosis (CF). While the respiratory microbiota is clearly associated with RTI pathogenesis in infants without CF, data on infants with CF is scarce. We compared nasal microbiota development between infants with CF and controls and assessed associations between early-life nasal microbiota, RTIs, and antibiotic treatment in infants with CF.

Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on the oropharyngeal metagenome in adolescents with cystic fibrosis.

Background: Triple modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) improves lung function and impacts upon the respiratory microbiome in people with Cystic fibrosis (pwCF) with advanced lung disease. However, adolescents with cystic fibrosis (CF) are less colonized with bacterial pathogens than adult pwCF but their microbiota already differs from healthy individuals. The aim of this study was to longitudinally analyze the impact of ETI on the respiratory metagenome in adolescents with predominantly mild CF lung disease.

Air pollution exposure during pregnancy and lung function in childhood: The LUIS study.

Background: The adverse effects of high air pollution levels on childhood lung function are well-known. Limited evidence exists on the effects of moderate exposure levels during early life on childhood lung function. We investigated the association of exposure to moderate air pollution during pregnancy, infancy, and preschool time with lung function at school age in a Swiss population-based study.

Lung structural and functional impairments in young children with cystic fibrosis diagnosed following newborn screening - A nationwide observational study.

Background: Non-invasive and sensitive clinical endpoints are needed to monitor onset and progression of early lung disease in children with cystic fibrosis (CF). We compared lung clearance index (LCI), FEV, functional and structural lung magnetic resonance imaging (MRI) outcomes in Swiss children with CF diagnosed following newborn screening.

Methods: Lung function (LCI, FEV) and unsedated functional and structural lung MRI was performed in 79 clinically stable children with CF (3 - 8 years) and 75 age-matched healthy controls.

Differences in autophagy marker levels at birth in preterm vs. term infants.

Background: Preterm infants are susceptible to oxidative stress and prone to respiratory diseases. Autophagy is an important defense mechanism against oxidative-stress-induced cell damage and involved in lung development and respiratory morbidity. We hypothesized that autophagy marker levels differ between preterm and term infants.

Possible effects of left pulmonary artery stenting in single ventricle patients on bronchial area, lung volume and lung function.

Background: Left pulmonary artery (LPA) stenting is often required in single ventricle (SV) patients. Due to their close anatomical relationship an LPA stent could potentially compress the left main bronchus (LMB). We assessed the impact of LPA stenting on bronchial size, pulmonary volumes, and lung function in a cohort of SV patients.

Data accuracy, consistency and completeness of the national Swiss cystic fibrosis patient registry: Lessons from an ECFSPR data quality project.

Background: Good data quality is essential when rare disease registries are used as a data source for pharmacovigilance studies. This study investigated data quality of the Swiss cystic fibrosis (CF) registry in the frame of a European Cystic Fibrosis Society Patient Registry (ECFSPR) project aiming to implement measures to increase data reliability for registry-based research.

Methods: All 20 pediatric and adult Swiss CF centers participated in a data quality audit between 2018 and 2020, and in a re-audit in 2022.

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-SBW-derived 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.

An interoperability framework for multicentric breath metabolomic studies.

Exhaled breath contains valuable information at the molecular level and offers promising potential for precision medicine. However, few breath tests transition to routine clinical practice, partly because of the missing validation in multicenter trials. Therefore, we developed and applied an interoperability framework for standardized multicenter data acquisition and processing for breath analysis with secondary electrospray ionization-high resolution mass spectrometry.

Variability of clinically measured lung clearance index in children with cystic fibrosis.

Rationale: The lung clearance index (LCI) is increasingly being used in the clinical surveillance of patients with cystic fibrosis (CF). However, there are limited data on long-term variability and physiologically relevant changes in LCI during routine clinical surveillance.

Objectives: To evaluate the long-term variability of LCI and propose a threshold for a physiologically relevant change.

External validation of the Predicting Asthma Risk in Children tool in a clinical cohort.

Introduction: The Predicting Asthma Risk in Children (PARC) tool uses questionnaire-based respiratory symptoms collected from preschool children to predict asthma risk 5 years later. The tool was developed and validated in population cohorts but not validated using a clinical cohort. We aimed to externally validate the PARC tool in a pediatric pulmonology clinic setting.

Associations of Mucosal Nerve Fiber Innervation Density with Hirschsprung-Associated Enterocolitis: A Retrospective Three-Center Cohort Study.

Objective:  Hirschsprung's disease (HSCR) is a congenital intestinal neurodevelopmental disorder characterized by the absence of enteric ganglion cells in the distal colon. Although Hirschsprung-associated enterocolitis (HAEC) is the most frequent life-threatening complication in HSCR, to date reliable biomarkers predicting the likelihood of HAEC are yet to be established. We established a three-center retrospective study including 104 HSCR patients surgically treated between 1998 and 2019.

Personalised therapeutic management of epileptic patients guided by pathway-driven breath metabolomics.

Background: Therapeutic management of epilepsy remains a challenge, since optimal systemic antiseizure medication (ASM) concentrations do not always correlate with improved clinical outcome and minimal side effects. We tested the feasibility of noninvasive real-time breath metabolomics as an extension of traditional therapeutic drug monitoring for patient stratification by simultaneously monitoring drug-related and drug-modulated metabolites.

Methods: This proof-of-principle observational study involved 93 breath measurements of 54 paediatric patients monitored over a period of 2.