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. Accuracy, consistency and completeness of variables and definitions were evaluated, and missing source data and informed consents (ICs) were assessed. RESULTS: The first audit included 601 out of 997 Swiss people with CF (60.3 %). Data quality, as defined by data correctness ≥95 %, was high for most of the variables. Inconsistencies of specific variables were observed because of an incorrect application of the variable definition. The proportion of missing data was low with <5 % for almost all variables. A considerable number of missing source data occurred for CFTR variants. Availability of ICs varied largely between centers (10 centers had >5 % of missing documents). After providing feedback to the centers, availability of genetic source data and ICs improved. CONCLUSIONS: Data audits demonstrated an overall good data quality in the Swiss CF registry. Specific measures such as support of the participating sites, training of data managers and centralized data collection should be implemented in rare disease registries to optimize data quality and provide robust data for registry-based scientific research.

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.

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.

Respiratory symptoms do not reflect functional impairment in early CF lung disease.

BACKGROUND: Lung disease can develop within the first year of life in infants with cystic fibrosis (CF). However, the frequency and severity of respiratory symptoms in infancy are not known. METHODS: We assessed respiratory symptoms in 50 infants with CF and 50 healthy matched controls from two prospective birth cohort studies. Respiratory symptoms and respiratory rate were documented by standardized weekly interviews throughout the first year. Infants performed multiple breath washout in the first weeks of life. RESULTS: We analyzed 4552 data points (2217 in CF). Respiratory symptoms (either mild or severe) were not more frequent in infants with CF (OR:1.1;95% CI:[0.76, 1.59]; p=0.6). Higher lung clearance index and higher respiratory rate in infants with CF were not associated with respiratory symptoms. CONCLUSIONS: We found no difference in respiratory symptoms between healthy and CF infants. These data indicate that early CF lung disease may not be captured by clinical presentation alone.

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.

Diagnosis in children with exercise-induced respiratory symptoms: A multi-center study.

OBJECTIVE: Exercise-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 primary care physician with the final diagnosis from the outpatient clinic and described diagnostic tests and treatments. DESIGN: An observational study of respiratory outpatients aged 0-16 years nested in the Swiss Paediatric Airway Cohort (SPAC). PATIENTS: We included children with EIS as the main reason for referral. Information about diagnostic investigations, final diagnosis, and treatment prescribed came from outpatient records. We included 214 children (mean age 12 years, range 2-17, 54% males) referred for EIS. RESULTS: 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%, 95%-CI 46%-60%). Spirometry, body plethysmography, and exhaled nitric oxide were performed in almost all, exercise-challenge tests in a third, and laryngoscopy in none. 91% of the children with a final diagnosis of asthma were prescribed inhaled medication and 50% of children with DB were referred to physiotherapy. CONCLUSIONS: Diagnosis given at the outpatient clinic often differed from the diagnosis proposed by the referring physician. Diagnostic evaluations, management, and follow-up differed between clinics and diagnostic groups highlighting the need for evidence-based diagnostic guidelines and harmonized procedures for children seen for EIS.

Elevated lung clearance index in infants with cystic fibrosis shortly after birth.

It is not known at what age lung function impairment may arise in children with cystic fibrosis (CF). We assessed lung function shortly after birth in infants with CF diagnosed by newborn screening.We performed infant lung function measurements in a prospective cohort of infants with CF and healthy controls. We assessed lung clearance index (LCI), functional residual capacity (FRC) and tidal breathing parameters. The primary outcome was prevalence and severity of abnormal lung function (±1.64 z-scores) in CF.We enrolled 53 infants with CF (mean age 7.8 weeks) and 57 controls (mean age 5.2 weeks). Compared to controls, LCI and FRC were elevated (mean difference 0.30, 95% CI 0.02-0.60; p=0.034 and 14.5 mL, 95% CI 7.7-21.3 mL; p<0.001, respectively), while ratio of time to peak tidal expiratory flow to expiratory time was decreased in infants with CF. In 22 (41.5%) infants with CF, either LCI or FRC exceeded 1.64 z-scores; three infants had both elevated LCI and FRC.Shortly after birth, abnormal lung function is prevalent in CF infants. Ventilation inhomogeneity or hyperinflation may serve as noninvasive markers to monitor CF lung disease and specific treatment effects, and could thus be used as outcome parameters for future intervention studies in this age group.