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.

Substances from unregulated drug markets - A retrospective data analysis of customer-provided samples from a decade of drug checking service in Zurich (Switzerland).

BACKGROUND: Drug checking services (DCS) are harm reduction interventions for people who consume illicit substances. Unregulated drug markets lead to samples with unexpected and variable contents. A retrospective data analysis of Zurich's DCS was performed to determine the nature of these samples. METHODS: This study aims to investigate the qualitative and quantitative properties of 16,815 customer-provided psychoactive drug samples analyzed chemically through the DCS in Zurich from 1st January 2011 to 31st December 2021. The main analytical method utilized for characterizing these substances was high-performance liquid chromatography and gas chromatography-mass spectrometry. Data sets are summarized using descriptive statistics. RESULTS: There was a 2.5-fold increase in the number of tested samples over the past decade. An overall proportion of 57.9% (weighted mean) of samples within our database demonstrates unexpected analytical findings and additional low sample contents during the observation period. Substantial differences in quality and quantity between substance groups were detected and an increase of sample quality and content over time was demonstrated. CONCLUSIONS: Chemical analysis reveals that over half of substances acquired from unregulated drug markets analyzed through DCS in Zurich are with low qualitative and quantitative properties, which may expose users to risks. Based on longitudinal analyses over a decade, this study contributes to the body of evidence that DCS may potentially manipulate unregulated drug markets towards providing better quality substances, as well as may stabilize these markets over time. The necessity for drug policy changes to make this service accessible in further settings was highlighted, as DCS still often take place in legal grey zones.

Use of the head-twitch response to investigate the structure-activity relationships of 4-thio-substituted 2,5-dimethoxyphenylalkylamines.

RATIONALE: 4-Thio-substituted phenylalkylamines such as 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2) and 2,5-dimethoxy-4-n-propylthiophenethylamine (2C-T-7) produce psychedelic effects in humans and have been distributed as recreational drugs. OBJECTIVES: The present studies were conducted to examine the structure-activity relationships (SAR) of a series of 4-thio-substituted phenylalkylamines using the head twitch response (HTR), a 5-HT2A receptor-mediated behavior induced by psychedelic drugs in mice. The HTR is commonly used as a behavioral proxy in rodents for human psychedelic effects and can be used to discriminate hallucinogenic and non-hallucinogenic 5-HT2A agonists. METHODS: HTR dose-response studies with twelve different 4-thio-substituted phenylalkylamines were conducted in male C57BL/6 J mice. To detect the HTR, head movement was recorded electronically using a magnetometer coil and then head twitches were identified in the recordings using a validated method based on artificial intelligence. RESULTS: 2C-T, the parent compound of this series, had relatively low potency in the HTR paradigm, but adding an α-methyl group increased potency fivefold. Potency was also increased when the 4-methylthio group was extended by one to three methylene units. Fluorination of the 4-position alkylthio chain, however, was detrimental for activity, as was the presence of a 4-allylthio substituent versus a propylthio group. 2C-T analogs containing a 4-benzylthio group showed little or no effect in the HTR paradigm, which is consistent with evidence that bulky 4-substituents can dampen agonist efficacy at the 5-HT2A receptor. Binding and functional studies confirmed that the compounds have nanomolar affinity for 5-HT2 receptor subtypes and act as partial agonists at 5-HT2A. CONCLUSIONS: In general, there were close parallels between the HTR data and the known SAR governing activity of phenylalkylamines at the 5-HT2A receptor. These findings further support the classification of 2C-T compounds as psychedelic drugs.

Pharmacological characterization of 3,4-methylenedioxyamphetamine (MDA) analogs and two amphetamine-based compounds: N,α-DEPEA and DPIA.

3,4-methylenedioxyamphetamine (MDA) is a psychoactive compound chemically related to the entactogen MDMA. MDA shares some of the entactogenic effects of MDMA but also exerts stimulant effects and psychedelic properties at higher doses. Here, we examined the pharmacological properties of MDA analogs and related amphetamine-based compounds detected in street drug samples or in sport supplements. We examined the key pharmacological mechanisms including monoamine uptake inhibition and release using human embryonic kidney 293 cells stably transfected with the respective human transporters. Additionally, we assessed monoamine transporter and receptor binding and activation properties. MDA, its fluorinated analogs, as well as the α-ethyl containing BDB and the dimeric amphetamine DPIA inhibited NET with the greatest potency and preferentially inhibited 5-HT vs. dopamine uptake. The ß­methoxy MDA analog 3C-BOH and the amphetamine-based N,α-DEPEA inhibited NET and preferentially inhibited dopamine vs. 5-HT uptake. The test drugs mediated efflux of at least one monoamine with the exception of DPIA. Most compounds bound to 5-HT2A and 5-HT2C receptors (Ki ≤ 10 µM) and several substances activated the 5-HT2A and 5-HT2B receptor as partial or full agonists. Furthermore, several compounds interacted with adrenergic receptors and the trace amine-associated receptor 1 (TAAR1) in the micromolar range. The pharmacological profiles of some fluorinated and nonfluorinated MDA analogs resemble the profile of MDMA. In contrast, 3C-BOH and N,α-DEPEA displayed more pronounced dopaminergic activity similar to amphetamine. Pharmacokinetics and pharmacodynamics studies are necessary to better establish the risks and therapeutic potential of the tested drugs.

Multichannel esophageal signals to monitor respiratory rate in preterm infants.

BACKGROUND: Apnea of prematurity cannot be reliably measured with current monitoring techniques. Instead, indirect parameters such as oxygen desaturation or bradycardia are captured. We propose a Kalman filter-based detection of respiration activity and hence apnea using multichannel esophageal signals in neonatal intensive care unit patients. METHODS: We performed a single-center observational study with moderately preterm infants. Commercially available nasogastric feeding tubes containing multiple electrodes were used to capture signals with customized software. Multichannel esophageal raw signals were manually annotated, processed using extended Kalman filter, and compared with standard monitoring data including chest impedance to measure respiration activity. RESULTS: Out of a total of 405.4 h captured signals in 13 infants, 100 episodes of drop in oxygen saturation or heart rate were examined. Median (interquartile range) difference in respiratory rate was 0.04 (-2.45 to 1.48)/min between esophageal measurements annotated manually and with Kalman filter and -3.51 (-7.05 to -1.33)/min when compared to standard monitoring, suggesting an underestimation of respiratory rate when using the latter. CONCLUSIONS: Kalman filter-based estimation of respiratory activity using multichannel esophageal signals is safe and feasible and results in respiratory rate closer to visual annotation than that derived from chest impedance of standard monitoring.

Developmental respiratory physiology.

Various developmental aspects of respiratory physiology put infants and young children at an increased risk of respiratory failure, which is associated with a higher rate of critical incidents during anesthesia. The immaturity of control of breathing in infants is reflected by prolonged central apneas and periodic breathing, and an increased risk of apneas after anesthesia. The physiology of the pediatric upper and lower airways is characterized by a higher flow resistance and airway collapsibility. The increased chest wall compliance and reduced gas exchange surface of the lungs reduce the pulmonary oxygen reserve vis-à-vis a higher metabolic oxygen demand, which causes more rapid oxygen desaturation when ventilation is compromised. This review describes the various developmental aspects of respiratory physiology and summarizes anesthetic implications.

Inflammatory bowel disease and the lung in paediatric patients.

The prevalence of inflammatory bowel disease (IBD) has increased over the past 20 years. Pulmonary involvement in paediatric IBD is rare but may be missed since the spectrum of symptoms is broad and mimics other diseases. The most important differential diagnoses of pulmonary manifestations of IBD are infections and therapy-related side-effects. There is no gold standard to diagnose respiratory manifestations in children with IBD. Diagnostic tests should be chosen according to history and clinical presentation. Treatment of respiratory manifestations of IBD includes inhaled or oral corticosteroids and initiation or step-up of immunomodulatory IBD therapies.

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.

Severe Acute Lung Injury After H2O2 Irrigation of an Aneurysmal Bone Cyst in an 8-Year-Old Girl: A Case Report.

An 8-year-old girl developed severe acute lung injury after irrigation of a pelvic aneurysmal bone cyst with H2O2 and filling with bone cement. Sudden profound oxygen desaturation occurred on the operating table when the patient was turned from the prone to the supine position. After a brief improvement in her oxygenation, the girl developed rapidly progressing severe respiratory failure necessitating reintubation and hour-long manual ventilation, while copious amounts of hemorrhagic frothy fluids were aspirated through the endotracheal tube. The patient started to improve after 24 hours and eventually made a full recovery. We hypothesize that the incident was caused by gas embolization and pulmonary endothelial damage by H2O2.

Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines.

3,4,5-Trimethoxyphenethylamine (mescaline) is a psychedelic alkaloid found in peyote cactus. Related 4-alkoxy-3,5-dimethoxy-substituted phenethylamines (scalines) and amphetamines (3C-scalines) are reported to induce similarly potent psychedelic effects and are therefore potential novel therapeutics for psychedelic-assisted therapy. Herein, several pharmacologically uninvestigated scalines and 3C-scalines were examined at key monoamine targets in vitro. Binding affinity at human serotonergic 5-HT1A, 5-HT2A, and 5-HT2C, adrenergic α1A and α2A, and dopaminergic D2 receptors, rat and mouse trace amine-associated receptor 1 (TAAR1), and human monoamine transporters were assessed using target specific transfected cells. Furthermore, activation of human 5-HT2A and 5-HT2B receptors, and TAAR1 was examined. Generally, scalines and 3C-scalines bound with weak to moderately high affinity to the 5-HT2A receptor (K i = 150-12,000 nM). 3C-scalines showed a marginal preference for the 5-HT2A vs the 5-HT2C and 5-HT1A receptors whereas no preference was observed for the scalines. Extending the 4-alkoxy substituent increased 5-HT2A and 5-HT2C receptors binding affinities, and enhanced activation potency and efficacy at the 5-HT2A but not at the 5-HT2B receptor. Introduction of fluorinated 4-alkoxy substituents generally increased 5-HT2A and 5-HT2C receptors binding affinities and increased the activation potency and efficacy at the 5-HT2A and 5-HT2B receptors. Overall, no potent affinity was observed at non-serotonergic targets. As observed for other psychedelics, scalines and 3C-scalines interacted with the 5-HT2A and 5-HT2C receptors and bound with higher affinities (up to 63-fold and 34-fold increase, respectively) when compared to mescaline.

Laryngeal reflex responses in pediatric anesthesia.

Laryngeal and respiratory reflexes are vitally important defense mechanisms against foreign body aspiration, safeguarding airway patency, and ventilation. These highly preserved automatisms easily overrule external influences like willpower or (anesthetic) medication. Prevention and anticipation are, therefore, the essential strategies to avoid adverse events and damage, and treatment is most effective in the early stage of the reflex response. The physiology and pathophysiology of the various defensive reflexes as well as a comprehensive anesthetic approach to prevention and treatment are outlined in this review.

Receptor Interaction Profiles of 4-Alkoxy-Substituted 2,5-Dimethoxyphenethylamines and Related Amphetamines.

Background: 2,4,5-Trimethoxyamphetamine (TMA-2) is a potent psychedelic compound. Structurally related 4-alkyloxy-substituted 2,5-dimethoxyamphetamines and phenethylamine congeners (2C-O derivatives) have been described but their pharmacology is mostly undefined. Therefore, we examined receptor binding and activation profiles of these derivatives at monoamine receptors and transporters. Methods: Receptor binding affinities were determined at the serotonergic 5-HT1A, 5-HT2A, and 5-HT2C receptors, trace amine-associated receptor 1 (TAAR1), adrenergic α1 and α2 receptors, dopaminergic D2 receptor, and at monoamine transporters, using target-transfected cells. Additionally, activation of 5-HT2A and 5-HT2B receptors and TAAR1 was determined. Furthermore, we assessed monoamine transporter inhibition. Results: Both the phenethylamine and amphetamine derivatives (K i = 8-1700 nM and 61-4400 nM, respectively) bound with moderate to high affinities to the 5-HT2A receptor with preference over the 5-HT1A and 5-HT2C receptors (5-HT2A/5-HT1A = 1.4-333 and 5-HT2A/5-HT2C = 2.1-14, respectively). Extending the 4-alkoxy-group generally increased binding affinities at 5-HT2A and 5-HT2C receptors but showed mixed effects in terms of activation potency and efficacy at these receptors. Introduction of a terminal fluorine atom into the 4-ethoxy substituent by trend decreased, and with progressive fluorination increased affinities at the 5-HT2A and 5-HT2C receptors. Little or no effect was observed at the 5-HT1A receptor for any of the substances tested (K i ≥ 2700 nM). Phenethylamines bound more strongly to the TAAR1 (K i = 21-3300 nM) compared with their amphetamine analogs (K i = 630-3100 nM). Conclusion: As seen with earlier series investigated, the 4-alkyloxy-substituted 2,5-dimethoxyamphetamines and phenethylamines share some trends with the many other phenethylamine pharmacophore containing compounds, such as when increasing the size of the 4-substituent and increasing the lipophilicity, the affinities at the 5-HT2A/C subtype also increase, and only weak 5-HT2A/C subtype selectivities were achieved. At least from the binding data available (i.e., high affinity binding at the 5-HT2A receptor) one may predict mainly psychedelic-like effects in humans, at least for some of the compound investigated herein.

Diagnosis of asthma in children: the contribution of a detailed history and test results.

INTRODUCTION: There are few data on the usefulness of different tests to diagnose asthma in children. AIM: We assessed the contribution of a detailed history and a variety of diagnostic tests for diagnosing asthma in children. METHODS: We studied children aged 6-16 years referred consecutively for evaluation of suspected asthma to two pulmonary outpatient clinics. Symptoms were assessed by parental questionnaire. The clinical evaluation included skin-prick tests, measurement of exhaled nitric oxide fraction (F eNO), spirometry, bronchodilator reversibility and bronchial provocation tests (BPT) by exercise, methacholine and mannitol. Asthma was diagnosed by the physicians at the end of the visit. We assessed diagnostic accuracy of symptoms and tests by calculating sensitivity, specificity, positive and negative predictive values and area under the curve (AUC). RESULTS: Of the 111 participants, 80 (72%) were diagnosed with asthma. The combined sensitivity and specificity was highest for reported frequent wheeze (more than three attacks per year) (sensitivity 0.44, specificity 0.90), awakening due to wheeze (0.41, 0.90) and wheeze triggered by pollen (0.46, 0.83) or by pets (0.29, 0.99). Of the diagnostic tests, the AUC was highest for F eNO measurement (0.80) and BPT by methacholine (0.81) or exercise (0.74), and lowest for forced expiratory volume in 1 s (FEV1) (0.62) and FEV1/forced vital capacity ratio (0.66), assessed by spirometry. CONCLUSION: This study suggests that specific questions about triggers and severity of wheeze, measurement of F eNO and BPT by methacholine or exercise contribute more to the diagnosis of asthma in school-aged children than spirometry, bronchodilator reversibility and skin-prick tests.

Prevalence of high-risk drug-drug interactions in paediatric inpatients: a retrospective, single-centre cohort analysis.

AIMS OF THE STUDY: Drug-drug interaction (DDI) screening programmes aim to increase the safety of medication by issuing alerts based on the severity of DDIs, since an increased risk of adverse drug events has been reported for some DDIs (clinically relevant alerts). However, not all DDI alerts may be clinically relevant, depending on the clinical decision support system (CDSS) interaction tool used and the target population. There are few data about the frequency and relevance of DDIs in the paediatric population. The objective of this study was to evaluate the prevalence and appropriateness of high-risk DDI alerts (drug combinations that are rated as “contraindicated” or “contraindicated by precaution” according to the Swiss CDSS interaction tool Pharmavista® (HCI Solutions AG, Bern, Switzerland)) in paediatric inpatients. METHODS: We carried out a retrospective, single-centre study examining a cohort of paediatric cases hospitalised between January and May 2017 on the surgery/orthopaedic and oncology wards at the University of Basel Children’s Hospital (UKBB), Switzerland. Drugs administered to the patients concomitantly were obtained from the medical records. DDI screening was performed using Pharmavista®. All DDIs detected were documented with their severity grading for each hospital day per case. The clinical relevance of DDI alerts for drug combinations rated as contraindicated or contraindicated by precaution was critically evaluated by a literature review. RESULTS: A total of 300 patient cases were assessed for “contraindicated” or “contraindicated by precaution” DDI alerts. Of these, none had “contraindicated” and five had DDI alerts rated as “contraindicated by precaution” (1.7%, 95% CI 0.6–4.1%). The corresponding drug combinations were tramadol/fentanyl/morphine-nalbuphine (n = 3), droperidol-ondansetron (n = 1) and methotrexate-metamizole (n = 1), given for a duration of 1–2 days. Adverse drug events (ADEs) due to these three combinations (QT prolongation with the combination droperidol-ondansetron, reduced effect of opioid agonists with nalbuphine and increased haematotoxicity with methotrexate-metamizole) were not documented in the patients’ medical records. CONCLUSIONS: The low prevalence of contraindicated DDIs suggests that Pharmavista® has a low risk of over-alerting when used in a Swiss paediatric hospital. However, the current literature suggests that the severity rating of established contraindicated DDIs could be partially downgraded, and that patient/population-specific evaluations of DDI alerts are needed.

A Swiss database and biobank to better understand and manage congenital lung anomalies.

Congenital lung anomalies are a group of rare malformations, often diagnosed during the prenatal period. Guidelines on how to manage these patients are currently under debate, especially with regard to prophylactic surgery in asymptomatic patients, or how to proceed with conservative follow-up. Currently, there is no clear consensus on management strategies. A Swiss congenital lung anomaly national database and biobank was created in 2016 to enable data recording and collection of surgical lung samples in order to help define the most appropriate management strategies. This national observational cohort study represents an important step towards a better understanding of the pathophysiology and clinical course of the diseases included under congenital lung anomalies, especially in the context of a small country like Switzerland.

Monoamine receptor interaction profiles of 4-aryl-substituted 2,5-dimethoxyphenethylamines (2C-BI derivatives).

Many ring-substituted phenethylamines exert psychedelic effects that are thought to be primarily mediated by interactions with serotonergic 5-hydroxytryptamine 2 (5-HT2A) receptors. The 2,5-dimethoxyphenethylamine (2C derivative) core structure with small lipophilic substituents at the 4-position seems to be particularly favorable for psychedelic effects. In contrast, 2C derivatives with bulky lipophilic substituents at the 4-position of the phenyl ring tend to display antagonist behavior at serotonin 5-HT2 receptor sites. To gain a better understanding of agonist and antagonist behavior of substituted phenethylamines, binding affinities and functional activation and inhibition of a series of 4'-aryl substituted 2,5-dimethoxyphenethylamine (2C-BI derivatives) at various monoamine receptors were determined. In addition, the interactions of the compounds with monoamine transporters were assessed. Various 2C-BI derivatives potently bound to human serotonergic and adrenergic receptors and to rat and mouse trace amine-associated receptor 1. Additionally, 2C-BI-8 and 2C-BI-12 activated serotonin 5-HT2A and 5-HT2B receptors at submicromolar concentrations. 2C-BI-1 and 2C-BI-7 were the only 2C-BI derivatives to activate human trace amine-associated receptor 1. 2C-BI-3 and 2C-BI-4 interacted with monoamine transporters but with low overall potency. In conclusion, the tested 2C-BI derivatives displayed diverse pharmacological profiles. The relatively high affinities of various 2C-BI derivatives at the serotonin 5-HT2A receptor indicate a high steric tolerance of the binding pocket. Potent partial activation of the serotonin 5-HT2A receptor by 2C-BI-8 and 2C-BI-12 suggests that these substances may potentially exert psychedelic effects similar to other compounds of the 2C family.

Damage control orthopedics applied in an 8-year-old child with life-threatening multiple injuries: A CARE-compliant case report.

RATIONALE: Damage control is a staged surgical approach to manage polytraumatized patients. The damage control approach comprises three steps. First, bleeding is controlled and fractures are stabilized temporarily; second, vital parameters are stabilized and the child is rewarmed in the intensive care unit; and third, the child is reoperated for definitive repair of injuries. We aimed to describe the feasibility of the damage control orthopedic approach in a child. PATIENT CONCERNS: An 8-year-old girl fell from the balcony of the 5th floor onto concrete pavement and was admitted to our accident and emergency ward in a stable cardiorespiratory state, but with gross deformity of the lower limbs, left thigh, and forearm. DIAGNOSES: The child had sustained multiple injuries with severe bilateral lung contusion, pneumothorax, fracture of first rib, liver laceration, stable spine fractures, transforaminal fracture of sacrum, pelvic ring fracture, displaced baso-cervical femoral neck fracture, displaced bilateral multifragmental growth plate fractures of both tibiae, fractures of both fibulae, displaced fracture of left forearm, and displaced supracondylar fracture of the humerus. INTERVENTION: In the initial operation, we performed closed reduction and K-wire fixation of the right tibia, closed reduction and external fixation of the left tibia, open reduction and screw osteosynthesis of the femoral neck fracture, closed reduction and K-wire fixation of the radius, and closed reduction of the supracondylar fracture. Subsequently, we transferred the girl to the pediatric intensive care unit for hemodynamic stabilization, respiratory therapy, rewarming, and treatment of crush syndrome. In a third step, 10 days after the injury, we managed the supracondylar fracture of the humerus by closed reduction and K-wire fixation. OUTCOMES: Growth arrest of the left distal tibial growth plate and osteonecrosis of the femoral head and neck, slipped capital femoris epiphysis (SCFE), and coxa vara of the right femur led to balanced leg length inequality 2 years after the injury. The lesion of the left sciatic nerve improved over time and the girl walked without walking aids and took part in school sports but avoided jumping exercises. LESSONS: We emphasize the importance of damage control principles when managing polytraumatized children.

Do clinical investigations predict long-term wheeze? A follow-up of pediatric respiratory outpatients.

INTRODUCTION: The contribution of clinical investigations to prediction of long-term outcomes of children investigated for asthma is unclear. AIM: We performed a broad range of clinical tests and investigated whether they helped to predict long-term wheeze among children referred for evaluation of possible asthma. METHODS: We studied children aged 6 to 16 years referred to two Swiss pulmonary outpatient clinics with a history of wheeze, dyspnea, or cough in 2007. The initial assessment included spirometry, fractional exhaled nitric oxide, skin prick tests, and bronchial provocation tests by exercise, methacholine, and mannitol. Respiratory symptoms were assessed with questionnaires at baseline and at follow-up 7 years later. Associations between baseline factors and wheeze at follow-up were investigated by logistic regression. RESULTS: At baseline, 111 children were examined in 2007. After 7 years, 85 (77%) completed the follow-up questionnaire, among whom 61 (72%) had wheeze at baseline, while at follow-up 39 (46%) reported wheeze. Adjusting for age and sex, the following characteristics predicted wheeze at adolescence: wheeze triggered by pets (odds ratio, 4.2; 95% CI, 1.2-14.8), pollen (2.8, 1.1-7.0), and exercise (3.1, 1.2-8.0). Of the clinical tests, only a positive exercise test (3.2, 1.1-9.7) predicted wheeze at adolescence. CONCLUSION: Reported exercise-induced wheeze and wheeze triggered by pets or pollen were important predictors of wheeze persistence into adolescence. None of the clinical tests predicted wheeze more strongly than reported symptoms. Clinical tests might be important for asthma diagnosis but medical history is more helpful in predicting prognosis in children referred for asthma.