Changes in epinephrine dispensings and allergy hospitalisations in Sweden in the years following the removal of autoinjector co-payments.

Introduction: To understand any possible healthcare system benefits and changes of behavior for the patients with the change in prescription co-payment in Sweden we aimed to provide an update on the trends of EAI dispensings and hospitalizations for the Swedish paediatric population (ages 0-19 years), from 2018 to 2022, including by sex and geographic region. Methods: Using publically-available, population-level aggregate data from Sweden's National Board of Health and Welfare, we extracted information on annual epinephrine (ATC C01CA24) dispensings per 1,000 inhabitants from 2018 to 2023, overall, as well as stratified by sex, age groups and geographic region; and on inpatient stays 2018-2022 (ICD-10 code T78), anaphylaxis and other allergic reactions, per 100,000 individuals. We compared these estimates to those for adults ages 18 + years, for whom prescription co-payments remained in place. Results: EAI dispensings remained stable for children and adults across the study period, with the exception of statistically significant decreases amongst dispensings for children across all ages in 2021 (6.65/1,000) and 2022 (7.37/1,000), compared to 2018 (8.63/1,000) (each year p = 0.03 compared to 2018 dispensings). National EAI dispensings did not statistically significantly differ from 2018 (8.63/1,000) to 2023 (6.70/1,000) amongst children. EAI dispensings for children ages 5 + years consistently exceed dispensings for adults per 1,000 inhabitants; only children aged 0-4 years had proportionately fewer dispensings. Children ages 0-4 years tended to be hospitalised more often than older children, albeit these differences were not statistically significant (all p > 0.97). Conclusion: Subsequent to the removal of out-of-pocket costs for EAI, dispensings did not increase for children, although more EAI were dispensed to children from age 5 years, compared to younger children. Allergy-related hospitalisations were highest amongst children ages 0-4, lower amongst children ages 5-14 years, and again higher amongst those ages 15-19 years.

Association of temperature and absolute humidity with incidence of exercise-induced bronchoconstriction in children.

AIM: Exercise test outdoors is widely used to diagnose asthma in children, but it is unclear how much outdoor air factors affect the results. METHODS: We analysed 321 outdoor exercise challenge tests with spirometry in children 6-16 years conducted due to suspicion of asthma or for assessing the effect of medication on asthma. We studied the association of FEV1 decrease and incidence of exercise-induced bronchoconstriction (EIB) with temperature, relative humidity (RH) and absolute humidity (AH). RESULTS: Asthma was diagnosed in 57% of the subjects. AH ≥5 g/m3, but not RH or temperature, was associated with the EIB incidence (p = 0.035). In multivariable logistic regression, AH ≥5 g/m3 was negatively associated (OR = 0.51, 95% CI [0.28─0.92], p = 0.026) while obstruction before exercise (OR = 2.11, 95% CI [1.16─3.86], p = 0.015) and IgE-mediated sensitisation were positively associated with EIB (OR = 2.24, 95% CI [1.11─4.51], p = 0.025). AH (r = -0.12, p = 0.028) and temperature (r = -0.13, p = 0.023) correlated with decrease in FEV1. In multivariable linear regression, only AH was associated with FEV1 decrease (coefficient = -0.044, 95% CI [-0.085 to -0.004], p = 0.033). CONCLUSION: AH of outdoor air associates with occurrence and severity of EIB in outdoor exercise tests in children. Care should be taken when interpreting negative outdoor exercise test results if AH of air is high.

Paediatric asthma hospitalisations continue to decrease in Finland and Sweden between 2015 and 2020.

We previously reported a decreasing incidence of paediatric asthma hospitalisations in Finland, but a rather stable trend in Sweden, between 2005 and 2014. We now aimed to investigate the incidence of paediatric asthma hospitalisations in these countries between 2015 and 2020, using Finland's National Hospital Discharge Register and Sweden's National Patient Register, which cover all hospitalisations in the respective countries. From 2015 to 2019, the incidence of paediatric asthma hospitalisations decreased by 36.7% in Finland and by 39.9% in Sweden and are increasingly approaching parity. In 2020, despite differences in COVID-19-related restrictions, asthma hospitalisations decreased by over 40%, thus warranting future research on the subject.

Exercise-induced bronchoconstriction is associated with air humidity and particulate matter concentration in preschool children.

BACKGROUND: Long-term exposure to air pollution is connected to asthma morbidity in children. Exercise-induced bronchoconstriction (EIB) is common in asthma, and the free running test outdoors is an important method for diagnosing asthma in children. It is not known whether momentary air pollution exposure affects the results of outdoor exercise tests in children. METHODS: We analyzed all reliable exercise challenge tests with impulse oscillometry in children (n = 868) performed between January 2012 and April 2015 at Tampere University Hospital. Pollutant concentrations (PM2.5 , NO2 , and O3 ) at the time of the exercise test were collected from public registers. We compared the pollutant concentrations with the proportion and severity of EIB and adjusted the analyses for air humidity and pollen counts. RESULTS: Pollution levels were rarely high (median PM2.5 6.0 µg/m3 , NO2 12.0 µg/m3 , and O3 47.0 µg/m3 ). The relative change in resistance at 5 Hz after exercise did not correlate with O3 , NO2 or PM2.5 concentrations (p values 0.065-0.884). In multivariate logistic regression, we compared the effects of PM2.5 over 10 µg/m³, absolute humidity (AH) over 10 g/m³ and alder or birch pollen concentration over 10 grains/m³. High (over 10 g/m3 ) AH was associated with decreased incidence (OR 0.31, p value 0.004), and PM2.5 over 10 µg/m³ was associated with increased incidence (OR 1.69, p value 0.036) of EIB. CONCLUSIONS: Even low PM2.5 levels may have an effect on EIB in children. Of the other properties of air, only AH was associated with the incidence of EIB.

Outdoor pollen concentration is not associated with exercise-induced bronchoconstriction in children.

BACKGROUND: Free running exercise test outdoors is an important method to diagnose asthma in children. However, the extent of how much exposure to pollens of outdoor air affects the results of the test is not known. METHODS: We analyzed all reliable exercise challenge tests with impulse oscillometry in children (n = 799) between January 2012 and December 2014 in Tampere University Hospital. Pollen concentrations at the time of the test were collected from the register of Biodiversity Unit of the University of Turku. We compared the frequency of exercise-induced bronchoconstriction and pollen concentrations. RESULTS: The analyses were restricted to birch and alder pollen as high counts of grass and mugwort pollen were so infrequent. The relative change in resistance at 5 Hz after exercise or the frequency of exercise-induced bronchoconstriction were not related to alder or birch pollen concentrations over 10 grains/m3 (p = 0.125-0.398). In logistic regression analysis comparing the effects of alder or birch pollen concentrations, immunoglobulin E (IgE)-mediated alder or birch allergy and absolute humidity over 10 g/m3 only absolute humidity was independently associated with change in airway resistance (odds ratio [OR]: 0.32, confidence interval [CI]: 0.13-0.67, p: 0.006). CONCLUSIONS: In our large clinical sample, outdoor air pollen concentration was not associated with the probability of exercise-induced bronchoconstriction in free running test in children while low absolute humidity was the best predictor of airway obstruction.

Prevalence and clinical significance of esophageal abnormalities in children with celiac disease.

Variable endoscopic and histological findings of esophageal lining are often detected in celiac disease, with unknown significance. We investigated the frequency and significance of such abnormalities in children. Macroscopic esophageal findings as reported by endoscopist and histological results by pathologist were compared between 316 celiac disease patients and 378 disease controls who had undergone upper gastrointestinal endoscopy with systematic esophageal biopsy sampling. Association between esophageal abnormalities and other clinical and histological characteristics of the disease was evaluated in celiac disease patients. Endoscopic esophageal findings were reported least often (3.8%) of all diseases in celiac disease, whereas histopathologic abnormalities were frequent (16.8%, n = 53). Children with celiac disease and esophageal histopathology reported more reflux than those with normal esophagus (5.7 vs. 0.8%, P = 0.032), whereas the groups were comparable in the frequency and severity of other symptoms, demographic data, prevalence of celiac disease-associated and other coexisting chronic conditions, family history of celiac disease, anthropometric and laboratory parameters, and degree of villous atrophy. Only 2 (3.7%) out of the 53 children with histologic findings had esophageal symptoms at diagnosis, and altogether seven were treated with acid blockers. Four children had increased number (≥15 eosinophils per high-power field) of esophageal eosinophils, but none of them had definite eosinophilic esophagitis. The remaining 45 children had only unspecific inflammation in the esophagus and reported no esophageal problems during a median of 6.9 years follow-up. To conclude, although relatively common, histopathological esophageal findings in celiac disease are mostly unspecific and without major clinical significance even in a long-term follow-up.

The use of short-acting beta-2 adrenergic receptor agonists for asthma increased among Finnish and Swedish children from 2006 to 2017.

AIM: Paediatric asthma hospitalisation has decreased in Finland, but has remained stable in Sweden. The reasons for these intercountry differences are unclear. The aim of this study was to explore the trend of dispensed asthma medication, including inhaled corticosteroids (ICS), among paediatric populations in the two countries. METHODS: We explored trends in dispensed asthma medication among paediatric populations aged 0-19 in Finland and Sweden from 2006 to 2017. The Finnish Statistics on Reimbursements for Prescription Medicines and The Swedish Prescribed Drug Register provided data on all dispensed asthma prescriptions. RESULTS: During the study period, the prevalence of dispensed ICS in paediatric populations was fairly stable in Finland and Sweden. Among children aged 0-4, ICS were 1.5 times more commonly dispensed in Sweden than in Finland. The prevalence of children dispensed short-acting beta-2 adrenergic receptor agonists (SABA) increased in both countries, but rose more in Finland (51%) than in Sweden (27%). CONCLUSION: Inhaled corticosteroids were more commonly dispensed for children aged 0-4 in Sweden than in Finland during the study period. This study showed an increasing prevalence of children dispensed SABA in Finland and Sweden, particularly in Finland. Differences and trends in asthma medication may effect asthma hospitalisation and asthma deaths.

Reduced expiratory variability index (EVI) is associated with controller medication withdrawal and symptoms in wheezy children aged 1-5 years.

BACKGROUND: Lung function testing is an essential part of diagnostic workup and monitoring of asthma, but young children are lacking easy, routine testing methods. However, recent discoveries show reduced tidal breathing variability measured using impedance pneumography (IP) at home during sleep as a sign of airway obstruction. In this study, we assessed (a) the discriminative capacity of expiratory variability index (EVI) between healthy controls and young children with recurrent wheeze on-and-off controller medication, (b) association between EVI and parentally perceived obstructive symptoms (need for bronchodilator) and (c) measurement success rate. METHODS: We included 68 patients (aged 1.0-5.6) and 40 healthy controls (aged 1.0-5.9 years). The patients were prescribed a three-month inhaled corticosteroid (ICS) treatment due to recurrent obstructive bronchitis. We measured EVI using IP at home at the end of the treatment (0W) and 2 (2W) and 4 (4W) weeks after ICS withdrawal. RESULTS: EVI was higher in controls than in patients, and significant within-patient reduction occurred at 4W as compared to 2W or 0W. Area under curve of the ROC curve (controls vs all patients) at 4W was 0.78 (95% CI 0.70-0.85). Children who were administered bronchodilator by parental decision had lower EVI than those without bronchodilator need at 4W, but not at 0W or 2W. Patients with parent-reported airway infection, but no bronchodilator need, had normal EVI. Measurement success rate was 94%. CONCLUSION: EVI was lower in patients than in controls and it reduced further after controller medication withdrawal, especially in the presence of parentally perceived wheeze symptoms. This technique shows a significant potential for routine lung function testing of wheezy young children.

Association of air humidity with incidence of exercise-induced bronchoconstriction in children.

BACKGROUND: The effects of humidity and temperature on results of free running test in children are not known. OBJECTIVE: Assess the relation of outdoor air temperature, relative humidity (RH), and absolute humidity (AH) to airway obstruction in children after free running exercise test. METHODS: We analyzed all exercise challenge tests with impulse oscillometry in children between January 2012 and April 2015 in the Tampere University Hospital. The associations of AH, RH, and temperature of outdoor air with change in airway resistance were studied using regression analysis and by comparing the frequency of exercise-induced bronchoconstriction (increase ≥40% in resistance at 5 Hz) at different levels of temperature and humidity. RESULTS: Overall, 868 children with reliable results were included (mean age: 5.4 years; range: 3.0-14.1). In regression analysis, the relative change in resistance at 5 Hz after exercise was related to temperature (regression coefficient = -0.223, P = .020) and AH (regression coefficient = -0.893, P = .002), but not to RH. If absolute air humidity was <5 g/m3 , exercise-induced bronchoconstriction (EIB) occurred in 17.6% of study subjects and at AH levels ≥10 g/m3 , it occurred in 5.9% of study subjects (P = .008). In multiple regression analysis comparing the effects of temperature and humidity and adjusting for covariates, only AH was independently associated with change in airway resistance (P = .009). CONCLUSION: High AH of air is associated with lower incidence of EIB after outdoor exercise test in children. A negative test result at AH ≥10 g/m3 should be interpreted with caution.

Very low asthma death incidence among Finnish children from 1999 to 2015.

BACKGROUND: The most recent reports concerning asthma fatalities in Finnish children are from 1998. Since that time, asthma care has improved and asthma-related hospitalizations have decreased. Yet, it is unknown whether pediatric asthma deaths have similarly decreased. OBJECTIVE: To investigate the epidemiology of asthma deaths in the Finnish pediatric population from 1999 onward and to describe the details of fatal asthma exacerbations. METHODS: We obtained copies of the death certificates from Statistics Finland of all Finnish children aged 0-19 years who died from asthma between 1999 and 2015. After analyzing the death certificates, the medical records of those with possible asthma death were evaluated in detail to confirm the diagnosis. Incidence rates (IR) of asthma deaths were estimated per 1 000 000 person-years by dividing the number of asthma deaths by the total number of person-years. RESULTS: Between 1999-2015, there were 6845 deaths among 0-19 year-old children, of which 21 were possible asthma deaths. Based on patient records and pathological findings, we identified four convincing asthma deaths: aged 7 months, 1 year, 2.5 years, and 19 years. None had known allergies or regularly used inhaled corticosteroids. No pre-school or school-aged children died from asthma in Finland between 1999 and 2015. The cumulative incidence of pediatric asthma deaths was 0.19 per million person-years. CONCLUSION: Four Finnish children died from asthma between 1999 and 2015. This corresponds to a total incidence of 0.19 per million person-years. No pre-school or school-aged children died from asthma in Finland during the study period.

Current state and future of pediatric allergology in Europe: A road map.

The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology-later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded. There are striking differences across Europe, and even within European countries, in relation to the training pathways for doctors seeing children with allergic disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and sponsored a workshop with the European Academy of Allergy and Clinical Immunology (EAACI) Pediatric Section. This collaboration focussed on the future of PA and specifically on education, research, and networking/ advocacy. The delegates representing many countries across Europe have endorsed the concept that optimal care of children with allergic diseases is delivered by pediatricians who have received dedicated training in allergy, or allergists who have received dedicated training in pediatrics. In order to meet the needs of children and families with allergic disease(s), the pediatric allergist is highly encouraged to develop several networks. Our challenge is to reinforce a clear strategic approach to scientific excellence to across our member base and to ensure and enhance the relevance of European pediatric research in allergy. With research opportunities in basic, translational, clinical, and epidemiologic trials, more trainees and trained specialists are needed and it is an exciting time to be a pediatric allergologist.

Trends in paediatric asthma hospitalisations - differences between neighbouring countries.

Paediatric asthma hospitalisation trends in Finland and Sweden over the past 10 years are unclear. We investigated the incidence of paediatric asthma hospitalisations in both countries from 2005 to 2014, using Finland's National Hospital Discharge Register and Sweden's National Patient Register which cover all hospitalisations in the respective countries. During the study period, the incidence of paediatric asthma hospitalisations decreased by 51% in Finland, but remained stable in Sweden. In both countries, asthma hospitalisations decreased over time among children aged 0-4 years, with unclear trends for older ages. The reasons for these intercountry differences are unclear, thus warranting future research.