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Aim: The aim of this cohort study was to evaluate doctor-diagnosed and self-reported asthma in young adults after early-childhood hospitalisation for wheezing. Methods: In this prospective-controlled follow-up, questionnaires were sent to 95 subjects aged 24–28 years, who had been hospitalised for their first episodes of wheezing under 24 months of age. Fifty-eight cases and 100 controls returned the questionnaires. Results: The risk of doctor-diagnosed asthma was 2.14-fold (95% confidence interval 0.61–7.41), and the risk of self-reported asthma 2.39-fold (1.14–4.99) in cases compared to controls. The increased risk of self-reported asthma remained as statistically significant in analyses adjusted for current smoking, overweight and allergic rhinitis. Study subjects presented with wheezing symptoms, use of bronchodilators and inhaled corticosteroids, and with seasonal symptoms presumptive for allergic rhinitis during the last 12 months, more often than controls. The identification of a respiratory syncytial virus or rhinovirus during hospitalisation in early childhood was not anymore associated with asthma risk in adulthood. As expected, previous asthma during early childhood was a strong risk factor for asthma in young adulthood. Conclusion: In this controlled questionnaire study, early-childhood hospitalisation for lower respiratory infection with wheezing was an independently significant risk factor of asthma in young adults. publishedVersion

Background Interleukin-17A (IL-17A) and IL-17F are involved in the pathogenesis of asthma and allergy. Interleukin-17 receptor A (IL-17RA), encoded by the IL17RA gene, is a common receptor for IL-17A and IL-17F. The aim of the present study was to evaluate the association of IL17RA gene variations with asthma, allergy, and lung function at school age in children prospectively followed up after hospitalization for bronchiolitis in early infancy. Methods Data on IL17RA rs4819553, rs4819554, and rs4819558 polymorphisms and clinical outcomes, including asthma and allergic rhinitis, were available for 145 former bronchiolitis patients at 5-7 years and for 125 at 11-13 years of age. One hundred children underwent impulse oscillometry at 5-7 years and 84 underwent flow-volume spirometry at 11-13 years of age. The IL17RA rs4819553, rs4819554 and rs4819558 were completely co-segregating in Finnish children in our previous studies. Results The distributions of the studied IL17RA wild versus variant genotypes and major versus minor allele frequencies did not differ between bronchiolitis cases and population controls. These variations showed no significant association with asthma or allergic rhinitis nor with lung function reduction at 5-7 or 11-13 years of ages. Only 5.6% to 6.4% of the variations were homozygous. Conclusions The IL17RA gene variations that were studied showed no association with susceptibility to severe bronchiolitis in infancy, nor with post-bronchiolitis asthma or lung function at school age. Future studies should evaluate other IL17RA polymorphisms and include more cases, and especially cases with homozygous variations.

Aim Our aim was to evaluate the impact of the 2014 Finnish Current Care Guidelines for paediatric lower respiratory tract infections (LRTIs), particularly on taking of chest radiographs. Methods This study used official national data and regional (Pirkanmaa) data on children aged 0-16 years who underwent chest radiographs in 2011 and 2015. We also collected data for LRTI diagnoses from local registers, including prescribed antibiotics and taking of chest radiographs. The local cohort comprised children aged 0-15 who presented to the primary care emergency room or to the hospital emergency department (Tampere university hospital) in November-December 2012-2015. Results Chest radiographs for Finnish children aged 0-16 fell from 2011 to 2015: by 15.9% nationally and by 16.9% in Pirkanmaa. When asylum seekers with chest radiographs for tuberculosis screening were excluded, the estimated national reduction was 29.9%. In the local cohort, chest radiographs increased from 82 to 139 (69.5%) between 2012/2013 and 2014/2015 as the occurrence of community-acquired pneumonia (CAP) increased. However, the proportion of patients with CAP who had chest radiograph taken tended to decrease from 84.6% to 71.3% (p = 0.078). Conclusion Decreases in national and regional chest imaging trends were observed after the 2014 guidance for children`s LRTI was introduced.

Background:Wheezing in early childhood has implications for respiratory morbidity in later life.Objectives:We evaluated respiratory health-related quality of life (HRQoL) in young adults ages 17‐20 years with a history of early childhood wheezing.Methods:Between 1992 and 1993, 100 children ages < 24 months were treated in the hospital for a lower respiratory tract infection with wheezing, and we followed up this cohort. In 2010, 49 of the patients (cases) and 60 population-based controls attended a clinical follow-up. St. George’s Respiratory Questionnaire (SGRQ) was used to evaluate respiratory HRQoL, expressed as symptom, activity, impact, and total scores.Results:The median (interquartile range) SGRQ symptom scores were higher (13.7 [3.8‐29.1]) in the 49 subjects (cases) with early childhood wheezing compared with the 60 population controls (7.8 [0.0‐18.3]; p = 0.019). However, there were no between-group differences in total scores or in other SGRQ domains. Current asthma was a major risk factor for reduced HRQoL. In univariate analyses, the median symptom scores were 20.2 in those with asthma and 7.8 in those without asthma (p Conclusion:Hospitalization for wheezing in early childhood mainly had indirect effects on HRQoL by increasing the risk of asthma.

Aim A review published in 2015 showed that 331 Bacillus Calmette-Guerin (BCG) osteitis cases were globally reported in 1976-2012. The 222 Finnish cases from 1960 to 1988 formed two-thirds of all cases. The present narrative review summarises epidemiological, clinical and immunological findings obtained from this Finnish cohort in relation to data from other countries. Methods Six reports including 93 BCG osteitis cases, which were not included in the 2015 review, were identified from PubMed. Results In all, 424 BCG osteitis cases have been published. Population-based data were available only from Finland and Taiwan. The BCG osteitis incidence in Finnish infants was 6.4/100 000/year in 1960-1988 compared to 3.4/100 000/year in Taiwanese infants in 1998-2012. The incidence in Finland increased to 36.9/100 000 in 1971-1977, and the vaccinations were temporarily discontinued. Over half of lesions were in lower limbs and nearly all were solitary in both cohorts. The outcomes after surgery and chemotherapy were good. Immunology of BCG osteitis was studied only in the Finnish cohort. There were deviations from population data in polymorphisms of genes regulating Toll-like receptors 1, 2 and 6, mannose-binding lectin and interleukin-17A. Conclusion BCG osteitis after vaccination is rare. Preliminary findings in innate immunity raise a question of genetic background.

Aim Evidence based on studies of the encoding genes suggests that interleukin-1 receptor-associated kinase-4 (IRAK4) plays a role in childhood asthma and allergy. Our aim was to evaluate the associations of six IRAK4 gene polymorphisms with presence of asthma and allergic rhinitis and use of inhaled corticosteroids (ICSs) for asthma at 5-7 and 11-13 years of ages after hospitalisation for bronchiolitis at younger than 6 months of age. Methods IRAK4 rs4251513, rs4251520, rs4251522, rs4251578, rs79154645 and rs13852554 polymorphisms were determined in 141 former bronchiolitis patients prospectively followed up until 5-7 and in 125 children until 11-13 years of age. Results The homozygous variant IRAK4 rs4251513 genotype was associated with the presence of asthma and allergic rhinitis and use of ICSs at 5-7 and 11-13 years of ages in univariate analyses. Statistical significance remained for the presence of asthma and use of ICSs but was lost in the case of allergic rhinitis in multivariate analyses. The adjusted odds ratios were 3.48 and 4.16 for asthma and 5.22 and 14.00 for ICS use at these two ages. Conclusion The homozygous variant IRAK4 rs4251513 genotype was constantly associated with post-bronchiolitis asthma and asthma medication in school-aged children.

Aim Interleukin-17F (IL-17F) is involved with asthma. The aim of this study was to evaluate the association of IL17F polymorphisms with childhood asthma after bronchiolitis in infancy. Methods We invited 166 children who were hospitalised for bronchiolitis at younger than 6 months of age to follow-up visits at 5-7 years and 11-13 years of ages. Asthma and allergy diagnoses, asthma-presumptive symptoms and use of inhaled corticosteroids (ICSs) were registered. Blood samples were available for IL17F rs763780 (T/C), rs11465553 (C/T) and rs7741835 (C/T) determinations in 165 cases. Results The presence of IL17F rs11465553 and rs7741835 variations showed no significant associations with any asthma or allergy outcome at either 5-7 years or 11-13 years of ages. Instead, children with the variant IL17F rs763780 genotype had used more often ICSs between the follow-up visits from 5-7 to 11-13 years (adjusted OR 3.58) than those with the wild genotype. Children with the variant IL17F rs763780 genotype reported more often doctor-diagnosed atopic dermatitis (adjusted OR 2.71) at 11-13 years of age than those with the wild genotype. Conclusion This prospective long-term follow-up study provided preliminary evidence on the association of the IL17F rs763780 polymorphism with asthma at school age after bronchiolitis in infancy.

AIM Interleukin (IL)-33, encoded by the IL33 gene, is associated with allergy and asthma. We evaluated IL33 rs1342326 polymorphism in relation to asthma, asthma medication and allergic rhinitis after infant bronchiolitis. METHODS IL33 rs1342326 polymorphism was studied in children, who were hospitalised for bronchiolitis at age younger than 6 months and who were prospectively followed until 5-7 years (N = 141) and 11-13 years (N = 125) of ages. RESULTS The presence of the wild AA vs variant AC or CC genotypes of the IL33 rs1342326 showed no significant associations with previous or current asthma at the mean ages of 6.4 or 11.7 years. However, 22.5% of children with the variant genotype used inhaled corticosteroids at the 5-7 years of visit (adjusted OR: 2.94, 95% CI: 1.04-8.33 vs those 8.9% with the wild genotype). The variant IL33 rs1342326 genotype was associated with allergic rhinitis at 6.4 years (adjusted OR: 2.17, 95% CI: 1.01-4.76) and 11.7 years (3.23, 1.18-9.09) of ages. CONCLUSION The frequent use of asthma control medication in 6.4-year-old children with IL33 rs1342326 polymorphism suggests that this variation may increase susceptibility to severe asthma at preschool age. The IL33 rs1342326 variant genotype was associated with a 3-fold risk of allergic rhinitis at school age.

BACKGROUND Recent data suggest that early-term births are associated with later respiratory morbidity (LRTI), and post-term births may decrease this risk. OBJECTIVES The objective was to determine the impact of early-term, late-term, and post-term birth on hospital admission for LRTI up to the age of seven years. Additionally, we explored maternal and perinatal factors associated with the risk of admission for LRTIs. METHODS The association of early-term (37+0 -38+6 weeks), late-term (41+0 -41+6 weeks), and post-term (≥42 weeks) birth with hospital admissions for lower respiratory tract infections (LRTI) in comparison with infants born full-term (39+0 -40+6 weeks) was assessed and early predictors of LRTI were established. The register study included 948 695 infants born in Finland in 1991-2008. Data were analysed in four-term subgroups. Hospital admissions for bronchiolitis/bronchitis and pneumonia were collected up to 7 years of age. Adjusted Cox proportional hazards models were used to assess risk factors of LRTI admissions. RESULTS The rates of hospital admission in the early-, full-, late-, and post-term groups were 6.7%, 5.5%, 5.1%, and 4.8% for bronchiolitis/bronchitis, and 2.8%, 2.4%, 2.3%, and 2.3% for pneumonia. Early-term birth was associated with an increased risk of admission for bronchiolitis/bronchitis (hazard ratio HR 1.21, 95% confidence interval CI 1.18, 1.23) and pneumonia (HR 1.16, 95% CI 1.12, 1.20), while late-term (HR 0.93, 95% CI 0.91, 0.95) and post-term births (HR 0.89, 95% CI 0.85, 0.93) were associated with a decreased risk of bronchiolitis/bronchitis admission compared with the full-term group. Maternal age ≤ 20 years, smoking during pregnancy, male sex, caesarean delivery, small for gestational age, 1-minute Apgar score

PubMed was reviewed on antibiotic treatment of community-acquired pneumonia (CAP) in children for the years 2011-2020, and three clinical trials in high-income and eight in low-income countries were found. Prospective studies combining laboratory and clinical findings for steering of antibiotic treatment found that five-day courses were equally effective as longer courses. No new antibiotics were launched for children's CAP during the last 10 years. Five-day courses are equally effective as 7- to 10-day courses for CAP in children. Stewardship of antibiotics needs lessening of exposure to antibiotics by better targeting their use and by shortening the lengths of antibiotic courses.

Background: There is an increased risk of asthma after viral wheezing episodes in early childhood, but unfortunately, prospective longitudinal data are lacking. The aim of this cohort study was to evaluate the risk of asthma in young adulthood after hospitalization for viral wheezing episodes in early childhood. Methods: The original cohort comprised 100 individuals aged

Bronchiolitis in infancy is the most common infectious reason for hospitalization of infants without any chronic underlying illness. Areas covered: This review focuses on the role of racemic epinephrine, systemic corticosteroids, hypertonic saline and high-flow oxygen therapy (HFOT) in the treatment of infants with bronchiolitis. Literature was searched from Pubmed covering the years 2009-2018 using the entries of bronchiolitis or viral bronchiolitis, and epinephrine, adrenaline, racemic epinephrine, racemic adrenaline, corticosteroids, hypertonic saline, high-flow oxygen therapy, or high-flow oxygen cannula. Expert commentary: Many randomized controlled trials (RCT) have proved the ineffectiveness of beta-agonists, anticholinergics, and inhaled corticosteroids in infants with bronchiolitis. An RCT from Norway suggested that there are bronchiolitis patients, who may benefit from well-timed, on-demand inhalations of racemic epinephrine. Based on two RCTs from Qatar and the United States, the benefits of systemic steroids are marginal and need repeated doses, which increases the risk of adrenal suppression. In new meta-analyses, inhalations of hypertonic saline did not substantially shorten the stay in hospital for bronchiolitis. In two recent RCTs from Australia and New Zealand, HFOT with warmed and humidified air-oxygen mixture was superior to traditional low-flow oxygenation. HFOT is the only new and promising approach for treatment of infants with bronchiolitis.

Background The transition from early childhood wheezing to persistent asthma is linked to lung function impairment over time. Little is known how the methods used to study lung function at different ages correlate longitudinally. Methods Sixty-four children with a history of hospitalization for bronchiolitis before 6 months of age were prospectively studied with impulse oscillometry (IOS) at the mean age of 6.3 years and these preschool IOS results were compared with flow-volume spirometry (FVS) measurements at mean age of 11.4 years. Results The baseline respiratory system resistance at 5 Hz (Rrs5) showed a modest statistically significant correlation with all baseline FVS parameters except FVC. The post-bronchodilator (post-BD) Rrs5 showed a modest statistically significant correlation with post-BD FEV1 and FEV1 /FVC. The bronchodilator-induced decrease in Rrs5 showed a modest statistically significant correlation with the percent increase in FEV1 . Baseline and post-BD respiratory reactance at 5 Hz (Xrs5) showed a modest statistically significant correlation with baseline and post-BD FVS parameters except post-BD FEV1 /FVC, respectively, and post-BD Xrs5 showed a strong correlation with post-BD FVC (ρ = 0.61) and post-BD FEV1 (ρ = 0.59). In adjusted linear regression, preschool Xrs5 remained as a statistically significant independent predictor of FVS parameters in adolescence; the one-unit decrease in the Z-score of preschool post-BD Xrs5 predicted 9.6% lower post-BD FEV1 , 9.3% lower post-BD FVC, and 9.7% lower post-BD MEF50 when expressed as %-predicted parameters. Conclusion Persistent post-BD small airway impairment in children with a history of bronchiolitis detected with IOS at preschool age predicted FVS results measured in early adolescence.

OBJECTIVE To evaluate the frequency and predictors of hospital admissions for lower respiratory tract infections (LRTIs) in moderately preterm (MP, 32+0 to 33+6 weeks) and late preterm (LP, 34+0 to 36+6 weeks) infants compared to term (T ≥37 weeks) and very preterm (VP

Toll-like receptors (TLR) are innate immunity molecules and our previous studies found that TLR1 gene polymorphism was associated with postbronchiolitis asthma at one to six years of age, as was TLR10 at five to seven years of age. This study examined any associations at 11-13 years of age.This prospective follow-up study was part of an ongoing evaluation of children admitted to Tampere University Hospital, Finland, for bronchiolitis in 2001-2004 at less than six months of age. We evaluated the association of TLR1 rs5743618 and TLR10 rs4129009 polymorphisms with asthma and asthma medication in 125 children aged 11-13 years.Associations were measured as adjusted odd ratios (aOR) with 95% confidence intervals (95% CI). The variant TLR1 rs5743618 (aOR 4.04, 95% CI 0.99-13.01) and TLR10 rs4129009 (aOR 7.02, 95% CI 1.56-31.53) genotypes increased the risk of needing inhaled corticosteroids (ICSs) at 11-13 years of age. The variant TLR10 genotype (aOR 7.69, 95% CI 1.35-43.95) increased the risk of persistent asthma continuing from five to seven years of age until 11-13 years of age. The results were similar when the combined genotypes were analysed. [Correction added on 3 October 2017, after online publication: The data in the variant TRL1 rs5743618 genotype were incorrect and have been corrected in this version.] CONCLUSION: Polymorphisms in both the TLR1 and TLR10 genes may increase the risk of asthma at 11-13 years after infant bronchiolitis.

Objective To assess the incidence and risk factors of asthma and atopic dermatitis by seven years of age after early-term (ET) (37+0 -38+6 weeks), full-term (FT) (39+0 -40+6 weeks), late-term (LT) (41+0 -41+6 weeks), and especially post-term (PT) (≥42 weeks) birth. Methods Altogether, 965 203 infants born between 1991 and 2008 in Finland were investigated in ET, FT, LT, and PT groups. Data on asthma medication reimbursement and hospital visits for atopic dermatitis were retrieved from national health databases. Results The frequencies of asthma medication reimbursement in the ET, FT, LT, and PT groups were 4.5%, 3.7%, 3.3%, and 3.2%, respectively. Hospital visits due to atopic dermatitis were most common after PT birth. Compared with FT births, ET births were associated with an increased risk of asthma (adjusted odds ratio (aOR), 95% confidence interval (CI) 1.20, 1.17-1.23), while LT (aOR, 95%CI 0.91, 0.89-0.93) births and PT (aOR, 95%CI 0.87, 0.83-0.92) births decreased this risk. PT birth (aOR, 95%CI 1.06, 1.01-1.10) predicted atopic dermatitis. From a population point of view, the most relevant risk factors for asthma were male sex, ET birth, smoking during pregnancy and birth by elective cesarean section, and for atopic dermatitis male sex, first delivery, birth in a level II hospital and birth by cesarean section. Conclusions Early-term birth was a predictor of asthma, and PT birth was associated with atopic dermatitis. Counseling against smoking and following strict indications for planned ET deliveries and cesarean sections may be means to reduce the risk of later asthma.

Background Interleukin-17 (IL-17A) is a mainly pro-inflammatory cytokine, and IL-17 signaling implicates in the development of allergic asthma. The polymorphism rs2275913 in the promoter region of the IL-17A gene has in previous studies been associated with asthma susceptibility. The objective was to evaluate the association between IL-17A rs2275913 (-197G>A) polymorphism and post-bronchiolitis asthma and/or allergic rhinitis in a prospective 11–13 years post-bronchiolitis follow-up. Methods 166 previously healthy full-term infants, hospitalized for bronchiolitis at age less than 6 months, were invited to follow-up visits at the ages of 5–7 years and 11–13 years. Asthma diagnoses and presumptive symptoms, allergic rhinitis and use of inhaled corticosteroids (ICS) were registered. Blood samples for IL-17A rs2275913 (-197G>A) polymorphism were obtained during hospitalization or at the 5–7 years control visit. Results There were no significant differences between children with the wild GG and variant GA or AA genotype in the severity of bronchiolitis during hospitalization or in the outcomes until the age 5–7 years. At 11–13 years of age, children with the variant GA or AA genotype had significantly less often current asthma, use of ICSs during last 12 months or allergic rhinitis than those with the wild GG genotype. The ICS use during last 12 months retained the statistical significance in adjusted analyses (adjusted OR 0.25), whereas current asthma and allergic rhinitis marginally lost it. Conclusions The IL-17A rs2275913 (-197G>A) polymorphism decreased the risk of post-bronchiolitis asthma at 11–13 years of age, but not earlier in life, in the present prospective, long-term follow-up study.

Increasing evidence shows that environmental factors in childhood play a role in development of irreversible airway obstruction. We evaluated early-life and preschool-age risk factors for irreversible airway obstruction in adolescence after bronchiolitis in infancy.This study is a secondary analysis of data collected during prospective long-term follow-up of our post-bronchiolitis cohort. Risk factor data were collected during hospitalisation and on follow-up visits at 5-7 and 10-13 years of ages. Lung function was measured from 103 participants with impulse oscillometry at 5-7 years of age and from 89 participants with flow-volume spirometry at 10-13 years of age.Asthma diagnosis at12 months of age showed a significant association with irreversible airway obstruction at 10-13 years of age independently from current asthma. Irreversible airway obstruction was less frequent in children with variant than wild genotype of the Toll-like receptor 4(TLR4) rs4986790, but the significance was lost in logistic regression adjusted for current asthma and weight status. Higher post-bronchodilator respiratory system resistance at 5 Hz and lower baseline and post-bronchodilator reactance at 5 Hz by impulse oscillometry at 5-7 years of age were associated with irreversible airway obstruction at 10-13 years of age.Asthma diagnosis during the first living year and worse lung function at preschool age increased the risk for irreversible airway obstruction at 10-13 years of age after bronchiolitis. TLR4 rs4986790 polymorphism may be protective for development of irreversible airway obstruction after bronchiolitis.

We undertook a cumulative meta-analysis for the efficacy of hypertonic saline (HS) compared to normal saline (NS) inhalations or no inhalations as controls in bronchiolitis. We performed literature searches from PubMed, Scopus, and by hand search until 20 June 2017. We accepted published randomized controlled trials of HS inhalations in children with bronchiolitis aged

Background Five studies carried out after bronchiolitis at less than 24 months of age, with a follow-up of more than 10 years, reported that atopic dermatitis, family asthma, early-life exposure to tobacco smoke and rhinovirus aetiology were early-life risk factors for later asthma. This study evaluated the long-term outcome at 11-13 years of age of children who were hospitalized for bronchiolitis in early infancy. Methods We previously prospectively followed 166 children hospitalized for bronchiolitis at less than 6 months of age until 5-7 years of age. The current study included a structured questionnaire, parental interviews, clinical examinations and bronchodilation test of 138 of those children at 11-13 years of age. Results Respiratory syncytial virus caused 66% of the bronchiolitis cases, and nearly half of the patients were exposed to tobacco smoke in early life. Doctor-diagnosed asthma was present in 13% of the former bronchiolitis patients at 11-13 years of age. Maternal asthma was the only independently significant risk factor in early life (adjusted OR 3.45, 95% CI 1.07-11.74), as was allergic rhinitis at 5-7 years of age (adjusted OR 4.06, 95% CI 1.35-12.25). Conclusions After bronchiolitis at less than 6 months of age, the risk of doctor-diagnosed asthma at 11-13 years was about twice that of the general Finnish population. Maternal asthma was the only independently significant early-life risk factor for current asthma at 11-13 years of age.

Aim Infants hospitalised for bronchiolitis undergo examinations and treatments not supported by current research evidence and we investigated practice variations with regard to Finnish children under the age of two. Methods This prospective, multicentre cohort study was conducted in paediatric units in three university hospitals in Finland from 2008 to 2010. Hospital medical records were reviewed to collect data on clinical course, testing and treatment. Data were analysed separately for children meeting our strict definition of bronchiolitis, aged under 12 months without a history of wheezing, and a loose definition, aged 12–23 months or with a history of wheezing. Results The median age of the 408 children was 8.1 months. Clinical management varied between the three hospitals when stratified by strict and loose bronchiolitis subgroup definitions: complete blood counts ranged from 15–95% vs 16–94%, respectively, and the other measures were chest x-ray (16–91% vs 14–72%), intravenous fluids (2–47% vs 2–41%), use of nebulised epinephrine (10–84% vs 7–50%), use of salbutamol (18–21% vs 13–84%) and use of corticosteroids (6–23% vs 60–76%). Conclusion The clinical management of bronchiolitis varied considerably with regard to the three hospitals and the two definitions of bronchiolitis. A stronger commitment to evidence-based bronchiolitis guidelines is needed in Finland.

Aim The impact of the emergence of antimicrobial resistant organisms has rarely been studied in children, including the healthcare costs of urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria. We evaluated the effect of ESBL on UTI healthcare costs and risk factors for paediatric UTIs. Methods This retrospective case–control study covered 2005–2014 and focused on children below 16 years of age treated in a University hospital: 22 children with UTIs caused by ESBL-producing bacteria and 56 ESBL-negative UTI controls. Results The median healthcare costs were 3929 Euros for the 22 ESBL patients and 1705 Euros for the 56 controls (p = 0.015). The mean and standard deviation length of hospital stay was 7.4 (5.9) days for the ESBL group and 3.6 (2.3) days for the controls (p = 0.007), and the figures for antibiotic treatment were 12.3 (5.5) days versus 5.8 (3.0) days (p < 0.001), respectively. The odd ratios for ESBL were underlying disease (6.63, p = 0.013), previous hospitalisation (6.07, p = 0.009) and antibiotic prophylaxis (5.20, p = 0.035). Conclusion Healthcare costs more than doubled when children had ESBL-related UTIs, mainly due to their increased length of stay. Effective oral antibiotics are urgently needed to treat paediatric infections caused by ESBL-producing bacteria.

Background Respiratory syncytial virus (RSV)- and rhinovirus (RV)-induced bronchiolitis are associated with an increased risk of asthma, but more detailed information is needed on virus types. Objective To study whether RSV or RV types are differentially associated with the future use of asthma control medication. Methods Over 2 consecutive winter seasons (2008-2010), we enrolled 408 children hospitalized for bronchiolitis at age less than 24 months into a prospective, 3-center, 4-year follow-up study in Finland. Virus detection was performed by real-time reverse transcription PCR from nasal wash samples. Four years later, we examined current use of asthma control medication. Results A total of 349 (86%) children completed the 4-year follow-up. At study entry, the median age was 7.5 months, and 42% had RSV, 29% RV, 2% both RSV and RV, and 27% non-RSV/-RV etiology. The children with RV-A (adjusted hazard ratio, 2.3; P = .01), RV-C (adjusted hazard ratio, 3.5; P < .001), and non-RSV/-RV (adjusted hazard ratio, 2.0; P = .004) bronchiolitis started the asthma control medication earlier than did children with RSV bronchiolitis. Four years later, 27% of patients used asthma control medication; both RV-A (adjusted odds ratio, 3.0; P = .03) and RV-C (adjusted odds ratio, 3.7; P

Aim This paper summarises variations in the genes encoding toll-like receptors (TLRs) in relation to the aetiology and outcome of infant bronchiolitis. It compares the literature with research carried out by our group. Methods A mini review was conducted to provide context for a study carried out at the Department of Paediatrics, Tampere University Hospital, Finland. In 2000-2004, 187 infants were hospitalised for bronchiolitis and then followed up: 129 at 1.5 years of age, 166 at 5-7 years of age and 138 at 11-13 years of age. Results The review showed that the Finnish bronchiolitis study was the only prospective study on the association between TLRs and the emergence of childhood asthma or lung function reduction after bronchiolitis in infancy. It found that TLR1 and TLR10 variant genotypes were associated with more asthma at 5-7 and 11-13 years, with inconsistent results for the other eight TLR genes. Large population-based studies were also identified that stressed the importance of the TLR2 subfamily members in childhood asthma. Conclusion Our study found that variations in the TLR1 and TLR10 genes increased the asthma risk after bronchiolitis. The mini review calls for further research on the TLR2 subfamily in bronchiolitis and childhood asthma.

Aim Meta-analyses of randomised controlled trials on infant bronchiolitis do not support medication. We summarised the current data and evaluated the real-life use of medication for infants treated for bronchiolitis in hospitals, including paediatric wards, emergency departments and paediatric intensive care units (PICU). Methods We searched PubMed for studies published from 2009 to 2018 that provided data on the real-life use of adrenaline, salbutamol, corticosteroids or antibiotics for infants hospitalised for bronchiolitis. Results The review identified 10 such studies and showed substantial variations in medication for infant bronchiolitis between different countries and even between different hospitals in the same country. A multi-centre study including 38 hospitals in eight countries reported that a mean of 29% infants admitted for bronchiolitis received drugs without any research-based evidence on their effectiveness, ranging from 9% in Australia and New Zealand to 58% in Spain and Portugal. In addition, an American prospective multi-centre study of 16 PICUs reported that bronchodilators were used by a mean of 60%, corticosteroids by 33% and antibiotics by 63%. Other studies reported that higher ages and a history of wheezing increased the use of medication. Conclusion There were substantial variations in bronchiolitis treatment between, and within, different countries.

Aim The united airway disease (UAD) hypothesis suggests that allergic rhinitis and asthma develop together. We evaluated the evidence for and against the UAD hypothesis at five to seven years of age after hospitalisation for bronchiolitis at less than six months. Methods This study used prospective follow-up data for 102 children hospitalised for bronchiolitis under the age of six months. We included the presence of previous and current asthma, prolonged rhinitis and skin prick tests (SPT) to common inhaled allergens and lung function by impulse oscillometry (IOS) at five to seven years of age. Bronchial hyper-reactivity (BHR) was assessed using the exercise challenge test and bronchodilation test. Results Current asthma, but not previous transient asthma, was associated with prolonged rhinitis and a positive SPT. BHR, which reflected reactive airways, but not lung function, was associated with respiratory allergy, namely the combination of current asthma, prolonged rhinitis and a positive SPT. Conclusion This post-bronchiolitis follow-up study suggested an association between respiratory allergy and reactive airways at five to seven years of age, which supported the UAD hypothesis. However, previous transient asthma and a reduction in lung function reduction did not support the hypothesis.

BACKGROUND Bacterial colonization during wheezing in early childhood has been associated with short-term relapses of wheezing, but no study has addressed the effects of Streptococcus pneumoniae colonization on long-term outcome of wheezing. The aim of the present study was therefore to evaluate whether pneumococcal (PNC) colonization during the first wheezing episode in early childhood is a determinant of asthma, atopy or lung function in the long term. METHODS In 1981-82 83 infants were hospitalized for first wheezing episode at

Summary Background Variations in the genes that regulate innate immunity responses may be associated with susceptibility to asthma or atopy after early-life bronchiolitis. The aim of this study was to evaluate the association between four different polymorphisms of the IL-10 gene at rs1800871, rs1800872, rs1800890, and rs1800896, either alone or in combination, and post-bronchiolitis asthma or allergies at 5–7 years of age. Methods Data on single nucleotide polymorphisms (SNP) of IL-10 rs1800896 (−1082G/A), rs1800871 (−819C/T), rs1800872 (−592C/A), and IL-10 rs1800890 (−3575T/A) were available for 135 children. Polymorphisms and their associations with asthma and allergies were studied in 135 preschool-aged children who had been hospitalized for bronchiolitis at age 0–6 months. Their parents were interviewed to record the children's history with asthma and allergies from infancy to the present. Results At 6.4 years (mean), asthma was present in 17 children (12.6%), while recurrent wheezing during the first 7 years of life was present in 39 (28.9%) children. Fifty-three (39.3%) study participants had current atopy (atopic eczema or allergic rhinitis). Eight (72%) of 11 children with the IL-10 rs1800896, IL-10 rs1800871, and IL-10 rs1800872 combination AA + CT + CA had current atopy (P = 0.02 vs. 38% in other genotype combinations). Twenty-three (56%) children with the IL-10 rs1800871C/T or IL-10 rs1800872C/A genotype had present atopy versus 34 (38%) with other IL-10 genotypes (P = 0.03). Between 2 years and 3 years of age, 27% of ATA haplotype carriers had asthma versus 13.7% of other haplotype carriers (P = 0.02). Conclusions IL-10 polymorphisms at rs1800871, rs1800872, rs1800890, and rs1800896 seem to be associated with elevated allergies and/or recurrent wheezing risk in later childhood, after early-life bronchiolitis. Pediatr Pulmonol. 2016; 9999:XX–XX. © 2016 Wiley Periodicals, Inc.

We evaluated the cost-effectiveness of high-flow nasal cannula (HFNC) to provide additional oxygen for infants with bronchiolitis, compared to standard low-flow therapy. The cost-effectiveness was evaluated by decision analyses, using decision tree modeling, and was based on real costs from our recently published retrospective case-control study. The data on the effectiveness of HFNC treatment were collected from earlier published retrospective studies, using admission rates to pediatric intensive care units (PICU). The analyses in the study showed that the expected treatment costs of each episode of infant bronchiolitis varied between €1,312-2,644 ($1,786-3,600) in the HFNC group and €1,598-3,764 ($2,175-5,125) in the standard treatment group. The PICU admission rates and consequential costs were lower for HFNC than for standard treatment. HFNC treatment proved more cost-effective than standard treatment in all the baseline analyses and was also more cost-effective in the sensitivity analyses, except for in the worst-case scenario analysis. In conclusion, our modeling demonstrated that HFNC was strongly cost-effective for infant bronchiolitis, compared to standard treatment because it was both more effective and less expensive. Thus, if children hospitalized for bronchiolitis need oxygen, it should be delivered as HFNC treatment. Pediatr Pulmonol. 2016;51:1393-1402. © 2016 Wiley Periodicals, Inc.

AIM In Finland, specialist paediatrics training is led by university hospitals, but half of it is carried out in regional central hospitals. We audited the training provided by four regional central hospitals in the tertiary care area covered by Tampere University Hospital, in 2003, 2008 and 2015. METHODS The audits comprised hospital visits and discussions with the chief doctor of the paediatric clinic, the trainees and the specialists who trained them. A modified version of the European Union of Medical Specialists 1997 protocol was used, and the key areas that performed poorly in the audits were followed up. RESULTS In 2008 and 2015, most of the key follow-up issues had improved, but two main areas in need of further development were identified in 2015. These were that educational objectives should be clarified, and their implementation systemically followed up, and that trainees should spend more time working in outpatient settings. CONCLUSION Since 2003, a marked improvement had taken place in the paediatric training provided by regional central hospitals, partly because of the increase in paediatric specialist resources. This study underlines the importance of repeat audits and the need for co-opera-tion between the university hospital and regional hospitals, including regular visits.

Background The incidence of invasive group A streptococcus (iGAS) infections varies in time and geographically for unknown reasons. We performed a nationwide survey to assess the population-based incidence rates and outcomes of children with iGAS infections. Methods We collected data on patients from hospital discharge registries and the electronic databases of microbiological laboratories in Finland for the period 1996-2010. We then recorded the emm types or serotypes of the strains. The study physician visited all university clinics and collected the clinical data using the same data entry sheet. Results We identified 151 children with iGAS infection. Varicella preceded iGAS infection in 20% of cases and fasciitis infection in 83% of cases. The annual incidence rate of iGAS infection was 0.93 per 100,000 in 1996-2000, 1.80 in 2001-2005 and 2.50 in 2006-2010. The proportion of emm 1.0 or T1M1 strains peaked in 1996-2000 and again in 2006-2010, to 44% and 37% of all typed isolates. The main clinical diagnoses of the patients were severe soft-tissue infection (46%), sepsis (28%), empyema (10%), osteoarticular infection (9%) and primary peritonitis (5%). Severe pain was the most typical symptom for soft-tissue infections. More than half of the patients underwent surgery and received clindamycin. The readmission rate was 7%, and the case fatality rate was 2%. Conclusions The incidence rate of pediatric iGAS infections tripled during our study. The increase was not, however, the result of a change in the strain types causing iGAS. Varicella immunization would likely have prevented a significant number of the cases.

Aim This was a follow-up of 28 schoolchildren with cows' milk allergy (CMA) who attended a randomised double-blind placebo-controlled oral immunotherapy (OIT) study. In the original study, 26 (92.9%) completed the six-month escalation phase, and 25 (89.3%) used milk daily at 12 months and 24 (85.7%) at 36 months. This study evaluated the outcome seven years later, with special attention paid to milk consumption and symptoms. Methods Outcome data were collected through a postal questionnaire completed three, four and five years after enrolment and by a phone questionnaire after seven years. We asked about the daily dose of milk products, any adverse reactions, any medication needed and possible discontinuation of daily milk consumption. Results Data were available at the seven-year point for 24 children and 14 (58.3%) of these continued to use milk (≥200 mL) or milk products (protein ≥6400 mg) daily for seven years. However, three (21.4%) of these still reported symptoms associated with milk consumption. Of the 10 remaining children, two children used milk products daily but consumed less due to symptoms and eight (33.3%) had discontinued milk consumption. Conclusion Oral immunotherapy was an effective and safe way of desensitising schoolchildren with persistent CMA.

Evidence-based guidelines are needed to harmonise and improve the diagnostics and treatment of children's lower respiratory tract infections. Following a professional literature search, an interdisciplinary working group evaluated and graded the available evidence and constructed guidelines for treating laryngitis, bronchitis, wheezing bronchitis and bronchiolitis. Conclusion Currently available drugs were not effective in relieving cough symptoms. Salbutamol inhalations could relieve the symptoms of wheezing bronchitis and should be administered via a holding chamber. Nebulised adrenaline or inhaled or oral glucocorticoids did not reduce hospitalisation rates or relieve symptoms in infants with bronchiolitis and should not be routinely used.

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.

Background: Infant bronchiolitis may lead to lung function reduction. However, reversibility of changes in lung function is less studied in adolescents after infant bronchiolitis. Methods: The aim of this study was to evaluate baseline and post-bronchodilator lung function at the age of 10-13 years after bronchiolitis in early infancy, with special focus on the RSV aetiology. Flow-volume spirometry with bronchodilation test was measured in 89 cases with early-life bronchiolitis and 108 controls without history of bronchiolitis at the mean age of 11.7 years. Parameters of flow-volume spirometry were analysed as sex-specific height-related %of-predicted values. We hypothesized that bronchiolitis in early infancy is associated with reduced lung function in early adolescence. Results: As continuous variables, forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC) after bronchodilation was lower in cases than controls. As categorised variables, FEV1 was pathological (under the 5th percentile of the national references) in 25% of cases before bronchodilation (controls 12%, p=0.020), in 18% of cases after bronchodilation (controls 5%, p=0.003), and FEV1/FVC was pathological in 25% of cases before bronchodilation (controls 13%, p=0.034). In the adjusted logistic regression, infant bronchiolitis was associated with pathological FEV1 before (odds ratio 2.4) and after (odds ratio 4.4) bronchodilation. The result was similar in RSV positive cases. Conclusions: Evidence of reduced FEV1 before and after bronchodilation was found at 10-13 years of age after infant bronchiolitis suggesting an irreversible bronchial obstruction.

AIM Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is involved with bronchiolitis and asthma. We evaluated associations between four IL-10 polymorphisms, namely rs1800871, rs1800872, rs1800890 and rs1800896, and post-bronchiolitis asthma in young adolescents. METHODS The cohort consisted of 125 children hospitalised for bronchiolitis at Tampere University Hospital, Finland, in 2000-2004, at less than six months of age. At 11-13 years, asthma diagnoses and asthma-presumptive symptoms, allergic rhinitis and use of inhaled corticosteroids (ICS) were registered. Data on the four polymorphisms and their genotypes, haplotypes and allele frequencies were analysed in relation to asthma, allergic rhinitis and asthma medication. RESULTS The variant IL-10 rs1800896 genotype was associated with less persistent asthma at five to seven and 11-13 years of age (4.3 versus 15.2%, p = 0.04) than the wild genotype and less ICS use during the previous 12 months (5.4 versus 18.2%, p = 0.03), as was the variant allele G. Allele A was associated with more persistent asthma and ICS use. The significant differences between the variant and wild genotypes were lost in adjusted logistic regression, but the direction of the association remained. CONCLUSION IL-10 rs1800896 gene polymorphism was associated with post-bronchiolitis asthma at 11-13 years of age in children hospitalised for bronchiolitis at less than six months of age.