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AIM: This study aimed to evaluate antibiotic prescriptions for children with otitis media (OM) in a large nationwide network of private clinics between 2014 and 2020. Special focus was paid to amoxicillin and amoxicillin-clavulanic acid prescriptions, which the national guidelines recommend for first-line drugs. We also focused on macrolides, which are commonly prescribed for respiratory tract infections in children but are not appropriate for OM cases. METHODS: The data were obtained from the electronic health records of about 250,000 annual visits in

This mini review summarises the available data on antibiotic stewardship programmes (ASP) for acute respiratory tract infections (ARTI) in paediatric outpatients, particularly the implementation and impact of programmes.PubMed was searched from 1 January 2012 to 31 December 2021 for papers with abstracts that used the terms respiratory tract infection, antibiotic, child and guideline. We then saw how many of these included the individual terms impact, implementation or stewardship. After exclusions, we included 10 papers that were published in English on children treated as outpatients for ARTIs. All of these included data on implementing and assessing the impact of ASPs.The primary care data were mainly from the United States. The ASP programmes did not influence antibiotic prescription rates, but broad-spectrum antibiotics decreased by 43-48%. The emergency department data were mainly from France and the antibiotic prescription rate decreased by 31-35% and the rate for broad-spectrum antibiotics by 63-71%. A nationwide register-based study from France confirmed these results.ASPs had a low impact on overall antibiotic prescription rates and a modest impact on prescribing broad-spectrum antibiotics. The implementation of ASP protocols needs further development, and more research is necessary on barriers to complying with ASPs.

This mini review summarised studies published over a 10-year period on the impact of guidelines for diagnosing and managing bronchiolitis in children, with a special focus on interventions that enhanced adherence during implementation.PubMed was searched from 1 December 2011 to 31 November 2021 for papers published in English that used the terms bronchiolitis, child or infant, guidelines and either implementation or impact. After the exclusion criteria had been applied, 27 articles were reviewed in more detail. Eight described protocols without any comparisons and were excluded. Ten of the 19 remaining studies evaluated the impact of bronchiolitis guidelines, and 9 examined the effects of interventions linked to their publication.Just releasing evidence-based guidelines had a poor impact, but this improved when local tailored current care, clinical practice or best-practice guidelines were issued. Even better results were achieved when all the staff treating bronchiolitis patients participated in the preparation and implementation of local guidelines. Adherence to the guidelines was as high as 85% when multidisciplinary, and multifaceted interventions were used to complement the publication of guidelines.Healthcare professionals need to work together to avoid children receiving bronchiolitis management that is unnecessary and not based on evidence.

Aim: We evaluated main trends in antibiotic prescriptions for children with lower respiratory tract infection (LRTI) by Terveystalo, Finland's largest private healthcare company. Methods: The study comprised of 89,359 children aged 0–17 years (57.2% boys) who visited Terveystalo primary care clinics from 2014 to 2020 with LRTI. The data were assessed by age, study year, location, the doctor's speciality and whether the diagnosis was bronchitis or community-acquired pneumonia (CAP). Results: There were gradual decreases in overall antibiotic prescription rates during the study period (37.0% in 2014 vs. 20.1% in 2020) and in prescribed macrolides (16.8% vs. 7.5%). Altogether, 31.3% of 72,737 children with bronchitis and 22.5% of those 16,622 with CAP-received antibiotics. Macrolides were the most frequently prescribed antibiotics for bronchitis, at more than 40%, without any substantial relative decrease during the study. Costs of antibiotics increased from 2014 to 2016 and then decreased in line with the reduction in prescriptions. However, there was still a marked overuse of antibiotics, especially macrolides, for children with bronchitis. The relative use of amoxicillin for CAP increased from 41.4% to 65.4% between 2016 and 2020, in line with current guidelines. Conclusion: Despite an overall reduction in prescribed antibiotics, some antibiotics were still overused, particularly macrolides for bronchitis. acceptedVersion

To evaluate the management of bronchiolitis in the paediatric intensive care unit (PICU) before and after publication of the national bronchiolitis guidelines in June 2015. All infants treated between 2016–2020 for bronchiolitis in the PICU of Tampere University Hospital at Conclusion: When post-guideline years were compared with pre-guideline years, the use of bronchodilators decreased in agreement, but the use of inhaled saline increased in disagreement with the guidelines. The use of respiratory support increased, evidently because of an introduction of the non-invasive HFOT treatment modality. What is Known:• Oxygen supplementation and respiratory support, when needed, are the cornerstones of bronchiolitis treatment.• Medicines are frequently given to infants with bronchiolitis, especially if intensive care is needed, although evidence of their effectiveness is lacking. What is New:• Nearly all (94%) infants who needed intensive care were treated with HFOT and 37% with nasal CPAP, and finally, only 9% were intubated, which reflects the effectiveness of non-invasive techniques.• When pre- and post-guideline eras were compared, use of racemic adrenaline decreased from 84 to 57%, but use of hypertonic saline increased up to 75%, which disagrees with the current guidelines.

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: Toll-interacting protein is a key factor in regulating innate immunity responses via gatekeeping Toll-like receptors. Genetic variance in innate immunity has been linked with susceptibility to infections. Children with viral bronchiolitis in infancy are at increased risk of later asthma. The aim was to evaluate the role of toll-interacting protein gene point mutations in severity of bronchiolitis and subsequent risk of asthma. Methods: Infants less than 6 months old were recruited during hospitalization due to bronchiolitis. In all, 166 children were prospectively followed up to age of 1.5, 6, and 11 years. Clinical data on viral etiology and severity markers, and further post-bronchiolitis asthma and lung function outcomes were compared with genetic differences in two single-nucleotide point mutations rs116938768 and rs5743854 in the toll-interacting protein gene. Results: Toll-interacting protein rs116938768 or rs5743854 did not show significant associations with severity markers or viral etiology of bronchiolitis. Follow-up data on current asthma or lung function at 6 or 11 years of age after bronchiolitis were not associated with the investigated mutations. Conclusion: Toll-interacting protein gene point mutations in rs116938768 or rs5743854 were not involved with the clinical course of viral bronchiolitis in early infancy, and did not predict post-bronchiolitis asthma or lung function reduction by the age of 11 years. 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.

The risk of asthma and lung function reduction is increased in children who have presented with wheezing associated with respiratory tract infection in early childhood. Three prospective cohort studies consisting of patients hospitalized for infection-associated wheezing at 25 years of age. These three cohorts are even globally the only cohorts consisting of early-childhood wheezers followed prospectively until adulthood. Initially, the studies were not controlled, and the risk of asthma and reduced lung function and the risk factors in question were assessed by analyses within the cohorts. Matched population-based controls without wheezing history in early childhood were recruited for the studies in adulthood. One follow-up included only questionnaire data without lung function results. Two studies included control visits, and one of them presented clinical and lung function data, and the other clinical and bronchial reactivity data. Respiratory syncytial virus was identified on admission in all three post-wheezing cohorts, and rhinoviruses in the newest cohort from the 1990`s. The present narrative review summarizes data on asthma and lung function reduction in adults aged >25 years after hospitalization for wheezing at age 25 years of age.

Upper respiratory tract infection (URTI) is a self-limiting viral infection and should not be treated with antibiotics. The aim was to evaluate antibiotic prescriptions for children with uncomplicated URTI in a large nationwide private clinic network between 2014 and 2020. Special focus was given to macrolide prescriptions and costs. The data were obtained from the electronic health records (EHR) of the largest private healthcare company in Finland (with about 250,000 paediatric visits annually across the country). The collected variables included diagnoses, age, visit year, speciality of the doctor, and prescribed antibiotics. The number of uncomplicated URTIs in Conclusion: Antibiotic prescriptions for uncomplicated URTIs, especially macrolides, decreased substantially during the 7-year surveillance period; however, 8.8% of children still received unnecessary antibiotics. To further reduce unwarranted antibiotic prescriptions, active interventions are needed that can be performed by applying the available EHR system. What is Known:• Upper respiratory tract infection (URTI) is the most common infection in children. Uncomplicated URTI is a self-limiting viral infection, and antibiotic treatment is not warranted. What is New:• Almost 9% of children with uncomplicated URTIs still received unnecessary antibiotics. Paediatricians prescribed antibiotics less often than general practitioners or ear, nose, and throat specialists. To further reduce unwarranted antibiotic prescriptions, active interventions are needed that can be performed by applying the available EHR system.

Aim: We evaluated antibiotic prescriptions issued for Finnish children with acute sinusitis by a nationwide private outpatient clinic network from 2014–2020. Data were compared before and after updated guidelines in 2018. Methods: The study comprised data on 45 296 children aged 2–17 years with acute sinusitis, namely diagnoses, ages, dates, the doctor's specialty and any antibiotics. We measured compliance with the updated 2018 Finnish guidelines, which recommended amoxicillin or amoxicillin-clavulanic acid for children under 12 years old, with doxycycline as an alternative for 12 years plus. Results: There were 6621–7585 visits per year for acute sinusitis in 2014–2019 and 2954 in 2020. Antibiotics were prescribed for 37.9%–41.6% of patients during the study years. Amoxicillin, including penicillin, accounted for 35.9% of prescriptions, followed by amoxicillin-clavulanic acid (26.9%). Macrolides accounted for 20.6% and, encouragingly, decreased by 38% from 2014–2019. Doxycycline accounted for 5.3%. Paediatricians, general practitioners (GPs) and ear, nose and throat specialists followed the guidelines in 75.1%, 73.8% and 66.7% of cases, respectively. GPs prescribed antibiotics more often than other physicians. Conclusion: Antibiotics were prescribed for about 40% of acute sinusitis visits by Finnish children from 2014–2019. Specialities differed with regard to prescribing rates and whether they followed the guidelines. publishedVersion

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

AIM The aim of the study was to evaluate the association of Toll-like receptor 4 (TLR4) gene variations with osteitis risk after Bacillus Calmette-Guerin (BCG) vaccination given at birth and with serum cytokine levels measured in adulthood. METHODS We determined the TLR4 rs4986790 single-nucleotide polymorphism (SNP) in 132 study subjects with BCG osteitis in infancy and compared the genotype distributions and allele frequencies between them and population controls. Serum concentrations of 11 cytokines measured in adulthood were compared between study subjects with the wild vs variant TLR4 rs4986790 genotype. RESULTS The genotypes and allele frequencies of the TLR4 rs4986790 SNP did not differ between BCG osteitis cases and population controls. Instead, subjects with the variant genotype presented with lower serum interleukin (IL) concentrations of the pro-inflammatory IL-6, IL-17A and IL-12 cytokines and with marginally lower interferon-γ concentrations, but with higher serum anti-inflammatory IL-4 concentration. The results concern also the TLR4 rs4986791, since these two SNPs are co-segregating in the Finnish population. CONCLUSION The findings suggest that TLR4 has no significant role in the emergence of osteitis after newborn BCG vaccination, but the variant genotypes of the TLR4 rs4986790 and rs4986791 may impair the production of pro-inflammatory cytokines.

Our aim was to construct and test an intervention programme to eradicate cough and cold medicine (CCM) prescriptions for children treated in a nationwide healthcare service company. The study was carried out in the largest private healthcare service company in Finland with a centralised electronic health record system allowing for real-time, doctor-specific practice monitoring. The step-by-step intervention consisted of company-level dissemination of educational materials to doctors and families, educational staff meetings, continuous monitoring of prescriptions, and targeted feedback. Outreach visits were held in noncompliant units. Finally, those physicians who most often prescribed CCM were directly contacted. During the intervention period (2017–2020), there were more than one million paediatric visits. Prescriptions of CCMs to children were completely eradicated in 41% of units and the total number of CCM prescriptions decreased from 6738 to 744 (89%). During the fourth intervention year, CCMs containing opioid derivatives were prescribed for only 0.2% of children aged Conclusion: The study showed that a nationwide systematic intervention to change cough medicine prescription practices is feasible and requires only modest financial investments. What is Known:• Cough and cold medicines (CCM) are not effective or safe, especially for children aged 6 years.• Although the use of CCMs has been declining, caregivers continue to administer CCMs to children, and some physicians still prescribe them even for preschool children. What is New:• A nationwide systematic intervention can significantly and cost effectively change CCM prescription habits of paediatricians, general practitioners, and other specialists.• Electronic health records provide additional tools for operative guideline implementation and real-time quality monitoring, including recommendations of useless or harmful treatments.

Interleukin (IL) 1 receptor-like 1, encoded by the IL1RL1 gene, is a receptor for IL-33. In European birth cohorts, IL1RL1 rs102082293, rs10204137 (rs4988955), rs13424006 and rs13431828 (rs13048661) variations were associated with asthma at school age. In a Dutch multi-centre study, IL1RL1 rs1921622 variation was associated with severe bronchiolitis. We evaluated the associations of these five IL1RL1 variations with asthma and lung function at school age after hospitalisation for bronchiolitis in infancy.Follow-up data, including impulse oscillometry at age 5-7 and flow-volume spirometry at age 11-13 years, and the IL1RL1 genotype data were available for 141 children followed until 5-7 and for 125 children followed until 11-13 age years after bronchiolitis in infancy. The IL1RL1 rs10204137 and rs4988955, and the IL1RL1 rs13048661 and rs13431828, are 100% co-segregating in the Finnish population.The variant IL1RL1 rs13048661/13431828 genotype was constantly associated with increased asthma risk by various definitions at 5-7 and 11-13 years of ages. The result was confirmed with analyses adjusted for current confounders and early-life environment-related factors. Statistical significances were lost, when maternal asthma and atopic dermatitis in infancy were included in the model.IL1RL1 rs13048661/13431828 variation was associated with post-bronchiolitis asthma outcomes at school age.

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Interleukin-33 (IL-33), a cytokine of the IL-1 family, has both pro-inflammatory and anti-inflammatory properties and shares a common receptor with IL-1. Single nucleotide polymorphism (SNP) at rs1342326 of the IL33 gene was associated with allergic rhinitis in preschool-aged children from five European countries (1), and has been associated with wheezing, asthma and hospitalisation for asthma in other child populations (2).

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.

Interleukin-1 receptor associated kinase-4 (IRAK4) encoded by the IRAK4 gene mediates signals of innate immunity. Single nucleotide polymorphisms (SNP) of the IRAK4 rs4251513 and rs4251520 were associated with an increased risk of early transient wheezing, when 94 SNPs were studied in 2007 Dutch and 7242 French children prospectively followed-up for eight years from birth (1).

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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.