Genetic susceptibility to acute viral bronchiolitis.

BACKGROUND: Acute viral bronchiolitis is a major cause of infant hospitalizations worldwide. Childhood bronchiolitis is considered a risk factor for asthma, suggesting shared genetic factors and biological pathways. Genetic risk loci may provide new insights into disease pathogenesis. METHODS: We conducted a genome-wide association study (GWAS) to examine the genetic contributions to bronchiolitis susceptibility in the FinnGen project data. We analyzed 1,465 infants hospitalized for bronchiolitis <2 years of age and 356,404 individuals without a history of acute lower respiratory infections (LRIs). RESULTS: GWAS identified associations (p<5×10-8) for variants in gasdermin B (GSDMB) and a missense variant in cadherin-related family member 3 (CDHR3). Children with bronchiolitis in infancy were more likely to develop asthma later in life compared to controls. The two associated loci were previously linked to asthma and susceptibility to wheezing illness by other causative agents than RSV. The identified loci associated with overall bronchiolitis, with larger effects in non-RSV than RSV-induced infection. CONCLUSION: Our results suggest that genetic variants in CDHR3 and GSDMB modulate susceptibility to bronchiolitis, especially when caused by viruses other than RSV. Severe bronchiolitis in infancy may trigger the development of asthma in genetically susceptible individuals, or it could be a marker of genetic predisposition to asthma.

Asthma and health-related quality of life at 16-20 years of age in a prospectively followed post-bronchiolitis cohort.

The aim was to evaluate asthma and health-related quality of life (HRQoL) outcomes in adolescents, after hospital-treated bronchiolitis experienced in less than 6 months of age. A prospective cohort study started in 2001-2004 and followed up 166 children hospitalised for bronchiolitis in early infancy. At 16-20 years of age, 76 cases and 41 population-based controls without a history of bronchiolitis participated in the current study. Clinical asthma, presumptive symptoms and HRQoL data were collected with a structured questionnaire and the St. Georges Respiratory Questionnaire (SGRQ). Flow-volume spirometry was measured before and after bronchodilator administration. Asthma was present in 21.1% of cases in the post-bronchiolitis cohort compared to 9.8% in the control group (p = 0.21). Also, 35.5% of cases and 19.5% of controls reported dyspnea during the last 12 months (p = 0.04). In addition, total SGRQ scores were higher in the bronchiolitis group (4.26) than in the control group (1.67, p < 0.001) referring to a reduced health-related quality of life. CONCLUSION: Viral bronchiolitis in early infancy was associated with increased respiratory symptoms and lower health-related quality of life at age 16-20 years. WHAT IS KNOWN: • The prevalence of asthma at the school age and adolescence is increased after hospitalisation required bronchiolitis in infancy compared to those without hospitalisation due to bronchiolitis. WHAT IS NEW: • Viral bronchiolitis requiring hospitalisation in early infancy was associated with increased respiratory symptoms, such as dyspnoea, and lower health-related quality of life at age 16-20 years in a prospectively followed post-bronchiolitis cohort.

Antibiotic Treatment Duration for Community-Acquired Pneumonia in Outpatient Children in High-Income Countries-A Systematic Review and Meta-Analysis.

BACKGROUND: The optimal treatment duration of community-acquired pneumonia (CAP) in children has been controversial in high-income countries. We conducted a meta-analysis to compare short antibiotic treatment (3-5 days) with longer treatment (7-10 days) among children aged ≥6 months. METHODS: On 31 January 2022, we searched PubMed, Scopus, and Web of Science databases for studies published in English from 2003 to 2022. We included randomized controlled trials focusing on antibiotic treatment duration in children with CAP treated as outpatients. We calculated risk differences (RDs) with 95% confidence intervals and used the fixed-effect model (low heterogeneity). Our main outcome was treatment failure, defined as need for retreatment or hospitalization within 1 month. Our secondary outcome was presence of antibiotic-related harms. RESULTS: A total of 541 studies were screened, and 4 studies with 1541 children were included in the review. Three studies had low risk of bias, and one had some concerns. All 4 studies assessed treatment failures, and the RD was 0.1% (95% confidence interval, -3.0% to 2.0%) with high quality of evidence. Two studies (1194 children) assessed adverse events related to antibiotic treatment, and the RD was 0.0% (-5.0% to 5.0%) with moderate quality of evidence. The diagnostic criteria varied between the included studies. CONCLUSIONS: A short antibiotic treatment duration of 3-5 days was equally effective and safe compared with the longer (current) recommendation of 7-10 days in children aged ≥6 months with CAP. We suggest that short antibiotic courses can be implemented in treatment of pediatric CAP.

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.

Twenty-one-year follow-up revealed guideline-concordant and non-concordant trends in intensive care of bronchiolitis.

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 < 12 months of age were included. The data were retrospectively collected from electronic patient records. The current results reflecting the post-guideline era were compared with previously published results for the pre-guideline 2000-2015 period. These two studies used identical protocols. Forty-six infants treated in the PICU were included. During the post-guideline era, inhaled adrenaline was given to 26 (57%), salbutamol to 7 (15%), and hypertonic saline inhalations to 35 (75%) patients. Forty-three patients (94%) received high-flow oxygen therapy (HFOT). Seventeen patients (37%) were treated with nasal continuous positive airway pressure (CPAP) and 4 (9%) with mechanical ventilation. 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.

Use of antibiotics contrary to guidelines for children's lower respiratory tract infections in different health care settings.

This study aimed to evaluate antibiotic prescriptions for children with lower respiratory tract infection (LRTI) in public and private primary care clinics and in a hospital's pediatric emergency department (PED) in 2012-2013 (pre-guideline) and in 2014-2015 (post-guideline). Special attention was paid to guideline compliance, especially regarding macrolide prescriptions, which the guidelines discourage. Retrospective data of 1431 children with LRTI in November-December 2012-2015 were collected from electronic registers and checked manually. Three diagnostic groups were analyzed: community-acquired pneumonia (CAP), wheezing bronchitis, and non-wheezing bronchitis. A comparison of the pre- and post-guideline periods revealed antibiotic prescription rates of 48.7% and 48.9% (p = 0.955) for all LRTIs, respectively, and 77.6% and 71.0% (p = 0.053) for non-wheezing bronchitis. The prescription rates for all LRTIs were 24.9% in PED and 45.9% in public (p < 0.001 vs. PED) and 75.4% in private clinics (p < 0.001 vs. PED and p < 0.001 vs. public clinics). During post-guideline periods, antibiotics were prescribed for CAP less often in private (56.3%) than in public clinics (84.6%; p = 0.037) or in PED (94.3%; p < 0.001 vs. private and p = 0.091 vs. public primary clinics). Macrolide prescriptions were highest in private clinics (42.8%), followed by public primary care clinics (28.5%; p < 0.05) and PED (0.8%; p < 0.05 vs. both public and private primary care). Amoxicillin was the predominant antibiotic in public primary care and PED and macrolides in private primary care. CONCLUSION:  Antibiotic prescribing for children with LRTI differed significantly between healthcare providers. CAP was undertreated and bronchitis overtreated with antibiotics in primary care, especially in the private clinics. WHAT IS KNOWN: • Clinical Treatment Guidelines tend to have modest effect on physicians' antibiotic prescribing habits. • Pediatric viral LRTIs are widely treated with unnecessary antibiotics. WHAT IS NEW: • Remarkable differences in antibiotic prescriptions in pediatric LRTIs between Finnish private and public providers were observed. • Overuse of macrolides was common especially in private clinics.

Antibiotic prescriptions for child sinusitis varied between specialties after Finnish guidelines were updated in 2018.

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.

Antibiotic prescribing for children with upper respiratory tract infection: a Finnish nationwide 7-year observational study.

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 < 18-year-old children was 156,187 (53.0% in boys). The prescription rate of antibiotics decreased from 18.0% in 2014 to 8.8% in 2020, and that of macrolides from 6.1 to 1.7%. The costs decreased accordingly. Paediatricians prescribed antibiotics less often than general practitioners or ear, nose, and throat specialists. 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.

Cough and cold medicine prescription rates can be significantly reduced by active intervention.

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 < 2 years. The decrease in prescriptions was greatest in general practitioners (5.2 to 1.1%). In paediatricians, the prescription rates decreased from 1.5 to 0.2%. The annual costs of CCMs decreased from €183,996 to €18,899 (89.7%). For the intervention, the developers used 343 h and the attended doctors used 684 h of work time during the 4-year intervention. The costs used for developing, implementing, reporting, evaluating, communicating, and data managing formed approximately 11% of total intervention costs. 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.

Local healthcare professionals need to work together to implement bronchiolitis guidelines that stop unnecessary tests and treatments.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Healthcare professionals need to work together to avoid children receiving bronchiolitis management that is unnecessary and not based on evidence.

Antibiotic stewardship programmes had a low impact on prescribing for acute respiratory tract infections in children.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

An increased asthma risk continued until young adulthood after early-childhood hospitalisation for wheezing.

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.

Interleukin 1 receptor-like 1 rs13408661/13431828 polymorphism is associated with persistent post-bronchiolitis asthma at school age.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: IL1RL1 rs13048661/13431828 variation was associated with post-bronchiolitis asthma outcomes at school age.

Antibiotic prescriptions for children with lower respiratory tract infections fell from 2014 to 2020, but misuse was still an issue.

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.

Antibiotic therapy in children with community-acquired pneumonia.

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.

The sixty-year story of Finnish Bacillus Calmette-Guérin (BCG) osteitis.

AIM: A review published in 2015 showed that 331 Bacillus Calmette-Guérin (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.

Toll-like receptor 10 rs10004195 variation may be protective against Bacillus Calmette-Guérin osteitis after newborn vaccination.

AIM: Toll-like receptor 1 (TLR1), TLR2, TLR6 and TLR10 form the TLR2 subfamily. In our previous controlled studies in 132 subjects with osteitis after newborn Bacillus Calmette-Guérin (BCG) vaccination, TLR1, TLR2 and TLR6 variations were associated with the risk of BCG osteitis. Now, we evaluated the role of ten single nucleotide polymorphisms (SNP) of the TLR10 gene in this cohort. METHODS: Five synonymous TLR10 SNPs (rs10004195, rs10856837, rs10856838, rs1109695 and rs11466652), and five missense TLR10 SNPs (rs11096955, rs11096957, rs11466649, rs11466653 and rs11466658) were determined by polymerase chain reaction (PCR)-based sequencing in 132 former BCG osteitis patients. RESULTS: TLR10 rs10004195 polymorphism was associated with the risk of BCG osteitis, compared to Finnish population controls. The variant genotype (AT/AA) was present in 13.6% of cases versus 26.2% of controls (p = 0.024). Correspondingly, the minor allele frequency (MAF) was lower (0.075) in cases than in controls (0.152; p = 0.009). There were no significant differences in the genotypes of the other nine studied TLR10 SNPs or in the corresponding MAFs between cases and controls. CONCLUSION: Among ten studied TLR10 gene polymorphisms, the variation only in the TLR10 rs10004195 was associated with the BCG osteitis risk after newborn BCG vaccination.

Interleukin-1 receptor-associated kinase-4 gene variation may increase post-bronchiolitis asthma risk.

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.

Interleukin 17F gene variations showed no association with BCG osteitis risk after newborn vaccination.

AIM: Interleukin-17 (IL-17) family cytokines promote the host defence against mycobacterial infections. We have previously shown an association between IL17A variations and Bacillus Calmette-Guérin (BCG) osteitis. This paper evaluates the association of three IL17F polymorphisms with BCG osteitis after newborn vaccination. METHODS: IL17F rs763780, rs11465553 and rs7741835 single nucleotide polymorphisms (SNPs) were studied in 132 adults, who presented with BCG osteitis in infancy. The genotypes and minor allele frequencies (MAFs) were compared between cases and Finnish population-based controls (N = 99) from the 1000 Genomes Project, and MAFs were compared between cases and allele data of Finnish subjects from the large Genome Aggregation Database. RESULTS: There were no significant differences between former BCG osteitis patients and population-based controls in the IL17F rs763780 (wild 84.4% vs 84.8%), rs11465553 (86.4% vs 91.9%) or rs7741835 (65.7% vs 67.7%) genotypes. Homozygous variant genotypes were only present in 1.5%, 0.8% and 3.8% of cases, respectively. Likewise, MAFs of the three IL17F SNPs did not substantially differ from those of 11 252, 11 939 and 1371 Finnish subjects, respectively, from the available Genome Aggregation Database. CONCLUSION: IL17F rs763780, rs11465553 and rs7741835 variations showed no association with the risk of BCG osteitis after newborn vaccination.

IL17F rs763780 single nucleotide polymorphism is associated with asthma after bronchiolitis in infancy.

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.