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.

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.

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.

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.

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 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.

Outpatient Antibiotic Prescribing for 357,390 Children With Otitis Media.

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 <18 years old children. The collected variables were all diagnoses, age, visit year, doctor's specialty, and prescribed antibiotics. Children with OM and upper respiratory tract infections were included, but those with lower respiratory tract infections were excluded. RESULTS: The number of children with OM was 357,390 (55.2% boys). Antibiotics were prescribed in 44.8% of cases, with the lowest proportion (44.1%) being in <2 years old children. The overall prescription rate decreased from 48.3% in 2014 to 41.4% in 2020. The rates were 19.3% and 18.1% for amoxicillin and 12.6% and 13.2% for amoxicillin-clavulanic acid, respectively. Macrolide prescriptions were reduced from 7.5% to 3.5%. Pediatricians prescribed antibiotics for 38.8%, general practitioners for 54.0% and ear, nose and throat physicians for 39.8% of children with OM. CONCLUSION: The selection of antibiotics for OM, when prescribed, was according to the recommendations (amoxicillin or amoxicillin-clavulanic acid) in 80.1% of pediatricians, 67.0% of general practitioners and 55.1% of ear, nose and throat physicians.

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.

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.

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.

Viral wheezing in early childhood as a risk factor for asthma in young adulthood: A prospective long-term cohort study.

Background and Aims: There is an increased risk of asthma after viral wheezing episodes in early childhood, but unfortunately, prospective longitudinal data until adulthood are mostly 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 <24 months who were hospitalized for viral wheezing episodes in 1992-1993. After the index episode, data on a diagnosis of asthma 1 year later and at median ages of 4.0, 7.2, and 12.3 years were recorded in follow-up visits. Forty-nine individuals attended the latest follow-up visit at the age of 17-20 years. Current asthma was diagnosed based on symptoms at the time of the last follow-up, use of inhaled corticosteroids and peak expiratory flow monitoring. Results: A total of 26 (53%) of the 49 cohort individuals had asthma at a mean age of 18.8 years. In multivariate analyses, a diagnosis of asthma 1 year after index hospitalization and at ages 4.0, 7.2, and 12.3 years were significant risk factors for current asthma (adjusted odds ratios [aORs] of 7.13, 8.86, 8.05, and 21.16, respectively). Atopic dermatitis in infancy (aOR: 4.20) and eosinophilia on admission (5.18) were also significant predictive factors for asthma. Conclusion: Over half (26/49) of the participants who had been hospitalized for viral wheezing episodes in early childhood had asthma in young adulthood. An asthma diagnosis at any age during childhood, as well as eosinophilia in early childhood, were independent significant predictive factors for asthma.

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.