Asthma and lung function in adulthood after a viral wheezing episode in early childhood.

BACKGROUND: Viral aetiology of infection has a significant role in the long-term outcome of early-childhood wheezing. OBJECTIVE: This study examines asthma and lung function in adulthood after early-childhood wheezing induced by respiratory syncytial virus (RSV) and rhinovirus (RV). METHODS: A total of 100 children were hospitalized for a wheezing episode at less than 24 months of age from 1992 to 1993 in Kuopio University Hospital (Finland). Adenovirus, influenza A and B virus, parainfluenza (1-3) virus, and RSV were tested on admission using antigen detection and antibody assays, and RSV and RV were tested by polymerase chain reaction (PCR). In 2010, 49 cases and 60 population controls attended a follow-up study, which included spirometry with bronchodilation test and fractionally exhaled nitric oxide (FENO ) measurements. RESULTS: Current asthma was present in 64% of the cases with RV-induced wheezing (OR 17.0 [95%CI 3.9-75.3] vs controls), in 43% of the cases with RSV-induced wheezing episode (6.1 [1.5-24.9] vs controls), and in 12% of the controls. The RV group showed significantly higher mean FENO values than the RSV group and controls. RV-positive cases had lower MEF50 before bronchodilation and higher MEF50, FEV1, and FEV1/FVC bronchodilation responses than controls. RSV-positive cases had lower FVC than controls before bronchodilation. CONCLUSION: Cases with RV- and RSV-induced early-childhood wheezing had increased risk for asthma in adulthood, and RV-positive cases had significantly higher FENO values than RSV-positive cases and controls. Compared to controls, RV-positive cases showed more bronchial reactivity, and RSV-positive cases showed lower FVC before bronchodilation in lung function testing. CLINICAL RELEVANCE: Children with RV- or RSV-induced wheezing in early childhood have an increased risk for asthma and lung function abnormalities in adulthood.

Risk factors for asthma after infant bronchiolitis.

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.

Quantity and diversity of environmental microbial exposure and development of asthma: a birth cohort study.

BACKGROUND: Early-life exposure to environmental microbial agents may be associated with the development of allergies. The aim of the study was to identify better ways to characterize microbial exposure as a predictor of respiratory symptoms and allergies. METHODS: A birth cohort of 410 children was followed up until 6 years of age. Bacterial endotoxin, 3-hydroxy fatty acids, N-acetyl-muramic acid, fungal extracellular polysaccharides (EPS) from Penicillium and Aspergillus spp., ß-D-glucan, ergosterol, and bacterial or fungal quantitative polymerase chain reactions (qPCRs) were analyzed from dust samples collected at 2 months of age. Asthma, wheezing, cough, and atopic dermatitis were assessed using repeated questionnaires. Specific IgEs were determined at the age of 1 and 6 years. RESULTS: Only few associations were found between single microbial markers and the studied outcomes. In contrast, a score for the total quantity of microbial exposure, that is, sum of indicators for fungi (ergosterol), Gram-positive (muramic acid) bacteria, and Gram-negative (endotoxin) bacteria, was significantly (inverted-U shape) associated with asthma incidence (P < 0.001): the highest risk was found at medium levels (adjusted odds ratio (aOR) 2.24, 95% confidence interval (95% CI) 0.87-5.75 for 3rd quintile) and the lowest risk at the highest level (aOR 0.34, 95% CI 0.09-1.36 for 5th quintile). The microbial diversity score, that is, sum of detected qPCRs, was inversely associated with risk of wheezing and was significantly (inverted-U shape) associated with sensitization to inhalant allergens. CONCLUSION: Score for quantity of microbial exposure predicted asthma better than single microbial markers independently of microbial diversity and amount of dust. Better indicators of total quantity and diversity of microbial exposure are needed in studies on the development of asthma.

Preschool asthma after bronchiolitis in infancy.

Asthma risk is lower after wheezing associated with respiratory syncytial virus (RSV) than with non-RSV infection in infancy. RSV is the main wheezing-associated virus in infants aged <6 months. We evaluated the outcome of children hospitalised for bronchiolitis at <6 months of age, with special focus on viral aetiology and early risk factors. Out of 205 infants hospitalised for bronchiolitis at <6 months of age, 127 (62%) attended a control visit at a mean age of 6.5 yrs and the parents of an additional 39 children were interviewed by telephone. Thus, follow-up data collected by identical structured questionnaires were available from 166 (81%) children. Viral aetiology of bronchiolitis, studied on admission by antigen detection or PCR, was demonstrable in 97% of cases. Current asthma was present in 21 (12.7%) children: 8.2% in the 110 former RSV patients versus 24% in non-RSV patients (p=0.01). 45 (27%) children had ever had asthma. In adjusted analyses, atopic dermatitis, non-RSV bronchiolitis and maternal asthma were independently significant early-life risk factors for asthma. The risk of asthma was lower after RSV bronchiolitis than after bronchiolitis caused by other viruses in children hospitalised at <6 months of age.

Exposure to microbial agents in house dust and wheezing, atopic dermatitis and atopic sensitization in early childhood: a birth cohort study in rural areas.

BACKGROUND: Early-life exposure to environmental microbial agents may be associated with development of wheezing and allergic diseases. OBJECTIVE: To assess the association of microbial exposure in rural homes with the risk of asthma, wheezing, atopic dermatitis and sensitization. METHODS: Birth cohorts of rural children (n = 1133), half from farmer families, were followed up from birth to 2 years of age by questionnaires in five European centres. Endotoxin and extracellular polysaccharides (EPS) of Penicillium and Aspergillus spp. were determined from living room floor and mother's mattress dust samples collected at 2 months of age. Specific IgE against 19 allergens was measured at 1 year of age. Discrete-time hazard models, generalized estimations equations (GEE) and logistic regression were used for statistical analyses. RESULTS: The incidence of asthma was inversely associated with the amount of dust (adjusted odds ratio (aOR) 0.73, 95% CI 0.58-0.93) and the loads (units/m(2)) of EPS (aOR 0.75, 95% CI 0.55-1.04) and endotoxin (aOR 0.79, 95% CI 0.60-1.05) in the mother's mattress. Similar associations were seen with wheezing and with living room floor dust. The microbial markers were highly correlated and their effects could not be clearly separated. The inverse associations were seen especially among non-farmers. The risk of sensitization to inhalant allergens increased with increasing endotoxin exposure from mattress dust. No associations were observed with concentrations (units/g) or with atopic dermatitis. CONCLUSION AND CLINICAL RELEVANCE: The amount and microbial content of house dust were inversely associated with asthma and wheezing, but due to high correlations between microbial agents and amount of dust, it was not possible to disentangle their individual effects. New ways to better measure and represent exposure to environmental microbes, including indexes of biodiversity, are needed especially among farmers.

Long-term efficacy of group-based treatment for childhood obesity compared with routinely given individual counselling.

OBJECTIVE: We investigated the long-term efficacy of two childhood obesity treatment programs, routine counselling (two appointments for children) and group treatment (15 sessions separately for children and parents) in a randomised controlled trial. As published earlier, group treatment was more effective than routine counselling in the treatment of 7-9 year-old obese children in the short term. DESIGN: The children's heights and weights were measured 2 and 3 years after the beginning of the intervention and changes in weight for height, body mass index (BMI) and BMI standard deviation scores were used as outcome measures. RESULTS: There were no significant differences between the treatment arms in the changes of outcome measures from baseline to 2- or 3-years follow-up visits. CONCLUSION: In conclusion, novel efforts are needed for the improvement of the long-term results of childhood obesity treatment programs.

Parapneumonic empyema in children before the era of pneumococcal vaccination.

BACKGROUND: During the past two decades, the incidence of paediatric empyema has increased in many countries. PURPOSE: The aim of this retrospective hospital chart review was to evaluate the incidence, aetiology and clinical and laboratory characteristics of parapneumonic empyema in children. SUBJECTS AND METHODS: Twenty-one patients were admitted to a university hospital from the area with a population of 84,000 children in 1991-2009. RESULTS: The annual incidence of parapneumonic empyema was 1.6/100,000 children in 1991-1998, 0.2/100,000 children in 1999-2005 and 2.7/100,000 children in 2006-2009. Bacterial aetiology was identified in 52% of the cases, and pneumococcus caused 45% of the cases with bacterial aetiology detected. The clinical and laboratory findings in children with and without pleural effusion on admission were surprisingly similar. The development of empyema in hospital during antibiotic therapy was associated with persistent fever and serum C-reactive protein (CRP) >200 mg/L for 48 h after admission. CONCLUSION: The incidence of parapneumonic empyema in children fluctuated but in the long run, increased in 1991-2009. Pneumococcus caused half of the cases with bacterial diagnosis available. Since 2010, pneumococcal vaccination has belonged to the general vaccination programme, and the effect on the incidence of empyema remains to be seen.

Hyperimmunoglobulinemia D and periodic fever syndrome in children. Review on therapy with biological drugs and case report.

UNLABELLED: Hyperimmunoglobulinemia D syndrome (HIDS) is a rare, autosomal recessively inherited autoinflammatory disease caused by mutations in the mevalonate kinase gene. HIDS usually starts in infancy with recurrent fever episodes lasting 3-7 days and recurring every 4-6 weeks, with only partial symptom decrease in adulthood. Fever is typically accompanied by abdominal pain, vomiting, diarrhoea and cervical lymphadenopathy, and sometimes by skin and joint symptoms. Blood leukocytes and serum C-reactive protein are elevated during the episode, and in addition, high levels of interleukine-1 (IL-1), IL-6 and tumour necrosis factor (TNF) and respective soluble receptors have been measured. Instead, serum immunoglobulin D (IgD) is usually normal until 3 years of age. Currently, there is no established treatment for HIDS. Thus far, four children have been successfully treated with etanercep, TNF-alpha inhibitor, and three children with anakinra, IL-1 receptor antagonist. CONCLUSION: This review summarizes currently available data on the use biological medicines for HIDS in children. A Finnish 1.5-year-old patient with disease onset at 6 months of age, treated successfully with anakinra, is presented.

Parent-reported food allergy requiring an avoidance diet in children starting elementary school.

AIM: To evaluate the prevalence of parent-reported food allergies requiring avoidance diet at early school age. METHODS: The school health nurses interviewed, by using a structured questionnaire on the required diet at school, the parents of all the 1542 children starting elementary school in a Finnish town with 210,000 inhabitants. RESULTS: An allergy to basic foods was found in 41 (2.7%) children: 1.5% to milk, 1.1% to eggs and 1.0% to grains. An allergy to nuts was present in 3.1% and to fruits and vegetables in 5.8%, both with known cross-sensitization to pollens. In all, 9.2% of the children reported some allergy. Milk, egg and grain allergies were associated with soy, nut and spice allergies. CONCLUSION: Over 2% of the 1542 Finnish first-graders reported allergies to basic foods (milk, eggs or grains) requiring special avoidance diets at school. The figure suggests that avoidance diets started in the first years of life still unnecessarily continued.

Respiratory medicines for children: current evidence, unlicensed use and research priorities.

This European Respiratory Society task force has reviewed the evidence for paediatric medicines in respiratory disease occurring in adults and children. We describe off-licence use, research priorities and ongoing studies. Off-licence and off-label prescribing in children is widespread and potentially harmful. Research areas in asthma include novel formulations and regimens, and individualised prescribing. In cystic fibrosis, future studies will focus on screened infants and robust outcome measures are needed. Other areas include new enzyme and antibiotic formulations and the basic defect. Research into pneumonia should include evaluation of new antibacterials and regimens, rapid diagnostic tests and, in pleural infection, antibiotic penetration, fibrinolytics and surveillance. In uncommon conditions, such as primary ciliary dyskinesia, congenital pulmonary abnormalities or neuromuscular disorders, drugs indicated for other conditions (e.g. dornase alfa) are commonly used and trials are needed. In neuromuscular disorders, the beta-agonists may enhance muscle strength and are in need of evaluation. Studies of antibiotic prophylaxis, immunoglobulin and antifungal drugs are needed in immune deficiency. We hope that this summary of the evidence for respiratory medicines in children, highlighting gaps and research priorities, will be useful for the pharmaceutical industry, the paediatric committee of the European Medicines Agency, academic investigators and the lay public.

Adulthood asthma after wheezing in infancy: a questionnaire study at 27 years of age.

BACKGROUND: Wheezing in early childhood is a heterogeneous condition, the longterm prognosis varying from total recovery to chronic asthma. Though short-term outcome has been actively studied, there is lack of data on long-term outcome until adulthood. The aim of the study was to evaluate the prevalence and risk factors of asthma at 26-29 years of age after early-life wheezing. METHODS: At the median age of 27.3 years (range 26.3-28.6), a questionnaire was sent to 78 study subjects hospitalized for wheezing at <24 months of age, and 59 (76%) answered. Asthma, allergy and weight status were compared with selected controls followed up from birth and with non-selected population controls recruited for this adulthood study. RESULTS: Doctor-diagnosed asthma was present in 20% of the former bronchiolitis patients, compared with 5% in the two control groups (OR 2.1, 95% CI 0.3-17.9 vs selected controls; OR 5.2, 95% CI 1.7-15.8 vs nonselected controls). The respective figures for current self-reported asthma were 41% and 7-10% (OR 11.4, 95% CI 2.3-56.1 vs selected controls; OR 12.2, 95% CI 4.4-33.7 vs nonselected controls). Current allergic rhinitis and current smoking were significantly associated with asthma, but current overweight or obesity was not. In multivariate analyses, early-life wheezing was an independent risk factor of adulthood asthma. CONCLUSION: An increased asthma risk in early-life wheezers continues, even after many symptom-free years at school age, at least until 27 years of age.

Allergic rhinitis in school-aged children with asthma - still under-diagnosed and under-treated? A retrospective study in a children's hospital.

Allergic rhinitis (AR) and asthma can be considered as manifestations of the same disease entity. The treatment of AR may improve also asthma symptoms. The aim of the study was to evaluate, how often AR is diagnosed and treated in patients with asthma. A retrospective chart review in the allergy and asthma unit of a secondary paediatric hospital. From 903 eligible 7- to 15-year-old children with doctor-diagnosed asthma, 372 were randomly included in the study. In all, 229 patients (61.6%, 95% CI: 56.5-66.4%) had symptoms presumptive for AR. The diagnosis of AR was recorded in the patient records only for 87 patients (23.4%, 95% CI: 19.4-28.0). There was evidence that children with AR or nasal symptoms had more severe asthma; 35% of the patients with AR, 23% with nasal symptoms without AR diagnosis and 12% without nasal symptoms required inhaled steroids and long-acting beta-agonists for asthma (p = 0.035). AR was both under-diagnosed and under-treated in school-aged children with doctor-diagnosed asthma.

Paediatrics in Berlin.

The aim of this report is to describe the highlights of the European Respiratory Society annual congress in Berlin, Germany. The best abstracts in asthma and allergy, cystic fibrosis, respiratory infection, paediatric and neonatal intensive care, paediatric investigative techniques (in particular respiratory physiology and bronchoscopy) and respiratory epidemiology are presented and set in the context of the current literature.