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Background Microbial exposures in early childhood direct the development of the immune system and their diversity may influence the risk of allergy development. We aimed to determine whether the indoor microbial diversity at early-life is associated with the development of allergic rhinitis and inhalant atopy. Methods The study population included children within two birth cohorts: Finnish rural-suburban LUKAS (N = 312), and German urban LISA from Munich and Leipzig study centers (N = 248). The indoor microbiota diversity (Chao1 richness and Shannon entropy) was characterized from floor dust samples collected at the child age of 2–3 months by Illumina MiSeq sequencing of bacterial and fungal DNA amplicons. Allergic rhinitis and inhalant atopy were determined at the age of 10 years and analyzed using logistic regression models. Results High bacterial richness (aOR 0.19, 95%CI 0.09–0.42 for middle and aOR 0.12, 95%CI 0.05–0.29 for highest vs. lowest tertile) and Shannon entropy were associated with lower risk of allergic rhinitis in LISA, and similar trend was seen in LUKAS. We observed some significant associations between bacterial and fungal diversity measured and the risk of inhalant atopy, but the associations were inconsistent between the two cohorts. High bacterial diversity tended to be associated with increased risk of inhalant atopy in rural areas, but lower risk in more urban areas. Fungal diversity tended to be associated with increased risk of inhalant atopy only in LISA. Conclusions Our study suggests that a higher bacterial diversity may reduce the risk of allergic rhinitis later in childhood. The environment-dependent heterogeneity in the associations with inhalant atopy – visible here as inconsistent results between two differing cohorts - suggests that specific constituents of the diversity may be relevant.

Genetic factors associated with bronchiolitis are inadequately characterized. We therefore inspected a selected subpopulation of our previous genome-wide association study (GWAS) of bronchiolitis for overlap with known quantitative trait loci (QTLs) to identify susceptibility loci that potentially affect mRNA and protein levels. GWAS included a Finnish–Swedish case–control population (n = 187), matched for age and site. We integrated GWAS variants (p

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

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

Background:Children with juvenile idiopathic arthritis (JIA) have been found to have reduced cardiorespiratory fitness and lower physical activity. Poor cardiorespiratory fitness is associated with a risk of cardiometabolic diseases.Objectives:The aim of this study was to study the levels of cardiorespiratory fitness, respiratory function and hemodynamic responses during and after maximal cycle ergometer exercise test in children with JIA aged 6-17 years and compare the results with healthy controls.Methods:Study group in this analysis consisted of 43 patients with JIA who were treated in Department of Pediatrics in Kuopio University Hospital, Finland and 40 healthy age- and sex matched controls. Maximal exercise tests were carried out with an electromagnetic cycle ergometer using a pediatric saddle module. Maximal workload per kilogram (Wmax/kg) was used as a measure of cardiorespiratory fitness and was presented relative to bodyweight. In addition the peak values of VO2per kilogram (VO2max/kg) were used as a measure of highest amount of oxygen that an individual can consume during exercise. Values of VO2maxwere collected from respiratory gases measured directly from breath by breath method and was presented relative to body weight.Physical activity and sedentary behavior (minutes per day) was assessed by the PANIC (Physical activity and nutrition in children -study) Physical Activity Questionnaire which the participants filled.Results:Statistical analyses were performed for 43 children with JIA and 40 controls. Mean age in JIA group was 12.09 years (95%Cl 11.04-13.14), and 11.72 years (95%CI 10.52-12.93) in controls (p=0.572). Mean body mass index for age (BMI) was 22.58 kg/m2(95%CI 21.54-23.62) in JIA and 18.95 kg/m2(95%CI 17.73-20.16) in controls (pMean Wmax/kg was 2.65 W/kg (95% CI 2.49-2.82) in JIA and 3.01 W/kg (95%CI 2.86-3.15) in controls thus Wmax/kg in JIA was 0.36 W/kg (11.8 %) lower than in controls, (p = 0.002). VO2max/kg was 37.00 (95%CI 33.96-40.84) ml/kg/min in JIA and 43.30 (95%CI 40.79-45.82) ml/kg/min in controls thus in JIA group mean VO2max/kg was 6.3 ml/kg/min (14.4 %) lower than in controls (p=0.001).Conclusion:Children with JIA were found to have significantly lower cardiorespiratory fitness. In addition, BMI in JIA patients was higher compared to healthy age- and sex-matched controls. Impaired cardiorespiratory fitness and higher BMI may predispose children with JIA to cardiometabolic comorbidities later in life. In addition to disease-control, more attention should be paid to maintaining good cardiorespiratory fitness and normal BMI in these patients already before adulthood.References:[1]M Nørgaard, M Twilt, LB Andersen & T Herlin (2016) Accelerometry-based monitoring of daily physical activity in children with juvenile idiopathic arthritis, Scandinavian Journal of Rheumatology, 45:3, 179-187,[2]Maggio, A.B.R., Hofer, M.F., Martin, X.E. et al. Reduced physical activity level and cardiorespiratory fitness in children with chronic diseases. Eur J Pediatr 169, 1187–1193 (2010)[3]Bohr, AH., Fuhlbrigge, R.C., Pedersen, F.K. et al. Premature subclinical atherosclerosis in children and young adults with juvenile idiopathic arthritis. A review considering preventive measures. Pediatr Rheumatol (2016)14: 3.Acknowledgments:Panu Karjalainen1, Timo Pitkänen1, Anneli Paloranta2, Kirsi Saastamoinen11University of Eastern Finland 2 Kuopio university hospital, FinlandDisclosure of Interests:None declared

Infant bronchiolitis may be the first manifestation of asthma.To evaluate the association of early-childhood risk or protective factors for asthma and lung function reduction in adults 30 years after bronchiolitis in infancy.Forty-seven former bronchiolitis patients attended the clinical study at the median age of 29.5 years, including doctoral examination and measurement of post-bronchodilator lung function with flow-volume spirometry. Data on early-life risk factors including blood eosinophil counts on admission for bronchiolitis and on convalescence 4-6 weeks after bronchiolitis were available.Low blood eosinophil count0.25 × 10E9/l on admission for bronchiolitis was a significant protective factor and high blood eosinophil count0.45 × 10E9/l on convalescence was a significant risk factor for asthma in adulthood independently from atopic status in infancy. Parental asthma and high blood eosinophil count0.45 × 10E9/l during bronchiolitis were significant risk factors for irreversible airway obstruction (FEV1/FVC ratio below the 5th percentile lower limit of normality after bronchodilation).Our adjusted analyses confirmed that eosinopenia during infant bronchiolitis predicted low asthma risk and eosinophilia outside infection predicted high asthma risk up to the age of 28-31 years. Parental asthma and eosinophilia during bronchiolitis were recognized as risk factors for irreversible airway obstruction.

Potential of modern thermal imaging for screening and differentiation of joint inflammation has not been assessed in child and juvenile patient populations, typically demanding groups in diagnostics of musculoskeletal disorders. We hypothesize that thermal imaging can detect joint inflammation in patients with juvenile idiopathic arthritis or autoimmune disease with arthritis such as systemic lupus erythematosus. To evaluate the hypothesis, we studied 58 children exhibiting symptoms of joint inflammation. First, the patients' joints were examined along clinical procedure supplemented with ultrasound imaging when deemed necessary by the clinician. Second, thermal images were acquired from patients' knees and ankles. Results of thermal imaging were compared to clinical evaluations in knee and ankle. The temperatures were significantly (pmax = 0.044, pmean < 0.001) higher in inflamed ankle joints, but not in inflamed knee joints. No significant difference was found between the skin surface temperatures of medial and lateral aspects of ankle joints. In knee joints the mean temperatures of medial and lateral aspect differed significantly (p = 0.004). We have demonstrated that thermal imaging may have potential for detecting joint inflammation in ankle joints of children. For knee joints our results are inconclusive and further research is warranted.

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.

Aim To evaluate the association between hospitalisation for respiratory syncytial virus lower respiratory tract infection (RSV LRTI) in infancy and asthma, respiratory health-related quality of life and lung function at 28–31 years of age. Methods In 2010, we carried out a 30-year follow-up on 43 adults admitted to Kuopio University Hospital, Finland, for RSV LRTI, 27 for bronchiolitis and 16 for pneumonia, between 1981 and 1982. Together with 86 population-based controls, they completed the Saint George's Respiratory Questionnaire and underwent prebronchodilator (pre-BD) and post-BD spirometry tests to measure percentage of predicted forced vital capacity (FVC%), percentage of predicted forced expiratory volume in 1 sec (FEV1%) and percentage of predicted FEV1/FVC (FEV1/FVC%). Results Both the pre-BD and post-BD FEV1% and FEV1/FVC% were significantly lower in former RSV LRTI patients than in the controls. The bronchiolitis patients had more asthma in adulthood than the controls and pneumonia in infancy was associated with lower St George's Respiratory Questionnaire (SGRQ) scores. Conclusion Respiratory tract infection LRTI hospitalisation in infancy was associated with an increased risk of permanent obstructive lung function reduction in adulthood. The asthma risk was higher after hospitalisation for bronchiolitis, than in the controls, and respiratory health-related quality of life was lower after hospitalisation for pneumonia.

In 169 Finnish infants hospitalized for bronchiolitis at age

SummaryBackground Recent studies have revealed that adulthood asthma has its origin in early childhood. Aim The aim of the present study was to evaluate the prevalence of asthma and respiratory health-related quality of life in adults 30 years after hospitalization for bronchiolitis or pneumonia in infancy. Methods Patients who were hospitalized for bronchiolitis or pneumonia at age under 24 months in 1981–1982 have been followed in repeated visits. In 2010, 48 of the 83 former patients with bronchiolitis (57.8%), 22 of the 44 former patients with pneumonia (50.0%), and 138 matched controls participated in the clinical study at the age of 28–31 years. The participants completed a structured questionnaire on respiratory symptoms, the Saint George's Respiratory Questionnaire (SGRQ), and underwent 2-week peak expiratory flow (PEF) monitoring. Asthma was defined as doctor-diagnosed and self-reported asthma based on doctor-prescribed medication for asthma, the presence of asthma-presumptive symptoms, and the results of home PEF monitoring. Results Both doctor-diagnosed asthma (31.3% vs. 10.9% adjusted P = 0.002) and self-reported asthma (35.4% vs. 14.5% 0.003), as well as repeated on-demand use of bronchodilators (35.4% vs. 14.5% 0.002), and regular use of inhaled corticosteroids (20.8% vs. 8.7% 0.023) were more common in former bronchiolitis patients than in controls. Former bronchiolitis and pneumonia patients had higher total SGRQ scores than controls. The median scores were 5.4 (IQ25–75 0.0–14.7, P

Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a genome-wide association study (GWAS) in which 5,300,000 single nucleotide polymorphisms (SNPs) were tested for association in a Finnish–Swedish population of 217 children hospitalized for bronchiolitis and 778 controls. The most promising SNPs (n = 77) were genotyped in a Dutch replication population of 416 cases and 432 controls. Finally, we used a set of 202 Finnish bronchiolitis cases to further investigate candidate SNPs. We did not detect genome-wide significant associations, but several suggestive association signals (p, published version, peerReviewed

Aims The aim of the study was to evaluate the association between weight status and asthma, allergy and respiratory symptoms in adolescents with bronchiolitis in infancy. Subjects and methods At age 15–18 years, a questionnaire was sent to 96 study subjects hospitalized for wheezing at age 0.78 in males and >1.16 in females) and only 3 (5.0%) were obese (BMI-SDS >1.70 in males and >2.10 in females) at 16.5 (median) years of age. Overweight or obesity had no significant association with doctor-diagnosed or self-reported asthma, allergy or the use of inhaled corticosteroids. The negative results were confirmed by adjusted analyses. Conclusion Weight status had no association with asthma or allergy in adolescence after wheezing in infancy.

Background and Aims Asthma risk is increased after bronchiolitis in infancy. Recent studies have suggested that the risk may be dependent on the causative virus. The aim of the study was to evaluate the asthma risk in adolescence in subjects hospitalized for rhinovirus or respiratory syncytial virus (RSV) bronchiolitis in infancy. Subjects and Methods At the median age of 16.5 years, a questionnaire was sent to 96 study subjects hospitalized for bronchiolitis at

Aim: Increasing evidence suggests that overweight children are at increased risk of asthma. The association between weight gain and allergy is more complex. The aim was to evaluate the association between overweight or obesity and asthma, allergy, bronchial reactivity or atopic sensitization at school age in children with bronchiolitis in infancy. Subjects and methods: Eighty-one children hospitalized for bronchiolitis at 1.3 SD from age- and gender-specific references meant overweight and BMI >2.0 SD obesity. Results: Current or previous overweight or obesity did not increase the risk of asthma, allergy, bronchial reactivity or atopic sensitization at 7.2 or 12.3 years of age. Previous and current obesity decreased the risk of atopic dermatitis, and current overweight and obesity decreased the risk of sensitization to outdoor allergens at 12.3 years of age. Conclusion: Previous or current overweight does not increase asthma or allergy risk but current obesity may decrease allergy risk at school age after bronchiolitis in infancy.

Background and purpose Recently, obesity has been connected with wheezing, asthma and reduced lung function. Most previous studies have been cross-sectional. The aim of the present follow-up study was to evaluate the association of preceding or current overweight or obesity with lung function at early and late school age after early childhood wheezing. Material and methods From the 100 children hospitalized for infection associated wheezing at 1.3 SD and >2.0 SD were defined to mean overweight and obesity, respectively. Results Overweight at both 7.2 and 12.3 years of age was associated with decreased FEV1/FVC (forced expiratory volume in 1 sec/forced vital capacity). Overweight and obesity at 7.2 years of age were associated with decreased FEV1/FVC and MEF50 (maximal expiratory flow at 50% of FVC) at 12.3 years of age. The results were similar by continuous and categorized analyses, being robust to adjustments for viral findings during early childhood wheezing and asthma maintenance medication at school age. Conclusion Overweight and obesity are significant risk factors for reduced lung function at school age after early childhood wheezing. Thus, early-life wheezers should avoid excessive weight gain during childhood. Pediatr. Pulmonol. 2011; 46:435–441. © 2010 Wiley-Liss, Inc.

Purpose of review To summarize the currently available data on the long-term outcome until young adulthood after early childhood wheezing. Asthma and lung function abnormalities were evaluated, with special attention to early-life risk factors. Recent findings In postbronchiolitis studies, 30-40% of the patients hospitalized for wheezing at less than 24 months of age have had asthma at 17-20 years of age. In the Tucson birth cohort study, the respective figure after wheezing at less than 36 months of age was 30% at 22 years of age. Relapses after many nonsymptomatic years have been common. In postbronchiolitis studies, lung function has been reduced in 31-36%, concerning also postbronchodilator measurements. Thus, the changes in airways seem to be structural, being present from infancy until adulthood, as found in the Tucson study. Parental asthma, repeated early-life wheezing and early passive smoking have been the most important early-life predictors of both adulthood asthma and lung function abnormalities. Summary Early childhood wheezing increases the risk for asthma and lung function abnormalities in young adulthood. Not only chronic childhood asthma continuing until adulthood but also asthma beginning in early adulthood seems to have its origin in early childhood.

Population-based birth cohort studies have documented that about 30% of children suffer from wheezing during respiratory infection before their third birthday. Recurrent wheezing is common in early childhood, but most patients outgrow their symptoms by school age. However, recent long-term postbronchiolitis follow-up studies from Sweden and Finland have revealed that asthma is present in about 40% of young adults and over half of the cases are relapses after many symptom-free years. In population studies, the principal predictors for later asthma have been parental asthma, recurrent wheezing, atopy and eosinophilia. In the Swedish postbronchiolitis study, atopic diathesis through the development of clinical atopy, and early passive smoking through bronchial hyper-reactivity or later active smoking led to adult asthma. The Finnish postbronchiolitis follow-up stressed early recurrence of wheezing, wheezing induced by less invasive viruses than respiratory syncytial virus (RSV), early-life atopy and eosinophilia and parental asthma as predictors for adult asthma. Conclusion: The majority of wheezing infants and children outgrow their symptoms by school age, but based on recent long-term follow-up studies, asthma relapses are common in young adults. These studies have highlighted parental asthma, maternal smoking and wheezing induced by other viruses than RSV as predictive factors for later asthma.

Background: Recent studies have stressed the influence of other viruses than respiratory syncytial virus (RSV) in the development of asthma in later childhood after bronchiolitis in infancy. However, the virus-specific prognosis until adulthood has remained obscure, due to lack of sufficiently long follow-up studies. The aim of the present study was to evaluate adult respiratory morbidity after bronchiolitis in infancy, focused on cases not caused by RSV. Methods: A total of 54 children hospitalized for bronchiolitis at age

Although eosinophilia in wheezing infants predicts subsequent wheezing, it is not known how long the association persists. Our aim was to evaluate the connection between blood eosinophilia in infancy and later wheezing/asthma until adulthood, with special attention paid to infection-induced changes in blood eosinophils. We have prospectively followed up 83 infants until adulthood after hospitalization for bronchiolitis in 1981-1982. Blood eosinophils were determined in a counting chamber on admission and on convalescence 4-6 weeks later. Data on recurrent wheezing and asthma were registered prospectively at five follow-ups until the age of 18-20 years. The median (25th-75th percentile) eosinophil count was 0.100 x 10E9/L (0.028-0.321) on admission and 0.231 x 10E9/L (0.119-0.368) on convalescence. Eosinophils during bronchiolitis or infection-induced changes in eosinophils were not associated with subsequent wheezing/asthma at any age during the follow-up. The result was similar in univariate and multivariate analyses. Respiratory syncytial virus (RSV) bronchiolitis patients had lower eosinophils on admission than non-RSV cases, but the changes induced by RSV or other infection did not differ significantly. In univariate analyses, elevated eosinophils on convalescence predicted later wheezing until 3-4 years of age. In multivariate analysis, adjusted for RSV etiology, age on admission, and histories of earlier wheezing and atopy, elevated eosinophils on convalescence predicted increased asthma risk at 2-3 years (OR, 2.26; 95% CI, 1.29-3.95), at 3-4 years (OR, 2.24; 95% CI, 1.27-3.95), and at 8.5-10 years (OR, 2.16; 95% CI, 1.01-4.64). Eosinophilia outside, but not during, infection predicted recurrent wheezing until preschool and early school years but not thereafter.

In the present cohort, 85% of infants hospitalized for wheezing outgrew their symptoms until puberty, but 30-40% had asthma, depending on criteria, again in young adulthood. The aim of this study was to determine early predictors for adulthood asthma, bronchial reactivity, and lung function abnormalities in infants hospitalized for bronchiolitis. Fifty-two children hospitalized for bronchiolitis at < 2 years of age were restudied at the median age of 19 years. Wheezing histories and early risk factors for later asthma were recorded prospectively during infancy. The follow-up study consisted of a written questionnaire, physical examination, flow-volume spirometry, methacholine inhalation challenge, home peak expiratory flow monitoring, and skin-prick tests. In univariate analyses, parental asthma and repeated wheezing at age the age of 0-1 years and 0-2 years predicted adulthood asthma. Repeated wheezing at age the age of 0-1 years predicted later bronchial reactivity. Onset and recurrence of wheezing at < 1 year of age, parental atopy and asthma, and maternal smoking during infancy were related to subnormal lung function parameters. In multivariate logistic regression, adjusted for sex, age on admission, current smoking, and atopy in infancy and, currently, repeated wheezing both at < 1 year and < 2 years of age was an independent predictor for adulthood asthma. Parental asthma and repeated wheezing predict adulthood asthma in infants hospitalized for bronchiolitis, and maternal smoking predisposes them to lung function impairment in adulthood.

To the Editors: In a previous issue of the European Respiratory Journal , Kusel et al. [1] reported very interesting 10-yr results of their prospective birth cohort study. Originally, 263 children at risk for asthma and allergy were recognised pre-natally and recruited as newborns, and 198 (75.3%) attended the 5-yr [2] and 147 (55.9%) the 10-yr follow-up study [1]. The drop-out rate of 44% is understandable but needs evaluation. The data were collected very carefully during the first year including diaries completed by parents and home visits with sampling for virus detection by PCR during all acute infections [2]. Respiratory infections were classified as upper (URI) and lower (LRI), and both URIs and LRIs further as wheezy and nonwheezy. At age 10 yrs, 18.4% of the 147 children had current asthma and 20.4% persistent wheeze [1]. During the first year of life, 35.8% had experienced at least one LRI with fever and/or wheeze. The figure was 26.5% …

A prospective >25-year follow-up study evaluated the outcome of patients hospitalized for respiratory syncytial virus (RSV) infection at

Hyvarinen MK, Kotaniemi-Syrjanen A, Reijonen TM, Piippo-Savolainen E, Korppi M. Eosinophil activity in infants hospitalized for wheezing and risk of persistent childhood asthma. Pediatr Allergy Immunol 2010: 21: 96–103. © 2009 John Wiley & Sons A/S Eosinophilic inflammation has a central role in the pathogenesis of asthma. We aimed to elucidate whether elevated blood eosinophil count (B-EOS), eosinophil cationic protein in serum (S-ECP) or in nasopharyngeal aspirate (NPA-ECP) predict later asthma after hospitalization for wheezing in infancy. In 1992–1993, 100 infants aged

Birth cohort studies have suggested that early exposure to furred pets protects from later asthma and allergy. The aim of the present study was to evaluate the association between exposure or sensitization to cat or dog in infancy, and later asthma and allergy assessed at the median ages of 4.0, 7.2 and 12.3 yr, in children who have wheezed at < 24 months of age. Exposure to cat and dog in infancy was assessed by interviewing the parents. The child was considered as sensitized, if the allergen-specific IgE to cat or to dog was ≥0.35 kU/1, or if there was a positive skin test response. When the 20 children with persistent childhood asthma (doctor-diagnosed asthma at all three control visits) were compared with the other 61 children, an early exposure to dog (OR = 0.14, p = 0.034)) decreased the asthma risk and an early sensitization to cat (OR = 5.92, p = 0.008) and dog (OR - 9.33, p = 0.001) increased the asthma risk. There were less cat and dog keeping in atopic families and the effect of sensitization was, but the effect of exposure was not, robust to adjustments in multivariate analyses. The present study demonstrates, in a long-term follow-up after early wheezing, that early sensitization to cat and dog increases the risk of later asthma but early exposure to cat or dog has no such effect. Dog keeping was less frequent in atopic families, which may explain that the protective effect of early exposure to dog was lost in multivariate analyses.

Early sensitization to inhaled allergens predicts later asthma and allergy until school age, but studies on early exposure have given conflicting results. The purpose of this study was to evaluate the association between early wheezing, early exposure, or sensitization to pets and pollens and later asthma or allergy until adulthood. We have prospectively followed-up a cohort of 83 infants hospitalized for bronchiolitis in 1981-1982. Cat and dog ownership (early exposure) and inhalant allergen-specific IgE measurements (early sensitization) were registered at

Background and aims Respiratory syncytial virus (RSV) bronchiolitis is the primary cause of hospital admission among children under two years and it is considered to be a risk factor for developing asthma later in life. Although some genetic variants associated with bronchiolitis have been identified by candidate gene studies, the genetic background of the disease is not well understood. Here, we aimed to identify genetic polymorphisms conferring susceptibility to severe bronchiolitis and subsequent asthma. Methods Case-control discovery cohorts with 94 cases of severe bronchiolitis and 94 controls collected in Finland and Sweden were genotyped with Illumina HumanOmniExpress BeadChip containing 700.000 SNPs. Replication population of 130 cases and 250 controls collected in Finland is being genotyped with HumanCoreExome BeadChip containing 500.000 SNPs. Respiratory outcomes of all the cohorts have been followed-up to 5–30 years of age. Association signals are further analysed in appropriate functional studies. Results In the discovery data set, several signals indicating association with bronchiolitis were identified. As an example, SNPs within ADAR (adenosine deaminase, RNA-specific) and KLRK1 (killer cell lectin-like receptor subfamily K, member 1) genes involved e.g. in immune responses showed suggestive associations (p-value ≤10 –4 ). Some of the SNPs previously reported to be associated with bronchiolitis showed weaker signals. Conclusions We found suggestive association signals for several SNPs. Associations observed both in the discovery population and in the replication cohort are regarded as plausible candidates for further studies. The most promising candidate genes will be analysed in functional studies to verify their potential role in bronchiolitis.

Background Joint pain and swelling are typical symptoms in children with juvenile idiopathic arthritis (JIA) and these are often related to inflammation of the joint. Juvenile osteochondritis dissecans (JOCD), that is separation of a bone-cartilage segment from the articular surface, can manifest with similar symptoms. Findings We studied thirteen cases of osteochondritis dissecans lesions (OCD) in children with JIA. There were nine girls and four boys with a mean age of 6.5 (2–12) years at the time of diagnosis of JIA. Mean time between diagnosis of JIA and manifestation of OCD was 5.5 (1–11) years. Indications for MRI were the presence of pain or discomfort in the joint, despite otherwise effective treatment, with no evidence from ultrasound examination of any obvious signs of active inflammation. The most common location of osteochondral lesion was the knee, although the ankle joint was affected in one case. Five patients had lesions in both knees. Operative treatment was needed in eight cases (joints). Conclusions Pain, and minor dysfunction of the joint are common complaints of children suffering from JIA. Earlier research has discounted the possibility of children who were not athletes presenting with this condition. However, this study demonstrates that these lesions also seem to be relatively common in patients with JIA. When there is no sign of inflammation, the possibility of OCD must therefore be considered in these children.

To the Editor: In response to our recent article1 Piippo-Savolainen et al. share data from their well- studied cohort of 83 subjects followed from early childhood for over 25 years for asthma and other pulmonary outcomes.2 Several factors make it difficult to make comparisons to our recent findings from the work highlighted by Piippo-Savolainen et al. including: the small sample size, the fact that their study was neither designed nor powered to address our study questions, differences between studies in how exposure and outcome variables were defined, and the lack of both a spectrum of bronchiolitis severity and a comparison group without bronchiolitis. Our population-based retrospective birth cohort study, the Tennessee Asthma Bronchiolitis Study (TABS), was designed to investigate the relationship between infant bronchiolitis and early childhood asthma. The definition of the risk factor of interest, bronchiolitis during infancy, differs significantly between the studies. Our measure of bronchiolitis severity was based on level of health care for bronchiolitis, including clinic visits, emergency department visits, and hospitalizations, as determined by ICD-9 diagnosis, with the risk period being only during infancy. Our inclusion of a comparison group of infants, who had no visit for bronchiolitis in their first year, allowed for the hypothesis-driven investigation of whether there was a severity-response relationship between the most advanced level of health care for bronchiolitis and subsequent early childhood asthma risk and morbidity. Piippo-Savolainen et al. have followed 83 children who were all hospitalized for bronchiolitis at

Objective To determine the outcome until adulthood after wheezing in infancy, compared with pneumonia in infancy and with controls. Design An 18- to-20-year prospective cohort study. Setting Pediatric department at a university hospital, providing primary hospital care for a defined population. Patients Fifty-four children hospitalized for bronchiolitis and 34 for pneumonia at younger than 2 years, and 45 controls with no early-life wheezing or hospitalization, were studied at median age 19 years. Main Outcome Measures A questionnaire on asthma symptoms and medication, physical examination, flow volume spirometry (FVS), methacholine inhalation challenge (MIC), home peak expiratory flow (PEF) monitoring, and skin prick testing (SPT) to common inhalant allergens. The 2 asthma definitions were physician-diagnosed asthma and previously diagnosed asthma with recent asthmatic symptoms (physician-diagnosed asthma included). Results By the 2 definitions, asthma was present in 30% (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.12-10.10) and in 41% (OR 1.38; 95% CI, 0.37-5.21) in the bronchiolitis group, in 15% (OR, 5.50; 95% CI, 1.87-16.14) and in 24% (OR, 2.07; 95% CI, 0.59-7.22) in the pneumonia group, and in 11% in the control group. After bronchiolitis, the FVS values were forced vital capacity (FVC), 108% (SD, 13%) of predicted; forced expiratory volume in 1 second, 98% (SD, 12%); forced expiratory volume in 1 second divided by FVC, 91% (SD, 7.6%); midexpiratory flow at 50% of the FVC, 74% (SD, 19%); and midexpiratory flow at 25% of the FVC, 74% (SD, 22%). Bronchial reactivity by MIC was present in 25 (48%) of 52 subjects in the bronchiolitis group, in 13 (42%) of 31 in the pneumonia group, and in 14 (32%) of 44 in the control group. The prevalence of atopy (positive SPTs) was 48% to 63% in the 3 groups. In a logistic regression adjusted for atopy and smoking, infantile bronchiolitis was an independent risk factor for asthma by both definitions. Conclusion The increased risk for asthma persists until adulthood after bronchiolitis in infancy.