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Background: Acute rhinovirus-induced wheezing is common in young children and may respond to systemic corticosteroid. There are no trials on the efficacy of inhaled beta₂-agonist in this clinical scenario. Objective: To study post hoc the short-term (up to 2 months) efficacy of inhaled beta2-agonist with and without oral corticosteroid in the first acute rhinovirus-induced severe wheezing episode in young hospitalized children. Methods: The study population came from two randomized controlled trials comparing oral prednisolone (2 mg/kg/d for 3 days) to placebo: Vinku (n = 35, NCT00494624) used high-dose regular nebulized salbutamol (0.15 mg/kg 2–4 h intervals) and Vinku2 (n = 60, NCT00731575, EudraCT 2006-007100-42) used inhaled salbutamol on-demand. Both studies used identical detailed follow-up assessments. The primary outcome of the former was the duration of hospitalization and of the latter the occurrence of and the time to a new physician-confirmed wheezing episode within 2 months after discharge. Treatment groups included salbutamol high-dose vs. salbutamol on-demand while adjusting for prednisolone status and acknowledging for interactions with exception of the duration of hospitalization in which prednisolone groups could not be fully used due to protocol differences. Results: Median age of subjects was 13 months, 32% were sensitized and 22% had doctor-diagnosed eczema. In the duration of hospitalization, salbutamol high-dose/placebo versus salbutamol on-demand/placebo groups did not differ (p = .12). In the occurrence of and time to relapse within 2 months, a significant group × treatment interaction was observed (both p = .02), such that high-dose group had less and longer time to relapses than on-demand group in prednisolone arm (both p < .05), but no difference was detected in placebo arm (both p > .26). Conclusions: In young, hospitalized children with first episode of rhinovirus-induced wheezing, high-dose inhaled salbutamol may interact with oral prednisolone. However, further trials are warranted.

Background Rhinovirus is the most common virus causing respiratory tract illnesses in children. Rhinoviruses are classified into species A, B and C. We examined the associations between different rhinovirus species and respiratory illness severity. Methods This is a retrospective observational cohort study on confirmed rhinovirus infections in 134 children 3-23 months of age, who were enrolled in 2 prospective studies on bronchiolitis and acute otitis media, respectively, conducted simultaneously in Turku University Hospital, Turku, Finland, between September 2007 and December 2008. Results Rhinovirus C is the most prevalent species in our study, and it was associated with severe wheezing and febrile illness. We also noted that history of atopic eczema was associated with wheezing. Conclusions Our understanding of rhinovirus C as the most pathogenic rhinovirus species was fortified. Existing research supports the idea that atopic characteristics are associated with the severity of the rhinovirus C-induced illness.

Background: Separating individuals with viral-induced wheezing from those with asthma is challenging, and there are no guidelines for children under 6 years of age. Impulse oscillometry, however, is feasible in 4-year-old children. Objective: To explore the use of impulse oscillometry in diagnosing and monitoring asthma in young children and evaluating treatment response to inhaled corticosteroid (ICS). Methods: A total of 42 children (median age 5.3 years, range 4.0-7.9 years) with physician-diagnosed asthma and lability in oscillometry were followed for 6 months after initiation of ICS treatment. All children performed the 6-minute free-running test and impulse oscillometry at 3 time points. After the baseline, they attended a second visit when they had achieved good asthma control and a third visit approximately 60 days after the second visit. A positive ICS response was defined as having greater than 19 points in asthma control test and no hyperreactivity on the third visit. Results: In total, 38 of 42 children responded to ICS treatment. Exercise-induced increases of resistance at 5 Hz decreased after ICS treatment (61% vs 18% vs 13.5%, P < .001), and running distance during the 6-minute test was lengthened (800 m vs 850 m vs 850 m, P = .001). Significant improvements in childhood asthma control scores occurred between the baseline and subsequent visits (21 vs 24 vs 24, P < .001) and acute physicians' visits for respiratory symptoms (1, (0-6) vs 0, (0-2), P = .001). Similar profiles were observed in children without aeroallergen sensitization and among those under 5 years of age. Conclusion: Impulse oscillometry is a useful tool in diagnosing asthma and monitoring lung function in young children. (C) 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc.

Rationale: Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing. Objectives: To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses. Methods: Longitudinal data from the COAST (Childhood Origins of Asthma) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for RV-A and RV-C (three types each) were determined using a novel PCR-based assay. Data were pooled from 14 study cohorts in the United States, Finland, and Australia, and mixed-effects logistic regression was used to identify factors related to the proportion of RV-C versus RV-A detection. Measurements and Main Results: In COAST, RV-A and RV-C infections were similarly common in infancy, whereas RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (P

Background: Exhaled nitric oxide (FeNO) measurements and eucapnic voluntary hyperventilation (EVH) tests have been used as diagnostic tools for asthma. Data on the impact of hyperventilation on the level of FeNO are limited. Aim: We aimed to evaluate whether EVH tests affect the level of FeNO in children aged 10–16 years. Methods: A total of 234 children aged 10–16 years had a 6‐min EVH test performed. In total, FeNO values for 153 of 234 children were measured before the test and within 15 min after the test. According to a baseline FeNO level of 20 ppb, children were divided into two groups: those with low values (FeNO < 20 ppb) and those with high values (FeNO ≥ 20 ppb). Results: The median age of the children was 13.4 years (interquartile range 12.3–15.3 years); 58% were boys and 42% were girls. Of these children, 51% were sensitized to aeroallergens. In 101 of 153 children (66%), the FeNO values decreased after the EVH test. In children with low and high baseline levels, the median level of FeNO decreased after the EVH test: 10.5 ppb before versus 9.5 ppb after (p < .011), and 31.0 ppb before versus 28.0 ppb after (p < .011), respectively. The decrease in FeNO after EVH test was not associated with induced bronchoconstriction expressed as a change in FEV1 (Rs = .19). Conclusions: The EVH test decreases FeNO levels. Therefore, FeNO should be measured before an EVH test is performed.

Background Wheezing illnesses among young children are common and are a risk factor for asthma. However, determinants of childhood bronchial reactivity, a key feature of asthma, are largely unknown. The aim of this study was to determine how patient characteristics during the first severe virus-induced wheezing episode are associated with pulmonary function at preschool age. Methods Study consisted of 76 children presenting with their first wheezing episode at the ages of 3 to 23 months. At study entry, viral etiology, rhinovirus genome load, atopic and clinical characteristics, and standardized questionnaire were analyzed. At 4-year follow-up visit, impulse oscillometry with exercise challenge was performed. Results At study entry, the mean age of the children was 12 months (SD 6.0), 57 (75%) were rhinovirus positive, and 22 (30%) were sensitized. At follow-up visit four years later, the mean age of the children was 60 months (SD 7.9) and 37 (49%) were using asthma medication regularly (discontinued before testing in 25 [68%] children). Bronchial reactivity (≥35% change in mean crude values of resistance) after exercise challenge or bronchodilation was present in nine (12%) children. Children with atopic sensitization at the time of the first wheezing episode were more often likely to develop bronchial reactivity (odds ratio 8.8, P = 0.03) than the children without sensitization. No other significant associations were found. Conclusions Atopic sensitization at the time of the first severe wheezing episode is an important early risk factor for increased bronchial reactivity at preschool age.

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

Asthma is responsible for approximately 25,000 deaths annually in Europe despite available medicines that maintain asthma control and reduce asthma exacerbations. Better treatments are urgently needed for the control of chronic asthma and reduction in asthma exacerbations, the major cause of asthma mortality. Much research spanning >20 years shows a strong association between microorganisms including pathogens in asthma onset, severity and exacerbation, yet with the exception of antibiotics, few treatments are available that specifically target the offending pathogens. Recent insights into the microbiome suggest that modulating commensal organisms within the gut or lung may also be a possible way to treat/prevent asthma. The European Academy of Allergy & Clinical Immunology Task Force on Anti‐infectives in Asthma was initiated to investigate the potential of anti‐infectives and immunomodulators in asthma. This review provides a concise summary of the current literature and aimed to identify and address key questions that concern the use of anti‐infectives and both microbe‐ and host‐based immunomodulators and their feasibility for use in asthma.

Background Previous findings show that corticosteroid treatment during the first acute wheezing episode may reduce recurrent wheezing in children with high rhinovirus genome load at 12-month follow-up. Longer-term effects have not been investigated prospectively. Methods After PCR-confirmation of rhinovirus from nasopharyngeal aspirate, 79 children with the first acute wheezing episode were randomized to receive orally prednisolone or placebo for three days. The initiation of asthma control medication before the age of 5 years was confirmed from medical record and/or from parental interview. The outcome was the time to initiation of regular asthma control medication. Interaction analysis examined rhinovirus genome load. Results Fifty-nine (75%) children completed the follow-up. Asthma control medication was initiated in 40 (68%) children at the median age of 20 months. Overall, prednisolone did not affect the time to initiation of asthma control medication when compared to placebo (p=0.99). Rhinovirus load modified the effect of prednisolone regarding the time to initiation of asthma control medication (p-value for interaction=0.04). In children with high rhinovirus load (>7000 copies/mL)(n=23), the risk for initiation of medication was lower in the prednisolone group compared to the placebo group (p=0.05). In the placebo group asthma medication was initiated to all children with high rhinovirus load (n=9) during the 14 months after the first wheezing episode. Conclusions Overall, prednisolone did not affect the time to initiation of asthma control medication when compared to placebo. However, prednisolone may be beneficial in first-time wheezing children whose episode was severe and associated with high rhinovirus load. (ClinicalTrials. gov, NCT00731575). This article is protected by copyright. All rights reserved.

Aim Infants hospitalised for bronchiolitis undergo examinations and treatments not supported by current research evidence and we investigated practice variations with regard to Finnish children under the age of two. Methods This prospective, multicentre cohort study was conducted in paediatric units in three university hospitals in Finland from 2008 to 2010. Hospital medical records were reviewed to collect data on clinical course, testing and treatment. Data were analysed separately for children meeting our strict definition of bronchiolitis, aged under 12 months without a history of wheezing, and a loose definition, aged 12–23 months or with a history of wheezing. Results The median age of the 408 children was 8.1 months. Clinical management varied between the three hospitals when stratified by strict and loose bronchiolitis subgroup definitions: complete blood counts ranged from 15–95% vs 16–94%, respectively, and the other measures were chest x-ray (16–91% vs 14–72%), intravenous fluids (2–47% vs 2–41%), use of nebulised epinephrine (10–84% vs 7–50%), use of salbutamol (18–21% vs 13–84%) and use of corticosteroids (6–23% vs 60–76%). Conclusion The clinical management of bronchiolitis varied considerably with regard to the three hospitals and the two definitions of bronchiolitis. A stronger commitment to evidence-based bronchiolitis guidelines is needed in Finland.

Background In children suffering from severe lower airway illnesses, respiratory virus detection has given good prognostic information, but such reports in the elderly are scarce. Therefore, our aim was to study whether the detection of nasopharyngeal viral pathogens and conventional inflammatory markers in the frail elderly correlate to the presence, signs and symptoms or prognosis of radiographically-verified pneumonia. Methods Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms (N = 382) were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory analyses included PCR diagnostics of nasopharyngeal swab samples for 14 respiratory viruses, C-reactive protein (CRP) and white blood cell count (WBC). Chest radiographs were systematically analysed by a study radiologist. The length of hospital stay, hospital revisit and death at ward were used as clinical endpoints. Results Median age of the patients was 83 years (range 76–90). Pneumonia was diagnosed in 112/382 (29%) of the studied episodes. One or more respiratory viruses were detected in 141/382 (37%) episodes and in 34/112 (30%) episodes also diagnosed with pneumonia. Pneumonia was associated with a WBC over 15 × 109/L (P = .006) and a CRP value over 80 mg/l (P

Background Persistent childhood asthma is mainly atopy driven. However, limited data exist on the risk factors for childhood asthma phenotypes. Objective We sought to identify risk factors at the first severe wheezing episode for current asthma 7 years later and separately for atopic and nonatopic asthma. Methods One hundred twenty-seven steroid-naive children with the first severe wheezing episode (90% hospitalized/10% emergency department treated) were followed for 7 years. The primary outcome was current asthma at age 8 years, which was also analyzed separately as atopic and nonatopic asthma. Risk factors, including sensitization, viral cause, and other main asthma risk factors, were analyzed. Results At study entry, median age was 11 months (interquartile range, 6-16 months); 17% were sensitized, and 98% were virus positive. Current asthma (n = 37) at 8 years was divided into atopic (n = 19) and nonatopic (n = 18) asthma. The risk factors for current atopic asthma at study entry were sensitization (adjusted odds ratio [OR], 12; P

BACKGROUND Susceptibility to rhinovirus (RV)-induced early wheezing episode has been recognized as an important risk factor for asthma, but the data on different RV species are limited. Our aim was to investigate the risk for recurrences in first-time wheezing children with special focus on RV species. METHODS First-time wheezing children (88 inpatients and 23 outpatients) were prospectively followed at 2-week, 2-month and 12-month time-points, and at first recurrence within 12 months. The respiratory virus etiology was analyzed using polymerase chain reaction. RV-positive samples were sequenced. The primary outcomes were time to a new physician-confirmed wheezing episode, time to a new RV-induced wheezing episode and time to the initiation of regular controller medication for asthma symptoms. RESULTS The median age of the children was 12 months (standard deviation, 6.0), 67% were males and 23% were sensitized. RV dominated in symptomatic and asymptomatic infections. Different RV strains were observed in 97% (67/69) of consecutive samples during follow-up. First-time wheezing children with RV-C and RV-A had an increased risk for a new physician-confirmed wheezing episode and a new RV-associated wheezing episode than non-RV group (all P < 0.05). Also, the risk for the initiation of regular controller medication was increased in RV-A and RV-C groups when compared with non-RV group (both P < 0.05). CONCLUSIONS RV causes reinfections with different strains in small children after the first wheezing episode. Both RV-A and RV-C affected children have an increased risk for recurrence, especially RV associated, and initiation of regular controller medication than those with other viruses.

Conserved protein antigens have been investigated as vaccine candidates against respiratory pathogens. We evaluated the natural development of antibodies against Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis proteins during childhood. Serum samples were collected from 50 healthy children from their first months to age 13 years (median sampling interval, 6 months). We also analyzed serum samples from 24 adults. Serum IgG antibodies against eight pneumococcal proteins (Ply, CbpA, PspA 1 and 2, PcpA, PhtD, StkP-C, and PcsB-N), three H. influenzae proteins, and five M. catarrhalis proteins were measured using a multiplexed bead-based immunoassay. Antibody levels were analyzed using multilevel mixed-effects regression and Spearman's correlation. Antibody levels against pneumococcal proteins peaked at 3 to 5 years of age and then reached a plateau. Antibody levels against H. influenzae proteins peaked during the second year and then stabilized. Antibody levels against M. catarrhalis proteins peaked during the first year and then slowly decreased. Peak antibody levels during childhood were higher than those of adults. Correlations among pneumococcal antibody levels were highest among anti-CbpA, anti-PcpA, and anti-PhtD antibodies ( r = 0.71 to 0.75; P < 0.001). The children presented 854 symptomatic respiratory infections on 586 occasions. Symptomatic respiratory infections did not improve prediction of antibody levels in the regression model. The maturation of immune responses against the investigated pneumococcal proteins shares similarities, especially among CbpA, PcpA, and PhtD. Antibody production against H. influenzae and M. catarrhalis proteins starts early in life and reaches peak levels earlier than antibody production against the pneumococcal proteins. Basal antibody levels are not related to the occurrence of symptomatic respiratory infections.

Objective Although bronchiolitis is generally considered a single disease, recent studies suggest heterogeneity. We aimed to identify severe bronchiolitis profiles using a clustering approach. Methods We analysed data from two prospective, multicentre cohorts of children younger than 2 years hospitalised with bronchiolitis, one in the USA (2007–2010 winter seasons, n=2207) and one in Finland (2008–2010 winter seasons, n=408). Severe bronchiolitis profiles were determined by latent class analysis, classifying children based on clinical factors and viral aetiology. Results In the US study, four profiles were identified. Profile A (12%) was characterised by history of wheezing and eczema, wheezing at the emergency department (ED) presentation and rhinovirus infection. Profile B (36%) included children with wheezing at the ED presentation, but, in contrast to profile A, most did not have history of wheezing or eczema; this profile had the largest probability of respiratory syncytial virus infection. Profile C (34%) was the most severely ill group, with longer hospital stay and moderate-to-severe retractions. Profile D (17%) had the least severe illness, including non-wheezing children with shorter length of stay. Two of these profiles (A and D) were replicated in the Finnish cohort; a third group (‘BC’) included Finnish children with characteristics of profiles B and/or C in the US population. Conclusions Several distinct clinical profiles (phenotypes) were identified by a clustering approach in two multicentre studies of children hospitalised for bronchiolitis. The observed heterogeneity has important implications for future research on the aetiology, management and long-term outcomes of bronchiolitis, such as future risk of childhood asthma.

Rationale: Rhinoviruses (RVs) are a major cause of symptomatic respiratory tract infection in all age groups. However, RVs can frequently be detected in asymptomatic individuals. Objectives: To evaluate the ability of host transcriptional profiling to differentiate between symptomatic RV infection and incidental detection in children. Methods: Previously healthy children younger than 2 years old (n = 151) were enrolled at four study sites and classified into four clinical groups: RV2 healthy control subjects (n = 37), RV1 asymptomatic subjects (n = 14),RV1 outpatients (n = 30), and RV1 inpatients (n = 70). Host responses were analyzed using whole-blood RNA transcriptional profiles. Measurements and Main Results: RV infection induced a robust transcriptional signature, which was validated in three independent cohorts and by quantitative real-time polymerase chain reaction with high prediction accuracy. The immune profile of symptomatic RV infection was characterized by overexpression of innate immunity and underexpression of adaptive immunity genes, whereas negligible changes were observed in asymptomatic RV1 subjects. Unsupervised hierarchical clustering identified two main clusters of subjects. The first included 93% of healthy control subjects and 100%ofasymptomatic RV1subjects, andthesecond comprised98% of RV1 inpatients and 88% of RV1 outpatients. Genomic scores of healthy control subjects and asymptomatic RV1 children were similar and significantly lower than those of RV1 inpatients and outpatients (P

In a prospective cohort of children hospitalized for bronchiolitis, we examined the rate of and characteristics associated with bronchiolitis relapse. Bronchiolitis relapse was documented in 22 (6%) of 391 children, and median time to relapse was 2 (interquartile range, 1-7) days. Relapse occurred more often in males. Prenatal smoking and smoke exposure in the home were also associated with relapse.

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

In this analysis of 2 prospective multicenter, multi-year cohorts of children hospitalized for bronchiolitis in the United States and Finland, 306 rhinovirus infections were genotyped. Rhinovirus-A and -C species were predominant in the US study, while rhinovirus-C species was predominant in the Finland study. In both cohorts, there were no significant between-species differences in clinical characteristics, including acute severity measures.

BACKGROUND The PreDicta cohort was designed to prospectively evaluate wheeze/asthma persistence in preschoolers in association with viral/microbial exposures and immunological responses. We present the cohort design and demographic/disease characteristics and evaluate unsupervised and predefined phenotypic subgroups at inclusion. METHODS PreDicta is a 2-year prospective study conducted in five European regions, including children 4-6 years with a diagnosis of asthma as cases and healthy age-matched controls. At baseline, detailed information on demographics, asthma and allergy-related disease activity, exposures, and lifestyle were recorded. Lung function, airway inflammation, and immune responses were also assessed. Power analysis confirmed that the cohort is adequate to answer the initial hypothesis. RESULTS A total of 167 asthmatic children (102 males) and 66 healthy controls (30 males) were included. Groups were homogeneous in respect to most baseline characteristics, with the exception of male gender in cases (61%) and exposure to tobacco smoke. Comorbidities and number and duration of infections were significantly higher in asthmatics than controls. 55.7% of asthmatic children had at least one positive skin prick test to aeroallergens (controls: 33.3%, P = .002). Spirometric and exhaled nitric oxide values were within normal limits; only baseline FEV0.5 and FEV1 reversibility values were significantly different between groups. Viral infections were the most common triggers (89.2%) independent of severity, control, or atopy; however, overlapping phenotypes were also common. Severity and control clustered together in an unsupervised analysis, separating moderate from mild disease. CONCLUSIONS The PreDicta cohort presented no differences in non-asthma related measures; however, it is well balanced regarding key phenotypic characteristics representative of "preschool asthma".

SummaryBackground In children, exercise-induced dyspnea is a common symptom that can be due to dysfunctional breathing. EVH test has bee used especially in elite athletes as bronchoprovocation test. Currently, there are only few studies on the EVH test. New research methods are required alongside the traditionally used tests especially due to dysfunctional breathing disorder. Purpose The purpose of the “pilot study” was to study the usability of the EVH test with real time biofeedback in children of 10–16 years of age in the diagnostics of exercise-induced dyspnea. Methods Six 10-16-year-old teenagers with history of exercise-induced dyspnea and three healthy control subjects were selected for the study. A 6-minute EVH test with realtime biofeedback was performed on the patients and the diagnosis was confirmed on the basis of clinical findings and spirometry follow-up either as normal, asthma or dysfunctional breathing. Results The study was successful in the patients. In the spirometry follow-up, three patients had bronchoconstriction (FEV1 decline over 10%), dysfunctional breathing condition was observed in three patients and three control patients experienced no symptoms. Only two DFB-patients didn't reach the target level of minute ventilation due to a clinical symptom (inspiratory stridor). Conclusion The EVH test was successful in the 10-16-year-old children having participated in the study and the test was well tolerated. Through the study, it was possible to provoke both dysfunctional breathing disorder and bronchoconstriction in the symptomatic patients. Based on the pilot study, EVH test seems to be usable in the diagnostics of pediatric exercise-induced dyspnea but larger studies are warranted to confirm our preliminary findings.

Background We investigated whether children with a higher respiratory syncytial virus (RSV) genomic load are at a higher risk of more-severe bronchiolitis. Methods > Two multicenter prospective cohort studies in the United States and Finland used the same protocol to enroll children aged Results Of 2615 enrolled children, 1764 (67%) had RSV bronchiolitis. Children with a low genomic load had a higher unadjusted risk of having a length of stay of ≥3 days (52%), compared with children with intermediate and those with high genomic loads (42% and 51%, respectively). In a multivariable model, the risk of having a length of stay of ≥3 days remained significantly higher in the groups with intermediate (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.20–1.69) and high (OR, 1.58; 95% CI, 1.29–1.94) genomic loads. Similarly, children with a high genomic load had a higher risk of intensive care use (20%, compared with 15% and 16% in the groups with low and intermediate genomic loads, respectively). In a multivariable model, the risk remained significantly higher in the group with a high genomic load (OR, 1.43; 95% CI, 1.03–1.99). Conclusion Children with a higher RSV genomic load had a higher risk for more-severe bronchiolitis.

Aim Infant swimming has been considered as a risk factor for wheezing, but the role that respiratory viruses play is unclear. We explored the effects of infant swimming on the risk of all wheezing illnesses and wheezing associated with rhinoviruses. Methods We followed up a birth cohort of 1827 children until 17 months of age, collecting data on infant swimming, other risk factors and physician-diagnosed bronchiolitis or recurrent wheezing. Viral diagnostics were performed in a subset of children with all respiratory tract infections. Results Data on infant swimming were obtained for 1038 children, with viral follow-up for 635 children. At least one wheezing illness was documented in 45/469 (9.6%) swimming children versus 39/569 (6.9%) nonswimming children (p = 0.11), and rhinoviruses were associated with wheezing in 11/296 (3.7%) swimming children versus 4/339 (1.2%) nonswimming children (p = 0.04). In adjusted logistic regression analyses, swimming had an odds ratio of 1.71 (p = 0.05) for bronchiolitis and 3.57 (p = 0.06) for rhinovirus-associated wheezing. An association between infant swimming and rhinovirus-associated wheezing was detected for children with atopic eczema (p = 0.006). Conclusion There may be a link between infant swimming and rhinovirus-induced wheezing illnesses in atopic infants.

In 169 Finnish infants hospitalized for bronchiolitis at age

Background Susceptibility to early rhinovirus-induced wheezing has been recognized as an important risk factor for childhood asthma, but data on the first wheezing episode are limited. The aim of this selected population study was to investigate virus etiology, atopic characteristics, and illness severity, as well as their interrelation, among first-time wheezing children. Methods We studied 111 first-time wheezing children aged between 3 and 23 months (88/23 in-/outpatients). The investigated factors included atopy, food, perennial and aeroallergen sensitization, eczema, atopic eczema, elevated blood eosinophil count, and parental allergic rhinitis, asthma, and smoking. Nasopharyngeal aspirates were analyzed for adenovirus, coronaviruses, enteroviruses, bocavirus-1 (also serologically confirmed), influenza viruses, metapneumovirus, parainfluenza viruses, rhinovirus, and respiratory syncytial virus using PCR methods. Results The mean age of the study patients was 12 months (standard deviation 6.0). Atopic characteristics could be found in 56%, atopic eczema in 16%, and sensitization in 23% of the cases. In all samples (100%), ≥1 viruses were detected as follows: rhinovirus (76%), respiratory syncytial virus (29%), bocavirus (18%, acute infections), and other viruses

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

The clinical data on the first wheezing episodes induced by different rhinovirus (RV) species are still limited. We aimed to investigate the prevalence of RV genotypes, sensitization status, and clinical characteristics of patients having a respiratory infection caused by either different RV species or other respiratory viruses. The study enrolled 111 patients (aged 3-23 months, 79% hospitalized, 76% with RV infection) with the first wheezing episode. RV-specific sequences were identified by partial sequencing of VP4/VP2 and 5' non-coding regions with 80% success rate. The investigated clinical and laboratory variables included atopic characteristics and illness severity, parental atopic illnesses, and parental smoking. Of the study children, 56% percent had >1 atopic characteristic (atopy, eczema and/or blood eosinophil count >0.4 × 109 /L) and 23% were sensitised to allergens. RV-C was detected in 58% of RV positive samples, followed by RV-A (20%) and RV-B (1.2%). Children with RV-A and RV-C induced wheezing were older (P = 0.014) and had more atopic characteristics (P = 0.001) than those with non-RV. RV-A and RV-C illnesses had shorter duration of preadmission symptoms and required more bronchodilator use at the ward than non-RV illnesses (both P

The purpose of this study was to examine the association between bacterial colonization/infection and respiratory outcomes in children younger than 3 years old who were hospitalized for their first wheezing episode. This was an observational study. The primary outcome was hospitalization time and the secondary outcomes included relapses within 2 months and time to recurrent wheezing (i.e. three physician confirmed wheezing episodes) within 12 months. Bacterial antibody assays for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae and Chlamydia pneumoniae were studied as well as nasopharyngeal bacterial culture for the three former and urine pneumococcal antigen. Nasopharyngeal bacterial culture was positive in 31/52 (60%) children, serologic evidence of bacterial infection was found in 17/96 (18%) children, urine pneumococcal antigen was positive in 24/101 (24%), and any bacterial detection method was positive in 53/106 (50%) children. The children with positive nasopharyngeal bacterial culture had longer duration of hospitalization (hazard ratio 2.4) and more often relapsed within two months than those with negative culture (odds ratio 7.3). In this study, half of the first time wheezing children had bacterial colonization or symptomatic or asymptomatic bacterial infection. The bacterial colonization (i.e. positive nasopharyngeal bacterial culture) was associated with longer duration of hospitalization and higher risk of recurrent wheezing.

Kotaniemi-Syrjanen A, Palosuo K, Jartti T, Kuitunen M, Pelkonen AS, Makela MJ. The prognosis of wheat hypersensitivity in children. Pediatr Allergy Immunol 2010: 21: e421–e428. © 2009 John Wiley & Sons A/S The study was aimed to determine the natural history of wheat hypersensitivity, to define risk factors for persistent wheat hypersensitivity, and to evaluate the development of respiratory allergy in children with wheat hypersensitivity. The development and subsequent disappearance of wheat hypersensitivity, clinical findings, skin prick test (SPT) reactivity, and the development of allergic rhinoconjunctivitis and asthma were charted retrospectively in 28 children with wheat hypersensitivity proven by the open oral challenge at the median age of 21 months (range 6 to 75 months). Appearance of skin symptoms during the diagnostic wheat challenge was related to SPT-positive wheat hypersensitivity, while the appearance of gastrointestinal symptoms alone was associated with SPT-negative wheat hypersensitivity (p = 0.002). Wheat was tolerated by 59%, 69%, 84%, and 96%, by age 4, 6, 10, and 16, respectively. Sensitization to gliadin with a SPT wheal of ≥5 mm at the time of the diagnostic challenge was associated with a slower course of recovery from wheat hypersensitivity (p = 0.019), and a SPT wheal of ≥3 mm to gliadin at any time was associated with the development of asthma (p = 0.022). SPT reactivity to wheat was associated with later SPT reactivity to birch pollen (p = 0.001), and the development of allergic rhinoconjunctivitis (p = 0.001). In conclusion, almost all children with wheat hypersensitivity can tolerate wheat by adolescence. Sensitization to gliadin is associated with a slower achievement of tolerance and an increased risk of asthma.

To analyze clinical characteristics and prevalence of rhinovirus infections in children in the hospital, we reviewed a retrospective dataset from a 20‐year period, and conducted a short‐term prospective study. Records of children and adolescents treated at our hospital during 1987–2006 with a documented rhinovirus infection were reviewed and compared with patients with other respiratory virus infections. Prospective study included all children ≥1 month of age admitted to pediatric infectious disease ward during an autumn period. Rhinoviruses were detected by reverse transcription‐PCR and/or culture, and sequence analysis was used for virus typing. In the retrospective study, the median age of 580 children with rhinovirus infection was 1.9 years (interquartile range, 1.0–4.3 years), and 27% had an underlying medical condition. Eighty‐four children (16% of in‐patients) were treated at pediatric intensive care unit. Twenty‐one children (4%) had a hospital‐acquired rhinovirus infection. In the prospective study, rhinoviruses were detected in 28% of 163 hospital episodes. Acute wheezing illness was diagnosed in 61% of children with rhinovirus and in 31% of children with respiratory syncytial virus, enterovirus, or no study virus (P

Accurate diagnosis of respiratory infections requires serologic analysis and PCR of serum., Human bocavirus (HBoV) is a widespread respiratory virus. To improve diagnostic methods, we conducted immunoglobulin (Ig) G and IgM enzyme immunoassays with recombinant virus–like particles of HBoV as antigen. Acute-phase and follow-up serum samples from 258 wheezing children and single serum samples from 115 healthy adults in Finland were examined. Our assays had a sensitivity of 97% and a specificity of 99.5%. Of adults, 96% had immunity; none had an acute infection. Of 48 children with serologically diagnosed acute HBoV infections, 45 were viremic and 35 had virus in nasopharyngeal aspirates (NPAs). Of 39 HBoV NPA PCR–positive children co-infected with another virus, 64% had a serologically verified HBoV infection. HBoV caused illness of longer duration than rhinovirus and of equal severity to that of respiratory syncytial virus. Among children with bronchiolitis, >25% had acute HBoV infections. Accurate HBoV diagnosis requires serologic analysis or PCR of serum; PCR of NPAs alone is insufficient.

Background: The prevalence of asthma and obesity is increasing concomitantly, but many aspects of this link are unclear. Our objective was to examine whether obesity is associated with asthma in three time points of life, and whether immunomodulatory adipokines, leptin and adiponectin are linked to overweight-associated asthma. Methods: We studied the association between obesity and asthma at ages 3–18 years [mean (SD), 10 years (5), n = 3582, year 1980], 9–24 years [16 years (5), n = 2764, 1986] and 24–39 years [32 years (5), n = 2620, 2001] in a prospective cohort study and further tested for associations with serum leptin and adiponectin concentrations. Data on allergy status, smoking and other laboratory values (serum insulin, plasma C-reactive protein and serum lipid values) were also analyzed. Results: Allergy and parental asthma were significantly associated with asthma at all ages. At ages 24–39 years, but not earlier, body mass index (BMI) (odds ratio, OR 1.05; P = 0.019) and female gender (OR 1.56; P = 0.031) were independently associated with asthma. Increase in BMI was also associated with incident asthma during adulthood (OR 1.08; P = 0.030). Levels of leptin, adiponectin or any other obesity-related biomarker were not independently associated with asthma. Conclusions: Asthma is linked with obesity in adults, but our results do not support a significant role for leptin, adiponectin or any other obesity-related biomarker studied in this association. Other factors should be sought for better understanding the connection between obesity and asthma.

To better understand the viral aetiology of recurrent and prolonged illnesses, nasal secretions were prospectively collected from 285 infants at increased risk of developing asthma. Of these, 27 infants had recurrent (at least five) moderate-to-severe respiratory illnesses (MSIs). The viral aetiology of the 150 MSIs and 86 scheduled visits was analysed by molecular diagnostics. The demographic and clinical data were compared with infants who had 0-4 MSIs. Frequently ill infants had higher exposure to other children and more wheezing illnesses than less symptomatic children. Viruses were detected in 136 (91%) out of 150 MSIs, 14 (67%) out of 21 mild illnesses and 29 (45%) out of 65 asymptomatic visits. Human rhinovirus was the most common aetiological agent (61, 43 and 35% in MSIs, mild illnesses and asymptomatic visits, respectively). Mixed viral infections were generally associated with more severe illnesses (27, 0 and 5%, respectively). Among the 27 frequently ill infants, only eight (5.3%) out of 150 MSIs were prolonged (> or =2 weeks duration). Considering all samples, detection of the same virus strain > or =2 weeks apart was unusual (5.3% of all 244 positive findings). Human rhinovirus infections occur early, pervasively and repetitively in these high-risk infants. Infants with prolonged or recurrent respiratory illnesses most often have a series of infections rather than persistent infection with one virus strain.

Background There is evidence that CD4 + CD25 high T-regulatory cells are important for establishing tolerance to allergens, but information in children is limited. Objective To test the hypothesis that greater numbers and function of CD4 + CD25 high T cells are associated with a reduced risk of childhood allergies and wheezing. Methods A cohort of 151 six-year-old children from atopic families was analyzed for peripheral blood CD4 + CD25 high and CD4 + CD25 int T cells by flow cytometry and for clinical and immunologic correlates of atopy. The associations between these variables were assessed by regression analysis. Results Factors positively associated with % CD4 + CD25 high /CD4 T cells were male sex, number of positive allergen-specific IgE tests, total IgE, season, and 1-month average total pollen count preceding blood draw. The percentage of CD4 + CD25 high /total CD4 T cells did not correlate with induced cytokine production, and correlated negatively with suppressive capacity of CD4 + CD25 + T cells ( r = –0.45; P = .034). The percentage of CD4 + CD25 int /CD4 T cells was 54% higher in pollen-sensitized children compared with nonsensitized children in spring ( P = .023 for interaction), and correlated positively with IL-5, IL-10, and IL-13 ( P ≤ .001 for all). Conclusion Our findings suggest that blood CD4 + CD25 high cells are a mixture of activated and regulatory T cells, and that these cells could be seasonally regulated by environmental factors such as pollen exposure. Clinical implications Seasonal increases in CD4CD25 high expression in children with allergy may represent systemic immune activation caused by pollen exposures.

Data on the efficacy of corticosteroids on respiratory picornavirus-induced wheezing are limited. To determine whether prednisolone is effective in rhinovirus- or enterovirus-induced recurrent wheezing, we conducted a controlled trial comparing oral prednisolone (2 mg/kg/day in three divided doses for 3 days) with placebo in hospitalized wheezing children and studied post hoc virus-specific efficacy in early wheezing (3 episodes, reported elsewhere) and in recurrent wheezing (or=3 episodes). Virus-negative children where excluded. Our primary endpoint was the time until children were ready for discharge. Secondary endpoints included oxygen saturation and exhaled nitric oxide during hospitalization, duration of symptoms, blood eosinophil count, and impulse oscillometry 2 wk after discharge, and occurrence of relapses during the following 2 months. Virus-specific effects were analyzed with interaction analysis in a multivariate regression model. During the study period, 661 patients were hospitalized, 293 randomized, and 59 were accepted in this analysis (mean age 2.6 yr, s.d. 1.3). Prednisolone did not significantly decrease the time until ready for discharge in all patients (prednisolone vs. placebo, medians, 18 vs. 24 h, p = 0.11). However, prednisolone decreased the time until ready for discharge in children with picornavirus infection (respectively, 12 vs. 24 h, p = 0.0022) and more specifically, in children with enterovirus infection (6 vs. 35 h, p = 0.0007). In the secondary endpoints, prednisolone decreased the duration of cough and dyspnea in rhinovirus-affected children (p = 0.033 for both). Prospectively designed clinical trial is needed to test the hypothesis that prednisolone reduces symptoms in picornavirus-affected wheezing children.

BACKGROUND: Human bocavirus is a newly discovered parvovirus. It has been detected primarily in children with acute lower respiratory tract infection, but its occurrence, clinical profile, and role as a causative agent of respiratory tract disease are not clear.METHODS: We investigated the presence of human bocavirus by quantitative polymerase chain reaction of nasopharyngeal aspirate specimens and selected serum samples obtained from 259 children (median age, 1.6 years) who had been hospitalized for acute expiratory wheezing. The samples were analyzed for 16 respiratory viruses by polymerase chain reaction, virus culture, antigen detection, and serological assays.RESULTS: At least 1 potential etiologic agent was detected in 95% of children, and >1 agent was detected in 34% of children. Human bocavirus was detected in 49 children (19%). A large proportion of the cases were mixed infections with other viruses, but human bocavirus was the only virus detected in 12 children (5%). High viral loads of human bocavirus were noted mainly in the absence of other viral agents, suggesting a causative role for acute wheezing. In addition, infections that had uncertain clinical relevance and low viral loads were prevalent. Human bocavirus DNA was frequently detected in serum specimens obtained from patients with acute wheezing, suggesting systemic infection.CONCLUSIONS: Human bocavirus is prevalent among children with acute wheezing and can cause systemic infection. Results suggest a model for bocavirus infection in which high viral loads are potentially associated with respiratory symptoms and low viral loads indicate asymptomatic shedding. Therefore, quantitative polymerase chain reaction analysis may be important for additional studies of human bocavirus.

Background Rhinovirus-induced early wheezing has been suggested as a new important risk factor for recurrent wheezing. Objective We sought to investigate the risk factors for recurrent wheezing and to determine post hoc the efficacy of prednisolone in risk groups. Methods We followed for 1 year 118 children (median age, 1.1 years) who had had their first episode of wheezing and had participated in a trial comparing prednisolone with placebo in hospitalized children. Demographics and laboratory data were obtained at study entry. The follow-up outcome was recurrent wheezing (3 physician-confirmed episodes). Results Recurrent wheezing was diagnosed in 44 (37%) children. Independent risk factors were age < 1 year, atopy, and maternal asthma. The probability of recurrent wheezing was higher in rhinovirus than respiratory syncytial virus (RSV)–affected children among placebo recipients (hazard ratio, 5.05; 95% CI, 1.00-25.41). Prednisolone decreased the probability of recurrent wheezing in children with eczema (0.15; 95% CI, 0.04-0.63) but not in those without eczema (1.89; 95% CI, 0.83-4.29; P = .007 for interaction). Prednisolone was associated with less recurrent wheezing in the rhinovirus group (0.19; 95% CI, 0.05-0.71), but not in the RSV (2.12; 95% CI, 0.46-9.76) or in the RSV/rhinovirus-negative groups (2.03; 95% CI, 0.83-5.00; P = .017 for interaction). Conclusion Rhinovirus-induced early wheezing is a major viral risk factor for recurrent wheezing. Prednisolone may prevent recurrent wheezing in rhinovirus-affected first-time wheezers. The presence of eczema may also influence the response to prednisolone. Clinical implications A prospective trial is needed to test the hypothesis that prednisolone reduces recurrent wheezing in rhinovirus-affected wheezing children.

We found that simultaneous post-exercise increase in nasal patency and bronchial obstruction occurs only in children with atopic asthma, but not in sensitized children without asthma. In healthy children, the increase in nasal patency is accompanied by bronchial dilatation.

Our aim was to evaluate the association between viral findings during bronchiolitis and the use of asthma controller medication (primary outcome) and systemic corticosteroids (secondary outcome) during the first post-bronchiolitis year.We enrolled 408 children hospitalized for bronchiolitis at24 months of age in a prospective, 3-center, 1-year follow-up study in Finland. Viruses were detected with polymerase chain reaction in nasopharyngeal aspirates. The parents underwent a structured interview during hospitalization. Twelve months later, the use of asthma medication was asked in a structured questionnaire. Multivariable logistic regression was used for statistical analysis.In total, 365 (89%) children completed the 1-year follow-up. The use of long-term asthma controller medication was highest in the rhinovirus-positive group (61% vs. 15% in respiratory syncytial virus-positive group; adjusted odd ratios, 7.5; 95% confidence interval: 3.7-15.3), followed by children negative for both respiratory syncytial virus and rhinovirus (36%; adjusted odd ratios, 2.6; 95% confidence interval: 1.3-5.3). Likewise, rhinovirus etiology was associated with more courses of systemic corticosteroids during the follow-up. The main findings were similar in a subset of infants aged12 months with first wheezing.Children hospitalized for rhinovirus-positive bronchiolitis used long-term asthma controller medication more often than those hospitalized for rhinovirus-negative bronchiolitis during first year after hospitalization.

The role of systemic corticosteroids in the treatment of early childhood wheezing in children is not clear.We sought to determine whether prednisolone is effective in rhinovirus-induced early wheezing.We conducted a controlled trial comparing oral prednisolone (2 mg/kg per day in three divided doses for 3 days) with placebo in 78 hospitalized children (mean age, 1.1 year; standard deviation, 0.7) experiencing their first or second episode of wheezing induced by rhinovirus or respiratory syncytial virus. Mixed viral infections were excluded. Our primary end point was the time until the patient was ready for discharge; secondary end points included oxygen saturation during hospitalization, duration of symptoms, occurrence of relapses during the next 2 months and blood eosinophil counts at discharge and 2 weeks later.In multivariate regression analysis, prednisolone did not influence the time until ready for discharge, but it decreased relapses during the subsequent 2-month period in rhinovirus-affected children (prednisolone versus placebo, 22% versus 56%; odds ratio, 19.06; 95% confidence interval, 2.52-144.03; P = 0.004) and in children with blood eosinophilsor = 0.2 x 10/L (respectively, 24% versus 71%; odds ratio, 10.57; 95% confidence interval, 1.99-56.22; P = 0.006). Rhinovirus-affected children had more blood eosinophils on admission (mean, 0.44 versus 0.086 x 10/L), had a higher prevalence of atopy (44% versus 8%) and were older (mean, 1.4 versus 0.9 years, P0.001 for all) than respiratory syncytial virus-infected children.Prednisolone reduced relapses during a 2-month period after first episodes of wheezing associated with rhinovirus infection or blood eosinophilsor = 0.2 x 10/L.

In a double-blind, randomized placebo-controlled crossover study, we characterized how terbutaline prolonged cardiac corrected QT interval (QTc). The study was carried out in six young and healthy male subjects in supine position. Escalating terbutaline doses were administered intravenously at infusion rates of 6 mL/h (10 microg terbutaline/min), 12 mL/h (20 microg terbutaline/min), and 18 mL/h (30 microg terbutaline/min). Terbutaline maximally prolonged QTc intervals on average by 60%, from 358 milliseconds (SD 28) to 456 milliseconds (SD 19). The effect was closely associated with a simultaneous decrease in plasma potassium concentration from 4.0 mmol/L (SD 0.1) to 2.5 mmol/L (SD 0.1). The final phase of slow ventricular repolarization, the interval between the apex and the end of T wave, was proven to be highly sensitive to the hypokalemic terbutaline actions, whereas the earlier repolarization phases were not strongly affected by terbutaline. Estimated by using the classic Nernst equation for membrane potentials, terbutaline-induced hypokalemia hyperpolarized ventricular myocardium from the resting level of -90 mV to -110 mV. The prolongation of QTc interval was related to ventricular hyperpolarization with a Pearson correlation coefficient of 0.91. Terbutaline-induced prolongation of QTc interval in healthy volunteers is in conformity with repolarization studies carried out in isolated canine heart ventricular preparations in which the cardiac ventricular cell membrane potential determines the duration of the final phase of slow ventricular repolarization.

The aim of this study was to characterize how different nonlinear methods characterize heart rate and blood pressure dynamics in healthy subjects at rest. The randomized, placebo-controlled crossover study with intravenous terbutaline was designed to induce four different stationary states of cardiovascular regulation system. The R-R interval, systolic arterial blood pressure, and heart rate time series were analyzed with a set of methods including approximate entropy, sample entropy, Lempel-Ziv entropy, symbol dynamic entropy, cross-entropy, correlation dimension, fractal dimensions, and stationarity test. Results indicate that R-R interval and systolic arterial pressure subsystems are mutually connected but have different dynamic properties. In the drug-free state the subsystems share many common features. When the strength of the baroreflex feedback loop is modified with terbutaline, R-R interval and systolic blood pressure lose mutual synchrony and drift toward their inherent state of operation. In this state the R-R interval system is rather complex and irregular, but the blood pressure system is much simpler than in the drug-free state.

To determine whether hospital length-of-stay (LOS) for bronchiolitis is influenced by the causative virus: respiratory syncytial virus (RSV) or rhinovirus.This prospective study was carried out in 3 university hospitals in Finland during 2 consecutive winter seasons. We enrolled consecutive children2 years of age hospitalized with an attending physician's diagnosis of bronchiolitis. All enrolled children were included in the primary analysis. A parallel analysis was also conducted using a stricter definition for bronchiolitis (age12 months and no history of wheeze). Polymerase chain reaction was used to test the nasopharyngeal aspirate samples for multiple respiratory pathogens.The median age of the 408 children was 8 months, 73% had no history of wheeze and their median hospital LOS was 2 days. 144 (35%) children had RSV only and 92 (23%) children rhinovirus only infections. Children with rhinovirus only had shorter duration of prehospital symptoms, higher disease severity score at entry and more often a history of wheezing (all P ≤ 0.001). Controlling for 7 demographic and clinical characteristics, those with rhinovirus only had shorter hospital LOS when compared with children with RSV only (adjusted odds ratio: 0.45; 95% confidence interval: 0.22-0.92; P = 0.03). The rhinovirus only finding was similar in the subset of 206 children with stricter diagnosis (adjusted odds ratio: 0.30; 0.06-1.49; P = 0.14).Hospital LOS is associated with rhinovirus etiology of bronchiolitis. Our data call attention to the importance of both RSV and rhinovirus testing in clinical research.

Aims To study the dose-response effects of intravenous terbutaline on the cardiovascular and respiratory autonomic nervous regulation. Methods The study followed a randomized, placebo-controlled crossover design in six healthy adult volunteers. The terbutaline dose ranged from 10 to 30 μg min−1. We continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry in supine and upright positions at baseline and during 3 h drug infusion. The periodic variability components of R-R intervals (time between successive heart beats) and SAP in relation to respiration were assessed using spectral analysis techniques. The regularity of the time series was assessed by approximate entropy (ApEn) and the convolutedness by fractal dimension (FD). Results Terbutaline dose-dependently decreased total variability of R-R intervals, low frequency (LF) variability of R-R intervals (10 s waves), high frequency (HF) variability of R-R intervals (respiratory variability), total variability of SAP, HF variability of SAP, baroreflex sensitivity, plasma potassium concentration, approximate entropy of R-R interval and of SAP as well as fractal dimension of R-R interval. Terbutaline dose-dependently increased heart rate, LF/HF ratios of R-R intervals and of SAP, LF variability of SAP, minute ventilation and plasma terbutaline concentration. Conclusions Terbutaline infusion decreases parasympathetic cardiovascular reactivity, baroreflex sensitivity, dimensionality of heart rate and plasma potassium concentration; it increases sympathetic dominance in cardiovascular autonomic balance, minute ventilation, and the regularity of heart rate and blood pressure time series.

Aims We wanted to study the effects of a 600 μg inhaled salbutamol dose on the cardiovascular and respiratory autonomic nervous regulation in eight children suffering from bronchial asthma. Methods In this randomized, double-blind, placebo-controlled, crossover study we continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry at baseline as well as 20 min and 2 h after the drug inhalation. The R–R interval (the time between successive heart beats) and SAP variabilities were assessed by using spectral analysis. Baroreflex sensitivity was assessed by using cross-spectral analysis. Results Salbutamol significantly decreased the total and low frequency (LF) variability of R–R intervals as well as the high frequency (HF) variability of R–R intervals and of SAP. Salbutamol significantly increased the LF/HF ratio of R–R intervals and of SAP, minute ventilation, heart rate and forced pulmonary function in comparison with placebo. The weight of the subjects significantly correlated positively with baroreflex sensitivity and negatively with heart rate after the salbutamol inhalation. Conclusions We conclude that the acute salbutamol inhalation decreases cardiovagal nervous responsiveness, increases sympathetic dominance in the cardiovascular autonomic balance, and has a tendency to decrease baroreflex sensitivity in addition to improved pulmonary function.

BackgroundPhysical exercise causes a decrease in nasal mucosal congestion and hence an increase in nasal patency. This nasal response has been studied only in adults. A correlation between nasal obstruction and asthma or allergic rhinitis has been previously found. This study evaluates the influences of atopy and asthma on nasal patency and the changes in nasal patency induced by physical exercise in preschool children.MethodsAn 8-minute exercise challenge test was conducted in 31 children aged between 4.1 and 6.4 years: 13 children had asthma, 17 were atopic, and 13 had neither asthma nor atopy. Nasal patency was measured with acoustic rhinometry at baseline and 10 minutes after the exercise.ResultsAt baseline, the total acoustic values were 17–25% larger in nonasthmatic children than in asthmatic children. Accordingly, the acoustic values in nonatopic children were 16–35% larger than in atopic children. After physical exercise, there was an overall increase in mean total nasal volume from 2.973 (SD = 0.647) to 3.405 cm3(SD = 0.705), indicating an improvement of 15% in nasal volume (p = 0.025). The increase in nasal patency was similar in asthmatic and nonasthmatic children, as well as in atopic and nonatopic children.ConclusionA significant increase in total nasal volume after physical exercise was found in all preschool children. The minimal cross-sectional areas remained smaller in asthmatic and atopic children after exercise, indicating partly irreversible nasal mucosal congestion in these children.

The incidence of parapneumonic empyema in children has increased worldwide, but the long-term anatomical and functional consequences in the lungs after empyema are not known.We investigated the long-term outcome of childhood empyema in 26 patients by physical examination, chest radiograph and magnetic resonance image (MRI) of the lungs, and pulmonary function tests.At follow-up 3-19 years (mean 8 years) after empyema, all patients had normal findings in the physical examination. Spirometry was normal in 80% of patients, and evidence of obstructive airway disease was detected in 16%. Thirty-six percent of patients had abnormal findings in the chest radiograph and 92% in the MRI of the lungs. In six patients, the MRI revealed significant pleural scarring (extension longer than 1 cm). Thirteen patients (50%) reported persistent respiratory symptoms, such as impaired tolerance of physical activity or prolonged cough after a common cold. During the follow-up four patients suffered a second pneumonia.The long-term recovery of children with parapneumonic empyema is good, since most patients subsequently have normal lung function, chest radiograph, and clinical recovery. Half of the patients reported subjective respiratory symptoms and most patients had minor lung abnormalities, mostly pleural scars, detected in the MRI many years after empyema. However, as long-term impairment of lung function was rarely found, the clinical significance of the anatomical residues seen in the lung MRI seems to be minor.