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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: Preschool wheeze is highly prevalent; 30%-50% of children have wheezed at least once before age six. Wheezing is not a disorder; it is a symptom of obstruction in the airways, and it is essential to identify the correct diagnosis behind this symptom. An increasing number of studies provide evidence for novel diagnostic tools for monitoring and predicting asthma in the pediatric population. Several techniques are available to measure airway obstruction and airway inflammation, including spirometry, impulse oscillometry, whole-body plethysmography, bronchial hyperresponsiveness test, multiple breath washout test, measurements of exhaled NO, and analyses of various other biomarkers.METHODS: We systematically reviewed all the existing techniques available for measuring lung function and airway inflammation in preschool children to assess their potential and clinical value in the routine diagnostics and monitoring of airway obstruction.RESULTS: If applicable, measuring FEV1 using spirometry is considered useful. For those unable to perform spirometry, whole-body plethysmography and IOS may be useful. Bronchial reversibility to beta2-agonist and hyperresponsiveness test with running exercise challenge may improve the sensitivity of these tests.CONCLUSIONS: The difficulty of measuring lung function and the lack of large randomized controlled trials makes it difficult to establish guidelines for monitoring asthma in preschool children.

Background B cells play a crucial role during rhinovirus (RV) infections by production of virus‐neutralizing antibodies. A main feature of common variable immunodeficiency (CVID) is hypogammaglobulinemia (HG). HG patients have severely reduced levels of antibody‐producing B cells and suffer from prolonged virus infections. Here, we addressed whether antiviral response of peripheral blood lymphocytes differs between HG patients and healthy individuals during natural RV infection. Methods Using fluorescence‐activated cell sorting, B‐cell subsets were analyzed. Simultaneously, CD19 + B cells, CD14 + monocytes, and CD3 + T cells were sorted from frozen peripheral blood mononuclear cells from 11 RV‐infected hypogammaglobulinemia patients, 7 RV‐infected control subjects, and 14 noninfected control subjects. Real‐time PCR was used to study expression of antiviral genes. A pan‐RV PCR was used to detect RV genome in all samples. Results In HG patients, total B‐cell numbers, as well as IgA + and IgG + switched memory B cells, were reduced while naive B cells and T cells were increased. STAT1 expression was increased in HG patients compared to controls in all lymphocyte subsets analyzed. The expression of antiviral genes IFITM1 and MX1 correlated with STAT1 expression in B cells and monocytes. RV RNA was found in 88.9% of monocytes from infected HG patients, 85.7% of monocytes from infected controls, and 7.1% of monocytes from uninfected controls. Conclusions We demonstrate an increased antiviral response in B cells and monocytes in HG patients and their correlation with STAT1 expression. Monocytes of infected HG patients and infected non‐HG controls carry RV RNA.

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.

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.

Crying combined with miscellaneous gastrointestinal symptoms are typical symptoms of infant with food allergy, but are also common among children with abnormal neurological development. Mutations in KAT6A gene is known to cause a syndrome characterized by developmental delay, hypotonia, cardiac defects, microcephaly, specific facial features and early feeding problems. However, these feeding problems have not earlier been specified. We present the first reported case of a DBPCFC confirmed food allergy in a child with KAT6A mutation whose feeding problems resolved with elimination diet. The present case does not establish proof of cause, but highlights the importance of careful clinical diagnostics despite other possible causes for feeding problems. Recognizing that early feeding problems these patients regularly have might be caused by food allergy is important for outcome and quality of life for these patients.

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.

SummaryBackground 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. Methods 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. Results 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. Conclusions 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. Pediatr Pulmonol. 2014; 49:1020–1027. © 2013 Wiley Periodicals, Inc.

Human rhinovirus (HRV) and respiratory syncytial virus (RSV) are commonly associated with bronchiolitis. The breaking point in the dominance is approximately 12 months--rhinovirus dominates in the older children. Predisposition may markedly increase the prevalence of HRV bronchiolitis. Especially, low interferon responses and atopy-related factors have been associated with HRV bronchiolitis. The former has been considered as a sign of poor antiviral defense, and the latter could be associated with atopic airway inflammation in wheezing children. Although recurrent wheezing is common after both RSV and HRV bronchiolitis, HRV bronchiolitis carries a markedly higher risk of persistent wheezing until 6 years of age and for childhood asthma. This association has been independent from atopy at 7.2 (median) years of age. The increased risk of asthma in adulthood after non-RSV bronchiolitis vs. RSV bronchiolitis in infancy (at the time when PCR was not available for HRV diagnosis) offers indirect evidence for the association between HRV bronchiolitis and chronic asthma.

Jartti T, Kuusipalo H, Vuorinen T, Soderlund-Venermo M, Allander T, Waris M, Hartiala J, Ruuskanen O. Allergic sensitization is associated with rhinovirus-, but not other virus-, induced wheezing in children. Pediatr Allergy Immunol 2010: 21: 1008–1014. © 2010 John Wiley & Sons A/S Background: Data on the link between atopy and viral wheeze are limited. Aim: To evaluate the association between IgE sensitization and viral infection in wheezing children. Methods: This is an observational study in hospitalized wheezing children (n = 247; median age 1.6 ; interquartile range 1.1, 2.9). Eighteen respiratory viral infections were studied using all available methods. A specific immunoglobulin E (IgE) sensitization for common food and aeroallergens and other atopy-related variables including total IgE, blood and nasal eosinophils, exhaled nitric oxide, eczema and atopic eczema, parental allergy and asthma, number of wheezing episodes, positive asthma predictive index or asthma and use of inhaled corticosteroid were correlated with specific viral etiology. Results: Atopy was closely associated with sole rhinovirus etiology (n = 58) but not with sole respiratory syncytial virus, sole enterovirus, sole human bocavirus, sole other virus, mixed viral, or virus negative etiology. The number of sensitizations was particularly associated with sole rhinovirus etiology (odds ratio 4.59; 95% confidence interval 1.78, 11.8; adjusted to age and sex), followed by aeroallergen sensitization (respectively; 4.18; 2.00, 8.72), total IgE level (2.06; 1.32, 3.21), food allergen sensitization (2.02; 1.08, 3.78), and nasal eosinophil count (1.52; 1.08, 2.13). Conclusions: According to our data, allergic sensitization is positively linked to rhinovirus-, but not other virus-, associated wheezing and calls attention for studies to test rhinovirus-associated wheezing as a part of asthma risk indices.

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

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.

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.

The purpose of this study was to compare the applicability of four different measures of heart rate variability (HRV) in the assessment of cardiac vagal outflow, with special reference to the effect of breathing pattern. The anticholinergic effects of an intravenous glycopyrrolate infusion (5 microg x kg(-1) x h(-1) for 2 h) during spontaneous and controlled (15 min(-1)) breathing rate were investigated in eight volunteers, and the effects of different fixed breathing rates (6-15-24 min(-1)) and hyperventilation in 12 subjects. Cardiac vagal activity was assessed by ECG recordings in which the following measures of HRV were computed: the high-frequency (HF) spectral component, the instantaneous RR interval (RRI) variability (SD1) analysed from the Poincare plots, the percentage of differences between successive RRIs greater than 50 ms (pNN50), and the square root of the mean squared differences of successive RRIs (RMSSD). On average, glycopyrrolate reduced the HF spectral component by 99.8%, SD1 by 91.3%, pNN50 by 100% and RMSSD by 97.0%. The change of breathing pattern from controlled to spontaneous decreased significantly the HF component and pNN50, but did not affect SD1 or RMSSD. Rapid breathing rate (24 min(-1)) decreased the HF component, but had no effects on the other measures. A controlled breathing rate is needed for a reliable assessment of cardiac vagal outflow by the spectral analysis technique. The quantitative geometrical analysis of short-term RRI variability from the Poincare plots and the time domain measure RMSSD were not significantly affected by changes in the breathing rate, suggesting that these indices are more suitable for the measurement of cardiac vagal outflow during the 'free-running' ambulatory conditions.

Asthma is associated with autonomic nervous imbalance: an increased bronchial sensitivity to cholinergic constrictors and possibly a decreased sensitivity to beta2-adrenergic dilators have been reported in this disease. Also, non-adrenergic and non-cholinergic (NANC) mediators have a small regulatory effect on airway function. These mediators contribute to the pathogenesis of asthma not only by regulating smooth muscle tone in the airways but also by affecting pulmonary blood flow, endothelial permeability and airway secretions. In many studies increased parasympathetic responsiveness has been associated with clinical asthma or the worsening of asthma in adults. However, most of the studies in children have not found association between autonomic dysfunction and asthma. Therefore, the autonomic dysfunction in asthma may be related to more advanced disease or long-term asthma medication in adults. This article briefly reviews the relationships between airway inflammation, beta2-agonist, anticholinergic and glucocorticoid medication as well as autonomic nervous function in asthma.

The effects of therapeutic 4 weeks' inhaled salmeterol treatment on the cardiovascular and respiratory autonomic nervous regulation was studied in 11 asthmatic children using inhaled corticosteroid medication. The study followed a randomized, double-blind, placebo-controlled cross-over design. The salmeterol dose was 50 micrograms twice daily. The 4-week salmeterol treatment increased baseline heart rate, low-frequency/high-frequency (LF/HF) variability ratio of R-R intervals, LF variability of systolic arterial pressure (SAP) and maximum tidal volume during the deep breathing test, as well as morning and evening peak expiratory flow (PEF) values. The 4-week salmeterol treatment decreased baseline HF variability of R-R intervals. As a response to the acute 600 micrograms of salbutamol, the changes in heart rate, HF variability of R-R intervals and diastolic blood pressure were significantly smaller after 4 weeks' salmeterol treatment. In conclusion, 4 weeks' therapeutic salmeterol treatment decreases basal cardiovagal reactivity, increases sympathetic dominance in the cardiovascular autonomic balance and improves pulmonary function. A tolerance develops in the cardiovascular response but not in the bronchodilatory response.

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.