Quality of life, stress and acute bronchiolitis in infancy and early development of atopic disease

By comparing morning salivary cortisol and health-related quality of life (QoL) in two-year-old toddlers, this study is a contribution to the understanding of the association between stress and early asthma development. We also detected negative effects from moderate to severe acute bronchiolitis requiring hospitalisation in the first year of life and asthma risk factors, mostly atopic dermatitis, on QoL nine months later. Ventilatory support indicated lower QoL. Cortisol was higher in infants during the stress of acute bronchiolitis than in controls. Although seeming contradictory, lower levels of cortisol coincided with lower QoL in the 203 two-year-old children with acute bronchiolitis in infancy, not in 155 controls. Adjustment for a possible causal link in the pathway, recurrent bronchial obstruction (rBO) as a proxy for asthma, indicates that early stage asthma partly explains this phenomenon. The two-year-old ones with rBO had lower cortisol, a sign of a weaker HPA axis, i.e. reduced interaction between the hypothalamus and the pituitary and adrenal glands. This is in accordance with studies showing lower cortisol in asthma and allergic disease, independent of medication

Quality of life, salivary cortisol and atopic diseases in young children

Abstract BACKGROUND: Children with atopic disease may have reduced health-related quality of life (QoL) and morning cortisol. Possible links between QoL, morning cortisol and atopic disease are unclear. We aimed to determine if QoL was associated with morning salivary cortisol at two years of age, and if asthma, atopic dermatitis and/or allergic sensitisation influenced this association. Secondarily, we aimed to determine if QoL at one year of age was associated with salivary cortisol one year later. METHODS AND FINDINGS: The Bronchiolitis All SE-Norway study included infants during hospitalisation for acute bronchiolitis in infancy (bronchiolitis group) and population-based control infants (controls). The present study included all 358 subjects with available Infant Toddler Quality of Life Questionnaire (ITQOL) from parents, consisting of 13 domains and morning salivary cortisol at two years of age. Answers from the same 0-100 score questionnaire, with optimal score 100 nine months after enrolment, was also available for 289 of these children at about one year of age. Recurrent bronchial obstruction was used as an asthma proxy. Atopic dermatitis was defined by Hanifin and Rajka criteria and allergic sensitisation by a positive skin prick test. Due to different inclusion criteria, we tested possible interactions with affiliation groups. Associations between QoL and cortisol were analysed by multivariate analyses, stratified by bronchiolitis and control groups due to interaction from affiliation grouping on results. At two years of age, QoL decreased significantly with decreasing cortisol in 8/13 QoL domains in the bronchiolitis group, but only with General health in the controls. The associations in the bronchiolitis group showed 0.06-0.19 percentage points changes per nmol/L cortisol for each of the eight domains (p-values 0.0001-0.034). The associations remained significant but diminished by independently including recurrent bronchial obstruction and atopic dermatitis, but remained unchanged by allergic sensitisation. In the bronchiolitis group only, 7/13 age and gender adjusted QoL domains in one-year old children were lower with lower cortisol levels at two years of age (p = 0.0005-0.04). CONCLUSIONS: At two years, most QoL domains decreased with lower salivary cortisol among children who had been hospitalised for acute bronchiolitis in infancy, but for one domain only among controls. Recurrent bronchial obstruction and to a lesser extent atopic dermatitis, weakened these associations that nevertheless remained significant. After bronchiolitis, lower QoL in one-year old children was associated with lower salivary cortisol at two years.The project was supported by a grant to the first author’s employer, Innlandet Hospital Trust, (Project no. 150189 to LBR) from a research fund foundation, Klosterstiftelsen. Klosterstiftelsen does not have any specific URL, but further information can be reached at https://www. purehelp.no/m/company/details/klosterstiftelsen/ 982953146. No commercial companies funded the study or authors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The other authors did not receive any specific funding for this work.publishedVersio

Morning salivary cortisol in young children: reference values and the effects of age, sex, and acute bronchiolitis

Abstract OBJECTIVE: To identify morning salivary cortisol reference values in infancy and at 2 years of age and to investigate the influence of age, sex and acute bronchiolitis. STUDY DESIGN: In this South-East Norwegian cohort study, 308 children hospitalized with moderate to severe acute bronchiolitis in infancy in 2010-2011 were compared with 223 healthy controls included in 2012 by measuring morning salivary cortisol levels at inclusion and at 2 years of age. Samples were collected shortly after awakening after 6 am. The influences of age, sex, and acute bronchiolitis were assessed by regression analysis. RESULTS: In infancy, cortisol values were higher in acute bronchiolitis, with an age- and sex-adjusted weighted mean group difference of 13.9 nmol/L (95% CI 8.1-19.7; P < .0001). The median level in reference group was 23.7 nmol/L (95% CI 9.7-119.6). At 2 years of age, sex but not inclusion groups differed, with significantly higher values in girls. The weighted mean of all boys' cortisol levels was 32.4 nmol/L, (95% CI 30.5-34.3), and all girls' levels were 36.9 nmol/L (95% CI 34.7-39.2; P < .003). CONCLUSIONS: Salivary cortisol levels were higher at 2 years of age than in infancy in the reference group, were higher in girls than in boys at 2 years of age, and were higher in infants at the time of acute bronchiolitis than in healthy infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00817466.publishedVersio

Parental severity assessment predicts supportive care in infant bronchiolitis

AIM: In infants with acute bronchiolitis, the precision of parental disease severity assessment is unclear. We aimed to determine if parental assessment at the time of hospitalisation predicted the use of supportive care, and subsequently determine the likelihood that the infant with acute bronchiolitis would receive supportive care. METHODS: From the Bronchiolitis ALL south-east Norway study, we included all 267, 0-12 month old, infants with acute bronchiolitis whose parents at the time of hospitalisation completed a three-item visual analogue scale (VAS) concerning Activity, Feeding and Illness. Respiratory rate, oxygen saturation (SpO2 ) and use of supportive care were recorded daily. By multivariate logistic regression analyses we included significant predictors available at hospital admission to predict the use of supportive care. RESULTS: The parental Activity, Feeding and Illness VAS scores significantly predicted supportive care with odds ratios of 1.23, 1.26 and 1.36, respectively. The prediction algorithm included parental Feeding and Illness scores, SpO2 , gender and age, with an area under the curve of 0.76 (95% CI 0.69, 0.81). A positive likelihood ratio of 2.1 gave the highest combined sensitivity of 81% and specificity of 61%. CONCLUSION: Parental assessment at hospital admission moderately predicted supportive care treatment in infants with acute bronchiolitis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00817466

Parental severity assessment predicts supportive care in infant bronchiolitis

Aim: In infants with acute bronchiolitis, the precision of parental disease severity assessment is unclear. We aimed to determine if parental assessment at the time of hospitalisation predicted the use of supportive care, and subsequently determine the likelihood that the infant with acute bronchiolitis would receive supportive care. Methods: From the Bronchiolitis ALL south‐east Norway study, we included all 267, 0–12 month old, infants with acute bronchiolitis whose parents at the time of hospitalisation completed a three‐item visual analogue scale (VAS) concerning Activity, Feeding and Illness. Respiratory rate, oxygen saturation (SpO2) and use of supportive care were recorded daily. By multivariate logistic regression analyses we included significant predictors available at hospital admission to predict the use of supportive care. Results: The parental Activity, Feeding and Illness VAS scores significantly predicted supportive care with odds ratios of 1.23, 1.26 and 1.36, respectively. The prediction algorithm included parental Feeding and Illness scores, SpO2, gender and age, with an area under the curve of 0.76 (95% CI 0.69, 0.81). A positive likelihood ratio of 2.1 gave the highest combined sensitivity of 81% and specificity of 61%. Conclusion: Parental assessment at hospital admission moderately predicted supportive care treatment in infants with acute bronchiolitis

Skin barrier function and Staphylococcus aureus colonization in vestibulum nasi and fauces in healthy infants and infants with eczema: A population-based cohort study

Atopic eczema (AE) is associated with Staphylococcus aureus (S. aureus) colonization and skin barrier dysfunction, often measured by increased transepidermal water loss (TEWL). In the present study, the primary aim was to see whether S. aureus colonization in the vestibulum nasi and/or fauces was associated with increased TEWL in infants with healthy skin and infants with eczema. Secondarily, we aimed to investigate whether TEWL measurements on non-lesional skin on the lateral upper arm is equivalent to volar forearm in infants. In 167 of 240 infants, recruited from the general population, TEWL measurements on the lateral upper arm and volar forearm, using a DermaLab USB, fulfilled our environmental requirements. The mean of three TEWL measurements from each site was used for analysis. The infants were diagnosed with no eczema (n = 110), possible AE (n = 28) or AE (n = 29). DNA samples were analysed for mutations in the filaggrin gene (FLG). Bacterial cultures were reported positive with the identification of at least one culture with S. aureus from vestibulum nasi and/or fauces. S. aureus colonization, found in 89 infants (53%), was not associated with increased TEWL (i.e. TEWL in the upper quartile), neither on the lateral upper arm or volar forearm (p = 0.08 and p = 0.98, respectively), nor with AE (p = 0.10) or FLG mutation (p = 0.17). TEWL was significantly higher on both measuring sites in infants with AE compared to infants with possible AE and no eczema. FLG mutation was significantly associated with increased TEWL, with a 47% difference in TEWL. We conclude that S. aureus in vestibulum nasi and/or fauces was not associated with TEWL, whereas TEWL measurements on the lateral upper arm and volar forearm appear equally appropriate in infants

Virus, allergic sensitisation and cortisol in infant bronchiolitis and risk of early asthma

Background Acute bronchiolitis during infancy and human rhinovirus (HRV) lower respiratory tract infections increases the risk of asthma in atopic children. We aimed to explore whether specific viruses, allergic sensitisation or cortisol levels during acute bronchiolitis in infancy increase the risk of early asthma, using recurrent wheeze as a proxy. Methods In 294 children with a mean (range) age of 4.2 (0–12) months enrolled during hospitalisation for acute infant bronchiolitis, we analysed virus in nasopharyngeal aspirates, serum specific immunoglobulin E against food and inhalant allergens, and salivary morning cortisol. These factors were assessed by regression analyses, adjusted for age, sex and parental atopy, for risk of recurrent wheeze, defined as a minimum of three parentally reported episodes of wheeze at the 2-year follow-up investigation. Results At 2 years, children with, compared to without, recurrent wheeze had similar rates of respiratory syncytial virus (RSV) (82.9% versus 81.8%) and HRV (34.9% versus 35.0%) at the acute bronchiolitis, respectively. During infancy, 6.9% of children with and 9.2% of children without recurrent wheeze at 2 years were sensitised to at least one allergen (p=0.5). Neither recurrent wheeze nor incidence rate ratios for the number of wheeze episodes at 2 years were significantly associated with specific viruses, high viral load of RSV or HRV, allergic sensitisation, or morning salivary cortisol level during acute bronchiolitis in infancy. Conclusion In children hospitalised with acute infant bronchiolitis, specific viruses, viral load, allergic sensitisation and salivary morning cortisol did not increase the risk of early asthma by 2 years of age

Morning salivary cortisol in young children: reference values and the effects of age, sex, and acute bronchiolitis

Abstract OBJECTIVE: To identify morning salivary cortisol reference values in infancy and at 2 years of age and to investigate the influence of age, sex and acute bronchiolitis. STUDY DESIGN: In this South-East Norwegian cohort study, 308 children hospitalized with moderate to severe acute bronchiolitis in infancy in 2010-2011 were compared with 223 healthy controls included in 2012 by measuring morning salivary cortisol levels at inclusion and at 2 years of age. Samples were collected shortly after awakening after 6 am. The influences of age, sex, and acute bronchiolitis were assessed by regression analysis. RESULTS: In infancy, cortisol values were higher in acute bronchiolitis, with an age- and sex-adjusted weighted mean group difference of 13.9 nmol/L (95% CI 8.1-19.7; P < .0001). The median level in reference group was 23.7 nmol/L (95% CI 9.7-119.6). At 2 years of age, sex but not inclusion groups differed, with significantly higher values in girls. The weighted mean of all boys' cortisol levels was 32.4 nmol/L, (95% CI 30.5-34.3), and all girls' levels were 36.9 nmol/L (95% CI 34.7-39.2; P < .003). CONCLUSIONS: Salivary cortisol levels were higher at 2 years of age than in infancy in the reference group, were higher in girls than in boys at 2 years of age, and were higher in infants at the time of acute bronchiolitis than in healthy infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00817466

Racemic Adrenaline and Inhalation Strategies in Acute Bronchiolitis

Acute bronchiolitis in infants, which frequently leads to hospitalization and sometimes requires ventilatory support, is occasionally fatal; it is usually viral in origin, with respiratory syncytial virus being the most common cause. The clinical disease is characterized by nasal flaring, tachypnea, dyspnea, chest retractions, crepitations, and wheezing. Bronchodilators are not recommended but are often used in the treatment of bronchiolitis, as are saline inhalations. Adrenaline reduces mucosal swelling, giving it an edge over the β2-adrenergic agonists, and has led to the frequent use of inhaled adrenaline, which has improved symptoms and reduced the need for hospitalization in outpatients with acute bronchiolitis. Among inpatients, however, inhaled adrenaline has not been found to reduce the length of the hospital stay. Assessment of the possible influences of age, sex, and status with respect to an asthma predisposition on the effect of inhaled adrenaline requires large multicenter studies. Inhaled nebulized solutions can be prescribed for use on demand or on a fixed schedule. We were unable to find documentation on the comparative efficacy of these two strategies in children with acute bronchiolitis. We tested the hypothesis that inhaled racemic adrenaline is superior to inhaled saline in the treatment of acute bronchiolitis in infancy and that administration on a fixed schedule is superior to administration on demand. We also assessed whether age, sex, or status with respect to allergic diseases influenced treatment efficacy. Including: Letter to the Editor. Skjerven Håvard Ove, Carlsen Kai-Håkon og Carlsen Karin C Lødrup. Inhaled adrenaline in acute bronchiolitis. The New England Journal of Medicine 2013;369:1076-7. http://dx.doi.org/10.1056/NEJMc130896

Characteristics.

<p>Characteristics of 240 infants, recruited from the general population in Oslo and Fredrikstad, Norway, of whom 167 were included and 73 excluded from the analyses. Exclusions were done due to crying during the measuring transepidermal water loss (n = 7) and/or measuring conditions not fulfilling strict environmental criteria for humidity and/or temperature (n = 66). All values are given as number (percentage), unless otherwise stated.</p><p>Characteristics.</p