Håvard Ove Skjerven

Racemic Adrenaline and Inhalation Strategies in Acute Bronchiolitis

BACKGROUND Acute bronchiolitis in infants frequently results in hospitalization, but there is no established consensus on inhalation therapy--either the type of medication or the frequency of administration--that may be of value. We aimed to assess the effectiveness of inhaled racemic adrenaline as compared with inhaled saline and the strategy for frequency of inhalation (on demand vs. fixed schedule) in infants hospitalized with acute bronchiolitis. METHODS In this eight-center, randomized, double-blind trial with a 2-by-2 factorial design, we compared inhaled racemic adrenaline with inhaled saline and on-demand inhalation with fixed-schedule inhalation (up to every 2 hours) in infants (<12 months of age) with moderate-to-severe acute bronchiolitis. An overall clinical score of 4 or higher (on a scale of 0 to 10, with higher scores indicating more severe illness) was required for study inclusion. Any use of oxygen therapy, nasogastric-tube feeding, or ventilatory support was recorded. The primary outcome was the length of the hospital stay, with analyses conducted according to the intention-to-treat principle. RESULTS The mean age of the 404 infants included in the study was 4.2 months, and 59.4% were boys. Length of stay, use of oxygen supplementation, nasogastric-tube feeding, ventilatory support, and relative improvement in the clinical score from baseline (preinhalation) were similar in the infants treated with inhaled racemic adrenaline and those treated with inhaled saline (P>0.1 for all comparisons). On-demand inhalation, as compared with fixed-schedule inhalation, was associated with a significantly shorter estimated mean length of stay--47.6 hours (95% confidence interval [CI], 30.6 to 64.6) versus 61.3 hours (95% CI, 45.4 to 77.2; P=0.01) - as well as less use of oxygen supplementation (in 38.3% of infants vs. 48.7%, P=0.04), less use of ventilatory support (in 4.0% vs. 10.8%, P=0.01), and fewer inhalation treatments (12.0 vs. 17.0, P<0.001). CONCLUSIONS In the treatment of acute bronchiolitis in infants, inhaled racemic adrenaline is not more effective than inhaled saline. However, the strategy of inhalation on demand appears to be superior to that of inhalation on a fixed schedule. (Funded by Medicines for Children; ClinicalTrials.gov number, NCT00817466; EudraCT number, 2009-012667-34.).

Acute bronchiolitis in infants, a review

Acute viral bronchiolitis is one of the most common medical emergency situations in infancy, and physicians caring for acutely ill children will regularly be faced with this condition. In this article we present a summary of the epidemiology, pathophysiology and diagnosis, and focus on guidelines for the treatment of bronchiolitis in infants. The cornerstones of the management of viral bronchiolitis are the administration of oxygen and appropriate fluid therapy, and overall a “minimal handling approach” is recommended. Inhaled adrenaline is commonly used in some countries, but the evidences are sparse. Recently, inhalation with hypertonic saline has been suggested as an optional treatment. When medical treatment fails to stabilize the infants, non-invasive and invasive ventilation may be necessary to prevent and support respiratory failure. It is important that relevant treatment algorithms exist, applicable to all levels of the treatment chain and reflecting local considerations and circumstances.

Virus Type and Genomic Load in Acute Bronchiolitis: Severity and Treatment Response With Inhaled Adrenaline

Abstract Background. Acute bronchiolitis frequently causes infant hospitalization. Studies on different viruses or viral genomic load and disease severity or treatment effect have had conflicting results. We aimed to investigate whether the presence or concentration of individual or multiple viruses were associated with disease severity in acute bronchiolitis and to evaluate whether detected viruses modified the response to inhaled racemic adrenaline. Methods. Nasopharyngeal aspirates were collected from 363 infants with acute bronchiolitis in a randomized, controlled trial that compared inhaled racemic adrenaline versus saline. Virus genome was identified and quantified by polymerase chain reaction analyses. Severity was assessed on the basis of the length of stay and the use of supportive care. Results. Respiratory syncytial virus (83%) and human rhinovirus (34%) were most commonly detected. Seven other viruses were present in 8%–15% of the patients. Two or more viruses (maximum, 7) were detected in 61% of the infants. Virus type or coinfection was not associated with disease severity. A high genomic load of respiratory syncytial virus was associated with a longer length of stay and with an increased frequency of oxygen and ventilatory support use. Treatment effect of inhaled adrenaline was not modified by virus type, load or coinfection. Discussion. In infants hospitalized with acute bronchiolitis, disease severity was not associated with specific viruses or the total number of viruses detected. A high RSV genomic load was associated with more-severe disease. Clinical Trials Registration. NCT00817466 and EudraCT 2009-012667-34.

Allergic diseases and the effect of inhaled epinephrine in children with acute bronchiolitis: follow-up from the randomised, controlled, double-blind, Bronchiolitis ALL trial

BACKGROUND Although use of inhaled bronchodilators in infants with acute bronchiolitis is not supported by evidence-based guidelines, it is often justified by the belief in a subgroup effect in individuals developing atopic disease. We aimed to assess if inhaled epinephrine during acute bronchiolitis in infancy would benefit patients with later recurrent bronchial obstruction, atopic eczema, or allergic sensitisation. METHODS In the randomised, double-blind, multicentre Bronchiolitis ALL trial, 404 infants with moderate-to-severe acute bronchiolitis were recruited from eight hospitals in Norway to receive either inhaled epinephrine or saline up to every second hour throughout the hospital stay. Randomisation was done centrally, and the two study medications (20 mg/mL racemic epinephrine or 0.9% saline) were prepared in identical bottles. The dose given depended on the infants weight: 0.10 mL, less than 5 kg; 0.15 mL, 5-6.9 kg; 0.2 mL, 7-9.9 kg; and 0.25 mL, 10 kg or more; all dissolved in 2 mL of 0.9% saline before nebulisation. The primary outcome was the length of hospital stay. In this follow-up study, 294 children were reinvestigated at 2 years of age with an interview, a clinical examination, and a skin prick test for 17 allergens, determining bronchial obstruction, atopic eczema, and allergic sensitisation, on which subgroup analyses were done. Analyses were done by intention to treat. The trial has been completed and is registered at ClinicalTrials.gov (number NCT00817466) and EUDRACT (number 2009-012667-34). FINDINGS Length of stay did not differ between patients who received inhaled epinephrine versus saline in the subgroup of infants who developed recurrent bronchial obstruction by age 2 years (143 [48.6%] of 294 patients; p(interaction)=0.40). However, the presence of atopic eczema or allergic sensitisation by the age of 2 years (n=77) significantly interacted with the treatment effect of inhaled epinephrine (p(interaction)=0.02); the length of stay (mean 80.3 h, 95% CI 72.8-87.9) was significantly shorter in patients receiving inhaled epinephrine versus saline in patients without allergic sensitisation or atopic eczema by 2 years (-19.9 h, -33.1 to -6.3; p=0.003). No significant differences were found in length of hospital stay in response to epinephrine or saline in children with atopic eczema or allergic sensitisation by 2 years (+16.2 h, -11.0 to 43.3; p=0.24). INTERPRETATION Contrary to our hypothesis, hospital length of stay for bronchiolitis was not reduced by administration of inhaled epinephrine in infants who subsequently developed atopic eczema, allergic sensitisation, or recurrent bronchial obstruction. The present study does not support an individual trial of inhaled epinephrine in acute bronchiolitis in children with increased risk of allergic diseases. FUNDING Medicines for Children Network, Norway.

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.

Children hospitalised with bronchiolitis in the first year of life have a lower quality of life nine months later

Acute bronchiolitis increases the risk of asthma, and reduced quality of life (QoL) is reported in children with asthma and allergy. However, the impact of asthma risk factors on QoL is unclear. This study investigated whether bronchiolitis and common asthma risk factors in infancy had an influence on later QoL.

Vitamin D levels and atopic eczema in infancy and early childhood in Norway: a cohort study.

Epidemiological data and the effect of sun exposure on atopic eczema (AE) suggest that vitamin D (vitD) may be involved in the pathogenesis.

The severity of acute bronchiolitis in infants was associated with quality of life nine months later

Acute bronchiolitis in infancy increases the risk of later asthma and reduced health‐related quality of life (QoL). We aimed to see whether the severity of acute bronchiolitis in the first year of life was associated with QoL nine months later.

The toxicity of E-cigarettes and children’s respiratory health

Electronic cigarettes (E-cig), also referred to as Electronic Nicotine Delivery System (ENDS), were initially developed in 2003 to reduce the harmful effects of tobacco smoking. Since then, E-cig have become widely available in many countries and are used by many young people who would be unlikely to take up cigarette smoking. However, the adverse effects on child health remain largely unknown. E-cigs are available through regulated sale in many countries, but easily accessible by the internet in others. Adverse effects may be ascribed to the nicotine itself, to the accompanying substances in the aerosol (often referred to as vapour) or to temperature modifications of the content. There is a lack of human studies to assess respiratory effects of nicotine exposure to the unborn or young child. Also assessing the effects of the vaping content apart from nicotine is challenging, with the huge variety of exposure by frequency, duration and content, but experimental studies are on the way that may indicate the level of harm by such products. This article will summarize what is currently known about the use of E-cigs in children and in pregnancy, and discuss adverse effects of direct or in utero exposure to E-cig on the respiratory health of children. We thereby hope to provide a background for discussing potential harms to the respiratory system of children by E-cig exposure in pregnancy and early post-natal life, in a setting where an increasing proportion of adolescent and young adults use E-cigs, marketed to be 95% less harmful than conventional cigarettes.

Preventing Atopic Dermatitis and ALLergies in Children - the PreventADALL study.

Reversing or aborting the increase in allergic and other immune-related non-communicable diseases (NCDs) in the western world, first observed for allergic rhinitis from the 1890ies1 , requires primary prevention strategies, probably on a general population level. The diseases are likely to be related to changes in lifestyle, environment or both2 , including reduced microbial diversity, increased use of xenobiotics in industrial and consumer products, exposure to tobacco or nicotinic products and variations in diets and nutritional elements. While some primary allergy preventive strategies may be effective in high risk children3 , the relevance for preventive strategies on a population level is unclear4 . This article is protected by copyright. All rights reserved.