Knut Øymar

Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma.

Background: Despite their potential for increased morbidity, 75% to 90% of asthmatic children do not receive influenza vaccination. Live attenuated influenza vaccine (LAIV), a cold-adapted, temperature-sensitive, trivalent influenza vaccine, is approved for prevention of influenza in healthy children 5 to 19 years of age. LAIV has been studied in only a small number of children with asthma. Methods: Children 6 to 17 years of age, with a clinical diagnosis of asthma, received a single dose of either intranasal CAIV-T (an investigational refrigerator-stable formulation of LAIV; n = 1114) or injectable trivalent inactivated influenza vaccine (TIV; n = 1115) in this randomized, open-label study during the 2002–2003 influenza season. Participants were followed up for culture-confirmed influenza illness, respiratory outcome, and safety. Results: The incidence of community-acquired culture-confirmed influenza illness was 4.1% (CAIV-T) versus 6.2% (TIV), demonstrating a significantly greater relative efficacy of CAIV-T versus TIV of 34.7% (90% confidence interval [CI] 9.4%–53.2%; 95% CI = 3.9%–56.0%). There were no significant differences between treatment groups in the incidence of asthma exacerbations, mean peak expiratory flow rate findings, asthma symptom scores, or nighttime awakening scores. The incidence of runny nose/nasal congestion was higher for CAIV-T (66.2%) than TIV (52.5%) recipients. Approximately 70% of TIV recipients reported injection site reactions. Conclusions: CAIV-T was well tolerated in children and adolescents with asthma. There was no evidence of a significant increase in adverse pulmonary outcomes for CAIV-T compared with TIV. CAIV-T had a significantly greater relative efficacy of 35% compared with TIV in this high-risk population.

Characteristics of asthma and airway hyper‐responsiveness after premature birth

Asthma‐like symptoms and airway hyper‐responsiveness (AHR) are frequently reported in children subsequent to premature birth and bronchopulmonary dysplasia (BPD). There is limited knowledge on the mechanisms underlying these respiratory manifestations. Generally, childhood asthma and AHR is described within a context of inheritance, allergy and eosinophilic airway inflammation, and often in relation to cigarette exposures. We investigated these factors in relation to current asthma and AHR in a population‐based cohort of 81 young people, born with gestational age ≤28 wk or birth weight ≤1000 g, and in a matched term‐born control population. In the pre‐term population, asthma and AHR were additionally studied in relation to neonatal respiratory morbidity. At follow up, more pre‐term than control subjects had asthma. Forced expiratory volume in first second (FEV1) was reduced, AHR was substantially increased, and the level of the urinary leukotriene metabolite E4 (U‐LTE4) was increased in the pre‐term population compared to the term‐born. In control subjects, asthma and AHR was associated with a pattern consistent with inheritance, allergy, airway inflammation, and cigarette exposures. In the pre‐terms, asthma and AHR was either unrelated or less related to these factors. Instead, AHR was strongly related to a neonatal history of BPD and prolonged requirement for oxygen treatment. In conclusion, asthma and AHR subsequent to extremely premature birth differed from typical childhood asthma with respect to important features, and AHR was best explained by neonatal variables. These respiratory manifestations thus seem to represent a separate clinical entity.

TTC7A mutations disrupt intestinal epithelial apicobasal polarity

Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is sometimes associated with a combined immunodeficiency (CID), leading to increased susceptibility to infections. The factors underlying this rare disease are poorly understood. We characterized the immunological and intestinal features of 6 unrelated MIA-CID patients. All patients displayed a profound, generalized lymphocytopenia, with few lymphocytes present in the lymph nodes. The thymus was hypoplastic and exhibited an abnormal distribution of epithelial cells. Patients also had profound disruption of the epithelial barrier along the entire gastrointestinal tract. Using linkage analysis and whole-exome sequencing, we identified 10 mutations in tetratricopeptide repeat domain–7A (TTC7A), all of which potentially abrogate TTC7A expression. Intestinal organoid cultures from patient biopsies displayed an inversion of apicobasal polarity of the epithelial cells that was normalized by pharmacological inhibition of Rho kinase. Our data indicate that TTC7A deficiency results in increased Rho kinase activity, which disrupts polarity, growth, and differentiation of intestinal epithelial cells, and which impairs immune cell homeostasis, thereby promoting MIA-CID development.

Long-term faecal carriage in infants and intra-household transmission of CTX-M-15-producing Klebsiella pneumoniae following a nosocomial outbreak

OBJECTIVES To investigate the duration of faecal carriage of CTX-M-15-producing Klebsiella pneumoniae in infants colonized during a nosocomial neonatal intensive care unit (NICU) outbreak after discharge from hospital, possible risk factors for long-term colonization and transmission to household contacts (HCs). METHODS Fifty-one infants colonized with two unrelated clones of CTX-M-15 K. pneumoniae [sequence type (ST) 17 and ST485] during an NICU outbreak and 60 HCs provided faecal and rectal samples, respectively, every 1-3 months after hospital discharge. Extended-spectrum β-lactamase (ESBL)-producing strains of K. pneumoniae were identified on Chrom ID ESBL agar and examined by antimicrobial susceptibility testing. blaCTX-M-15 was detected by PCR and DNA sequencing. Clonal relationship was examined by PFGE. RESULTS The median carriage time in infants after discharge was 12.5 months (IQR 9.5-17.5). Stable antimicrobial susceptibility patterns in PFGE-related strains confirmed the intestinal persistence of both outbreak strains. Risk factors for prolonged faecal carriage in infants were delivery by caesarean section [hazard ratio (HR) 2.4, 95% CI 1.1-5.5, P = 0.029] and treatment with antibiotics during hospitalization (HR 4.5, 95% CI 1.6-12.6, P = 0.004). Transmission of CTX-M-15 K. pneumoniae was observed in 9/28 (32%) households. Median carriage length in parents was 2.5 months (IQR 1.0-5.0) (P < 0.001 compared with infants). CONCLUSIONS Infants may be long-term faecal carriers of ESBL-producing K. pneumoniae after colonization during hospitalization in the neonatal period. Delivery by caesarean section and antibiotic treatment during hospitalization are possible risk factors for prolonged carriage. Faecal ESBL carriage in infants represents a reservoir for intra-household spread of ESBL-producing K. pneumoniae.

Serum eosinophil cationic protein and interleukin-5 in children with bronchial asthma and acute bronchiolitis

The aim of our study was to evaluate the clinical applicability of serum eosinophil cationic protein (ECP), interleukin‐5 (IL‐5) and total eosinophil counts in childhood asthma and bronchiolitis. These parameters were measured in 44 children aged 12‐84 months with moderate and mild asthma during symptomatic and asymptomatic phases of disease. Fifteen of the patients were included at the time of admission to hospital due to an acute asthmatic attack, and ten of these were also examined one month after discharge. None of the patients were treated with glucocorticoids or cromoglycate at any time during the study. Serum ECP was significantly increased in the children with acute asthma compared to children with stable moderate asthma, stable mild asthma, as well as to controls. There was no difference between the groups with stable asthma or between stable asthma and controls, and there was large overlap between all groups of asthmatics and controls. Detectable levels of circulating IL‐5 were demonstrated in eight of 15 children with acute asthma, with significantly higher levels in atopic children, whereas all samples from children with stable asthma and controls were negative. The results suggest that even though serum ECP and IL‐5 increases during acute asthmatic attacks, these parameters cannot alone be used to discriminate between different groups of young children with stable asthma, nor between asthmatics and healthy controls. In addition, the same parameters of eosinophil inflammation were examined in serum samples from 25 children aged 1‐17 months undergoing their first episode of acute bronchiolitis. Children with acute respiratory syncytial virus (RS V) bronchiolitis had significantly higher levels of serum ECP than those with RSV negative disease, whereas the total eosinophil counts were significantly decreased in all patients with acute bronchiolitis. Serum IL‐5 was only detected in two children with acute bronchiolitis. The results suggest that the inflammation in RSV bronchiolitis differs from that induced by other viruses.

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.

The outcome after severe bronchiolitis is related to gender and virus.

To cite this article: Mikalsen IB, Halvorsen T, Øymar K. The outcome after severe bronchiolitis is related to gender and virus. Pediatric Allergy Immunology 2012: 23: 391–398.

Incidence, clinical characteristics and outcome in Norwegian children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome; a population-based study.

To describe the incidence, epidemiology, clinical presentation and clinical outcome of children with the syndrome of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) in a population‐based study.

Acute facial nerve palsy in children: How often is it Lyme borreliosis?

Acute facial nerve palsy in children may be caused by infection by Borrelia burgdorferi, but the incidence of facial nerve palsy and the proportion of facial nerve palsy caused by Lyme borreliosis may vary considerably between areas. Furthermore, it is not well known how often facial nerve palsy caused by Lyme borreliosis is associated with meningitis. In this population-based study, children admitted for acute facial nerve palsy to Stavanger University Hospital during 9 y from 1996 to 2004 were investigated by a standard protocol including a lumbar puncture. A total of 115 children with facial nerve palsy were included, giving an annual incidence of 21 per 100,000 children. 75 (65%) of these were diagnosed as Lyme borreliosis, with all cases occurring from May to November. Lymphocytic meningitis was present in all but 1 of the children with facial nerve palsy caused by Lyme borreliosis where a lumbar puncture was performed (n = 73). In this endemic area for Borrelia burgdorferi, acute facial nerve palsy in children was common. The majority of cases were caused by Lyme borreliosis, and nearly all of these were associated with lymphocytic meningitis.

C-reactive protein in the periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome

Aims: To evaluate levels of C‐reactive protein (CRP) during febrile episodes in children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA).