| 1. |
- Hammar, Katarina Stenberg, et al.
(författare)
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Subnormal levels of vitamin D are associated with acute wheeze in young children
- 2014
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 103:8, s. 856-861
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This study evaluated risk factors for acute wheeze in preschool children and investigated whether subnormal levels of vitamin D were associated with increased risk for acute wheeze, atopy or viral/bacterial respiratory infections. Methods: We recruited 130 children with acute wheeze, aged 6 months to 4 years, from paediatric emergency departments in Stockholm, Sweden, and 101 age-matched controls with no history of wheeze or sensitisation to airborne allergens. Parents answered standardised questionnaires, and blood samples were analysed for specific IgE to airborne and food allergens and levels of 25 hydroxyvitamin D (25(OH)D). Nasopharyngeal virus samples were collected during the emergency department visit in the group of children with wheeze, and a subset were also tested for bacteria. Results: Vitamin D insufficiency (25(OH)D < 75 nmol/L (30 ng/mL)) was associated with an odds ratio of 2.7 (95% confidence interval 1.1-6.2) for acute wheeze. However, no association was found between vitamin D insufficiency and atopy, presence of virus or bacteria or recurrent infections. Children older than 24 months were particularly at risk of subnormal vitamin D levels, irrespective of wheezing history. Conclusion: Our findings support the hypothesis that subnormal levels of vitamin D are associated with acute wheeze in young children.
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| 2. |
- Konradsen, Jon R
(författare)
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Investigating problematic severe asthma in children : a translational approach
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Children with problematic severe asthma (PA) have persistent symptoms and/or severe exacerbations despite treatment with high doses of currently available asthma medications. The term PA includes children who are difficult to treat due to unidentified exacerbating factors (e.g. allergens or environmental hazards, comorbidities, psychological and social issues, and/or poor adherence) and those lacking identifiable aggravating factors but, nonetheless, do not respond well to asthma therapy. Children with PA are a heterogeneous group of patients with varying clinical presentations, pulmonary function and patterns of inflammation. This thesis is based on the results of a Swedish nationwide cross-sectional study in which school aged children with PA (n=57) were compared to age matched peers with persistent, but controlled asthma (CA), (n=39). The major objectives were to identify distinguishing features of children suffering from PA, to differentiate between children who were difficult to treat and those who were severely resistant to therapy and to investigate novel and potentially clinical relevant biomarkers of PA. PA was defined by insufficient asthma control despite high doses of inhaled corticosteroids. The protocol included a detailed characterization of: history and clinical presentation; pulmonary function; bronchial hyperresponsiveness; inflammatory biomarkers in blood (including white blood cells, interleukin-5 and chitinases (chitotriosidase and the chitinase-like protein YKL-40)), urine (EPX) and exhaled air (FeNO); allergy (IgE antibodies, component resolved allergy diagnostics, basophil allergen threshold sensitivity (CD-sens)); morphology (computerized tomography of sinuses and lungs (in the PA group only)). The major distinguishing features of children with PA involve familial background (heredity, socioeconomic status), clinical presentation (comorbidities and triggering factors) and pathophysiological differences including degree of airway obstruction, bronchial hyperresponsiveness and inflammatory profile (IL-5, number of eosinophilic and neutrophilic cells in blood). Sixty percent of children with PA had therapy-resistant asthma, with the remainder being difficult to treat due to identified aggravating factors. Individual IgE-responses were similar between children with PA and CA. Children with PA were more often multi-sensitized to > 3 single lipocalin (nMus m 1, rEqu c 1, Fel d 4, rCan f 1, 2), kallikrein (rCan f 5) and secretoglobin (rFel d 1) allergens compared to children with CA. Cat-allergic children with PA had higher allergen sensitivity, as measured by CD-sens, compared to cat-allergic peers with CA. Furthermore, CD-sens correlated with clinical markers of asthmatic disease, including asthma control and biomarkers of eosinophilic inflammation. YKL-40 levels and chitotriosidase activity were increased in the serum of children with PA, and YKL-40 specifically correlated with airway remodelling (as assessed by computerized tomography) and blood neutrophils in children severely resistant to asthma therapy. By employing a comprehensive and standardized clinical assessment we have discerned specific features of children with PA and identified children who are severely resistant to therapy. We have applied two novel methods of allergy diagnostics (Component resolved diagnostics and CD-sens) and found that these two methods provide relevant information when investigating children with PA. Finally, our findings confirm that YKL-40 is a potential biomarker of asthma severity and airway remodeling. A translational research approach is necessary when investigating associations between disease mechanisms and clinical presentation in complex diseases.
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| 3. |
- Konradsen, Jon R., et al.
(författare)
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Severe childhood asthma and allergy to furry animals : Refined assessment using molecular-based allergy diagnostics
- 2014
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 25:2, s. 187-192
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Tidskriftsartikel (refereegranskat)abstract
- Background Infants born prematurely are often treated with supplemental oxygen, which can increase their risk for airway hyper-responsiveness (AHR), asthma, reduced lung function, and altered responses to respiratory viral infections later in childhood. Likewise, exposure of newborn mice to hyperoxia alters baseline pulmonary mechanics and the host response to influenza A virus infection in adult mice. Here, we use this mouse model to test the hypothesis that neonatal hyperoxia also promotes AHR and exacerbated allergen-induced symptoms in adult mice. Methods Baseline lung mechanics and AHR measured by methacholine provocation were assessed in adult male and female mice exposed to room air or 100% oxygen (hyperoxia) between post-natal days 0-4. AHR and lung inflammation were evaluated after adult female mice were sensitized with ovalbumin (OVA) plus alum and challenged with aerosolized OVA. Results Baseline lung compliance increased and resistance decreased in adult female, but not male, mice exposed to neonatal hyperoxia compared with siblings exposed to room air. Neonatal hyperoxia significantly enhanced methacholine-induced AHR in female mice, but did not affect allergen-induced AHR to methacholine or lung inflammation. Conclusion Increased incidence of AHR and asthma is reported in children born prematurely and exposed to supplemental oxygen. Our findings in adult female mice exposed to hyperoxia as neonates suggest that this AHR reported in children born prematurely may reflect non-atopic wheezing due to intrinsic structural changes in airway development.
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