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Predictive factors for airway hyperresponsiveness in children with respiratory symptoms.

Asthma diagnosis is a challenging condition, particularly in patients without obstructive pattern and reversibility on spirometry. Determination of airway hyperresponsiveness (AHR) may be helpful, but the procedure is time-consuming and not always practical.

Upper and lower airway pathology in young children with allergic- and non-allergic rhinitis.

Allergic- and non-allergic rhinitis are very common diseases in childhood in industrialized countries. Although these conditions are widely trivialized by both parents and physicians they induce a major impact on quality of life for the affected children and a substantial drainage of health care resources. Unfortunately, diagnostic specificity is hampered by nonspecific symptom history and lack of reliable diagnostic tests which may explain why the pathology behind such diagnoses is poorly understood. Improved understanding of the pathophysiology of allergic- and non-allergic rhinitis in young children may contribute to the discovery of new mechanisms involved in pathogenesis and help direct future research to develop correctly timed preventive measures as well as adequate monitoring and treatment of children with rhinitis.

Asthma is a common comorbidity in subjects with allergic rhinitis and epidemiological surveys have suggested a close connection between upper and lower airway diseases expressed as the "united airways concept". Furthermore, an association between upper and lower airway diseases also seems to exist in non-atopic individuals. Nevertheless, the nature of this association is poorly understood and there is a paucity of data objectivizing this association in young children.

The aim of this thesis was to describe pathology in the upper and lower airways in young children from the COPSAC birth cohort with investigator-diagnosed allergic- and non-allergic rhinitis. Nasal congestion is a key symptom in both allergic- and non-allergic rhinitis, and eosinophilic inflammation is a hallmark of the allergic diseases.

In paper I, we studied nasal eosinophilia and nasal airway patency assessed by acoustic rhinometry in children with allergic rhinitis, non-allergic rhinitis and healthy controls. Allergic rhinitis was significantly associated with nasal eosinophilia and irreversible nasal airway obstruction suggesting chronic inflammation and structural remodeling of the nasal mucosa in children already at age 6 years. Non-allergic rhinitis exhibited no change in the nasal airway patency, but some nasal eosinophilia albeit less than children with allergic rhinitis. These findings suggest different pathology in allergic- and non-allergic rhinitis which may have important clinical implications for early pharmacological treatment of rhinitis in young children.

In paper II, we utilized the nasal airway patency end-points derived from paper I to examine whether upper and lower airway patency are associated. Upper airway patency was assessed by acoustic rhinometry before and after intranasal α-agonist and lower airway patency by spirometry before and after inhaled β2-agonist. Upper and lower airway patencies were strongly associated and independent of body size, rhinitis and asthma. The association was consistent for both baseline values and for decongested nasal airway patency and post-β2 FEV1. Blood and nasal eosinophilia were also associated with nasal airway obstruction. This suggests generalized diminished airway dimensions as a novel susceptibility factor for concurrent symptoms of asthma and rhinitis in early childhood and supports the notion of a common pathophysiology in asthma and rhinitis. The clinical interpretation of these findings is that all children presenting either rhinitis or asthma should be considered inflamed in the entire respiratory tract. In paper III, we aimed to describe asthma and intermediary asthma end-points associated with allergic- and non-allergic rhinitis in preschool-aged children. At age 7 years, we evaluated prevalence of asthma, eczema, food sensitization, and filaggrin mutations; levels of total IgE, FeNO, and blood-eosinophils; lung function and bronchial responsiveness to cold dry air.

We found that asthma was similarly associated with allergic- and non-allergic rhinitis suggesting a link between upper and lower airway diseases beyond an allergy associated inflammation. Only children with allergic rhinitis had increased bronchial responsiveness and elevated FeNO suggesting different endotypes of asthma symptoms in young children with allergic- and non-allergic rhinitis. We also found bronchial hyperresponsiveness and raised values of FeNO in children with allergic rhinitis without asthma suggesting sub-clinical bronchial inflammation and supporting the allergic disease process to involve both upper and lower airways.

In conclusion, these observations objectively show marked differences in nasal pathology in young children with allergic- and non-allergic rhinitis and lend support to a close connection between upper and lower airway diseases partly from an allergy driven process, but equally from non-allergic mechanisms.

Association between Domestic Mould and Mould Components, and Asthma and Allergy in Children: A Systematic Review.

Critical reviews over the past 10 years have found increased respiratory and allergic health outcomes for children living in damp and mouldy environments. However, recent studies have suggested that early childhood exposure to specific mould components may actually protect children from developing allergy. We conducted a systematic review of observational studies published in English from 1980 to July 2010.

This review was conducted according systematic guidelines for meta-analyses of observational studies (MOOSE). The literature was searched using a computerised bibliographic database, PubMed. In order to increase the quality of the reviewed studies, meta-analyses of the effects of visible mould exposure on allergic health outcomes were calculated and we evaluated the findings according to the Bradford Hill criteria for evidence of causation.

The literature search identified 1398 peer reviewed scientific publications, and 61 studies that fulfilled the inclusion criteria were included in this review.

We observed increased risks of allergic respiratory health outcomes in children exposed to visible mould and mould spores. These findings were confirmed by the results of the meta-analysis and in line with the evaluation criteria according to Bradford Hill. Visible mould was positively associated with asthma (OR=1.49 (95% CI=1.28-1.72)), wheeze (1.68 (1.48-1.90)) and allergic rhinitis (1.39 (1.28-1.51)). However, there was a tendency of lower risk for allergic health outcomes in children exposed to mould derived components such as (1,3)-β-D-glucan and Extracellular polysaccharides (EPS).

These findings suggest that home environments with visible mould and mould spore exposure increase the risk for allergic respiratory health outcomes in children. However, further investigations are needed to examine the effects of exposure to mould derived components as the current literature is inconclusive.

In order to disentangle the different effects of overall microbial exposure on children's health, research should focus on specific microbial markers in the home, in combination with new assessment techniques such as recently developed molecular methods.

Chronic Obstructive Pulmonary Disease Patient Well-Being and Its Relationship with Clinical and Patient-Reported Outcomes: A Real-Life Observational Study.

Quality of life is an umbrella concept that refers to all aspects of a person's life, including health status and well-being. While health status measure focuses on the impact of the disease on physical functioning, well-being represents the self-representation of the emotional states related to the disease itself.

Objectives: The objective of this study was to evaluate the psychological well-being and its determining factors in a real-life chronic obstructive pulmonary disease (COPD) population and to evaluate if patients with a different well-being differ in illness perception, health status and alexithymia.

Methods: Psychological well-being (Psychological General Well-Being Index), health status (SF-36), illness perception (Illness Perception Questionnaire), alexithymia (Toronto Alexithymia Scale), as well as clinical parameters were assessed in COPD out-patients.

Results: One hundred and sixty-four patients, with a mean forced expiratory volume in 1 s of 58.5%, were recruited. Forty percent of them had a moderately/severely impaired well-being, not correlated with forced expiratory volume in 1 s and the Charlson index value but significantly with the Medical Research Council score (p = 0.0001) that appeared to be the dominant factor. Patients with impaired well-being showed a different illness perception in terms of correct identification of symptoms, disease consequences, emotional representation and confidence in treatment compared with those having a positive well-being. The latter presented a lower alexithymia prevalence and a better health status.

Conclusions: In order to minimize the disease-negative effects on patients' lives, assessment of well-being and its determining factors, as well as planning specific behavioural, educational and therapeutic interventions seem to be relevant and useful.

Occupational sensitization to soy allergens in workers at a processing facility.

Exposure to soy antigens has been associated with asthma in community outbreaks and in some workplaces. Recently, 135 soy flake processing workers (SPWs) in a Tennessee facility were evaluated for immune reactivity to soy. Allergic sensitization to soy was common and was five times more prevalent than in health care worker controls (HCWs) with no known soy exposure.

Objective To characterize sensitization to soy allergens in SPWs.

Methods Sera that were positive to soy ImmunoCAP (n=27) were tested in IgE immunoblots. Wild-type (WT) and transgenic (TG) antigens were sequenced using nanoscale Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry (nanoUPLC MS/MS). IgE reactivity towards 5-enolpyruvylshikimate-3-phosphate synthase (CP4-EPSP), a protein found in TG soy, was additionally investigated. De-identified sera from 50 HCWs were used as a control.

Results Immunoblotting of WT and TG soy flake extracts revealed IgE against multiple soy antigens with reactivity towards 48, 54, and 62 kDa bands being the most common. The prominent proteins that bound SPW IgE were identified by nanoUPLC MS/MS analysis to be the high molecular weight soybean storage proteins, β-conglycinin (Gly m 5), and Glycinin (Gly m 6). No specific IgE reactivity could be detected to lower molecular weight soy allergens, Gly m 1 and Gly m 2, in soybean hull (SH) extracts. IgE reactivity was comparable between WT and TG extracts; however, IgE antibodies to CP4-EPSP could not be detected.

Conclusions and Clinical Relevance SPWs with specific IgE to soy reacted most commonly with higher molecular weight soybean storage proteins compared with the lower molecular weight SH allergens identified in community asthma studies. IgE reactivity was comparable between WT and TG soy extracts, while no IgE reactivity to CP4-EPSP was observed. High molecular weight soybean storage allergens, Gly m 5 and Gly m 6, may be respiratory sensitizers in occupational exposed SPWs.

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