Obesity lowers the threshold of allergic sensitization and augments airway eosinophilia in a mouse model of asthma

Clinical and epidemiological studies show a close association between obesity and the risk of asthma development. The underlying cause-effect relationship between metabolism, innate and adaptive immunity, and inflammation remains to be elucidated.

Pediatric severe asthma is characterized by eosinophilia and remodeling without T(H)2 cytokines

BACKGROUND: The pathology of pediatric severe therapy-resistant asthma (STRA) is little understood. OBJECTIVES: We hypothesized that STRA in children is characterized by airway eosinophilia and mast cell inflammation and is driven by the T(H)2 cytokines IL-4, IL-5, and IL-13. METHODS: Sixty-nine children (mean age, 11.8 years; interquartile range, 5.6-17.3 years; patients with STRA, n = 53; control subjects, n = 16) underwent fiberoptic bronchoscopy, bronchoalveolar lavage (BAL), and endobronchial biopsy. Airway inflammation, remodeling, and BAL fluid and biopsy specimen T(H)2 cytokines were quantified. Children with STRA also underwent symptom assessment (Asthma Control Test), spirometry, exhaled nitric oxide and induced sputum evaluation. RESULTS: Children with STRA had significantly increased BAL fluid and biopsy specimen eosinophil counts compared with those found in control subjects (BAL fluid, P < .001; biopsy specimen, P < .01); within the STRA group, there was marked between-patient variability in eosinophilia. Submucosal mast cell, neutrophil, and lymphocyte counts were similar in both groups. Reticular basement membrane thickness and airway smooth muscle were increased in patients with STRA compared with those found in control subjects (P < .0001 and P < .001, respectively). There was no increase in BAL fluid IL-4, IL-5, or IL-13 levels in patients with STRA compared with control subjects, and these cytokines were rarely detected in induced sputum. Biopsy IL-5(+) and IL-13(+) cell counts were also not higher in patients with STRA compared with those seen in control subjects. The subgroup (n = 15) of children with STRA with detectable BAL fluid T(H)2 cytokines had significantly lower lung function than those with undetectable BAL fluid T(H)2 cytokines. CONCLUSIONS: STRA in children was characterized by remodeling and variable airway eosinophil counts. However, unlike in adults, there was no neutrophilia, and despite the wide range in eosinophil counts, the T(H)2 mediators that are thought to drive allergic asthma were mostly absent.

Exhaled nitric oxide in symptomatic children at preschool age predicts later asthma

Prediction of asthma in young children with respiratory symptoms is hampered by the lack of objective measures applicable in clinical routine. In this prospective study in a preschool children cohort, we assessed whether the fraction of exhaled nitric oxide (FeNO), a biomarker of airway inflammation, is associated with asthma at school age.

SWIVIT--Swiss video-intubation trial evaluating video-laryngoscopes in a simulated difficult airway scenario: study protocol for a multicenter prospective randomized controlled trial in Switzerland

Video-laryngoscopes are marketed for intubation in difficult airway management. They provide a better view of the larynx and may facilitate tracheal intubation, but there is no adequately powered study comparing different types of video-laryngoscopes in a difficult airway scenario or in a simulated difficult airway situation.

Regular treatment with salmeterol and inhaled steroids for chronic asthma: serious adverse events

Epidemiological evidence has suggested a link between beta2-agonists and increased asthma mortality. There has been much debate about possible causal links for this association, and whether regular (daily) long-acting beta2-agonists are safe. This is an updated systematic review.

Cytokine and anti-cytokine therapy for asthma

Cytokines play a critical role in the pathogenesis of asthma. Asthma resolution may depend on the correction of dysregulated cytokine expression, which is a characteristic feature of this chronic inflammatory disease. It is, therefore, not surprising that attempts have been made to either block cytokines present at elevated levels or to substitute cytokines that are insufficiently expressed in asthma. In this article, the results of these studies are discussed, and the obtained insights regarding asthma pathogenesis and new treatment options are summarized.

[Eosinophilia, diarrhea and asthma in a young woman]

We present the case of a young woman that was diagnosed with Churg-Strauss syndrome. The classical as well as the atypical symptoms, signs and findings are discussed in the context of clinically relevant differential diagnoses. The diagnostic criteria and the relevant aspects of pathogenesis, clinical course and treatment are reviewed. In addition, the similarities and differences with respect to the other idiopathic interstitial eosinophilic pneumopathies are described.

[Acute "difficult" gastrointestinal bleeding]

Gastrointestinal bleeding with its point of origin outside the reach of conventional gastro- and colonoscopy represents an extraordinary diagnostic and therapeutic challenge. Bleeding may originate from the small bowel distal to the duodenojejunal junction (middle gastrointestinal bleeding) or from the biliary tree (haemobilia) or from the pancreatic ductal system (haemosuccus pancreaticus). This particular type of gastrointestinal bleeding is often intermittend and caused by a variety of different pathologies. Angiography is the diagnostic method of choice for further investigation. It allows precise localization of the bleeding site and simultaneous interventional therapy (embolization/coiling). The importance of further diagnostic modalities such as scintigraphy, capsule endoscopy, push-enteroscopy and double-balloon-enteroscopy is discussed.

Granzyme B, a novel mediator of allergic inflammation: its induction and release in blood basophils and human asthma

Histamine, leukotriene C4, IL-4, and IL-13 are major mediators of allergy and asthma. They are all formed by basophils and are released in particularly large quantities after stimulation with IL-3. Here we show that supernatants of activated mast cells or IL-3 qualitatively change the makeup of granules of human basophils by inducing de novo synthesis of granzyme B (GzmB), without induction of other granule proteins expressed by cytotoxic lymphocytes (granzyme A, perforin). This bioactivity of IL-3 is not shared by other cytokines known to regulate the function of basophils or lymphocytes. The IL-3 effect is restricted to basophil granulocytes as no constitutive or inducible expression of GzmB is detected in eosinophils or neutrophils. GzmB is induced within 6 to 24 hours, sorted into the granule compartment, and released by exocytosis upon IgE-dependent and -independent activation. In vitro, there is a close parallelism between GzmB, IL-13, and leukotriene C4 production. In vivo, granzyme B, but not the lymphoid granule marker granzyme A, is released 18 hours after allergen challenge of asthmatic patients in strong correlation with interleukin-13. Our study demonstrates an unexpected plasticity of the granule composition of mature basophils and suggests a role of granzyme B as a novel mediator of allergic diseases.

Parental understanding of wheeze and its impact on asthma prevalence estimates

The epidemiology of wheeze in children, when assessed by questionnaires, is dependent on parents' understanding of the term "wheeze". In a questionnaire survey of a random population sample of 4,236 children aged 6-10 yrs, parents' definition of wheeze was assessed. Predictors of a correct definition were determined and the potential impact of incorrect answers on prevalence estimates from the survey was assessed. Current wheeze was reported by 13.2% of children. Overall, 83.5% of parents correctly identified "whistling or squeaking" as the definition of wheeze; the proportion was higher for parents reporting wheezy children (90.4%). Frequent attacks of reported wheeze (adjusted odds ratio (OR) 3.0), maternal history of asthma (OR 1.5) and maternal education (OR 1.5) were significantly associated with a correct answer, while the converse was found for South Asian ethnicity (OR 0.6), first language not English (OR 0.6) and living in a deprived neighbourhood (OR 0.6). In summary, the present study showed that misunderstanding could lead to an important bias in assessing the prevalence of wheeze, resulting in an underestimation in children from South Asian and deprived family backgrounds. Prevalence estimates for the most severe categories of wheeze might be less affected by this bias and questionnaire surveys on wheeze should incorporate measures of parents' understanding of the term wheeze.

The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma. The SAPALDIA Cohort Study

BACKGROUND: IL-18 is a pleiotrophic cytokine involved in both, T-helper type 1 (Th1) and Th2 differentiation. Recently genetic variants in the IL-18 gene have been associated with increased risk of atopy and asthma. OBJECTIVE: To examine the relationship of a genetic, haplotype-tagging promotor variant -137G/C in the IL-18 gene with atopic asthma in a large, well-characterized and population-based study of adults. METHODS: Prospective cohort study design was used to collect interview and biological measurement data at two examination time-points 11 years apart. Multivariate logistic regression analysis was used to assess the association of genotype with asthma and atopy. RESULTS: The G-allele of the IL-18 promotor variant (-137G/C) was associated with a markedly increased risk for the prevalence of physician-diagnosed asthma with concomitant skin reactivity to common allergens. Stratification of the asthma cases by skin reactivity to common allergens revealed an exclusive association of IL-18 -137 G-allele with an increased prevalence of atopic asthma (adjusted odds ratio (OR): 3.63; 95% confidence interval: (1.64-8.02) for GC or GG carriers vs. CC carriers), and no according association with asthma and concomitant negative skin reactivity (adjusted OR: 1.13; 0.66-1.94). The interaction between IL-18 -137G/C genotype and positive skin prick test was statistically significant (P=0.029). None of 74 incident asthma cases with atopy at baseline exhibited the CC genotype. CONCLUSION: Our results strongly suggest that this variant of the IL-18 gene is an important genetic determinant involved in the development of atopic asthma.