Asthma is a disorder of the airways involving various inflammatory cells and mediators and characterised by bronchial hyperresponsiveness, chronic inflammation and structural alterations in the airways, also known as remodelling. IgE is an important mediator of allergic reactions and has a central role in allergic asthma pathophysiology, as it is implicated in both the early and late phase allergic response. Moreover, clinical and mechanistic evidence has lately emerged, implicating IgE in the development of airway remodelling. The use of monoclonal antibodies targeting IgE, such as omalizumab, has proven very effective in improving respiratory symptoms and quality of life, while reducing asthma exacerbations, emergency room visits and the use of systemic corticosteroids in allergic severe asthma. These effects are believed to be mainly mediated by omalizumab's inhibitory effect on the initiation and further propagation of the allergic inflammation cascade. However, there is evidence to suggest that anti-IgE treatment remains effective long after it has been discontinued. In part, these findings could be attributed to the possible ameliorating effects of anti-IgE treatment on airway remodelling. In this review, we discuss recent findings supporting the notion that anti-IgE treatment modulates the complex immune responses that manifest clinically as asthma and ameliorates airway remodelling changes often observed in allergic severe asthma phenotypes. @ERSpublications Anti-IgE treatment suppresses the inflammatory airway response and markers of remodelling in allergic asthma http://ow.ly/Som4i

Background Osteopontin (OPN) is a glycoprotein that has been associated with inflammation and fibrosis. Severe refractory asthma (SRA) is characterised by an intense inflammatory and remodelling process. The aim of this study was to investigate the levels of OPN in sputum supernatants of patients with SRA, to compare them with milder forms of the disease and to investigate their possible association with mediators and cells involved in the inflammatory and remodelling process. Methods 33 patients with SRA, 29 with moderate asthma, 21 with steroid-naïve asthma and 20 healthy subjects were studied. All subjects underwent lung function tests, bronchial hyper-responsiveness assessment and sputum induction for cell count identification and measurement of OPN, vascular endothelial growth factor, transforming growth factor b1 (TGF-b1), cysteinyl leukotrienes, interleukin 13 (IL-13), eosinophilic cationic protein (ECP) and IL-8 in sputum supernatants. Results Median (IQR) OPN levels (pg/ml) were significantly higher in patients with SRA than in those with moderate asthma, steroid-naive asthma and healthy control subjects (1840 (1125e11000) vs 130 (100e210) vs 100 (67e130) vs 50 (42e70), respectively, p<0.001). Regression analysis showed a significant association between log OPN and sputum eosinophils, cysteinyl leukotrienes, IL-13, TGF-b1 and ECP. TGF-b1 represented the strongest association with OPN. The above associations were not observed in milder forms of the disease or in healthy subjects. Conclusions The results indicate that OPN levels are higher in SRA than in less severe forms of the disease. Moreover, OPN is associated with mediators involved in both the inflammatory and remodelling process such as TGF-b1, IL-13 and cysteinyl leukotrienes only in SRA.

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SUMMARYIntravesical administration of BCG is a relatively simple procedure used successfully in the treatment of superficial transitional cell carcinoma of the urinary bladder. It is usually well tolerated with few major side effects. The authors report the case of an 80-year-old man who presented with sepsis, jaundice, hepatic and pulmonary failure 10 days after his last BCG instillation therapy, that was attributed to concurrent granulomatous hepatitis and pneumonitis due to Mycobacterium bovis dissemination. In rare instances severe life-threatening complications occur in relation with BCG instillation immunotherapy that may involve multiple organs and have different presentations and require a high index of suspicion and clinical awareness in a wide range of medical specialties. BACKGROUND

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Asthma is a heterogeneous disease usually characterised by chronic airway inflammation. It is defined by a history of symptoms such as wheeze, shortness of breath, chest tightness and cough, along with variable airflow limitation [1]. Recently, “cluster” analyses have provided insight into specific subtypes among asthma patients, which share phenotypic characteristics.

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