Novel therapies for severe asthma in children and adults.

The heterogeneous nature of asthma requires personalised treatments. Monoclonal antibody treatments showed good efficacy, and should be considered when symptoms are poorly controlled despite good inhaler technique, compliance and controlled comorbidities. http://ow.ly/UWpg30hImQh.

Anti-IgE treatment, airway inflammation and remodelling in severe allergic asthma: current knowledge and future perspectives.

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.

Concurrent granulomatous hepatitis, pneumonitis and sepsis as a complication of intravesical BCG immunotherapy.

Intravesical 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.

Levels of angiopoietins 1 and 2 in induced sputum supernatant in patients with COPD.

Pathological features of chronic obstructive pulmonary disease (COPD) include lung vascular remodeling and angiogenesis. Angiopoietin-1 (Ang-1), is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. We determined the levels of angiopoietins in sputum supernatants of patients with COPD and investigated their possible association with mediators and cells involved in the inflammatory and remodeling process. Fifty-nine patients with COPD, 25 healthy smokers and 20 healthy non-smokers were studied. All subjects underwent lung function tests, sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-ß1, MMP-2, LTB4, IL-8, albumin measurement in sputum supernatants. Airway vascular permeability (AVP) index was also assessed. Ang-2 levels were significantly higher in patients with COPD compared to healthy smokers and healthy non-smokers [median, interquartile ranges pg/ml, 267 (147-367) vs. 112 (67-171) and 98 (95-107), respectively; p<0.001]. Regression analysis showed a significant association between Ang-2 levels and AVP index, VEGF, IL-8 and MMP-2 levels in COPD, the strongest being with VEGF. Our results indicate that induced sputum Ang-2 levels are higher in COPD compared to healthy smokers and healthy non-smokers. Moreover, Ang-2 is associated with AVP, IL-8, MMP-2, and VEGF, indicating a possible role for Ang-2 in the pathogenesis of the disease.

Increased levels of osteopontin in sputum supernatant in severe refractory asthma.

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 beta1 (TGF-beta1), 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 (1125-11000) vs 130 (100-210) vs 100 (67-130) vs 50 (42-70), respectively, p<0.001). Regression analysis showed a significant association between log OPN and sputum eosinophils, cysteinyl leukotrienes, IL-13, TGF-beta1 and ECP. TGF-beta1 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-beta1, IL-13 and cysteinyl leukotrienes only in SRA.

Exhaled nitric oxide and exhaled breath condensate pH in severe refractory asthma.

BACKGROUND: Distinct inflammatory cellular phenotypes of severe refractory asthma (SRA) have been reported. Fractional exhaled nitric oxide (FeNO) primarily is related to eosinophilic inflammation. Exhaled breath condensate (EBC) pH has been suggested as a noninvasive tool in the assessment of patients with asthma. We sought to determine whether FeNO and EBC pH could identify the presence and type of the underlying cellular inflammation in patients with SRA. METHODS: Twenty-nine patients with SRA, 27 patients with moderate asthma, and 17 healthy subjects underwent FeNO measurement, EBC collection for pH measurement, and sputum induction for cell count identification. RESULTS: FeNO was significantly higher and pH significantly lower in patients with SRA than in the other groups. In SRA, FeNO levels of > 19 parts per billion were associated with a sensitivity of 0.78 and a specificity of 0.73 for sputum eosinophilia, whereas FeNO levels of < 19 parts per billion were associated with a sensitivity of 0.63 and a specificity of 0.9 for sputum neutrophilia irrespective of the presence of eosinophils. The pH failed to predict the cellular profile in SRA, but a cutoff value of < 7.37 could predict sputum eosinophilia in moderate asthma. CONCLUSIONS: In patients with SRA, different FeNO threshold values can identify those with predominant eosinophilia as well as those with neutrophilia. FeNO levels were reduced in patients with predominant neutrophilia regardless of the concomitant presence of eosinophilia. Although pH could not identify the cellular profile in SRA, it seemed to be a better index for predicting eosinophilia in moderate asthma.