Search

This article discusses a study published in the journal Respirology that examines the impact of Staphylococcal enterotoxin-specific IgE sensitization on the effectiveness of omalizumab therapy in severe asthma. The study found that Staphylococcus aureus, a bacteria commonly found in the upper airways, produces Staphylococcal enterotoxins (SEs) that can stimulate the production of specific IgE antibodies. High levels of SE-IgE have been associated with severe late-onset asthma. The study conducted a prospective observational study to evaluate the clinical efficacy of omalizumab in patients with severe asthma who are allergic and non-allergic to aeroallergens, with and without positive SE-IgE. The results provide valuable insights into the characteristics of these patient groups. The study found that omalizumab reduced acute exacerbation rates and improved asthma control in patients with allergic asthma, regardless of SE-IgE sensitization. However, in non-allergic asthma patients, only those with SE-IgE sensitization responded to omalizumab. The study also discovered that patients who responded well to omalizumab had higher levels of eosinophils and lower levels of neutrophils in their sputum. Additionally, the addition of clarithromycin to omalizumab treatment improved asthma control in patients who had a poor or partial response to omalizumab. [Extracted from the article]

Bronchial specimens from patients with well-controlled asthma who had more intact airway epithelium were used for comparison with specimens from patients with severe asthma. Severe asthma: PP4 expression in the denuded epithelium of patients with severe asthma was very low. Loss of PP4 contributes to diesel exhaust particles-induced epithelial barrier integrity disruption and alarmins release. [Extracted from the article]

Background and objective: Circulating fibrocytes act as precursors of myofibroblasts, contribute to airway remodelling in chronic asthma and migrate to injured tissues by expressing CXCR4 and CCR7. Anti‐IgE therapy improves severe allergic asthma (SAA) control and airway remodelling in T2‐high SAA. The effects of anti‐IgE therapy on fibrocyte activities were investigated in this study. Methods: The expression of CCR7, CXCR4, ST2 and α‐SMA (α‐smooth muscle actin) in both circulating and cultured fibrocytes from all patients with asthma was measured, and was repeated after omalizumab treatment in SAA. Fibrocytes recruitment, proliferation and transformation were also measured in response to anti‐IgE therapy. Results: Omalizumab effectively improved asthma control and pulmonary function in T2‐high SAA, associated with a decline in serum levels of IL‐33 and IL‐13. Omalizumab down‐regulates CXCR4 and CCR7 expression of fibrocytes, which could suppress fibrocyte recruitment into the lungs. Omalizumab also suppressed the increased number of fibrocytes and α‐SMA+ fibrocytes within the cultured non‐adherent non‐T (NANT) cells after 3–7 days of culture. The decrease in serum levels of IL‐33 by omalizumab contributed to the effectiveness in inhibiting fibrocyte recruitment, proliferation and myofibroblast transformation through IL‐33/ST2 axis. The elevated IL‐13 expression in SAA patients potentiated the effects of IL‐33 by increasing ST2 expression. Conclusion: Omalizumab reduced the number of circulating fibrocytes, cell and number of fibrocytes as well as α‐SMA+ fibrocytes after 3–7 days of culture in SAA patients. IL‐33 and IL‐13 may be implicated in the effectiveness of omalizumab in inhibiting fibrocyte activation contributing partly to the clinical benefits in reducing lamina propria and basement membrane thickening. [ABSTRACT FROM AUTHOR]

Summary: Background: Omalizumab, a recombinant monoclonal anti‐IgE antibody, was developed for the treatment of severe allergic asthma. Not all these patients respond to omalizumab. Objective: This study aimed to evaluate whether the proinflammatory cytokine profiles in the severe allergic asthma patients were different between who responded and nonresponded to omalizumab therapy. Methods: A prospective study was conducted to examine type 2 cytokines and epithelium‐derived cytokines in the bronchial tissues by immunohistochemistry, Western blot and PCR analysis among patients with severe allergic asthma before and after omalizumab therapy. Results: Fourteen of 23 patients with unstable severe allergic asthma improved their asthma control after 4 months of omalizumab treatment (Responders), while nine failed to improve (Non‐Responders). Most of Responders were type 2‐high endotype (12/14) with upregulated expression of IL‐33, IL‐25 and TSLP in their bronchial tissues, while most of Non‐Responders were type 2‐low endotype (8/9). Repeated bronchoscopic biopsy was done in nine responders after omalizumab treatment and showed a decline in IL‐13, IL‐33, IL‐25 and TSLP expression in the bronchial tissues. Among 14 Responders who continued omalizuamb treatments to a total 12 months, six patients achieved a well control of asthma (ACT ≥ 23), while eight patients required additional treatment for asthma symptoms and had more rhinosinusitis comorbidities and a mixed eosinophilic and neutrophilic inflammation in their bronchial tissues. Conclusion: Most of the severe allergic asthma patients who benefited from omalizumab treatment were IL‐33, IL‐25 and TSLP aggravated type 2‐high endotype. Rhinosinusitis or with a mixed eosinophilic and neutrophilic airway inflammation should be evaluated in patients who partially responded to omalizumab treatment. [ABSTRACT FROM AUTHOR]