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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]

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]

Background: The efficacy of antifungal therapy in fungal-associated severe asthma remains controversial. Objective: We aimed to evaluate the differences in the clinical presentation and response to antifungal therapy between severe asthmatics with fungal sensitization and positive fungal isolates. Methods: This retrospective study included 73 patients with severe asthma from January 2004 to December 2017. We examined the presentation, medication, exacerbations, pulmonary function, serum IgE, blood eosinophils, and sputum culture results. Follow-up care was provided to each patient for minimum 3 years. Results: We classified the patients into four groups: group 1, neither fungal sensitization nor fungal isolates in the sputum (n=16); group 2, positive fungal sensitization (n=16); group 3, positive fungal isolates (n=31); and group 4, concomitant positive fungal sensitization and positive fungal isolates (n=10). There were four participants in group 2, 15 in group 3, and 6 in group 4 had received itraconazole therapy for 3 months. Patients in group 3 presented with lower serum IgE level than those in groups 2 and 4. Antifungal therapy significantly improved ACT score during the first year in groups 3 (from 18 [15– 22] to 24 [23– 24], p=0.0004) and resulted in a long-lasting ACT improvement till the third year in group 3 (from 18 [15– 22] to 24 [22– 24], p=0.0013). Conclusion: Antifungal therapy could effectively control the symptoms in patients with severe asthma with positive fungal isolates, contrary to those with merely fungal sensitization; therefore, highlighting the need for a more precise treatment strategy in future for fungal-associated severe asthma. [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]

Background: Patients with severe asthma have increased airway remodelling and elevated numbers of circulating fibrocytes with enhanced myofibroblastic differentiation capacity, despite being treated with high doses of corticosteroids, and long acting β2-adrenergic receptor (AR) agonists (LABAs). We determined the effect of β2-AR agonists, alone or in combination with corticosteroids, on fibrocyte function.Methods: Non-adherent non-T cells from peripheral blood mononuclear cells isolated from healthy subjects and patients with non-severe or severe asthma were treated with the β2-AR agonist, salmeterol, in the presence or absence of the corticosteroid dexamethasone. The number of fibrocytes (collagen I+/CD45+ cells) and differentiating fibrocytes (α-smooth muscle actin+ cells), and the expression of CC chemokine receptor 7 and of β2-AR were determined using flow cytometry. The role of cyclic adenosine monophosphate (cAMP) was elucidated using the cAMP analogue 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) and the phosphodiesterase type IV (PDE4) inhibitor, rolipram.Results: Salmeterol reduced the proliferation, myofibroblastic differentiation and CCR7 expression of fibrocytes from healthy subjects and non-severe asthma patients. Fibrocytes from severe asthma patients had a lower baseline surface β2-AR expression and were relatively insensitive to salmeterol but not to 8-Br-cAMP or rolipram. Dexamethasone increased β2-AR expression and enhanced the inhibitory effect of salmeterol on severe asthma fibrocyte differentiation.Conclusions: Fibrocytes from patients with severe asthma are relatively insensitive to the inhibitory effects of salmeterol, an effect which is reversed by combination with corticosteroids. [ABSTRACT FROM AUTHOR]

Background: Although the prevalence of both obstructive sleep apnoea (OSA) and asthma are both increasing, little is known about the impact of OSA on the natural history of lung function in asthmatic patients.Methods: A total of 466 patients from our sleep laboratory were retrospectively enrolled. Of them, 77 patients (16.5%) had asthma with regular follow-up for more than 5 years. Their clinical characteristics, pulmonary function, emergency room visits, and results of polysomnography results were analysed.Results: The patients were divided into three groups according to the severity of the apnoea-hypopnea index (AHI). The decline in FEV1 among asthma patients with severe OSA (AHI > 30/h) was 72.4 ± 61.7 ml/year (N = 34), as compared to 41.9 ± 45.3 ml/year (N = 33, P = 0.020) in those with mild to moderate OSA (5 < AHI ≤ 30) and 24.3 ± 27.5 ml/year (N = 10, P = 0.016) in those without OSA (AHI ≤ 5). For those patients with severe OSA, the decline of FEV1 significantly decreased after continuous positive airway pressure (CPAP) treatment. After multivariate stepwise linear regression analysis, only AHI was remained independent factor for the decline of FEV1 decline.Conclusions: Asthmatic patients with OSA had substantially greater declines in FEV1 than those without OSA. Moreover, CPAP treatment alleviated the decline of FEV1 in asthma patients with severe OSA. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-5 plays an important role in maintaining the survival of eosinophils via the specific a-subunit of its receptor. Apoptosis, a form of programmed cell death, is thought to represent a mechanism that promotes the resolution of eosinophilic inflammation in asthma. The aim of our present study is to investigate whether IL-5 acts in an autocrine fashion on eosinophil apoptosis in asthmatics. Immunoreactivities of intracellular IL-5 and IL-5 receptor a-subunit (Ra) were detected uniquely on the eosinophils. The magnitude of IL-5 and IL-5 Ra expression on eosinophils was significantly higher in asthmatics than that of normal subjects ( p [ABSTRACT FROM AUTHOR]