The Effectiveness of Biological Agents on Chronic Rhinosinusitis with Nasal Polyposis in Patients with Comorbid Asthma: A Multicenter Real-Life Study from Türkiye.

Background and Objectives: Real-life data on the efficacy of biologic agents (BAs) on asthma-comorbid CRSwNP are needed. Our primary goal is to investigate the effects of BAs on CRSwNP symptoms, as well as endoscopic and tomography scores. Our secondary goal is to show a reduction in the frequency of acute sinusitis exacerbations and the need for surgery. Materials and Methods: We conducted a multicenter, retrospective, real-life study. We screened the patients with asthma-comorbid CRSwNP treated with omalizumab or mepolizumab. A total of 69 patients (40 F/29 M; omalizumab n = 55, mepolizumab n = 14) were enrolled. We compared the visual analog scale (VAS), sinonasal outcome test-22 (SNOT-22), nasal congestion score (NCS), Lund-Mackay computed tomography score (LMS), and total endoscopic polyp scores (TPS) before and after BAs. We evaluated the endoscopic sinus surgery (ESS) and acute exacerbations of chronic rhinosinusitis (AECRS) frequencies separately, according to the BAs. Results: The overall median (min-max) age was 43 (21-69) years. The median (min-max) of biologic therapy duration was 35 (4-113) months for omalizumab and 13.5 (6-32) for mepolizumab. Significant improvements were seen in VAS, SNOT-22, and NCS with omalizumab and mepolizumab. A significant decrease was observed in TPS with omalizumab [95% CI: 0-4] (p < 0.001), but not with mepolizumab [95% CI: -0.5-2] (p = 0.335). The frequency of ESS and AECRS were significantly reduced with omalizumab [95% CI: 2-3] (p < 0.001) and [95% CI: 2-5] (p < 0.001); and mepolizumab [95% CI: 0-2] (p = 0.002) and [95% CI: 2-8.5] (p < 0.001), respectively. There was no significant difference in LMS with either of the BAs. Conclusions: Omalizumab and mepolizumab can provide a significant improvement in the sinonasal symptom scores. BAs are promising agents for CRSwNP patients with frequent exacerbations and multiple surgeries.

Doxycycline may be more clinically effective in type 2 chronic rhinosinusitis nasal polyp comorbid with asthma.

OBJECTIVE: Chronic rhinosinusitis with nasal polyp (CRSwNP) is one of the major phenotypes of chronic rhinosinusitis (CRS) with a high symptom burden. Doxycycline can be used as add-on therapy in CRSwNP. We aimed to evaluate short-term efficacy of oral doxycycline on visual analog scale (VAS) and SNOT-22 (Sino-nasal outcome test) score for CRSwNP. METHODS: Visual analog score (VAS) for nasal symptoms and total SNOT-22 scores of 28 patients who applied with the diagnosis of CRSwNP and received 100 mg doxycycline for 21 days were analyzed in this retrospective cohort study. Doxycycline efficacy was also evaluated in subgroups determined according to asthma, presence of atopy, total IgE and eosinophil levels. RESULTS: After 21-day doxycycline treatment, there was a significant improvement in VAS score for post-nasal drip, nasal discharge, nasal congestion, and sneeze, and total SNOT-22 score (p = 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). No significant improvement was observed in VAS score for the loss of smell (p = 0.18). In the asthmatic subgroup, there were significant improvements in all VAS scores and total SNOT-22 score after doxycycline. In the non-asthmatic subgroup, there was no significant change in any of the VAS scores, but total SNOT-22 score was significantly improved (42 [21-78] vs. 18 [9-33]; p = 0.043). Improvement in VAS score for loss of smell is significant in only some subgroups like asthmatic patients, non-atopic patients, and patients with eosinophil >300 cell/µL. CONCLUSIONS: Doxycycline can be considered as an add-on treatment for symptom control in patients especially with CRSwNP comorbid with asthma.

The Role of Long-Acting Antimuscarinic Agents in the Treatment of Asthma.

The journey of using anticholinergics in the treatment of asthma started with anticholinergic-containing plants such as Datura stramonium and Atropa belladonna, followed by ipratropium bromide and continued with tiotropium, glycopyrronium, and umeclidinium. Although antimuscarinics were used in the maintenance treatment of asthma over a century ago, after a long time (since 2014), it has been recommended to be used as an add-on long-acting antimuscarinic agent (LAMA) therapy in the maintenance treatment of asthma. The airway tone controlled by the vagus nerve is increased in asthma. Allergens, toxins, or viruses cause airway inflammation and inflammation-related epithelial damage, increased sensory nerve stimulation, ganglionic and postganglionic acetylcholine (ACh) release by inflammatory mediators, intensification of ACh signaling at M1 and M3 muscarinic ACh receptors (mAChRs), and dysfunction of M2 mAChR. Optimal anticholinergic drug for asthma should effectively block M3 and M1 receptors, but have minimal effect on M2 receptors. Tiotropium, umeclidinium, and glycopyrronium are anticholinergic agents with this feature. Tiotropium has been used in a separate inhaler as an add-on treatment to inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA), and glycopyrronium and umeclidinium have been used in a single inhaler as a combination of ICS/LABA/LAMA in asthma in recent years. Guidelines recommend this regimen as an optimization step for patients with severe asthma before initiating any biologic or systemic corticosteroid therapy. In this review, the history of antimuscarinic agents, their effectiveness and safety in line with randomized controlled trials, and real-life studies in asthma treatment will be discussed according to the current data.

Biological therapy management from the initial selection of biologics to switching between biologics in severe asthma.

The aim of this review is to elaborate the management of biologic therapy from initial selection to switching biologics in severe asthma. A nonsystematic review was performed for biological therapy management in severe asthma. Depending on clinical characteristics and biomarkers, selecting the preferred biologic based on super-responder criteria from previous studies may result in adequate clinical efficacy in most patients. On the other hand, no matter how carefully the choice is made, in some patients, it may be necessary to discontinue the drug due to suboptimal clinical response or even no response. This may result in the need to switch to a different biological therapy. How long the biological treatment of patients whose asthma is controlled with biologics will be continued and according to which criteria they will be terminated remains unclear. It has been shown that in patients with a long history of good response to biologics, asthma control may be impaired when biologics are discontinued, while it may persist in others. Therefore, discontinuation of biologics may be a viable strategy in a particular patient group. Clinicians should make the best use of all predictive factors to identify patients who will most benefit from each biologic. Patients who do not meet a predefined response criterion after sufficient time for response evaluation and who are eligible for one or more alternative biological agents should be offered the opportunity to switch to another biologic. There is no consensus on when the biologics used in severe asthma that produce favorable results should be discontinued. In our opinion, treatment should continue for at least five years, as premature termination may potentially deteriorate asthma control.

Venom immunotherapy and difficulties encountered before and during immunotherapy: Double sensitization, systemic reactions, treatment with omalizumab, and high dose VIT.

BACKGROUND: Venom immunotherapy (VIT) is the most effective treatment method to prevent recurrent systemic reactions to Hymenoptera stings. In this study, the demographic characteristics of VIT patients, the success rates of VIT, the difficulties we encountered during VIT, and solutions for these difficulties in our clinic were presented. METHODS: We retrospectively analyzed patients with venom allergy who applied venom immunotherapy between 2013- 2020. Data on age, gender, Hymenoptera species with the first reaction, grade of the reaction, beekeeping history, skin prick and specific IgE and component results, double sensitization, blood groups, and reactions with VIT and/or sting during built-up and maintenance periods were recorded. RESULTS: A total of 73 patients were enrolled in the study. The median time from the first sting reaction to the application to the allergy outpatient clinic was 12 (0.5-24) months. The first sting reaction of 38 (52.1%) of the patients was with honey bees, and 24 (32.9%) were with wasps. Double positivity was present in 29 (40%) of the patients in prick results and 26 (36%) serologically. There was no correlation between the severity of first reactions and Apis Mellifera or Vespula prick diameters (p = 0.643; r = -0.056; p = 0.462; r = 0.089, respectively). High-dose VIT was administered to 4 patients. Omalizumab has been used as an alternative agent to achieve the maintenance dose in 2 patients with frequent systemic reactions during VIT. DISCUSSION: Most patients were able to tolerate VIT. Double positivity is one of the most common difficulties before VIT. In patients who develop systemic reactions in the VIT maintenance phase, a maintenance dose increase should be considered in the maintenance phase. Adding omalizumab does not seem to be a permanent solution in patients who develop a severe systemic reaction.

Discontinuing Omalizumab Treatment in Super-Responder Patients with Allergic Severe Asthma: Can the Baseline Total IgE Level Be Used as a Biological Marker to Decide Discontinuing Omalizumab Treatment?

BACKGROUND: Although there are many studies presenting the efficacy of omalizumab in severe asthma, the data about the optimal treatment duration are still debated. OBJECTIVE: In this study, we aimed to investigate the clinical effects of omalizumab discontinuation after 5 years of treatment in patients with omalizumab super-responders, the persistence of response and to compare the features of patients, whose symptoms are still well controlled and those who relapsed and re-treated with omalizumab. METHODS: Clinical and laboratory data of 100 adult patients diagnosed with allergic severe asthma and treated with omalizumab between 2008 and 2020 were evaluated retrospectively. Demographic, clinical, functional, and laboratory parameters of the patients who were re-treated with omalizumab and those who did not need to be re-treated were compared. RESULTS: There were 14 super-responder patients, who were treated with omalizumab for 5 years, and the treatment was discontinued then. Omalizumab was not restarted in 9 patients (64%) and was restarted in 5 (36%) patients. No significant difference was presented between these two groups in terms of demographic, clinical, functional, and laboratory parameters. The baseline total IgE levels of patients, who were re-treated with omalizumab, was found to be higher than those who were not, but this difference was not statistically significant (440 [229-864] IU/mL vs. 164 [85-293] IU/mL; p = 0.053, respectively). CONCLUSION: One of 3 patients was re-treated with omalizumab due to loss of asthma control after discontinuation of the treatment. Therefore, omalizumab's immunomodulatory effect may seem to persist in a majority of cases after discontinuation. Also, higher baseline total IgE levels might help to predict the cases that need re-treatment after discontinuation.

[Long-term macrolide therapy in asthma]. / Astimda uzun süreli makrolid tedavisi.

Macrolides are antibiotics with antiviral, anti-inflammatory and immunomodulatory effects in together with their bacteriostatic effects. In addition to its beneficial effects on chronic respiratory diseases such as COPD, cystic fibrosis, diffuse panbronchiolitis, and bronchiectasis, its effects on uncontrolled severe asthma and asthma exacerbations have been the subject of research in recent years. In randomized controlled trials, azithromycin, a macrolide, has been shown to reduce asthma exacerbations and significantly improve asthma-related quality of life in both eosinophilic and non-eosinophilic asthma phenotypes. However, there are also differences such as doses, durations and some studies not showing its effectiveness in severe eosinophilic asthma. In the GINA report, azithromycin can be recommended as an add-on therapy in patients with uncontrolled non-T2 severe asthma despite high-dose inhaled corticosteroid/ long-acting beta2-agonist/long-acting antimuscariniric treatments, or in T2 severe asthma patients whose asthma is not under control despite biologic therapy. In this review, the use of macrolides, especially azithromycin, in the treatment of asthma, immunomodulatory activities and safety profiles are discussed on the basis of current studies and guidelines.

Blood hyperreosinophilia: A diagnostic challenge.

A very detailed differential diagnosis is necessary to investigate the causes of blood hypereosinophilia. In the differential diagnosis of hypereosinophilia with pulmonary involvement, primary and secondary eosinophilic lung diseases should be kept in mind, and more specific diagnoses should be considered in those with a history of nasal polyposis and asthma. Here, it was aimed to present a case of organ-limited hypereosinophilia with asthma and nasal polyposis.

Effectiveness of mepolizumab therapy on symptoms, asthma exacerbations, steroid dependence, and small airways in patients with severe eosinophilic asthma

Background/aim: The efficacy of mepolizumab has been largely demonstrated in clinical trials in patients with severe eosinophilic asthma (SEA). However, reports on experience with mepolizumab in a real-life cohort are limited. Moreover, data about the effectiveness of mepolizumab on small airways is scarce. This study evaluated the effectiveness of mepolizumab therapy on symptoms, asthma exacerbations, blood eosinophils, steroid dependence, and small airways in a real-life cohort of patients with SEA. Materials and methods: We retrospectively analyzed patients with SEA who were receiving fixed-dose mepolizumab. The effects of mepolizumab on clinical, laboratory, functional parameters were evaluated at 12th, 24th, and 52nd weeks. Small airways were assessed with the FEF 25-75. Results: A total of 41 patients were enrolled in the study. Mepolizumab significantly reduced asthma exacerbation rates, reduced mOCS dose, and improved asthma control test (ACT) scores at 12th, 24th, and 52nd weeks. However, we found no significant changes in FEV1 and FEF25-75 values at baseline, 12th, 24th, and 52nd weeks (78.9 ± 23.3%, 82.9 ± 23.4%, 81.9 ± 23.9%, and 78.9 ± 23.5% for FEV1; 45.1 ± 23.1%, 48.8 ± 23.5%, 48.7 ± 23.1%, and 41.0 ± 20.1% for FEF25-75, respectively) Conclusion: In this study, mepolizumab significantly improved all outcomes (symptom scores, asthma exacerbations, OCS sparing, and blood eosinophils) except functional parameters. Still, despite the dose reduction in mOCS dosage, no significant deterioration was observed in FEV1 and FEF25-75 values.