CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-β1 and IL-8

Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.

Successful treatment of nasal polyps with low dose aspirin for asipirin sensitive patients

Aspirin-exacerbated respiratory disease (AERD) represents a severe form of chronic rhinosinusitis (CRS) characterized by nasal polyposis, bronchial asthma and aspirin intolerance. The following syndrome is difficult to manage. In this report, we present a case of hypersensitivity to acetylsalicylic acid (AsA) together with bronchial asthma and nasal polyps. This case proves that desensitization for aspirin is one of the alternative methods of treatment for nasal polyps and aspirin-induced asthma for people hypersensitive to aspirin.

Azithromycin for chronic eosinophilic rhinosinusitis with nasal polyp: a placebo-controlled trial

BACKGROUND: Chronic eosinophilic rhinosinusitis with nasal polyps (CRSwNP eosinophilic) is characterised by the formation of benign and bilateral nasal polyps. We aimed to compare the effectiveness of azithromycin as an immunomodulator with the use of a placebo in patients presenting with CRSwNP concomitant with asthma and aspirin intolerance after 3 months of treatment and at a 1-year follow-up. METHODOLOGY: We performed a randomised, double-blind, placebo-controlled trial. Patients received 500 mg azithromycin orally three times/week for 12 weeks. Improvement was evaluated by staging, the Sino-Nasal Outcome Test (SNOT-22), and nasal polyp biopsy. Data collected at pretreatment and 3 months posttreatment were compared. Quality of life was evaluated at the 1-year follow-up. RESULTS: Twenty-seven and 21 patients were treated with azithromycin and a placebo, respectively. The medication was well tolerated overall. Twenty patients (74%) in the azithromycin group and three patients (14%) in the placebo group were not refer- red for surgery at the end of the 3-month treatment. Regarding subjective improvement, there was a median decrease only in the azithromycin group, and the between-group difference was significant. SNOT-22 improvement was maintained in the azithromy- cin group at the 1-year follow-up. CONCLUSIONS: Azithromycin could be considered a therapeutic option for patients presenting with CRSwNP concomitant with asthma and aspirin intolerance.

Clinical-Cytological-Grading and phenotyping in patients with chronic rhinosinusitis with nasal polyps: the relevance in clinical practice

Chronic rhinosinusitis (CRS) includes two main phenotypes: without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP). CRSwNP may be associated with comorbidity, mainly concerning asthma, aspirin intolerance, and allergy. CRSwNP patients may also be evaluated by clinical-cytological grading (CCG). The current study investigated the prevalence and characteristics of the different CCG and phenotypes in CRSwNP outpatients examined in clinical practice. This retrospective cross-sectional study enrolled 791 consecutive CRSwNP outpatients (424 males, mean age 48.8 years). In the total population, asthma was a common comorbidity (30.8%) as well as aspirin intolerance (24.8%), and allergy (50.8%). As concerns CCG-grading, 210 (26.5%) outpatients had low-grade, 366 (46.3%) medium, and 215 (27.2%) high. As regards cytological phenotypes, 87 (11%) had neutrophilic type, 371 (46.3%) eosinophilic, 112 (14.2%) mast cell, and 221 (27.9%) mixed. High-grade CCG was significantly associated with more frequent asthma, aspirin intolerance, allergy, recurrent surgery, and mixed cytological phenotype. Low-grade CCG was characterized by fewer comorbidities and operations, and neutrophilic phenotype. Therefore, the present study confirmed that CCG is a useful tool in the management of outpatients with CRSwNP. CRSwNP is frequently associated with asthma, aspirin intolerance, and allergy comorbidity. High-grade CCG is frequently characterized by a mixed cytological phenotype, thus, by more severe progress. These real-world outcomes underline that CRSwNP deserves adequate attention for careful management and optimal identification of the best-tailored therapy; CCG and cytological phenotyping could be fruitful tools in clinical practice. Asthma and aspirin intolerance should be adequately investigated in all CRS patients.

Cilostazol for Chinese Patients with Aspirin Intolerance after Coronary Drug-Eluting Stent Implantation

Background Cilostazol-based dual antiplatelet therapy (DAPT) is widely used in patients with aspirin intolerance after coronary drug-eluting stent (DES) implantation in China. However, this empirical strategy is not recommended or even mentioned in Chinese or international guidelines due to a lack of evidence from large-scale studies. We aimed to explore the efficacy and safety of cilostazol-based DAPT in this special population. Methods In this cohort study, patients were grouped according to the DAPT strategy that they received after coronary DES implantation. The primary efficacy endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs). Angiographic follow-up and major bleeding events were also recorded. Results A total of 918 patients receiving cilostazol-based DAPT due to aspirin intolerance were enrolled, matched with 918 patients receiving aspirin-based DAPT. After 15-month prospective follow-up, the cilostazol group had lower risk of MACCE (5.1% vs. 7.6%, propensity score adjusted hazard ratio = 0.671 [95% confidence interval 0.462–0.974], p = 0.036) compared with the aspirin group. Lower rate of coronary lesion progression was also found through follow-up angiography in the cilostazol group (17.4% vs. 23.6%, p = 0.022), especially in nontarget lesions (12.1% vs. 17.6%, p = 0.019). The two groups had the same risk of major bleeding events (0.8% vs. 0.4%, p = 0.364). Conclusion In the current study, cilostazol is a good substitute for aspirin in patients who have aspirin intolerance but need DAPT after coronary DES implantation in China. However, large-scale randomized controlled trials were still required to further confirm its efficacy and safety.

Montelukast Has no Impact on the Systemic Production of TGFβ-1 in Patients with Nasal Polyposis Associated with Aspirin Intolerance

Introduction Nasal polyposis is a disease characterized by a mechanical dysfunction of the nasal mucosa, closely related to the unique makeup of its extracellular matrix, which develops as the result of an anomalous tissue remodeling process.Transforming growth factor beta 1 (TGF-β1) is reduced not only in the nasal polypoid tissue, but also in the plasma of aspirin-intolerant patients. These patients exhibit an imbalance in the production of eicosanoids characterized by an increase in leukotrienes. Thus, it is important that the relationship between the production of leukotrienes and TGF-β1 be assessed. Objective To evaluate the effects of the cysteinyl leukotriene (CysLT) receptor antagonist montelukast on the systemic production of TGF-β1 in patients with nasal polyposis, with or without concomitant aspirin intolerance. Methods The sample comprised 48 individuals with diagnosis of nasal polyposis and 15 healthy controls for comparison of the baseline TGF-β1 levels in the peripheral blood and after treatment with CysLT receptor antagonist montelukast in the nasal-polyposis group. Results There was no difference in the change in TGF-β1 levels after the treatment with montelukast in the subgroup of patients with polyposis and asthma (p = 0.82) and in the subgroup with polyposis, asthma, and aspirin intolerance (p = 0.51). Conclusion we found no impact of the therapy with a leukotriene receptor blocker on the production of TGF-β1, making the antileukotriene therapy a highly questionable choice for the treatment of nasal polyposis, particularly from the standpoint of seeking to modify the remodeling process in this disease.

Analysis of the impact of bronchial asthma and hypersensitivity to aspirin on the clinical course of chronic sinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease with still not enough known pathogenesis despite the development of genetics, immunological and microbiological research. The number of patients with CRS has been constantly growing. The coexistence of CRS, bronchial asthma and aspirin intolerance (aspirin triad) is an adverse prognostic factor with higher risk of recurrences. The aim of study was to compare the severity of CRSwNP depending of coexistence of bronchial asthma and/or aspirin intolerance. The research was performed in the group of 204 patients operated 2009-2013 with 5 years follow-up. Higher nasal polyps growth in groups of patients with aspirin triad and CRSwNP and bronchial asthma in endoscopic examination (p=0,0005 and p=0,0030 respectively) and CT-scan according to Lund-Mackay point scale (p<0,0001 and p=0,0009) was showed. Also, these patients presented increased severity of nasal symptoms before surgical treatment according to VAS scale (p=0,0126 for CRSwNP with bronchial asthma; p=0,0390 for aspirin triad). Similarly, 6 months after surgery the same groups of patients presented higher severity of the disease symptoms (p<0,0001 for aspirin triad’ patients; p=0,0174 for CRSwNP and bronchial asthma’ patients) . Patients with aspirin triad had also statistically more surgeries in past (p=0,001), what proves that recurrences in this group are very likely to be observed in spite of the use of proper conservative treatment. No such differences have been shown in the group of patients with CRSwNP and isolated aspirin intolerance (without bronchial asthma). Allergy to inhaled allergens, hypersensitivity to aspirin are factors significantly worsening the course of CRSwNP. It would be advisable to consider, despite a lack of history of aspirin intolerance, a hypersensititvity to aspirin test in patients with particularly severe CRSwNP, especially those associated with bronchial asthma. It also seems reasonable to carry out such a test on every patient with newly diagnosed CRSwNP and bronchial asthma in order to be able to plan further treatment in this group of patients accordingly including biological treatment with antimonoclonal therapy against interleukin 4, 5 or13.