Oxidative stress in nonallergic nasal polyps associated with bronchial hyperresponsiveness

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of upper airway with unknown etiology. NP is frequently associated with asthma; the interaction between these comorbidities remains interesting. Oxidative stress has been implicated in the pathophysiology of NP and asthma. The aim of this study is to investigate the significance of oxidative stress in sinonasal microenvironments by evaluating its association with clinopathological parameters and its impacts on the pathogenesis of bronchial hyperresponsiveness (BHR) in NP. METHODS: Polyp biopsy specimens were obtained from 20 nonallergic patients; control mucosas were obtained from 20 volunteers. The levels of free radicals in the tissues and in blood were determined by a sensitive chemiluminescence (CL) method. NP patients were substratified into three subgroups, NP without BHR, NP with asymptomatic BHR, and NP with BHR and asthma by the results of provocative testing. Four histological characteristics of NP, inflammatory cells, eosinophil infiltration, edema and fibrosis were estimated and applied to correlate with the tissue-CL. RESULTS: The mean CL level in polyp-tissues, but not in blood, was higher than in the control specimens. In NP patients, tissue-CL was associated with endoscopy score; high tissue-CL levels were positively correlated with the abundance of inflammatory cells and eosinophils. Tissue-CL and endoscopy score were associated with BHR/asthma phenotype. CONCLUSION: These results suggest an important role for oxidative stress in the pathophysiology of NP and a causal relation between oxidative stress and inflammatory cells, especially the eosinophils. Free radical levels in polyp-tissues associated with NP severity and with BHR/asthma phenotype in nonallergic NP patients.     

Distinct features of chronic rhinosinusitis with and without nasal polyps

BACKGROUND: Based on the presence of nasal polyps on endoscopy, chronic rhinosinusitis (CRS) may be clinically divided in CRS with nasal polyps and CRS without nasal polyps. It is unclear, whether CRS with nasal polyps and CRS without nasal polyps represent different disease entities or just different stages of one single disease. In case of one disease, only minor histopathological differences between CRS with small early-stage polyps (CRSNP((+))) and CRS without nasal polyps (CRSNP(-)) were expected. METHODS: Patients with CRSNP((+)) confined to the infundibular region or CRSNP(-) were selected. Histochemical and immunohistochemical characterization of ethmoidal mucosa was performed on formalin-fixed and paraffin-embedded tissue specimens. Frequency and distribution of eosinophils, neutrophils, mast cells, IgE(+) cells, macrophages, B- and T-cell subsets, natural killer cells, plasma cells and goblet cells were assessed. In addition, the thickness of the basal membrane was evaluated. RESULTS: Nine CRS patients without detectable polyps, and 11 patients with small early-stage polyps confined to the infundibular region were selected. Despite adjacent polyp stage, the amount of round cell infiltration (P < 0.05), number of eosinophils (P < 0.05), and plasma cells (P < 0.01) significantly differed in the ethmoidal specimens from patients of the two groups. CONCLUSION: Substantial histopathological differences were observed in ethmoidal mucosa of CRSNP((+)) and CRSNP(-) patients. Thus, the results of this investigation support the concept that CRS with nasal polyps and CRS without nasal polyps are two different disease entities rather than different stages of one single disease, but may also be interpreted as a higher degree of inflammation.     

Nasal inflammation and bronchial reactivity to methacholine in atopic children with respiratory symptoms

BACKGROUND: In atopic subjects, dysfunctions of the upper and lower airways frequently coexist and allergic rhinitis seems to constitute a risk factor for the occurrence of asthma in predisposed individuals. AIM OF THE STUDY: To evaluate whether in atopic subjects nasal inflammation could reflect changes in respiratory functions, 11 allergic children, sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and 10 nonatopic controls (ctrs) were studied. METHODS: All subjects underwent nasal brushing to detect percentages of nasal eosinophils (Eos %) and intercellular adhesion molecule-1 (ICAM-1) expression by nasal epithelial cells. In the same day pulmonary function tests, i.e. forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flows at 25-75% of the vital capacity (FEF25-75%) and methacholine (MCh) bronchial inhalation challenge were also evaluated. RESULTS: Pulmonary function parameters were not significantly different in allergic children and in ctrs (P > 0.05), while a significant increase in bronchial reactivity to MCh, expressed as Pd20 MCh, was detected in the former population (P < 0.05). As compared with ctrs, allergic children showed elevated Eos % and ICAM-1 expression (P < 0.05). When nasal inflammation and pulmonary function parameters were compared, a significant correlation was found between nasal Eos % and bronchial reactivity to MCh (P = 0.002). CONCLUSIONS: These data support the concept of significant links between upper and lower respiratory tract involvement in atopic children sensitized to HDM.     

Immunological mechanisms underlying chronic rhinosinusitis with nasal polyps

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and quality-of-life impacting disorder, with an underlying immunological mechanism similar to other conditions such as eosinophilic asthma or atopic eczema.

Areas covered: This review article summarizes the most recent evidence on the main immunological mechanisms involved in the pathogenesis and the perpetuation of CRSwNP, with a particular focus on the key role of epithelium-derived inflammation as a consequence of the interaction with the airborne environment.

Expert commentary: The increase in knowledge of the immunology of CRSwNP leads to the development of therapeutical strategies based upon the use of biologic agents that, according to a personalized and precision medicine approach, will provide each single patient with the most suitable immunological treatment.     

Topical nasal lysine aspirin in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis with nasal polyposis

Chronic rhinosinusitis patients with nasal polyps can be aspirin sensitive or aspirin tolerant. The majority belong to the latter group. They tolerate intake of aspirin or other non-steroidal anti-inflammatory drugs, whereas aspirin-sensitive patients have an adverse reaction (asthma, rhinitis and/or urticaria). Diagnosis of aspirin sensitivity is important for the patient, but is rarely undertaken in routine ENT or respiratory medicine practice. Treatment of nasal polyps is by a combination of medical therapy and surgery. Oral and topical steroids form the mainstay of medical therapy, which is aimed at reducing inflammation and symptom improvement. Surgery helps with polyps causing severe nasal obstruction. Despite these therapies, recurrences are common in aspirin sensitive patients. Any adjunctive therapy to prevent or prolong recurrence would be welcome. One such possibility is topical nasal lysine-aspirin. This is an area under current debate and this non-systematic review aims to provide evidence of its use, to date, in aspirin sensitive and aspirin tolerant nasal polyp patients.     

Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine

Nasal polyp tissue which contains mast cells and eosinophils is similar to the inflamed airway mucosa in cellular composition and mediator content. This investigation assessed the effect of desloratadine (DL), on activation of cells in nasal polyp tissue. Polyps were obtained from 22 patients with chronic rhinosinusitis [nine aspirin acetylosalitic acid (ASA)-sensitive and 13 ASA-tolerant]. Polyp tissue was dispersed by digestion, and preincubated with DL and incubated with anti-immunoglobulin E (IgE) or calcium ionophore. LTC4, eosinophil cationic protein (ECP) and tryptase concentrations in supernatants were measured by immunoassays. Desloratadine (1, 10 and 50 microM) inhibited calcium ionophore-induced LTC4 release by a mean of 29%, 50% and 63% respectively, and anti-IgE-induced LTC4 release by a mean of 27%, 35% and 39% respectively. Calcium ionophore-induced tryptase release was inhibited 60% and 69% by 10 and 50 microM of DL, respectively, and anti-IgE-induced tryptase release was inhibited 33%, 47% and 66% for 1, 10 and 50 microM of DL. Desloratadine 10 microM and 50 microM inhibited ECP release by and 45% and 48% respectively. Polyp tissue from ASA-sensitive patients when compared with ASA-tolerant patients released at baseline significantly more ECP (medians 120.0 microg/ml, range: 69.0-182.0 vs 63.4 microg/ml, range: 3.7-172.0; P <0.05), but similar amounts of tryptase and LTC4. This study demonstrated that DL inhibits activation of both eosinophils and mast cells derived from a site of airway mucosal inflammation.     

Genetics and phenotyping in chronic sinusitis

Chronic sinusitis with nasal polyposis historically has been treated as a single monolithic clinical disorder. Just as asthma is now accepted as numerous heterogeneous diseases, chronic sinusitis should also be viewed as comprising several diseases with varying causes, with each one characterized by distinct histologic and gene and protein expression patterns. This includes recognition of the need to define these diseases based on the presence or absence of an eosinophilic infiltrate but also on additional distinctions based on unique agents that drive their development and perpetuation. As a collection of heterogeneous diseases, proper differential diagnosis is required to delineate appropriate therapeutic intervention. This review will focus on recognized distinct presentations of chronic sinus disease, including distinguishing the clinical presentations, cellular and molecular characteristics, genetic differences, and current treatment options for each.     

Nasal biomarker profiles in acute and chronic rhinosinusitis

BACKGROUND: Clinical manifestations of rhinosinusitis include acute rhinosinusitis, chronic rhinosinusitis (CRS) with nasal polyps and CRS without polyps. OBJECTIVE: Possible mechanisms defining these three forms of rhinosinusitis should be investigated assessing biomarker profiles in nasal secretions. METHODS: Fifteen cytokines, three cellular activation markers and total IgE were determined in nasal secretions of seven patients with acute rhinosinusitis, 12 patients with CRS without polyps, 13 patients with CRS with polyps and six healthy controls. Principal component analysis was used to extract relevant factors. RESULTS: Irrespective of the clinical manifestation, all biomarkers assessed were increased in patients with rhinosinusitis when compared with controls (P<0.001). Principal component analysis allowed the extraction of three factors explaining 83% of data variance. The general inflammatory activation was mainly reflected by the first factor. The second factor differentiated acute from CRS. This factor correlated with IL-12, which is involved in pathogen-related immune activation by antigen-presenting cells. It was also positively correlated with IL-4, IL-10 and IL-13, which play an important role in the resolution of infections. The third factor differentiated CRS with polyps from CRS without polyps (P=0.001). It represented IL-5 and nasal IgE (nIgE), whereas eosinophil cationic protein and tryptase were not specific for CRS with polyps. CONCLUSION: In mucosal infection, numerous inflammatory mediators are activated. Simple correlations of few biomarkers with a specific disease process bear the risk of overestimating a possibly unspecific effect. To assess biomarker profiles, more complex analytic tools may be more appropriate to delineate mechanisms underlying mucosal disease. Using principal component analysis, it was found that high nIgE and IL-5 levels are specific for CRS with nasal polyps.