An open audit of montelukast, a leukotriene receptor antagonist, in nasal polyposis associated with asthma

BACKGROUND: Nasal polyposis occurs frequently in patients with intrinsic asthma, especially in those who are aspirin sensitive. It can be difficult to treat effectively, even with surgery and regular topical intranasal corticosteroids many patients are still symptomatic. OBJECTIVE: To investigate the response to montelukast, a leukotriene D4 receptor antagonist, as an add-on therapy to topical and inhaled corticosteroids in patients, both aspirin sensitive (AS) and aspirin tolerant (AT), with nasal polyposis and asthma. METHODS: Nasal polyposis symptoms were assessed by visual analogue scales; nasal polyps were assessed by nasendoscopy and via the measurement of nasal volumes by acoustic rhinometry. The nasal airway was assessed by nasal inspiratory peakflow (NIPF). Asthma was monitored using symptom scores and peak expiratory flow measurements. Aspirin sensitivity was assessed by history together with intranasal lysine aspirin challenge. Upper and lower airway nitric oxide measurements were made before and during treatment. RESULTS: Clinical subjective improvement in nasal polyposis occurred in 64% AT (P < 0.01), patients and 50% AS patients (P > 0.05); asthma improvement in 87% AT and 61% AS patients (P < 0.05 for both). Objective changes in peak flow occurred only in AT patients (P < 0.05). Acoustic rhinometry, nasal inspiratory peak flow and nitric oxide levels did not change significantly in any group, however, correlations were seen between nitric oxide levels and polyp scores and between nitric oxide levels and acoustic rhinometry changes. Improvement on montelukast therapy was not associated with any of the following variables: age, sex, skin prick test positivity, disease duration or aspirin sensitivity. (P > 0.05 for all). CONCLUSION: The findings are consistent with a subgroup of nasal polyps/asthma patients in whom leukotriene receptor antagonists are effective. This is not related to aspirin sensitivity. Further placebo-controlled studies need to be undertaken.     

Treatment of chronic rhinosinusitis with intranasal amphotericin B: a randomized, placebo-controlled, double-blind pilot trial

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common chronic diseases. Its etiology is unknown, and there is a paucity of effective medical treatments. OBJECTIVE: We tested the hypothesis that intranasal antifungal treatment improves the objective computed tomography (CT) findings (inflammatory mucosal thickening), nasal endoscopy stages, and symptoms of CRS. METHODS: A randomized, placebo-controlled, double-blind, single-center trial used amphotericin B to treat 30 randomly selected patients with CRS. Patients were instructed to instill 20 mL amphotericin B (250 mug/mL) or placebo to each nostril twice daily for 6 months. The primary outcome was a quantitative reduction in inflammatory mucosal thickening on CT scans of a standardized coronal cut. Secondary outcome measures were endoscopic scores, patient symptom scores, and levels of intranasal inflammatory mediators. RESULTS: Twenty-four patients completed the 6 months of treatment. Patients receiving amphotericin B achieved a relative reduction in the percentage of mucosal thickening on CT scans (n = 10; -8.8%) compared with placebo (n = 14; +2.5%; P = .030). Likewise, the changes in the endoscopic scores improved in the amphotericin B group compared with placebo ( P = .038). Between-group comparisons of the changes in the intranasal mucus levels of eosinophil-derived neurotoxin showed a reduction in the amphotericin B group and an increase in the placebo group ( P = .046); levels of IL-5 showed similar tendencies ( P = .082). CONCLUSION: Intranasal amphotericin B reduced inflammatory mucosal thickening on both CT scan and nasal endoscopy and decreased the levels of intranasal markers for eosinophilic inflammation in patients with CRS.     

Evidence-based management of nasal polyposis by intranasal corticosteroids: from the cause to the clinic

Background: Nasal polyposis is an inflammatory disorder involving the mucosa of the nose and paranasal sinuses and affecting approximately 2-4% of the general population. Methods: A literature search of Medline and Embase was conducted to obtain an overview of the epidemiology, pathophysiology, and current treatment of nasal polyposis, focusing on evidence-based efficacy of intranasal corticosteroids (INSs) as primary and postoperative therapy. Recent research on INSs in nasal polyp treatment, along with notable historic findings, was reviewed. Results: Nasal polyps are mostly characterized by eosinophil infiltration, a complex inflammation of nasal mucosa, and possibly production of polyclonal IgE. Current treatment modalities include INSs, oral corticosteroids, and surgery; surgery is generally limited to those with an insufficient response to medical treatment. Because of their effects on eosinophil-dominated inflammation, INSs and oral corticosteroids are the primary medical treatment strategies. The very low (≤1%) systemic bioavailability of newer INSs minimizes the systemic adverse effects seen with oral corticosteroids. Conclusion:Based on randomized, controlled trials, guidelines recommend INSs as first-line therapy for nasal polyps and for care after polypectomy. Clinical data suggest INSs are effective in reducing polyp size and relieving nasal symptoms. INS treatment has also reduced nasal polyp recurrence in patients undergoing functional endoscopic sinus surgery. Treatment with these mainstay options has been found to improve quality of life, which, along with symptom improvement, is a key factor in disease treatment.     

Paradoxical low nasal nitric oxide in nasal polyposis

BACKGROUND: Nitric oxide (NO) is synthesized in the respiratory tract. Three isoforms of NO synthase have been described in man, with the inducible form related to inflammatory disease. In the paranasal sinuses constitutive production of nitric oxide has been demonstrated, with levels of 20-25 p.p.m. being found in sinus puncture. Nasal polyposis is a chronic inflammatory condition in which inducible nitric oxide synthase (iNOS) expression is elevated in nasal polyp epithelium. OBJECTIVES: 1. Measurement of upper airway nitric oxide in nasal polyposis patients compared with those with allergic rhinitis, and with normal controls. 2. To assess the effect of polyp treatment on nasal NO levels. METHODS: NO levels (parts per billion) were measured in nasal and pulmonary exhaled air using a LR 2000 Logan Sinclair nitric oxide gas analyser. This utilizes the chemiluminescence principle. Eighty-two patients were studied: 44 with rhinitis, but without polyps, and 38 with nasal polyps. NO levels were compared with those of 20 normal controls. In 23 further polyp patients, levels were measured pre- and post-treatment and the changes were compared with alterations in polyp size, as assessed by rigid nasendoscopy. RESULTS: Nasal NO levels were significantly lower (Kruskal-Wallis, P = 0.000, chi2 = 27.5, d.f. = 3) in patients with polyps than those found in uncomplicated allergic rhinitis. NO levels were correlated directly with extent of polyposis as graded by the Lund-McKay index. Successful treatment, with reduction in polyp volume, was associated with a rise in NO levels (P = 0.042). CONCLUSION: NO levels are low in nasal polyposis, despite high levels of iNOS, possibly related to blockage of the ostiomeatal complex and failure of NO generated constitutively in the sinuses to reach the nasal airway. A rise in the NO levels is seen with successful polyp treatment, and is proportional to the reduction in endoscopically assessed polyp size, suggesting that with both medical and surgical therapy, the ostiomeatal complex obstruction is decreasing. We propose the following scenario. Nasal NO levels are the result of two processes: inducible NO production by inflamed nasal mucosa plus constitutive sinus mucosal production, detectable in normals. In uncomplicated allergic rhinitis with patent sinus ostia NO levels tend to be elevated, but when inflammation is sufficient to obstruct sinus ostia (as in nasal polyps), NO levels fall because sinus NO makes the major contribution.     

The accuracy of symptom-based definition of chronic rhinosinusitis

OBJECTIVE: Currently, the diagnosis of chronic rhinosinusitis (CRS) is a symptom-based definition. This study aims to study, verify and evaluate the predictive value of the symptom-based definition of CRS and compare this with objective tests. METHODS: Seven hundred and sixty-eight adults, who were referred from primary care centers as patients who met the definition of CRS, were enrolled in the study. The patients were divided into two groups according to their allergic status. The patients were subjected to nasal endoscopy and computed tomography (CT) on the same day. RESULTS: The results showed 73.15% of the nonallergic patients with symptom-based diagnosed CRS and 65.34% of the allergic patients with symptom-based diagnosed CRS had no CT and endoscopic pathology (Endoscopic score 0 + CT score 0). Nasal discharge was the most common major symptom in all patients from both groups who had pathologic endoscopic and/or CT scan scores. CONCLUSIONS: It is well established that symptoms are very important in the diagnosis of CRS. However, two major symptoms are insufficient for diagnosis. Therefore, endoscopy and CT have important differential diagnostic roles. Our study showed that in patients with three major symptoms, CT pathology may be sufficient for definitive diagnosis. However, in patients with two major symptoms such as nasal discharge and/or low grade nasal polyposis, endoscopy becomes considerably more important due to inspective findings. If no endoscopic findings are found, the importance of the CT scans is increased.     

Nasal nitric oxide: longitudinal reproducibility and the effects of a nasal allergen challenge in patients with allergic rhinitis

BACKGROUND: Exhaled nitric oxide (eNO) is a validated noninvasive marker of airway inflammation in asthma. In patients with allergic rhinitis (AR), increased levels of nasal nitric oxide (nNO) have also been measured. However, the applicability of nNO as a marker of upper airway inflammation awaits validation. AIM: To test the longitudinal reproducibility of standardized nNO measurements in patients with AR and the effects of nasal allergen challenge. METHODS: Twenty patients with clinically stable, untreated AR participated in a combined study design. First, reproducibility of nNO was tested over 1, 7, and 14-21 days. Subsequently, the effect of nasal allergen challenge on nNO was studied in a placebo-controlled, parallel design. Nasal NO was measured with a chemoluminescence analyzer. Ten subjects randomly underwent a standardized nasal allergen challenge; 10 subjects received placebo. Response to nasal challenge was monitored by composite symptom scores. RESULTS: There was a good reproducibility of nNO up to 7 days [coefficient of variation (CV) over 1 (16.45%) and 7 days (21.5%)], decreasing over time [CV (14-21 days): 38.3%]. As compared with placebo, allergen challenge caused a significant increase in symptom scores (P < 0.001), accompanied by a decrease in nNO at 20 min postchallenge (P = 0.001). Furthermore, there was a gradual increase in nNO at 7 h, reaching significance at 24-h postallergen (P = 0.04). CONCLUSIONS: Similar to eNO in asthma, nNO is a noninvasive marker, potentially suitable to monitor upper airway inflammation following allergen-induced late response. Present data show a good reproducibility of nNO measurements, decreasing over time, probably because of subclinical seasonal influences.     

Amphotericin B nasal lavages: not a solution for patients with chronic rhinosinusitis

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common chronic diseases. Recently, it has been suggested that an exaggerated immune response to fungi is crucial in the pathogenesis of the disease. On the basis of this hypothesis, intranasal treatment with amphotericin B should benefit patients with CRS. Data from 2 uncontrolled and 2 controlled trials are conflicting, however. OBJECTIVE: To clarify the role of intranasal antifungal drugs in the treatment of CRS, we conducted a large, double-blind, placebo-controlled, multicenter study comparing the effectiveness of amphotericin B nasal lavages with placebo. METHODS: A total of 116 randomly selected patients with CRS were instructed to instill 25 mL amphotericin B (100 microg/mL) or placebo to each nostril twice daily for 3 months. Primary outcomes included a reduction in total visual analog scale (VAS) score and nasal endoscopy score. Secondary outcome measures included peak nasal inspiratory flow, polyp score, quality of life (Short Form-36, Rhinosinusitis Outcome Measure-31), and individual VAS scores. RESULTS: Analysis was based on intention to treat and involved all patients randomly assigned. Mean VAS scores, Short Form-36 and Rhinosinusitis Outcome Measure-31 data, peak nasal inspiratory flow values, nasal endoscopy scores, and polyp scores were similar in both treatment groups at the time of randomization, and no significant differences were observed after 13 weeks of treatment. CONCLUSION: Amphotericin B nasal lavages in the described dosing and time schedule do not reduce clinical signs and symptoms in patients with CRS. CLINICAL IMPLICATIONS: Amphotericin B nasal lavages in the described dosing and time schedule are ineffective and therefore not advised in the treatment of patients with CRS.     

Differentiation of chronic sinus diseases by measurement of inflammatory mediators

Background:  Chronic rhinosinusitis (CRS) clinically is a heterogeneous group of sinus diseases, which may cover different disease entities, or may represent a disease continuum. Studying inflammatory cells and mediators in clearly defined disease subgroups may lead to a better differentiation of chronic sinus diseases.
Methods:  Sinonasal mucosal tissue from 10 nasal polyp (NP) patients, 13 cystic fibrosis patients (CF-NP), eight CRS subjects without polyps, and nine control patients were stained for CD3, CD25, CD68, CD20, myeloperoxidase (MPO), CD138 and tissue homogenates were assayed for eotaxin, interleukin (IL)-1 β , IL-2sR α , IL-5, interferon (IFN)- γ , IL-8, transforming growth factor (TGF)- β 1, tumor necrosis factor- α , and MPO by enzyme-linked immunosorbent assay or UNICAP system.
Results:  Nasal polyp and CF-NP showed increased numbers and activation of T cells, while only NP displayed an increase in plasma cells. Nasal polyp had significantly higher levels of eosinophilic markers [eosinophils, eotaxin, and eosinophil cationic protein (ECP)] compared with CRS, controls and CF-NP. Chronic rhinosinusitis was characterized by a Th1 polarization with high levels of IFN- γ and TGF- β , while NP showed a Th2 polarization with high IL-5 and immunoglobulin (Ig) E concentrations. Nasal polyp and CF-NP were discriminated by edema from CRS and controls, with CF-NP displaying a very prominent neutrophilic inflammation.
Conclusion:  Based on cellular and mediator profiles, we suggest that CRS, NP, and CF-NP are distinct disease entities within the group of chronic sinus diseases.     

Fluticasone propionate aqueous nasal spray provided significantly greater improvement in daytime and nighttime nasal symptoms of seasonal allergic rhinitis compared with montelukast.

BACKGROUND: The safety and efficacy of intranasal corticosteroids for the treatment of allergic rhinitis is well documented in the literature. Additionally, an expert panel has concluded that intranasal corticosteroids are the first line of therapy when obstruction is a major component of rhinitis. Montelukast is a leukotriene receptor antagonist recently approved for the treatment of seasonal allergic rhinitis (SAR). OBJECTIVE: This randomized, double-blind, double-dummy, parallel-group study was conducted to compare the effectiveness of a 15-day course of intranasal fluticasone propionate 200 microg, once daily (FP200QD), to oral montelukast 10 mg, once daily (MON10QD), in relieving daytime and nighttime nasal symptoms associated with SAR. METHODS: The intent-to-treat (ITT) analysis population consisted of 705 eligible males and females (> or = 15 years) with SAR randomized to either FP200QD (N = 353) or MON10QD (N = 352). The primary efficacy endpoint was the mean change from baseline in subject-rated daytime total nasal symptom scores (the sum of four individual scores: nasal congestion, itching, rhinorrhea, and sneezing), evaluated via visual analog scales, and averaged over weeks 1 to 2. Secondary endpoints included the four daytime individual nasal symptom scores, the nighttime total, and individual nasal symptom scores (each evaluated on a four-point scale from 0 to 3). RESULTS: Statistically significant differences favoring FP200QD over MON10QD were observed for the mean change from baseline in daytime total nasal symptom scores (P < 0.001), daytime individual nasal symptom scores (P < 0.001), nighttime total (P < 0.001), and all individual nasal symptom scores (P < or = 0.002) over the 15-day treatment period. FP200QD and MON10QD were both well tolerated. CONCLUSIONS: The results of this well controlled study demonstrated that FP200QD was consistently superior to MON10QD with regard to every efficacy endpoint evaluated, including daytime and nighttime nasal congestion, in subjects with SAR.     

Role of nasal nitric oxide in the resolution of experimental rhinovirus infection

BACKGROUND: Human rhinovirus (HRV) infections are associated with exacerbations of asthma, chronic obstructive pulmonary disease, and sinusitis. Nitric oxide (NO) might play an important role in host defense through its potent antiviral properties. Previous studies have shown that HRV infection in human subjects increased nasal epithelial expression of type 2 nitric oxide synthase (NOS2), an isoform of the enzyme that produces NO. OBJECTIVE: We sought to investigate whether increases in exhaled NO (eNO) would accompany the increased NOS2 expression and would be associated with clearance of the virus. METHODS: Six human subjects were infected with HRV-16 intranasally. eNO from nasal and lower airways was measured by means of direct measurement at multiple controlled flow rates. eNO was monitored at baseline (day 1) and on days 2 to 5, 8, 14, and 42 after infection. Nasal lavages were performed on days 1 to 5 and 8, and nasal scrapings were performed on days 1 to 4. NOS2 mRNA expression in nasal cells was measured by using quantitative real-time RT-PCR. Viral shedding in nasal lavage fluid was monitored by using real-time RT-PCR and bioassay. RESULTS: Peak HRV titers and symptom scores were correlated on day 3, and HRV persisted until day 5 (n=4) or day 8 (n=2). Infection was associated with transient but significant increases in lymphocytes and monocytes in nasal lavage fluid. Significant increases in both nasal and lower airway eNO concentrations accompanied HRV infection and were positively correlated. Increased nasal eNO concentrations on day 3 were associated with increased expression of NOS2 mRNA in nasal scrapings. Symptom scores on day 4 were inversely correlated with the increases in nasal eNO concentration. CONCLUSIONS: We conclude that increased production of NO occurs as part of the host response to HRV infection and speculate that NO plays a beneficial role in viral clearance.     

Subjective and objective markers of treatment response in patients with seasonal allergic rhinitis.

BACKGROUND: Although there is a recognized association between upper and lower allergic airways disease, it is unknown how seasonal allergic rhinitis (SAR) therapy will effect sensitive markers of airway function in patients with no history of asthma. OBJECTIVE: To prospectively evaluate subjective and objective markers of treatment response in 26 patients with SAR who have been screened to exclude a diagnosis of asthma. METHODS: The patients' usual treatment, with antihistamine alone (n = 13) or in combination with intranasal corticosteroid (n = 13), was withheld for 1 week to achieve a baseline and then resumed. Measurements were made after baseline and after 2 and 4 weeks of treatment for nasal peak inspiratory flow rate (nPIFR); airways resistance (Raw) and specific conductance (sGaw); and nasal nitric oxide (NO). Patients reported their symptom (nasal, throat and eye) scores, daily activity scores, and ocular sodium cromoglycate usage over the preceding 24 hours. RESULTS: Compared with baseline, there were significant (P < .05) improvements with nPIFR, symptom scores and cromoglycate usage at 2 and 4 weeks of treatment. There was no significant suppression for NO at 2 or 4 weeks. There was a significant correlation between nPIFR and nasal symptoms (r = -0.52, P < .001). After 4 weeks of treatment there were significant (P < .05) improvements in sGaw (143.3% predicted) and Raw (91.6% predicted) compared with baseline (sGaw: 111.8%, Raw: 104.2% predicted). CONCLUSION: Treatment of SAR improves upper and lower airway parameters but not NO. Nasal PIFR correlates significantly with nasal symptoms.     

Randomized placebo-controlled trial comparing fluticasone aqueous nasal spray in mono-therapy, fluticasone plus cetirizine, fluticasone plus montelukast and cetirizine plus montelukast for seasonal allergic rhinitis

BACKGROUND: Corticosteroids are considered to be particularly effective in reducing nasal congestion and are therefore recommended as first-line treatment in allergic rhinitis patients with moderate to severe and/or persistent symptoms. OBJECTIVE: We compared the clinical efficacy of fluticasone propionate aqueous nasal spray (FPANS) 200 microg given once daily, administered in mono-therapy or combined therapy with a H1 receptor antagonist (cetirizine, CTZ) or with a leukotriene antagonist (montelukast, MSK), and the combined therapy of CTZ plus MSK in the treatment of patients affected by allergic rhinitis to Parietaria during natural pollen exposure. In addition, we examined the effect of the treatment on eosinophil counts and eosinophil cationic protein (ECP) in nasal lavage performed at beginning of season, during season and at the end of the season. METHODS: One hundred patients aged 12-50 years (mean+/-SD 31.8+/-9.6) with a history of moderate to severe Parietaria pollen-induced seasonal allergic rhinitis were selected. A randomized, double-blind, double dummy, placebo (PLA)-controlled, parallel-group study design was used. Patients were treated FPANS 200 microg once daily (n=20) or with FPANS 200 microg once daily, plus CTZ (10 mg) in the morning (n=20), or with FPANS 200 microg once daily, plus MSK (10 mg) in the evening (n=20) or with CTZ (10 mg) in the morning plus MSK in the evening (n=20) or matched PLA (n=20). Assessment of efficacy was based on scores of daily nasal symptoms and on eosinophil counts and ECP in nasal lavage. RESULTS: All treatments showed significant differences (P<0.001) compared with PLA in terms of total symptom, rhinorrhea, sneezing and nasal itching scores. Concerning nasal congestion on waking and daily only the groups treated with FPANS in mono-therapy or in combined therapy showed significant differences compared with PLA. Comparing the group treated with FPANS alone and the groups treated with FPANS plus CTZ, we found significant differences for total symptom score (P=0.04) and for nasal itching (P=0.003). The comparison between FPANS plus CTZ and FPANS plus MSK showed significant difference for nasal itching (P=0.003). Finally, there were significant differences between the group treated with FPANS and the group treated with CTZ plus MSK for total symptom score (P=0.009), for nasal congestion on waking (P<0.001) and nasal congestion daily (P<0.001). Also the comparisons between the group treated with FPANS plus CTZ and the group treated with CTZ plus MSK demonstrated significant differences (P<0.001) for total symptom, for nasal congestion on waking and for nasal congestion on daily, for rhinorrhea (P=0.04) and for nasal itching (P=0.003) scores. Concerning the comparison between the group treated with FPANS plus MSK and the group treated with CTZ plus MSK we found significant differences for total symptom score (P=0.005), for nasal congestion on waking (P<0.001) and for nasal congestion on daily (P<0.001). No other differences were observed between the groups. Concerning blood eosinophil counts, significant differences were found between the treatments with FPANS in mono-therapy or in combined therapy with PLA group during and at the end of the season (P=0.0003 and P<0.0001, respectively). Concerning eosinophils and ECP in nasal lavage, all treatments showed significant differences (P<0.001) compared with PLA. Besides, there were significant differences (P<0.001) between the groups treated with FPANS alone or in combined therapy and the group treated with CTZ plus MSK. CONCLUSION: The results of this comparative study demonstrate that FPANS is highly effective for treating patients affected by allergic rhinitis, with efficacy exceeding that of CTZ plus MSK in combined therapy. In addition, the regular combined therapy of FPANS plus CTZ or plus MSK would not seem to offer substantial advantage with respect to FPANS in mono-therapy in patients affected by seasonal allergic rhinitis.     

Airway function and nasal inflammation in seasonal allergic rhinitis and asthma

BACKGROUND: Allergic rhinitis (AR) and asthma are frequently associated and characterized by a Th2-dependent inflammation. Nasal and bronchial obstruction may be objectively measured. OBJECTIVE: The aim of this study was to evaluate the relationships among upper and lower airway function and nasal inflammation in subjects with seasonal allergic rhinitis (SAR) and asthma. METHODS: Twenty out-patients (12 males and eight females, mean age: 23.4+3.6 years) with SAR and asthma were evaluated during the pollen season. All of them showed a moderate-severe grade of nasal obstruction. Total symptom score, rhinomanometry, spirometry, nasal lavage, and nasal scraping were obtained in all subjects. Eosinophils were counted by conventional staining; IL-4 and IFN-gamma were measured by immunoassay on fluids recovered from nasal lavage. RESULTS: Functional parameters, i.e. nasal airflow and forced expiratory volume in 1 s (FEV(1)), were correlated with nasal eosinophils (R(2)>0.83, P<0.001). Inflammatory parameters, i.e. eosinophils were correlated with immunological parameters, i.e. IL-4 and IFN-gamma levels (R(2)=0.93, P<0.001). Nasal symptoms were correlated with nasal airflow (rho=-0.71, P< or =0.01) and eosinophils (rho=0.72, P<0.01). Nasal airflow was correlated with FEV(1) (r=0.89, P<0.0001). CONCLUSIONS: This study demonstrates the close connection between Th2 cytokines and eosinophil infiltration in the nose. There is also clear evidence concerning the relationships between eosinophils infiltration and cytokines levels. Nasal eosinophils can be regarded as the most important predictors of upper and lower airway functions. These findings constitute first evidence of a relationship among nasal Th2-related inflammation and nasal and bronchial airflow in patients with SAR and asthma.     

Early effects of aspirin desensitization treatment in asthmatic patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin (ASA)-exacerbated respiratory disease (AERD) is characterized by aggressive inflammation of the respiratory tract and often requires topical and/or systemic corticosteroids to maintain partial control of this disease. Previous studies have revealed that ASA desensitization and subsequent treatment with ASA is associated with clinical improvement in AERD. OBJECTIVE: The aim of the present study was to determine the effect of daily ASA treatment for the first 4 weeks after ASA desensitization. METHODS: Thirty-eight patients underwent ASA oral challenge followed by ASA desensitization and daily ASA therapy. Changes in nasal and asthma symptoms, combined with changes in oral prednisone, were recorded daily during 4 weeks before and after desensitization. Severity of symptoms ranged from a scale of 1 to 5 (1 = asymptomatic and 5 = most severe symptoms). For statistical analyses the sum of nasal symptoms and asthma symptoms was calculated. Olfactory scores were also analyzed. RESULTS: Nasal and asthma symptom scores, as well as olfactory scores, improved significantly (P < 0.0001). For the 15 patients taking prednisone, their mean doses decreased from 10.7 to 5.9 mg daily (P = 0.0003). CONCLUSIONS: Our study suggests that ASA desensitization treatment is effective during the first 4 weeks of daily treatment with ASA.     

Depression symptoms and lost productivity in chronic rhinosinusitis

Background

Chronic rhinosinusitis (CRS) is associated with significant losses of patient productivity that cost billions of dollars every year. The causative factors for decreases in productivity in patients with CRS have yet to be determined.

Epithelial–Mesenchymal Transition in Chronic Rhinosinusitis: Differences Revealed Between Epithelial Cells from Nasal Polyps and Inferior Turbinates

The pathogenesis of chronic rhinosinusitis (CRS) remains unclear to date. The tissue remodeling in nasal polyps may be the result of inflammatory mediators and may involve epithelial–mesenchymal transition (EMT) and EMT-associated features such as cell motility in nasal epithelial cells (NECs). We determined whether NEC in nasal polyps of CRS already display features of EMT in vivo or respond with EMT to growth factor stimulation in vitro. Nasal polyp tissues expressed both epithelial and mesenchymal markers. Primary NEC from inferior turbinates and nasal polyps responded to the EMT-inducing agents transforming growth factor (TGF)-β1 and epidermal growth factor (EGF) with different expression patterns of EMT markers (E-cadherin, N-cadherin, Snail, Slug, Twist), however, only NEC from nasal polyps were susceptible to TGF-β1 and EGF-dependent cell migration. Our data suggest that a partial EMT is associated with the pathogenesis of nasal polyps in CRS patients. Furthermore, we show for the first time that epithelial cells from both nasal polyps and inferior turbinates were able to undergo an EMT-like process following exposure to TGF-β1 or EGF in vitro but that only NEC from nasal polyps responded with enhanced cell motility. Our data suggest that NEC from CRS patients have undergo partial EMT and that this process may be involved in the pathogenesis of CRS.

     

Nasal polyposis and its impact on quality of life: comparison between the effects of medical and surgical treatments

BACKGROUND: Nasal polyposis (NP) is not a life-threatening disorder but may have a great impact on the quality of life (QoL). The objective of this study: (i) to investigate the health burden incurred by NP compared with the Spanish general population using the Short Form-36 Health Survey (SF-36) questionnaire; (ii) to compare the QoL outcome after medical or surgical treatment; and (iii) to assess and compare the effect of medical and surgical treatment on nasal symptoms. METHODS: About 109 patients with nasal polyps were included. Fifty-three patients were randomly allocated to receive oral prednisone for 2 weeks and 56 to undergo endoscopic sinus surgery. All patients administered intranasal budesonide for 12 months. Patients were evaluated for nasal symptoms, polyp size, and QoL. RESULTS: In comparison with the Spanish general population, patients with NP had worse scores on all SF-36 domains except for physical functioning. Nonasthmatic patients with NP had better QoL than asthmatic patients with NP on role physical functioning, body pain, and vitality (P <0.05). At 6 and 12 months, a significant improvement on all of SF-36 domains was observed after both medical and surgical treatment reaching the levels of general population (P <0.05). Nasal symptoms and polyp size improved after both medical and surgical treatment at 6 and 12 months (P <0.05). CONCLUSION: These results suggest that NP has considerable impact on a patient's QoL and that both medical and surgical treatment led to similar effects in improving QoL.     

High frequency of macrophages expressing elevated level of CD80, PD-Ls and TLR1 in nasal polyps of CRS patients

Identification of the association between tissue biomarkers, their surrogates in blood and clinical features, could provide new diagnostic tools and facilitate adequate choices of therapeutic interventions for selected patients suffering from CRS. The aim of present study was the assessment of macrophages in the polyp tissue and monocytes in the peripheral blood in the course of CRSwNP, and their functional immunophenotype. We analyzed 31 patients with CRSwNP. Nasal mucosa tissue was obtained via functional endoscopic sinus surgery (FESS). The control group included 10 patients with deviated nasal septum (DNS). Fluorochrome stained cells were proceed to acquisition using FACS Canto flow cytometer, and the results were analyzed using the software FACS Diva. In our study, we observed a significantly higher level of CD80, CD274, CD273 and TLR1 in nasal polyps compared to blood samples from patients with CRSwNP. This finding may suggest the importance of the PD-1 pathway as a therapeutic target in CRS and an important role for TLR1 in nasal polyp formation and maintenance. Our results may provide some insight into potential future targets of recurrent nasal polyp treatment and contribute to a better understanding of the inflammatory process in Chronic Rhinosinusitis.     

Symptoms of persistent allergic rhinitis during a full calendar year in house dust mite-sensitive subjects

BACKGROUND: Little is known about the natural course of persistent rhinitis symptoms over a prolonged period. OBJECTIVE: To describe the frequency and severity of nasal symptoms and quality of life (QoL) in house dust mite-sensitive persistent rhinitic subjects and to determine if medication use was related to symptoms. METHODS: Rhinitics and controls were telephoned fortnightly for 1 year to monitor symptoms. QoL was measured every 3 months. RESULTS: Thirty-seven rhinitics and 19 controls completed the study. Total nasal symptom scores (TNSS) were 'high' for 65% (95% CI +/- 6%) of the year in rhinitic subjects. When TNSS increased by 1, the likelihood of nasal medication use increased by 25% (95% CI: 7-46%). General and specific QoL were worse in rhinitic subjects than controls (P < 0.04 and <0.0001). Rhinitics with pollen allergy (n = 21) had seasonal variation in the frequency of high nasal symptom scores (P = 0.02). CONCLUSION: Nasal symptom scores were consistently high in rhinitics, and their QoL was worse than controls, even in general QoL. An increase in nasal symptom score increased the likelihood of nasal medication use. These findings help to characterize the course of persistent rhinitis over a previously unstudied period of 1 year.