montelukast and Nasal-Polyps

Topics: Acetates; Chronic Disease; Cyclopropanes; Humans; Leukotriene Antagonists; Nasal Polyps; Quinolines; Rhinitis; Sinusitis; Sulfides

This review focuses on the role of cysteinyl leukotrienes (cysLTs) in nasal allergy. The purpose was to provide knowledge of the role of cysLTs in the pathophysiology of nasal allergy and the role of antileukotrienes in the treatment of nasal allergies. Materials and methods We conducted a literature review.. The proinflammatory effects of cysLTs have been well described in asthma. Antileukotrienes have proved to be an effective anti-inflammatory treatment for asthma patients. Similar to pathogenesis of asthma, cysLTs exert potent inflammatory effects in the upper airways and play a role in the pathogenesis of allergic rhinitis and other nasal allergies.. Antileukotriene treatment appears to be beneficial in nasal allergies. Allergic rhinitis is a complex, IgE-mediated inflammatory disease of the upper airways. It is the most common allergic disease, occurring in 10% to 30% of adults and up to 30% of children. It may be perennial or seasonal. Sneezing, itching, watery rhinorrhea, and nasal obstruction are classic symptoms. It may impair cognition, school/work performance and productivity, behavior, mood, and quality of life. On physical examination, clear secretions, nasal congestion, pink-bluish nasal mucosa, the allergic salute, and allergic shiners may be detected. Allergic rhinitis is a common comorbid condition with asthma, sinusitis, otitis media, nasal polyposis, and respiratory infections.

Topics: Acetates; Anti-Allergic Agents; Collagen; Cyclopropanes; Eosinophils; Goblet Cells; Humans; Immunoglobulin E; Interleukin-4; Leukotriene Antagonists; Leukotrienes; Loratadine; Mucociliary Clearance; Nasal Mucosa; Nasal Polyps; Quinolines; Rhinitis, Allergic, Perennial; Sulfides

Eosinophils and mast cells are among the key cells in inflammatory diseases like chronic rhinosinusitis (CRS) and asthma. Leukotriene antagonists have proven to be effective in the treatment of asthma, but data about their efficacy in CRS are scarce, whereas data on montelukast as an add-on treatment to intranasal corticosteroids (INCS) in a postoperative setting are completely lacking.. Prospective, randomized, open-label trial.. In this trial with long-term follow-up, we evaluated the efficacy of montelukast as an add-on treatment to INCS in postoperative CRS with nasal polyp (CRSwNP) patients. CRSwNP patients (N = 72) undergoing endoscopic sinus surgery were randomized in two arms for the postoperative treatment. One group (N = 36) received INCS in monotherapy, whereas the other group (N = 36) received INCS in association with montelukast for 1 year. The efficacy of montelukast with INCS was evaluated by assessing both subjective (total five-symptom score [T5SS]) and objective (nasal polyp score [NPS], Lund-Mackay [LMK] score, and subjective olfactometry [Barcelona Smell Test 24]) outcome parameters and compared with the gold standard of INCS in monotherapy.. After 1 year of surgery, T5SS, NPS, and LMK score were significantly reduced in patients treated with either INCS or INCS plus montelukast, without significant differences between the two treatment arms. Improvement of smell loss by olfactometry was also observed with no differences between arms. Similar findings were observed at 3 and 6 months.. These results suggest that the addition of montelukast to INCS should not be recommended in the treatment of postoperative CRSwNP patients.. 1b Laryngoscope, 1743-1751, 2018.

Topics: Acetates; Administration, Intranasal; Adrenal Cortex Hormones; Adult; Aged; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Endoscopy; Female; Follow-Up Studies; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Paranasal Sinuses; Postoperative Period; Prospective Studies; Quinolines; Rhinitis; Sinusitis; Sulfides; Treatment Outcome

Cysteinyl leukotriene (LT) has been proposed in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study sought to examine the expression of the LT receptor (LTR) in CRSwNP patients and evaluate the potential role of LTR antagonist (LTRA) in the management of eosinophilic CRSwNP (ECRS) patients.. Nasal polyps and uncinate process tissues were collected from 18 ECRS patients, 13 non-eosinophilic CRSwNP (non-ECRS) patients, and 16 control subjects. The messenger RNA (mRNA) and protein expression of LTR (cysteinyl leukotriene receptor 1 [CysLT1R] and cysteinyl leukotriene receptor 2 [CysLT2R]) was examined using quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, and Western blot analysis. Moreover, the effects of LTRA and steroids on total nasal symptom scores (TNSS) of uncontrolled ECRS patients were evaluated.. The mRNA and protein expression of CysLT1R and CysLT2R was significantly increased in polyp tissues compared with healthy controls (p < 0.05). Compared with the non-ECRS subset, the ECRS subset showed significantly increased expression of CysLT1R and CysLT2R, as well as leukotriene C4 (LTC4) and leukotriene D4 (LTC4) levels (p < 0.05). Moreover, combined LTRA and steroids significantly decreased TNSS more than steroids alone in uncontrolled ECRS patients (p < 0.01).. Our findings indicate that LTR was differentially expressed between ECRS and non-ECRS patients, and that LTRA may be used as an additional therapy for ECRS patients.

Topics: Acetates; Adult; Anti-Inflammatory Agents; Biomarkers; Blotting, Western; Budesonide; Case-Control Studies; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Eosinophils; Female; Humans; Leukotriene Antagonists; Leukotrienes; Male; Middle Aged; Nasal Polyps; Prospective Studies; Quinolines; Receptors, Leukotriene; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis; Sinusitis; Sulfides; Treatment Outcome

The aim of our study was to compare the effects of montelukast and mometasone furoate nasal spray on the postoperative course of patients with nasal polyposis.. Fifty patients diagnosed with nasal polyposis between March 2006 and August 2007 were included in the study. All patients underwent bilateral endoscopic sphenoethmoidectomy and were randomized postoperatively into two groups. Group A (n = 25) received 10 mg montelukast per day and group B (n = 25) received 400 µg mometasone furoate nasal spray twice daily. All patients were followed up for 6 months. Sino-Nasal Outcome Test (SNOT)-22 scores, polyp grades, computerized tomography (CT) scores (Lund-Mackay), eosinophils in peripheral blood and polyp tissue were evaluated before and after surgery.. There was a significant reduction in SNOT-22 scores in both groups throughout the study period. There was a significant difference in the recurrence rate between both groups with a marginal advantage of mometasone furoate nasal spray. Eosinophils in peripheral blood were found to be effective on the recurrence rate (p < 0.05).. In conclusion, both drugs seem to have a complementary action and further studies are needed to determine which patients should receive which treatment.

Topics: Acetates; Administration, Intranasal; Adult; Aged; Anti-Inflammatory Agents; Cyclopropanes; Endoscopy; Eosinophils; Ethmoid Sinus; Female; Follow-Up Studies; Humans; Leukotriene Antagonists; Male; Middle Aged; Mometasone Furoate; Nasal Polyps; Nasal Sprays; Pregnadienediols; Prospective Studies; Quinolines; Secondary Prevention; Sphenoid Sinus; Sulfides; Tomography, X-Ray Computed; Treatment Outcome

Leukotrienes, especially LTC4, are important inflammatory mediators in allergic and nonallergic inflammation of the entire airways. Of particular interest are numerous theories regarding the pathogenesis of aspirin intolerance with subsequent hyperproduction of leukotrienes and inhibition of cyclooxygenase.. To examine the influence of the cysteinyl-leukotriene receptor antagonist montelukast on clinical symptoms and inflammatory markers in nasal lavage fluid in patients with bronchial asthma and nasal polyps, and determine its dependency on aspirin sensitization.. Twenty-four patients (7 women, 17 men; median age, 55.5 years) with nasal polyps and controlled asthma (n=12 with aspirin intolerance) were treated with 10 mg montelukast once daily for 6 weeks in a blinded, placebo-controlled fashion. The placebo phase was randomly assigned 4 weeks before (n=12) or after treatment (n=12). Symptom score, rhinoendoscopy, rhinomanometry, smears for eosinophils, and nasal lavages for the determination of different mediators were performed.. Compared to placebo, there were significant improvements in the nasal symptom score and airflow limitation as well as a reduction in the inflammatory mediators in nasal lavage fluid after treatment. Furthermore, reduced eosinophils in nasal smears and peripheral blood were observed 2 and 6 weeks after treatment.. Leukotriene 1 receptor blockade led to a significant decrease in eosinophil inflammation accompanied by a reduction in other mediators such as neurokinin A and substance P in the nasal lavage fluid of patients with nasal polyps and asthma, with or without aspirin intolerance.

Topics: Acetates; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Asthma, Aspirin-Induced; Cell Count; Cyclopropanes; Cysteine; Eosinophils; Female; Humans; Leukotriene Antagonists; Leukotrienes; Male; Middle Aged; Nasal Lavage Fluid; Nasal Polyps; Neurokinin A; Quinolines; Substance P; Sulfides; Treatment Outcome

Chronic rhinosinusitis associated with asthma is often difficult to treat effectively with intranasal corticosteroids alone. Thus, the aim of this study was to evaluate the effectiveness of combination treatment with an intranasal corticosteroid and a leukotriene-receptor antagonist (montelukast) in reducing the size of nasal polyps.. The subjects of this study were 20 patients with chronic rhinosinusitis associated with adult-onset asthma, which was being treated with inhaled corticosteroids. All patients were treated with intranasal fluticasone propionate, 200 microg/day, and montelukast, 10 mg/day, for 1 year. The size of nasal polyps and the score of sinus shadows were assessed with nasal endoscopy and computed tomography (CT), respectively, before and after treatment. The peripheral blood eosinophil counts were also evaluated before and after treatment.. Nasal polyps were significantly smaller after both 6 months (p<0.01) and 12 months of treatment (p<0.01) than before treatment. The decrease in the shadow score was statistically significant after both 6 months (p<0.01) and 12 months of treatment (p<0.01). Significant reductions in peripheral blood eosinophil counts were also seen after both 6 months (p<0.05) and 12 months of treatment (p<0.01). A significant correlation was found between the rate of change in the peripheral blood eosinophil count and that in the CT score after both 6 months (r=0.578, p=0.012) and 12 months (r=0.625, p=0.007).. Combined treatment with intranasal fluticasone propionate and montelukast, for at least 1 year, is effective for chronic rhinosinusitis associated with adult-onset asthma.

Topics: Acetates; Administration, Intranasal; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Anti-Allergic Agents; Asthma; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Eosinophils; Female; Fluticasone; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Quinolines; Rhinitis, Allergic, Perennial; Sinusitis; Sulfides; Tomography, X-Ray Computed; Treatment Outcome

To examine the potential of montelukast, a leukotriene receptor antagonist, as an adjunct to oral and inhaled steroid in subjects with chronic nasal polyps.. Prospective, randomized controlled trial.. Thirty-eight consecutive adult patients with bilateral nasal polyps were randomized into two groups. Eighteen subjects were treated with oral prednisolone for 14 days and budenoside nasal spray for 8 weeks. Twenty subjects received similar treatment with additional oral montelukast for 8 weeks. Subjects completed a modified nasal ICSD symptom score at 8 and 12 weeks after beginning treatment and the SF-36 quality of life questionnaire at 12 weeks.. Symptom scores improved in both groups after treatment. Subjects treated with montelukast reported significantly less headache (P = 0.013), facial pain (P = 0.048) and sneezing (P = 0.03) than controls. Four weeks after completing treatment, no significant differences were recorded.. Montelukast therapy may have clinical benefit as an adjunct to oral and inhaled steroid in chronic nasal polyposis, but effects are not maintained after cessation of treatment.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adult; Aged; Aged, 80 and over; Budesonide; Cohort Studies; Cyclopropanes; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Prednisolone; Quinolines; Sulfides; Treatment Outcome

Sulfido-Leukotrienes are important inflammatory mediators of bronchial asthma, intolerance of acetylsalicylic acid (ASA), polyposis nasi and allergic rhinitis. Receptorantagonists like Montelukast constitute a well-established asthma- and ASA intolerance-therapy. The aim of our study was to evaluate changes in patients Health-Related-Quality-of-Life (HRQL) during Montelukast-monotherapy of nasal polyposis.. The study was performed in a prospective, double blind and placebo-controlled matter. The study included 30 patients of our ENT outpatient's dept. (77 % male, mean age 49 yrs), suffering from nasal polyposis grade II to IV. Polyps were endoscopically graded, nasal Eosinophilic Cationic Protein (ECP) was measured, and HRQL-score was taken prior to and four weeks after Montelukast-(0 - 0 - 10 mg) compared to placebo. An established HRQL-questionnaire - including 25 items, summarized in 6 symptom-groups - was used. Given was a symptom-score of 1 (not troubled) to 4 (extremely troubled).. Patients treated with Montelukast improved their nasal symptoms (Delta HRQL-score 0.58 +/- 0.94, P < 0.01), practical problems (Delta HRQL-score 0.42 +/- 0.71, P < 0.05), headaches (Delta HRQL-score 0.38 +/- 0.56, P < 0.05), non-nasal symptoms (Delta HRQL-score 0.35 +/- 0.92, P < 0.05), sleep (Delta HRQL-score 0.26 +/- 0.71) and emotional problems (Delta HRQL-score 0.18 +/- 0.75). Intranasal ECP (Delta 210.67 ng/ml +/- 332.68) and polyp grading (Delta 0.72 +/- 1.77) tended to improve as well, but did not reach statistical significance. Patients treated with placebo revealed no significant changes neither in HRQL-score, ECP, nor polyp grading.. Montelukast-therapy of nasal polyposis significantly improved patient's HRQL in 4 out of 6 symptom-groups. Measuring HRQL proofed to constitute a more sensitive tool than looking at eosinophilic parameters of inflammation or polyp size.

Topics: Acetates; Cyclopropanes; Data Interpretation, Statistical; Double-Blind Method; Eosinophil Cationic Protein; Female; Follow-Up Studies; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Mucosa; Nasal Polyps; Placebos; Prospective Studies; Quality of Life; Quinolines; Sensitivity and Specificity; Sulfides; Surveys and Questionnaires; Time Factors; Treatment Outcome

This was a prospective double blind comparative study on 40 patients. It compared the effects of the leukotriene receptor antagonist montelukast and beclomethasone nasal spray on the post-operative course of patients with sinonasal polyps. All patients underwent endoscopic sphenoethmoidectomy and were randomized post-operatively into two groups. Group I: 20 patients (9 females and 11 males) age 17 to 67 (32.4 +/- 9.5 years), receiving 10 mg montelukast orally daily and Group II: 20 patients (6 females and 14 males) age 17 years to 57 years (33.5 +/- 11.9 years), receiving 400 ug beclomethasone local sprays daily. All patients were followed up for 1 year and a symptom score was recorded throughout this period. There was a significant reduction in symptom scores in both groups throughout the study period. In the montelukast group improvement was more marked in itching, post-nasal discharge and headache. The control of sneezing and rhinorrhea was comparable in both groups with a marginal advantage of montelukast. Steroids had a more marked effect on smell disturbances and obstruction. There was no difference in the recurrence rate or in the need for rescue medications between both groups. Both drugs seem to have a complementary action and further studies are needed to determine which patients should receive which treatment.

Topics: Acetates; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Beclomethasone; Chi-Square Distribution; Cyclopropanes; Double-Blind Method; Female; Glucocorticoids; Headache; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Olfaction Disorders; Postoperative Care; Postoperative Complications; Prospective Studies; Pruritus; Quinolines; Sneezing; Sulfides

Twenty-four consecutive patients with symptomatic nasal polyposis and nonallergic or perennial rhinitis who were undergoing chronic nasal steroid therapy were prospectively evaluated for response to adjunctive oral montelukast sodium therapy.. The patients were undergoing daily intranasal steroid sprays for a minimum of 6 months before being started on montelukast sodium 10 mg by mouth per day for 3 months while intranasal steroids were continued. The patients were given a validated symptom score survey at the start and end of therapy, with a lower score indicating fewer symptoms. The nasal polyps were submitted to biopsy before and after treatment to determine their degree of eosinophilia. Eosinophilia was graded in a blinded fashion by an independent pathologist on a scale of 0 to 3, with 3 being severe. Patients with seasonal allergies were excluded, and the studied patients were treated during the winter season to avoid confounding by potential seasonal allergic responses.. The patients tended to improve on montelukast therapy in terms of their symptom scores and polyp eosinophil counts. The symptoms improved in 17 patients (71%) and remained the same or worsened in 7 patients (29%). The symptom score for the group improved from a pretreatment value of 33.4 (SD, 7.73) to a posttreatment value of 23.3 (SD, 13.73; p < .001). In addition, the eosinophilia score improved from 2.3 (SD, 0.68) to 1.5 (SD, 0.82; p < .01). The improvement was most noticeable in the patients with perennial allergies.. These results suggest that montelukast appears to be beneficial for some patients with nasal polyposis. Patients with perennial allergies and nasal polyposis seem more likely to respond to the treatment than those with nonallergic nasal polyposis.

Topics: Acetates; Administration, Intranasal; Biopsy; Cyclopropanes; Eosinophilia; Humans; Leukotriene Antagonists; Nasal Polyps; Prospective Studies; Quinolines; Sulfides; Treatment Outcome

AERD (aspirin-exacerbated respiratory disease) is a severe form of an inflammatory disease of the upper airway system. Therapy remains challenging due to a complex underlying pathophysiology.. To evaluate the efficacy of postoperative antileukotriene therapy concerning recurrence of nasal polyposis in patients with AERD and to compare it with AD (aspirin desensitization) over time.. In this retrospective study we analyzed AERD patients (N = 61) after functional endoscopic sinus surgery (FESS). Patients were treated at our institution postoperatively with topical mometasone (control group, N = 22), leukotriene-receptor-antagonists (montelukast [MT], N = 18) or underwent an aspirin desensitization (N = 21). Subjective parameters as assessed by SNOT (sinonasal outcome test) questionnaire and endoscopic endonasal examination (polyposis grading) were evaluated throughout a follow-up period of 6-9 and >12 (long-term) months after surgery.. Endoscopic endonasal examinations 6-9 months after sinus surgery showed a good disease control in all 3 groups with significant reduction in polyp grading in the AD group. After a follow-up period of more than 12 months, MT and AD patients had significantly less polyp recurrences as compared to the topical treatment group. Subjective sinonasal symptoms revealed that hyposmia and nasal obstruction were prominent factors in all 3 groups throughout the follow-up period. MT group showed significant improvement in sinonasal symptoms over time.. Postoperative treatment with leukotriene-receptor-antagonists and aspirin desensitization both significantly reduce nasal polyp recurrence. MT has a positive effect on subjective sinonasal outcomes and patients' quality of life over time.

Topics: Acetates; Adult; Aged; Allergens; Aspirin; Asthma, Aspirin-Induced; Cyclopropanes; Desensitization, Immunologic; Endoscopy; Follow-Up Studies; Humans; Leukotriene Antagonists; Middle Aged; Nasal Polyps; Postoperative Period; Quality of Life; Quinolines; Retrospective Studies; Rhinoplasty; Sulfides; Treatment Outcome

Leukotriene signaling is essential in many diseases, including asthma, allergic rhinitis, atherosclerosis and inflammatory bowel disease. Nevertheless, the expression of cysteinyl leukotrienes (CysLTs) and its receptors (CYSLTRs) in different types of nasal polyps (NPs), and the role of their antagonist in the treatment of refractory chronic rhinosinusitis with nasal polyps (CRSwNP) are not well understood. The following study investigates the expression of CysLTs and CYSLTRs in different types of NPs, as well as the role of leukotriene receptor antagonist (montelukast) in refractory NPs. Our data showed that CysLTs and CYSLTRs were significantly elevated in CRSwNP group (p < 0.05), particularly in IL-5

Topics: Acetates; Adult; Cyclopropanes; Cysteine; Cytokines; Enterotoxins; Female; Gene Expression Regulation; Humans; Leukotriene Antagonists; Leukotrienes; Male; Middle Aged; Nasal Polyps; Quinolines; Receptors, Leukotriene; Sinusitis; Sulfides

Topics: Acetates; Adult; Cyclopropanes; Endoscopy; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Pilot Projects; Quinolines; Sulfides

Aspirin-exacerbated respiratory disease (AERD) has been recognized in adults with chronic asthma. Samter's triad is a subset of AERD where adult patients develop nasal polyps, asthma, and sensitivity to aspirin. This condition is thought not to occur before the third decade of life. We report a 13-year-old boy with nasal polyps who suffered a life-threatening exacerbation of asthma during a graded aspirin challenge. Resuscitation required positive pressure ventilation and inotropic support. Our observations confirm that classical Samter's triad can occur in children. We suggest that graded aspirin challenges in children are undertaken in a facility with equipment and staff trained for resuscitation. Consideration should be given to this rare complication when prescribing nonsteroidal anti-inflammatory drugs in the perioperative period. Suspicion of this condition merits referral to an immunologist for desensitization to aspirin.

Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma; Asthma, Aspirin-Induced; Bronchodilator Agents; Cranial Sinuses; Critical Care; Cyclopropanes; Epinephrine; Humans; Male; Nasal Polyps; Quinolines; Respiration, Artificial; Respiratory Tract Diseases; Sulfides; Tomography, X-Ray Computed

To determine whether MUC gene expression could be down-regulated in nasal polyps by the leukotriene receptor antagonist montelukast, we developed a system in which nondisrupted human nasal polyps could be successfully implanted into severely immunocompromised mice, and in which the histopathology of the original nasal polyp tissue could be preserved for long periods. In addition, the histopathologic changes in the human nasal polyps were carefully examined to determine the origin of the submucosal glands (SMGs) that develop in true nasal polyps found in the anterior third of the nose.. Small, nondisrupted pieces of human nasal polyp tissues were subcutaneously implanted into NOD-scid IL-2rgamma(null) mice. Xenograft-bearing mice were treated with either montelukast or saline solution. Xenografts at 8 to 12 weeks after implantation were examined histologically, and expression of MUC genes 4, 5AC, and 7 was studied in the polyps before implantation and in the 8-week xenograft. Alzet pumps were inserted into the mice, and montelukast (Singulair) was continuously delivered to determine its effect on goblet cell hyperplasia, mucus production, and the enlargement of nasal polyps over an 8-week period.. The xenografts were maintained in a viable and functional state for up to 3 months and retained a histopathology similar to that of the original tissue, but with a noticeable increase in goblet cell hyperplasia and marked mucus accumulation in the SMGs. MUC4 and MUC5AC were significantly increased in the xenograft 8 weeks after implantation, but MUC7 was significantly decreased compared to the preimplantation polyps. Inasmuch as MUC7 is found exclusively in serous glands, the findings suggest that serous glands are not found in polyps in the anterior third of the nose. The histopathologic findings confirm the original findings of Tos et al suggesting that the SMGs are derived from pinching-off of the epithelium of the enlarging polyp following inflammatory changes. These SMGs have the same epithelium as surface epithelium and consist of multiple goblet cells that secrete periodic acid Schiff stain-positive mucin into the interior of the SMGs. A progressive increase in the volume of the xenografts was observed, with little or no evidence of mouse cell infiltration into the human leukocyte antigen-positive human tissue. An average twofold increase in polyp volume was found 2 months after engraftment. Montelukast did not decrease the growth of the xenograft in the 8-week NOD-scid mice, nor did it affect MUC gene expression.. The use of innate and adaptive immunodeficient NOD-scid mice homozygous for targeted mutations in the IL-2 gamma-chain locus NOD-scid IL-2r gamma(null) for establishing engraftment of nondisrupted pieces of human nasal polyp tissues represents a significant advancement in studying chronic inflammation over a long period of time. In the present study, we utilized this humanized mouse model to confirm our prediction that MUC genes 4 and 5AC are highly expressed and significantly increased over those of preimplanted polyps. The overexpression of these 2 MUC genes correlates with both the goblet cell hyperplasia and the excessive mucus production that are found in nasal polyp xenografts. MUC7, which is primarily associated with the submucosa, as opposed to MUC4 and MUC5AC, which are primarily expressed in the epithelium, was significantly decreased in the nasal polyp xenografts. Montelukast had no significant effect on MUC gene expression in the xenografts. In addition to the MUC gene expression patterns, the histology of the xenografts supports the concept that mucinous glands that are characteristic of true nasal polyps are significantly different from those in the mucosa found in the lateral wall of the nose in patients with chronic sinusitis without nasal polyps. The mucinous glands seen in nasal polyps (which appear to be derived from an invagination of hyperplastic epithelial mucosa containing large numbers of goblet cells) are histologically distinct from the seromucinous glands found in the submucosa of hyperplastic middle turbinates. The data presented here establish a humanized mouse model as a viable approach to study nasal polyp growth, to assess the therapeutic efficacy of various drugs in this chronic inflammatory disease, and to contribute to our understanding of the pathogenesis of this disease.

Topics: Acetates; Animals; Anti-Inflammatory Agents; Biomarkers, Tumor; Cyclopropanes; Disease Models, Animal; Gene Expression Regulation; Goblet Cells; Humans; Mice; Mice, SCID; Mucin 5AC; Mucin-4; Mucins; Nasal Mucosa; Nasal Polyps; Quinolines; Salivary Proteins and Peptides; Sulfides

Nasal polyposis is a chronic inflammatory disease of the upper respiratory tract that affects around 2% of the population and almost 67% of patients with aspirin-intolerant asthma. Polyps are rich in mast cells and eosinophils, resulting in high levels of the proinflammatory cysteinyl leukotrienes.. To better understand the role of the proinflammatory leukotrienes in nasal polyposis, we asked the following questions: (1) How do nasal polyps produce leukotriene C(4) (LTC(4))? (2) Can LTC(4) feed back in a paracrine way to maintain mast cell activation? (3) Could a combination therapy targeting the elements of this feed-forward loop provide a novel therapy for allergic disease?. We have used immunohistochemistry, enzyme immunoassay, and cytoplasmic calcium ion (Ca(2+)) imaging to address these questions on cultured and acutely isolated human mast cells from patients with polyposis.. Ca(2+) entry through store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels in polyps produced LTC(4) in a manner dependent on protein kinase C. LTC(4) thus generated activated mast cells through cysteinyl leukotriene type I receptors. Hence Ca(2+) influx into mast cells stimulates LTC(4) production, which then acts as a paracrine signal to activate further Ca(2+) influx. A combination of a low concentration of both a CRAC channel blocker and a leukotriene receptor antagonist was as effective at suppressing mast cell activation as a high concentration of either antagonist alone.. A drug combination directed against CRAC channels and leukotriene receptor antagonist suppresses the feed-forward loop that leads to aberrant mast cell activation. Hence our results identify a new potential strategy for combating polyposis and mast cell-dependent allergies.

Topics: Acetates; Arachidonate 5-Lipoxygenase; Calcium; Calcium Channel Blockers; Calcium Channels; Calcium Signaling; Cyclopropanes; Humans; Hydroxyurea; Leukotriene Antagonists; Leukotriene C4; Mast Cells; Nasal Polyps; Quinolines; Receptors, Leukotriene; Sulfides; Thapsigargin

Corticosteroids are agents that suppress the immune system. Their suppressive activity is predominantly restricted to cell-mediated immunity, with a marginal inhibitory effect on humoral immunity.. To describe an acquired reversible B-cell deficiency in a patient treated with low-dose corticosteroids for 36 years.. A broad range of T- and B-cell parameters were studied over time, during and after discontinuation of corticosteroid therapy. Published works on this topic in animal and human models are reviewed. The findings unique to this patient are highlighted.. While undergoing long-term corticosteroid therapy, a patient developed a clinical and immunologic picture suggestive of common variable immunodeficiency, with predominantly qualitative and quantitative B-cell abnormalities. These abnormalities resolved within 2 years after tapering of corticosteroid therapy.. Long-term low-dose corticosteroid use may reversibly decrease B-cell counts and specific antibody responses.

Topics: Acetates; Agammaglobulinemia; Albuterol; Anti-Asthmatic Agents; Antibodies, Bacterial; Antibody Formation; Asthma; B-Lymphocytes; Cyclopropanes; Drug Therapy, Combination; Female; Humans; Immunoglobulin G; Immunologic Memory; Lymphopenia; Methylprednisolone; Middle Aged; Nasal Polyps; Pneumococcal Vaccines; Quinolines; Sinusitis; Sulfides; T-Lymphocyte Subsets

The present study aimed to establish whether anxiety and depression in nasal polyposis play a role in genesis of the disease, or are a consequence of symptoms. Anxiety levels were evaluated in state and trait forms, and depression, in 30 consecutive patients presenting nasal polyposis before and after effective 7 months' medical treatment with nasal mometasone, loratadine and montelukast. Before and at the end of treatment, patients were asked to fill in the State and Trait Anxiety Inventory and the Zung self-rating depression scale. In 63.15% of patients with high levels of state anxiety before therapy, these were reduced (p < 0.004) after treatment. In 61.9% of patients with high levels of trait anxiety before treatment, these were reduced (p < 0.002) after treatment. There were no significant differences in depression. Anxiety in nasal polyposis is present both as a state and as a trait, and is significantly reduced after effective medical treatment, showing that anxiety is a reversible consequence of nasal polyposis in most cases.

Topics: Acetates; Administration, Intranasal; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Anxiety; Cyclopropanes; Depression; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Loratadine; Male; Middle Aged; Mometasone Furoate; Nasal Polyps; Pregnadienediols; Quinolines; Severity of Illness Index; Sulfides; Surveys and Questionnaires; Time Factors

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.. 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.. 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.. 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).. 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.

Topics: Acetates; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma; Bleeding Time; Cyclopropanes; Female; Humans; Inspiratory Capacity; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Nitric Oxide; Peak Expiratory Flow Rate; Quinolines; Sensitivity and Specificity; Skin Tests; Sulfides

In a high rate of cases with recurrent polyposis an association with ASS-intolerance is detectable despite missing pulmonary symptoms. New examinations of a disturbed arachidonic acid metabolism lead to the development of new therapeutical options. Treatment with leukotriene-receptor antogonists (LTA) showed primarily good results in therapy of ASS-associated asthma.. 18 patients with ASS-intolerance trias - diagnosed by oral provocation - were treated with the LTA Montelukast, after undergoing sinus surgery. Patients underwent a diagnostic pathway of provocation including four groups: recurrent chronic sinusitis, excessive polyposis, polyposis associated with asthma and anaphylactic symptoms after oral ASS-intake. Clinically we examined the following parameters periodically after sinus surgery: nasal and pulmonal symptoms by scoring levels, recurrency of polypoid hyperplasia by endoscopic follow-ups and serum ECP-levels. To evaluate antiinflammatory tissue effects of LTA EG1/EG2 labelled cells and cytokine levels of Interleukin 5 in mucosa samples of the lower turbinate were analysed under LTA-therapy.. Under therapy with LTA we saw a beneficial effect on nasal and pulmonary symptoms and a significant reduction of recurrent polyposis in endoscopic examinations in relation to the untreated group. Results were proven by a permanent reduction of serum ECP-level. A reduction of the rate of EG2-positive cells according to decreased Interleukin 5 levels in the nasal mucosa unter LTA-treatment assumed antiinflammatory effects on ASS-associated polyposis.. We could demonstrate antiinflammatory effects of Leukotriene-Receptor-Antagonists primarily during postoperative treatment of patients with ASS-associated nasal polyps.

Topics: Acetates; Adult; Anti-Asthmatic Agents; Aspirin; Asthma; Cyclopropanes; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Quinolines; Recurrence; Sulfides

Topics: Acetates; Adrenal Cortex Hormones; Cyclopropanes; Drug Therapy, Combination; Humans; Leukotriene Antagonists; Nasal Polyps; Paranasal Sinus Diseases; Quinolines; Recurrence; Sulfides

There is a high incidence of post-surgical recurrences of nasal polyps (NP) in patients suffering from the ASA Syndrome. The numerous theories as to the pathogenesis of the ASA Syndrome include an increase in lipoxygenase-mediated arachidonic acid metabolism, with the subsequent hyperproduction of leukotrienes (LT), and an inhibition of the cycloxygenase. Therefore, based on the information acquired on the immunobiological action mechanism of montelukast, a cysteinyl-LT receptor antagonist, it appeared worth testing the effectiveness of this substance in preventing post-surgical NP recurrences in a group of ASA Syndrome patients. After taking a case history, filling out a questionnaire scoring nasal symptoms, undergoing rhinoendoscopy and rhinomanometry, 40 patients suffering from ASA-Syndrome and NP (age range 30-72 years) were recruited for the study. They were uniformly classified according to Lund and Mackay using high resolution CT of the nose and paranasal sinuses performed after at least 1 month of nasal medical treatment. All the patients underwent microendoscopic anterior-posterior ethmoidectomy and bilateral maxillary antrostomy. After removing the nasal packing, the only treatment administered was 10 mg of montelukast/die for 6 months, with the drug suspended for 1 months after the first 3 months of treatment. The monthly follow-up included rhinoendoscopy, rhinomanometry and the questionnaire to score symptoms. After the seventh month a new CT was performed and compared with the pre-operative CT. In a control group of subjects, homogeneous with the test group, momethasone furoate nasal spray was administered at a dose of 100 mcg per nostril/die and loratadin tablets 10 mg/die. The results obtained in the patients treated with montelukast were analogous with those obtained in the second group, and during follow-up all patients showed total absence of any local recurrence, good nasal patency and no significant nasal symptom score on the questionnaire. In no case did the comparative CT, performed after the seventh month, show any signs of recurrence. The patients taking the montelukast reported a significant reduction in the use of steroids and bronchodilator inhalants during the course of the study than did the second group; indeed the number of asthmatic episodes dropped and they reported an improvement in the quality of life. Based on these results, the authors suggest that the use of montelukast in the treatment of post-surgical NP recurrences

Topics: Acetates; Adult; Aged; Aspirin; Asthma; Cyclopropanes; Drug Hypersensitivity; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Neoplasm Recurrence, Local; Quinolines; Sulfides; Syndrome