蒿属花粉过敏变应性鼻炎与HLA-DQA1、 DQB1基因的关系

目的 :研究北京地区蒿属花粉过敏变应性鼻炎 (AR)患者HLA DQA1、DQB1基因与蒿属花粉过敏易感性的关系。方法 :用聚合酶链反应 序列特异性引物技术 (PCR SSP) ,检测HLA DQA1、DQB1基因型在 4 1例以蒿属花粉过敏为主的AR患者及 4 1例对照组间的分布 ,并统计分析了二者间的分布差异。结果 :4 1例变应性鼻炎患者DQA1 0 2 0 1、DQB1 0 6 0 2基因频率 (2 4 .39%、4 .88% )明显低于对照者 (46 .34%、2 6 .83% ) ,而DQA1 0 30 2基因频率 (5 8.5 4 % )明显高于对照者 (14 .6 3% ) ,具有统计学意义。结论 :提示HLA DQA1 0 2 0 1、DQB1 0 6 0 2基因可能是AR发病的抗性基因 ,而DQA1 0 30 2可能是AR发病的易感性基因。     

HLA patterns in patients with nasal polyposis

The etiology of nasal polyposis is still unknown, although risk factors include Aspirin intolerance, asthma, cystic fibrosis and primary ciliary dyskinesia. We studied frequencies of HLA A, B, DR and DQ in patients with nasal polyposis in order to determine a possible genetic component in the multifactorial pathogenesis of nasal polyps. Previous work has suggested an association of HLA-A1B8 with nasal polyposis and Aspirin intolerance. We investigated 89 patients with nasal polyposis, 11 of whom had Aspirin-intolerance, 19 asthma and 22 allergies to inhalation allergens. HLA patterns of these patients were compared to the ones of 1,070 healthy controls. No significant association of HLA-A1B8 was found with nasal polyps in the Aspirin-sensitive subgroup of our patients, but a significant association was seen with HLA-A74 and nasal polyposis. Received: 26 February 1998 / Accepted: 25 March 1999     

Nasal polyps, bronchial asthma and aspirin sensitivity.

The ASA triad comprises bronchial asthma, acetylsalicylic acid (ASA) sensitivity and nasal polyps. It presents as chronic rhinitis followed by bronchial asthma and ASA sensitivity, and later nasal polyps. The pathogenesis of the ASA triad may involve interrelationships between disease in the upper and lower airway and hypersensitivity to cyclo-oxygenase inhibiting medications. Treatment of the nasal polyps has been shown to improve the patients' asthma.     

Aspirin sensitivity: long term follow-up after up to 3 years of adaptive desensitization using a maintenance dose of 100 mg of aspirin a day

BACKGROUND: The full clinical picture of aspirin intolerance, Sampter's triad, is associated with nasal polyposis, clinical sensitivity to most non steroidal antiinflammatory drugs (NSAID) and intrinsic bronchial asthma. But the triad can be incomplete and nasal polyposis can be the first clinical symptom of aspirin sensitivity. Although the exact mechanisms of aspirin intolerance as well as those of desensitization remain obscure, an in vitro assay on eicosanoid metabolism has been proven to be helpful in diagnosis and treatment as it correlates well to the individual severity of clinical symptoms. METHODS: For this investigation 30 patients, who were undergoing adaptive desensitization for aspirin intolerance, were followed-up between 1 and 3 years. They received a maintenance dose of oral aspirin of only 100 mg a day after an initial application of higher doses. Their clinical course as well as their in vitro parameters of eicosanoid release were monitored throughout the individual observation period. RESULTS: Desensitization was successful in 25 of the 30 patients regarding the recurrence rate of nasal polyps, severity of bronchial asthma and sense of smell. There was a clear positive correlation between clinical and in vitro parameters. Discontinuing of aspirin therapy lead to worsening of clinical symptoms, regardless of the prior duration of treatment. CONCLUSIONS: This article reviews the role of the in vitro assay and presents a desensitization protocol that can be maintained as a long term treatment without adverse side effects. Results suggest that the recurrence rate of nasal polyps after surgical therapy can be reduced using this protocol, however, only long term treatment can secure a beneficial outcome over time.     

HLA antigens,nasal polyps and asthma

HLA antigens, nasal polyps and asthma HLA typing has been performed on a selected series of 29 patients with nasal polyps, with or without asthma. Despite the small series there was a significant increase in the haplotype A1/B8 in patients with both nasal polyps and asthma. No association was found in those with polyps alone. However, those with both conditions, who were positive for A1/B8, had more severe polyp disease. Three out of 4 patients with nasal polyps, asthma and sensitivity to aspirin were positive for A1/B8. In patients with nasal polyps, tissue typing might be of use in predicting both those who are most at risk of developing asthma, and also those who are most likely to have severe polyp disease. The association of A1/B8 with severe polyp disease and asthma, may imply that abnormalities of immune response are likely to be associated with the pathogenesis of both conditions.     

Prostaglandins, leukotrienes, and other arachidonic acid metabolites in nasal polyps and nasal mucosa

Prostaglandins (PGs) and leukotrienes (LTs) are known to play an important role in allergic inflammatory reactions. The triad of aspirin sensitivity, nasal polyposis, and asthma led us to suspect that PGs, LTs and other arachidonic acid metabolites may be involved in the pathogenesis of nasal polyps. The purpose of this study was to determine arachidonic acid metabolites and to measure concentrations of PGs and LTs in nasal polyps and nasal mucosa. Samples of nasal polyps and nasal mucosa were obtained at the time of polypectomies and nasal procedures. Metabolites of arachidonic acid in tissue were determined by incubation of tissue-homogenates with 14C-arachidonic acid and analyses with thin-layer chromatography and high performance liquid chromatography (HPLC). Levels of PGE2, 6-keto-PGF1 alpha, thromboxane (Tx)B2, 15-hydroxyeicosatetraenoic acid (HETE), LTC4, LTB4 were measured by radioimmunoassay. The predominant arachidonic acid metabolite in both nasal polyps and mucosa with 15-HETE. The HPLC analysis showed that the predominant metabolite in nasal polyp was 15-HETE, especially in polyps from aspirin sensitive patients. Levels of 15-HETE and PGE2 were higher in polyps from patients with a history of allergy than from nonallergic patients. Levels of LTC4 and LTB4 in nasal polyps were determined. The findings of this study will help to explain biochemical basis of the pathogenesis of aspirin-sensitive nasal polyps and to develop better medical treatment for them.     

Woakes' syndrome: the problems of infantile nasal polyps

Usually, nasal polyposis in early childhood (children aged less than 5 years) is caused by cystic fibrosis of Kartagener's syndrome. In later age groups, recurrent sinus infections, allergy and ASA disease (asthma, aspirin intolerance and nasal polyps) have to be taken into consideration. Four cases of early childhood polyposis are reported which fit into none of these etiological groups. This newly defined Woakes' syndrome comprises recurrent nasal polyposis with broadening of the nose, frontal sinus aplasia, bronchiectasis, and dyscrinia (production of highly viscous mucus). The disease seems to be hereditary. The possible origins of the disease are discussed.     

Subclinical aspirin sensitivity in subjects with nasal polyposis

It is unclear whether subclinical airway responses to aspirin occur in subjects with nasal polyps and/or asthma without overt sensitivity. Sixty-three subjects without known aspirin sensitivity (13 controls, 17 nasal polyps alone, 15 nasal polyps and asthma and 18 asthma alone) inhaled increasing concentrations of nebulized lysine aspirin. Forced expiratory volume in 1 s (FEV1), symptoms and other potential markers of an airway response were measured. Four subjects (one polyps alone, one asthma alone, two with both) had a positive response to lysine aspirin predefined as symptoms plus a >10% fall in FEV1 from baseline. However, there was no evidence of a general subclinical response in any of the subject groups: mean (95% CI) change in FEV1; control 0.07 (-0.02,0.16) L, nasal polyps alone -0.05 (-0.16,0.05) L, nasal polyps with asthma -0.03 (-0.10,0.04) L, asthma alone -0.03 (-0.09,0.03) L. We concluded that in the absence of a suggestive clinical history, only a small proportion of patients with nasal polyposis are likely to be sensitive to aspirin. There is no evidence of general subclinical sensitivity to aspirin in subjects with nasal polyps and no relevant history.     

The prevalence of Samter's triad in patients undergoing functional endoscopic sinus surgery

We conducted a retrospective study to determine the prevalence of Samter's triad (nasal polyps, asthma, and aspirin sensitivity) in 208 consecutively presenting patients who had undergone functional endoscopic sinus surgery (FESS) for chronic rhinosinusitis from September 2001 through August 2003. Overall, Samter's triad was found in 10 patients (4.8%); subgroup analyses showed that the prevalence of Samter's triad was 5.9% in adults, 9.4% in patients with nasal polyps alone, 16.9% in patients with asthma alone, and 25.6% among patients with both polyps and asthma. On average, patients with Samter's triad had undergone approximately 10 times as many previous FESS procedures as had the patients without Samter's triad (mean: 5.2 vs. 0.53; p < 0.001). In addition to Samter's triad, four other factors were independently and significantly associated with a higher number of previous FESS procedures: nasal polyps alone, asthma alone, both polyps and asthma, and cystic fibrosis alone. Finally, at 6 months following their most recent surgery, patients with Samter's triad had significantly higher rates of symptom recurrence (nasal obstruction, facial pain, postnasal drip, and anosmia) and a recurrence of nasal polyps.     

Initial surgical treatment for chronic frontal sinusitis: a pilot study

OBJECTIVES: The initial surgical treatment for chronic frontal sinusitis is not well defined. Our objective was to determine the effectiveness of anterior ethmoidectomy for chronic frontal sinusitis. METHODS: Patients with chronic frontal sinusitis who underwent anterior ethmoidectomy as initial surgical treatment were reviewed. Data were collected from computed tomography scans with use of the Lund-Mackay scale. Data on demographics, comorbidities, management, postoperative recovery, and follow-up were collected. RESULTS: Seventy-seven patients representing 121 diseased frontal sinuses met the inclusion criteria. The respiratory comorbidities were asthma alone (8.3%), asthma and polyps (6.6%), aspirin triad (5.8%), and cystic fibrosis (0.8%). Nineteen of 121 frontal sinuses (15.7%) belonged to smokers. Fourteen of 121 frontal sinuses (11.5%) exhibited postoperative evidence of disease. Of these 14 frontal sinuses, 10 (8.3%) underwent revision surgery. Frontal sinuses of patients with aspirin triad, with both nasal polyposis and asthma, or with inter-frontal sinus septal cells were more likely to fail Draf I surgery (p < .05). CONCLUSIONS: Anterior ethmoidectomy for drainage of frontal sinuses appears to be effective initial surgical treatment for chronic frontal sinusitis. Patients with aspirin triad, both asthma and polyposis, or inter-frontal sinus septal cells are more likely to fail this procedure.     

The importance of timely diagnosis of aspirin-exacerbated respiratory disease for patient health and safety

BackgroudAspirin-exacerbated respiratory disease (AERD) is a difficult-to-treat syndrome where timely diagnosis and initiation of disease-specific therapies are pertinent to improved patient outcomes.ObjectiveTo characterize the most common timeline for development of the clinical triad [asthma, nasal polyposis, and reactions to nonsteroidal anti-inflammatory drugs (NSAIDs)], identify barriers to prompt diagnosis of AERD, and describe indications for an aspirin challenge to facilitate accurate diagnosis.MethodsSix hundred ninety-seven patients with diagnosed AERD and history of at least one sinus surgery to remove nasal polyps were identified in the Brigham and Women's Hospital AERD registry. Patient reported age at disease onset of asthma, nasal polyposis, and age of first NSAID reaction were obtained from 2013 to 2019 at enrollment.ResultsOf the 697 patients identified, diagnosis of asthma preceded diagnosis of nasal polyposis and first NSAID reaction, although there was considerable variability between patients.ConclusionsPrompt diagnosis of AERD is important for patient and provider education and improved care of this difficult-to-treat population of patients. Consider diagnostic aspirin challenge in patients without historical reactions to NSAIDs who have an otherwise compatible clinical history, specifically in patients who take daily low-dose aspirin, leukotriene modifiers, avoid NSAIDs, or who are severely symptomatic at baseline where it would be difficult to identify an acute worsening of symptoms.     

ASA disease: the clinical relationship of nasal polyposis to ASA intolerance

We studied the complex relationship between nasal polyposis and ASA (acetylsalicylic acid) intolerance in 154 patients with nasal polyps. The clinical histories of all patients were reviewed, and diagnostic tests for immune or allergic causes and the responsiveness of patients to challenges with ASA-substitutive drugs were analyzed. A third of our patients tested were found to have positive personal histories of atopy and 35% showed ASA intolerance. Although 40% had bronchial asthma, only 16.8% of all patients had positive tests for allergy. We were unable to find a specific mechanism to explain the relationship between nasal polyposis and ASA intolerance and further investigations are still required.     

ASA disease: the clinical relationship of nasal polyposis to ASA intolerance

Summary We studied the complex relationship between nasal polyposis and ASA (acetylsalicylic acid) intolerance in 154 patients with nasal polyps. The clinical histories of all patients were reviewed, and diagnostic tests for immune or allergic causes and the responsiveness of patients to challenges with ASA-substitutive drugs were analyzed. A third of our patients tested were found to have positive personal histories of atopy and 35% showed ASA intolerance. Although 40% had bronchial asthma, only 16.8% of all patients had positive tests for allergy. We were unable to find a specific mechanism to explain the relationship between nasal polyposis and ASA intolerance and further investigations are still required.     

Nasal polyposis, bronchial asthma and analgesic intolerance

A retrospective case-control study was conducted in 1042 arbitrarily selected bronchial asthma patients (197 patients with AIA and 845 controls with normal analgesic tolerance). Two thirds of all AIA patients reported one or more diseases in the region of the upper airways. Quite different from the control group, highly significant coincidence of AIA with nasal polyposis (42.6%), paranasal sinus diseases (39%), and chronic rhinitis (42,1%) was recorded in the AIA patients. AIA was characterized by stronger inclination to recurrence of nasal polyps and more frequent negative impact of polypectomy upon the course of asthma. The classical triad of "intrinsic asthma - nasal polyps - analgesic intolerance" was established in 39% of the AIA patients. The pathogenetic factors causing the association of asthma with polyps and the even more strongly association of AIA with polyps are still unknown. The presumed pathogenetic relationship between chronic hyperplastic alterations in the upper airways and the phenomenon of AIA might be caused by disorders in phospholid metabolism (liberation of arachidonic acid, lipoxygenase products, radical mechanisms).     

Vascular endothelial growth factor in nasal polyps: a comparison of asthmatic and non‐asthmatic patients

The cause of nasal polyps remains unknown, although there is a well‐recognized clinical association between nasal polyposis and asthma. The characteristic histological features of nasal polyps include large quantities of extracellular fluid. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis and vascular permeability. This study aimed to compare expression of VEGF in nasal polyps from patients with asthma and those with no apparent respiratory disease. Twenty‐four asthmatic and 35 non‐asthmatic patients were studied using immunohistochemistry for VEGF. VEGF expression was identified in endothelial, inflammatory and epithelial cells. There was significantly greater endothelial expression of VEGF in asthmatic patients (P < 0.05). Greater epithelial expression was observed in asthmatic patients but this did not reach statistical significance (P = 0.07). There was no difference in the density of inflammatory cells expressing VEGF. Differences between the two groups may reflect differences in disease severity or in the nature of the inflammatory process.     

High Levels of Nitric Oxide Synthase Activity are Associated with Nasal Polyp Tissue from Aspirin-sensitive Asthmatics

The pathogenesis of aspirin intolerance remains unclear. Inducible nitric oxide synthase (iNOS) expression is upregulated in nasal polyp epithelium, implying a role for nitric oxide (NO) in its formation. We decided to compare iNOS activity in polyp tissue from patients with and without aspirin intolerance. Nasal polyp tissue was collected from 15 patients undergoing routine nasal polypectomy. These patients were classified into three groups: Group A comprised patients with nasal polyps without asthma; Group B contained patients with nasal polyps and asthma; and Group C comprised patients with nasal polyps, asthma and aspirin sensitivity. All subjects in Group C had a history of aspirin-induced reaction and a confirmatory intranasal challenge with lysine-aspirin. NOS activity was measured by the ability of tissue homogenates to convert 3,4-L-arginine to L-citrulline in an L-N G -nitro-L-arginine-inhibitable fashion. The iNOS activity (picomoles) in polyp tissue from the 3 groups was: A, 248.72 &#45 220.79; B, 23.71 &#45 41.06; and C, 549.71 &#45 132.11. Thus, nasal polyps from patients with Samter's triad had a significantly higher iNOS activity ( p = 0.004; one-way ANOVA). This finding does not correlate simply with disease severity or with the occurrence of asthma and could indicate another important facet of aspirin-induced airways disease.     

High levels of nitric oxide synthase activity are associated with nasal polyp tissue from aspirin-sensitive asthmatics

The pathogenesis of aspirin intolerance remains unclear. Inducible nitric oxide synthase (iNOS) expression is upregulated in nasal polyp epithelium, implying a role for nitric oxide (NO) in its formation. We decided to compare iNOS activity in polyp tissue from patients with and without aspirin intolerance. Nasal polyp tissue was collected from 15 patients undergoing routine nasal polypectomy. These patients were classified into three groups: Group A comprised patients with nasal polyps without asthma; Group B contained patients with nasal polyps and asthma; and Group C comprised patients with nasal polyps, asthma and aspirin sensitivity. All subjects in Group C had a history of aspirin-induced reaction and a confirmatory intranasal challenge with lysine-aspirin. NOS activity was measured by the ability of tissue homogenates to convert 3,4-L-arginine to L-citrulline in an L-N(G)-nitro-L-arginine-inhibitable fashion. The iNOS activity (picomoles) in polyp tissue from the 3 groups was: A, 248.72+/-220.79; B, 23.71+/-41.06; and C, 549.71+/-132.11. Thus, nasal polyps from patients with Samter's triad had a significantly higher iNOS activity (p = 0.004; one-way ANOVA). This finding does not correlate simply with disease severity or with the occurrence of asthma and could indicate another important facet of aspirin-induced airways disease.     

Clinical factors influencing the eosinophil infiltration of nasal polyps

AIMS AND METHODS: Our study, based on a retrospective chart analysis, was aimed 1) to describe the varying degree of eosinophil infiltration in a series of 263 adult patients operated on diffuse and bilateral nasal polyposis (NPS) after failure of medical treatment, in 15 cystic fibrosis patients with bilateral nasal polyps, and in 31 patients with chronic sinusitis without polyps (18 bilateral, 13 unilateral) 2) to search for clinical factors that might influence the degree of eosinophil infiltration. Eosinophil infiltration was expressed semi-quantativity as a percentage of inflammatory cells. RESULTS: Our study confirms that eosinophil infiltration is a striking feature of nasal polyposis. All patients with chronic sinusitis showed less than 10% eosinophils (mean +/- SEM = 2 +/- 2%) whereas 88% of patients with NPS showed more than 10% eosinophils (50 +/- 2%). Cystic fibrosis lied in between with 40% of patients showing more than 10% eosinophils. In idiopathic bilateral NPS the number of eosinophils was increased in patients with asthma (58 +/- 3%) and even more in Widal's triad (75 +/- 4%). Atopic patients did not have more eosinophils (52 +/- 5%). Patients treated with systemic steroids within two months before surgery showed decreased eosinophil infiltration (22 +/- 3% vs 50 +/- 2 for treated versus untreated) whereas patients treated with topical steroids did not (47 +/- 2%). CONCLUSIONS: Thus, a link might exist between clinical presentation and eosinophil infiltration. Chronic sinusitis and nasal polyps are probably not the same disease. Eosinophils appear as a link between nasal polyps, asthma and aspirin intolerance. Atopic status does not modify eosinophil infiltration of nasal polyps. Systemic steroids appear significantly more effective to reduce the eosinophil infiltrate than topical steroids in our selected group of operated patients.     

Outcome analysis of endoscopic sinus surgery in patients with nasal polyps and asthma

OBJECTIVE: To investigate the efficacy of endoscopic sinus surgery (ESS) in the management of chronic sinusitis and asthma in patients with nasal polyps and steroid-dependent asthma. STUDY DESIGN: Retrospective chart review. METHODS: The study included 17 patients who underwent ESS with nasal polyps, steroid-dependent asthma with or without aspirin sensitivity and a minimum of 1 year postoperative follow-up. Nine patients were ASA sensitive, and eight patients were ASA tolerant. Chronic sinusitis and asthma were evaluated using subjective (patient complaints) and objective (computed tomography scans, pulmonary function tests, steroid doses) criteria. Preoperative data were compared with data obtained 12 to 18 months postESS. Tissue samples were graded for degree of inflammation and edema. RESULTS: Thirteen of the 17 (76.5%) patients reported improved clinical symptoms postESS. The postoperative Lund-Mackay scores were statistically lower for the 17 patients (P <.0001). The group experienced improvement in postoperative forced expiratory volume at 1 second (FEV1) (P <.014). Twelve of 17 (70.6%) experienced reduction in systemic steroid usage (P <.048). The ASA sensitive patients did not have a statistical improvement in postoperative FEV1 (P >.08) and sinonasal symptoms (P >.16) compared with the ASA tolerant group. Polyp tissue from the ASA sensitive patients demonstrated more edema and more inflammation on average than ASA tolerant polyps, but the results were not statistically significant. CONCLUSION: ESS demonstrates a beneficial effect on the sinonasal and asthma symptomatology in patients with nasal polyps and asthma using objective measures. Subset of aspirin-tolerant patients have statistically better outcome for sinonasal symptoms and pulmonary function testing than aspirin-sensitive patients.     

Outcome analysis of endoscopic sinus surgery for chronic sinusitis in patients having Samter's triad

A study was conducted to assess outcome analysis in acetylsalicylic acid (ASA) triad patients after endoscopic sinus surgery (ESS). The control group consisted of patients with chronic sinusitis, with or without asthma, who had also undergone ESS. The study group contained 18 patients with the classic triad who were compared with 22 controls. The study was conducted in retrospective fashion highlighting clinical presentation, radiologic evaluation, surgical findings, and recurrence rate of nasal polyps. Although both groups had a relatively similar age of onset of symptoms, the symptomatic picture was different in the two groups. Radiologic evaluation of the nose and paranasal sinuses revealed more extensive involvement of the sinuses in ASA triad patients. Furthermore, ASA triad patients underwent a greater number of repeat operations. This review suggests that ASA triad patients respond less well to surgical intervention and that other treatment modalities should perhaps be explored.