Inflammatory rheumatism and nasal polyposis

Summary We report five cases of seronegative inflammatory rheumatism associated with nasal polyposis. The patients were four women and one man, mean age 49.5 years (range 42 – 59 yrs.). Two patients had polyarthralgia predominating in the hands, wrists and knees and two patients had symmetrical acromelic polyarthritis. The fifth patient, a woman, had oligoarticular arthritis. In a single female patient, X-rays showed moderate erosions of both tarsometatarsal bones. The inflammatory syndrome was moderate with mean ESR 23 (12 – 38) and immunological investigations were negative except for the presence of pANCA (50 – 200 U) in three patients. HLA - A1, B8, and Bw35 antigens were found in three of the five patients.In all cases, nasal and sinus polyposis (NSP) preceded rheumatism and the joint symptoms were accompanied by worsening of the ENT symptoms.NSP was confirmed by CT scan of the nasal fossae and sinuses. Polyps were surgically removed in four patients and the histology showed neither granuloma nor vasculitis.In four patients the joint symptoms, which responded poorly to nonsteroidal anti-inflammatory drugs (NSAIDs), improved markedly after ENT treatment (surgery and topical steroids) and synthetic antimalarials. The concomitant course of the joint and ENT symptoms suggests there may be a link between inflammatory rheumatism and NSP.     

Aspirin intolerance and nasal polyposis

Chronic rhinosinusitis with nasal polyposis usually develops in aspirin-sensitive patients with asthma. Arachidonic acid metabolism appears to be abnormal in the nasal polyps of aspirin-sensitive patients with asthma. These abnormalities are characterized by a low production of prostaglandin E2 (PGE2) and a high release of cysteinyl leukotrienes. Moreover, cyclooxygenase-2 is markedly downregulated in polyps from aspirin-sensitive patients with asthma. This abnormality may explain the low production of PGE2 in nasal polyps and may account for the increased susceptibility to the inhibitory effects of aspirin. Nasal instillation or ingestion of aspirin induces a nasal reaction in most aspirinsensitive patients with asthma. This reaction is accompanied by the influx of eosinophils and a concomitant increase in cysteinyl leukotrienes, tryptase, and eosinophil cationic protein release. The aspirin nasal challenge is a very safe test with a moderate sensibility and high specificity that can be used in the diagnosis of aspirin intolerance. The similarities in the reaction between the nose and airways in aspirin-sensitive patients provide compelling evidence for common pathogenic mechanisms for nasal polyps, chronic rhinosinusitis, and bronchial asthma.     

Role of cytokines in nasal polyposis.

Chronic hyperplastic sinusitis and nasal polyposis (CHS/NP) is associated with significant morbidity. The response to medical treatment is often unsatisfactory, and surgery often provides only temporary relief. The genesis and pathophysiology of polyps are poorly understood. There has been increasing interest in the role of inflammatory mediators such as cytokines and chemokines in the pathogenesis of chronic sinusitis and nasal polyposis. Recent data from several investigators offer insights into the cellular content of polyps and their capacity to produce cytokines and orchestrate the inflammatory process.     

The molecular biology of nasal polyposis

The molecular biologic events in the development of nasal polyps are now becoming unraveled. It appears that eosinophils are the dominant inflammatory cell present in this tissue. The events leading up to the extravasation of eosinophils into the lamina propria nasal polyps are regulated by the proinflammatory cytokines tumor necrosis factor-a and interleukin-1b. These cytokines upregulate very late antigen-4 on the surface of eosinophils and vascular cell adhesion molecule-1 on the surface of the endothelial blood vessel. Chemokines such as RANTES (regulated upon activation, normal T-cell expressed and secreted) and eotaxin are responsible for the movement of eosinophils into the lamina propria of the nasal polyp. The release of major basic protein has an effect on alteration of the epithelial architecture and on the sodium and chloride flux into and out of the apical epithelial cell of the tissue. Finally, the alteration of the surface epithelium results in a defect in the migration of the cystic fibrosis transmembrane regulator protein to the apical surface. These two events, the release of major basic protein from the eosinophil and the alteration of the architecture of the surface epithelium, lead to an increase in sodium absorption and resultant edema: the hallmark of the pathology of the nasal polyp.     

Activation state of circulating eosinophils in nasal polyposis

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease with an uncertain pathophysiology. It is characterized by polyps rich in eosinophils, with an activation status already investigated at the tissue level. In a group of CRSwNP patients, we assessed the activation status of circulating eosinophils in the blood before migration into tissues.

Methods

Thirteen patients with CRSwNP and 16 healthy volunteers were enrolled. Several biologic parameters were studied: blood count of eosinophils; plasma eosinophil cationic protein; oxidative metabolism by chemiluminescence at baseline or when activated by phorbol 12‐myristate 13‐acetate or platelet‐activating factor, with or without interleukin‐5 (IL‐5); percent of granulosar cells; and mean fluorescence intensity (MFI) by flow cytometry.

Results

The mean number of eosinophils was significantly higher in patients with CRSwNP, whose eosinophils showed increased oxidative metabolism in the basal or activated state significantly decreasing in the presence of IL‐5. There was also a higher percentage of CD49d⁺, CD25⁺, and CCR3⁺ cells in patients, and a nonsignificant decrease in descending order in MFI between the control group, patients with normal eosinophil levels, patients with hypereosinophilia, and patients with aspirin‐exacerbated respiratory disease.

Conclusion

This study demonstrates a priming state of circulating eosinophils in CRSwNP patients when compared with healthy controls, as evidenced by the extent of oxidative metabolism, with increased sensitivity to IL‐5 and by the observed variations of percent and MFI of CD49d, CCR3, and CD25. This priming is thus found at the peripheral level and occurs before the migration of eosinophils to polyps, reflecting the systemic and not just local nature of abnormalities in CRSwNP.

     

Progress in surgical management of chronic rhinosinusitis and nasal polyposis

Endoscopic sinus surgery (ESS) remains the treatment of choice for medically refractory chronic rhinosinusitis (CRS) with or without nasal polyposis (NP). ESS has undergone review, reassessment, and substantial refinement. Several advances (eg, powered instrumentation, image guidance, adjunctive intraoperative procedures) have expanded the scope of cases amenable to ESS, decreased operative time and intraoperative blood loss, and improved safety. Procoagulant nasal/sinus packing and refinements of technique have decreased the need for postoperative removal of packing, thus decreasing morbidity. Methods to reduce synechia formation (ie, mitomycin-c) have been explored, with mixed results. Novel methods of sinusotomy (eg, balloon catheter dilatation of the sinus ostia) have had limited but interesting short-term results. We can expect further advances in ESS with better patient outcomes. However, continued elucidation of the underlying pathophysiology of CRS and NP are essential to long-term improvement.     

Comparison of medical and surgical treatment of nasal polyposis

Nasal polyposis is the end result of a variety of pathologic processes. The aims of treatment are to relieve nasal blockage, restore olfaction, and improve sinus drainage. Treating any accompanying rhinitis is also an aim, which requires that medical treatment be given to all patients with an inflammatory problem. Most forms of nasal polyp recur after treatment, whether medical or surgical. There are few direct comparisons of medical and surgical treatment in the literature. Those that exist suggest that most patients should be treated medically, with surgery reserved for patients who respond poorly. Large prospective randomized trials of surgical versus medical therapy are needed in groups of well-characterized patients to determine the optimum approach for each and to decrease relapse rates. Topical corticosteroids are the mainstay of treatment. All patients with inflammatory polyps should receive topical corticosteroid treatment in the long-term, unless there is a compelling contraindication. Adverse effects of surgery are rare but can be devastating. The major side effects of medical therapy are those of oral corticosteroids, which need to be used carefully. The choice of topical corticosteroid is important because long-term use is necessary; the least absorbed should be used. No cost-benefit analysis has been undertaken in this area, although medical therapy is probably cheaper and involves less work/school absence than sinonasal surgery, even when the latter is performed with an endoscope.     

Role of thymic stromal lymphopoietin in the pathogenesis of nasal polyposis

IntroductionPolyposis is an end form of chronic mucosal inflammation in a number of disorders and has an important impact on patient’s life quality. Thymic stromal lymphopoietin (TSLP) is involved in many inflammatory processes such as asthma and allergic rhinitis (AR). The aim of this study is to elucidate the role of TSLP in the pathogenesis of polyposis.MethodsNinety-four patients with nasal polyposis (NP) and/or allergic rhinitis (AR) were treated with inferior turbinectomy and polyp resection. Levels of TSLP in the nasal epithelial layer were measured; expression of TSLP receptor and OX40 ligand (OX40L) was assessed in isolated nasal mucosal dendritic cells (DC); tumor necrosis factor (TNF), interleukin (IL)-4 and interferon (IFN)-γ expressions were determined in isolated nasal mucosal CD4⁺ T cells.ResultsThe levels of TSLP in nasal epithelial layer were higher in the NP group than in the non-NP group. Higher expression of TSLP receptor and OX40L were detected in DCs of NP nasal mucosa. TNF-α⁺ IL-4⁺CD4⁺ T cells were detected in NP/AR nasal mucosa; TNF⁺ IFN-γ⁺ CD4⁺ T cells were identified in NP/non-AR nasal mucosa. TSLP-primed DCs drove naive CD4⁺ T cells to become TNF⁺ IL-4⁺ CD4⁺ T cells, whereas TSLP/lipopolysaccharide-primed DCs induced naive CD4⁺ T cells to become TNF⁺ IFN-γ⁺ T cells.ConclusionsThe data indicate that TSLP is involved in the pathogenesis of polyposis.     

Cyclooxygenases and the pathogenesis of chronic rhinosinusitis and nasal polyposis

Cyclooxygenase (COX) enzymes catalyze the rate-limiting steps in prostaglandin synthesis. Prostaglandins have an important role in several physiological processes such as maintenance of gastrointestinal integrity and pathological processes such as inflammation and neoplasia. Several mechanisms have been proposed for the development of chronic rhinosinusitis, but the common final pathway seems to be an integrated process involving the mucosal epithelium, matrix, and inflammatory cells and mediators. Upper and lower airway pathologies coexist and share common etiopathogenic mechanisms, and nasal polyposis is often associated with asthma and aspirin sensitivity. The cellular source of COX activity in acute and chronic inflammation, as in chronic rhinosinusitis, is poorly understood. COX theory postulated that inhibition of COX broke down biochemical reactions that lead to the development of asthma attacks. This article focuses on COX in the pathogenesis of chronic rhinosinusitis and nasal polyposis.     

DCBLD2 gene variations correlate with nasal polyposis in Korean asthma patients

Background  

Nasal polyps are abnormal lesions that cause airway obstruction and can occur along with other respiratory diseases. On account of its association with aspirin exacerbated respiratory disease (AERD), the human discoidin, CUB and LCCL domain containing 2 (DCBLD2) is hypothesized to be a candidate gene for the development of nasal polyps in asthma patients.     

Loss of nocturnal decline of blood pressure in patients with nasal polyposis

The objective of this study was to assess the blood pressure pattern in patients with nasal polyposis. Twenty-seven patients with nasal polyposis (18 males and 9 females), ranging in age from 15 to 72 years (mean 37.1 years) were eligible for inclusion in the study. All patients were hospitalized overnight before surgery. After the basal blood pressure measurements were taken, non-invasive ambulatory blood pressure monitoring was carried out. Oxygen saturation was measured via a finger probe and venous blood sampling was taken for catecholamine level during the full night. All measurements were repeated 4 months after nasal surgery. Mean values for nocturnal decline in blood pressure and heart rate before surgery were less marked than those measured after surgery. Mean decline values (+/- SD) were; 4.6 +/- 2.4 mmHg for systolic blood pressure, 5.8 +/- 3.8 mmHg for diastolic blood pressure, and 7.9 +/- 3.9 beats/min for heart rate before surgery, 9.3 +/- 2.8 mmHg, 8.5 +/- 4.1 mmHg and 10.4 +/- 4.3 beats/min after surgery (p < 0.01), respectively. Whereas mean and minimum SaO2 (%) significantly increased (p < 0.01), catecholamine levels decreased (p < 0.05 for adrenaline, p < 0.01 for noradrenaline) after surgery. A correlation was found between BMI and blood pressure as well as between duration of obstruction and blood pressure. Patients who snored had higher blood pressure values than those who did not. Our data show that in cases of nasal polyposis, hypoxia, hypercapnia, snoring, and sleep disorders may develop and persons with nasal polyposis and snoring have an increased risk of hypertension and loss of nocturnal decline in blood pressure.