Transforming growth factor-beta in allergic inflammatory disease of the upper airways: friend or foe?

TGF-beta is a multi-functional cytokine with a huge array of effects on a variety of cell types. It is rapidly emerging as a key major player in the way the airway epithelium behaves and its ability to repair itself. This is not only of relevance to allergic airway diseases such as asthma and allergic rhinitis, which are increasing in prevalence worldwide, but in many other diseases. The full impact any disruption of TGF-beta signalling may have in the development and persistence of allergic inflammatory airway diseases is yet to be fully realized and remains the subject of ongoing research. There has been a recent revival of interest in the role of regulatory T cells in controlling allergic inflammation. Evidence is emerging of a significant contribution by TGF-beta to this regulatory process. This review aims to summarize current knowledge relating to TGF-beta in relation to allergic inflammatory upper airways disease, and attempts to clarify some of the discrepancies and inconsistencies in this area. It also considers the therapeutic implications of novel TGF-beta therapy, including potential future applications in the treatment of nasal polyposis and reduction of post-operative scar tissue formation following endoscopic sinus surgery.

Allergic fungal sinusitis (AFS)--earlier diagnosis and management.

AIM: To evaluate the criteria for diagnosing allergic fungal sinusitis and to maintain permanent drainage and ventilation, while preserving the integrity of mucosa. METHODS: This is a prospective study of 251 patients with chronic rhinosinusitis with or without polyposis, of whom 199 were treated surgically. Mucus sample collection, nasal secretion culture, surgical specimen handling and histological evaluation of surgical specimens are described. The management included wide local endoscopic sinus debridement, adequate sinus aeration, post-operative use of steroids and antifungal therapy. RESULTS: Fungal cultures of nasal secretions were positive in 201 (80.01 per cent) of 251 patients. Of the 199 surgical cases, fungal elements were found in 156 histological specimens (62.1 per cent). Allergic mucin was found in 182 patients (91.45 per cent). Nasal obstruction and proptosis were the commonest presentations. All pre-operative versus post-operative changes in AFS-associated complaints reached statistical significance of p < 0.001. The ethmoid sinus was commonly involved with adjacent lamina papyracea exhibiting demineralization in 26.6 per cent of cases. Intracranial extension was seen in 15 cases. Recurrence was noted in 11 cases. CONCLUSION: Comprehensive treatment with endoscopic sinus surgery, steroids and antifungal therapy is needed. AFS is readily recurrent. Long-term follow up is important.

Vagotomy reverses established allergen-induced airway hyperreactivity to methacholine in the mouse.

We evaluated the role of vagal reflexes in a mouse model of allergen-induced airway hyperreactivity. Mice were actively sensitized to ovalbumin then exposed to the allergen via inhalation. Prior to ovalbumin inhalation, mice also received intratracheally-instilled particulate matter in order to boost the allergic response. In control mice, methacholine (i.v.) caused a dose-dependent increase in respiratory tract resistance (RT) that only modestly decreased if the vagi were severed bilaterally just prior to the methacholine challenge. Sensitized and challenged mice, however, manifested an airway reactivity increase that was abolished by severing the vagi prior to methacholine challenge. In an innervated ex vivo mouse lung model, methacholine selectively evoked action potential discharge in a subset of distension-sensitive A-fibers. These data support the hypothesis that the major component of the increased airway reactivity in inflamed mice is due to a vagal reflex initiated by activation of afferent fibers, even in response to a direct (i.e., smooth muscle)-acting muscarinic agonist.

Treatment of allergic fungal sinusitis: a comparison trial of postoperative immunotherapy with specific fungal antigens.

OBJECTIVE: To determine the effect of immunotherapy (IT) with fungal antigens on clinical outcome in patients with allergic fungal sinusitis (AFS). STUDY DESIGN: Prospective case control. METHODS: In this comparison study, 22 patients meeting the diagnostic criteria of allergic fungal sinusitis (AFS) were evaluated after a mean of 33 months' therapy. All received similar treatment consisting of endoscopic sinus surgery, corticosteroids, and antibiotics as needed for complicating purulent sinusitis. Eleven patients received postoperative immunotherapy (IT) with fungal and nonfungal antigens to which sensitivity had been demonstrated, while the remaining 11 received no immunotherapy. RESULTS: The effect of IT was to significantly improve patient outcome as assessed objectively by an AFS endoscopic mucosal staging system (P < .001) and a sinusitis-specific quality-of-life scale, the Chronic Sinusitis Survey (P = .002). In addition, IT was shown to reduce reliance on systemic (P < .001) and topical nasal (P = .043) corticosteroid therapy to control disease. Follow-up was similar in the two groups and was not a determinant of differences in outcome (P = .7). CONCLUSIONS: Results from this study indicate that specific IT with fungal antigens improves patient outcome in AFS.

Allergic fungal sinusitis secondary to dermatiaceous fungi--Curvularia lunata and Alternaria.

Allergic fungal sinusitis is a newly recognized entity consisting of a pansinusitis with allergic mucinous infiltrates in all involved sinuses. The disease process itself is very different from all other types of rhinosinusitis. Pathophysiologically the disease is a combination of both IgE-mediated and antibody-antigen reactions to the specific fungal antigens. Here we present two cases of allergic fungal sinusitis--one caused by Curvularia lunata species (an ubiquitous soil fungi), another caused by Alternaria. Only one other case of allergic fungal sinusitis caused by curvularia in which extensive immunologic testing was done has appeared in the literature. No reports of alternaria causing allergic fungal sinusitis have appeared in the literature. Diagnostic criteria for allergic fungal sinusitis include radiologic evidence of pansinusitis in an atopic individual; findings at surgery of allergic mucin; positive fungal cultures; and specific immunologic testing, including both humoral and cellular arms of the immune system. Treatment options for allergic fungal sinusitis are discussed and include surgery alone, surgery and steroids, or steroids alone. The role of allergy immunotherapy injections remains to be defined. In general, fungal infections--and especially phaeohyphomycosis--are very rare, but appear to be increasing in frequency, especially in the paranasal sinus region.

Long-term results of ethmoid surgery.

This paper investigates the results of nonendoscopic intranasal ethmoid surgery on 146 patients who were followed up for 6 to 13 years. These patients are divided into four groups: 1) infection without allergy, 2) infection with allergy, 3) infection with polyps and no allergy, and 4) infection with polyps and allergy. These groups are evaluated as to the long-term results of surgical treatment with or without concurrent allergic desensitization. The great majority of patients benefited from the surgical treatment regardless of their allergic status. Postoperatively, the allergic patients had more subjective symptoms than those having only infection. A major conclusion was that the long-term benefit to the patient as a result of the operation performed by experienced hands does override the potential risks of ethmoid surgery.

Functional endoscopic sinus surgery and allergy.

The principles of functional endoscopic surgery require adequate sinus ventilation and drainage to avoid chronic disease states. The techniques employed by Messerklinger, Stammberger, and Kennedy have been demonstrated to be safe and effective. Careful evaluation of patients preoperatively with a careful allergy history and at least screening allergy tests, either intradermal or radioallergosorbent, is essential. Once the diagnosis of allergic rhinitis is established, the onset of therapy should precede surgical intervention to aid in appropriate surgical patient selection and to obtain the maximal symptomatic and functional relief postoperatively.

[92 cases of allergic-type nasal polyp. A methodology for its etiological characterization]. / Estudo de 92 casos de polipo nasal de tipo alergico. Uma metedologia para a sua caracterização etiológica.

The etiopathogenesis of nasal allergic polyps is poorly understood; an immunological mediated mechanism is commonly admitted. A clinic-pathological study of 92 cases of nasal polyps is reported. The occupational and or environmental background of the patients was recorded. Appropriate histochemical techniques were applied to identify pollutants within the lesions. Iron, wood, cement, cork, paper, glass, tobacco, textile fibres and chalk could be identified. The follow-up of patients at 12 years after excision of polyps revealed a decrease in recurrence whenever exposure to pollutants was discontinued. The etiology of nasal allergic polyps is probably related to the inhalation of some foreign materials reported.

Allergic disease and associated concurrent medical illnesses.

This retrospective study examined the pattern of medical illnesses, surgical procedures, and medication usage among 249 patients with allergic rhinitis contrasted with a comparison group of 253 patients with cerumen impaction. Results revealed that allergic patients experienced more frequent nasal and abdominal surgery, a higher prevalence of pulmonary and gastrointestinal disease, and used nasal sprays, antihistamines, and psychoactive medications more often than the comparison group. Implications for otolaryngology nursing practice are discussed.

Outcome of endoscopic sinus surgery in children with allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a morbid condition in children with chronic rhinosinusitis. The study goal was to determine whether children with AR who are undergoing endoscopic sinus surgery (ESS) will have a poor outcome. METHODS: The study population consisted of 141 patients who underwent ESS between January 1994 and December 2002. The outcome of ESS was measured at least 1 year after the operation. RESULTS: The overall success rate was 80%. Children with an allergy had 77% success rate compared with children with no allergy who had an 84% success rate (p = 0.25). Children with AR who were on treatment before surgery had an 84% success rate compared with 62% for those children with AR but were not treated (p = 0.022). CONCLUSION: ESS in children with AR does not have a poorer outcome. Treatment of the allergy before surgery may improve the success of ESS.

[Pathogenic treatment of nasal allergy]. / Tratamentul patogenic al alergiei nazale.

Starting from the idea that in nasal allergy the nasal conchae--especially the inferior conchae--represent the organs of shock, and that histologic studies have shown the existence in the mucosa and erectile tissue of antibody-forming lymphocytes and plasma cells, the authors assumed that by removing this tissue they might prevent the formation of the antibodies concerned, and hence avoid conflict with the antigen. This would represent an immunosuppressive action, the only method according to allergologists to obtain recovery in allergies. Starting in 1976, the authors performed mucotomy of the tips and lower edges of the inferior conchae and sometimes of the middle conchae, obtaining recovery of all the 40 operated patients with nasal allergy, recovery checked in the course of four years.

Surgery in allergic nasal and paranasal disease.

This paper summarizes an ENT surgeon's view of allergic rhinitis and deals with the presenting complaints and symptoms of allergic and non-allergic rhinitis, suggests the important features of the history and examination and indicates the more important special investigations; the medical and surgical treatments available to deal with the symptoms of rhinitis are discussed.

[Late results of endonasal ethmoid bone operation with special reference to polypous sinusitis]. / Spätergebnisse nach endonasaler Siebbeinoperation unter besonderer Berücksichtigung der polypösen Sinusitis.

Out of total of 164 patients with chronic sinusitis undergoing intranasal microsurgery, 94 patients were submitted to a detailed analysis one year later. The patients were divided into groups of polypoid and hyperplastic sinusitis, depending on the morphological appearances and the histology of the tissue removed. Patients with polyps showed a significantly higher rate of recurrent (47%) than patients with hyperplastic sinusitis (8.6%). Allergy or bronchial asthma did not influence significantly the rate of recurrence in patients with nasal polyposis, whereas patients with a hyperplastic sinusitis showed a higher recurrence rate if they were atopic as well. However, even patients with polypoid sinusitis gained marked long-term relief of nasal obstruction and other symptoms.

Allergic fungal sinusitis caused by Bipolaris (Drechslera) hawaiiensis.

Depending on the aggressiveness of the pathogen and a patient's immunocompetence, fungal polypoid pansinusitis or allergic fungal sinusitis (AFS) may be a life-threatening disease. Apart from the clinical findings, its diagnosis is based on the demonstration of mucinous material with abundant eosinophils in the paranasal sinuses (indicating an allergic process), cultivation of the causative pathogen and immunocompetence of the patient. In a 20-year-old immigrant Sudanese woman, AFS due to Bipolaris (Drechslera) hawaiiensis was diagnosed. Because of intracranial extension, the disease had led to erosion of the cranial base and orbit with amaurosis on the right side and focal epilepsy. In addition to endonasal microsurgical pansinus operations, local irrigation therapy with amphothericin B was accompanied by systemic treatment with itraconazole after in vitro cultivation of the pathogen and determination of its sensitivities. Interdisciplinary management included a combination of endonasal surgery with debridement of infected tissues and wide drainage of the sinuses without removal of skull bone or the dural lesion in addition to specific antimycotic treatment. Injury to adjacent anatomical structures must be avoided in any case to prevent systemic or possibly lethal dissemination of infection.

Allergic fungal sinusitis: CT findings.

PURPOSE: To determine the computed tomographic (CT) findings in patients with allergic fungal sinusitis. MATERIALS AND METHODS: The authors retrospectively reviewed CT scans and surgical and histopathologic reports in 45 patients (27 male, 18 female; age range, 8-68 years) with allergic fungal sinusitis from multiple institutions. The median age (25 years) and demographics of the patients were determined. Two head and neck radiologists together evaluated the CT scans for the presence of intrasinus high-attenuation areas, extent of sinus involvement, bone expansion and thinning, bone erosion, and extension of disease into the adjacent soft tissues. RESULTS: Allergic fungal sinusitis was more common in male patients and in patients aged 20-30 years. All patients had increased intrasinus attenuation at non-contrast material-enhanced CT. Multiple sinus involvement occurred in 43 patients. Bilateral involvement was more common than unilateral disease. Forty-four patients had complete opacification of at least one of the involved sinuses; 43 of these patients had expansion of an involved sinus, 42 had remodeling and thinning of the bony sinus walls, and 41 had erosion of the sinus wall. CONCLUSION: Allergic fungal sinusitis is a distinct clinical entity with nonspecific symptoms that may be initially suggested by the CT findings. These findings should alert the clinician to the possibility of allergic fungal sinusitis and prompt other diagnostic studies to establish the diagnosis and treatment plan.

Tratamiento de la rinitis alérgica en la embarazada / Treatment of allergic rhinitis during pregnancy

El tratamiento de la rinitis alérgica (RA) en la paciente embarazada se ve obstaculizado por el temor que el especialista experimenta al intentar utilizar medicamentos que podrían provocar problemas en el desarrollo del feto. Este dilema es especialmente acentuado cuando la embarazada está en sus primeros meses de embarazo. Sin embargo, la persistencia de síntomas y las molestias que la rinitis alérgica le ocasiona a la paciente coloca al especialista en una disyuntiva importante: cómo tratar a la enferma sin provocar daños en el niño en gestación. La FDA ha clasificado los medicamentos que en estos casos pueden utilizarse y el metaanálisis de estudios realizados en embarazadas avala la prescripción de los fármacos que aquí se aconsejan. Es factible, además, realizar algunos procedimientos quirúrgicos durante el embarazo sin que ello involucre riesgo en la paciente ni en el feto.