Allergic bronchopulmonary aspergillosis and related allergic syndromes

While allergic bronchopulmonary aspergillosis (ABPA) is well recognized as a fungal complication of asthma, severe asthma with fungal sensitization (SAFS) is not. In ABPA the total immunoglobulin E (IgE) is usually >1,000 IU/mL, whereas in SAFS it is <1,000 IU/mL, and either skin prick tests or fungus-specific IgE tests are positive. ABPA may present with any severity of asthma, and occasionally with no asthma or cystic fibrosis, the other common underlying disease. SAFS is a problem in patients with poorly controlled asthma and occasionally presents in the intensive care unit (ICU). Production of mucous plugs and coughing paroxysms is more common in ABPA. Certain underlying genetic defects seem to underpin these remarkable phenotypic differences. From a management perspective both ABPA and SAFS respond to both high doses of corticosteroids and oral antifungal agents, with ～60% response rate in both ABPA and SAFS with itraconazole. In 50% of patients itraconazole boosts inhaled corticosteroid exposure, sometimes leading to cushingoid features. Second-line therapy data are scant, but we have shown that 70 to 80% of patients who tolerate either voriconazole or posaconazole also respond. Other useful therapies include nebulized hypertonic saline to aid expectoration of thick sputum and long-term azithromycin for its anti-inflammatory effect on the airways. Omaluzimab is useful in some patients with SAFS and occasionally in ABPA. Complications of ABPA include bronchiectasis, typically central in distribution, and chronic pulmonary aspergillosis. Most patients with ABPA and SAFS can be stabilized for long periods with inhaled corticosteroids and itraconazole or another antifungal agent. Novel immunotherapies are on the horizon.     

Fungal sensitisation in severe asthma is associated with the identification of Aspergillus fumigatus in sputum

Background: Fungal sensitisation is an important factor in severe asthma, not only for allergic bronchopulmonary aspergillosis (ABPA) but also the more recently described severe asthma with fungal sensitisation (SAFS). It is not known whether these diseases are driven by the presence of airway fungal colonisation. We aimed to determine if both SAFS and ABPA were associated with airway isolation of Aspergillus fumigatus and whether the frequency of isolation changed following anti-fungal treatment. Methods: Sputum samples were collected from patients with SAFS, ABPA and a control group without fungal sensitisation. We recorded details of antifungal treatment, serum IgE and A. fumigatus specific IgE levels. In a subgroup (n = 9) we recorded serial sputum PCR measurements before and during itraconazole therapy. Results: 244 sputum samples were provided by 135 patients, 41(17%) ABPA, 168(69%) SAFS, and 35(14%) controls. Sputum Aspergillus fumigatus PCR was positive in 61 SAFS patients (70%) and 6 ABPA patients (50%) not on anti-fungal treatment at the time of the test, compared to 3 (9%) in controls (χ² = 37.90, p < 0.001). Consequently, 19 patients with SAFS who were taking antifungal treatment (23%) were significantly less likely to be PCR positive than the 61 patients not on treatment (70%) (χ² = 36.66, p < 0.001). All 9 patients assessed serially during therapy had positive sputum PCR pre-treatment and all became negative during itraconazole treatment. Conclusion: We have shown that isolation of fungus from the airway of severe asthma patients with fungal sensitisation is very common, supporting the hypothesis of a mechanistic link between fungal colonisation and sensitisation.     

Voriconazole and posaconazole improve asthma severity in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization

Rationale and objectives. Severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) are progressive allergic fungal lung diseases whose effective treatment remains to be established. Current treatment with itraconazole is associated with a 40% failure rate and adverse events (AEs). We assessed the effect of voriconazole or posaconazole as second- and third-line therapies. Methods. We conducted a retrospective review of adult asthmatic patients with either ABPA or SAFS receiving voriconazole or posaconazole. Clinical, radiological, and immunological evaluation was used to assess response. Results. There were 25 patients, ABPA (n = 20) or SAFS (n = 5), 10 males, median age = 58 years. All patients had failed itraconazole (n = 14) or developed AEs (n = 11). There were 33 courses of therapy analyzed, 24 with voriconazole and 9 with posaconazole. Clinical response to voriconazole was observed in 17/24 (70%) patients at 3 months, 15/20 (75%) at 6 months, and 12/16 (75%) at 12 months compared with 7/9 (78%) at 3, 6, and 12 months for posaconazole. Eighteen of 24 (75%) patients discontinued oral corticosteroids (OCS), 12 of them within 3 months of therapy. Asthma severity was downgraded from severe to moderate (n = 8) and moderate to mild (n = 1) asthma in 9 of 24 (38%) asthmatic patients. There was a marked reduction in OCS and short-acting beta-2 agonist use, health-care utilization due to asthma, and improvement in overall health status. Furthermore, there was a statistically significant reduction in immunological markers appearing at 9 months (p = .008) for total IgE and at 12 months for radioallergosorbent test IgE for Aspergillus fumigatus (p = .0056). Six of 23 (26%) patients on voriconazole had AEs requiring discontinuation before 6 months compared with none on posaconazole (p = .15). Four relapsed (57%), one at 3 months and three at 12 months after discontinuation. Conclusion. Both voriconazole and posaconazole are potentially effective alternative treatment options for SAFS and ABPA and may improve asthma control and reduce severity, though larger prospective studies are required to support these retrospective study findings.     

真菌致敏的严重支气管哮喘三例并文献复习

目的 探讨真菌致敏的严重支气管哮喘(SAFS)的临床特点,提高对该病的诊治水平.方法 回顾性分析杭州市第一人民医院自2005年5月至2009年6月收治的3例SAFS患者的临床特点、治疗方案及预后,同时结合相关文献进行复习.结果 3例患者中女性2例、男性1例,年龄分别为55岁、52岁和61岁,哮喘病史4～40余年;均为哮喘反复发作,真菌皮肤试验阳性,血清IgE＜1000 IU/ml,痰培养均有烟曲霉生长,胸部高分辨CT均未发现支气管扩张和肺部浸润影.2例患者血清半乳甘露聚糖(GM)抗原检测阳性.3例患者确诊SAFS后,加用抗真菌治疗4～22个月,临床喘息症状缓解,复查GM转阴.结论 对于哮喘反复发作且常规治疗效果不佳的患者,如果真菌皮肤试验阳性而 IgE又无明显增高,应考虑到SAFS的可能,加用抗真菌治疗可控制喘息症状.     

Voriconazole and Posaconazole Improve Asthma Severity in Allergic Bronchopulmonary Aspergillosis and Severe Asthma with Fungal Sensitization

Rationale and objectives. Severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) are progressive allergic fungal lung diseases whose effective treatment remains to be established. Current treatment with itraconazole is associated with a 40% failure rate and adverse events (AEs). We assessed the effect of voriconazole or posaconazole as second- and third-line therapies. Methods. We conducted a retrospective review of adult asthmatic patients with either ABPA or SAFS receiving voriconazole or posaconazole. Clinical, radiological, and immunological evaluation was used to assess response. Results. There were 25 patients, ABPA (n = 20) or SAFS (n = 5), 10 males, median age = 58 years. All patients had failed itraconazole (n = 14) or developed AEs (n = 11). There were 33 courses of therapy analyzed, 24 with voriconazole and 9 with posaconazole. Clinical response to voriconazole was observed in 17/24 (70%) patients at 3 months, 15/20 (75%) at 6 months, and 12/16 (75%) at 12 months compared with 7/9 (78%) at 3, 6, and 12 months for posaconazole. Eighteen of 24 (75%) patients discontinued oral corticosteroids (OCS), 12 of them within 3 months of therapy. Asthma severity was downgraded from severe to moderate (n = 8) and moderate to mild (n = 1) asthma in 9 of 24 (38%) asthmatic patients. There was a marked reduction in OCS and short-acting beta-2 agonist use, health-care utilization due to asthma, and improvement in overall health status. Furthermore, there was a statistically significant reduction in immunological markers appearing at 9 months (p = .008) for total IgE and at 12 months for radioallergosorbent test IgE for Aspergillus fumigatus (p = .0056). Six of 23 (26%) patients on voriconazole had AEs requiring discontinuation before 6 months compared with none on posaconazole (p = .15). Four relapsed (57%), one at 3 months and three at 12 months after discontinuation. Conclusion. Both voriconazole and posaconazole are potentially effective alternative treatment options for SAFS and ABPA and may improve asthma control and reduce severity, though larger prospective studies are required to support these retrospective study findings.     

Correlation of IgE antibody titer to Aspergillus fumigatus with decreased lung function in cystic fibrosis

Obstructive pulmonary disease is a typical feature of cystic fibrosis (CF) and is often associated with bronchial hyperreactivity. Positive skin-test reactions to Aspergillus fumigatus antigens are frequently seen even in nonatopic patients with CF. Full-fledged allergic bronchopulmonary aspergillosis (ABPA) has been estimated to occur in 10% of patients with CF. The relationship between lung function and presence of IgE antibodies to Aspergillus antigens in patients without ABPA is not clear. In 148 outpatients with CF (aged 6-34 years) specific immunoglobulin E (IgE) to Aspergillus fumigatus antigens, basic lung-function parameters, and bronchial response to salbutamol were measured. Multiple regression was performed for age, weight as percentile for actual height (indicating general condition), and Aspergillus RAST. Aspergillus IgE was present in 46% of patients; 19% had RAST class 3 or 4. Independent negative correlations of Aspergillus RAST with FEV1, FEF50%, FEF25%, RV, Chrispin Norman score, and sRaw (P less than 0.05) were found. Bronchodilator sensitivity did not correlate significantly with age and weight percentile. However, Aspergillus RAST did correlate significantly with bronchodilator response measured by sRaw (P less than 0.05). High titers of Aspergillus RAST might serve as a selective criterion for patients to be included in future studies evaluating broncholytic or antiphlogistic therapies.     

Treatment of allergic bronchopulmonary aspergillosis (ABPA) in CF with anti‐IgE antibody (omalizumab)

Allergic bronchopulmonary aspergillosis (ABPA) results from IgE induced pulmonary response to aspergillus species. Recognition and management of ABPA is challenging in cystic fibrosis (CF) patients because changes in symptoms, lung function and chest radiograph are similar to that seen in CF related pulmonary infection. Standard therapy for ABPA includes systemic steroids and adjunctive use of antifungal agents. Little has been published regarding the use of monoclonal anti‐IgE antibody in those with ABPA. We report a CF patient with her third exacerbation of ABPA who was treated with monoclonal anti‐IgE (omalizumab) antibody; she had unfavorable side effects with prednisone therapy. This therapy resulted in improvement of pulmonary symptoms and lung function not achieved with antibiotics or prednisone alone. Pediatr. Pulmonol. 2008; 43:1249–1251. © 2008 Wiley‐Liss, Inc.     

变态反应性支气管肺曲霉病研究进展

变态反应性支气管肺曲霉病(allergic bronchopulmonary aspergillosis,ABPA)与烟曲霉引起的变态反应相关,常发生在哮喘和肺囊性纤维化患者中.ABPA可引起血清总IgE水平升高,外周血嗜酸粒细胞增多,肺浸润和中心性支气管扩张,严重者可导致肺纤维化等肺组织的不可逆破坏.故ABPA的早期明确诊断和及时治疗十分重要.本文将对近年来ABPA的发病机制、临床分期、诊断标准、辅助检查及治疗研究新进展进行介绍.     

Efficacy and safety of nebulised amphotericin B (NAB) in severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA)

Background and rationale: Antifungal therapy for severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) remains poorly studied. We assessed the efficacy and safety of NAB as second and third line therapy in SAFS and ABPA. Methods: 21 adult asthmatics with SAFS (n?=?11) and ABPA (n?=?10) who had either failed itraconazole (n?=?8), voriconazole proceeded by itraconazole (n?=?5) or developed adverse events (AEs) to either agent (n?=?7) were treated with 10mg of NAB (Fungizone) twice daily. We audited clinical and immunological response, using the Asthma Quality of Life Questionnaire (AQLQ-J) scores, asthma control, FEV1, healthcare utilisation and IgE. Patients were followed up for 12 months. Results: Twenty-one patients were treated (SAFS, n?=?11) and (ABPA, n?=?10), M: F?=?8:12, median age 65 years (range, 24–78). The median duration of therapy was 30 days (0–1825). Clinical benefit was observed in three (14.3 %) in which overall mean AQLQ-J score improved by?+?2.9, mean FEV1 improved by 0.5 L and there was improvement in overall asthma control. Seven (33%) failed initial dose (bronchospasm). Eleven (52.4%) discontinued within 12 months of therapy due to delayed bronchospasm (n?=?3, within 4 weeks), equipment problems (n?=?2, within 4 weeks) and lack of clinical benefit (n?=?4, within 16 weeks). Conclusion: Our data suggest that the overall efficacy of NAB in this group of patients is poor and associated with bronchospasm. However, the excellent response in 3 patients, suggest it may be considered when other alternatives have been exhausted. Overcoming the initial bronchospasm may improve tolerability.     

呼出气一氧化氮检测在变应性支气管肺曲霉菌病诊疗中的应用

目的探讨呼出气一氧化氮(FeNO)检测在变应性支气管肺曲霉菌病(ABPA)诊疗中的应用,为ABPA的诊疗及管理提供新思路。方法收集2016年12月至2020年1月于河南省人民医院呼吸内科确诊的30例ABPA患者作为观察组;同期收集就诊于河南省人民医院呼吸内科非ABPA哮喘患者74例作为对照组,其中完善烟曲霉特异性血清免疫球蛋白E(IgE)及血清总IgE者41例。回顾性分析2组患者临床资料。结果2组患者年龄、性别及病程相比较,差异无统计学意义。观察组患者烟曲霉特异性IgE、血清总IgE、血嗜酸粒细胞计数、FeNO均高于对照组(t值分别为4.049、8.077、2.051、2.894,P值均<0.05)。spearman相关系数分析结果显示FeNO与ABPA具有一定相关性(r=-0346,P<005)。结论FeNO与ABPA的诊断具有一定的相关性,可为ABPA患者诊疗提供帮助。     

Allergic bronchopulmonary aspergillosis: disease pattern in central Arabia

Despite a high prevalence of asthma in Saudi Arabia, allergic bronchopulmonary aspergillosis (ABPA) has not been reported. We reviewed the medical records in a large university hospital in Saudi Arabia where thousands of asthmatics are being followed up. Over a 9-year period starting January 1986, the diagnosis of ABPA was made in 10 patients only. Delay in diagnosis was common and in some patients the disease was confused with fungal pneumonia, tuberculosis or tumours. Aspergillus fumigatus was isolated from one patient only and different Aspergillus species were cultured from respiratory secretions of the others. Corticosteroids were uniformly effective in all patients with active disease. Low humidity may account for this apparent rarity of ABPA, although it is possible that some cases are overlooked. Further work is needed on the prevalent fungi in the Arabian environment and their potential health effects and particularly on the prevalence of allergic bronchopulmonary fungal disease.     

烟曲霉致敏的呼吸道疾病患者对其他真菌致敏的sIgE水平及相关性分析

目的 探讨呼吸道疾患者对真菌致敏的免疫球蛋白E (specific ImmunoglobulinE,sIgE)水平及多重致敏现象.方法 筛选广州医科大学附属第一医院烟曲霉sIgE阳性且级别大于等于三级的哮喘或变态反应性支气管肺曲霉菌病(ABPA)成人患者,分为烟曲霉致敏哮喘组及ABPA组.采用ImmunoCAP 1000荧光酶联免疫系统检测患者血清点青霉、分支孢霉、烟曲霉、白假丝酵母霉、链格孢霉与长蠕孢霉sIgE浓度.结果 ABPA患者烟曲霉sIgE显著高于烟曲霉致敏哮喘患者(P＜0.05)[26.7 (13.3,54.3) kU/L vs 12.7 (5.90,33.4) kU/L]、白假丝酵母sIgE[7.90 (1.40,6.00) kU/L vs 1.00 (0.40,6.00) kU/L]、点青霉sIgE[17.6 (6.80,37.6) kU/L vs 4.30 (4.30,4.30) kU/L]、链格孢sIgE[2.60 (1.70,16.0)kU/L vs 0.90 (0.40,2.10) kU/L].所有患者皆有多重霉菌致敏现象,各霉菌sIgE水平存在不同程度相关,最优尺度分析显示烟曲霉与链格孢霉关系最近(Cronbach's Alpha=95.7％).结论烟曲霉菌致敏患者常伴多重霉菌过敏现象,或因霉菌间分泌相同的致敏蛋白引起,多种霉菌sIgE浓度的检测或可作为真菌致敏哮喘辅助检查.     

9例变应性支气管肺曲菌病误诊为肺结核临床分析

目的探讨变态反应性支气管肺曲菌病(ABPA)的临床特点及误诊为肺结核的原因。方法分析9例误诊为肺结核的ABPA的临床表现、发病、影像学表现、诊断和治疗的特点及误诊原因。结果 9例病例均有慢性咳嗽、咳痰,5例有胸闷、喘息,所有病例长时间的误诊。胸部CT显示:单侧和(或)两侧片状浸润影,呈游走,中心性支气管扩张,外周血嗜酸粒细胞增高,血清总IgE高,烟曲菌抗原皮内试验呈速发反应阳性。9例患者用激素及伊曲康唑治疗后症状改善,X线影像学明显吸收。结论 ABPA与肺结核有相似的临床表现和胸部X线影像学表现,临床医生应提高对ABPA的认识。     

Steroid-sparing effect of omalizumab for allergic bronchopulmonary aspergillosis and cystic fibrosis

Allergic bronchopulmonary aspergillosis (ABPA) is a complication commonly encountered in patients with CF that produces significant respiratory morbidity. Chronic airway colonization with Aspergillus induces strong inflammatory responses with high IgE levels. Current guidelines for therapy include prolonged courses of systemic corticosteroids as the main therapeutic strategy. However this has the potential to induce significant detrimental side effects in children. Omalizumab is a humanized monoclonal antibody directed against IgE that prevents its binding to high- and low-affinity receptors on effector cells. It has been shown to be effective in improving asthma control in patients with a strong allergic component. We present our long term experience with the use of Anti-IgE therapy in three children with CF and ABPA (mean age at start of therapy 14.2 years) who were steroid dependent. All three were already experiencing significant side effects from chronic steroid therapy. After the start of Omalizumab these children have experienced significant and sustained clinical improvements at the same time that they were discontinued from chronic systemic steroids. Our experience suggests that IgE blockade has tremendous potential as a strategy to control this disease in steroid dependent patients.     

变态反应性支气管肺曲霉菌病11例临床分析

目的 分析变态反应性支气管肺曲霉菌病(ABPA)的临床与影像学特点,以提高认识,减少误诊.方法 对我院确诊的11例ABPA患者的临床资料进行回顾性分析.结果 11例确诊ABPA患者,年龄46～85岁,平均年龄(67±12)岁,男性5例,女性6例.主要临床表现为喘息11例,咳嗽、咯痰10例(其中咳痰栓者3例),咯血2例...     

Successful treatment of allergic bronchopulmonary aspergillosis with erythromycin and fluconazole]

A 30-year-old woman was admitted to our hospital because of productive cough, wheezing, and the disclosure of abnormal shadows on chest X-ray films. The patient was given a diagnosis of allergic bronchopulmonary aspergillosis (ABPA) based on eight findings: asthma, eosinophilia, elevated serum IgE concentrations, immediate skin reactivity to Aspergillus antigen, the presence of precipitating antibodies against Aspergillus antigen, lung infiltration, central bronchiectasis, and repeated culture of Aspergillus fumigatus in sputum. Because she refused steroids, we administered erythromycin. The volume of her sputum subsequently decreased, her symptoms were brought under control, and her serum IgE fell, but the lung infiltrates did not clear. Discontinuation of erythromycin resulted in exacerbation of the patient's asthmatic symptoms, with high fever, increased sputum volume and IgE levels, and worsening lung infiltrates. These symptoms responded well to oral prednisolone medication, but sputum culture was still positive for Aspergillus fumigatus. Following discontinuation of prednisolone, the patient was treated with erythromycin, to which oral fluconazole was added for 16 months. Subsequent sputum cultures were negative for Aspergillus fumigatus, and for 7 years thereafter the patient remained in remission. Erythromycin and anti-fungal drugs may be worth trying in cases of allergic bronchopulmonary aspergillosis.     

Factors effecting impact of Aspergillus fumigatus sensitization in cystic fibrosis

The clinical impact of Aspergillus fumigatus (Af) sensitization in cystic fibrosis (CF) is controversial. We examined the effect of Af sensitization (Afs) on pulmonary function and growth using a retrospective cohort analysis over two 5-year study periods: 1996-2000 (19 Afs cases and 19 controls) and 2001-2005 (24 Afs cases and 23 controls). Sensitization was defined as Af specific radioallergosorbent test (RAST) >or= 17.5 iu/ml and total serum IgE level >or=150 iu/ml. We examined the impact of changing treatment schedules over these periods. Afs cases had lower median FEV(1) %predicted (%PR) compared to matched controls 1996: 67 versus 80, P < 0.01; 2001: 78 versus 93, P < 0.01. Afs cases in the 2001 cohort had a higher FEV(1) %PR compared to Afs cases in the 1996 cohort: 78 versus 67, P < 0.01. For the 1996 Afs cohort FEV(1) %PR fell significantly over 5 years but not for the 2001 Afs cohort. Af RAST and total IgE reflected the changes in pulmonary function. Children in the 2001 Afs cohort were prescribed significantly more oral antifungal treatment (odds ratio 4.3, 95%CI 1.2-15.7, P = 0.03). Afs children continue to have poorer lung function compared to controls but this observational, hypothesis generating study, suggests that the use of antifungal treatment is associated with better lung function.     

Adjunctive therapy of allergic bronchopulmonary aspergillosis with itraconazole.

Itraconazole is a new orally active antifungal triazole with impressive activity against Aspergillus spp. Six patients with allergic bronchopulmonary aspergillosis (ABPA), aged 14 to 49 years, were treated with oral itraconazole (200 mg twice daily) for a mean of 3.9 months (range, one to six months; three patients continue on therapy). Two patients received two courses. Three patients had underlying cystic fibrosis, and three had severe asthma; four of the six required continuous high-dose systemic prednisone (mean, 43 mg/day; confidence interval [CI], 23 to 63 mg/day) at the start of therapy. In those treated for two months or longer, the mean total serum IgE level fell from 2,462 U/ml (CI, 752 to 4,202 U/ml) to 502 U/ml (CI, 123 to 880 U/ml) during each course, and the mean daily steroid dosage was decreased to a mean of 24 mg/day (CI, 11 to 37 mg/day). All patients experienced improvement in pulmonary function during the trial, with mean FEV, increasing from 1.43 to 1.77L/sec and mean FVC from 2.3 to 2.9 L in those treated for two months or longer. The mean steady-state serum concentration of itraconazole was 5.1 micrograms/ml (range, 1.8 micrograms/ml to 7.3 micrograms/ml); the patient with the lowest concentrations had the least significant clinical response. Cultures of sputum from two of three patients became negative for A fumigatus during therapy. No adverse clinical effects occurred except loss of libido in one patient. We conclude that oral itraconazole may be an effective adjunctive therapy in ABPA, possibly by clearing the airway of Aspergillus, and that randomized trials of this agent are warranted to better define its usefulness in this disorder.     

Role of intravenous immunoglobulin in severe steroid-dependent asthma

Abstract
Background :  Subgroups of asthma patients have extremely severe respiratory symptoms that require chronic use of steroids for disease control. These patients are at risk of significant side-effects from chronic exposure to high doses of oral steroids. Intra­venous immunoglobulin (IVIG) has immunomodulatory properties as shown by its use in some immune disorders. A few trials have suggested a possible benefit in individuals with severe asthma.
Aims :  To evaluate the role of IVIG as an adjunctive therapy in steroid-dependent asthma, monitoring the outcomes of lung function and measured reduction in oral steroid requirement
Method :  Seven patients with severe steroid-dependent asthma were given IVIG at a dose of 1 g/kg each month for 6 months. Baseline pulmonary function tests and immunoglobulin levels were obtained. At the end of 6 months, the end-points observed were lung function and the degree of reduction in the dose of oral steroids. The number of hospital admissions during the 12 months following commencement of IVIG was compared with the preceding 12 months.
Results :  There was a significant reduction in daily prednisolone dose from 56 ± 31 mg to 39 ± 35 mg ( P  = 0.04, Wilcoxon rank sum test) and a decrease in the number of hospital admissions from 5.9 ± 2.9 to 3.6 ± 3.5 ( P  = 0.04). No significant improvement occurred in lung function.
Conclusion :  IVIG provides a potentially important adjunctive therapy in severe steroid-dependent asthma, reducing steroid requirement and decreasing hospital admissions, but not improving lung function. (Intern Med J 2003; 33: 341−344)     

Allergic Fungal Rhinosinusitis and the Unified Airway: the Role of Antifungal Therapy in AFRS

Allergic fungal sinusitis (AFS) or rhinosinusitis (AFRS) is a form of polypoid chronic rhinosinusitis that is believed to be due to hypersensitivity to fungal antigens. The disease is characterized by type 1 hypersensitivity to fungal allergens, dramatically elevated total serum IgE, accumulation of thick eosinophil-laden mucin with non-invasive fungal hyphae within the paranasal sinuses, nasal polyposis, and sinus bony remodeling. Because of many clinicopathologic similarities to allergic bronchopulmonary aspergillosis (ABPA), these conditions can be considered analogous examples of disease in the unified airway. However, these conditions rarely occur together and their treatment differs. The treatment of AFRS relies upon surgical removal of fungal hyphae in eosinophilic mucin, while antifungal therapy is used to clear fungi from the airways in ABPA. Several uncontrolled studies suggest there may be some benefit to antifungal agents in AFRS, but randomized trials of topical and systemic antifungal therapies have not shown beneficial results in chronic rhinosinusitis (CRS). Antifungal treatment within the sinonasal cavities does not appear to be an effective approach for most chronic sinusitis, and antifungal therapy for AFRS is unproven.