5例变应性支气管肺曲菌病长期误诊临床分析

变应性支气管肺曲菌病(ABPA)是人体对曲霉菌(主要是烟曲霉)产生超敏反应引起的一种疾病.因该病较为少见、临床医师对其认识不足、大多医院缺少烟曲霉特异性检查手段等因素,病人往往被长期误诊误治,严重影响患者预后.本文将对江苏省人民医院呼吸科5例确诊ABPA患者进行临床分析,以提高对该病的认识,减少误诊.     

变态反应性支气管肺曲菌病1例

变态反应性支气管肺曲菌病（ABPA）的特征是机体对存在于支气管分支内的烟曲菌抗原呈现免疫反应，并出现肺浸润和近端支气管扩张。现将我院收治的1例患者相关资料报告如下并文献复习。     

19例变态反应性支气管肺曲霉病临床分析

目的总结分析不同类型变态反应性支气管肺曲霉病（allergic bronchopulmonary aspergillosis,ABPA）的临床特点，提高对ABPA的认识，做到早诊断早治疗。方法分析中山医院近5年确诊的19例ABPA患者的临床资料，分为变态反应性支气管肺曲菌病-血清IgE增高型组和变态反应性支气管肺曲菌病-中心支气管扩张型组，比较两组病人的临床症状和实验室特点。结果19例ABPA患者中男11例，女8例，在确诊前被误诊为肺结核的有8例，误诊为肺癌的有3例，其他诊断包括支气管哮喘、过敏性肺炎、Wegener肉芽肿等。两组病人在年龄、性别、症状等方面差别无统计学意义，但ABPA伴中心型支气管扩张组的嗜酸粒细胞和血清总IgE水平比血清IgE增高型的ABPA组升高（P〈0.01），而第一秒用力呼气容积占预计值百分比则降低（P〈0.01）。结论不伴中心型支气管扩张的ABPA可能是疾病的早期或侵袭性较弱的一种形式，为避免肺功能出现不可逆的改变，对气喘、肺部出现游走性浸润影、嗜酸性粒细胞及IgE升高者应进一步查肺CT、烟曲菌特异性IgE和烟曲菌抗原皮内试验，以及早确诊并治疗。     

变应性支气管肺曲菌病的诊治最新进展

变应性支气管肺曲菌病(allergic bronchopulmonary aspergillosis,ABPA)是机体对烟曲霉过敏引起的一种免疫性肺部疾病,最常见于哮喘和囊性纤维化患者.诊断标准包括慢性哮喘的临床表现、反复肺浸润与支气管扩张、血嗜酸粒细胞增高、血清总IgE增高及烟曲霉皮肤试验阳性等.由于许多ABPA患者症状轻微或无症状,对于哮喘患者一定要想到ABPA的可能,并进一步筛查皮肤试验,以防漏诊.早期诊断可早期给予糖皮质激素治疗,但激素可能要长期应用,激素联合较新的唑类抗真菌药可能更有效.本文对近几年来ABPA的流行病学、发病机制、诊断及处理进行综述.     

变态反应性支气管肺曲霉病诊治的研究进展

变态反应性支气管肺曲霉病(allergic bronchopulmonary aspergillosis,ABPA)与烟曲菌感染引起的变态反应相关.ABPA可引起血清总IgE升高,外周血嗜酸粒细胞升高,肺浸润和中心性支气管扩张.若未得到有效治疗可发生肺组织结构的不可逆破坏,最终导致呼吸衰竭,故ABPA的早期诊断和早期治疗十分重要.ABPA的治疗取决于疾病的分期、临床表现、血清总IgE、肺功能和影像学检查,以往多以口服糖皮质激素治疗为主,目前普遍推荐口服糖皮质激素加抗真菌的联合治疗方案,以达到控制机体对烟曲菌抗原的过敏反应,清除寄生于气道内的烟曲菌的目的.本文将对近年ABPA诊治进展作一综述.     

变应性支气管肺曲菌病治疗中需警惕感染

目的对长期以糖皮质激素治疗的变应性支气管肺曲菌病(allergic bronchopulmonary aspergillosis,ABPA),鉴别病情出现反复的原因。方法收集ABPA病情趋于活动的患者,并长期随访观察以明确诊断。结果 ABPA患者在予糖皮质激素和抗真菌药物治疗过程中,病情出现反复,确诊并发细菌感染后给予抗感染治疗,病情得到控制。结论ABPA治疗过程中需警惕并发感染,以避免误诊误治。     

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。     

变态反应性支气管肺曲菌病的诊断和治疗

变态反应性支气管肺曲菌病(Allergic bronchopulmonary aspergillosis简称ABPA)是宿主对在支气管内生长的曲菌呈现变态反应的一种疾病。Henderson等研究肺部曲菌病在慢性肺病患者中的发生率,发现46例哮喘符合本病者为11%。有人认为本病占支气管哮喘病例的8%。有的作者作回顾性调查,证实在皮质类固醇依赖性哮喘患者中,本     

呼吸系统曲霉菌病重叠综合症的新进展

肺部曲霉菌病是少见病,但近年逐年增多,包括变应性支气管肺曲菌病(allergic bronchopulmonary aspergillosis,ABPA)、曲菌球(aspergilloma)、慢性坏死性肺曲菌病(chronic necrotizing aspergillosis,CNA)、侵袭性肺曲菌病(invasive pulmonary aspergillosis,IPA)及全身播散性曲菌病等5型.其中ABPA、曲菌球甚至IPA可合并变应性曲霉菌性鼻窦炎(allergic Aspergillus sinusitis,AAS),可能与基础病及其治疗等因素有关.本文就近期文献报告的呼吸系统曲霉菌病重叠综合症作一综述.     

变应性支气管肺曲菌病长期漏诊1例及文献复习

变应性支气管肺曲菌病（ABPA）是一种变态反应性疾病,也称哮喘性肺嗜酸粒细胞浸润症,临床上容易出现误诊和漏诊,如不经治疗最终可发展为支气管扩张及肺间质纤维化、病情反复不愈,因此早期诊断、充分治疗对患者的预后及转归有重要意义。我科有1例长期误诊为肺结核并进行全疗程正规抗痨治疗而效果不理想病例,在诊断ABPA后给予激素治疗效果明显,现报道如下：     

Allergic bronchopulmonary aspergillosis in cystic fibrosis: role of atopy and response to itraconazole

STUDY OBJECTIVES: (1) To determine the relationship between IgE levels and the prevalence of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients, (2) to establish the usefulness of assessing atopy as an identifying risk factor for ABPA, (3) to evaluate the clinical course of patients receiving and not receiving itraconazole as reflected in oral steroid dose requirements and number of acute episodes of ABPA, and (4) to determine the role of acute episodes of ABPA in pulmonary exacerbations of CF. DESIGN: Retrospective review of online clinical database and medical records. SETTING: CF clinic and inpatient services of Lucile Salter Packard Children's Hospital at Stanford. PATIENTS: One hundred seventy-two patients with CF for whom serial serum total IgE levels were measured over a 5-year study period, 1992 to 1996. INTERVENTIONS: We reviewed records of patients followed up at the CF Center at Stanford who had serum total IgE measured between January 1, 1992, and December 31, 1996. Total IgE and Aspergillus fumigatus (Af) specific IgE antibodies were measured by commercial fluorometric solid-phase immunoassay. Precipitating antibodies to Af were measured by double immunodiffusion. Patients who were diagnosed as having ABPA were treated with itraconazole unless significant liver dysfunction was present. Oral steroid dosing requirements and acute episodes of ABPA for days with vs days without itraconazole were compared. MEASUREMENTS AND RESULTS: Serum total IgE was elevated (> 1 SD > geometric mean for age) in 51% of patients tested. IgE > 500 IU/mL, chosen as a screening cutoff for evaluating possible ABPA, was present in 19% of patients at some time during the study period. Atopy (defined as > or = 1 IU/mL IgE antibody to > or = 1 allergen) was present in 61% of 104 patients tested for specific allergen sensitization. ABPA was diagnosed in 16 patients (9%). ABPA occurred in 22% of atopic CF patients but only in 2% of nonatopic patients (p = 0.001). Six percent of pulmonary exacerbations requiring hospitalization were associated with acute episodes of ABPA. Over the study period, itraconazole use was associated with a reduced average daily oral steroid dose of 47% (p = 0.05) and a reduction in the number of acute ABPA episodes by 55% (p < 0.001). CONCLUSIONS: Screening for atopy may be a cost-effective way to select CF patients for periodic monitoring with total serum IgE levels, since there is an increased risk of ABPA developing in atopic CF patients. Itraconazole treatment of ABPA is safe and associated with fewer acute episodes of ABPA despite reduction in average daily oral steroid dose.     

Chemokines indicate allergic bronchopulmonary aspergillosis in patients with cystic fibrosis

RATIONALE: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a Th2 immune response. Mouse models suggest a critical role for the Th2 chemokines thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in ABPA. OBJECTIVES: To determine whether serum levels of TARC and MDC characterize ABPA in patients with cystic fibrosis (CF) and to examine longitudinally if levels of TARC and MDC indicate ABPA exacerbations in patients with CF. METHODS: Levels of TARC and MDC and levels of Th1 (IL-12 and IFN-gamma) and Th2 (IL-4, IL-5, and IL-13) cytokines were analyzed in serum of 16 patients with CF with ABPA, six non-CF patients with asthma with ABPA, 13 patients with CF colonized with Aspergillus fumigatus, six patients with CF sensitized to A. fumigatus, 12 atopic patients with CF, and 13 non-CF atopic control subjects by ELISA. The longitudinal course of TARC, MDC, and IgE levels was assessed during ABPA episodes. RESULTS: Patients with ABPA had significantly higher serum levels of TARC compared with the other patient groups. Cytokine levels did not differ among the patient groups. Longitudinally, levels of TARC indicated ABPA exacerbations in patients with CF more clearly than IgE levels. In patients with CF and ABPA, levels of TARC correlated positively with specific IgE to A. fumigatus and rAsp f4. CONCLUSIONS: Serum levels of TARC differentiate patients with CF or patients with asthma with ABPA from patients with CF colonized with or sensitized to A. fumigatus, atopic patients with CF, and atopic control subjects. Longitudinally, levels of TARC indicate ABPA exacerbations, suggesting TARC as a marker for identification and monitoring of ABPA in patients with CF.     

Allergic bronchopulmonary aspergillosis in cystic fibrosis: reported prevalence, regional distribution, and patient characteristics. Scientific Advisory Group, Investigators, and Coordinators of the Epidemiologic Study of Cystic Fibrosis.

OBJECTIVES: Using the large database from the Epidemiologic Study of Cystic Fibrosis (ESCF), the objectives of this study were to (1) estimate the reported prevalence of allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF); (2) compare reported prevalence rates across geographic regions; (3) compare reported prevalence rates between patient subgroups based on demographic and disease characteristics; and (4) describe the ABPA group with regard to their sex, age, and disease severity. STUDY DESIGN: All patients > or = 5 years of age enrolled in ESCF between December 1993 and May 1996 were eligible. Criteria for the diagnosis of ABPA were defined by the ESCF guidelines. Prevalence rates for ABPA were calculated, and potential risk factors for the diagnosis of ABPA were analyzed, including sex, age, pulmonary function, diagnosis of asthma, presence of wheeze, and positive respiratory culture for Pseudomonas. RESULTS: There were 14,210 eligible patients enrolled in ESCF during this period, and ABPA was diagnosed in 281 patients (2%). Regional prevalence varied from 0.9% in the Southwest to 4.0% in the West. Increased prevalence rates occurred in female patients, the adolescent age group, and subjects with lower lung function, wheeze, asthma, and positive Pseudomonas cultures. Although most ABPA patients had evidence of airway obstruction, 10% had an FEV1 of > 100% of predicted. The rates of wheeze (17%) and asthma (30%) were lower than expected in the ABPA group. CONCLUSIONS: This observational study found a reported prevalence rate of ABPA of 2% of CF patients in a large database. This rate was lower than the 5 to 15% rate reported in smaller studies, suggesting that ABPA is underdiagnosed in the CF population. There was wide regional variation in reported prevalence rates, which is unexplained at this time. The characteristics of the patients with ABPA and the epidemiologic risk factors for diagnosis of ABPA were described. Simplified diagnostic criteria were adapted for ESCF with the intent of increasing awareness of ABPA among the participants in this study.     

Mild,moderate, and severe forms of allergic bronchopulmonary aspergillosis: a clinical and serologic evaluation

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disorder induced by Aspergillus species colonizing the bronchial tree. There are patients with asthma who fulfill the diagnostic criteria of ABPA by serologic evaluation (specific IgE/IgG to Aspergillus fumigatus), bronchography, CT, and or conventional linear tomography. OBJECTIVE: To identify different forms of ABPA based on various diagnostic criteria. METHODS: Eighteen patients with asthma fulfilling the criteria of ABPA were evaluated in the present study. Six patients each received a diagnosis of ABPA serologic positive (ABPA-S), ABPA with central bronchiectasis (ABPA-CB), and ABPA with central bronchiectasis and other radiologic features (ABPA-CB-ORF). RESULTS: The spirometric changes in the ABPA-S group (group 1) were mild, in the ABPA-CB group (group 2) were moderate, and in the ABPA-CB-ORF group (group 3) were severe. Absolute eosinophil count was raised in each group but was maximum (1,233 micro L) in severe form of disease (group 3). Specific IgE against A fumigatus was raised in each group, and the maximum was 47.91 IU/mL in ABPA-CB-ORF. CT scan findings of the ABPA-S group were normal without central bronchiectasis. The exacerbation in symptoms was maximum in group 3 compared to other groups. CONCLUSION: The present observations suggest that ABPA includes mild (ABPA-S), moderate (ABPA-CB), and severe (ABPA-CB-ORF) forms of disease. It is recommended, therefore, that the disease should be diagnosed early, treated at the mild form of disease (ABPA-S), and prevented from leading to ABPA-CB or ABPA-CB-ORF.     

Prevalence of allergic bronchopulmonary aspergillosis in cystic fibrosis in an area with a high frequency of atopy

BACKGROUND: Lower airway colonisation with Aspergillus fumigatus and the complicating hypersensitivity reaction allergic bronchopulmonary aspergillosis (ABPA) is well recognised in patients with cystic fibrosis (CF). There is a wide range in reported prevalence of ABPA in CF. Differences in predisposing factors such as atopy and climatic humidity, but also differences in reporting may in part explain this observation. In the Australian population there is a high frequency of atopy and the climate is relatively humid. PATIENTS AND METHODS: Children and adolescents with CF (n = 277) from the CF Clinic, Children's Hospital at Westmead, Sydney, Australia were included in a retrospectively conducted study of Aspergillus colonisation and ABPA (1998-2003). RESULTS: The prevalence of Aspergillus colonised patients increased significantly from 7.4% in 1998 to 18.8% in 2002. No seasonal variation in initial positive Aspergillus culture or in humidity was observed. A total of 13 patients (4.7%) were diagnosed with ABPA over the study period, with a significant increase in prevalence from 0.3% in 1998 to 4.0% in 2002. In addition, the criteria used for reporting ABPA in the study population were in agreement with the recently published diagnostic criteria for ABPA in CF. CONCLUSIONS: In spite of a high frequency of atopy and a relatively humid climate in the Sydney area, Aspergillus colonisation and ABPA in CF patients was not disproportionate. Moreover, criteria for reporting of ABPA in this setting was not different from that in the Northern Hemisphere.     

Allergic bronchopulmonary aspergillosis: lessons from 126 patients attending a chest clinic in north India

AIMS AND OBJECTIVES: To describe the experience of screening patients with asthma for allergic bronchopulmonary aspergillosis (ABPA) presenting to a chest clinic. The clinical, serologic, radiologic, and treatment aspects including outcome of ABPA are also described. METHODS: All consecutive patients with asthma presenting to the chest clinic over a period of 2 years were screened with an Aspergillus skin test. Patients who were found to be positive were further investigated for ABPA. Patients were also arbitrarily classified as ABPA-seropositive (ABPA-S), ABPA with central bronchiectasis (ABPA-CB), and ABPA-CB with other radiologic findings (ABPA-CB-ORF) based on the high-resolution CT findings. RESULTS: Five hundred sixty-four patients were screened using an Aspergillus skin test; 223 patients (39.5%) were found to be positive, and ABPA was diagnosed in 126 patients (27.2%). There were 34 patients (27%) with ABPA-S, 42 patients with ABPA-CB, and 50 patients with ABPA-CB-ORF. Fifty-nine patients (46.8%) had received antitubercular therapy in the past. The vast majority of patients had bronchiectasis at presentation to our hospital. High-attenuation mucous impaction was noted in 21 patients (16.7%). There was no significant difference between the stages of ABPA and the duration of illness, the severity of asthma, and the serologic findings (ie, absolute eosinophil count, IgE levels [total] and IgE levels [for Aspergillus fumigatus]). The median duration of follow-up was 13 months (range, 9 to 38 months). All patients went into "remission" at 6 weeks. Twenty-five patients had a "relapse" during the course of their treatment. One hundred nine patients had "complete remission," 17 patients were classified as having "glucocorticoid-dependent ABPA," and 7 patients were classified as having "end-stage ABPA." CONCLUSIONS: There is a high prevalence of ABPA in asthmatic patients presenting at our hospital. The disease entity is still underrecognized in India; the vast majority of patients have bronchiectasis at presentation, and almost half are initially misdiagnosed as having pulmonary tuberculosis. There is a need to redefine the definitions of ABPA and the optimal dose/duration of glucocorticoid therapy. This study reinforces the need for the routine screening of asthmatic patients with an Aspergillus skin test.     

Clinical significance of hyperattenuating mucoid impaction in allergic bronchopulmonary aspergillosis: an analysis of 155 patients

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a disease that presents with diverse clinicoradiologic manifestations. High-attenuation mucus (HAM) is a characteristic radiologic finding seen in patients with ABPA; however, the clinical significance of the entity remains unknown. AIMS AND OBJECTIVES: To describe the outcome of patients with ABPA who were demonstrated to have HAM, and compare with the outcome of patients without HAM. METHODS: All consecutive patients with asthma presenting to the Chest Clinic of this institute over a 4-year period were screened with an Aspergillus skin test. Patients with positive findings were further investigated, and the diagnosis of ABPA was confirmed based on predefined criteria. The patients were further classified into two groups based on the presence of HAM on HRCT scan. RESULTS: During the study period, 755 patients were screened for ABPA using the Aspergillus skin test; 291 patients (38.5%) had positive findings, and ABPA was diagnosed in 155 patients (mean age, 33.98 years; 76 women). Twenty-nine patients (18.7%) with ABPA were identified to have HAM on HRCT scans at presentation. The baseline characteristics were similar between the two groups, but patients with HAM had higher mean eosinophil counts, higher mean serum total IgE, and higher Aspergillus fumigatus-specific IgE levels. On multivariate analysis, both the severity of bronchiectasis and HAM predicted relapse of ABPA (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.13 to 1.42; and OR, 3.61; 95% CI, 1.23 to 10.61, respectively). Failure to achieve complete remission was influenced by the severity of bronchiectasis but not by HAM (OR, 1.55; 95% CI, 1.29 to 1.85; and OR, 3.41; 95% CI, 0.89 to 13.1, respectively). CONCLUSIONS: HAM impaction in ABPA is associated with initial serologic severity and frequent relapses but does not seem to influence complete remission.     

Sensitization to Aspergillus antigens and occurrence of allergic bronchopulmonary aspergillosis in patients with asthma

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA), which is predominantly a disease of asthmatic subjects, is caused by hypersensitivity to Aspergillus antigens. Screening for Aspergillus sensitization in asthmatic subjects could identify those who are at risk for ABPA. Few studies have shown that fungal sensitization could be an important risk factor for asthma severity. We sought to determine the frequency of sensitization to Aspergillus antigens in asthmatic subjects and its effect on disease severity. We also determined the occurrence of ABPA in these subjects. DESIGN: Prospective study of consecutive patients with asthma. SETTING: Tertiary university referral hospital, outpatient department. PATIENTS AND METHODS: One hundred five asthmatic subjects and 26 volunteers underwent skin testing with aeroallergens, including Aspergillus, serum precipitins against Aspergillus antigens, and specific IgG against Aspergillus fumigatus, total serum IgE levels, and routine blood and radiologic investigations. ABPA was diagnosed when all eight major criteria were fulfilled. RESULTS: Thirty patients (28.5%) had a positive skin reactivity to Aspergillus antigens. Eleven patients (10.4%) had positive specific reactions to IgG, and 8 patients (7.6%) demonstrated positive reactions to serum precipitins. Eight of these 30 patients (26.6%) received diagnoses of ABPA, which was 7.6% of the total. None of the control subjects were sensitized to Aspergillus antigens. The patients were classified into the following four groups: negative skin test results; positive reactions to aeroallergens other than Aspergillus; positive reactions to aeroallergens including Aspergillus antigens; and patients with ABPA. Based on clinical and serologic parameters, patients with Aspergillus-sensitive asthma and ABPA had a significantly more severe form of the disease. CONCLUSIONS: Sensitization to the mold Aspergillus increases the severity of asthma. ABPA should be excluded in all patients with Aspergillus-sensitive asthma.     

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.