Chest radiographic and computed tomographic manifestations in allergic bronchopulmonary aspergillosis

AIM: To investigate the chest radiographic and high resolution computed tomography (HRCT) chest manifestations in glucocorticoid-na?ve allergic bronchopulmonary aspergillosis (ABPA) patients. METHODS: This is a prospective observational study and includes 60 consecutive glucocorticoid-na?ve patients with ABPA who underwent chest radiography and HRCT of the chest (1.25 mm every 10 mm) in the routine diagnostic workup for ABPA. RESULTS: Chest radiographs were normal in 50% of cases. Of the remainder, most patients demonstrated permanent findings in the form of parallel line and ring shadows suggesting bronchiectasis. Consolidation was detected in 17 cases but in the majority, the corresponding HRCT chest scan showed mucus-filled bronchiectatic cavities. Chest HRCT was normal in 22 patients, while central bronchiectasis (CB) was demonstrated in the remaining 38 patients. Bronchiectasis extended to the periphery in 33%-43% depending on the criteria used for defining CB. The other findings observed on HRCT were mucoid impaction, centrilobular nodules and high-attenuation mucus in decreasing order of frequency. CONCLUSION: Patients with ABPA can present with normal HRCT chest scans. Central bronchiectasis cannot be considered a characteristic feature of ABPA as peripheral bronchiectasis is commonly observed. Consolidation is an uncommon finding in ABPA.

Complete withdrawal of glucocorticoids after dupilumab therapy in allergic bronchopulmonary aspergillosis:A case report

BACKGROUND Allergic bronchopulmonary aspergillosis(ABPA)is an allergic reaction to Aspergillus species that aggravates bronchial asthma.Previous studies demonstrated the glucocorticoid-sparing effect of dupilumab in patients with ABPA.There is no report of complete withdrawal of glucocorticoids after dupilumab.CASE SUMMARY The patient was a 54-year-old woman with bronchial asthma treated with inhaled corticosteroids and a long-acting beta-2 agonist.She consulted our institution for productive cough and fever in March 2017.Chest computed tomography scan revealed mucoid impaction,and the bronchial lavage fluid culture was positive for Aspergillus fumigatus.The diagnosis was ABPA.The patient was treated with oral glucocorticoids from April 2017 to November 2017.In January 2019,she had bronchial asthma exacerbation,and a chest computed tomography scan showed recurrent mucoid impaction.She was treated with oral glucocorticoids and itraconazole.In February 2020,during tapering of oral glucocorticoid,she had the third episode of bronchial asthma exacerbation and a mucoid impaction.The patient was treated with dupilumab in addition to oral glucocorticoid and itraconazole.The clinical response improved,and oral glucocorticoid was discontinued in June 2020.CONCLUSION This is the first case of ABPA in which complete withdrawal of glucocorticoid was possible after treatment with dupilumab.

Value of eosinophil count in bronchoalveolar lavage fluid for diagnosis of allergic bronchopulmonary aspergillosis: A case report

BACKGROUND An immediate hypersensitive immune response to Aspergillus fumigatus antigens is one of the main characteristic features of allergic bronchopulmonary aspergillosis(ABPA).As ABPA is an allergic respiratory disease,immunoglobulin E and peripheral-blood eosinophilia have been used as diagnostic indicators.However,eosinophilia in bronchoalveolar lavage fluid(BALF)has not been considered in the diagnostic criteria for ABPA.CASE SUMMARY We present a case of ABPA in which the eosinophil count in peripheral blood was not increased,whereas the eosinophil percentage in BALF reached 60%.After antifungal and hormone therapy,imaging revealed very good resolution of lung infiltration.CONCLUSION The value of the eosinophil count in BALF for the diagnosis of ABPA is worthy of the clinician's attention,especially when the patient’s clinical features lack specificity and the diagnostic parameters are negative.

Allergic bronchopulmonary aspergillosis with marked peripheral blood eosinophilia and pulmonary eosinophilia:A case report

BACKGROUND Allergic bronchopulmonary aspergillosis(ABPA)is an immune-related pulmonary disease caused by sensitization of airway by Aspergillus fumigatus.The disease manifests as bronchial asthma and recurring pulmonary shadows,which may be associated with bronchiectasis.The diagnosis of ABPA mainly depends on serological,immunological,and imaging findings.Pathological examination is not necessary but may be required in atypical cases to exclude pulmonary tuberculosis,tumor,and other diseases through lung biopsy.CASE SUMMARY An 18-year-old man presented with recurrent wheezing,cough,and peripheral blood eosinophilia.Chest computed tomography showed pulmonary infiltration.There was a significant increase in eosinophils in bronchoalveolar lavage fluid.There was no history of residing in a parasite-endemic area or any evidence of parasitic infection.Pathologic examination of bronchoalveolar lavage fluid excluded fungal and mycobacterial infections.The patient was receiving medication for comorbid diseases,but there was no temporal correlation between medication use and clinical manifestations,which excluded drug-induced etiology.Histopathological examination of lung biopsy specimen showed no signs of eosinophilic granulomatosis with polyangiitis,IgG4-related diseases,or tumors.The diagnosis of ABPA was considered based on the history of asthma and the significant increase in serum Aspergillus fumigatus-specific immunoglobulin(Ig)E.Eosinophil-related diseases were excluded through pathological biopsy,which showed typical pathological manifestations of ABPA.CONCLUSION The possibility of ABPA should be considered in patients with poorly controlled asthma,especially those with eosinophilia,lung infiltration shadows,or bronchiectasis.Screening for serum IgE,Aspergillus fumigatus-specific IgE and IgG,and alveolar lavage can help avoid misdiagnosis.

High attenuation mucoid impaction in allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis(ABPA) is a complex hypersensitivity syndrome triggered against antigens of Aspergillus fumigatus,a fungus that most commonly colonizes the airways of patients with bronchial asthma and cystic fibrosis.It presents clinically with refractory asthma,hemoptysis and systemic manifestations including fever,malaise and weight loss.Radiologically,it presents with central bronchiectasis and recurrent episodes of mucus plugging.The mucus plugs in ABPA are generally hypodense but in up to 20% of patients the mucus can be hyperdense on computed tomography.This paper reviews the literature on the clinical significance of hyperattenuated mucus in patients with ABPA.

Allergic bronchopulmonary aspergillosis:Lessons for the busy radiologist

The probability of a radiologist interpreting a disease correctly is not only influenced by their training and experience but also on the knowledge of a particular entity.This editorial reviews certain myths and realities associated with radiological manifestations of allergic bronchopulmonary aspergillosis(ABPA).ABPA is a hypersensitivity disorder against the antigens of Aspergillus fumigatus.Although commonly manifesting with central bronchiectasis(CB),the disorder can present without any abnormalities on high-resolution computed tomography(HRCT) of the chest,so-called serologic ABPA(ABPA-S).HRCT of the chest should not be used in screening or in the initial diagnostic work up of asthmatics,as asthma without ABPA can manifest with findings of CB.High-attenuation mucus(HAM) is the pathognomonic sign of ABPA and is very helpful in the diagnosis of ABPA complicating asthma and cystic fibrosis.Instead of classifying ABPA based on the presence and absence of CB into ABPA-CB and ABPA-S respectively,ABPA should be classif ied as ABPA-S,ABPACB and ABPA-CB-HAM.The classif ication scheme based on HAM not only identifies an immunologically severe disease but also predicts a patient with increased risk of recurrent relapses.

Allergic fungal rhinosinusitis accompanied by allergic bronchopulmonary aspergillosis: A case report and literature review

BACKGROUND Concomitant allergic fungal rhinosinusitis(AFRS)and allergic bronchopulmonary aspergillosis(ABPA)are extremely rare,with no more than 20 cases reported in the English literature.CASE SUMMARY A 52-year-old female patient complained of right-sided nasal obstruction,rhinorrhea,sneezing,epistaxis,and hyposmia for a period of around 5 mo.Nasal examination detected paleness and edema of the nasal mucous membrane and a polyp in the right middle meatus.A computed tomography(CT)scan of the sinuses revealed a ground-glass opacity filling the right maxillary and ethmoid sinuses,along with bone absorption in the medial wall of the right maxillary sinus.Magnetic resonance images were obtained with T1-weighted,T2-weighted,and gadolinium-enhanced T1-weighted sequences.A well-defined mass,located in the right maxillary and ethmoid sinuses and displaying obvious hypointense features,was observed on both T1-and T2-weighted images,with peripheral enhancement on gadolinium-enhanced T1-weighted images.The patient also has a 20-year history of cough and dyspnea.Chest CT revealed columned and cystiform bronchiectasis in the bilateral bronchus,surrounded by a large number of spotted and funicular high-density lesions.The level of serum total IgE was>5000 kU/L.Serum IgE levels related to house dust and aspergillus showed a positive result,with the values being 3.5 kU/L and 1.2 kU/L.We performed functional endoscopic sinus surgery under local anesthesia.After surgery,topical glucocorticoids and saline irrigation were applied in the nasal cavity until the present time.An oral glucocorticoid(methylprednisolone 16 mg/d)and antifungal agent(itraconazole 200 mg/d)were also used for a period of 4 wk.Montelukast was prescribed at 10 mg/d until the present time.An endoscopic examination showed that the patient was recovering well at 3 mo after surgery.CONCLUSION Since different specialists treat ABPA and AFRS,their coexistence may be overlooked.AFRS accompanied by ABPA requires surgical therapy combined with medical control to improve the symptoms.

Validation of proposed diagnostic criteria for allergic bronchopulmonary aspergillosis

To the Editor:Allergic bronchopulmonary aspergillosis(ABPA)is an allergic lung disease caused by hypersensitivity to antigens from Aspergillus,and it most commonly occurs in patients with asthma or cysticbrosis.[1]The main clinical characteristics of the disease are those related to elevated serum immunoglubulin(Ig)E level,positive Aspergillus fumigatus(A.fumigatus)specic IgE/IgG,repeated pulmonary inltration,and bronchiectasis.However,due to the lack of unied diagnostic criteria and screening methods,ABPA is always underdiagnosed.In 2021,new diagnostic criteria were proposed for allergic bronchopulmonary mycosis(ABPM)in the Japanese population.

Aspirin induced asthma accompanied with allergic bronchopulmonary aspergillosis： a case report

In this paper, we describe a patient with a rather severe form of aspirin-induced asthma （AIA） and allergic bronchopulmonary aspergillosis （ABPA）. The patient is a man born in 1948, who first presented with rhinorrhea, nasal congestion and chronic urticaria, and had an episode of asthma after ingestion of non-steroidal anti-inflammatory drugs （NSAIDs） for the further eight years. He was diagnosed as AIA and the symptoms decreased in frequency when avoiding NSAIDs. At the age of 45, he presented with unusual symptoms, such as malaise, fever, and coughing. The diagnosis of ABPA was made based on his clinical features, such as the symptoms of asthma, typical pulmonary imaging, positive skin test, and high levels of the total IgE （T-IgE） and sIgE. Itraconazole accompanied with oral prednisone prevented pulmonary disease from developing.

Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis

Background:Previous research demonstrated that a homozygous mutation of g.136372044G>A(S12N)in caspase recruitment domain family member 9(CARD9)is critical for producing Aspergillus fumigatus-induced(Af-induced)T helper 2(T_(H)2)-mediated responses in allergic bronchopulmonary aspergillosis(ABPA).However,it remains unclear whether the CARD9^(S12N)mutation,especially the heterozygous occurrence,predisposes the host to ABPA.Methods:A total of 61 ABPA patients and 264 controls(including 156 healthy controls and 108 asthma patients)were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA.A series of in vivo and in vitro experiments,such as quantitative real-time polymerase chain reaction,flow cytometry,and RNA isolation and quantification,were used to illuminate the involved mechanism of the disease.Results:The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients,regardless of Aspergillus sensitivity.Relative to healthy controls without relevant allergies,the mutation of p.S12N was associated with a significant risk of ABPA(OR:2.69 and 4.17 for GA and AA genotypes,P=0.003 and 0.029,respectively).Compared with patients with asthma,ABPA patients had a significantly higher heterozygous mutation(GA genotype),indicating that p.S12N might be a significant ABPA-susceptibility locus(aspergillus sensitized asthma:OR:3.02,P=0.009;aspergillus unsensitized asthma:OR:2.94,P=0.005).The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9^(S12N),which contributes to its functional alterations to facilitate Af-induced T_(H)2-mediated ABPA development.In terms of mechanism,Card9 wild-type(Card9^(WT))expression levels decreased significantly due to Af-induced decay of its messenger RNA compared to the heterozygous Card9 S12N.In addition,ABPA patients with heterozygous CARD9^(S12N)had increased Af-induced interleukin-5 production.Conclusion:Our study provides the genetic evidence showing that the heterozygous mutation of CARD9^(S12N),followed by allele expression imbalance of CARD9^(S12N),facilitates the development of ABPA.

Allergic bronchopulmonary aspergillosis coexists with hereditary bisalbuminemia

The electrophoresis of a patient＇s serum proteins occasionally reveals two distinct fractions of serum albumin.This rare phenomenon is called bisalbuminemia.Bisalbuminemia can be classified into two types,a rare hereditary one and non-hereditary bisalbuminemia.There have been many reports about non-hereditary bisalbuminemia,which is mainly caused by the excess-use of antibiotics such as penicillin.Hereditary bisalbuminemia （or alloalbuminemia） is a rare,autosomal,and incomplete dominant hereditary condition characterized by the presence of two distinct fractions of serum albumin by electrophoresis.Scheurlen1 reported the first case of this disease in 1955.The first case of hereditary bisalbuminemia in China was reported by Ying et al2 in 1980.Since then,approximately 130 cases of bisalbuminemia from 21 different families have been reported in China.Here,we described a new family with hereditary bisalbuminemia,which was discovered with a patient complained of refractory asthma.Keywords：hereditary bisalbuminemia; allergic bronchopulmonary aspergillosis

A Case of Invasive Pulmonary Aspergillosis Resulted from the Treatment of Chronic Eczema

This was an advanced male(87-year-old)with refractory chronic eczema for over 40 years,based on his allergic constitution,accompanied with chronic kidney disease due to primary hypertension(CKD,phase 3).It was so difficult to tolerate the severe itching that the glucocorticoids(GC)had to be applied to it,but some new-onset respiratory symptoms,such as cough,dyspnea after exertion etc.,occurred to this patient.Some classical IPA images were found on his pulmonary CT scanning,which were further comfirmed by the positive findings of GM-test,and then a final diagno­sis of IPA was accordingly established.Unfortunately,a persistent fever emerged after starting an antifungal therapy to the patient,and his IL-2 level was detected to be superhigh.As a response to allergic fever,GC was carefully given intravenously again to treat it,and it turned out to be totally improved since then;suggesting that systemic thinking(integrated with the other clinical evidences)is essential to diagnose IPA,and GC can also be used to improve its symptoms with the existence of antifungal therapy.

Bronchoscopy and Pathology Findings in an Unusual Case of Allergic Bronchopulmonary Mycosis

The diagnosis of allergic bronchopulmonary mycosis(ABPM)is usually made on clinical,serologic,and roentgenographic findings.However,the indicators in such diagnostic criteria still lack specificity,which results in a high rate of misdiagnosis.A 47-year-old woman was diagnosed with“tuberculosis”or“pneumonia”for 10years and after thoracoscopic right upper lung resection the following chest CT showed right lung atelectasis.Brown sputum was seen in the right bronchus via bronchoscopy.Reviewing the surgical pathology specimen,the bronchi were found to be generally cystic dilated,and a large amount of mucus was retained and formed a mucus plug.The final diagnosis of the case was ABPM.The current diagnostic criteria of ABPM do not emphasize the role of bronchoscopy and pathological examination,but bronchoscopy and pathological examination still have important value for some atypical cases with suspected ABPM.

奥马珠单抗治疗变应性支气管肺曲霉病的疗效与安全性:一项真实世界研究

目的探讨奥马珠单抗治疗变态反应性支气管肺曲霉病(allergic bronchopulmonary aspergillosis,ABPA)的疗效与安全性。方法回顾性分析2018年11月至2023年12月复旦大学附属中山医院收治的奥马珠单抗治疗的26例ABPA患者(奥马珠单抗组),以及同期收治的泼尼松联合伊曲康唑治疗的24例ABPA患者(对照组)的临床资料。主要观察指标是奥马珠单抗治疗后ABPA急性发作次数和口服糖皮质激素节约效应,次要观察指标是治疗后呼吸道症状、外周血嗜酸性粒细胞计数、血清总IgE水平、烟曲霉sIgE水平、肺功能[第1秒用力呼气容积占预计值百分比(FEV_(1)%pred)]、呼出气一氧化氮(fraction of exhaled nitric oxide,FeNO)、胸部CT表现和治疗相关不良反应。结果奥马珠单抗组用药6个月和12个月后的ABPA急性发作次数分别为0(0,0)次/6个月和0(0,1)次/6个月,差异无统计学意义(P=0.157),均较基线次数[1(1,2)次/6个月]显著降低(P<0.001)。口服泼尼松剂量由治疗前的10(5,15)mg/d减少至治疗6个月后的3.125(0,5)mg/d(P<0.001),治疗12个月后剂量为0(0,3.125)mg/d,显著低于基线剂量(P=0.003),但与治疗6个月的剂量差异无统计学意义(P=0.438)。与治疗前相比,奥马珠单抗治疗12个月后的FeNO水平显著降低[26(13,36)×10^(﹣9)vs 30(18,56)×10^(﹣9),P=0.049],血嗜酸性粒细胞计数、总IgE水平、烟曲霉sIgE水平和FEV_(1)%pred治疗前后差异无统计学意义。奥马珠单抗治疗6个月后,23例(88.5%)患者呼吸道症状缓解,8例(8/16,50%)患者黏液栓明显吸收。与对照组相比,奥马珠单抗组治疗12个月后停用口服泼尼松的患者比例更高(P=0.035)。奥马珠单抗治疗期间,4例(15.4%)患者出现丙氨酸氨基转移酶轻度升高,1例患者合并肝细胞癌。结论奥马珠单抗可有效减少ABPA急性发作次数,减少口服糖皮质激素的剂量,改善FeNO,有助于黏液栓吸收,具有较高的安全性。

全外显子组基因测序辅助诊断原发性纤毛运动障碍

2021年12月,复旦大学附属中山医院收治1例29岁男性患者。该患者反复咳嗽、咳痰、喘息,血清总IgE明显升高,烟曲霉特异性IgE阳性,肺功能检查提示极重度混合性通气功能障碍,结合胸部CT结果,考虑支气管扩张症、变应性支气管肺曲霉菌病。结合其低水平呼出气一氧化氮(fractional exhaled nitric oxide,FeNO)和鼻呼出气一氧化氮(nasal nitric oxide,nNO)、出生后咳嗽不愈、父母近亲结婚等,考虑原发性纤毛运动障碍(primary ciliary dyskinesia,PCD)等遗传性疾病可能。全外显子组测序(whole exome sequencing,WES)结果显示,患者CCDC40基因14号外显子纯合突变,确诊PCD。

从风邪论治过敏性支气管肺曲霉病

肺为娇脏,易受风邪侵袭,而风邪与过敏性支气管肺曲霉病(ABPA)的发病与进展密切相关。风邪贯穿ABPA的全程,主要为风袭肺卫、风伏肺脏、风毒损络等病机表现。辨治ABPA要重视风邪,根据不同阶段的病机特点酌情配伍风药,通过益气疏风、祛风宣肺、搜风通络等治法,使表邪解、伏风去、肺络通。在ABPA外邪袭肺阶段运用益气固表疏风之品,以充盛肺气,祛风外出,固护腠理,防止内入;风伏肺脏为防治该病的关键一环,治疗上采用祛风宣肺,理气化痰,令风无所遁伏;风毒损络阶段祛风解毒,破除癥瘕,搜风通络并举,使风毒除、癥瘕破、络脉通。

变应性支气管肺曲霉病的临床特征及急性加重影响因素

目的研究变应性支气管肺曲霉病(ABPA)的临床特征和急性加重影响因素,以促进其诊断和治疗。方法回顾性分析2013年2月至2023年3月在安徽省胸科医院首次诊断为ABPA的57例患者的临床和误诊特征,根据随访资料分析其急性加重的影响因素。结果咳嗽、咳痰和喘息是ABPA最常见症状。31例合并哮喘,45例合并支气管扩张。47例有误诊史。合并哮喘容易被误诊(χ^(2)=7.584,P=0.006),伴有中心性支气管扩张(χ^(2)=3.978,P=0.046)和粘液栓(χ^(2)=4.102,P=0.043)不易被误诊。其中35例患者随访2年,13例出现急性加重。与非急性加重者相比,急性加重者总IgE水平更低(Z=-2.133,P=0.033)、支气管扩张比例更高(P=0.015)。结论ABPA临床表现不典型,误诊率和复发率高。总IgE水平低及合并支扩是急性加重的影响因素,可作为临床监测指标。

变态反应性支气管肺曲菌病患者血清IgE和嗜酸粒细胞水平及其临床意义

目的探讨变态反应性支气管肺曲菌病(ABPA)患者临床特征及血清免疫球蛋白E(IgE)、嗜酸粒细胞水平变化,分析其对ABPA的诊断效能。方法回顾性分析2016年3月至2024年3月收治的210例ABPA患者(观察组)和200例同期体检健康志愿者(对照组)的临床资料,比较2组血清IgE、嗜酸粒细胞计数、嗜酸粒细胞百分比。分析ABPA患者的肺功能、影像学特征,比较不同临床特征ABPA患者血清IgE、嗜酸粒细胞计数、嗜酸粒细胞百分比,并分析血清IgE与嗜酸粒细胞计数相关性。受试者工作特征曲线分析血清IgE、嗜酸粒细胞计数对ABPA的诊断效能。结果ABPA患者临床表现主要为咳嗽、咳痰、喘息;肺功能主要表现为阻塞性通气功能障碍,影像学特征以支气管扩张、黏液栓为主。ABPA患者血清烟曲霉特异性IgE为(8.76±2.97)kU/L、特异性免疫球蛋白G为(2294.85±654.13)U/mL。观察组血清IgE、嗜酸粒细胞计数、嗜酸粒细胞百分比高于对照组(P<0.05)。病程≥12个月ABPA患者血清IgE水平明显高于病程<12个月患者,有支气管扩张、黏液栓影像学征象ABPA患者嗜酸粒细胞计数水平高于无支气管扩张、黏液栓影像学征象患者(P<0.05)。ABPA患者血清IgE与嗜酸粒细胞计数呈正相关(P<0.05)。血清IgE、嗜酸粒细胞计数诊断ABPA的曲线下面积分别为0.885(95%CI:0.822,0.947)、0.829(95%CI:0.754,0.905)。结论咳嗽、咳痰、喘息是ABPA患者的主要临床症状,肺功能多表现为阻塞性通气功能障碍,影像学特征以支气管扩张和黏液栓为主,患者血清IgE、嗜酸粒细胞水平存在明显异常,可能与支气管扩张、有黏液栓及病程有关,二者对ABPA均有一定诊断价值。

Relationship between chronic rhinosinusitis and lower airway diseases: An extensive review

Signifcant links between allergic rhinitis and asthma have been reported, and the united airway disease hypothesis is supported by numerous findings in epidemiologic, physiologic, pathologic, and immunologic studies. The impact of allergic rhinitis on asthma has been esta-blished. On the other hand, the relationship between chronic rhinosinusitis and lung diseases has been under investigation. Chronic rhinosinusitis is a common disease, and the high prevalence of chronic rhinosinusitis in some kinds of lung diseases has been reported. Recent studies suggest that the treatment of chronic rhinosinusitis has beneficial effects in the management of asthma. Here, we present an overview of the current research on the relationship between chronic rhinosinusitis and lower airway diseases including asthma, chronic obstructive pul-monary disease, cystic fibrosis, diffuse panbronchiolitis, primary ciliary dyskinesia, idiopathic bronchiectasis, and allergic bronchopulmonary aspergillosis.

变应性支气管肺曲霉病的诊断和治疗新进展

变应性支气管肺曲菌病是肺部真菌疾病中的主要疾病之一,在临床并不罕见,但其诊断较难,容易误诊漏诊,且治疗效果不稳定,本文总结了其诊断和治疗的新进展。