Pseudomembranous necrotizing tracheobronchial aspergillosis:an analysis of 16 cases

1236Chin Med J 2012;125(7):1236-1241Original articlePseudomembranous necrotizing tracheobronchial aspergillosis:an analysis of 16 casesHUANG Hai-dong, LI Qiang, HUANG Yi, BAI Chong, WU Ning, WANG Qing, YAO Xiao peng and CHEN BinKeywords: aspergillus; infection; pseudomembranous necrotizing tracheobronchial aspergillosis;flexible bronchoscope; diagnosis; interventional therapyBackground In our clinical practice we have beenaiway obstruction; we termed the condition as pseudomembranous necrotizing tracheobronchial asperilosis (PNTA). Inthis study we analyzed the clinical data from patients with PNTA, so as to guide the diagnosis and treatment of theMethods A total of 16 PNTA patients were treated in Changhai Hospital from January 2000 to January 2009. Theirclinical data, including the demographic information, clinical symptoms, imaging findings, bronchoscopy findings,treatment strategies and efficacy, and prognosis, were retrospectively analyzed.Results AlI 16 patients were found to have primary systemic immunodeficiency diseases and/or damage of the focalairways. Nine patients (9/16, 56.3%) had pulmonary and tracheobronchial tumors, 5/16 (31 .3%) had tracheobronchialinvolvement secondary to non-pulmonary tumors, and 2/16 (12.5%) had lung transplantation. The most common causesof PNTA included local radiotherapy (10/16, 62.5%), repeated chemotherapy (7/16, 43.8%) and recurrent interventiontherapy by bronchoscope (4/16, 25.0%). Aspergillus fumigatus was the most frequent pathogen (62.5%, 10/16). Themain clinical manifestations included progressive dyspnea (14/16, 87.5%) and iritable cough (12/16, 75.0%). Thetrachea was involved in 9/16 patients (56 .3%), right main bronchus in 10/16 (62.5%). AI 16 patients were treated withsystemic ati-asperillosis agents, local anti-aspergillosis agents with amphotericin B inhnalation and direct perfusion ofamphotericin B by bronchoscope, and interventional treatment by bronchoscope to ensure an unobstructed airway. Thetotal eficiency was 31.3%.Conclusions PNTA is an infectious disease caused by asperilus and it mainly involves the trachea, primary bronchusand segmental bronchus. A. fumigatus is the most common pathogen. PNTA can pose a severe clinical threat and oftenoccurs after systemic immunodeficiency and/or local airway damage, with the main symptoms including dyspnea andiritable cough. Bronchoscopic findings supply the main evidence for diagnosis of PNTA. Treatment of PNTA is dificultand requires a long course. Systemic and local anti-asperilosis agents plus bronchoscopy debridement can improve theprognosis of the disease.ungal infections have been on the rise during recentMETHODS1 years due to the increased number ofimmune-compromised hosts and the abuse of antibioticsPatientsThe respiratory system is exposed to the extemalThe 16 patients were hospitalized in the Department ofenvironment and is vulnerable to fungal infections.Respiratory Diseases from Jan. 2000 to Jan. 2009 (TableAccording to the statistics of the Beijing Union Hospital,1). The demographic information, clinical symptoms andthe morbidity from fungal infections in 2003 nearlysigns, imaging findings， primary diseases， possiblequadrupled that of the 1990's in China. Cases ofinducement, infection location, etiology, treatment andaspergillosis have been increasing since the early 1990's,prognosis of patients were retrospectively analyzed. Thewith deep infection seen mostly in cancer patients,clinical properties were summarized to guide the futurepatients with immunodeficiency or recipients of organdiagnosis and treatment of the disease.transplantation, most frequently infiltrating the lung andbronchial tree.' We have observed a group of patientsDOI: 10.3760/cmaj_issn.036-6999.2012.07.009with airway aspergillosis, who are most likely to haveDepartment of Respiratory Diseases, Changhai Hospital, Secondairway obstruction, and we termed the conditionMilitary Medical University, Shanghai 200433, China (Huang HD,pseudomembranous. necrotizingtracheobronchialLi Q, Huang Y,中国煤化工P)aspergillosis (PNTA).2Treatment of PNTA is difiult.4Department oHospital ofTo gain more information on thecondition，wePudong New AreaYHCNMHGenB)Correspondence to: Dr. Ll Qlang，Department of Respiratoryretrospectively analyzed the clinical data of 16 PNTADiseases, Changhai Hospital, Second Military Medical University,patients who were pathologically or etiologicallyShanghai 200433， China (Tel: 86-21-81873231. Fax:confirmed from Jan. 2000 to Jan. 2009 in our hospital.86-21-81873231. Email: liqressh@yahoo.com.cn)Chinese Medical Jourmnal 2012;125(7):1236-12411237Table 1. Summary of patients with pseudomembranous necrotizing tracheobronchial aspergillosisCase Gender Age (years)Primary diseasesInfection sitesOutcomesMalePulmonary squamousRadiotherapy andRight main bronchus AspergillusItraconazoleProgressivecell carcinomachemotherapy2 MaleThymus cancerTrachea and right main Asperillus Amphotericin B liposome Progressivebronchusfumigatus(hemoptysisasphyxia)ThymomaTracheaAspergillusCaspofungin/ImprovednigerAmphotericin B nebulizedand perfused4 Male0Mediastina lymphomaLong term exposure toLeft main bronchus Aspergillusbroad-spectrum antibiotics andimmunosuppressants5FemaleEsphageal cancer Radioherapy, chemotherapAsperilus Amphotericin B nebulized Progressiveand recurrenttherapy by bronchoscope.6 Male .73RadiotherapyRight main bronchus Aspergillus Amhotericin B nebulized Stable7 Male70COPD, right lungLong- term exposure to Right main bronchus AspergillusVoriconazoleCuretransplantation5:PulmonaryChemotherapyTrachea, right main AspergillusItraconazole 1adenocarcinomabronchus and rightflavusintermedius bronchus9 Male5CAdenoid cysticRadiotherapy, long termAspergillus Amphotericin B nebulized Improvedcarcinoma of trachea exposure to broad-spectrumand prfusedantibioticsLong-term exposure toRight main bronchus AspergillsItaconazole 1 voriconazole/ Cureterreusand perfuses1 FemaleRadiotherpy and recurrentAspergillus Amphotericin B nebulized Stablecarcinoma of tracheaintervention therapy bybronchoscope2 Female41Radiotherapy and recurrent Trachea, right main Aspergilus Amphotericin B nebulized Progressiveintervention therapy by bronchus and left main fumigatus13 Male51Pulmonary squamous Chemotherapy and recurrent Right main bronchus AspergillusAmphotericin B/sydowi Amphotericin B nebulized14 Female 58Radiotherapy and long-termTrachea, right main Aspergillus Amphotericin B ncbulized Progressiveexposure to broad-sectrum bronchus and left main fumigatus15 Male5eRight main bronchus Aspergillus Itraconazole/ Amphotericin Progressivefumigatus B nebulized and perfused16 Male62Esophageal cancerfunigausDiagnosis criteriamucosa is smooth under bronchoscope, total relief ofExtensive airway pseudomembrane formation, caused byairway stenosis, and elimination of pathogenic fungus; (2)necrotic tissue and metabolites of aspergillus, was foundimproved: relief of clinical symptoms, improved imagein all the 16 patients by bronchoscopy. Airwayfindings, decreased lesion area under bronchoscope, andobstruction or constriction was diagnosed when thepartial relief of airway obstruction; (3) stable: with noairway was≥50% of the original caliber. A diagnosis wasnoticeable improvement of the clinical symptoms, and nomade when samples of the lesion (biopsy, cytology orapparent changes in image findings and bronchoscopybronchial fluid) met one of the following two criteria: (1)examination; (4) progressive: symptoms aggravated,Biopsy pathology of the lesion confirmed aspergilluslesions increased by imaging and bronchoscopyinfection, with the culture of a type of aspergillus. (2)examination, worsened airway obstruction or seeding ofLesion smear or bronchial fluid positive for aspergillusfungal infection.'hyphae and spores, with the positive culture of a type ofaspergillus.'RESULTS中国煤化工Assessment of outcomesGeneral finThe outcome of patients was assessed according to theFrom Januar:YHCN MHGa total of 18 612relief of clinical symptoms and the improvement ofpatients underwent bronchoscopic examination in ourlesions under the bronchoscope, and they were divideddepartment, and 16 were confirmed to have PNTA, with ainto the following four results: (1) cure: clinicalmorbidity of 0.86%. The 16 patients included 12 malessymptoms disappeared, normal image findings, bronchialand 4 females, with a male to female ratio of 3:1. The.1240Chin Med J 2012;125(7):1236-1241treatment duration in our responsive patients was 3.5Otol Rhinol Laryngol 1998; 98: 718-720.months.Walsh TJ， Anaissie EJ, Denning DW, Herbrecht R,Kontoyiannis DP, Mar KA, et al. Treatment of aspergillosis:Bronchoscopic debridement is an effective way to keepclinical practice guidelines of the Infectious Disease Societythe airway open, and it is suitable for patients with centralof America. Clin Infect Dis 2008; 46: 327-360.airway stenosis and involvement in the main bronchi orLI Q. Obstructive tracheal or bronchial asperilosis. Chin Jabove. For patients with rubbery pseudomembranousIntemn Med (Chin) 2006; 45: 686-688.tissues, systemic and local perfusion of anti-aspergillusAL-Alawi A， Ryan CF, Flint JD, Muller NL.agents should be given first; when the tissue becomes softAsperillus-related lung disease. Can Respir J 2005; 12it can be removed step by step using bronchoscopic377-387. .biopsy forceps. The manipulation of the bronchoscopeHuang Y, Bai C, Li Q. Invasive aspergillosis of the airways:should be very careful, since aspergillus infection mayanalysis of 19 cases. Chin J Infect Chemother (Chin) 2005; 5:penetrate the full thickness of the bronchial wall,201-204.including the cartilage and even the blood vessels around 7. Singhal P, Usuda K, Mehta AC. Post-lung transplantationthe bronchi, making the wall very fragile, which is likelyAspergilus niger infection. Heart Lung Transplant 2005; 24:to be damaged by improper manipulation of the1446-1447.bronchoscope, causing rupture of arteries and hemoptysisSancho JM, Ribera JM, Rosell A, Munoz C, Feliu E. Unusualasphyxia.-92.25 Berlinger et al2 reported that an AIDSinvasive bronchial aspergillosis in a patient with acutepatient died of hemoptysis asphyxia during electriclymphoblastic leukemia. Haematologica 1997; 82: 701-702.coagulation of a granuloma by bronchoscopy. In ourKrenke R， Kolkowska-Lesniak A， Palynyczko Gstudy, one patient suffering from thymus cancer hadProchorec Sobieszek M， Konopka L. 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