Acute Airway Obstruction Due to Necrotizing Tracheobronchial Aspergillosis in Immunocompromised Patients: A New Clinical Entity

Berlinger, Norman T.; Freeman, Todd J.

doi:10.1177/000348948909800911

Cited by 50 publications

(48 citation statements)

References 6 publications

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“…Therefore, it is possible that these lesions were responsible for the death of some mice. Disease confined to large airways, a pattern that is observed less commonly than bronchopneumonia, may result in acute airway obstruction in humans and has been reported after resolution of neutropenia (4,22). However, the presence of more distal lesions in the mice at earlier times after infection (data not shown) and the consistent finding of extensive parenchymal inflammation in which only hyphal remnants were observed suggest that these inflammatory lesions were sufficient to cause death.…”

Section: Discussionmentioning

confidence: 79%

“…Following centrifugation at 290 ϫ g for 10 min at 4°C and washing, the pellet was passed through a 70-m-pore-size filter. Red blood cells were lysed by incubation of the cell suspension in 0.17 M NH 4 Cl (pH 7.0) at 4°C for 10 min. Fluorochrome-or biotin-conjugated MAbs to cell surface markers or isotype-matched controls were produced in rats, except as indicated below, and were obtained from Pharmingen (San Diego, Calif.) (CD3-allophycocyanin (APC) [ was purified from concentrated cell supernatants by protein G chromatography, conjugated to Alexa-488 (Molecular Probes, Eugene, Oreg.)…”

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confidence: 99%

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The Pathogenesis of Fatal Outcome in Murine Pulmonary Aspergillosis Depends on the Neutrophil Depletion Strategy

2005

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Aspergillus fumigatus causes invasive disease in severely immunocompromised hosts but is readily cleared when host innate defenses are intact. Animal models for evaluation of therapeutic strategies to combat invasive aspergillosis that closely mimic human disease are desirable. We determined optimal dosing regimens for neutrophil depletion and evaluated the course of infection following aerosol infection in mice by determining survival, organ fungal burden, and histopathology in mice in which neutropenia was induced by three methods, administration of granulocyte-depleting monoclonal antibody RB6-8C5 (MAb RB6), administration of cyclophosphamide, and administration of both agents. Administration of either individual agent resulted in a requirement for relatively high conidial inocula to achieve 100% mortality in both BALB/c and C57BL/6 mice, although the infection appeared to be somewhat more lethal in C57BL/6 mice. Death following induction of neutropenia with MAb RB6 occurred when a relatively low fungal burden was present in the lung and may have been related to the inflammatory response associated with neutrophil recovery. In contrast, administration of both agents reduced the lethal inoculum in each mouse strain by approximately 1 log 10 , and C57BL/6 mice that received both agents had a higher fungal burden and less inflammation in the lung at the time of death than BALB/c mice or mice of either strain that received MAb RB6 alone. Our data suggest that the relationship among fungal burden, inflammation, and death is complex and can be influenced by the immunosuppression regimen, the mouse strain, and the inoculum.

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Section: Discussionmentioning

confidence: 79%

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confidence: 99%

The Pathogenesis of Fatal Outcome in Murine Pulmonary Aspergillosis Depends on the Neutrophil Depletion Strategy

2005

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“…To our knowledge, there have been only four case reports published concerning this type of Aspergillus infection after bone marrow transplan- tation. [2][3][4][5] Here we report a patient with Aspergillus tracheobronchitis who deteriorated rapidly despite intensive antifungal therapy. This report exemplifies the difficulties in early diagnosis and instigation of appropriate treatment for patients with Aspergillus tracheobronchitis after stem cell transplantation.…”

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confidence: 91%

Aspergillus tracheobronchitis after allogeneic bone marrow transplantation

Machida

Kami

Kanda

et al. 1999

Bone Marrow Transplant

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Summary:We describe a patient who developed Aspergillus tracheobronchitis after BMT. She complained of progressive dyspnea on day +165 and her respiratory function deteriorated rapidly. Although neither early chest Xrays nor CT scans were negative, bronchoscopy revealed formation of a pseudomembrane around the bronchial walls. Based upon pathological and microbiological examinations, she was diagnosed as having invasive Aspergillus tracheobronchitis. Retrospectively analyzed, the Aspergillus circulating antigen detection tests became positive before clinical symptoms developed, and may be beneficial for early diagnosis of Aspergillus tracheobronchitis. This form of aspergillosis should be regarded as one of the serious complications after BMT. Keywords: bone marrow transplantation; aspergillus; tracheobronchitis; steroid; pseudomembrane Aspergillus infection is a potentially fatal complication in bone marrow transplant recipients. Despite the improvement in prophylaxis and treatment, it is still associated with a high morbidity and mortality. 1 Invasive pulmonary aspergillosis (IPA), the most common form of Aspergillus infection in bone marrow transplant recipients, usually affects the lung parenchyma and occasionally disseminates to a variety of organs. A small number of patients, however, develop invasive tracheobronchitis as a local manifestation. Clinical characteristics of this disease are quite different from those of IPA. To improve the prognosis of Aspergillus infection, early diagnosis and prompt initiation of intensive antifungal treatment are requisites, but both the optimal diagnostic methods and treatments remain to be established. Because of its low incidence, we have little information on this type of Aspergillus infection. To our knowledge, there have been only four case reports published concerning this type of Aspergillus infection after bone marrow transplan- tation. 2-5 Here we report a patient with Aspergillus tracheobronchitis who deteriorated rapidly despite intensive antifungal therapy. This report exemplifies the difficulties in early diagnosis and instigation of appropriate treatment for patients with Aspergillus tracheobronchitis after stem cell transplantation.

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“…6 this unusual manifestation which could previously be studied only at necropsy. Removal of the vocal cord lesions during biopsy may also facilitate the relief of symptoms in these patients.…”

Section: Discussionmentioning

confidence: 99%

Aspergillus laryngotracheobronchitis presenting as stridor in a patient with peripheral T cell lymphoma.

Kuo

Lee²,

Yang³

et al. 1996

Thorax

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radiograph and computed tomographic scan were normal. Aspergillus fumigatus was isolated repeatedly from the sputum from day 9 onwards, and blood cultures were negative for bacteria and fungi. Broad spectrum antibiotics and granulocyte colony-stimulating factor were administered. His fever gradually subsided and the white blood cell count increased to 7.2 x 109/l on day 24 with an absolute neutrophil count of 4.5 x 1 09/l. However, the hoarseness and productive cough persisted. The oxygen saturation of haemoglobin while breathing room air was 95%. Bronchoscopic examination, performed on day 25, disclosed the presence of creamy-white, exophytic lesions on the upper surface of both vocal cords and the supraglottic area in a symmetrical fashion ( fig 1A). Mobility of both cords was impaired. The epiglottis was normal. Beyond the vocal cords there was diffuse tracheobronchitis with erythematous and oedematous mucosa. Multiple raised cream-coloured plaques were found throughout the tracheal mucosa. A single ulcer with overlying fibrinous exudate was also noted over the right main bronchus (fig 1 B). There was no evidence of distal airway involvement. The exophytic lesions on both vocal cords were removed with the biopsy forceps as completely as possible. Both vocal cords were then found to have been partially destroyed with ulcers on their upper surface. Histologically, the tenacious plugs from both vocal cords consisted of numerous septate branching hyphae consistent with Aspergillus species, admixed with mucus and inflammatory cells. Systemic treatment with amphotericin B was introduced on day 26 at a dose of 1 mg/kg per day. The patient's cough and hoarseness improved gradually and stridor was no longer audible after two days of treatment. His voice had returned to almost normal one week later. Follow up bronchoscopy two weeks later showed that the lesions on the vocal cords and trachea had disappeared, with almost complete healing of the ulcer on the right main bronchus. Cytological examination of the bronchial washing fluid did not reveal any hyphal elements. Follow up fungal culture of the sputum was also negative. Because of severe systemic side effects amphotericin B was discontinued on day 45 at a cumulative dose of 1080 mg. Treatment was continued with oral itraconazole, 200 mg twice daily. The patient's respiratory symptoms continued to improve and the follow up chest radiographs remained clear. Unfortunately, the patient had a relapse of his lymphoma and exacerbation of the haemophagocytic syndrome. Chemotherapy was resumed under cover of strong antibiotics but the patient died on the 53rd hospital day from septic shock.

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Acute Airway Obstruction Due to Necrotizing Tracheobronchial Aspergillosis in Immunocompromised Patients: A New Clinical Entity

Cited by 50 publications

References 6 publications

The Pathogenesis of Fatal Outcome in Murine Pulmonary Aspergillosis Depends on the Neutrophil Depletion Strategy

The Pathogenesis of Fatal Outcome in Murine Pulmonary Aspergillosis Depends on the Neutrophil Depletion Strategy

Aspergillus tracheobronchitis after allogeneic bone marrow transplantation

Aspergillus laryngotracheobronchitis presenting as stridor in a patient with peripheral T cell lymphoma.

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