Corticosteroid treatment as a risk factor for invasive aspergillosis in patients with lung disease.

Invasive pulmonary aspergillosis usually occurs in severely immunocompromised or neutropenic patients. Six patients with invasive aspergillosis are described whose only defence impairment was underlying lung disease and corticosteroid treatment. Cough, fever, and sputum production were the usual reasons for presentation and four patients developed the sepsis syndrome. Radiographic findings included de novo cavitation in three patients and rapid radiographic progression in four. Aspergillus species were isolated from respiratory secretions of all patients early in the course of the disease. Treatment was effective in only two patients and the subsequent progress of the others was consistent with a chronic necrotising process. Invasive pulmonary aspergillosis is uncommon in patients with respiratory diseases receiving corticosteroids, but should be considered when pneumonia and cavitary infiltrates occur.     

The diagnostic yield of prebronchoscopy sputa and bronchial washings in patients with biopsy-proven pulmonary tuberculosis

We report on a series of 35 patients with pulmonary tuberculosis diagnosed by flexible fibre-optic bronchoscopy and transbronchial lung biopsy after 3 sputum specimens had been microscopy-negative. This study re-evaluates this invasive procedure. Additional prebronchoscopy specimens of expectorated sputum yielded the diagnosis in 7 of 16 cases (43.8%) on microscopy. Sputum culture results were positive in 12 of 33 (36.4%). Pleural fluid culture was diagnostic in 1 case, and in another miliary tuberculosis was demonstrated on bone marrow trephine biopsy. The availability of these results could therefore have obviated the need for bronchoscopy in 14 of the 35 patients (40%). Bronchial washings were positive for acid-fast bacilli on microscopic examination in 13 of 34 cases (38.2%) and culture-positive in only 18 of 34 (52.9%), and should therefore not be the sole procedure utilised when bronchoscopy is performed. Transbronchial lung biopsy remains a valuable procedure to confirm pulmonary tuberculosis in patients whose sputum is culture-negative for mycobacteria.     

Quantification of cytomegalovirus (CMV) viral load by the hybrid capture assay allows for early detection of CMV disease in lung transplant recipients.

BACKGROUND: We prospectively compared the hybrid capture system (HCS) assay with conventional cell culture and shell vial assay for the detection of cytomegalovirus (CMV) infection and disease in the lung transplant population. METHODS: Between January 1999 and February 2000, 34 lung transplant patients at Loyola University Medical Center, who were considered to be at risk for CMV disease, underwent surveillance testing for CMV cell culture, shell vial assay and HCS assay according to a pre-determined schedule. In addition, bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy were performed at regular intervals and for clinical indications. All BAL samples were sent for CMV cultures and biopsy specimens were analyzed for histopathologic evidence of CMV by immunoperoxidase staining using antibody to early immediate nuclear antigen. RESULTS: Ten patients developed CMV disease/syndrome during the course of the study. The sensitivity, specificity, positive predictive value and negative predictive value were >90% for the HCS assay. The sensitivity of the HCS assay (90%) was statistically significantly higher than the sensitivity of either the SV assay (40%) or the cell culture (50%). In addition, the HCS assay was able to detect CMV 50 +/- 67 days prior to clinical evidence of CMV disease and an average of 36 days prior to the other detection techniques. CONCLUSION: The HCS assay is a sensitive diagnostic technique able to reliably detect CMV disease earlier than other diagnostic methods in the lung transplant population. Future studies may be able to evaluate whether pre-emptive anti-viral therapy targeted to specific viral loads using the HCS assay will be beneficial in preventing morbidity associated with CMV disease.     

Diagnostic fibreoptic bronchoscopy in the immunocompromised host with pulmonary infiltrates.

Nineteen immunocompromised patients with pulmonary infiltrates underwent diagnostic fibreoptic bronchoscopy with transbronchial forceps and brush biopsy. A specific diagnosis was obtained in 21/25 procedures (10/11 focal lesions and 11/14 diffuse legions). The most common diagnosis was infection, and organisms isolated included bacteria, fungi, Pneumocystis carinii, and herpes simplex. A pneumothroax requiring tube drainage occurred in two cases and mild lung parenchymal bleeding was noted in two others. It is concluded that fibreoptic bronchoscopy with forceps and brush biopsy can be performed safely with an excellent diagnostic yield in immunocompromised hosts with lung lesions. Supplemental oxygen should be administered during fibreoptic procedures in these patients and platelet transfusions should be given when thrombocytopenia is present.     

The initial pulmonary evaluation of the immunocompromised patient

Practical approaches to the initial evaluation of solid organ transplant patients, BMT patients, and HIV-infected patients with pulmonary disease are summarized in Figures 2, 3, and 4. These algorithms are meant to be used as guidelines for the clinician. The clinical setting will ultimately determine the extent and speed of the evaluation. Patients who are recipients of solid organ transplants and have pulmonary symptoms may have focal or diffuse changes or may have normal chest radiographs. In all these groups, sputum is obtained by expectation. If a pathogen is found in any of the groups, it is treated. When no pathogen is found on sputum examination in patients with focal disease, empiric antibiotic therapy is given. If the patients do not improve on the empiric antibiotics, then bronchoscopy is performed. Some centers proceed directly to bronchoscopy before antibiotics are started in the hope of directing antibiotic therapy. Patients who have a normal CXR or diffuse infiltrates and no identified pathogen on examination of sputum undergo bronchoscopy, and the protocol is followed until a diagnosis is made (see Fig. 2). Patients who have received a BMT and who present with pulmonary symptoms are treated as shown in Figure 3. The CXR will reveal if the infiltrate is focal or diffuse. Those with focal infiltrates are treated with broad-spectrum antibiotics for 48 to 72 hours. If the symptoms and signs do not show some resolution, then bronchoscopy is usually performed. The effect of diffuse infiltrates in BMT patients depends to a large extent how far along in recovery from the transplant the patient is when they develop the infiltrates. During the first 30 days posttransplant, pulmonary edema commonly occurs, and the infiltrates may resolve with diuresis. If the patient is not clinically fluid overloaded or they do not respond to the diuretic therapy, then bronchoscopy with BAL is indicated. Finally, many HIV-infected patients may present with pulmonary symptoms. They may have a normal CXR or a diffuse or focal pattern (Fig. 4). All patients are subjected to sputum induction to identify a pathogen. If one is identified, it is treated. Should the patient not respond to treatment adequately or a pulmonary pathogen is not found, then bronchoscopy with BAL, protected specimen brush, or a transbronchial biopsy is attempted. The above schema is a general guideline to the initial evaluation of pulmonary disorders in the ICP. The respiratory abnormality is found in most of the cases if these algorithms are closely followed. If the patient does not improve or deteriorates further, additional diagnostic procedures such as video-assisted thorascopic lung biopsy or CT-directed transthoracic needle biopsy may be needed.     

Diagnosis of pulmonary disease in human immunodeficiency virus infection: role of transbronchial biopsy and bronchoalveolar lavage.

The value of transbronchial biopsy and bronchoalveolar lavage was assessed in the diagnosis of pulmonary disease in patients infected with the human immunodeficiency virus (HIV). Seventy four transbronchial biopsy and 66 bronchoalveolar lavage specimens (60 paired specimens) from 80 examinations in 64 patients were reviewed. Pneumocystis carinii was the most common pathogen isolated (43 patients). Bronchoalveolar lavage was superior to transbronchial biopsy for the diagnosis of this pathogen, the sensitivities being 90% and 56%. Cytomegalovirus was identified three times by lavage and once by transbronchial biopsy. Neither method detected Kaposi's sarcoma in the one patient shown to have it by open lung biopsy. The complication rate in a concurrent study of bronchoscopy with transbronchial biopsy in 74 consecutive HIV positive patients was 22%. This study does not support the use of transbronchial biopsy in these patients.     

Comparison of biopsy-proven Pneumocystis carinii pneumonia in acquired immune deficiency syndrome patients and renal allograft recipients

Pneumonia unresponsive to antibacterial agents in patients with acquired immune deficiency syndrome (AIDS) has become a new indication for lung biopsy. In 14 patients, transbronchial or open-lung biopsy demonstrated Pneumocystis carinii. An additional 12 patients, who were immunosuppressed after renal transplantation, were seen with P. carinii pneumonia. The diagnosis was established by transbronchial biopsy in the majority of patients. All patients were treated initially with trimethoprim plus sulfamethoxazole. Pentamidine was added after diagnosis if improvement did not occur. Both groups demonstrated reversal in the T cell helper: suppressor ratio. We compared these two groups of immunocompromised patients with respect to clinical presentation, lung pathology, response to therapy, and survival. Patients with AIDS were seen with a two- to three-week prodrome of fever, lymphadenopathy, weight loss, and malaise followed by hypoxia and leukopenia within 12 hours. Transplant patients became acutely ill with fever and hypoxia within 24 to 36 hours. In both groups, chest roentgenogram showed bilateral diffuse infiltrates; sputum cultures were generally negative; and lung biopsy demonstrated Gomori-Jones periodic acid-methenamine-silver-positive P. carinii. Mortality was substantially higher in patients with AIDS (50% versus 8%). This difference may be explained by the fact that the T cell defect in AIDS has an infectious cause, while the defect in the renal allograft recipient is pharmacologically mediated.     

Rapid diagnosis of sputum negative miliary tuberculosis using the flexible fibreoptic bronchoscope.

Acid fast bacilli are seldom identified by direct staining of sputum smears in patients with miliary tuberculosis, so that delays in diagnosis are common. We report 41 patients with miliary tuberculosis who had negative sputum smears and who underwent bronchoscopy, bronchial brushing, and transbronchial biopsy. In two patients the procedure was repeated. A definitive diagnosis was obtained from bronchoscopy in 34 patients (83%). Bronchial brushings yielded Mycobacterium tuberculosis in 24 of 42 bronchoscopies (57%), 13 from direct smear and a further 11 from culture only. Transbronchial biopsies were diagnostic in 30 of 41 procedures (73%), 28 from histological appearances, one from direct smear of the biopsy specimen, and another exclusively from culture. A rapid diagnosis was established in most patients (27/34), either by direct smear of brushings or biopsy specimens only (5), by histological examination only (14), or by both direct smear of brushings and biopsy specimens only (5), by histological examination only (14), or by both direct smear of brushings and histological examination (8). The diagnosis was confirmed later in a further seven patients by culture of brushings or specimens; in five of these non-caseating granulomas were initially found by histological examination. Fibreoptic bronchoscopy is a valuable technique for rapidly establishing the diagnosis of miliary tuberculosis.     

Legionnaires' disease after heart transplantation

The cases of 8 heart transplant recipients with legionnaires' disease are reviewed. The diagnosis in each patient was made by fluorescent antibody stains or direct culture of the sputum, transtracheal aspirate, or fine needle aspirate of the lung. All patients were successfully treated with erythromycin alone or in combination with rifampin. Radiographic and clinical variations of legionnaires' disease as seen in the immunocompromised host are presented.     

Role of fibreoptic bronchoscopy in the diagnosis of mycobacterial diseases.

From January 1976 to December 1981 mycobacteria were recovered for the first time from the respiratory tract of 179 patients. Twenty-three patients had undergone fibreoptic bronchoscopy during initial investigation after three or more expectorated sputum specimens were negative for acid-fast bacilli. Three of these patients had nodular lesions on the chest radiograph and the diagnosis of mycobacterial disease was made only after thoracotomy. In the remaining 20 patients bronchial brushings yielded a positive culture in 19, while bronchial brushing was negative in one patient in whom culture of sputum before bronchoscopy had been positive. In eight of these 19 patients (group A) bronchial brushing was the only source that gave a positive result from culture, while in 11 patients (group B) both bronchial brushing and prebronchoscopy sputum yielded positive cultures. When these two groups were compared no difference was seen in their clinical presentation or radiographic findings but there was a notable difference in the quality of the presentation or radiographic findings but there was a notable difference in the quality of the prebronchoscopy sputum. Six of eight patients in group A had poor prebronchoscopy sputum, while 10 of 11 in group B had good prebronchoscopy sputum. It is concluded that, if a patient is unable to produce sputum or is able to produce only a poor specimen, fibreoptic bronchoscopy may be a useful means of obtaining additional material for culture.     

Bronchoscopy findings in invasive pulmonary aspergillosis.

Two patients with invasive aspergillosis had unusual endobronchial appearances at fibreoptic bronchoscopy. Diagnosis was achieved by endobronchial biopsy.     

Aspergillus galactomannan antigen in the bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in lung transplant recipients

BACKGROUND: The clinical utility of Platelia Aspergillus enzyme immunoassay (EIA) for galactomannan (GM) antigen detection in bronchoalveolar lavage (BAL) for the diagnosis of invasive aspergillosis (IA) in lung transplant recipients is not known. METHODS: BAL fluid samples from consecutive lung transplant recipients who underwent bronchoscopy were prospectively analyzed for GM. RESULTS: A total of 333 BAL samples from 116 patients were tested. Invasive aspergillosis was documented in 5.2% (6/116) of the patients. Samples analyzed included 9 BALs from two patients with proven IA, 19 BALs from four patients with probable IA, and 305 BALs from 110 patients without IA. At the index cutoff value of > or =0.5, the sensitivity was 60%; specificity was 95%, with positive and negative likelihood ratios of 14 and 0.41, respectively. Increasing the index cutoff value to > or =1.0 yielded a sensitivity of 60%, a specificity of 98%, and the positive and negative likelihood ratios of 28 and 0.40, respectively. Two of six patients with IA receiving antifungal prophylaxis had false-negative results. CONCLUSIONS: A Platelia EIA index cut-off > or =1.0 in the BAL fluid in a lung transplant recipient with a compatible clinical illness may be considered as suggestive of IA.     

Bronchoscopic evaluation of peripheral lung tumours.

The results obtained from fibreoptic bronchoscopy preformed under fluoroscopic guidance were evaluated in a prospective study of 71 consecutive patients with a peripheral lung lesion more than 2 cm in diameter on the chest radiograph. A peripheral lung lesion was defined as a lesion that was not seen within the bronchial tree at fibreoptic bronchoscopy. Small volume washings, bronchoalveolar lavage, transbronchial biopsy, and bronchial brushings were carried out and fluid or tissue was sent for cytological or histological examination as appropriate. Of the 71 patients, 51 were subsequently shown to have malignant disease. In 38 of the patients the diagnosis of malignancy was made by bronchoscopy, from histological specimens alone or in conjunction with cytological specimens in 33, from brushings alone in two, and from bronchoalveolar lavage fluid alone in three patients. There were no important complications. Thus fibreoptic bronchoscopy in conjunction with fluoroscopic screening appears to be an effective and safe method for the initial investigation of a peripheral lung lesion more than 2 cm in diameter.     

Lung infections: the radiologist's perspective

Imaging plays a key role in lung infections. A CT scan must be carried out when there is a strong clinical suspicion of pneumonia that is accompanied by normal, ambiguous, or nonspecific radiography, a scenario that occurs most commonly in immunocompromised patients. CT allows clinicians to detect associated abnormalities or an underlying condition and it can guide bronchoalveolar lavage or a percutaneous or transbronchial lung biopsy. An organism can vary in how it is expressed depending on the extent to which the patient is immunocompromised. This is seen in tuberculosis in patients with AIDS. The infective agents vary with the type of immune deficiency and some infections can quickly become life-threatening. Clinicians should be aware of the complex radiological spectrum of pulmonary aspergillosis, given that this diagnosis must be considered in specific settings.     

Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management.

BACKGROUND: Invasive aspergillosis is a serious opportunistic infection in lung transplant recipients. It has not been fully discerned whether there are differences in the characteristics, risk factors and outcome of Aspergillus infection in single as compared with bilateral lung transplant recipients. METHODS: English-language articles identified by a MEDLINE search through December 2000 and bibliographies were used as data sources to identify cases of Aspergillus infections in lung transplant recipients. The studies selected had to have provided a definition of invasive aspergillosis to distinguish colonization from infection. RESULTS: The median incidence of Aspergillus infections in lung transplant recipients was 6.2%. In total, 58% (45 of 78) of the Aspergillus infections were tracheobronchitis or bronchial anastomotic infections, 32% (25 of 78) were invasive pulmonary, and 22% (25 of 78) were disseminated infections. Single lung transplant recipients with Aspergillus infections were significantly older (p = 0.006), more likely to have had chronic obstructive pulmonary disease as an underlying illness (p = 0.05), more likely to have developed Aspergillus infections later after transplantation (p = 0.019), and tended to have a higher incidence of invasive aspergillosis (p = 0.11) than all other lung transplant recipients. Overall mortality in lung transplant recipients with Aspergillus infections was 52%. Single lung transplant recipients (p = 0.03), and patients with late-onset infections (occurring at least 3 months after transplantation ([p = 0.045]) infections had significantly higher mortality. CONCLUSIONS: Single lung transplant recipients with Aspergillus infections had an overall greater morbidity and poorer outcome than other types of lung transplant recipients. Recognition of the unique characteristics of Aspergillus infections in single lung (vs bilateral or heart-lung) transplant recipients has implications relevant for the management of lung transplant recipients with aspergillosis.     

Cerebral aspergillosis. Apropos of 4 cases

Four patients with aspergillosis of the central nervous system collected in less than two years are reported. Three patients had hematologic malignancies (acute myelogenous leukemia, Hodgkin's disease) and were treated with corticosteroids and chemotherapy. One patient received antimicrobial agents fort a post operative meningitis (after acoustic neuroma surgery). Analysis of these cases and review of literature available us to point out the increased frequency of invasive and cerebral aspergillosis particularly in immunocompromised hosts treated by cytotoxic drugs or broad spectrum antibiotic therapy. Diagnosis is very difficult because: --there are non specific radiologic features for aspergillus granuloma, abscess, aneurysm or meningitis, --blood and cerebrospinal fluid cultures are invariably negative, --serologic tests have limited value in immunosuppressed patients (poor capacity to elaborate antibodies). Diagnosis can be made only by surgical biopsy who isolate fungal elements. However diagnosis in greatest cases is only made at autopsy. Treatment consist by antifungal drugs administered intravenously and surgery when it is possible. Prognosis of cerebral aspergillosis is very poor and mortality rate very high about 70%.     

肝移植术后肺曲霉菌感染的诊治

目的：探讨肝移植术后肺曲霉菌感染的诊治方法。方法：肝移植术后患者常规进行痰培养,应用二性霉素B、伊曲康唑和氟康唑等抗真菌药物治疗,回顾性分析了3例肺部曲霉菌感染患者的诊治经过。结果：54例肝移植患者有3例发生肺曲霉菌感染,治愈1例,死亡2例。结论：（1）过度免疫抑制是导致肺曲霉素感染的重要因素。（2）二性霉素B治疗肺曲霉感染有效。（3）为降低二性霉素B的毒副作用和增强疗效,治疗方法上可采用渐进性给药、间断性给药、低浓度给药、联合给药,真菌培养阴性后用伊曲康唑巩固治疗2-3周。     

The utility of cytopathology testing in lung transplant recipients.

BACKGROUND: Lung transplant recipients routinely undergo bronchoscopy, during which bronchoalveolar lavage (BAL) fluid and transbronchial biopsies are usually obtained. These specimens are typically sent for microbiology, histopathology and cytopathology testing. Cytopathology testing is expensive, and its diagnostic value is questionable. We hypothesized that cytopathology specimens have no additional diagnostic yield beyond that of microbiology and histopathology testing in the routine care of our lung transplant patients. METHODS: We reviewed all bronchoscopies performed on a cohort of patients who underwent lung transplantation between February 1999 and August 2002 at our institution. Demographic data, immunosuppressive therapy and the incidence of opportunistic infections in this cohort of 65 patients were reviewed. To ascertain the diagnostic value of cytopathology testing, microbiology and histopathology results from bronchoalveolar lavage and transbronchial biopsy tests were compared with cytopathology results. RESULTS: Three hundred sixty-six bronchoscopies were reviewed. Microbiologic and histopathology identified 51 cytomegalovirus-, 157 fungus- and 13 mycobacteria-positive specimens as well as respiratory syncitial virus, influenza A and B, enterovirus, actinomyces, Nocardia and mycoplasma. Cytopathology of BAL fluid identified only 3 cytomegalovirus- and 13 fungus-positive specimens. The only unique diagnoses made by cytopathology were 1 case of Aspergillus and 1 unidentifiable fungal element. CONCLUSIONS: We conclude that routine cytopathology testing has little additive diagnostic value in bronchoscopic specimens from lung transplant recipients. Cytopathology results did not alter patient management in any of our 366 cases. Centers should consider discontinuing routine use of cytopathology testing of BAL fluid for surveillance or clinically indicated bronchoscopy, because the yield of this expensive test is extremely low in the setting of lung transplantation.     

The clinical assessment of selected patients with bronchogenic carcinoma.

This paper describes the clinical management of patients with malignant cells in their sputum and a normal chest roentgenogram and those with asymptomatic peripheral pulmonary masses. The source of malignant cells in the sputum of patients with no roentgenographic abnormalities can be localized by tantalum bronchography and fiberoptic bronchoscopy. Peripheral pulmonary masses can be diagnosed preoperatively by needle biopsy or transbronchial fiberoptic bronchoscopy with little morbidity and no mortality. These procedures are not necessary, however, if there is firm clinical and roentgenographic evidence of malignancy. Bronchogenic carcinomas presenting as asymptomatic circumscribed peripheral pulmonary masses have a 25% incidence of occult mediastinal lymph node metastases. In view of this relatively high incidence of metastasis, we think mediastinoscopy should routinely be performed prior to thoracotomy is asymptomatic patients with a peripheral pulmonary mass and no roentgenographic evidence of mediastinal widening.