Diane E. Stover

Bronchoalveolar Lavage in the Diagnosis of Diffuse Pulmonary Infiltrates in the Immunosuppressed Host

The usefulness of bronchoalveolar lavage in the diagnosis of pulmonary infiltrates in the immunosuppressed patient was studied in 97 patients. In immunosuppressed patients, the available diagnostic procedures are often invasive and have variable yield and a potential for serious complications. Bronchoalveolar lavage had an overall diagnostic yield of 66% (61 of 92 diseases). It was most effective in the diagnosis of opportunistic infections, including infection with Pneumocystis carinii (18 of 22 cases), cytomegalovirus pneumonia (10 of 12 cases), fungal pneumonia (5 of 6 cases), and mycobacterial disease (4 of 5 cases). The technique was also helpful in suspected pulmonary hemorrhage (7 of 9 cases) but was less useful for diagnosing malignancy (10 of 22 cases) and drug-induced toxicity (6 of 15 cases). Findings of bronchoalveolar lavage could be combined with those of transbronchial biopsies, brushings, and washings in the diagnosis of most of the diseases. The procedure was safe, even in thrombocytopenic patients and those requiring mechanical ventilatory support. Bronchoalveolar lavage is a valuable procedure for evaluation of pulmonary disease in the immunosuppressed host.

Cytomegalovirus Pneumonia after Bone Marrow Transplantation Successfully Treated with the Combination of Ganciclovir and High-Dose Intravenous Immune Globulin

STUDY OBJECTIVE To assess the efficacy of the combination of the antiviral agent ganciclovir (9-1,3 dihydroxy-2-propoxymethylguanine) and high-dose intravenous immune globulin for treating cytomegalovirus interstitial pneumonitis after allogeneic bone marrow transplantation. DESIGN Nonrandomized prospective trial of combined treatment with two drugs; findings in these patients were compared with those in control patients treated with either of the two drugs alone. SETTING Medical, pediatric, and intensive care units of a tertiary-care cancer treatment center. PATIENTS Consecutive cases of 10 patients in the study group and of 11 patients in a historical control group with evidence of cytomegalovirus pneumonia after bone marrow transplantation for treatment of leukemia or congenital immune deficiency. INTERVENTIONS Study Group (10 patients): ganciclovir, 2.5 mg/kg body weight, three times daily for 20 days, plus intravenous immune globulin, 500 mg/kg every other day for ten doses. Patients were then given ganciclovir, 5 mg/kg.d three to five times a week for 20 more doses, and intravenous immune globulin, 500 mg/kg twice a week for 8 more doses. Control Group (11 patients): ganciclovir alone (2 patients), 5 mg/kg twice a day for 14 to 21 days; cytomegalovirus hyperimmune globulin (5 patients), 400 mg/kg.d for 10 days; and intravenous immune globulin (4 patients), 400 mg/kg.d for 10 days. MEASUREMENTS AND MAIN RESULTS Responses were observed in all patients treated with combination therapy; 7 of 10 patients were alive and well, and had no recurrence of disease at a median of 10 months after therapy. No therapeutic benefit was observed, and none of the 11 patients treated with either ganciclovir or intravenous immune globulin alone survived (P = 0.001 by Fisher exact test). CONCLUSIONS Ganciclovir, when combined with high-dose intravenous immune globulin, appears to have significantly altered the outcome of patients with cytomegalovirus pneumonia after allogeneic bone marrow transplantation.

Spectrum of pulmonary diseases associated with the acquired immune deficiency syndrome

Over a four-year period, 130 patients with the acquired immune deficiency syndrome were studied to assess the incidence and spectrum of pulmonary disease associated with this illness. In 61 patients (47 percent), respiratory abnormalities were either present on admission or later developed. Multiple pathologic processes were present simultaneously in 24 patients and serial pulmonary problems developed in seven patients. Infection was the most common cause of pulmonary parenchymal disease and was due to Pneumocystis carinii (35 patients), cytomegalovirus (21 patients), Mycobacterium avium-intracellulare (13 patients), and bacteria (four patients). Noninfectious causes of parenchymal lung diseases were also frequently seen and included Kaposis sarcoma (eight patients), non-specific pneumonitis (seven patients), and adult respiratory distress syndrome (four patients). Significant pleural disease was present in six cases and was usually related to Kaposis sarcoma. A bronchospastic disorder developed in four patients. Pulmonary function tests, in particular the diffusing capacity and the difference between rest and exercise alveolar-arterial oxygen tension, were helpful in screening for pulmonary diseases. Patterns of clinical features and radiographic abnormalities were recognized and suggested specific diagnoses. Overall mortality from respiratory causes identified during the study was 41 percent, but varied markedly with the etiologic agent. Respiratory failure, however, carried a 100 percent mortality despite the underlying cause.

Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia.

STUDY OBJECTIVE To determine the effect of previous aerosolized pentamidine therapy on diagnosis and presentation of Pneumocystis carinii pneumonia. DESIGN A retrospective study. SETTING A tertiary care hospital. PATIENTS Fifty-two consecutive patients with P. carinii pneumonia and underlying infection with the human immunodeficiency virus (HIV) who had bronchoscopy. Twenty-one patients who were on aerosolized pentamidine therapy served as the study group. Thirty-one patients who had not received the drug served as the control group. MEASUREMENTS AND MAIN RESULTS The yield of bronchoalveolar lavage for P. carinii pneumonia was 62% for the study group and 100% for the control group (P less than 0.05). This lower yield was significant for the subset of patients having their first episode of P. carinii pneumonia. The yield of transbronchial biopsy was similar for both groups of patients (81% compared with 84%). The yield of bronchoscopy was not influenced by use of zidovudine. Review of lavage specimen slides suggested that there may be fewer organisms present in patients receiving aerosolized pentamidine. An atypical roentgenographic presentation of upper lobe predominant infiltrates was seen in 38% of the study patients and 7% of the control patients. In addition, pneumothoraces and cystic changes were also frequently seen in the study patients. Gallium scans, when done, were also atypical in the study group. Markers of the severity of disease, however, were similar in both groups. CONCLUSION The yield of bronchoalveolar lavage for P. carinii pneumonia in HIV-infected patients is lower in patients receiving aerosolized pentamidine. Unusual roentgenographic presentations and atypical gallium scans are also found in this setting.

Pulmonary Kaposi's sarcoma in the acquired immune deficiency syndrome: Clinical, radiographic, and pathologic manifestations

Pulmonary Kaposis sarcoma related to the acquired immune deficiency syndrome (AIDS) has not been well characterized. To define the clinical, radiographic, and pathologic features of this entity, 11 autopsy-proved cases of pulmonary Kaposis sarcoma were reviewed. The most common clinical symptoms were dyspnea and cough, but hemoptysis and stridor were also found. Nodular infiltrates and pleural effusions were the most commonly found radiographic abnormalities. Pulmonary function tests were sensitive in detecting the pulmonary abnormalities due to Kaposis sarcoma. A low diffusion capacity, lack of arterial desaturation with exercise, and obstruction to airflow were suggestive of pulmonary involvement with this malignancy. Although endobronchial Kaposis sarcoma was visualized at bronchoscopy as cherry-red, slightly raised lesions, bronchial biopsy specimens always showed no abnormalities. Transbronchial brushings and biopsy specimens and analysis of pleural fluid were also not helpful in establishing a diagnosis. In the seven subjects with extensive parenchymal Kaposis sarcoma at autopsy, the pleura was always involved. Eight subjects had involvement of the tracheobronchial tree. In all of the subjects, pulmonary Kaposis sarcoma was a significant cause of morbidity, and in three of 11 subjects (27 percent) it was the direct cause of death.

Lobectomy improves ventilatory function in selected patients with severe COPD

BACKGROUND Patients often undergo limited resection instead of lobectomy for non-small cell lung cancer because of a low preoperative forced expiratory volume in 1 second (FEV1). Our goal is to define criteria that will preoperatively identify a group of patients who will not lose further function after lobectomy. METHODS Patients who underwent lobectomy with a preoperative FEV1 of less than 80% of predicted were retrospectively identified. Data collected included preoperative and postoperative pulmonary function tests, age, sex, the lobe resected, and preoperative ventilation-perfusion scan result. RESULTS Thirty-two patients were included in this study. The median preoperative FEV1 was 60% of predicted (1.65 L) and the mean change in FEV1 was a loss of 7.8% after lobectomy. The patients were divided into two groups. Group 1 (n = 13) had a preoperative FEV1 of less than or equal to 60% of predicted (median, 49%; 1.35 L) combined with an FEV1 to forced vital capacity ratio of less than or equal to 0.6. Group 2 (n = 19) includes all other patients (median preoperative FEV1, 69% of predicted; 1.87 L). The mean changes in FEV1 after lobectomy were +3.7% and -15.7% for groups 1 and 2, respectively (p < 0.005). A chronic obstructive pulmonary disease index was defined and then calculated for each patient. The relationship between this index and the change in FEV1 after lobectomy for all 32 patients appears linear (r = -0.43; p = 0.015). CONCLUSIONS Patients with a very low preoperative FEV1 and FEV1 to forced vital capacity ratio are less likely to lose ventilatory function after lobectomy and may actually improve it.

Rapid Immunodiagnosis of Cytomegalovirus Pneumonia by Bronchoalveolar Lavage Using Human and Murine Monoclonal Antibodies

Bronchoalveolar lavage material from 54 immunocompromised patients with interstitial pneumonia was examined by immunofluorescence with cytomegalovirus-specific monoclonal antibodies. Twelve patients (22%) had cytomegalovirus detected in their lavaged cells, and 9 of these patients (17%) had proven cytomegalovirus pneumonitis. This assay detected all samples with cytomegalovirus when the virus was detected by established methods either at the time of lavage or after any other procedure in the subsequent 2 months; that is, it had a sensitivity of 100%. Cytomegalovirus could be detected within 3 hours of the lavage, and a clear correlation was seen between the number of fluorescent cells and the presence of cytomegalovirus pneumonia. All 9 patients with pneumonitis had more than 0.5% fluorescent cells, whereas the 3 patients in whom cytomegalovirus was detected without pneumonia had significantly fewer fluorescent cells. This method provides a sensitive, rapid, and quantifiable system for detection of cytomegalovirus, facilitating the early diagnosis and treatment of cytomegalovirus pneumonia.

Organizing Pneumonia as a Side Effect of Ipilimumab Treatment of Melanoma

Ipilimumab is one of the newly developed human monoclonal antibodies used in the treatment of metastatic melanoma. Its primary mechanism of action is a specific blockade of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a T-cell receptor responsible for inhibition of lymphocyte activation. By blocking CTLA-4, ipilimumab enhances immune responses against tumor cells, but also exposes normal tissues to an increased risk of autoimmune phenomena as a potential side effect. In this report, we describe the case of a 58-year-old woman with metastatic melanoma who was treated with ipilimumab in the weeks prior to the onset of severe nonresolving dyspnea and cough. Extensive workup revealed organizing pneumonia as the cause of her hypoxemic respiratory failure and treatment with steroids led to a resolution of her pulmonary disease. To our knowledge, this is the first report of pulmonary toxicity caused by ipilimumab, which manifested on pathology as organizing pneumonia.

Significance of non-calcified pulmonary nodules in patients with extrapulmonary cancers

Background: This study sought to determine the rate and patterns of malignancy in patients with extrapulmonary cancers and non-calcified pulmonary nodules, and to develop a statistical model to guide clinicians regarding choice of patients for diagnostic biopsy. Method: The medical records of 151 patients evaluated at the Memorial Sloan-Kettering Cancer Center between January 1999 and December 2001 for non-calcified pulmonary nodules were reviewed. Nodules were considered malignant based on the results of a diagnostic biopsy, and were considered benign if their appearance remained stable 2 years after the initial study, if they resolved, or if a biopsy showed a non-malignant condition. Results: Sixty four of 151 patients (42%) were diagnosed with malignant nodules; 32 had newly diagnosed lung cancers, 28 had metastatic spread of their primary cancers, and four had lesions that were either new cancers or of undetermined aetiology. On univariate analysis the likelihood of malignancy increased with nodule size, tobacco exposure, and the finding of a solitary nodule. On multivariable analysis only nodule size and tobacco exposure were predictive of malignancy. The model had good predictive accuracy (area under the curve 0.751) but had insufficient discrimination for use as a clinical tool to determine which patients should undergo diagnostic biopsy. Conclusion: Nearly half the non-calcified pulmonary nodules identified in this series were malignant. Lung cancer was more common than metastatic disease. These findings support the need for close interval follow up and a low threshold for diagnostic biopsy in patients with extrapulmonary cancers and non-calcified pulmonary nodules. In smokers, such lesions should raise concern for lung cancer.

A newly recognized syndrome -radiation-related bronchiolitis obliterans and organizing pneumonia: A case report and literature review

Bronchiolitis obliterans and organizing pneumonia (BOOP) is a syndrome that has been associated with a variety of underlying disorders, including infection, collagen vascular diseases and toxic fume inhalation. Rarely, however, BOOP has been associated with radiation- or chemotherapy-induced pulmonary toxicity. Over the past 3 years, several case series have reported BOOP in the unique setting of radiation in breast cancer patients. This study describes our experience with this newly recognized syndrome and a review of the English-language literature on this syndrome.