Chemotherapy-associated pulmonary toxic reactions during treatment for breast cancer.

Chemotherapy-related pneumonitis developed in eight patients during treatment for breast cancer. Six were receiving adjuvant therapy and two were being treated for metastatic disease. Fever, chills, dyspnea, and dry cough were the initial symptoms. Observations from chest roentgenograms varied from normal to bilateral interstitial-alveolar infiltrates. Results of pulmonary function tests were markedly abnormal, with a decreased diffusing capacity being the most characteristic abnormality. The pneumonitis developed in six patients while receiving 20 mg or less per day of prednisone and appeared temporarily related to tapering of steroid therapy in four patients. All patients recovered clinically, although prednisone therapy of 60 mg/day or its equivalent was required in three cases. Mild pulmonary function abnormalities persisted. Drug-induced pneumonitis should be considered in the differential diagnoses of patients with breast cancer in whom unexplained fever, dyspnea, or infiltrates develop during multidrug chemotherapy.

Effect of Perioperative ß-Blockers on Pulmonary Complications among Patients with Chronic Obstructive Pulmonary Disease Undergoing Lung Resection Surgery.

The aim of this study is to determine if COPD patients undergoing lung resection with perioperative ß-blocker use are more likely to suffer postoperative COPD exacerbations than those that did not receive perioperative ß-blockers. Methods. A historical cohort study of COPD patients, undergoing lung resection surgery at Memorial Sloan-Kettering Cancer Center between 2002 and 2006. Primary outcomes were the rate of postoperative COPD exacerbations, defined as any initiation or increase of glucocorticoids for documented bronchospasm. Results. 520 patients with COPD were identified who underwent lung resection. Of these, 205 (39%) received perioperative ß-blockers and 315 (61%) did not. COPD was mild among 361 patients (69% of all patients), moderate in 117 patients (23%), and severe in 42 patients (8%). COPD exacerbations occurred among 11 (5.4%) patients who received perioperative ß-blockers and among 20 (6.3%) patients who did not. Secondary outcomes, which included respiratory failure, 30-day mortality, and the presence or absence of any cardiovascular complication, ICU transfer, cardiovascular complication, or readmission within 30 days, did not differ in prevalence between the two groups. Conclusions. This study implies that perioperative ß-blockers use among COPD patients undergoing lung resection surgery does not impact the rate of exacerbations.

Pneumocystis carinii pneumonia in patients with primary brain tumors.

All histologically documented episodes of Pneumocystis carinii pneumonia in adult patients with primary brain tumors treated at Memorial Sloan-Kettering Cancer Center, New York, NY, since 1981, were retrospectively reviewed. Pneumocystis carinii pneumonia was histologically documented 11 times in 10 patients. During the same 8-year interval, approximately 587 adults were seen at the center for a brain tumor, 90% of whom received ongoing therapy. Therefore, in at least 1.7% (10/587) of our patients with brain tumors, P carinii pneumonia developed. The median duration of dexamethasone therapy at the onset of P carinii pneumonia symptoms was 2.75 months. Symptoms began during tapering of steroid therapy in eight episodes. Bronchoscopy was diagnostic in the eight cases in which it was performed. Four episodes (40%) were fatal. Trimethoprim-sulfamethoxazole prophylaxis may be indicated in some patients with brain tumors, especially during tapering of steroid therapy.

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 Kaposi's 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 Kaposi's 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.

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

Pulmonary Kaposi's 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 Kaposi's 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 Kaposi's 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 Kaposi's 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 Kaposi's sarcoma at autopsy, the pleura was always involved. Eight subjects had involvement of the tracheobronchial tree. In all of the subjects, pulmonary Kaposi's sarcoma was a significant cause of morbidity, and in three of 11 subjects (27 percent) it was the direct cause of death.

Severe bleomycin-induced pneumonitis. Clinical features and response to corticosteroids.

Ten (3 percent) of 287 patients receiving combination chemotherapy developed severe bleomycin-induced pneumonitis. The course and the response to therapy in these patients are summarized in this report. The dose of bleomycin received varied from 136 to 588 units, with toxic effects occurring in six patients who had received less than 200 units. Dyspnea and dry cough were the presenting symptoms in nine patients; one was asymptomatic. Roentgenograms were abnormal in nine cases, with five showing bilateral infiltrates. Four patients had asymmetric abnormalities, with radiographic involvement of only a single lung in two of these. Pulmonary function tests were abnormal, with a decreased diffusing capacity. Seven patients were treated with corticosteroid therapy, and significant clinical and radiographic improvement was noted; however, pulmonary function tests remained abnormal and could not be used to monitor the response. Prolonged therapy with corticosteroids was required over many months to maintain improvement. Tapering of the steroid dosage led to recurrence of clinical symptoms and radiographic infiltrates in five patients. Mortality was 60 percent, with three early deaths in untreated patients and three late deaths which occurred 12 to 15 months after diagnosis. In this study, patients with severe bleomycin-induced pneumonitis had symptomatic improvement and roentgenographic clearing following corticosteroid therapy.

Unusual etiology of cough in a woman with asthma.

A case of multiple symmetric lipomatosis (Madelung's disease) acquired through chronic use of corticosteroids is reported. Presumed symptoms of asthma, which consisted of a barking cough, were treated with escalating doses of steroids. We postulate that excessive use of steroids led to extensive mediastinal fatty infiltration with narrowing of the trachea and mainstem bronchi as noted both radiographically and bronchoscopically. When the steroids were tapered, there was marked improvement of the patient's symptoms and resolution of the upper airway intrathoracic obstruction. When patients with asthma are receiving optimal therapy and fail to improve, other causes for their symptoms should be considered.

Endobronchial Pneumocystis carinii infection in a patient with the acquired immune deficiency syndrome.

We report a case of endobronchial Pneumocystis carinii infection in a patient who most likely had the acquired immune deficiency syndrome (AIDS). Although many unusual manifestations of Pneumocystis pneumonia have been reported in patients with AIDS, this is the first case of P carinii presenting as an endobronchial mass.

Pulmonary cell populations in the immunosuppressed patient. Bronchoalveolar lavage findings during episodes of pneumonitis.

Bronchoalveolar lavage (BAL) cell populations were determined in 47 immunosuppressed patients during episodes of pulmonary disease. Thirty six patients had AIDS and 11 had conventional causes of immunosuppression. Pulmonary disease was due to a variety of infectious and noninfectious causes and was similar in both groups. In the AIDS patients, the mean BAL cell proportions were 64.2 +/- 3.7 percent alveolar macrophages (MACS), 28.7 +/- 3.4 percent lymphocytes, 3.5 +/- 1.8 percent polymorphonuclear cells (PMN) and 1.6 +/- 0.6 percent eosinophils (EOS). The non-AIDS group had similar findings in the BAL, with 59.3 +/- 8.3 percent MACS, 34.8 +/- 7.2 percent lymphocytes, 5.5 +/- 1.7 percent PMN and 0.4 +/- 0.2 percent EOS. The most striking finding in each group was a significant increase in both the proportion and absolute number of lymphocytes compared to controls. This was in marked contrast to the peripheral blood findings of lymphopenia. There was no characteristic cell profile diagnostic of any specific pulmonary disease. There was also no direct relationship of the cells present to respiratory symptoms, roentgenographic abnormalities or survival from pulmonary disease. This study demonstrates that although there was wide individual variation in lavage findings, a local pulmonary inflammatory reaction consisting predominantly of lymphocytes occurs in the immunosuppressed host during episodes of lung disease. The significance of this lymphocyte alveolitis and the complex host pathogen interaction responsible for determining the cell populations present in the lungs of these patients requires further study.

Bilateral bronchoalveolar lavage in the diagnosis of opportunistic pulmonary infections.

To further improve the diagnostic value of bronchoscopy in the immunosuppressed population presenting with diffuse pulmonary infiltrates, we prospectively investigated the utility of bilateral bronchoalveolar lavage (BAL). We performed 62 bronchoscopies on 52 immunosuppressed patients. Of the 52 patients, 33 had pulmonary infections. The yield for Pneumocystis carinii pneumonia on bilateral BAL was 94 percent (31/33), compared to the 84 percent (51/61) previously obtained with unilateral BAL in our institution. The recovery of P carinii was unilateral in four of five patients without AIDS and in four of 26 patients with AIDS. Transbronchial biopsy gave a yield of 85 percent (11/13). In ten patients with definitive cytomegalovirus (CMV) pneumonia, recovery of CMV by combined culture and cytology was 100 percent. Of nine bronchoscopies with positive cytology for CMV, five showed cytopathologic changes in the BAL from both sides and four in the BAL from one side only. No complications were seen in the 14 patients with thrombocytopenia or the five patients receiving mechanical ventilation. Our findings indicate that bilateral BAL significantly increases the yield for recovery of P carinii (p less than 0.02) and CMV (p less than 0.001) in immunosuppressed patients.

Lung transplantation for chemotherapy-induced pulmonary fibrosis.

A 26-year-old man cured of childhood acute lymphoblastic leukemia underwent a single lung transplant for drug-induced pulmonary toxicity 9 years after the completion of chemotherapy. It is not known whether patients cured of a malignancy who undergo organ transplantation are at increased risk of malignancy as compared to other organ transplant recipients. There was no evidence of recurrent or secondary malignancy in this case. Since single lung transplantation has been effective for idiopathic pulmonary fibrosis, it should be considered for patients cured of a malignancy who develop chemotherapy-induced pulmonary fibrosis.

Fiberoptic bronchoscopy in allogeneic bone marrow transplantation: findings in the era of serum cytomegalovirus antigen surveillance.

STUDY OBJECTIVES: Pulmonary complications occur in half of allogeneic bone marrow transplantation (BMT) patients. The incidence of these complications has been reduced by prophylaxis against Pneumocystis carinii pneumonia, preemptive therapy in patients at high risk for cytomegalovirus (CMV) reactivation, and, more recently, screening for serum CMV antigen. Since fiberoptic bronchoscopy (FOB) has historically been the primary diagnostic test to evaluate BMT patients with pulmonary disease, a review was performed to determine the impact, if any, that current prophylaxis and screening policies may have had on FOB utility. DESIGN: The records of 174 adult patients undergoing BMT between January 1997 and December 1999 were reviewed to determine the diagnostic yield of FOB and the frequency by which FOB altered management. RESULTS: Sixty-one patients underwent 76 bronchoscopies. FOB was diagnostic in 32 patients (42.1% of cases) and directly changed management in 24 patients (31.6% of cases). Half of these changes included the withdrawal of an antimicrobial agent. The most common findings were infection (32 cases) and diffuse alveolar hemorrhage (6 cases). CMV was the most prevalent infection identified, but FOB resulted in the addition of antiviral therapy to only two patients. P carinii pneumonia was not diagnosed in any patient studied. CONCLUSIONS: These data suggest a changing spectrum of pulmonary disease in BMT patients. FOB has limited impact on the diagnoses of CMV disease or P carinii pneumonia with current prophylaxis and screening strategies. It may be useful in identifying other infectious etiologies and in eliminating unnecessary antimicrobials.

Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) remains an important complication of AIDS. Advances have been made in establishing the taxonomy of the organism but the life cycle of the organism and pathogenetic mechanisms of disease remain obscure. In HIV patients the incidence of PCP has decreased because of widespread use of prophylaxis and survival of those with PCP has improved with use of adjunctive corticosteroid therapy. Less toxic drug therapies are still needed as well as better noninvasive diagnostic techniques.

Pulmonary function tests.

The clinical significance of pulmonary function tests (including blood gas analysis) lies in their sensitivity for detecting PCP. PCP has most consistently been found to cause abnormalities in the DLCO and the exercise arterial blood gas; both are highly sensitive for the presence of Pneumocystis infection. These tests are more sensitive for the detection of PCP than are the resting arterial blood gas and chest x-ray. Therefore, measuring these values can be especially helpful in evaluating HIV-infected individuals who have pulmonary symptoms but whose resting arterial blood gas and/or chest radiograph are normal. The advantage of performing the exercise test over measuring the DLCO is that the exercise test is simple. It can be done without pulmonary function equipment and without a technologist. Furthermore, since many AIDS patients with non-PCP pulmonary disorders maintain "normal" exercise tests despite abnormal DLCO, it can be useful in evaluating patients for PCP who have known underlying lung disease with progressive symptoms. Measurement of lung volumes and spirometry lacks both sensitivity and specificity for detecting pulmonary disease in general and PCP in particular. Spirometry is helpful in detecting airways obstruction, which is not an uncommon finding in AIDS patients. The etiology, clinical significance, and treatment of obstructive ventilatory defects in the AIDS population remains unclear.

Approach to the patient with pulmonary disease.

The approach to the HIV-infected patient with pulmonary disease is summarized by the algorithms in Figures 3 and 4. These are not intended to be followed in a rigid step-wise fashion. Rather, the practitioner's knowledge of the patient with his or her accompanying medical risks influences the path taken, including the depth and the speed of the evaluation. For example, the patient with cough who is afebrile and breathing at 18 breaths a minute, with a normal chest radiograph and a CD4 count of 350 cells/mm3, is reasonably treated with a macrolide or cephalosporin for bacterial bronchitis and clinical follow-up while awaiting cultures (see Fig. 4). A febrile patient with a cough productive of thin mucus, but known to have a CD4 count of 60 cells/mm3 should be started on anti-PCP therapy while being evaluated for PCP with an induced sputum and if nondiagnostic, a bronchoscope despite a normal chest radiograph. Screening can be as simple as placing an oximeter on the patient's finger in the clinic. If the oxygen saturation of a patient with a normal chest radiograph is low, then the patient should be hospitalized and begun on treatment for PCP while diagnostic evaluation is initiated. If the oxygen saturation is normal, the patient can be exercised to elicit desaturation. If there is no desaturation, PCP is unlikely. If the results are equivocal (i.e., a decrease in saturation, but less than 3%), rest and exercise arterial blood gases can be performed, along with a Dlco-Gallium scanning can be done in patients known to have abnormal Dlco or those who cannot exercise. Patients with focal infiltrates who have acute onset of symptoms (see Fig. 4) commonly have bacterial infections, but the possibility of PCP or TB should not be dismissed. Induced sputum should be examined if TB or PCP is suspected. Patients who are severely ill might go quickly to bronchoscopy without awaiting improvement on empiric therapy. The patient with diffuse infiltrates (see Fig. 4) needs no screening because the presence of disease is apparent from the radiograph. The diagnostic part quickly leads to bronchoscopy for these patients and the initiation of therapy for PCP when suspected. In patients with known pulmonary KS, gallium scanning can be helpful to rule out acute infection, but bronchoscopy is warranted if the patient is severely ill, or at high risk for PCP. This approach should avoid unnecessary procedures in patients with simple bacterial infections, without missing opportunistic infections and tumors.

Bronchiolitis obliterans organizing pneumonia in cancer: a case series.

Bronchiolitis obliterans with organizing pneumonia (BOOP) is an infrequently encountered clinical condition that can mimic a number of other pathologic lung processes. The presentation of this treatable condition in cancer patients has not been described in any large series. We conducted a retrospective study of patients with BOOP at Memorial Sloan-Kettering Cancer Center, NewYork, NY, U.S.A. from January 1992 to December 1999. The type and treatment of primary cancer, clinical and radiographic features of initial BOOP presentation, and outcome following therapy were recorded. Forty-three patients with an underlying diagnosis of cancer were found on lung biopsy to have BOOP as an isolated entity. BOOP was encountered in patients with a variety of clinical presentations, and many types of malignancies. The symptom patterns were non-specific, as were the physiological abnormalities. The only clear relationship between the underlying malignancyand the diagnosis of BOOP at presentation was in the chest radiographic findings. Patients with solid organ tumors were more likely to have nodular or mass like radiographic abnormalities (81%) than to have diffuse infiltrates (19%). We observed the opposite pattern in patients with hematologic malignancies (22% vs.67%). The vast majority of patients recovered from this condition. In conclusion, For cancer patients, BOOP represents a treatable cause of lung disease with protean manifestations. BOOP can mimic pulmonary malignancy and pulmonary infection. In cancer patients, the evaluation of new pulmonary symptoms accompanied by radiographic changes should include a consideration of this diagnosis.

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.

Pulmonary complications in cancer patients.

Pulmonary complications of cancer and cancer therapy represent a broad spectrum of disease. Early diagnosis and treatment are essential to achieve an optimal outcome.