Impact of lung transplant operation on bronchiolitis obliterans syndrome in patients with chronic obstructive pulmonary disease.

Previous studies suggest that bilateral (BLT) compared with single lung transplantation (SLT) for patients with chronic obstructive pulmonary disease (COPD) results in improved long-term survival. The effect of transplant operation on bronchiolitis obliterans syndrome (BOS) is unknown. A retrospective study of all lung transplant recipients with pre-transplant diagnoses of COPD at the University of Toronto and at Duke University was performed. Data collected were age, gender, date and type of transplant, acute rejection, survival, presence and time of BOS. 221 (bilateral n = 101, single n = 120) patients met our criteria. Patients with BLT were younger (53.0 vs. 55.3 years; p = 0.034), more likely to be male (56.3% vs. 42.4%; p = 0.039) and more likely to be transplanted at the University of Toronto (79.6% vs. 16.1%; p < 0.001). Freedom from BOS was similar at 1 year post-transplant. However, BLT recipients were more commonly free from BOS 3 years (57.4% vs. 50.7%) and 5 years (44.5% vs. 17.9%) post-transplant (p = 0.024). Survival of BLT was better than SLT recipients at 3 and 5 years post-transplant (BLT vs. SLT: 67.5% vs. 61.1% and 60.7% vs. 34.1%, respectively; p = 0.018). Similar trends on survival were observed after development of BOS. BLT results in lower rates of BOS in patients with COPD that are eligible for both SLT and BLT.

Epstein-Barr virus serology and posttransplant lymphoproliferative disease in lung transplantation.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is now a widely recognized complication of lung transplantation. In the current study, we present our experience with PTLD over a 15-year period, which includes the incidence rates in 242 lung allografts and the relative risk of developing PTLD in 146 patients with known pretransplantation Epstein-Barr virus (EBV) status. METHODS: Inpatient and outpatient charts of 300 consecutive lung transplant recipients between 1984 and 1999 were retrospectively reviewed. RESULTS: Twelve cases of PTLD were observed for a total incidence rate of 5.0%. Ten of these patients had pretransplantation EBV testing, and the consequent increase in relative risk for patients who were EBV negative was 6.8-fold. The mean time between organ transplantation and tissue diagnosis of PTLD was 17.6 months. Total 1-year survival rate from the time of diagnosis for the cohort was 58%, whereas 2-year survival rate was 50%. Median survival for the six patients who died was 4.5 months. CONCLUSIONS: These data suggest that although EBV seronegativity does carry a 6.8-fold increase in the relative risk of developing PTLD, long-term survival despite the development of PTLD can be achieved, and thus EBV seronegativity by itself should not be considered a contraindication to lung transplantation.

Osteoporosis and lung transplantation: a prospective study.

STUDY OBJECTIVE: Osteoporosis is a well-recognized complication of lung transplantation that may significantly impair the quality of life of transplant recipients. We performed a prospective study of bone mineral density (BMD) before and after transplantation to determine the degree of bone mass loss associated with lung transplantation Patients and design: We conducted a prospective study of BMD in 28 patients with various end-stage respiratory diseases pretransplantation and 6 to 12 months posttransplantation. The BMD of the lumbar spine (LS) and femoral neck (FN) were measured. All 28 patients were treated only with vitamin D and calcium supplementation posttransplant. The primary endpoint was the percentage change in BMD. The secondary endpoint was the incidence of fractures posttransplant. A univariate analysis was conducted to determine the various risk factors associated with bone mass loss pretransplant and posttransplant. RESULTS: Prior to transplantation, moderate to severe bone disease was evident. The mean (+/- SD) pretransplant T score (the number of SDs from the peak bone mass) and Z score (the number of SDs from the age-matched mean) for the LS were -1.72 +/- 1.37 and -1.44 +/- 1.31, respectively. The mean pretransplant T score and Z score for the FN were -2.65 +/- 1.01 and -1.5 +/- 1.43, respectively. Within 6 to 12 months posttransplant, the mean BMD for the LS decreased by 4.76% (p < 0.001), while the mean BMD for the FN decreased by 5.3% (p < 0.001). Five of the 28 patients (18%) suffered osteoporotic fractures posttransplant, while no fractures were documented pretransplant. The cumulative steroid dose posttransplant was associated with a drop in BMD for the LS and FN (r = 0.39, p = 0.039 and r = 0.63, p < 0.001, respectively), while a negative association was found between cumulative steroid use pretransplant and baseline LS and FN T scores (r = -0.4, p = 0. 02 and r = -0.43, p = 0.023, respectively). CONCLUSION: Within 6 to 12 months after lung transplantation, there is a significant decrease in BMD at both the LS and FN levels (approximately 5%) despite vitamin D and calcium supplementation. This drop in BMD is associated with a relatively high incidence of osteoporotic fractures posttransplant.

Lymphoproliferative disorders after lung transplantation: imaging features.

PURPOSE: To define the imaging features of lymphoproliferative disorders that occur after lung transplantation. MATERIALS AND METHODS: In a retrospective review of the cases of 246 patients who had undergone lung transplantation (62 single- and 184 double-lung transplants) between 1987 and 1997, the authors found nine patients (seven men and two women, aged 16-59 years [mean, 42.2 years]) with posttransplantation lymphoproliferative disorders. All imaging, clinical, and pathologic findings pertaining to these disorders were reviewed. RESULTS: Eight of the nine patients had isolated intrathoracic disease. The most common abnormality (six patients) was the presence of multiple, well-defined pulmonary nodules. These nodules, when multiple, had basilar and peripheral predominance. Other abnormal features included hilar or mediastinal adenopathy (two patients), a consolidated upper lobe (one patient), a pleural mass (one patient), and bulky abdominal lymphadenopathy (one patient with pathologically proved Hodgkin lymphoma). Three patients had nodules with a surrounding area of ground-glass opacity (halo sign), and one patient had multiple ill-defined areas of centrilobular opacity. Air bronchograms were not often seen, and pleural effusions were absent. CONCLUSION: The presence of well-defined pulmonary nodules in a patient who has undergone lung transplantation should raise concern about the possibility of posttransplantation lymphoproliferative disorder. In such cases, performance of pathologic studies should be expedited.

Pulmonary complications following bone marrow transplantation.

Pulmonary complications are a common cause of morbidity and mortality after bone marrow transplantation. Some of these complications are infectious and related to the degree of ongoing immunosuppression, and thus vary with the posttransplant marrow reconstitution and the need for continued immunomodulating drugs. Noninfectious complications are related to previous chemotherapy, the transplantation protocol and conditioning regimen, and, in allogeneic transplants, the presence of graft-versus-host disease. The various complications are classified based on their timing after the transplant procedure. A diagnostic and therapeutic approach is outlined and the prognosis is discussed.

Idiopathic small airways pathology in patients with graft-versus-host disease following allogeneic bone marrow transplantation.

In a retrospective analysis (July 1979 to March 1984) of 120 allogeneic adult bone marrow transplant recipients, we identified seven patients with small-airway disease for whom no microbiologic agent was detected. Six had pulmonary function studies demonstrating air flow obstruction. Five of the seven patients had an open-lung biopsy showing pathologic changes within small airways; these varied from early bronchiolar wall damage to bronchiolitis obliterans. The inflammatory cell infiltrate was peribronchiolar, and consisted of polymorphonuclear leukocytes and lymphocytes in varying proportions. Three of the seven patients recovered following increased immunosuppressive therapy; the other four died. Because all seven patients had acute and chronic graft-versus-host disease, in the absence of any identifiable pathogen, we postulate that small-airway damage represents one of the facets of graft-versus host-disease. An additional analysis of 26 patients with respiratory symptomatology and available histologic material supports the hypothesis that small-airway disease in bone marrow transplant patients represents a risk factor for the subsequent development of respiratory opportunistic infections.

Pulmonary tumor embolism: a critical review of clinical, imaging, and hemodynamic features.

Pulmonary tumor embolism is a common finding at autopsy but is generally perceived as a difficult diagnosis to make ante mortem. After a retrospective review of 164 reported cases of pulmonary tumor embolism, we identified a typical profile of clinical, laboratory, and imaging features that may permit confident clinical diagnosis in most patients with this condition. The clinical features include a documented or suspected underlying malignancy, acute to subacute onset of dyspnea, and signs of cor pulmonale. Supportive laboratory features are hypoxemia or increased alveolar-arterial oxygen gradient, and invasive or noninvasive evidence of pulmonary artery hypertension. Typical imaging findings are normal chest radiographs; multiple, subsegmental, peripheral perfusion defects on ventilation-perfusion lung scans; and delayed filling with or without subsegmental filling defects but without a thrombus on pulmonary angiogram. Radiolabeled monoclonal antibody imaging and pulmonary microvascular cytology sampling techniques are promising diagnostic tests for early diagnosis of pulmonary tumor embolism.

Small-airways disease in recipients of allogeneic bone marrow transplants. An analysis of 11 cases and a review of the literature.

In a retrospective review of 116 consecutive allogeneic bone marrow transplants (BMT), severe obstructive airways disease was identified in 11 patients. Lung pathology demonstrated bronchiolitis in 9 patients and physiologic studies showed small-airways disease consistent with bronchiolitis in the other 2. None of the 5 patients with associated infection survived, while 3 of the 6 patients without an identified pathogen stabilized or improved. Analysis of the 11 cases presented and all 25 cases reported in the literature (1982 to 1985) supports the conclusion that graft-versus-host disease is a major risk factor for bronchiolitis in BMT recipients. Among the proposed mechanisms for the development of bronchiolitis after allogeneic BMT, the 2 most likely are graft-versus-host disease directly causing bronchiolitis, and increased immunosuppressive therapy given for graft-versus-host disease predisposing to viral bronchiolitis. The available evidence would suggest that it is prudent to obtain serial pulmonary function tests even in asymptomatic patients post-BMT, and particularly in those with chronic graft-versus-host disease, in the hope that early detection will allow for early intervention that will arrest or reverse the progression of the obstructive airways disease.

Prevention of acute pulmonary edema after bone marrow transplantation.

In a retrospective review of 21 bone marrow transplantation procedures (BMT), we identified ten episodes of acute pulmonary edema coinciding with significant weight gain in the second week after BMT. When we prospectively observed nine consecutive BMT recipients, six patients developed acute pulmonary edema associated with significant (p less than 0.05) weight gain and an increase in echocardiographically determined left ventricular end diastolic diameter. These findings led to a prospective prophylactic intervention study of 30 consecutive BMT patients. Prophylactic intervention consisting of reduced fluid volume of parenteral alimentation, and diuretic therapy was instituted at any clinical sign of fluid overload. No episode of pulmonary edema occurred. The dramatic difference--acute pulmonary edema occurred in 16/30 untreated vs 0/30 treated cases--suggests that this post-BMT complication is critically related to fluid balance and can be prevented by careful clinical examination, close monitoring of weight change, avoidance of fluid overload and the appropriate use of diuretic therapy.

Pleuropulmonary melioidosis in a Cambodian refugee.

A 47-year-old Cambodian refugee presented with an acute respiratory illness that featured consolidation of the lower lobe of the left lung and progressive involvement of the adjacent pleura caused by Pseudomonas pseudomallei. Initial difficulty in identifying the organism resulted in an inadequate duration of therapy. Chronic pleural disease followed, and the organism became resistant to many antibiotics during therapy. A diagnosis of pleuropulmonary melioidosis should be entertained and the microbiology laboratory alerted when patients with pneumonia who are from endemic areas are encountered, so that a diagnosis can be made early and the appropriate treatment begun.

Tumor-associated peripheral eosinophilia: two unusual cases.

Peripheral eosinophilia is a rare but recognized accompaniment of malignant disease. Two unusual cases, one with a histiocytic lymphoma and the other with cervical carcinoma, are described. In the first patient, pulmonary infiltrates developed at the height of the eosinophilia and in the second, the peripheral eosinophilia heralded the onset of disseminated disease. Tumor-associated peripheral eosinophilia is reviewed, and it is concluded that peripheral eosinophilia associated with a malignant setting is a marker of extensive disease and is thus associated with a poor prognosis.

Invasive aspergillosis in a "healthy" patient.

A case of invasive aspergillosis complicated by the formation of an aspergilloma is described. The patient, a 48-year-old man, was apparently healthy except for mild alcoholic steatosis of the liver. A review of the literature revealed that 5 of the 14 previously reported cases of invasive aspergillosis in seemingly immunocompetent hosts were associated with liver disease. Immunologic investigation in this case revealed transient cutaneous anergy during the acute illness and normal lymphocyte function. Assessment of polymorphonuclear leukocyte function, however, showed abnormalities of phagocytosis as well as impairment of intracellular bactericidal activity. These abnormalities may have contributed to a relative immunodeficiency. Impairment of immune function may play a role in the pathogenesis of invasive aspergillosis in some apparently healthy patients.

Changes in respiratory variables of grain handlers and civic workers during their initial months of employment.

The health effects of employment as a grain handler were studied by examining workers on two occasions, firstly, immediately before or soon after they were hired and again about two and a half months after they were employed. Over this time there was a substantial increase in the prevalence of cough, sputum, and eye irritation, accompanied by small pulmonary function changes suggestive of a restrictive ventilatory defect. No comparable changes in symptoms were observed over a similar number of months in grain handlers employed for an average of nine years or in control workers consisting of newly hired or long term civic outside labourers. The long term grain handlers, however, developed a similar change in their pulmonary function. These findings indicate the occurrence of a change in the health of grain elevator workers after a relatively brief duration of employment.

Computed tomographic diagnosis of pulmonary sequestration.

Two cases of pulmonary sequestration demonstrated by CT scans of the chest are described. In one, CT demonstrated the anomalous artery. This finding may obviate the need for angiography when surgery is not contemplated.

A systematic controlled study of pulmonary abnormalities in rheumatoid arthritis.

We have conducted a prospective comparison of 155 rheumatoid patients and 95 control subjects. Both groups were selected without regard to respiratory status, but were comparable in age, sex and smoking experience. The prevalence of respiratory symptoms, of past respiratory illnesses and of pulmonary function findings of airway obstruction was similar in both groups. However, the rheumatoids showed an increased frequency of chest crackles and abnormal chest radiographs, and had pulmonary function changes suggestive of a restrictive ventilatory defect. These pulmonary abnormalities were associated with smoking, the presence of nonpulmonary extraarticular features, the level of rheumatoid disease activity and treatment with oral corticosteroid or gold.