Tropical pulmonary eosinophilia

Tropical pulmonary eosinophilia (TPE) usually affects people living in the tropics, especially those in Southeast Asia, India, and certain parts of China and Africa. However, owing to the rising frequency of world-wide travel and the migration between continents, this disease is increasingly seen in the West, where the diagnosis can be easily missed since it is rarely encountered and can mimic many other conditions. Cases of TPE have typically been reported to masquerade as acute or refractory bronchial asthma. TPE results from a hypersensitivity reaction to lymphatic filarial parasites found in endemic regions. There is evidence that it is more likely to occur in nonimmune individuals, ie, visitors to endemic regions, than in individuals of endemic populations who have developed immunity to filarial infections. Clinical features include paroxysmal cough, wheezing and dyspnea, and systemic manifestations such as fever and weight loss. A history of residence in a filarial endemic region and a finding of peripheral eosinophilia >3,000/mm3 should initiate a consideration of this disease. Other criteria for the diagnosis of TPE include absence of microfilariae in the blood, high titers of antifilarial antibodies, raised serum total IgE >1,000 U/mL, and a favorable response to the antifilarial, diethylcarbamazine, which is the recommended treatment. This disease, if left untreated or treated late, may lead to long-term sequelae of pulmonary fibrosis or chronic bronchitis with chronic respiratory failure. Herein lies the importance of early diagnosis and treatment of TPE.     

Tropical pulmonary eosinophilia. Report of a case

Tropical pulmonary eosinophilia (TPE) is an unusual manifestation of filarial infection, most commonly found in South-East Asia and caused by immunologic hyperresponsiveness to Wuchereria bancrofti and Brugia malayi. This report concerns a case of TPE in a 25-year-old Indian male who had been living in Italy for two years and was admitted to hospital with chest pain. Diethylcarbamazine therapy proved effective in rapidly eliminating symptoms and pulmonary abnormalities, as well as normalizing of laboratory findings.     

Loa loa infection as a cause of migratory angioedema: report of three cases from the Texas Medical Center

Loa loa is a filarial parasite that is endemic in West and Central Africa. Expatriates infected with L. loa commonly develop characteristic migratory angioedema called Calabar swellings. We describe three patients who presented with classical Calabar swellings for whom the diagnosis of loiasis was delayed. Unusual features that were present included a leukocytoclastic vasculitis seen on skin biopsy (case 1), a relatively short exposure to an area of endemicity (cases 1 and 3), and a normal eosinophil count on initial evaluation (cases 2 and 3). We discuss the characteristic clinical manifestations of, pathological findings of, and therapy for loiasis. With the increased frequency of international travel, L. loa infection must be considered in the differential diagnosis for patients with migratory angioedema, urticarial vasculitis, or eosinophilia.     

Surgical management in atypical pulmonary tuberculosis (MAIS complex)

Forty-four patients with Mycobacterium avium-intracellulare-scrofulaceum (MAIS) complex pulmonary infection who had a surgical procedure for management of their disease are reviewed. Relapse occurred in three cases and two patients died as a late result of their surgery. This gave a satisfactory treatment result in 89% of cases. The follow-up period was from nine months to 14 years after surgery. It is suggested that, despite the advent of modern antituberculosis drugs, resection of lung tissue is still the treatment of choic in suitable cases.     

Bronchiolitis obliterans organizing pneumonia (BOOP)--chronic organized pneumonia (COP). Diagnosis, therapy and course

Cryptogenic organizing pneumonia (COP) or bronchiolitis obliterans organizing pneumonia (BOOP) designates a disease characterized by particular histopathological features. Symptoms and clinical findings are more or less typical and the etiology of the disease is unknown in most of the cases. We report on 7 patients in whom the diagnosis was established by open lung biopsy during a workup for persistent pulmonary infiltrates. The clinical findings, the radiological features and the course during treatment with corticosteroids are analyzed. In all patients the symptoms improved. In two cases we observed relapses after discontinuing the corticosteroids or diminishing the dose. These relapses again responded to steroids, but in one patient progressive pulmonary restriction was noticed despite continuous treatment.     

Pediatric lung transplantation. Indications, techniques, and early results

From July 1990 to April 1993, 36 lung transplantations in 33 patients were performed in our pediatric transplant program (0.25 to 23 years, mean age 10.3 years). Eight children had been continuously supported with a ventilator for 3 days to 4.5 years before transplantation and three were supported by extracorporeal membrane oxygenation. Indications for lung transplantation in this pediatric population included the following: cystic fibrosis (n = 13), pulmonary hypertension, and associated congenital heart disease (n = 10), pulmonary atresia, ventricular septal defect and nonconfluent pulmonary arteries (n = 3), pulmonary fibrosis (n = 6), and acute respiratory distress syndrome (n = 1). Three children underwent retransplantation for acute graft failure (n = 2) or chronic rejection (n = 1). Pulmonary fibrosis was related to complications of treatment of acute of myelogenous leukemia with bone marrow transplantation in two children and to bronchiolitis obliterans, bronchopulmonary dysplasia, interstitial pneumonitis, and Langerhans cell histiocytosis in four others. Thirteen children underwent lung transplantation and concomitant cardiac repair. Bilateral lung transplantation, ventricular septal defect closure and pulmonary homograft reconstruction of the right ventricular outflow tract to the transplanted lungs was performed in three children by means of a new technique that avoids the need for combined heart-lung transplantation. Two patients had ventricular septal defect closure and single lung transplant for Eisenmenger's syndrome, two had ligation of a patent ductus arteriosus and transplantation, three additional children underwent atrial septal defect closure and lung transplantation, and two underwent lung transplantation for congenital pulmonary vein stenosis. Eight early deaths and three late deaths occurred (actuarial 1-year survival 62%). Lung transplantation in children has been associated with acceptable early results, although modification of the adult implantation technique has been necessary. Lung transplantation and repair of complex congenital heart defects is possible; heart-lung transplantation may only be required for patients with severe left heart dysfunction and associated pulmonary vascular disease. Bronchiolitis obliterans remains a major concern for long-term graft function in pediatric lung transplant recipients.     

Biologic and clinical effects of continuous infusion interleukin-2 in patients with non-small cell lung cancer

BACKGROUND: Interleukin-2 (IL-2) has shown antitumor activity in some neoplasms, such as melanoma and renal carcinoma, but toxicity derived from bolus administration is significant, particularly at the cardiorespiratory level. METHODS: To test feasibility, antitumor activity, pulmonary and systemic immunologic effects, and pulmonary function changes of continuous-infusion recombinant IL-2 given to patients with non-small cell lung cancer, eleven subjects with Stage III-IV disease were treated in a standard pulmonary medicine unit with a dose of 18 million IU/m2/day from day 1 to day 13 with 1-day rest on day 7. A second induction course was given after a 3-week rest. In patients with nonprogressive disease, four maintenance courses of 6 days' duration at the same dose were planned. Immunologic tests, including lymphocyte phenotype analysis and assays for the detection of tumor necrosis factor (TNF) and of anti-IL-2 antibodies, were performed before and after treatment in serum and bronchoalveolar lavage fluid (BAL). Cardiopulmonary function tests, including spirometry, arterial blood gas analysis, diffusion capacity, and echocardiography, were obtained before, during, and after treatment. RESULTS: Twenty-one cycles (15 induction courses plus 6 maintenance courses) were administered. No patient was able to complete the six planned courses, and only 3 patients entered the maintenance phase. Reasons for discontinuation included progressive disease in five cases, toxicity in three cases, and patient request in three cases. The most common side effects were fever, hypotension, oliguria, and elevated serum creatinine and liver enzyme levels. No patient required intubation or intensive care. No objective response was seen, and the median survival time was 10 months. Lymphocytosis and eosinophilia were observed in all patients. Surface marker analysis revealed a statistically significant increase in the percentage of CD3+, CD4+, CD25+ and DR+ cells in peripheral blood. Lymphoid cells derived from BAL disclosed an increased natural killer activity after IL-2 treatment, and TNF was increased in BAL fluid. Pulmonary function tests evidenced an increased alveolar-arterial difference for oxygen allied with a decrease of forced expiratory volume in 1 second, forced vital capacity, and carbon monoxide transfer coefficient consistent with a significant, albeit not clinically relevant, interstitial lung defect. CONCLUSION: Continuous-infusion IL-2 is feasible in patients with advanced lung cancer even outside an intensive care unit, but overall compliance is poor. Although clinical pulmonary toxicity is negligible, small but statistically significant alterations of the pulmonary function are evident. In addition, this regimen produces a significant activation of the immune system at the pulmonary level.     

Eosinophil recruitment to the lung in a murine model of allergic inflammation. The role of T cells, chemokines, and adhesion receptors

Eosinophil accumulation is a distinctive feature of lung allergic inflammation. Here, we have used a mouse model of OVA (ovalbumin)-induced pulmonary eosinophilia to study the cellular and molecular mechanisms for this selective recruitment of eosinophils to the airways. In this model there was an early accumulation of infiltrating monocytes/macrophages in the lung during the OVA treatment, whereas the increase in infiltrating T-lymphocytes paralleled the accumulation of eosinophils. The kinetics of accumulation of these three leukocyte subtypes correlated with the levels of mRNA expression of the chemokines monocyte chemotactic peptide-1/JE, eotaxin, and RANTES (regulated upon activation in normal T cells expressed and secreted), suggesting their involvement in the recruitment of these leukocytes. Furthermore, blockade of eotaxin with specific antibodies in vivo reduced the accumulation of eosinophils in the lung in response to OVA by half. Mature CD4+ T-lymphocytes were absolutely required for OVA-induced eosinophil accumulation since lung eosinophilia was prevented in CD4+-deficient mice. However, these cells were neither the main producers of the major eosinophilic chemokines eotaxin, RANTES, or MIP-1alpha, nor did they regulate the expression of these chemokines. Rather, the presence of CD4+ T cells was necessary for enhancement of VCAM-1 (vascular cell adhesion molecule-1) expression in the lung during allergic inflammation induced by the OVA treatment. In support of this, mice genetically deficient for VCAM-1 and intercellular adhesion molecule-1 failed to develop pulmonary eosinophilia. Selective eosinophilic recruitment during lung allergic inflammation results from a sequential accumulation of certain leukocyte types, particularly T cells, and relies on the presence of both eosinophilic chemoattractants and adhesion receptors.     

Three cases of Pasteurella multocida infection in the respiratory tract

Pasteurella multocida (P. multocida) is well recognized as "normal flora" in the upper respiratory tract of cats, dogs and other animals. Recently, various infections due to P. multocida in human have been noted as pulmonary infections in the patients with chronic pulmonary diseases as well as skin abscesses or septicemia after an animal bite or scratch. We report here three cases of respiratory tract infections caused by P. multocida. The first two patients had acute exacerbation of bronchiectasis caused by P. multocida and the other patients with pulmonary emphysema developed pneumonia. These three patients improved by antibiotic therapy. In Japan, P. multocida respiratory tract infection is rare, but it may become more common in the future. Therefore, it seems to be important to take this pathogen into consideration in the management of chronic lung disease.     

Herd immunity to filarial infection is a function of vector biting rate

Despite the existence of an impressive body of work on human immune responses against filarial infections, the occurrence of a protective response to infection remains unclear. Here, we use a combined modelling and comparative data analysis framework to address this issue for human infections with the filarial parasite, Wuchereria bancrofti. By analogy with previous work, the analysis involves the comparison of observed field patterns of infection with epidemiological patterns predicted by a mathematical model of parasite immunity. Unlike most other human helminths, which are transmitted by ingestion or dermal penetration, exposure to infection with lymphatic filariasis can be measured explicitly in terms of vector mosquito biting rates, thereby also allowing, probably for the first time, examination of the suggested role of exposure in generating herd immunity to macroparasites. Observed field patterns in this study were derived from 19 different published studies, which gave parallel estimates of community exposure rates and the corresponding age--prevalence patterns of infection, while predictions of the epidemiological impact of herd immunity were obtained using a catalytic model framework. The results provide the first conclusive evidence to date that variations in the observed age--prevalence patterns of infection in filariasis can be effectively explained by the occurrence of an exposure-driven acquisition of herd immunity. We discuss this result in terms of implications for the new World Health Organization-led initiative for the global control of this parasitic disease.     

Pulmonary infarcts can mimic pulmonary metastases from renal cancer

PURPOSE: Spontaneous regression of pulmonary metastases from renal cell carcinoma is a rare but well documented event. We present 2 recent cases that were radiographically consistent with pulmonary metastases from renal cell carcinoma but were pathologically shown to be pulmonary infarcts with no evidence of metastatic cells. Stable pulmonary infarcts can be misconstrued as metastatic disease in patients with renal cell carcinoma while resolving pulmonary infarcts may represent a subpopulation of patients with apparent spontaneous regression. Clinical implications of these findings are discussed. MATERIALS AND METHODS: Clinical and pathological data from 2 patients with large primary renal tumors, venous thrombi and lung masses were reviewed. Data from these cases, as well as pertinent urological and pathological literature, are presented. RESULTS: Although preoperative assessment was consistent with stage IV renal cell carcinoma, pathological examination of the lung masses in these patients showed no evidence of tumor cells. CONCLUSIONS: Pulmonary infarcts may mimic resolving or stable pulmonary metastasis in patients with renal cell carcinoma. Accurate clinical staging is crucial for the prognosis and treatment of renal cell carcinoma. Mistaking pulmonary infarcts for metastatic lesions can lead to inaccurate prognoses and inappropriate treatment.     

Activation of eosinophils in the airways of lung transplantation patients

Eosinophils are important inflammatory cells involved in liver and renal allograft rejection. The role of these cells is less well defined in lung allograft rejection. Eosinophils may be activated in lung rejection and release cytotoxic eosinophil cationic protein (ECP). Other states of disease in lung transplant recipients, such as cytomegalovirus (CMV) and bacterial infection, may also be associated with activated eosinophils. We postulated that ECP may be detectable and elevated in the airway lavage samples obtained from lung transplant patients and may contribute to disease pathogenesis. METHODS: Fifty BAL samples were collected from 38 lung transplant patients. Their most recent pulmonary function test results within 1 week of collection were noted. The samples were analyzed for the concentration of ECP, WBC count and differential cell count, and total protein level. The results were analyzed to identify the presence of disease or abnormal lung function associated with a positive ECP test. Student's t test was used and a p value of <0.05 was considered significant. RESULTS: We found that ECP levels were elevated in 36% (n=14) of the patients. Those patients with a positive test result were more likely to have acute rejection, CMV disease, or the presence of a cultured pathogen in BAL compared to patients with a negative test result (p<0.01). CONCLUSIONS: The presence of BAL ECP is associated with disease in lung transplant patients. Since ECP is directly cytotoxic, it may contribute to disease pathogenesis.     

Neurogenic disorders of heart and lung function in acute cerebral lesions

Incidence and clinical significance of cardiopulmonary complications of acute cerebral lesions are still unclear. Neurogenic pulmonary edema (NPE) is characterized as an acute, protein-rich lung edema occurring shortly after cerebral lesions associated with an acute rise of intracranial pressure. NPE is infrequently diagnosed, usually in association with head trauma. Pathophysiological mechanisms include a rise of the pulmonary vascular hydrostatic pressure either due to sympathetic innervation with pulmonary vasoconstriction or increased left-atrial pressure following systemic arterial hypertension or an increase in pulmonary capillary permeability. In contrast to NPE, cardiac complications are frequently observed, most consistently in patients with subarachnoid hemorrhage. Typical ECG changes are repolarization abnormalities, similar to those observed in coronary heart disease, and cardiac arrhythmias. The CK-MB may be slightly elevated; echocardiographic findings show a depressed left-ventricular function. Pathological examination reveals myofibrillar necrosis. Cardiac complications are explained with overactivity of the sympathetic innervation and high levels of circulating catecholamines. For adequate treatment, close cardiac monitoring is required in all patients with acute cerebral lesions.     

Recognition and management of pulmonary hypertension

Pulmonary hypertension (mean pulmonary arterial pressure > 20mm Hg at rest or > 30mm Hg during exercise) occurs (i) as primary pulmonary hypertension (no known underlying cause), (ii) as persistent pulmonary hypertension of the newborn or (iii) secondary to a variety of lung and cardiovascular diseases. In the last 10 to 15 years there have been significant advances in the medical management of this debilitating and life-threatening disorder. The main drugs in current use are anticoagulants (warfarin, heparin) and vasodilators, especially oral calcium antagonists, intravenous prostacyclin (prostaglandin I2; epoprostenol) and inhaled nitric oxide. Calcium antagonists, (e.g. nifedipine, diltiazem) are used chiefly in primary pulmonary hypertension. They are effective in patients who give a pulmonary vasodilator response to an acute challenge with a short acting vasodilator (e.g. prostacyclin, nitric oxide or adenosine), and are used in doses greater than are usual in the treatment of other cardiovascular disorders. Prostacyclin, given by continuous intravenous infusion, is effective in patients even if they do not respond to an acute vasodilator challenge. The long term benefit in these patients is thought to reflect the antiproliferative effects of the drug and/or its ability to inhibit platelet aggregation. It is used either as long term therapy or as a bridge to transplantation. Inhaled nitric oxide, which is used mainly in persistent pulmonary hypertension of the newborn, has the particular benefit of being pulmonary selective, due to its route of administration and rapid inactivation. Anticoagulants have a specific role in the treatment of pulmonary thromboembolic pulmonary hypertension and are also used routinely in patients with primary pulmonary hypertension. Nondrug treatments for pulmonary hypertension include (i) supplemental oxygen (> or = 15 h/day), which is the primary therapy in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease and (ii) heart-lung or lung transplantation, which nowadays is regarded as a last resort. Different types of pulmonary hypertension require different treatment strategies. Future advances in the treatment of pulmonary hypertension may come from the use of drug combinations, the development of new drugs, such as endothelin antagonists, nitric oxide donors and potassium channel openers, or the application of gene therapy.     

Acute, life-threatening complications of lung transplantation

Acute, life-threatening complications of lung transplantation are common in all reported series. The clinical courses and images of 70 patients who underwent heart-lung (n = 5), bilateral sequential lung (n = 31), or single-lung (n = 38) transplantation were retrospectively reviewed. Sixty-five acute, life-threatening complications occurred in 26 patients (37%) within 3 months after transplantation. Nine deaths occurred as a result of these complications for a mortality rate due to acute complications of 13%. The deaths were a result of bleeding (n = 4), sepsis (n = 2), severe acute rejection and adult respiratory distress syndrome (n = 1), multiorgan failure (n = 1), and diffuse alveolar damage and respiratory failure (n = 1), a distribution of causes similar to those in other reported series. Specific diagnoses that can be made with imaging include hemothorax, lung torsion, pneumomediastinum, pulmonary embolism, pneumothorax, bronchial anastomotic dehiscence, lung collapse, paralysis of the diaphragm, and sternal dehiscence.     

Sensitivity and specificity of a rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism

BACKGROUND: Patients with suspected pulmonary embolism often have nondiagnostic lung scans and may present in circumstances where lung scanning is unavailable. Levels of D-dimer, a fibrin-specific product, are increased in patients with acute thrombosis; this may simplify the diagnosis of pulmonary embolism. OBJECTIVE: To determine the sensitivity and specificity of a whole-blood D-dimer assay in patients with suspected pulmonary embolism and in subgroups of patients with low pretest probability of pulmonary embolism or nondiagnostic lung scans. DESIGN: Prospective cohort. SETTING: Four tertiary care hospitals. PATIENTS: 1177 consecutive patients with suspected pulmonary embolism. MEASUREMENTS: All patients underwent an assessment of pretest probability by use of a standardized clinical model, a D-dimer assay, ventilation-perfusion lung scanning, and bilateral compression ultrasonography. Patients in whom pulmonary embolism was not initially diagnosed were followed for 3 months. Accordingly, patients were categorized as positive or negative for pulmonary embolism. RESULTS: Of the 1177 patients, 197 (17%) were classified as positive for pulmonary embolism. Overall, the D-dimer assay showed a sensitivity of 84.8% and a specificity of 68.4%. In 703 patients (3.4%) with a low pretest probability of pulmonary embolism, the likelihood ratio associated with a negative D-dimer test result was 0.27, resulting in a posterior probability of 1.0% (95% CI, 0.3% to 2.2%). In 698 patients with nondiagnostic lung scans (previous probability, 7.4%), the likelihood ratio associated with a negative D-dimer test result was 0.36, resulting in a posterior probability of 2.8% (CI, 1.4% to 4.8%). CONCLUSIONS: A normal D-dimer test result is useful in excluding pulmonary embolism in patients with a low pretest probability of pulmonary embolism or a nondiagnostic lung scan.     

Salmonella lung involvement in patients with HIV infection

STUDY OBJECTIVE: To determine the frequency, clinical features, and outcome of lung involvement in HIV-infected patients having nontyphoid strains of Salmonella bacteremia. DESIGN: A retrospective clinical study. PATIENTS AND SETTING: We studied the records of all HIV-infected patients with Salmonella bacteremia diagnosed at a university tertiary hospital from January 1987 to December 1995. RESULTS: Lung involvement was found in 18 (35.3%) of 51 HIV-infected individuals with Salmonella bacteremia. Six of 18 (33.3%) were diagnosed as having definite Salmonella pulmonary infection by isolation of Salmonella from respiratory specimens, while probable Salmonella lung disease was considered in two patients who developed lung abscesses without the identification of any pathogen. Predisposing factors for focal disease, such as prior lung disease or Salmonella serotype, were equally prevalent regardless of the presence of Salmonella pulmonary involvement. Cavitary infiltrates or abscess formation were seen in five of the eight patients. With the exception of one patient coinfected with Nocardia asteroides who died 1 month later, all patients were cured with antibiotic treatment. Superinfection with other pulmonary pathogens (10 cases, 56%) was more frequent than Salmonella pneumonia; the most frequent alternative diagnosis was Pneumocystis carinii pneumonia (5 cases, 28%), pyogenic bacterial infection (17%), and tuberculosis (11%). CONCLUSIONS: In HIV-infected patients with Salmonella bacteremia, lung involvement is frequent, although there were no significant factors to explain this association. Cavitary disease was the most common radiologic pattern, and focal lung disease due to Salmonella does not seem to be associated with a worse prognosis. Coinfection and superinfection with other respiratory pathogens are more common than isolated Salmonella lung disease, and therefore, additional diagnostic procedures must be considered in the evaluation of these patients.     

Hypercapnic respiratory acidosis precipitated by hypercaloric carbohydrate infusion in resolving septic acute respiratory distress syndrome: a case report

Complications may occur when nutritional support is administered either parenterally or enterally. Inappropriate nutritional formulas with high carbohydrate loads can precipitate respiratory failure in patients with compromised lung function, induce respiratory distress which manifests as dyspnea and tachypnea in an originally normal lung condition, produce hypercapnic acidosis in mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) as well as patients recovering from acute respiratory distress syndrome (ARDS) without chronic lung disease, or result in difficult weaning. Hypercaloric mixed substrates administered either parenterally or enterally can also have profound impacts on gas exchange and energy expenditure. This report describes a patient who experienced exacerbation of respiratory distress and hypercapnic acidosis during recovery from septic ARDS as the result of a nutritionally-related increase in CO2 production. As carbohydrate calories were decreased, CO2 production diminished and the hypercapnia was resolved. The importance of indirect calorimetry cannot be overemphasized during tailoring of nutritional support for the critically ill patients.     

Fatal eosinophilic disease following autologous bone marrow transplantation

A 15-year-old girl developed massive, fatal eosinophilic disease following autologous bone marrow transplantation (BMT) for Hodgkin's disease (HD). Prior to autologous BMT, the erythrocyte sedimentation rate (ESR) was elevated, with active HD, but eosinophilia was absent. Post-autologous BMT, ESR and peripheral eosinophilia were observed to correlate with respiratory symptoms. Initial evaluation revealed no recurrent tumor, infection or other identifiable etiology. A diagnosis of chronic eosinophilic pneumonia was made following lung biopsy. A complete response was initially achieved with steroid therapy; however, when steroid therapy was tapered, the eosinophilia and elevated ESR recurred with worsening respiratory symptoms. Terminally, severe pulmonary disease developed and recurrent HD was found in lung, lymph nodes and bone marrow. During episodes of eosinophilia, the patient's serum stimulated her bone marrow as well as control marrow to produce predominantly eosinophilic colonies. Eosinophilic colony production was not observed with patient's sera obtained prior to or during autologous BMT or with control sera. This patient died of eosinophilic inflammatory disease following autologous BMT. The etiology of this disease was not definitely identified but appeared to be due to an eosinophilic-stimulating factor which developed after autologous BMT.