Hassan F. Nadrous

Pulmonary Cryptococcosis in Nonimmunocompromised Patients

BACKGROUND Cryptococcus neoformans can cause serious systemic infections requiring systemic antifungal therapy in immunocompromised hosts. However, isolated pulmonary cryptococcosis in nonimmunocompromised hosts has been reported to resolve spontaneously without treatment. STUDY OBJECTIVE s: To determine the role of antifungal therapy in the management of isolated pulmonary cryptococcosis in nonimmunocompromised hosts. DESIGN Retrospective study. SETTING Tertiary care, referral medical center PATIENTS Thirty-six nonimmunocompromised subjects with isolated pulmonary cryptococcosis who received diagnoses at the Mayo Clinic (Rochester, MN) from 1976 to 2001. INTERVENTIONS None. MEASUREMENTS AND RESULTS Of 42 nonimmunocompromised subjects with cryptococcal infections, 36 (86%) had isolated pulmonary cryptococcosis. The mean (+/- SD) age of these 36 patients was 61 +/- 15 years (range, 14 to 88 years), and the groups included 17 men (47%) and 19 women (53%). Twenty-four patients (67%) were symptomatic, and 12 patients (33%) were asymptomatic. The most common presenting symptoms were cough, dyspnea, and fever. Cultures of sputum and bronchial washings most commonly yielded the diagnosis. Cerebrospinal fluid examination was performed in 11 patients (31%) and was negative in all of them. Follow-up information was available on 25 patients (69%) with a median duration of 19 months (range, 1 to 330 months). Twenty-three of these patients (92%) had resolution of their disease (no treatment, 8 patients; surgical resection only, 6 patients; and antifungal therapy, 9 patients). The condition of the two remaining patients had improved. There was no documented treatment failure, relapse, dissemination, or death in any of these 25 patients. CONCLUSIONS Our findings suggest that an initial period of observation without the administration of antifungal therapy is a reasonable option for nonimmunocompromised subjects with pulmonary cryptococcosis in the absence of systemic symptoms or evidence of dissemination, as well as after surgical resection for focal cryptococcal pneumonia.

Aerosol granulocyte-macrophage colony-stimulating factor for pulmonary alveolar proteinosis

Recently, granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies have been found in many patients with pulmonary alveolar proteinosis (PAP). The present study reports a retrospective case series of patients who used aerosolised GM-CSF in the treatment of idiopathic PAP. Between 1999 and 2003, 12 patients elected to receive aerosolised GM-CSF (250 µg b.i.d. every other week) in lieu of whole-lung lavage or observation. Patient characteristics, pulmonary function tests, arterial blood gas analysis, laboratory values and chest radiographs were extracted from the patients medical records. Of the six patients tested, all had GM-CSF neutralising antibodies. Additionally, abnormalities in GM-CSF gene expression (one patient), receptor expression (two patients) and ability to upregulate adhesion molecules (one patient) were found. All patients except one had a positive response (mean improvements in arterial oxygen tension, alveolar–arterial oxygen gradient, carbon monoxide diffusing capacity of the lung and forced vital capacity were 17.1 mmHg, 18.4 mmHg, 16.6% pred and 13.5% pred, respectively). Two patients made a complete recovery and were disease free 1 and 2 yrs after discontinuing treatment. Four patients showed complete response to both the initial course or when treated again for recurrence after discontinuation of treatment. One patient required dose escalation (500 µg b.i.d.) with complete response. GM-CSF was well tolerated without late toxicity after median (range) follow-up of 30.5 (3–68) months. In conclusion, aerosolised granulocyte-macrophage colony-stimulating factor is safe and effective in treating pulmonary alveolar proteinosis providing an alternative to whole-lung lavage or subcutaneous granulocyte-macrophage colony-stimulating factor.

Impact of Angiotensin-Converting Enzyme Inhibitors and Statins on Survival in Idiopathic Pulmonary Fibrosis*

STUDY OBJECTIVES To assess the clinical relevance of angiotensin-converting enzyme inhibitors (ACEI) and 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) in the context of idiopathic pulmonary fibrosis (IPF). BACKGROUND IPF is a progressive interstitial lung disease for which there is no effective treatment. ACEI and statins have been shown to possess antifibrotic properties in experimental models in vitro and in vivo. DESIGN, SETTING, AND PATIENTS Retrospective review of the effects of ACEI and statins on survival of 478 patients with IPF seen at Mayo Clinic Rochester from 1994 through 1996. Fifty-two patients (11%) were receiving ACEI, 35 patients (7%) were receiving statins, and 5 patients (1%) patients were receiving both at their initial visit. RESULTS For subjects receiving ACEI, the median survival from the index visit was 2.2 years, compared to 2.9 years for subjects not receiving ACEI (p = 0.088). The median survival was 2.9 years if patients were receiving statins or not (p = 0.573). There was also no significant difference in survival between patients with IPF receiving either ACEI or statins vs those receiving neither at the index visit (2.5 years vs 3 years, respectively; p = 0.066). After adjusting for age, gender, recommended IPF treatment, smoking status, prior oxygen use, FVC, diffusion capacity for carbon monoxide, coronary artery disease, congestive heart failure, diabetes mellitus, and hypertension, there were no differences in survival between those subjects receiving either ACEI, statins, or both vs neither. CONCLUSIONS These data do not suggest a beneficial effect of ACEI and/or statins on survival in patients with IPF.

Chronic Nitrofurantoin-Induced Lung Disease

OBJECTIVE To reassess the clinical and radiological features of chronic nitrofurantoin-induced lung disease and eventual clinical outcome. PATIENTS AND METHODS We retrospectively reviewed the medical records of 18 patients with chronic nitrofurantoin-induced lung disease who were seen at the Mayo Clinic in Rochester, Minn, from January 1, 1997, to December 31, 2002. RESULTS The median age of the 18 patients was 72 years (range, 47-90 years) at the time of diagnosis; 17 (94%) were women. Onset of symptoms occurred after a median interval of 23 months (range, 10-144 months) following the initiation of nitrofurantoin therapy for the prevention of recurrent urinary tract infections. All patients presented with persistent dyspnea and cough associated with lung infiltrates detected on chest radiography. Ten computed tomograms were available for review and revealed bilateral areas of ground-glass opacities in all cases and showed subpleural Irregular linear opacities and patchy consolidation in some cases. Nitrofurantoin therapy was discontinued in all patients, and most improved subsequently; 9 patients received corticosteroid therapy. CONCLUSIONS Chronic nitrofurantoin-induced lung disease is seen predominantly in older women who present with respiratory symptoms after a year or more of nitrofurantoin therapy. Associated radiological features are relatively nonspecific but usually include bilateral areas of ground-glass opacities on computed tomography of the chest. Cessation of nitrofurantoin therapy leads to improvement and suffices in the management of some patients, although corticosteroid therapy may be helpful in those more severely affected.

Idiopathic Pulmonary Fibrosis in Patients Younger Than 50 Years

OBJECTIVE To assess clinical, radiological, histopathologic, and prognostic differences in younger patients with idiopathic pulmonary fibrosis (IPF). PATIENTS AND METHODS This study consisted of patients younger than 50 years with IPF who were seen at the Mayo Clinic in Rochester, Minn, from January 1, 1994, to December 31, 2000. Clinical, radiological, and histopathologic data were abstracted from clinical records. Total lung capacity using plethysmography, vital capacity, diffusing capacity for carbon monoxide using the single-breath method, and alveolar volume using single-breath neon wash-in were measured. RESULTS Our study population was composed of 16 men and 6 women with a median age of 45 years (range, 28-49 years). Median survival was 2.1 years, with 1- and 2-year survival rates of 68% and 53%, respectively. Of the 22 patients, 2 were current smokers, 14 were former smokers, and 6 had never smoked. Three patients had familial pulmonary fibrosis, 21 had bibasilar inspiratory crackles, and 10 had digital clubbing. Median total lung capacity was 56.2%, vital capacity was 51.0%, diffusing capacity was 45.5%, and alveolar volume was 65.0%. CONCLUSION Although previous studies have suggested that younger age is a favorable prognostic factor in patients with IPF, we found that younger patients have the same poor prognosis as do older patients with this disorder. We observed no distinguishing differences in the clinical, radiological, and histopathologic features compared with those in older patients in whom the disorder is more common. Lung transplantation should be considered early in the treatment of younger patients with IPF.

The role of autopsy in the intensive care unit.

OBJECTIVE To identify the frequency and spectrum of clinically relevant diagnoses found at autopsy but not determined before death in adult patients admitted to an intensive care unit (ICU). PATIENTS AND METHODS We retrospectively reviewed medical records and autopsy reports of patients admitted to ICUs from January 1, 1998, to December 31, 2000. Disagreements between autopsy and antemortem diagnoses were classified as type I or type II errors. A new major diagnosis with potential for directly impacting therapy was considered a type I error. Type II errors included important findings that would not have likely changed therapy. RESULTS Of 1597 deaths in all ICUs during the study period, autopsies were performed in 527 patients (33%). Autopsy reports were available in 455 patients, of whom 19 (4%) had type I errors and 78 (17%) had type II errors. The most common type I error was cardiac tamponade. There were no significant differences in age, sex, or length of stay in the ICU or hospital among patients with and without diagnostic errors or among patients with type I and II errors. Seventy-eight patients had 81 type II errors. Organ transplant recipients had more type I or II errors than did nontransplant patients (35% vs 20%; P = .04). CONCLUSIONS Diagnoses with impact on therapy and outcome are missed in approximately 4% of deaths of adult patients admitted to the ICU. Transplant recipients are especially likely to have occult conditions for which additional therapy might be indicated.

Glomus tumor of the trachea: Value of multidetector computed tomographic virtual bronchoscopy

Glomus tumor of the trachea is extremely rare. We report a case of tracheal glomus tumor in a 39-year-old man who presented with hemoptysis. The diagnosis was made after bronchoscopic biopsy of a tumor involving the posterior wall of the upper trachea. Thin-section multidetector computed tomography of the chest was performed before surgical resection, with multiplanar re-formations and 3-dimensional virtual bronchoscopic reconstruction. Tracheal sleeve resection with reconstruction was successful, and pathological studies confirmed complete resection and the diagnosis of glomus tumor. The patient was disease-free 3 months postoperatively. To our knowledge, this is the first reported case in which additional computed postprocessing was used to help evaluate the extent of such a tumor.

Agnogenic myeloid metaplasia with pleural extramedullary leukemic transformation

Agnogenic myeloid metaplasia (AMM) is one of the myeloproliferative disorders, and is usually accompanied by extramedullary hematopoiesis (EMH) in various organs, mainly in the liver, spleen and lymph nodes. Extramedullary hematopoiesis and/or leukemic transformation of EMH in the pleura is a rare occurrence and is usually asymptomatic. Pleural involvement is usually diagnosed on postmortem examination. Herein we describe a 71-year-old man with newly diagnosed agnogenic myeloid metaplasia who was evaluated for progressively worsening dyspnea, pulmonary hypertension and bilateral pleural effusions. EMH involving the lungs and pleura was suspected. A sulfur colloid technetium 99m bone marrow scan performed to detect extramedullary hematopoiesis was negative. The diagnostic thoracentesis yielded bloody fluid that contained a large population of myeloblasts, indicating pleural leukemic transformation. The patient received 100 cGy to the whole lung for treatment of pulmonary hypertension due to EMH. This was followed by 1500 cGy total dose of radiation to the left lung for pleural extramedullary leukemic transformation. Pleural effusions resolved and repeat echocardiography showed reduction of the pulmonary artery pressure. Three months later he had leukemic transformation involving the skin and lymph nodes. Four months after radiation therapy, he had full-blown acute myeloid leukemia. He received 2 cycles of Gemtuzumab ozogamicin (MylotargR), allopurinol and hydroxyurea. Three months after initiation of chemotherapy, he deteriorated and received salvage chemotherapy of prednisone, VP-16 and imatinib mesylate (GleevecR). He was hospitalized for neutropenic fever and was diagnosed to have pulmonary aspergillosis. He died of multisystem failure 8½ months after being diagnosed with AMM.

Tracheal Myxoma: A Rare Benign Tracheal Tumor

Benign tracheal tumors are rare. We describe a 39-year-old man who underwent resection of a tracheal myxoma, a previously unrecognized benign tracheal neoplasm. He presented with a 9-month history of wheezing, cough, and dyspnea on exertion. Treatment with bronchodilators and corticosteroids administered by inhalation and systemically did not diminish his symptoms. Pulmonary function tests showed a pattern of airflow limitation consistent with variable extrathoracic obstruction. Chest radiography and computed tomography revealed a tracheal mass. Tracheal resection of the tumor with reconstruction was curative. The patient is free of disease 7 years after surgery.

Rare tracheal chondroid hamartoma masquerading as asthma in a 14-year-old girl

BACKGROUND Tracheal hamartomas are rare in all age groups and have not been previously described in adolescence. OBJECTIVE To report the first case of a tracheal chondroid hamartoma presenting as exercise intolerance and wheezing and previously misdiagnosed and treated as asthma. METHODS Symptoms, pulmonary function tests, chest x-ray examination, chest computed tomography, and histologic examination of the specimen were performed. RESULTS The pulmonary function tests obtained throughout several years revealed progressive decreases (approximately 30% of predicted) in peak expiratory flow and forced expiratory volume in 1 second (approximately 50% of predicted). The inspiratory and expiratory flow-volume curve suggested a fixed central airway obstruction. Both the chest x-ray examination and computed tomography revealed an intraluminal tracheal tumor that was surgically excised. Histologic examination revealed a chondroid hamartoma. CONCLUSIONS Rare benign primary tracheal tumors, including chondroid hamartoma, can present in adolescence with asthma-like symptoms for years and should be considered in the differential diagnosis, especially in the setting of appropriately abnormal spirometry or when asthma is very difficult to control.