Evaluation of the Diagnostic Accuracy and Clinical Utility of Fungal Profile Plus Polymerase Chain Reaction Assay in Pulmonary Infections.

Background: Pulmonary infections due to Aspergillus, Mucorales, and Nocardia have high morbidity and mortality, in part due to diagnostic challenges. Commercially available molecular assays on bronchoalveolar lavage fluid (BALF) may have increased sensitivity over currently available diagnostic options. Our aim was to characterize the diagnostic performance of assays for each of these pathogens in our patient population. Methods: The medical records of patients whose BALF was tested by polymerase chain reaction (PCR) for Aspergillus, Mucorales, and Nocardia between 2019 and 2021 were reviewed in a cross-sectional manner. European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) definitions of "proven," "probable," and "possible" infection were used, including histopathology, serology, and culture. We used (1) "proven" or "probable" infection by EORTC criteria, (2) improvement or stabilization on targeted antimicrobial therapy, and (3) absence of a more likely diagnosis as the reference standard. Results: The Aspergillus PCR assay demonstrated the highest agreement with the diagnostic reference standard, with 31.25% (10/32) sensitivity and 97.17% (206/212) specificity. Positive and negative predictive values were 62.50% (10/16) and 90.35% (206/228), respectively. No Mucorales or Nocardia infections were identified by the diagnostic reference standard, so the sensitivity could not be calculated. The specificity of Mucorales and Nocardia targets was 98.35% and 96.69%, respectively. Conclusions: Our data demonstrated relatively poor clinical sensitivity for all 3 constituent PCR assays in our patient population, suggesting a limited role for this test in the diagnosis of Aspergillus, Mucorales, or Nocardia.

Bronchoscopic features, associations, and outcomes of organizing pneumonia following allogeneic hematopoietic stem cell transplantation.

Organizing pneumonia (OP) is a poorly understood complication of hematopoietic stem cell transplant (HSCT). We identified 15 patients diagnosed with OP following HSCT and described their clinical course. CT chest findings were remarkable for multifocal infiltrates that were predominantly consolidating or ground glass opacities. Bronchoalveolar lavage (BAL) was performed on 14 patients with five having lymphocytosis (> 25% lymphocytes), three with eosinophilia (> 5% eosinophils), three with neutrophilia (> 30% neutrophils), and three with normal cell counts. Flow cytometry was analyzed on BAL fluid in 13 patients with 11 having a CD4/CD8 of < 0.9. Initial treatment with 0.3-1.0 mg/kg prednisone resulted in improvement in symptoms, in radiographic findings, and in pulmonary function testing for the majority of patients. Six patients had recurrence of OP after completing treatment. Eleven patients had evidence of extra-pulmonary graft-versus-host disease prior to diagnosis of OP, and seven patients were diagnosed with an upper respiratory tract infection (URI) within 8 weeks of OP diagnosis. Most patients respond well to prednisone with significant improvement in pulmonary function, but risk of recurrence is high after cessation of steroid treatment. Risk factors for the development of OP may include prior URI.

Effect of Rituximab on Pulmonary Function in Bronchiolitis Obliterans Syndrome due to Graft-Versus-Host-Disease.

PURPOSE: Rituximab is an anti-CD20 monoclonal antibody that is used to suppress B-cell function in graft-versus-host-disease (GVHD). We sought to determine the effects of rituximab treatment on lung function in those patients with bronchiolitis obliterans syndrome (BOS) as a manifestation of GVHD. METHODS: Thirteen patients were treated with rituximab with a diagnosis of BOS and a significant reduction in the forced expiratory volume in 1 s (FEV1) after hematopoietic stem cell transplantation (HSCT). The changes in their pulmonary function for 12 months following treatment with rituximab were followed, along with other intervention performed and daily average dosing of prednisone. RESULTS: Following rituximab administration, there was an improvement in the slope of decline in lung function from -5.12 ml/month prior to rituximab infusion to -0.31 ml/month after 3 months and to +2.27 ml/month 12 months later. Seven of the 13 patients had an increase in their FEV1 after treatment with rituximab. Additionally, the mean daily dose of prednisone decreased from 27 mg prior to rituximab treatment to 11 mg 12 months after treatment. Nine out of 13 patients survived 12 months after rituximab treatment. All of the patients with improvement in FEV1 following rituximab treatment were receiving concomitant extracorporeal photopheresis. CONCLUSION: Rituximab is safe with the potential to stabilize or improve lung function in patients with BOS after HSCT and should be considered as a treatment option in those patients.

A 19-Year-Old College Student With Headache, Photophobia, and Flulike Illness.

CASE PRESENTATION: A 19-year-old previously healthy man presented, minimally responsive, in respiratory distress to an ED after a 2-week history of headache, photophobia, and neck stiffness. Associated symptoms included low-grade fevers, malaise, and dark urine. He had no recent travel, ill contacts, consumption of undercooked meat, new sexual contacts, or illicit drug use. The patient resided in a campus dormitory and did not consume alcohol or tobacco.

Effect of extracorporeal photopheresis on lung function decline for severe bronchiolitis obliterans syndrome following allogeneic stem cell transplantation.

Extracorporeal photopheresis (ECP) is a commonly used treatment for severe graft-versus-host-disease (GVHD). We sought to evaluate the effects of ECP over a prolonged period on forced expiratory volume in 1 s (FEV1) in patients with pulmonary GVHD. We identified eight patients who developed new airflow obstruction following allogeneic stem cell transplantation and a substantial decline in FEV1 despite receiving corticosteroids and standard therapy for pulmonary GVHD. Those eight patients were treated with ECP for a period of 1 year, with a primary endpoint of FEV1 change during this treatment period. Over the first 3 months of ECP, there was no further decline in FEV1 in seven of the eight patients. However, over the 1 year period, only two of the eight patients had stability in FEV1. The rate of FEV1 decline was substantially less once ECP was initiated, though the median FEV1 continued to decline over 1 year of therapy. All patients survived through the first year of ECP therapy. There was a significant decrease in the median dose of prednisone per patient throughout the 12 months of ECP treatment. ECP shows promise in slowing rate of decline of FEV1 in pulmonary GVHD, though the effects may not be long lived. J. Clin. Apheresis 31:347-352, 2016. © 2015 Wiley Periodicals, Inc.

Role of bronchoalveolar lavage in the diagnosis of pulmonary infiltrates in immunocompromised patients.

PURPOSE OF REVIEW: To describe the role of bronchoalveolar lavage (BAL) in the evaluation of pulmonary disease in immunocompromised patients. RECENT FINDINGS: Recent discoveries in this field are largely in two areas: the array of diagnostic testing performed on BAL fluid and technical details that can enhance the yield from this procedure. Regarding diagnostic testing, the addition of new assays, including Aspergillus galactomannan antigen assay, respiratory viral panels, and Pneumocystis jirovecii PCR, has improved the diagnostic yield of BAL over conventional cultures and stains. To improve the diagnostic yield of the procedure itself, it should be done early in the clinical course, with the BAL in the anatomic area most affected, and with a preprocedural computed tomography of the chest to properly plan the procedure. SUMMARY: Bronchoscopic evaluation with BAL can provide important diagnostic information in immunocompromised patients with pulmonary diseases and should be routinely performed when clinically indicated and able to be completed safely.

Pulmonary manifestations of the pre-engraftment syndrome after umbilical cord blood transplantation.

Pre-engraftment syndrome (PES) is a condition occurring after umbilical cord blood transplantation (UCBT) characterized by fever and erythematous skin rash prior to neutrophil engraftment. We sought to determine the incidence and characterize the pulmonary manifestations of PES. A retrospective review of patients who underwent UCBT at the University of Kansas Medical Center over a 5-year period was performed. Data collected included patient baseline characteristics, presence of PES, pulmonary findings, treatments, and survival. Forty-four patients underwent UCBT with 22 of those patients developing PES. Full-intensity myeloablative conditioning regimen was found to be a risk factor for development of PES. Of those 22 patients, 13 had resting hypoxemia. The most common radiographic findings included diffuse ground glass opacities with pleural effusions. Fifteen patients with PES received corticosteroids, of which 12 had improvement in fevers and rash. These patients had a trend toward worse mortality than those not receiving corticosteroids. There was a nonsignificant trend toward worse survival in patients with PES and hypoxemia compared to those without hypoxemia. PES is a common complication following cord blood transplantation, with hypoxemia being present in over half of patients with PES. Hypoxemia with PES and treatment with corticosteroids may portend a worse prognosis.

Association of bronchoalveolar lavage yield with chest computed tomography findings and symptoms in immunocompromised patients.

INTRODUCTION: Fiber-optic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) is a common procedure performed in immunocompromised patients with undiagnosed pulmonary pathology. Identifying patients with the highest potential diagnostic yield may help to avoid morbidity in patients unlikely to benefit from the procedure. We sought to determine which patient factors, specifically chest computed tomography (CT) findings, affected diagnostic yield of BAL. METHODS: Retrospective chart review of immunocompromised patients who underwent FOB with BAL from 01/01/2010 to 12/31/2011 at an academic medical center was performed. The lung lobe lavaged, characteristics of pulmonary infiltrate on radiograph, patient symptoms, and diagnostic yield were collected. A positive diagnostic yield was defined as a positive microbiological culture, finding on cytopathologic staining, diffuse alveolar hemorrhage, alveolar eosinophilia or a positive immunologic or nucleic acid assay. RESULTS: The overall diagnostic yield was 52.6%. Infiltrates that were predominantly reticular or nodular by CT had a lower diagnostic yield than predominantly consolidated, ground-glass, or tree-in-bud infiltrates (36.5% vs. 61.2%, P = 0.0058). The diagnostic yield was significantly improved in patients with both fever and chest symptoms compared to patients without symptoms (61.3% vs. 29.6%, P = 0.0066). CONCLUSION: CT findings of reticular and nodular infiltrates portend a worse diagnostic yield from BAL than those that are alveolar in nature. Symptomatic patients are more likely to have diagnostic FOB with BAL than asymptomatic patients.

Utility of galactomannan antigen detection in bronchoalveolar lavage fluid in immunocompromised patients.

Diagnosis of invasive pulmonary aspergillosis (IPA) is a challenging process in immunocompromised patients. Galactomannan (GM) antigen detection in bronchoalveolar lavage (BAL) fluid is a method to detect IPA with improved sensitivity over conventional studies. We sought to determine the diagnostic yield of BAL GM assay in a diverse population of immunocompromised patients. A retrospective review of 150 fiberoptic bronchoscopy (FOB) with BAL for newly diagnosed pulmonary infiltrate in immunocompromised patients was performed. Patient information, procedural details and laboratory studies were collected. BAL and serum samples were evaluated for GM using enzyme-linked immunoassay. Of 150 separate FOB with BAL, BAL GM was obtained in 143 samples. There were 31 positive BAL GM assays. In those 31 positive tests, 13 were confirmed as IPA, giving a positive predictive value of 41.9%. There was one false negative BAL GM. Of the 18 false positive BAL GM, 4 were receiving piperacillin-tazobactam and 11 were receiving an alternative beta-lactam antibiotic. BAL GM assay shows excellent sensitivity for diagnosing IPA. There was a significant number of false positive BAL GM assays and several of those patients were receiving beta-lactam antibiotics at the time of bronchoscopy.

Electromagnetic navigational bronchoscopy in the diagnosis of lung lesions.

BACKGROUND: The diagnosis of pulmonary lesions that are not bronchoscopically visible is a challenging process. Electromagnetic navigation bronchoscopy (ENB) is a new technology designed to diagnose peripheral pulmonary lesions. We sought to determine whether diagnostic yield from ENB was affected by bronchus sign, lesion location, or size. METHODS: Data were obtained retrospectively from all patients undergoing ENB at our institution since 2008. ENB was performed by 3 separate proceduralists at our institution from November 2008 until July 2011 using the superDimension/InReach system. Patient selection and modalities of specimen collection were at the discretion of the proceduralist. All procedures were performed using general anesthesia and fluoroscopy. Lesion size, location, diagnosis from ENB, and eventual diagnosis were recorded. RESULTS: Fifty-five individuals underwent ENB between 2008 and 2011. The average lesion size was 3.0 cm and the majority of lesions were located in the upper lobes (34/55 lesions). Of the 55 patients, in 41, a diagnosis was established from ENB, a diagnostic yield of 74.5%. Thirty-six patients were eventually diagnosed with a malignancy, of whom 25 were diagnosed by ENB, yielding a sensitivity for malignancy of 69.4%. The negative predictive value for malignancy with an ENB procedure was 54.2%. There were 2 cases of postprocedure respiratory failure, but there were no cases of pneumothorax. Bronchus sign, lesion size, and location did not affect the diagnostic yield. CONCLUSIONS: ENB shows an acceptable diagnostic yield with an excellent safety profile in the diagnosis of pulmonary lesions. The use of fluoroscopy and general anesthesia may improve the diagnostic yield.

Small-cell prostate carcinoma: A retrospective analysis of five newly reported cases.

Five cases of small-cell carcinoma (SCC) of prostate were identified, at the Rhode Island Hospital and the Miriam Hospital from 1984 to 2006, with an average age of 71 years at the time of diagnosis. Three of these patients had a prior diagnosis of prostatic adenocarcinoma, with all of the five patients receiving anti-androgen treatment. The average time between the diagnosis of adenocarcinoma and of SCC in these patients was 6.7 years. The PSA levels varied greatly, with two patients possessing markedly elevated levels and the remaining patients with normal levels. Approximately 3/5 patients developed liver metastases, 2/5 patients had bone metastases, and 1/5 patients developed carcinomatous meningitis. Of the four patients who expired, the median survival time after diagnosis of SCC was 3.6 months (0.5-12 months).