Kyle R. Brownback

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.

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.

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.

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.

Okadaic acid augments utrophin in myogenic cells

Duchenne muscular dystrophy is a fatal childhood disease caused by mutations that abolish the expression of dystrophin in muscle. Utrophin is a paralogue of dystrophin and can functionally replace it in skeletal muscle. A potential therapeutic approach is to increase utrophin levels in muscle. One way to achieve this aim is to increase the expression of the utrophin gene at a transcriptional level via promoter activation. In this study, we have shown that utrophin A mRNA levels can be induced by okadaic acid in murine myogenic C2C12 cells. We have found that a utrophin A promoter reporter can be induced by Sp1 in C2C12 myoblasts, but not in myotubes. This activation can be enhanced by okadaic acid treatment. Our data suggest that this induction is due to Sp1 phosphorylation during myogenesis and thus, utrophin expression in muscle could be regulated by treatment with phosphatase inhibitors. Control of utrophin promoter activation could then be used to increase the expression of utrophin, and thus ameliorate the symptoms of Duchenne muscular dystrophy.

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.

Severe diabetic ketoacidosis following ingestion of a caffeinated alcoholic beverage

A 53-year-old male with a past medical history of type I diabetes mellitus presented to our emergency department after being found obtunded at home following ingestion of a large amount of the caffeinated alcoholic beverage 4 Loko. The patient had profound hyperkalaemia, diabetic ketoacidosis and acute renal failure. He was admitted to the intensive care unit and was aggressively resuscitated with intravenous fluids. He was treated with insulin and sodium bicarbonate and had complete resolution of his acidosis and hyperkalaemia. Since their introduction, caffeinated alcoholic beverages have become increasingly popular, with expected sales of several billion dollars in 2011. The caffeine present in these beverages masks the depressant effect of alcohol and may thus lead to greater alcohol intake and make risk-taking behaviours more common. These beverages have not been studied in those with chronic medical conditions. As this case exemplifies, they may lead to excessive morbidity in those susceptible patients.

Safety of nintedanib for treatment of fibrotic lung disease after allogeneic hematopoietic stem cell transplantation

Graft-versus-host-disease (GVHD) of the lung is most commonly manifested as bronchiolitis obliterans syndrome (BOS) and may occur in up to half of patients with GHVD [1]. Typical treatments include systemic corticosteroids coupled with inhaled steroids, inhaled beta agonists, macrolides, and various other therapies [1–5]. Pro-fibrotic mediators, including platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), may play a role in the development of BOS [6, 7]. Nintedanib is a tyrosine kinase inhibitor that mediates multiple pro-fibrotic growth factors, including PDGF, VEGF, and fibroblast growth factor [8]. This drug can slow the rate of disease progression and reduce the risk of exacerbations in idiopathic pulmonary fibrosis (IPF) [9]. Potential side effects of nintedanib include diarrhea, nausea, increased liver enzymes, hemorrhage, and arterial thrombosis. Because of its mechanism of action, nintedanib may be a potential treatment option for patients with BOS due to pulmonary GVHD. Pirfenidone, an anti-fibrotic agent also approved for treatment of IPF [10], has had preliminary studies showing efficacy in a murine model of chronic GVHD [11]. Based on its favorable side effect profile, we sought to examine the efficacy of nintedanib when utilized in patients with fibrotic lung disease after allogeneic hematopoietic stem cell transplantation (HSCT) and determine whether this drug can be safely used in this patient population. We present two cases of patients treated with nintedanib following allogeneic HSCT.

Different location, same results?: Editorial

See DOI: 10.1111/resp.13049