Elizabeth Guy

Genome-wide association study of smoking behaviours in patients with COPD

Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a dopamine beta-hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in patients with COPD. Methods GWAS were conducted in four independent cohorts encompassing 3441 ever-smoking patients with COPD (Global Initiative for Obstructive Lung Disease stage II or higher). Untyped SNPs were imputed using the HapMap (phase II) panel. Results from all cohorts were meta-analysed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2×10−7. No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p<10−6. Nominally significant associations with candidate SNPs within cholinergic receptors, nicotinic, alpha 3/5 (CHRNA3/CHRNA5; eg, p=0.00011 for SNP rs1051730) and cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6; eg, p=2.78×10−5 for a non-synonymous SNP rs1801272) regions were observed for lifetime average CPD, however only CYP2A6 showed evidence of significant association with current CPD. A candidate SNP (rs3025343) in DBH was significantly (p=0.015) associated with smoking cessation. Conclusion The authors identified two candidate regions associated with age at smoking initiation in patients with COPD. Associations of CHRNA3/CHRNA5 and CYP2A6 loci with CPD and DBH with smoking cessation are also likely of importance in the smoking behaviours of patients with COPD.

Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients with Suspected Tuberculosis from Low and Higher Prevalence Settings

BACKGROUND The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well asrpoBmutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. METHODS Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. RESULTS Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB(+)] sputum, 59.3% with AFB smear-negative [AFB(-)] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB(+), 71.4% if AFB(-)), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB(+)/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. CONCLUSIONS In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation.

Pulmonary-renal syndromes in the intensive care unit

Renal disease associated with pulmonary hemorrhage is seen in a variety of clinical disorders and is a common cause of admission to intensive care units. Recent advances in the understanding of the pathogenesis of these disorders have improved the therapeutic options significantly and have favorably influenced the course of many of these disorders. This article discusses rheumatologic diseases that involve both the kidney and lungs, with emphasis on pathogenesis and therapeutic options. Common pulmonary-renal syndromes including anti-glomerular basement membrane disease and anti-neutrophil cytoplasmic autoantibodies-associated vasculitis.

Pulmonary Tuberculosis: Role of Radiology in Diagnosis and Management.

Tuberculosis is a public health problem worldwide, including in the United States-particularly among immunocompromised patients and other high-risk groups. Tuberculosis manifests in active and latent forms. Active disease can occur as primary tuberculosis, developing shortly after infection, or postprimary tuberculosis, developing after a long period of latent infection. Primary tuberculosis occurs most commonly in children and immunocompromised patients, who present with lymphadenopathy, pulmonary consolidation, and pleural effusion. Postprimary tuberculosis may manifest with cavities, consolidations, and centrilobular nodules. Miliary tuberculosis refers to hematogenously disseminated disease that is more commonly seen in immunocompromised patients, who present with miliary lung nodules and multiorgan involvement. The principal means of testing for active tuberculosis is sputum analysis, including smear, culture, and nucleic acid amplification testing. Imaging findings, particularly the presence of cavitation, can affect treatment decisions, such as the duration of therapy. Latent tuberculosis is an asymptomatic infection that can lead to postprimary tuberculosis in the future. Patients who are suspected of having latent tuberculosis may undergo targeted testing with a tuberculin skin test or interferon-γ release assay. Chest radiographs are used to stratify for risk and to assess for asymptomatic active disease. Sequelae of previous tuberculosis that is now inactive manifest characteristically as fibronodular opacities in the apical and upper lung zones. Stability of radiographic findings for 6 months distinguishes inactive from active disease. Nontuberculous mycobacterial disease can sometimes mimic the findings of active tuberculosis, and laboratory confirmation is required to make the distinction. Familiarity with the imaging, clinical, and laboratory features of tuberculosis is important for diagnosis and management. ©RSNA, 2017.

Use of string test and stool specimens to diagnose pulmonary tuberculosis

SUMMARY Background The Xpert MTB/RIF (MTB/RIF) test has advanced the field of tuberculosis (TB) diagnostics; however, depending on age and HIV status, 10–85% of individuals with presumed pulmonary TB (PTB) are unable to produce sputum. Methods The feasibility of using MTB/RIF and culture on stool and string test specimens from 13 adult patients with presumed PTB was studied. Results The string test was well tolerated with a median Wong Baker Faces score of 2. The string test had 100% sensitivity and specificity by MTB/RIF and 87.5% sensitivity and 100% specificity by culture. In stool, Mycobacterium tuberculosis DNA was detected in all cases of culture-confirmed PTB. Conclusion The string test and stool provide diagnostic specimens that warrant further investigation.

Fatal Progressive Membranous Obliterative Bronchitis: A Sequela of Influenza?

Occlusion of the bronchial orifices by tissue-like structures is an uncommonly reported finding: it has been referred to as bronchial webs, bronchial synechiae, vanishing bronchus syndrome, or membranous obliterative bronchitis. It differs from bronchiolitis obliterans, a well-described clinical entity that involves smaller airways not visualized on bronchoscopy. Although initially only recognized as a congenital condition, later reports have described it in situations where chronic inflammation results in the irritation of the airways. Here we report a case of a woman with postinfectious bronchiectasis who developed membranous occlusion of multiple subsegmental bronchi, resulting in progressive airflow obstruction and postobstructive collapse of involved lung parenchyma. This process eventually caused her demise. It the first report of membranous occlusion of the bronchi in an adult who does not have cystic fibrosis or a history of lung transplantation. Clinicians should be aware of this entity, and further research could help illuminate its pathogenesis and management.

Use of Indwelling Pleural Catheter for Recurrent Pleural Effusion Due to Postpericardiotomy Syndrome: A Case Report.

Pleural effusion secondary to postpericardiotomy syndrome (PPS) is a relatively common complication after cardiac surgery. These effusions and syndrome complex usually respond well to anti-inflammatory agents. The use of indwelling pleural catheter (IPC) for nonmalignant recurrent pleural effusions is growing. We report the use of IPC for a case of recurrent pleural effusion due to PPS in a gentleman that could not tolerate anti-inflammatory medications. To our knowledge, there has been no other report of the use of IPC due to recurrent pleural effusion from PPS.

Predictors and patterns of weight gain during treatment for tuberculosis in the United States of America

OBJECTIVES Patients with tuberculosis (TB) often present with weight loss. Lack of weight gain with TB treatment has been associated with treatment failure. The purpose of this study was to examine patterns of weight gain in patients with TB and determine the disease characteristics that predict weight gain. METHODS This was a retrospective cohort study of adults with TB treated in a county health system in the USA. Demographic, clinical, radiographic, and microbiological data were recorded in addition to monthly weights during treatment. RESULTS Overall, patients had a significant change in weight over the course of treatment (p<0.0001). After 2 months of treatment, 31.9% of patients had gained at least 5% body weight; by the end of treatment, 62.4% of patients had gained at least 5% weight. Patients who gained weight did so in a linear fashion throughout treatment. Cavitary and extensive disease, a positive smear, and a positive culture were predictors of weight gain (p<0.05). No patients had relapses during the time period of the study. CONCLUSIONS Only a subset of patients treated for TB gain significant weight. A greater burden of disease was predictive of weight gain.

Bronchobiliary Fistula Localized by Cholescintigraphy with Single-Photon Emission Computed Tomography

Biliptysis is an important clinical feature to recognize as it is associated with bronchobiliary fistula, a rare entity. Bronchobiliary fistulas have been diagnosed with planar cholescintigraphy. However, cholescintigraphy with single-photon emission computed tomography (SPECT) can better spatially localize a bronchobiliary fistula as compared to planar cholescintigraphy alone, and is useful for preoperative planning if surgical treatment is required. Here, we present the case of a 23-year-old male who developed a bronchobiliary fistula in the setting of posttraumatic and postsurgical infection, which was diagnosed and localized by cholescintigraphy with SPECT.

Tuberculosis reactivation in hepatocellular carcinoma: association with transarterial chemoembolization

Abstract Transarterial chemoembolization (TACE) is an important therapeutic option for patients with hepatocellular carcinoma (HCC). We discuss five patients with HCC and tuberculosis (TB) reactivation following TACE. Screening patients for latent TB infection at diagnosis of cirrhosis or HCC should be considered because of the immunosuppression inherent in both the diseases and their treatments.