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Cryptococcus neoformans is a yeast than can result in isolated or disseminated infections. This case report describes an immunocompetent patient presenting with airway obstruction secondary to laryngeal crypotococcoma, mimicking a laryngeal malignancy, and describes associated management. A 68-year-old immunocompetent female with a new positron emission tomography-avid laryngeal lesion was intubated after acute respiratory decompensation. Airway evaluation revealed diffuse mucosal changes throughout the endolarynx with significant loss of normal native tissue architecture. Operative biopsy confirmed infection of C neoformans. The patient was treated with extended-course fluconazole. This case reinforces characteristic physical and histologic findings described for laryngeal cryptococcal infection. Laryngoscope, 129:926-929, 2019.
© 2018 The American Laryngological, Rhinological and Otological Society, Inc.
OBJECTIVES/HYPOTHESIS - Idiopathic subglottic stenosis (iSGS) is a rare and devastating extrathoracic obstruction involving the lower laryngeal and upper tracheal airway. It arises without known antecedent injury or associated disease process. Persistent mucosal inflammation and a localized fibrotic response are hallmarks of the disease. Despite the initial clinical description of iSGS more than 40 year ago, there have been no substantive investigations into the pathogenesis of this enigmatic and progressive airway obstruction. In these studies, we present the initial characterization of the molecular pathogenesis underlying the fibrosing phenotype of iSGS.
METHODS - Utilizing 20 human iSGS and healthy control specimens, we applied histologic, immunohistochemical, molecular, and immunologic techniques.
RESULTS - We demonstrate significant activation of the canonical IL-23/IL-17A pathway in the tracheal mucosa of iSGS patients, as well as identify γδ T cells as the primary cellular source of IL-17A.
CONCLUSION - Our results suggest that aberrant mucosal immune activation is a component in of the pathogenesis of iSGS. Most critically, our work offers new targets for future therapeutic intervention.
LEVEL OF EVIDENCE - NA Laryngoscope, 126:E356-E361, 2016.
© 2016 The American Laryngological, Rhinological and Otological Society, Inc.
OBJECTIVES/HYPOTHESIS - Idiopathic subglottic stenosis (iSGS) is a rare and potentially life-threatening disease marked by recurrent and progressive airway obstruction frequently requiring repeated surgery to stabilize the airway. Unknown etiology and low disease prevalence have limited the ability to characterize the natural history of iSGS and resulted in variability in surgical management. It is uncertain how this variation relates to clinical outcomes.
STUDY DESIGN - Medical record abstraction.
METHODS - Utilizing an international, multi-institutional collaborative, we collected retrospective data on patient characteristics, treatment, and clinical outcomes. We investigated variation between and within open and endoscopic treatment approaches and assessed therapeutic outcomes; specifically, disease recurrence and need for tracheostomy at last follow-up.
RESULTS - Strikingly, 479 iSGS patients across 10 participating centers were nearly exclusively female (98%, 95% confidence interval [CI], 96.1-99.6), Caucasian (95%, 95% CI, 92.2-98.8), and otherwise healthy (mean age-adjusted Charlson Comorbidity Index 1.5; 95% CI, 1.44-1.69). The patients presented at a mean age of 50 years (95% CI, 48.8-51.1). A total of 80.2% were managed endoscopically, whereas 19.8% underwent open reconstruction. Endoscopic surgery had a significantly higher rate of disease recurrence than the open approach (chi(2) = 4.09, P = 0.043). Tracheostomy was avoided in 97% of patients irrespective of surgical approach (95% CI, 94.5-99.8). Interestingly, there were outliers in rates of disease recurrence between centers using similar treatment approaches.
CONCLUSION - Idiopathic subglottic stenosis patients are surprisingly homogeneous. The heterogeneity of treatment approaches and the observed outliers in disease recurrence rates between centers raises the potential for improved clinical outcomes through a detailed understanding of the processes of care.
LEVEL OF EVIDENCE - 4. Laryngoscope, 126:1390-1396, 2016.
© 2015 The American Laryngological, Rhinological and Otological Society, Inc.
BACKGROUND - The contribution of environmental tobacco smoke (ETS) exposure to pulmonary morbidity in children with sickle cell anemia (SCA) is poorly understood. We tested the hypothesis that children with SCA and ETS exposure would have an increased prevalence of obstructive lung disease and respiratory symptoms compared with children with SCA and no ETS exposure.
METHODS - Parent reports of ETS and respiratory symptom frequency were obtained for 245 children with SCA as part of a multicenter prospective cohort study. One hundred ninety-six children completed pulmonary function testing. Multivariable regression models were used to evaluate the associations between ETS exposure at different time points (prenatal, infant [birth to 2 years], preschool [2 years to first grade], and current) and lung function and respiratory symptoms.
RESULTS - Among the 245 participants, a high prevalence of prior (44%) and current (29%) ETS exposure was reported. Of the 196 children who completed pulmonary function testing, those with parent-reported infant and current ETS exposure were more likely to have airway obstruction (defined as an FEV1/FVC ratio below the lower limit normal) compared with unexposed children (22.0% vs 3.1%, P < .001). Those with ETS exposure also had a lower forced expiratory flow, midexpiratory phase/FVC ratio (0.82 vs 0.97, P = .001) and were more likely to have evidence of bronchodilator responsiveness (23% vs 11%, P = .03). Current and prior ETS exposure and in utero smoke exposure were associated with increased frequency of respiratory symptoms.
CONCLUSIONS - ETS exposure is associated with evidence of lower airway obstruction and increased respiratory symptoms in SCA.
In addition to parenchymal fibrosis, fibrotic remodeling of the distal airways has been reported in interstitial lung diseases. Mechanisms of airway wall remodeling, which occurs in a variety of chronic lung diseases, are not well defined and current animal models are limited. The authors quantified airway remodeling in lung sections from subjects with idiopathic pulmonary fibrosis (IPF) and controls. To investigate intratracheal bleomycin as a potential animal model for fibrotic airway remodeling, the authors evaluated lungs from C57BL/6 mice after bleomycin treatment by histologic scoring for fibrosis and peribronchial inflammation, morphometric evaluation of subepithelial connective tissue volume density, TUNEL (terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling) assay, and immunohistochemistry for transforming growth factor β1 (TGFβ1), TGFβ2, and the fibroblast marker S100A4. Lung mechanics were determined at 3 weeks post bleomycin. IPF lungs had small airway remodeling with increased bronchial wall thickness compared to controls. Similarly, bleomycin-treated mice developed dose-dependent airway wall inflammation and fibrosis and greater airflow resistance after high-dose bleomycin. Increased TUNEL(+) bronchial epithelial cells and peribronchial inflammation were noted by 1 week, and expression of TGFβ1 and TGFβ2 and accumulation of S100A4(+) fibroblasts correlated with airway remodeling in a bleomycin dose-dependent fashion. IPF is characterized by small airway remodeling in addition to parenchymal fibrosis, a pattern also seen with intratracheal bleomycin. Bronchial remodeling from intratracheal bleomycin follows a cascade of events including epithelial cell injury, airway inflammation, profibrotic cytokine expression, fibroblast accumulation, and peribronchial fibrosis. Thus, this model can be utilized to investigate mechanisms of airway remodeling.
Airflow obstruction is an independent risk factor for cardiovascular events in the general population. The affected vascular bed and contribution of emphysema to cardiovascular risk are unclear. We examined whether an obstructive pattern of spirometry and quantitatively defined emphysema were associated with subclinical atherosclerosis in the carotid, peripheral and coronary circulations. The Multi-Ethnic Study of Atherosclerosis recruited participants aged 45-84 yrs without clinical cardiovascular disease. Spirometry, carotid intima-media thickness (IMT), ankle-brachial index (ABI) and coronary artery calcium (CAC) were measured using standard protocols. Percentage of emphysema-like lung was measured in the lung windows of cardiac computed tomography scans among 3,642 participants. Multiple linear regression was used to adjust for cardiac risk factors, including C-reactive protein. Decrements in forced expiratory volume in 1 s (FEV(1)) and FEV(1)/forced vital capacity ratio were associated with greater internal carotid IMT, particularly among smokers (p=0.03 and p<0.001, respectively) whereas percentage emphysema was associated with reduced ABI regardless of smoking history (p=0.004). CAC was associated with neither lung function (prevalence ratio for the presence of CAC in severe airflow obstruction 0.99, 95% CI 0.91-1.07) nor percentage emphysema. An obstructive pattern of spirometry and emphysema were associated distinctly and independently with subclinical atherosclerosis in the carotid arteries and peripheral circulation, respectively, and were not independently related to CAC.
OBJECTIVES - Several studies have identified airflow obstruction as a risk factor for lung cancer independent of smoking history, but the risk associated with the presence of radiographic evidence of emphysema has not been extensively studied. We proposed to assess this risk using a quantitative volumetric CT scan analysis.
METHODS - Sixty-four cases of lung cancer were identified from a prospective cohort of 1,520 participants enrolled in a spiral CT scan lung cancer screening trial. Each case was matched to six control subjects for age, sex, and smoking history. Quantitative CT scan analysis of emphysema was performed. Spirometric measures were also conducted. Data were analyzed using conditional logistic regression making use of the 1:6 set groups of 64 cases and 377 matched control subjects.
RESULTS - Decreased FEV(1) and FEV(1)/FVC were significantly associated with a diagnosis of lung cancer with ORs of 1.15 (95% CI, 1.00-1.32; P = .046) and 1.29 (95% CI, 1.02-1.62; P = .031), respectively. The quantity of radiographic evidence of emphysema was not found to be a significant risk for lung cancer with OR of 1.042 (95% CI, 0.816-1.329; P = .743). Additionally, there was no significant association between severe emphysema and lung cancer with OR of 1.57 (95% CI, 0.73-3.37).
CONCLUSIONS - We confirm previous observations that airflow obstruction is an independent risk factor for lung cancer. The absence of a clear relationship between radiographic evidence of emphysema and lung cancer using an automated quantitative volumetric analysis may result from different population characteristics than those of prior studies, radiographic evidence of emphysema quantitation methodology, or absence of any relationship between emphysema and lung cancer risk.
BACKGROUND - Very severe chronic obstructive pulmonary disease causes cor pulmonale with elevated pulmonary vascular resistance and secondary reductions in left ventricular filling, stroke volume, and cardiac output. We hypothesized that emphysema, as detected on computed tomography (CT), and airflow obstruction are inversely related to left ventricular end-diastolic volume, stroke volume, and cardiac output among persons without very severe lung disease.
METHODS - We measured left ventricular structure and function with the use of magnetic resonance imaging in 2816 persons who were 45 to 84 years of age. The extent of emphysema (expressed as percent emphysema) was defined as the percentage of voxels below -910 Hounsfield units in the lung windows on cardiac computed tomographic scans. Spirometry was performed according to American Thoracic Society guidelines. Generalized additive models were used to test for threshold effects.
RESULTS - Of the study participants, 13% were current smokers, 38% were former smokers, and 49% had never smoked. A 10-point increase in percent emphysema was linearly related to reductions in left ventricular end-diastolic volume (-4.1 ml; 95% confidence interval [CI], -3.3 to -4.9; P<0.001), stroke volume (-2.7 ml; 95% CI, -2.2 to -3.3; P<0.001), and cardiac output (-0.19 liters per minute; 95% CI, -0.14 to -0.23; P<0.001). These associations were of greater magnitude among current smokers than among former smokers and those who had never smoked. The extent of airflow obstruction was similarly associated with left ventricular structure and function, and smoking status had similar modifying effects on these associations. Percent emphysema and airflow obstruction were not associated with the left ventricular ejection fraction.
CONCLUSIONS - In a population-based study, a greater extent of emphysema on CT scanning and more severe airflow obstruction were linearly related to impaired left ventricular filling, reduced stroke volume, and lower cardiac output without changes in the ejection fraction.
2010 Massachusetts Medical Society
Lung disease is a common cause of morbidity among children with sickle cell disease (SCD). Although cross-sectional studies of children with SCD describe abnormal pulmonary function, the pattern of lung function growth in these children compared to children in the general population is not known. To provide preliminary evidence that growth of lung function is attenuated in children with SCD, we conducted a retrospective cohort study of children with hemoglobin SS (HbSS) ages 6-19 years who received at least two spirometry assessments for clinical care. The growth of lung function in these cases was compared to age, gender, and race-specific children without SCD or respiratory complaints from the Harvard Six Cities Study (H6CS). Seventy-nine children with HbSS contributed 363 spirometry measurements (mean per child = 4.6, median = 4.0, range = 2-17) and 255 controls contributed 1,543 spirometry measurements (mean per child = 6.1, median = 6.0, range = 2-13). Longitudinal forced expiratory volume in 1 sec (FEV(1)) was lower for boys and girls with HbSS compared to children in the general population, P = 0.031 and P = 0.002, respectively. When compared to the H6CS cohort, girls with HbSS showed lower longitudinal forced vital capacity (FVC) (P < 0.001) and FEV(1)/FVC (0.038); there was no difference in FVC or FEV(1)/FVC between boys in the HbSS and H6CS cohort. We conclude that growth of lung function is reduced in children with HbSS compared to children in the general population. Gender may influence the risk of developing abnormal lung function and airway obstruction in children with HbSS.
(c) 2008 Wiley-Liss, Inc.