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Wongviriyawong C.,Harvard University | Wongviriyawong C.,Massachusetts Institute of Technology | Harris R.S.,Pulmonary and Critical Care Unit | Zheng H.,Harvard University | And 3 more authors.
Journal of Applied Physiology | Year: 2012

Heterogeneity in narrowing among individual airways is an important contributor to airway hyperresponsiveness. This paper investigates the contribution of longitudinal heterogeneity (the variability along the airway in crosssectional area and shape) to airway resistance (Raw). We analyzed chest high-resolution computed tomography scans of 8 asthmatic (AS) and 9 nonasthmatic (NA) subjects before and after methacholine (MCh) challenge, and after lung expansion to total lung capacity. In each subject, Raw was calculated for 35 defined central airways with >2 mm diameter. Ignoring the area variability and noncircular shape results in an underestimation of Raw (%U total) that was substantial in some airways (̃50%) but generally small (median <6%). The average contribution of the underestimation of Raw caused by longitudinal heterogeneity in the area (%U area) to %U total was 36%, while the rest was due to the noncircularity of the shape (%U shape). After MCh challenge, %U area increased in AS and NA (P < 0.05). A lung volume increase to TLC reduced %U total and %U area in both AS and NA (P < 0.0001, except for %U total in AS with P < 0.01). Only in NA, %U shape had a significant reduction after increasing lung volume to TLC (P < 0.005). %U area was highly correlated, but not identical to the mean-normalized longitudinal heterogeneity in the cross-sectional area [CV 2(A)] and %U shape to the average eccentricity of the elliptical shape. This study demonstrates that Raw calculated assuming a cylindrical shape and derived from an average area along its length may, in some airways, substantially underestimate Raw. The observed changes in underestimations of Raw with the increase in lung volume to total lung capacity may be consistent with, and contribute in part to, the differences in effects of deep inhalations in airway function between AS and NA subjects. Copyright © 2012 the American Physiological Society. Source


Hariri L.P.,Massachusetts General Hospital | Hariri L.P.,Harvard University | Mark E.J.,Harvard University | Suter M.J.,Pulmonary and Critical Care Unit | Suter M.J.,Massachusetts General Hospital
Archives of Pathology and Laboratory Medicine | Year: 2012

Optical coherence tomography (OCT) is a nondestructive, high-resolution imaging modality, providing crosssectional, architectural images at near histologic resolutions, with penetration depths up to a few millimeters. Optical frequency domain imaging is a second-generation OCT technology that has equally high resolution with significantly increased image acquisition speeds and allows for large area, high-resolution tissue assessments. These features make OCT and optical frequency domain imaging ideal imaging techniques for surface and endoscopic imaging, specifically when tissue is unsafe to obtain and/ or suffers from biopsy sampling error. This review focuses on the clinical impact of OCT in coronary, esophageal, and pulmonary imaging and the role of the pathologist in interpreting high-resolution OCT images as a complement to standard tissue pathology. Source


Lee S.-D.,University of Ulsan | Xie C.-M.,Sun Yat Sen University | Yunus F.,University of Indonesia | Itoh Y.,Astrazeneca | And 3 more authors.
Respirology | Year: 2016

Background and objective Triple combination therapy with tiotropium plus budesonide/formoterol has improved lung function and reduced exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) in Western countries, but no such data exist for East Asian patients. This study aimed to evaluate the efficacy and tolerability of adding budesonide/formoterol to tiotropium compared with tiotropium alone in East Asian patients with severe/very severe COPD. Methods This 12-week, randomized, parallel-group, multicentre, open-label study was conducted in East Asia. After a 14-day run-in period during which patients received tiotropium 18 μg once daily, patients were randomized to tiotropium (18 μg once daily) + budesonide/formoterol (160/4.5 μg 2 inhalations twice daily) or tiotropium alone (18 μg once daily). The primary endpoint was change from baseline in pre-dose forced expiratory volume in 1 s (FEV1) to the mean of values measured at Weeks 1, 6 and 12. Results Pre-dose FEV1 significantly increased from baseline with tiotropium plus budesonide/formoterol (n = 287) versus tiotropium alone (n = 291) (5.0% vs 0.6%; treatment difference: 4.4% (95% CI: 1.9-6.9), P = 0.0004). Triple therapy also reduced the COPD exacerbation rate by 40.7% (P = 0.0032) and prolonged time to first exacerbation (38.6% risk reduction, P = 0.0167) versus tiotropium alone and markedly improved health-related quality of life (HRQoL), measured using the St George's Respiratory Questionnaire. Incidence of adverse events was 26% for both groups. Conclusions In East Asian patients with severe/very severe COPD, adding budesonide/formoterol to tiotropium was associated with significant improvements in FEV1 and HRQoL and lower COPD exacerbation rates. Treatment was generally well tolerated. Clinical trial registration: NCT01397890 at Clinicaltrials.gov The effects of adding ICS/LABA (budesonide/formoterol) therapy to tiotropium therapy in East Asian patients with severe and very severe COPD were assessed in this randomized phase IV study. This is the first study to assess the effects of budesonide/formoterol in addition to tiotropium in this patient group. © 2015 Asian Pacific Society of Respirology. Source


Su C.-W.,Chung Shan Medical University | Huang Y.-W.,Chung Shan Medical University | Huang Y.-W.,Pulmonary and Critical Care Unit | Chen M.-K.,Chung Shan Medical University | And 4 more authors.
Medicine (United States) | Year: 2015

Oral cancer, the fourth most common cancer among men in Taiwan, is associated with environmental carcinogens. Tissue inhibitor of metalloproteinase-3 (TIMP3), a member of the TIMP family, is the only protein that binds to the extracellular matrix for suppressing cancer cell growth, angiogenesis, migration, and invasion. The association of TIMP3 polymorphism with oral cancer susceptibility, however, has not yet been reported. In this study, 1947 participants-1200 healthy male controls and 747 male patients with oral cancer-were recruited. Allelic discrimination of TIMP3 1296 T>C (rs9619311), TIMP3 C>T (rs9862), and TIMP3 C>T (rs11547635) polymorphisms were assessed through real-time polymerase chain reaction. The authors discovered that individuals carrying the polymorphic rs9862 allele are more susceptible to oral cancer [odds ratio (OR), 1.5; 95% confidence interval (CI), 1.2-1.9; adjusted OR (AOR), 1.6; 95% CI, 1.2-2.1] after adjustment for betel quid chewing, alcohol, and tobacco consumption. Among 601 betel quid chewers, the TIMP3 polymorphism rs9862 T/T carriers had a 32.2-fold (95% CI, 20.2-51.3) increased oral cancer risk compared with those carrying C/C and not chewing betel quid. In addition, the authors observed a significant association between rs9862 variants and large tumors (OR, 1.5; 95% CI, 1.0-2.3) development. Moreover, TIMP3 plasma levels significantly increased in oral cancer patients who have large tumor or carry T allele rs9862 polymorphism. In conclusion, these results suggest that gene-environment interactions between the TIMP3 rs9862 polymorphisms and betel quid may alter oral cancer susceptibility and tumor growth in Taiwanese men. © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source


Serena Cirio F.T.,Pulmonary and Critical Care Unit | Stefano Nava M.D.,Pulmonary and Critical Care Unit
Respiratory Care | Year: 2011

BACKGROUND: The O2 Flow Regulator (Dima, Bologna, Italy) is a new automated oxygen regulator that titrates the oxygen flow based on a pulse-oximetry signal to maintain a target S pO2. We tested the device's safety and efficacy. METHODS: We enrolled 18 subjects with chronic lung disease, exercise-induced desaturation, and on long-term oxygen therapy, in a randomized crossover study with 2 constant-work-load 15-min cycling exercise tests, starting with the patient's previously prescribed usual oxygen flow. In one test the oxygen flow was titrated manually by the respiratory therapist, and in the other test the oxygen flow was titrated by the O2 Flow Regulator, to maintain an S pO2 of 94%. We measured S pO2 throughout each test, the time spent by the respiratory therapist to set the device or to manually regulate the oxygen flow, and the total number of respiratory-therapist titration interventions during the trial. RESULTS: There were no differences in symptoms or heart rate between the exercise tests. Compared to the respiratory-therapist-controlled tests, during the O2 Flow Regulator tests S pO2 was significantly higher (95 ± 2% vs 93 ± 3%, P =.04), significantly less time was spent below the target S pO (171 ± 187 s vs 340 ± 220 s, P <.001), and the O2 Flow Regulator tests required significantly less respiratory therapist time (5.6 ± 3.7 min vs 2.0 ± 0.1 min, P =.005). CONCLUSIONS: The O2 Flow Regulator may be a safe and effective alternative to manual oxygen titration during exercise in hypoxic patients. It provided stable S pO2 and avoided desaturations in our subjects. © 2011 Daedalus Enterprises. Source

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