Professor - University Medical Line, Medicine - Pulmonary, Allergy & Critical Care Medicine
Section Chief, Pulmonary, Critical Care and Sleep Medicine, VA Palo Alto Health Care System (2010 - Present)
Associate Chief for PACCM Faculty Affairs, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University School of Medicine (2018 - Present)
Medical Director, TeleQuit Smoking Cessation Program, Veterans Integrated Service Network 21, Veterans Health Administration (2006 - Present)
Chair, Clinical Bioethics Committee and Ethics Consultation Service, VA Palo Alto Health Care System (2001 - Present)
Chair, Research & Development Committee, VA Palo Alto Health Care System (2023 - Present)
Director, Board of Directors, Palo Alto Veterans Institute for Research (2023 - Present)
Member, Administrative Panel on Human Subjects in Medical Research, Panel 3, Stanford University (2008 - Present)
Member, Scientific Review Subcommittee, VA Palo Alto Health Care System (2008 - Present)
Honors & Awards
William A. Nelson Award for Excellence in Health Care Ethics, Veterans Health Administration (2011)
Clean Air Award for Medical Research, Breathe California (2010)
Outstanding Service Award, American Lung Association of San Francisco and San Mateo Counties (2006)
Faculty Teaching Award, Division of Pulmonary and Critical Care Medicine, Stanford University (2002)
Faculty Teaching Award, Division of Pulmonary and Critical Care Medicine, Stanford University (2000)
Cecile Lehman Mayer Research Award Finalist, American College of Chest Physicians (1996)
Research Award, Foundation for Occupational Health and Research (1996)
Walter Travel Fund Award, American Lung Association (1995)
Research Award, Foundation for Fellows in Asthma Research (1995)
Boards, Advisory Committees, Professional Organizations
Member, VA Executive Committee of Cooperative Study #595 “Pulmonary Health and Deployment to Southwest Asia and Afghanistan (2016 - Present)
Fellowship, University of California, San Francisco, Pulmonary and Critical Care Medicine (1996)
Residency, Columbia Presbyterian Medical Center, New York, NY, Internal Medicine (1992)
M.D., Columbia University, College of Physicians and Surgeons (1989)
Current Research and Scholarly Interests
My principal area of academic interest is in occupational and environmental lung disease. I have conducted experimental research studying the acute effects of toxic inhalational exposure and observational research analyzing exposure-effects relationships in selected populations. I have a secondary area of academic interest in medical ethics.
A Study to Assess the Efficacy and Safety of PT009 Compared to PT005 on COPD Exacerbations Over a 52-Week Period in Subjects With Moderate to Very Severe COPD (Sophos)
This is a Phase III randomized, double-blind, parallel group, multi-center, 52-week COPD exacerbation and lung function study with PT009 320/9.6 μg, PT009 160/9.6 μg and PT005 9.6 μg, all administered BID.
A Comparison of Symbicort® pMDI 2 x 160/4.5 μg Bid and 2 x 80/4.5 μg Bid With Formoterol Turbuhaler® 2 x 4.5 μg Bid and Placebo in Patients With COPD
The purpose of this study is to compare Symbicort in a pressurized metered-dose inhaler (pMDI) with formoterol and placebo in the long-term maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).
Stanford is currently not accepting patients for this trial. For more information, please contact Ware Kuschner, (650) 493 - 5000.
A Study Comparing the Efficacy, Safety and Tolerability of Fixed Dose Combination (FDC) of FF/UMEC/VI With the FDC of FF/VI and UMEC/VI; Administered Once-daily Via a Dry Powder Inhaler (DPI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
The study evaluates the efficacy of fluticasone furoate/umeclidinium bromide/vilanterol (FF/UMEC/VI) to reduce the annual rate of moderate and severe exacerbations compared with dual therapy of FF/VI or UMEC/VI in subjects with COPD. Published studies which assessed the use of an 'open' triple therapy (use of Inhaled Corticosteroid [ICS]/ Long-acting Muscarinic Receptor Antagonists [LAMA])/ Long Acting Beta-Agonist [LABA] delivered via multiple inhalers) in moderate-severe COPD patients, reported improvements in lung function, Health Related Quality of Life (HRQoL), hospitalization rates and rescue medication use, compared to dual therapy (ICS/LABA) or LAMA alone. These studies have also shown similar safety profile with dual or monotherapy doses for periods of up to one year. Given the clinical experience with FF, UMEC and VI, and that the associated risks with these compounds are anticipated from their known pharmacology, the potential benefit of a new therapy option in patients with moderate to severe COPD supports the further development of the closed triple combination (delivered via one inhaler). In the current study subjects meeting all inclusion/exclusion criteria will complete 2-week run-in period; 52 week treatment period and a 1-week safety follow-up period. Eligible subjects will be randomized to one of the following double-blind treatment groups FF/UMEC/VI 100 micrograms (mcg)/62.5 mcg/25 mcg once daily (QD), FF/VI 100 mcg/25 mcg QD, or UMEC/VI 62.5 mcg/25 mcg QD
Stanford is currently not accepting patients for this trial.
Chronic respiratory symptoms following deployment-related occupational and environmental exposures among US veterans.
Occupational and environmental medicine
Characterise inhalational exposures during deployment to Afghanistan and Southwest Asia and associations with postdeployment respiratory symptoms.Participants (n=1960) in this cross-sectional study of US Veterans (Veterans Affairs Cooperative Study 'Service and Health Among Deployed Veterans') completed an interviewer-administered questionnaire regarding 32 deployment exposures, grouped a priori into six categories: burn pit smoke; other combustion sources; engine exhaust; mechanical and desert dusts; toxicants; and military job-related vapours gas, dusts or fumes (VGDF). Responses were scored ordinally (0, 1, 2) according to exposure frequency. Factor analysis supported item reduction and category consolidation yielding 28 exposure items in 5 categories. Generalised linear models with a logit link tested associations with symptoms (by respiratory health questionnaire) adjusting for other covariates. OR were scaled per 20-point score increment (normalised maximum=100).The cohort mean age was 40.7 years with a median deployment duration of 11.7 months. Heavy exposures to multiple inhalational exposures were commonly reported, including burn pit smoke (72.7%) and VGDF (72.0%). The prevalence of dyspnoea, chronic bronchitis and wheeze in the past 12 months was 7.3%, 8.2% and 15.6%, respectively. Burn pit smoke exposure was associated with dyspnoea (OR 1.22; 95% CI 1.06 to 1.47) and chronic bronchitis (OR 1.22; 95% CI 1.13 to 1.44). Exposure to VGDF was associated with dyspnoea (OR 1.29; 95% CI 1.14 to 1.58) and wheeze (OR 1.18; 95% CI 1.02 to 1.35).Exposures to burn pit smoke and military occupational VGDF during deployment were associated with an increased odds of chronic respiratory symptoms among US Veterans.
View details for DOI 10.1136/oemed-2023-109146
View details for PubMedID 37968126
Sinusitis and Rhinitis Symptoms Following Deployment-related Occupational and Environmental Exposures Among US Veterans
AMER THORACIC SOC. 2023
View details for Web of Science ID 000995814705072
Impact of PTSD and Obstructive Sleep Apnea on Cognition in Older Adult Veterans.
Journal of geriatric psychiatry and neurology
Background: Posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) are highly prevalent and comorbid among older adult male veterans. Both PTSD and OSA are independently associated with cognitive deficits in older adults, but little research regarding the impact of comorbid PTSD and OSA among older adults exists. Purpose: The current study aimed to examine the independent and interactive effects of PTSD and OSA on cognitive functioning in older adult veterans. Study Sample: Older adult male veterans with (n= 106) and without PTSD (n= 69), ranging in age from 55 to 89 (M= 63.35). Data Collection: Participants underwent polysomnography evaluation to assess severity of OSA symptoms and comprehensive neuropsychological evaluation to assess cognitive functioning in 3 domains: attention and processing speed, learning and memory, and executive functioning. Results: Multiple regression analyses showed that the interaction between PTSD and OSA did not predict cognitive performance. However, PTSD significantly predicted poorer attention and processing speed, and increased OSA severity predicted poorer learning and memory. Conclusions: While PTSD and OSA did not have a synergistic detrimental impact on cognition, each independently predicted poorer cognitive functioning within certain domains, suggesting that older adults with these comorbid conditions may experience a wider array of cognitive difficulties.
View details for DOI 10.1177/08919887221149132
View details for PubMedID 36592096
Positive- and Negative-Pressure Ventilation Characterized by Local and Global Pulmonary Mechanics.
American journal of respiratory and critical care medicine
There is continued debate regarding the equivalency of positive pressure ventilation (PPV) and negative pressure ventilation (NPV). Resolving this question is important because of the different practical ramifications of the two paradigms.We sought to investigate the parallel between PPV and NPV and determine whether or not these two paradigms cause identical ventilation profiles by analyzing the local strain mechanics when the global tidal volume and inflation pressure was matched.A custom-designed electromechanical apparatus was utilized to impose equal global loads and displacements on the same ex-vivo healthy porcine lung using PPV and NPV. High-speed high-resolution cameras recorded local lung surface deformations and strains in real-time and differences between PPV and NPV global energetics, viscoelasticity, as well as local tissue distortion were assessed.During initial inflation, NPV exhibited significantly more bulk pressure-volume compliance than PPV, suggestive of earlier lung recruitment. NPV settings also showed reduced relaxation, hysteresis, and energy loss compared to PPV. Local strain trends were also decreased in NPV, with reduced tissue distortion trends compared to PPV as revealed through analysis of tissue anisotropy.Apparently contradictory previous studies are not mutually exclusive. Equivalent changes in transpulmonary pressures in PPV and NPV lead to the same changes in lung volume and pressures, yet local tissue strains differ between PPV and NPV. While limited to healthy specimens and ex-vivo experiments in the absence of a chest cavity, these results may explain previous reports of better oxygenation and less lung injury in NPV.
View details for DOI 10.1164/rccm.202111-2480OC
View details for PubMedID 36194677
The Role of Health Care Costs in Understanding Patient Preferences of Providers
CLINICAL MEDICINE & RESEARCH
2022; 20 (2): 69
View details for Web of Science ID 000822081500001
Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia.
Intensive care medicine
PURPOSE: Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes.METHODS: This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40mg loading bolus was followed by 40mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1year of follow-up.RESULTS: Between January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57-1.40). There were no significant differences in secondary outcomes or complications.CONCLUSIONS: In patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.
View details for DOI 10.1007/s00134-022-06684-3
View details for PubMedID 35723686
Chronic Respiratory Symptoms Following Deployment-Related Occupational and Environmental Exposures Among US Veterans
AMER THORACIC SOC. 2022
View details for Web of Science ID 000792480404038
- Reducing moral distress associated with rationing of healthcare resources. Ethics, medicine, and public health 2021; 18: 100655
INTERVENTION AMONG PAP USERS NEWLY DIAGNOSED WITH OSA IMPROVES LONG-TERM ADHERENCE IN VETERANS WITH SLEEP APNEA AND PTSD
OXFORD UNIV PRESS INC. 2021: A175
View details for Web of Science ID 000698984300442
- Aspirin for Primary Prevention of Atherosclerotic Cardiovascular Disease and Colorectal Carcinomas. Clinical medicine & research 2021
- Management of Sarcoidosis-Associated Pulmonary Hypertension. Clinical medicine & research 2020
A NOVEL COGNITIVE-BEHAVIORAL THERAPY TO INCREASE PAP ADHERENCE IN VETERANS WITH POSTTRAUMATIC STRESS DISORDER: PRELIMINARY RESULTS
OXFORD UNIV PRESS INC. 2020: A249
View details for Web of Science ID 000554588500651
Necrobiotic Mass in Crohn's Disease: A Case Report
AMER THORACIC SOC. 2020
View details for Web of Science ID 000556393500391
Respiratory Health after Military Service in Southwest Asia and Afghanistan An Official American Thoracic Society Workshop Report
ANNALS OF THE AMERICAN THORACIC SOCIETY
2019; 16 (8): E1–E16
Since 2001, more than 2.7 million U.S. military personnel have been deployed in support of operations in Southwest Asia and Afghanistan. Land-based personnel experienced elevated exposures to particulate matter and other inhalational exposures from multiple sources, including desert dust, burn pit combustion, and other industrial, mobile, or military sources. A workshop conducted at the 2018 American Thoracic Society International Conference had the goals of: 1) identifying key studies assessing postdeployment respiratory health, 2) describing emerging research, and 3) highlighting knowledge gaps. The workshop reviewed epidemiologic studies that demonstrated more frequent encounters for respiratory symptoms postdeployment compared with nondeployers and for airway disease, predominantly asthma, as well as case series describing postdeployment dyspnea, asthma, and a range of other respiratory tract findings. On the basis of particulate matter effects in other populations, it also is possible that deployers experienced reductions in pulmonary function as a result of such exposure. The workshop also gave particular attention to constrictive bronchiolitis, which has been reported in lung biopsies of selected deployers. Workshop participants had heterogeneous views regarding the definition and frequency of constrictive bronchiolitis and other small airway pathologic findings in deployed populations. The workshop concluded that the relationship of airway disease, including constrictive bronchiolitis, to exposures experienced during deployment remains to be better defined. Future clinical and epidemiologic research efforts should address better characterization of deployment exposures; carry out longitudinal assessment of potentially related adverse health conditions, including lung function and other physiologic changes; and use rigorous histologic, exposure, and clinical characterization of patients with respiratory tract abnormalities.
View details for DOI 10.1513/AnnalsATS.201904-344WS
View details for Web of Science ID 000478856300001
View details for PubMedID 31368802
Acute Respiratory Distress Syndrome: Etiology, Pathogenesis, and Summary on Management.
Journal of intensive care medicine
The acute respiratory distress syndrome (ARDS) has multiple causes and is characterized by acute lung inflammation and increased pulmonary vascular permeability, leading to hypoxemic respiratory failure and bilateral pulmonary radiographic opacities. The acute respiratory distress syndrome is associated with substantial morbidity and mortality, and effective treatment strategies are limited. This review presents the current state of the literature regarding the etiology, pathogenesis, and management strategies for ARDS.
View details for DOI 10.1177/0885066619855021
View details for PubMedID 31208266
- Alternative Explanation for Spread of Klebsiella Pneumoniae Infection from Pyogenic Liver Abscess into Thorax. The American journal of the medical sciences 2019
- Nonpharmacologic and Medication Minimization Strategies for the Prevention and Treatment of ICU Delirium: A Narrative Review JOURNAL OF INTENSIVE CARE MEDICINE 2019; 34 (3): 183-190
Lactic Acidosis and The Role of Sodium Bicarbonate: A Narrative Opinion.
Shock (Augusta, Ga.)
Lactic acidosis occurs commonly and can be a marker of significant physiologic derangements. However what an elevated lactate level and acidemia connotes and what should be done about it is subject to inconsistent interpretations. This review examines the varied etiologies of lactic acidosis, the physiologic consequences, and the known effects of its treatment with sodium bicarbonate. Lactic acidosis is often assumed to be a marker of hypoperfusion, but it can also result from medications, organ dysfunction, and sepsis even in the absence of malperfusion. Acidemia causes deleterious effects in almost every organ system but it can also have positive effects, increasing localized blood flow and oxygen delivery, as well as providing protection against hypoxic cellular injury. The use of sodium bicarbonate to correct severe acidemia may be tempting to clinicians, but previous studies have failed to show improved patient outcomes following bicarbonate administration. Bicarbonate use is known to decrease vasomotor tone, decrease myocardial contractility, and induce intracellular acidosis. This suggests that mild to moderate acidemia does not require correction. Most recently, a randomized control trial found a survival benefit in a subgroup of critically ill patients with serum pH levels <7.2 with concomitant acute kidney injury. There is no known benefit of correcting serum pH levels ≥ 7.2, and sparse evidence supports bicarbonate use <7.2. If administered, bicarbonate is best given as a slow IV infusion in the setting of adequate ventilation and calcium replacement to mitigate its untoward effects.
View details for DOI 10.1097/SHK.0000000000001415
View details for PubMedID 31318832
Nonpharmacologic and Medication Minimization Strategies for the Prevention and Treatment of ICU Delirium: A Narrative Review.
Journal of intensive care medicine
Delirium is a multifactorial entity, and its understanding continues to evolve. Delirium has been associated with increased morbidity, mortality, length of stay, and cost for hospitalized patients, especially for patients in the intensive care unit (ICU). Recent literature on delirium focuses on specific pharmacologic risk factors and pharmacologic interventions to minimize course and severity of delirium. While medication management clearly plays a role in delirium management, there are a variety of nonpharmacologic interventions, pharmacologic minimization strategies, and protocols that have been recently described. A PubMed search was performed to review the evidence for nonpharmacologic management, pharmacologic minimization strategies, and prevention of delirium for patients in the ICU. Recent approaches were condensed into 10 actionable steps to manage delirium and minimize medications for ICU patients and are presented in this review.
View details for PubMedID 29699467
- An innovative programme for premedical students. The clinical teacher 2017; 14 (3): 228
- Comment on "Early Innovative Immersion: A Course for Pre-Medical Professions Students Using Point-of-Care Ultrasound". Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine 2017; 36 (5): 1074-1075
- On "Does Timing of Internal Medicine Residency Interview Affect Likelihood of Matching?" Southern medical journal 2017; 110 (3): 209-?
Telephone care co-ordination for tobacco cessation: randomised trials testing proactive versus reactive models.
We conducted two parallel studies evaluating the effectiveness of proactive and reactive engagement approaches to telephone treatment for smoking cessation.Patients who smoked and were interested in quitting were referred to this study and were eligible if they were current smokers and had an address and a telephone number. The data were collected at 35 Department of Veterans Affairs (VA) sites, part of four VA medical centres in both California and Nevada. In study 1, participants received multisession counselling from the California Smokers' Helpline (quitline). In study 2, they received self-help materials only. Patients were randomly assigned by week to either proactive or reactive engagement, and primary care staff were blind to this assignment. Providers gave brief advice and referred them via the electronic health record to a tobacco co-ordinator. All patients were offered cessation medications.Using complete case analysis, in study 1 (quitline), patients in the proactive condition were more likely than those in the reactive condition to report abstinence at 6 months (21.0% vs 16.4%, p=0.03). No difference was found between conditions in study 2 (self-help) (16.9% vs 16.5%, p=0.88). Proactive outreach resulted in increased use of cessation medications in both the quitline (70.1% vs 57.6%, p<0.0001) and the self-help studies (74.5% vs 48.2%, p<0.0001).Proactive outreach with quitline intervention was associated with greater long-term abstinence. Both studies resulted in high rates of medication use. Sites should use a proactive outreach approach and provide counselling whenever possible.NCT00123682.
View details for DOI 10.1136/tobaccocontrol-2016-053327
View details for PubMedID 28190003
Spiritual Care in the Intensive Care Unit: A Narrative Review.
Journal of intensive care medicine
Spiritual care is an important component of high-quality health care, especially for critically ill patients and their families. Despite evidence of benefits from spiritual care, physicians and other health-care providers commonly fail to assess and address their patients' spiritual care needs in the intensive care unit (ICU). In addition, it is common that spiritual care resources that can improve both patient outcomes and family member experiences are underutilized. In this review, we provide an overview of spiritual care and its role in the ICU. We review evidence demonstrating the benefits of, and persistent unmet needs for, spiritual care services, as well as the current state of spiritual care delivery in the ICU setting. Furthermore, we outline tools and strategies intensivists and other critical care medicine health-care professionals can employ to support the spiritual well-being of patients and families, with a special focus on chaplaincy services.
View details for PubMedID 28604159
Long-Term Impact Of Non Invasive Open Ventilation (niovtm) On Dyspnea In Patients With Chronic Obstructive Pulmonary Disease And Idiopathic Pulmonary Fibrosis
AMER THORACIC SOC. 2017
View details for Web of Science ID 000400372505516
Fdg Pet-CT Suvmax And Circulating Tumor Microemboli Identify Recurrence In Patients With Non-Small Cell Lung Cancer
AMER THORACIC SOC. 2017
View details for Web of Science ID 000400372500266
Molecular profiling of single circulating tumor cells from lung cancer patients
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2016; 113 (52): E8379-E8386
Circulating tumor cells (CTCs) are established cancer biomarkers for the "liquid biopsy" of tumors. Molecular analysis of single CTCs, which recapitulate primary and metastatic tumor biology, remains challenging because current platforms have limited throughput, are expensive, and are not easily translatable to the clinic. Here, we report a massively parallel, multigene-profiling nanoplatform to compartmentalize and analyze hundreds of single CTCs. After high-efficiency magnetic collection of CTC from blood, a single-cell nanowell array performs CTC mutation profiling using modular gene panels. Using this approach, we demonstrated multigene expression profiling of individual CTCs from non-small-cell lung cancer (NSCLC) patients with remarkable sensitivity. Thus, we report a high-throughput, multiplexed strategy for single-cell mutation profiling of individual lung cancer CTCs toward minimally invasive cancer therapy prediction and disease monitoring.
View details for DOI 10.1073/pnas.1608461113
View details for PubMedID 27956614
Viral Respiratory Infections of Adults in the Intensive Care Unit.
Journal of intensive care medicine
2016; 31 (7): 427-441
Viral lower respiratory tract infections (LRTIs) are an underappreciated cause of critical illness in adults. Recent advances in viral detection techniques over the past decade have demonstrated viral LRTIs are associated with rates of morbidity, mortality, and health care utilization comparable to those of seen with bacterial community acquired and nosocomial pneumonias. In this review, we describe the relationship between viral LRTIs and critical illness, as well as discuss relevant clinical features and management strategies for the more prevalent respiratory viral pathogens.
View details for DOI 10.1177/0885066615585944
View details for PubMedID 25990273
Emotional Support for Health Care Professionals: A Therapeutic Role for the Hospital Ethics Committee.
Journal of social work in end-of-life & palliative care
2016; 12 (3): 277-288
Hospital ethics committees (HECs) are typically charged with addressing ethical disputes, conflicts, and dilemmas that arise in the course of patient care. HECs are not widely viewed as having a therapeutic role for health care professionals who experience psychological distress or anticipatory grief in the course of discharging professional duties. A case is presented in which an ethics consultation was requested, chiefly, to secure emotional support for health care professionals who had been asked by a patient to discontinue life-sustaining treatments. As the case demonstrates, HECs may be called upon to provide emotional support and reassurance to health care professionals who willingly carry out psychologically difficult actions, even though these actions may be ethically uncontroversial. In providing this service, the HEC may not necessarily engage in its customary activity of deliberating an ethics issue and resolving a conflict but may still provide valuable assistance, as in the case presented.
View details for DOI 10.1080/15524256.2016.1200519
View details for PubMedID 27462956
Impact Of Non Invasive Open Ventilation (niov) On Dyspnea And Quality Of Life In Patients With Chronic Obstructive Pulmonary Disease (COPD) And Idiopathic Pulmonary Fibrosis (ipf)
AMER THORACIC SOC. 2016
View details for Web of Science ID 000390749606652
Plasma Timp-1 Identifies Lung Cancer In Smokers
AMER THORACIC SOC. 2016
View details for Web of Science ID 000390749607473
Patient-Specific Airway Wall Remodeling in Chronic Lung Disease.
Annals of biomedical engineering
2015; 43 (10): 2538-2551
Chronic lung disease affects more than a quarter of the adult population; yet, the mechanics of the airways are poorly understood. The pathophysiology of chronic lung disease is commonly characterized by mucosal growth and smooth muscle contraction of the airways, which initiate an inward folding of the mucosal layer and progressive airflow obstruction. Since the degree of obstruction is closely correlated with the number of folds, mucosal folding has been extensively studied in idealized circular cross sections. However, airflow obstruction has never been studied in real airway geometries; the behavior of imperfect, non-cylindrical, continuously branching airways remains unknown. Here we model the effects of chronic lung disease using the nonlinear field theories of mechanics supplemented by the theory of finite growth. We perform finite element analysis of patient-specific Y-branch segments created from magnetic resonance images. We demonstrate that the mucosal folding pattern is insensitive to the specific airway geometry, but that it critically depends on the mucosal and submucosal stiffness, thickness, and loading mechanism. Our results suggests that patient-specific airway models with inherent geometric imperfections are more sensitive to obstruction than idealized circular models. Our models help to explain the pathophysiology of airway obstruction in chronic lung disease and hold promise to improve the diagnostics and treatment of asthma, bronchitis, chronic obstructive pulmonary disease, and respiratory failure.
View details for DOI 10.1007/s10439-015-1306-7
View details for PubMedID 25821112
- Quantitative Emphysema Score as a Predictor of Morbidity in Transthoracic Needle Aspiration Biopsy AMER COLL CHEST PHYSICIANS. 2015
Does The White Blood Cell Count Assist With Solitary Pulmonary Nodule Diagnosis?
AMER THORACIC SOC. 2015
View details for Web of Science ID 000377582804215
The IBV Valve trial: a multicenter, randomized, double-blind trial of endobronchial therapy for severe emphysema.
Journal of bronchology & interventional pulmonology
2014; 21 (4): 288-297
Lung volume reduction surgery improves quality of life, exercise capacity, and survival in selected patients but is accompanied by significant morbidity. Bronchoscopic approaches may provide similar benefits with less morbidity.In a randomized, sham procedure controlled, double-blind trial, 277 subjects were enrolled at 36 centers. Patients had emphysema, airflow obstruction, hyperinflation, and severe dyspnea. The primary effectiveness measure was a significant improvement in disease-related quality of life (St. George's Respiratory Questionnaire) and changes in lobar lung volumes. The primary safety measure was a comparison of serious adverse events.There were 6/121 (5.0%) responders in the treatment group at 6 months, significantly >1/134 (0.7%) in the control group [Bayesian credible intervals (BCI), 0.05%, 9.21%]. Lobar volume changes were significantly different with an average decrease in the treated lobes of -224 mL compared with -17 mL for the control group (BCI, -272, -143). The proportion of responders in St. George's Respiratory Questionnaire was not greater in the treatment group. There were significantly more subjects with a serious adverse event in the treatment group (n=20 or 14.1%) compared with the control group (n=5 or 3.7%) (BCI, 4.0, 17.1), but most were neither procedure nor device related.This trial had technical and statistical success but partial-bilateral endobronchial valve occlusion did not obtain clinically meaningful results. Safety results were acceptable and compare favorably to lung volume reduction surgery and other bronchial valve studies. Further studies need to focus on improved patient selection and a different treatment algorithm.ClinicalTrials.gov NCT00475007.
View details for DOI 10.1097/LBR.0000000000000110
View details for PubMedID 25321447
- MicroRNA footprints of circulating tumor cells in patients with non-small cell lung cancer AMER ASSOC CANCER RESEARCH. 2014
Circulating Tumor Microemboli Diagnostics for Patients with Non-Small-Cell Lung Cancer
JOURNAL OF THORACIC ONCOLOGY
2014; 9 (8): 1111-1119
Circulating tumor microemboli (CTM) are potentially important cancer biomarkers, but using them for cancer detection in early-stage disease has been assay limited. We examined CTM test performance using a sensitive detection platform to identify stage I non-small-cell lung cancer (NSCLC) patients undergoing imaging evaluation.First, we prospectively enrolled patients during 18F-FDG PET-CT imaging evaluation for lung cancer that underwent routine phlebotomy where CTM and circulating tumor cells (CTCs) were identified in blood using nuclear (DAPI), cytokeratin (CK), and CD45 immune-fluorescent antibodies followed by morphologic identification. Second, CTM and CTC data were integrated with patient (age, gender, smoking, and cancer history) and imaging (tumor diameter, location in lung, and maximum standard uptake value [SUVmax]) data to develop and test multiple logistic regression models using a case-control design in a training and test cohort followed by cross-validation in the entire group.We examined 104 patients with NSCLC, and the subgroup of 80 with stage I disease, and compared them to 25 patients with benign disease. Clinical and imaging data alone were moderately discriminating for all comers (Area under the Curve [AUC] = 0.77) and by stage I disease only (AUC = 0.77). However, the presence of CTM combined with clinical and imaging data was significantly discriminating for diagnostic accuracy in all NSCLC patients (AUC = 0.88, p value = 0.001) and for stage I patients alone (AUC = 0.87, p value = 0.002).CTM may add utility for lung cancer diagnosis during imaging evaluation using a sensitive detection platform.
View details for PubMedID 25157764
- An evaluation of a clinical decision support tool. American journal of medicine 2014; 127 (5)
Stage I Lung Adenocarcinoma Tumor Density And Contour Do Not Predict Circulating Tumor Cell Burden
AMER THORACIC SOC. 2014
View details for Web of Science ID 000209838202778
Toxic inhalational exposures.
Journal of intensive care medicine
2013; 28 (6): 323-333
Respirable toxicants are a spectrum of irritant and nonirritant gases, vapors, fumes, and airborne particles that can be entrained into the body through the respiratory tract, resulting in exposures that cause pulmonary injury and/or systemic disease. Sources of respirable toxicants include structural fires, industrial accidents, domestic mishaps, and intentional releases of injurious agents on the battleground (warfare) or in civilian settings (acts of terrorism). Acute toxic inhalational exposures may result in respiratory failure, multisystem organ dysfunction, and death. Management of victims includes assessment and protection of the airway, monitoring and treatment of systemic toxicity, and delivery of exposure-specific and nonspecific therapies that improve outcomes. Treatments may include antidotes, hyperbaric oxygen, and other nonspecific life-supporting interventions.
View details for DOI 10.1177/0885066611432541
View details for PubMedID 22232204
Thrombocytopenia in the intensive care unit.
Journal of intensive care medicine
2013; 28 (5): 268-280
Thrombocytopenia is a common laboratory finding in critically ill patients admitted to the intensive care unit. Potential etiologies of thrombocytopenia are myriad, ranging from acute disease processes and concomitant conditions to exposures and drugs. The mechanism of decreased platelet counts can also be varied: laboratory measurement may be spurious, platelet production may be decreased, or platelet destruction or sequestration may be increased. In addition to evaluation for the cause of thrombocytopenia, the clinician must also guard against spontaneous bleeding due to thrombocytopenia, prophylax against bleeding resulting from an invasive procedure performed in the setting of thrombocytopenia, and treat active bleeding related to thrombocytopenia.
View details for DOI 10.1177/0885066611431551
View details for PubMedID 22232201
- Authors' reply. Clinical medicine & research 2013; 11 (3): 106-?
- Developing a non-invasive, diagnostic test for stage I non-small cell lung cancer using circulating tumor cells. AMER ASSOC CANCER RESEARCH. 2013
The diagnosis and management of pleural effusions in the ICU.
Journal of intensive care medicine
2013; 28 (1): 24-36
Pleural effusions are common in critically ill patients. Most effusions in intensive care unit (ICU) patients are of limited clinical significance; however, some are important and require aggressive management. Transudative effusions in the ICU are commonly caused by volume overload, decreased plasma oncotic pressure, and regions of altered pleural pressure attributable to atelectasis and mechanical ventilation. Exudates are sequelae of pulmonary or pleural infection, pulmonary embolism, postsurgical complications, and malignancy. Increases in pleural fluid volume are accommodated principally by chest wall expansion and, to a lesser degree, by lung collapse. Studies in mechanically ventilated patients suggest that pleural fluid drainage can result in improved oxygenation for up to 48 hours, but data on clinical outcomes are limited. Mechanically ventilated patients with pleural effusions should be semirecumbant and treated with higher levels of positive-end expiratory pressure. Rarely, large effusions can cause cardiac tamponade or tension physiology, requiring urgent drainage. Bedside ultrasound is both sensitive and specific for diagnosing pleural effusions in mechanically ventilated patients. Sonographic findings of septation and homogenous echogenicity may suggest an exudative effusion, but definitive diagnosis requires pleural fluid sampling. Thoracentesis should be carried out under ultrasound guidance. Antibiotic regimens for parapneumonic effusions should be based on current pneumonia guidelines, and anaerobic coverage should be included in the case of empyema. Decompression of the pleural space may be necessary to improve respiratory mechanics, as well as to treat complicated effusions. While small-bore catheters inserted under ultrasound guidance may be used for nonseptated effusions, surgical consultation should be sought in cases where this approach fails, or where the effusion appears complex and septated at the outset. Further research is needed to determine the effects of pleural fluid drainage on clinical outcomes in mechanically ventilated patients, to evaluate weaning strategies that include pleural fluid drainage, and to better identify patients in whom pleural effusions are more likely to be infected.
View details for DOI 10.1177/0885066611403264
View details for PubMedID 22080544
An observational study of circulating tumor cells and (18)F-FDG PET uptake in patients with treatment-naive non-small cell lung cancer.
2013; 8 (7)
We investigated the relationship of circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by (18)F-fluorodeoxyglucose (FDG) uptake since both have been associated with patient prognosis.We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or "HD-CTCs"). We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis.We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0-3.6) and median maximum standardized uptake value (SUVmax) was 7.2 (IQR 3.7-15.5). More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were weakly correlated with partial volume corrected tumor SUVmax (r = 0.27, p-value = 0.03) and not correlated with tumor diameter (r = 0.07; p-value = 0.60). For a given partial volume corrected SUVmax or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease.CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.
View details for DOI 10.1371/journal.pone.0067733
View details for PubMedID 23861795
View details for PubMedCentralID PMC3702496
A case report of a pneumothorax caused by aggressive use of an incentive spirometer in a patient with emphysema.
A 68 year old man presented to the Emergency Department with a small pneumothorax following aggressive use of an incentive spirometer. The patient had a baseline chest radiograph consistent with emphysema. He was initially treated with oxygen in the Emergency Department with resolution of his symptoms. The pneumothorax resolved spontaneously over a period of three days. The development of the pneumothorax was likely due to the patient's repeated forceful inspiratory maneuvers in the setting of emphysema and lung hyperinflation. Inspiratory resistive breathing can cause large negative swings in intrathoracic pressure which may result in mechanical stress of lung tissue. This is the first report of a secondary pneumothorax associated with use of an incentive spirometer. Patients with bullous emphysema should be counseled to avoid frequent high intensity maneuvers with an incentive spirometer if the potential benefits of the procedure are marginal.
View details for DOI 10.4187/respcare.02130
View details for PubMedID 23232741
Modeling the effects of obstructive sleep apnea and hypertension in Vietnam veterans with PTSD
SLEEP AND BREATHING
2012; 16 (4): 1201-1209
The present work aimed to extend models suggesting that obstructive sleep apnea (OSA) is associated with worse cognitive performance in community-dwelling older adults. We hypothesized that in addition to indices of OSA severity, hypertension is associated with worse cognitive performance in such adults.The PTSD Apnea Clinical Study recruited 120 community-dwelling, male veterans diagnosed with PTSD, ages 55 and older. The Rey Auditory Verbal Learning Test (RAVLT) and Color-Word Interference Test (CWIT) were measures of auditory verbal memory and executive function, respectively. Apnea-hypopnea index (AHI), minimum and mean pulse oximeter oxygen saturation (min SpO(2), mean SpO(2)) indicators were determined during standard overnight polysomnography. Multivariate linear regression and receiver operating characteristic (ROC) curve analyses were performed.In regression models, AHI (β = -4.099; p < 0.01) and hypertension (β = -4.500; p < 0.05) predicted RAVLT; hypertension alone (β = 9.146; p < 0.01) predicted CWIT. ROC analyses selected min SpO(2) cut-points of 85% for RAVLT (κ = 0.27; χ² = 8.23, p < 0.01) and 80% for CWIT (κ = 0.25; χ² = 12.65, p < 0.01). Min SpO(2) cut-points and hypertension were significant when added simultaneously in a regression model for RAVLT (min SpO(2), β = 4.452; p < 0.05; hypertension, β = -4.332; p < 0.05), and in separate models for CWIT (min SpO(2), β = -8.286; p < 0.05; hypertension, β = -8.993; p < 0.01).OSA severity and presence of self-reported hypertension are associated with poor auditory verbal memory and executive function in older adults.
View details for DOI 10.1007/s11325-011-0632-8
View details for Web of Science ID 000311301700038
View details for PubMedID 22193972
Respiratory Health in Home and Leisure Pursuits
CLINICS IN CHEST MEDICINE
2012; 33 (4): 715-?
Many home-based and leisure activities can generate hazardous respirable exposures. Routine domestic activities and a variety of hobbies, avocations, and leisure pursuits have been associated with a spectrum of respiratory tract disorders. Indoor environments present a special risk for high-intensity exposures and adverse health effects. There are important knowledge gaps regarding the prevalence of specific health hazards within and across communities, exposure-response effects, population and individual susceptibilities, best management strategies, the adverse health effects of mixed exposures, and long-term clinical outcomes following exposures. The home environment presents special health risks that should be part of the health assessment.
View details for DOI 10.1016/j.ccm.2012.08.001
View details for Web of Science ID 000312619600010
View details for PubMedID 23153611
- Lung diseases associated with occupational and environmental exposures subsume a wide spectrum of conditions. Clinics in chest medicine 2012; 33 (4): xi-xii
The pharmacology of airway management in critical care.
Journal of intensive care medicine
2012; 27 (5): 298-305
This review provides an update on the pharmacology of airway management, emphasizing medications and management strategies widely used in an intensive care unit setting. Induction agents, muscle relaxants, opioids, sedative-hypnotics, and adjunctive agents are reviewed in the context of emergent airway management. Throughout this review, we emphasize the utility of considering a broad set of pharmacologic agents and approaches for airway management of the critically ill patient.
View details for DOI 10.1177/0885066611402154
View details for PubMedID 21436166
Hemoptysis due to breath-hold diving following chemotherapy and lung irradiation.
Clinical medicine & research
2012; 10 (3): 137-139
Breath-hold diving, also known as free-diving, describes the practice of intentional immersion under water without an external supply of oxygen. Pulmonary hemorrhage with hemoptysis has been reported as a complication of immersion and breath-hold diving in young healthy athletes. We report the case of a 60-year-old man with a history of radiation and chemotherapy for breast carcinoma, who developed the abrupt onset of hemoptysis in the setting of swimming and breath-hold diving. A computed tomography (CT) scan of the chest demonstrated an area of ground glass opacification, suggestive of pulmonary hemorrhage, superimposed on a background of reticular opacities within the prior radiation field. A follow-up CT scan of the chest, obtained 2 months after presentation, demonstrated resolution of the ground glass opacification, but persistence of fibrotic features attributable to prior radiation therapy. We postulate that prior irradiation of the chest resulted in lung injury and fibrosis which, in turn, rendered the affected region of the lung susceptible to "stress failure," due to an increase in the transcapillary pressure gradient arising from immersion and breath-hold diving. Patients with a history of lung injury resulting from chest irradiation should be cautioned about pulmonary hemorrhage and hemoptysis as a potential complication of swimming and breath-hold diving.
View details for DOI 10.3121/cmr.2011.1038
View details for PubMedID 22537760
View details for PubMedCentralID PMC3421363
The diagnostic yield of CT-guided percutaneous lung biopsy in solid organ transplant recipients
2012; 26 (4): 615-621
Despite the widespread use of computed tomography(CT)-guided percutaneous lung biopsy (PLB) in immunocompetent patients, the diagnostic yield and safety in solid organ transplant (SOT)recipients is unknown. The purpose of this investigation was to determine the test performance of CT-PLB in SOT recipients.We performed a 10-yr single-center, retrospective analysis among heart, lung, kidney, and liver transplant recipients. We included all adult patients who underwent a PLB of a parenchymal lung nodule following their transplantation.Within the study period, 1754 SOTs were performed, of which 45 biopsies met study criteria. Overall, the incidence of PLB in SOT was 3%.PLB established a diagnosis in 24 of 45 cases. The yield of PLB was better for combined biopsy technique (fine-needle aspiration biopsy [FNAB]) and core biopsy than for FNAB alone (odds ratio [OR]: 4.2, 95% confidence interval [CI]: 1.2, 15.6), and for lesions that were malignant (OR: 10.0, 95%CI: 1.8, 75.4) or caused by an invasive fungal infection (OR: 5.0, 95% CI:1.1, 27.9). Complications occurred in 13% (6/45) of patients.CT-guided PLB is a safe modality that provides a moderate yield for diagnosing pulmonary nodules of malignant or fungal etiology in SOT recipients.
View details for DOI 10.1111/j.1399-0012.2011.01582.x
View details for Web of Science ID 000307344400032
View details for PubMedID 23050274
View details for PubMedCentralID PMC3473075
- Correlating circulating tumor cells with F-18-FDG positron emission tomography (PET) uptake in patients with treatment naive non-small cell lung cancer: A pilot study AMER ASSOC CANCER RESEARCH. 2012
Missed Opportunities to Counsel Patients With Malignant Pleural Mesothelioma About Causation and Potential Compensation
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
2012; 343 (3): 206-209
Malignant pleural mesothelioma (MPM) is a lethal malignancy strongly associated with occupational exposure to asbestos. The aims of this study were to assess the quality of counseling provided to patients with MPM about the causation of MPM and the potential for compensation.The authors conducted a structured retrospective chart review of patients with a diagnosis of MPM. They abstracted demographic data, occupational and environmental history and exposure data. They also searched for documentation of patient education and counseling.The authors identified 16 patients with a new diagnosis of MPM during the study period. A job title was documented at least once in the records of 12 (75%) patients. Documentation of occupational exposure to asbestos was found in the records of 12 (75%) patients. Two patients (13%) were presumed to have had bystander exposure to asbestos. Education about MPM causation and counseling about opportunities for compensation were documented in the record of 1 patient (6%).Among patients with MPM, documentation of some elements of an occupational history, including an occupational asbestos exposure history, was common. Advice to pursue compensation for potential occupation related MPM was rare. Physicians may be missing opportunities to provide beneficial information to patients with newly diagnosed MPM regarding potential legal redress and compensation.
View details for DOI 10.1097/MAJ.0b013e3182297912
View details for Web of Science ID 000300767600006
View details for PubMedID 21817877
- Bronchogenic squamous cell carcinoma mass with central photopenia on FDG-PET scan. Clinical medicine & research 2012; 10 (1): 36-37
- Constrictive Bronchiolitis in Soldiers NEW ENGLAND JOURNAL OF MEDICINE 2011; 365 (18): 1744-1744
- Racial Disparities in End-of-Life Care ARCHIVES OF INTERNAL MEDICINE 2011; 171 (10): 949-950
- Passive leg raising for monitoring volume status and predicting fluid responsiveness CRITICAL CARE MEDICINE 2011; 39 (2): 420-420
- Palliative Care for Pulmonary Patients AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2011; 183 (3): 416-416
Perioperative intravascular fluid assessment and monitoring: a narrative review of established and emerging techniques.
Anesthesiology research and practice
2011; 2011: 231493-?
Accurate assessments of intravascular fluid status are an essential part of perioperative care and necessary in the management of the hemodynamically unstable patient. Goal-directed fluid management can facilitate resuscitation of the hypovolemic patient, reduce the risk of fluid overload, reduce the risk of the injudicious use of vasopressors and inotropes, and improve clinical outcomes. In this paper, we discuss the strengths and limitations of a spectrum of noninvasive and invasive techniques for assessing and monitoring intravascular volume status and fluid responsiveness in the perioperative and critically ill patient.
View details for DOI 10.1155/2011/231493
View details for PubMedID 21785588
View details for PubMedCentralID PMC3139886
Missed Opportunities To Counsel Patients With Malignant Pleural Mesothelioma About Potential For Legal Redress
AMER THORACIC SOC. 2011
View details for Web of Science ID 000208770304537
Electronic cigarettes and thirdhand tobacco smoke: two emerging health care challenges for the primary care provider.
International journal of general medicine
2011; 4: 115-120
PRIMARY CARE PROVIDERS SHOULD BE AWARE OF TWO NEW DEVELOPMENTS IN NICOTINE ADDICTION AND SMOKING CESSATION: 1) the emergence of a novel nicotine delivery system known as the electronic (e-) cigarette; and 2) new reports of residual environmental nicotine and other biopersistent toxicants found in cigarette smoke, recently described as "thirdhand smoke". The purpose of this article is to provide a clinician-friendly introduction to these two emerging issues so that clinicians are well prepared to counsel smokers about newly recognized health concerns relevant to tobacco use. E-cigarettes are battery powered devices that convert nicotine into a vapor that can be inhaled. The World Health Organization has termed these devices electronic nicotine delivery systems (ENDS). The vapors from ENDS are complex mixtures of chemicals, not pure nicotine. It is unknown whether inhalation of the complex mixture of chemicals found in ENDS vapors is safe. There is no evidence that e-cigarettes are effective treatment for nicotine addiction. ENDS are not approved as smoking cessation devices. Primary care givers should anticipate being questioned by patients about the advisability of using e-cigarettes as a smoking cessation device. The term thirdhand smoke first appeared in the medical literature in 2009 when investigators introduced the term to describe residual tobacco smoke contamination that remains after the cigarette is extinguished. Thirdhand smoke is a hazardous exposure resulting from cigarette smoke residue that accumulates in cars, homes, and other indoor spaces. Tobacco-derived toxicants can react to form potent cancer causing compounds. Exposure to thirdhand smoke can occur through the skin, by breathing, and by ingestion long after smoke has cleared from a room. Counseling patients about the hazards of thirdhand smoke may provide additional motivation to quit smoking.
View details for DOI 10.2147/IJGM.S16908
View details for PubMedID 21475626
View details for PubMedCentralID PMC3068875
- Abnormal FDG-PET findings in particulate-induced lung disease. Clinical medicine & research 2010; 8 (3-4): 125-?
Efficacy and safety of ipratropium bromide/albuterol delivered via Respimat (R) inhaler versus MDI
2010; 104 (8): 1179-1188
We compared the efficacy and safety of ipratropium bromide/albuterol delivered via Respimat inhaler, a novel propellant-free inhaler, versus chlorofluorocarbon (CFC)-metered dose inhaler (MDI) and ipratropium Respimat inhaler in patients with COPD. This was a multinational, randomized, double-blind, double-dummy, 12-week, parallel-group, active-controlled study. Patients with moderate to severe COPD were randomized to ipratropium bromide/albuterol (20/100mcg) Respimat inhaler, ipratropium bromide/albuterol MDI [36mcg/206mcg (Combivent Inhalation Aerosol MDI)], or ipratropium bromide (20mcg) Respimat inhaler. Each medication was administered four times daily. Serial spirometry was performed over 6h (0.15min, then hourly) on 4 test days. The primary efficacy variable was forced expiratory volume in 1s (FEV(1)) change from test day baseline at 12 weeks. A total of 1209 of 1480 randomized, treated patients completed the study; the majority were male (65%) with a mean age of 64 yrs and a mean screening pre-bronchodilator FEV(1) (percent predicted) of 41%. Ipratropium bromide/albuterol Respimat inhaler had comparable efficacy to ipratropium bromide/albuterol MDI for FEV(1) area under the curve at 0-6h (AUC(0-6)), superior efficacy to ipratropium Respimat inhaler for FEV(1) AUC(0-4) and comparable efficacy to ipratropium Respimat inhaler for FEV(1) AUC(4-6). All active treatments were well tolerated. This study demonstrates that ipratropium bromide/albuterol 20/100mcg inhaler administered four times daily for 12 weeks had equivalent bronchodilator efficacy and comparable safety to ipratropium bromide/albuterol 36mcg/206mcg MDI, and significantly improved lung function compared with the mono-component ipratropium bromide 20 mcg Respimat inhaler. [Clinical Trial Identifier Number: NCT00400153].
View details for DOI 10.1016/j.rmed.2010.01.017
View details for Web of Science ID 000280178900012
View details for PubMedID 20172704
Tiotropium as a first maintenance drug in COPD: secondary analysis of the UPLIFT (R) trial
EUROPEAN RESPIRATORY JOURNAL
2010; 36 (1): 65-73
The aim of the present study was investigate the long-term effect of tiotropium as first maintenance respiratory medication in chronic obstructive pulmonary disease (COPD). A 4-yr, randomised, multicentre, double-blind, parallel-group, placebo-controlled trial (Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) was conducted. Analysis focused on the effect of tiotropium versus matching placebo in the 810 (13.5%) COPD patients not on other maintenance treatment (long-acting beta-agonists, inhaled corticosteroids, theophyllines or anticholinergics) at randomisation. Spirometry, health-related quality of life (St George's Respiratory Questionnaire (SGRQ) score), exacerbations of COPD and mortality were also analysed. 403 patients (mean+/-sd age 63+/-8 yrs, post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 53+/-12% predicted) received tiotropium and 407 (64+/-8 yrs of age, post-bronchodilator FEV(1) 51+/-12% pred) received placebo. Post-bronchodilator FEV(1) decline was 42+/-4 mL.yr(-1) in the tiotropium group and 53+/-4 mL.yr(-1) in the placebo group (p = 0.026). At 48 months, the morning pre-dose FEV(1) was 134 mL higher in the tiotropium group compared to the placebo group (p<0.001). SGRQ total score declined more slowly in the tiotropium group (difference of 1.05+/-0.34 units.yr(-1); p = 0.002). This was particularly significant for the impact (difference of 1.08+/-0.37 units.yr(-1); p = 0.004) and activity (1.44+/-0.40 units.yr(-1); p<0.001) domains, but not for symptoms (0.26+/-0.50 units.yr(-1); p = 0.6). At 48 months, the difference in total score was 4.6 units (p<0.001) with tiotropium compared to placebo. In patients with COPD who are not on maintenance therapy, tiotropium is associated with significant benefits in disease progression.
View details for DOI 10.1183/09031936.00127809
View details for Web of Science ID 000279394100013
View details for PubMedID 20185426
Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial
2009; 374 (9696): 1171-1178
The beneficial effects of pharmacotherapy for chronic obstructive pulmonary disease (COPD) are well established. However, there are few data for treatment in the early stages of the disease. We examined the effect of tiotropium on outcomes in a large subgroup of patients with moderate COPD.The Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) study was a randomised, double-blind, placebo-controlled trial undertaken in 487 centres in 37 countries. 5993 patients aged 40 years or more with COPD were randomly assigned to receive 4 years of treatment with either once daily tiotropium (18 microg; n=2987) or matching placebo (n=3006), delivered by an inhalation device. Randomisation was by computer-generated blocks of four, with stratification according to study site. In a prespecified subgroup analysis, we investigated the effects of tiotropium in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II disease. Primary endpoints were the yearly rates of decline in prebronchodilator forced expiratory volume in 1 s (FEV(1)) and in postbronchodilator FEV(1), beginning on day 30 until completion of double-blind treatment. The analysis included all patients who had at least three measurements of pulmonary function. This study is registered with ClinicalTrials.gov, number NCT00144339.2739 participants (mean age 64 years [SD 9]) had GOLD stage II disease at randomisation (tiotropium, n=1384; control, n=1355), with a mean postbronchodilator FEV(1) of 1.63 L (SD 0.37; 59% of predicted value). 1218 patients in the tiotropium group and 1157 in the control group had three or more measurements of postbronchodilator pulmonary function after day 30 and were included in the analysis. The rate of decline of mean postbronchodilator FEV(1) was lower in the tiotropium group than in the control group (43 mL per year [SE 2] vs 49 mL per year [SE 2], p=0.024). For prebronchodilator pulmonary function, 1221 patients in the tiotropium group and 1158 in the control group had three or more measurements and were included in the analysis. The rate of decline of mean prebronchodilator FEV(1) did not differ between groups (35 mL per year [SE 2] vs 37 mL per year [SE 2]; p=0.38). Health status, measured with the St George's Respiratory Questionnaire, was better at all timepoints in the tiotropium group than in the control group (p=0.006 for all timepoints). Time to first exacerbation and time to exacerbation resulting in hospital admission were also longer in the tiotropium group than in the control group (hazard ratio 0.82, 95% CI 0.75-0.90, and 0.74, 0.62-0.88, respectively).Tiotropium seemed to reduce the rate of decline of postbronchodilator FEV(1) in patients with GOLD stage II COPD. This finding and the other improvements in outcomes suggest that treatment of COPD should begin at an early stage of the disease.Boehringer Ingelheim and Pfizer Pharmaceuticals.
View details for DOI 10.1016/S0140-6736(09)61298-8
View details for Web of Science ID 000270688200033
View details for PubMedID 19716598
Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials
2009; 374 (9691): 685-694
The phosphodiesterase-4 inhibitor roflumilast can improve lung function and prevent exacerbations in certain patients with chronic obstructive pulmonary disease (COPD). We therefore investigated whether roflumilast would reduce the frequency of exacerbations requiring corticosteroids in patients with COPD.In two placebo-controlled, double-blind, multicentre trials (M2-124 and M2-125) with identical design that were done in two different populations in an outpatient setting, patients with COPD older than 40 years, with severe airflow limitation, bronchitic symptoms, and a history of exacerbations were randomly assigned to oral roflumilast (500 microg once per day) or placebo for 52 weeks. Primary endpoints were change in prebronchodilator forced expiratory volume in 1 s (FEV(1)) and the rate of exacerbations that were moderate (glucocorticosteroid-treated) or severe. Analysis was by intention to treat. The trials are registered with ClinicalTrials.gov, number NCT00297102 for M2-124, and NCT00297115 for M2-125.Patients were assigned to treatment, stratified according to smoking status and treatment with longacting beta(2) agonists, and given roflumilast (n=1537) or placebo (n=1554). In both studies, the prespecified primary endpoints were achieved and were similar in magnitude. In a pooled analysis, prebronchodilator FEV(1) increased by 48 mL with roflumilast compared with placebo (p<0.0001). The rate of exacerbations that were moderate or severe per patient per year was 1.14 with roflumilast and 1.37 with placebo (reduction 17% [95% CI 8-25], p<0.0003). Adverse events were more common with roflumilast (1040 [67%]) than with placebo (963 [62%]); 219 (14%) patients in the roflumilast group and 177 (12%) in the placebo group discontinued because of adverse events. In the pooled analysis, the difference in weight change during the study between the roflumilast and placebo groups was -2.17 kg.Since different subsets of patients exist within the broad spectrum of COPD, targeted specific therapies could improve disease management. This possibility should be explored further in prospective studies.Nycomed.
View details for Web of Science ID 000269422500024
View details for PubMedID 19716960
The effect of an inhaled corticosteroid on glucose control in type 2 diabetes.
Clinical medicine & research
2009; 7 (1-2): 14-20
To determine the effect of inhaled corticosteroid (ICS) therapy on glucose control in adults with type 2 diabetes mellitus and coexisting asthma or chronic obstructive pulmonary disease (COPD).A prospective randomized, double-blind, double-dummy placebo-controlled, crossover investigation of inhaled steroids and oral leukotriene blockers.A United States Department of Veterans Affairs Health Care System outpatient setting.Adults with type 2 diabetes and asthma or COPD.Subjects (n=12) were randomized to receive either inhaled fluticasone propionate (440 microg twice daily) and oral placebo, or inhaled placebo and oral montelukast (10 mg/day). After 6 weeks, subjects were switched to the opposite therapy for 6 weeks. The primary outcome measure was the change in the percentage of glycosylated hemoglobin (%HbA1c) at 6 weeks relative to the baseline value.Ten patients completed the study. The difference between the mean within-subject changes in %HbA1c associated with 6-week periods of fluticasone and the mean changes associated with montelukast therapy was small but statistically significant (mean difference=0.25; P<0.025). Neither fluticasone nor oral montelukast therapy for 6 weeks led to a significantly different mean % HbA1c compared with the relevant baseline (mean differences=0.11 and -0.14, respectively).The absence of a clinically significant within-subject difference in the changes in %HbA1c associated with fluticasone versus oral montelukast therapy, or between either therapy or baseline does not warrant recommending changes in therapy for asthma or diabetes in patients with these co-morbid conditions. However, we suggest that clinicians carefully monitor blood glucose control when diabetic patients initiate ICS, especially with higher dosages.
View details for DOI 10.3121/cmr.2009.824
View details for PubMedID 19251584
View details for PubMedCentralID PMC2705276
- Clinical Guidelines and Clinicians' Intentions in End-Of-Life Care Response CHEST 2009; 135 (6): 1697-1697
Occupational History Quality in Patients With Newly Documented, Clinician-Diagnosed Chronic Bronchitis
2009; 135 (2): 378-383
Approximately 15% of cases of COPD, including chronic bronchitis, is attributable to occupational exposures. An occupational history is essential to identify exposures responsible for work-related chronic bronchitis.We conducted a structured retrospective analysis of the medical records of veterans, 18 to 70 years of age, newly diagnosed with chronic bronchitis in order to achieve the following: (1) to assess the quality of documented occupational histories; and (2) to characterize the management of patients with a history of exposure to a potentially hazardous respiratory substance. We also analyzed occupational exposure data reported by patients on a structured questionnaire.Sixty patients were included in the final analysis. A total of 6,150 notes were reviewed. Occupational status was documented in the records of 54 patients (90%). A description of occupational duties was recorded in 32 records (53%), and work exposure data in 26 records (43%). Clinicians concluded that occupational exposures potentially contributed to chronic bronchitis in three patients (5%). A recommendation for exposure avoidance was documented for six patients (10%). On the questionnaire, most patients reported a history of occupational exposure to respirable substances and symptoms of cough and/or shortness of breath.Details about job duties and occupational respiratory exposures were documented in the records of approximately half of patients with newly diagnosed chronic bronchitis. Patient self-reports of occupational exposures and respiratory symptoms were common. A determination that occupational exposures contributed to chronic bronchitis was rare. Few patients were counseled to take measures to avoid occupational exposures. Work-related chronic bronchitis may be incompletely assessed and undermanaged by clinicians.
View details for DOI 10.1378/chest.08-1559
View details for Web of Science ID 000263251800020
View details for PubMedID 18719054
Implementation of ICU Palliative Care Guidelines and Procedures A Quality Improvement Initiative Following an Investigation of Alleged Euthanasia
2009; 135 (1): 26-32
Ethical conflicts are commonly encountered in the course of delivering end-of-life care in the ICU. Some ethical concerns have legal dimensions, including concerns about inappropriate hastening of death. Despite these concerns, many ICUs do not have explicit policies and procedures for withdrawal of life-sustaining treatments. We describe a US Office of Inspector General (OIG) investigation of end-of-life care practices in our ICU. The investigation focused on care delivered to four critically ill patients with terminal diseases and an ICU nurse's concern that the patients had been subjected to euthanasia. The OIG investigation also assessed the validity of allegations that patient flow in and out of our ICU was inappropriately influenced by scheduled surgeries and that end-of-life care policies in our ICU were not clear. Although the investigation did not substantiate the allegations of euthanasia or inappropriate ICU patient flow, it did find that the policies that discuss end-of-life care issues were not clear and allowed for wide-ranging interpretations. Acting on the OIG recommendations, we developed a quality improvement initiative addressing end-of-life care in our ICU, intended to enhance communication and understanding about palliative care practices in our ICU, to prevent ethical conflicts surrounding end-of-life care, and to improve patient care. The initiative included the introduction of newly developed ICU comfort care guidelines, a physician order set, and a physician template note. Additionally, we implemented an educational program for ICU staff. Staff feedback regarding the initiative has been highly favorable, and the nurse whose concerns led to the investigation was satisfied not only with the investigation but also the policies and procedures that were subsequently introduced in our ICU.
View details for DOI 10.1378/chest.08-1685
View details for Web of Science ID 000262304300008
View details for PubMedID 19136403
- Nurses' roles in discussions of do not resuscitate orders with patients and families CRITICAL CARE MEDICINE 2008; 36 (12): 3281-3281
Understanding and Identifying Bias and Confounding in the Medical Literature
SOUTHERN MEDICAL JOURNAL
2008; 101 (12): 1240-1245
Bias and confounding are types of error that may be encountered in the collection, analysis, or interpretation of research data. Bias and confounding may result in erroneous research conclusions with adverse consequences for patients and health care providers. In this article, we provide clinician-friendly descriptions and examples of bias (including surveillance, information, selection, lead, length, and publication) and confounding. The purpose of the article is to help clinicians to recognize two important sources of error in research and in turn to help clinicians to assess the validity and generalizability of a research report.
View details for Web of Science ID 000261778000015
View details for PubMedID 19005435
A 4-year trial of tiotropium in chronic obstructive pulmonary disease
NEW ENGLAND JOURNAL OF MEDICINE
2008; 359 (15): 1543-1554
Previous studies showing that tiotropium improves multiple end points in patients with chronic obstructive pulmonary disease (COPD) led us to examine the long-term effects of tiotropium therapy.In this randomized, double-blind trial, we compared 4 years of therapy with either tiotropium or placebo in patients with COPD who were permitted to use all respiratory medications except inhaled anticholinergic drugs. The patients were at least 40 years of age, with a forced expiratory volume in 1 second (FEV(1)) of 70% or less after bronchodilation and a ratio of FEV(1) to forced vital capacity (FVC) of 70% or less. Coprimary end points were the rate of decline in the mean FEV(1) before and after bronchodilation beginning on day 30. Secondary end points included measures of FVC, changes in response on St. George's Respiratory Questionnaire (SGRQ), exacerbations of COPD, and mortality.Of a total of 5993 patients (mean age, 65+/-8 years) with a mean FEV(1) of 1.32+/-0.44 liters after bronchodilation (48% of predicted value), we randomly assigned 2987 to the tiotropium group and 3006 to the placebo group. Mean absolute improvements in FEV(1) in the tiotropium group were maintained throughout the trial (ranging from 87 to 103 ml before bronchodilation and from 47 to 65 ml after bronchodilation), as compared with the placebo group (P<0.001). After day 30, the differences between the two groups in the rate of decline in the mean FEV(1) before and after bronchodilation were not significant. The mean absolute total score on the SGRQ was improved (lower) in the tiotropium group, as compared with the placebo group, at each time point throughout the 4-year period (ranging from 2.3 to 3.3 units, P<0.001). At 4 years and 30 days, tiotropium was associated with a reduction in the risks of exacerbations, related hospitalizations, and respiratory failure.In patients with COPD, therapy with tiotropium was associated with improvements in lung function, quality of life, and exacerbations during a 4-year period but did not significantly reduce the rate of decline in FEV(1). (ClinicalTrials.gov number, NCT00144339.)
View details for DOI 10.1056/NEJMoa0805800
View details for Web of Science ID 000259903100003
View details for PubMedID 18836213
- Does statin use attenuate lung function decline? AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2008; 177 (6): 671-671
- Measuring airborne particulates with a light scattering monitor AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2008; 177 (5): 556-557
Preliminary results from a study of telephone care coordination for smoking cessation
31st Annual Meeting of the Society-of-General-Internal-Medicine
SPRINGER. 2008: 376–377
View details for Web of Science ID 000254237100782
Care coordination to increase referrals to smoking cessation telephone counseling: A demonstration project
132nd Annual Meeting of the American-Public-Health-Association
AMER MED PUBLISHING, M W C COMPANY. 2008: 141–48
To test the effectiveness of a care coordination program for telephone counseling in raising referral and treatment rates for smoking cessation.A demonstration project implementing a smoking cessation care coordination program offering telephone counseling and medication management to patients referred from primary care.The study was performed at 18 Veterans Health Administration (VA) sites in California. Participants were VA patients receiving primary care. We randomly allocated 10 of 18 sites to receive the Telephone Care Coordination Program, which included simple 2-click referral, proactive care coordination, medication management, and 5 follow-up telephone calls. Each patient received a 30- to 45-minute counseling session from the California Smokers' Helpline. Patients at control sites received usual care.During 10 months, we received 2965 referrals. We were unable to reach 1156 patients (39%), despite at least 3 attempts. We excluded 73 patients (3%), and 391 patients (13%) were not interested. We connected the remaining 1345 patients (45%) to the Helpline. At 6-month followup, 335 patients (11% of all referrals and 25% of participating patients) were abstinent. Providers at intervention sites reported referring many more patients to telephone counseling than providers at control sites (15.6 vs 0.7 in the prior month).The program generated a large number of referrals; almost half of the patients referred were connected with the Helpline. Long-term abstinence was excellent. These results suggest that managed care organizations may be able to improve tobacco control by implementing a similar system of care coordination.
View details for Web of Science ID 000253928700003
View details for PubMedID 18333706
ENHANCED ACUTE RESPONSES IN AN EXPERIMENTAL EXPOSURE MODEL TO BIOMASS SMOKE INHALATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE
EXPERIMENTAL LUNG RESEARCH
2008; 34 (10): 631-662
Chronic obstructive pulmonary diseases (COPD) may increase air pollution-related mortality. The relationship of immune mechanisms to mortality caused by fine particulates in healthy and COPD populations is incompletely understood. The objective of this study was to determine whether fine particulates from a single biomass fuel alter stress and inflammation biomarkers in people with COPD. Healthy and COPD subjects were exposed to smoke in a controlled indoor setting. Immune responses were quantified by measuring cell surface marker expression with flow-cytometric analysis and mRNA levels with quantitative reverse transcriptase-polymerase chain reactions in whole blood before and after exposure. Preexposure COPD subjects had more leukocytes, mainly CD14(+) monocytes and neutrophils, but fewer CD3(+) T cells. Fifty-seven of 186 genes were differentially expressed between healthy and COPD subjects' peripheral blood mononuclear cells (PBMCs). Of these, only nuclear factor (NF)-kappa B1, TIMP-1, TIMP-2, and Duffy genes were up-regulated in COPD subjects. At 4 hours post smoke exposure, monocyte levels decreased only in healthy subjects. Fifteen genes, particular to inflammation, immune response, and cell-to-cell signaling, were differentially expressed in COPD subjects, versus 4 genes in healthy subjects. The authors observed significant differences in subjects' PBMCs, which may elucidate the adverse effects of air pollution particulates on people with COPD.
View details for DOI 10.1080/01902140802322256
View details for Web of Science ID 000261737300001
View details for PubMedID 19085563
- Critical care nurses responses to patient photographs displayed at the bedside HEART & LUNG 2007; 36 (5): 385-385
- Critical care nurses responses to patient photographs displayed at the bedside HEART & LUNG 2007; 36 (5): 385-385
Ethical triage and scarce resource allocation during public health emergencies: tenets and procedures.
2007; 85 (3): 16-25
Public health emergencies may result in mass casualties and a surge in demand for hospital-based care. Healthcare standards may need to be altered to respond to an imbalance between demands for care and resources. Clinical decisions that involve triage and scarce resource allocation may present unique ethical challenges. To address these challenges, the authors detailed tenets and procedures to guide triage and scarce resource allocation during public health emergencies. The authors propose health care organizations deploy a Triage and Scarce Resource Allocation Team to over-see and guide ethically challenging clinical decision-making during a crisis period. The authors' goal is to help healthcare organizations and clinicians balance public health responsibilities and their duty to individual patients during emergencies in as equitable and humane a manner as possible.
View details for PubMedID 17711810
Aspiration syndromes: 10 clinical pearls every physician should know
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE
2007; 61 (5): 846-852
Aspiration syndromes are clinically and pathologically classified into three sets of disorders: (i) large airway mechanical obstruction caused by foreign bodies; (ii) aspiration pneumonitis; and (iii) aspiration pneumonia. In this article, we discuss the common clinical presentations, risk factors, radiographic features and methods of management of these disorders. We highlight recent recommendations and controversies surrounding the prevention of aspiration pneumonia in the critically ill patient. Finally, we review ethical dilemmas surrounding feeding and aspiration risk concerns in debilitated and demented patients.
View details for DOI 10.1111/j.1742-1241.2007.01300.x
View details for Web of Science ID 000245608700022
View details for PubMedID 17493092
Outdoor air pollution: Particulate matter health effects
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
2007; 333 (4): 235-243
Numerous investigations studying multiple populations across a variety of environmental settings have demonstrated a strong association between ambient air particulate matter and cardiopulmonary morbidity and mortality. In most studies, the effect size of ambient air particulate pollution on health outcomes is small. However, the exposed population worldwide is very large. Accordingly, particulate air pollution appears to be an important public health hazard that makes an important contribution to the total burden of disease and death in populations across the world. Much of the evidence linking ambient air particulates with adverse health effects is derived from population-based, observational research with potential unidentified confounding exposures, precluding definitive assessments about causation and providing limited mechanistic insights. A growing body of research suggests particulate-associated adverse health effects result from the induction of proinflammatory responses in the lower respiratory tract. Ambient air particulates may increase lung cancer risk.
View details for Web of Science ID 000246509200008
View details for PubMedID 17435418
Outdoor air pollution: Counseling and exposure risk reduction
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
2007; 333 (4): 257-260
Air pollution is monitored on a daily basis in large population centers in the United States and reported to the general public through a variety of media outlets as the Air Quality Index. This index is based on current national air quality standards for criteria air pollutants established by the US Environmental Protection Agency. Patients at increased risk for adverse effects of inhaled air pollutants include those who have been diagnosed with chronic lung disease and cardiovascular disease, including asthma, chronic obstructive pulmonary disease, coronary artery disease, congestive heart failure, and peripheral vascular disease, although others may also be at risk during periods of unusually high pollutant levels. These patients should be educated regarding what symptoms may be related to poor air quality and how they can monitor the Air Quality Index to modify their activity to prevent symptoms and other adverse events. Heavy outdoor exertion should be avoided on days expected to have poor air quality, or performed earlier in the day on days when outdoor activity cannot be avoided. We recommend advising patients in clear, strong, personalized language that air pollution is harmful and that persons with cardiopulmonary disease are at elevated risk of experiencing a serious adverse health effect from exposure.
View details for Web of Science ID 000246509200011
View details for PubMedID 17435421
Outdoor air pollution: Nitrogen dioxide, sulfur dioxide, and carbon monoxide health effects
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
2007; 333 (4): 249-256
Nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide are important ambient air pollutants. High-intensity, confined space exposure to NO2 has caused catastrophic injury to humans, including death. Ambient NO2 exposure may increase the risk of respiratory tract infections through the pollutant's interaction with the immune system. Sulfur dioxide (SO2) contributes to respiratory symptoms in both healthy patients and those with underlying pulmonary disease. Controlled human exposure studies have demonstrated that experimental SO2 exposure causes changes in airway physiology, including increased airways resistance. Both acute and chronic exposure to carbon monoxide are associated with increased risk for adverse cardiopulmonary events, including death. However, studies have not demonstrated a clear dose-dependent health risk response to increasing amounts of these pollutants except at high concentrations. In addition, a number of studies examining the effects of ambient level exposure to NO2, SO2, and CO have failed to find associations with adverse health outcomes.
View details for Web of Science ID 000246509200010
View details for PubMedID 17435420
Outdoor air pollution: Ozone health effects
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
2007; 333 (4): 244-248
Ozone is a respiratory irritant associated with a spectrum of adverse health events. Ground-level ozone has been shown to cause decreases in lung function and has been associated with other important respiratory health effects. Some reports suggest short-term increases in ozone lead to increased cardiopulmonary mortality. Other studies have found no association between exposure and measured health effects. Outdoor air pollution consists of multiple copollutant exposures complicating definitive assessments about ambient air ozone exposure-effect relations.
View details for Web of Science ID 000246509200009
View details for PubMedID 17435419
Outdoor air pollution: Overview and historical perspective
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
2007; 333 (4): 230-234
Outdoor air pollution is a significant public health hazard in population centers throughout the world. Recognition of air pollution as a nuisance dates back many centuries. Decades of research have established a strong link between air pollution and a spectrum of adverse health effects. Health care practitioners rarely consider the health risk of air pollution in the course of patient care and generally do not provide risk modification strategies as part of patient management. The purpose of this article is to provide front line clinicians with: 1) an overview of the evolution in scientific understanding about air pollution and its health effects, 2) an introduction to the hazards contemporary air pollution presents to patients, and 3) an introduction to the contributions of specific pollutants to outdoor air quality.
View details for Web of Science ID 000246509200007
View details for PubMedID 17435417
- The asthma epidemic NEW ENGLAND JOURNAL OF MEDICINE 2007; 356 (10): 1073-1073
Principles and procedures of medical ethics case consultation
BRITISH JOURNAL OF HOSPITAL MEDICINE
2007; 68 (3): 140-144
Ethical conflicts are common in hospital medicine. This article reviews core medical ethics principles, describes models for conducting hospital-based ethics case consultations, and highlights the contributions of hospital ethics committees to high quality patient care.
View details for Web of Science ID 000245198000005
View details for PubMedID 17419461
- The ethics of palliative sedation as a therapy of last resort. American Journal of Hospice and Palliative Medicine 2007; 23: 483-491
Risk indexes for exacerbations and hospitalizations due to COPD
2007; 131 (1): 20-28
The ability to predict exacerbations in patients with COPD might permit more rational use of preventive interventions. Our objective was to develop risk indexes for exacerbations and hospitalizations due to exacerbations that might be applied to the individual patient.Spirometry, demographics, and medical history were obtained at baseline in 1,829 patients with moderate-to-very severe COPD who entered a trial of inhaled tiotropium. Information about exacerbations and hospitalizations due to exacerbation was collected during the 6-month follow-up period. Analyses of first outcomes were modeled using univariable and multivariable Cox proportional hazards regressions.During follow-up, 551 patients had at least one exacerbation and 151 patients had at least one hospitalization due to exacerbation. In the multivariable model for exacerbation, older age, percentage of predicted FEV(1), duration of COPD, a productive cough, antibiotic or systemic corticosteroid use for COPD in the prior year, hospitalization for COPD in the prior year, and theophylline use at baseline predicted a higher risk. In the multivariable model for hospitalization, older age, percentage of predicted FEV(1), unscheduled clinic/emergency department visits for COPD in the prior year, any cardiovascular comorbidity, and prednisone use at baseline were associated with greater risk. Both the exacerbation and the hospitalization models provided moderately good discrimination, the validated concordance indexes being 0.66 and 0.73, respectively. Methods for calculating risk in individual patients are provided.Spirometry along with a few questions directed to the patient are strongly predictive of exacerbations and related hospitalizations over the ensuing 6 months.
View details for DOI 10.1378/chest.06-1316
View details for Web of Science ID 000243548100007
View details for PubMedID 17218552
- Cyclophosphamide in scleroderma lung disease NEW ENGLAND JOURNAL OF MEDICINE 2006; 355 (11): 1173-1173
Quality of occupational history assessments in working age adults with newly diagnosed asthma
99th International Conference of the American-Thoracic-Society
AMER COLL CHEST PHYSICIANS. 2006: 455–62
Approximately 10 to 15% of new-onset asthma in adults is attributable to occupational exposure. The occupational history is the most important instrument in the diagnosis of occupational asthma (OA).To assess the quality of occupational histories obtained by health-care providers and to measure the prevalence of clinician-diagnosed OA in a population at elevated risk for OA.An academic US Department of Veteran Affairs medical center.One hundred ninety-seven adults (age range, 18 to 55 years) with newly diagnosed asthma who had completed pulmonary function testing (PFT) and a structured respiratory health questionnaire.We conducted a structured retrospective comparison of occupational respiratory health history documented by clinicians with data documented by patients on a structured questionnaire. We analyzed PFT results to assess physiologic impairment. We also conducted a structured examination of the actions taken by health-care providers based on their occupational history assessments.Patient self-reports of respiratory exposures and symptoms were common. A job title was documented by one or more clinicians in 75% of patient medical records. Additional occupational history data were charted much less frequently. A diagnosis of OA was made in only 2% of patients. Clinical action to address OA was documented for only one patient.Clinicians who manage adults with newly diagnosed asthma take incomplete occupational histories. We detected discordance between the occupational exposure histories documented by patients and those charted by clinicians. OA may go unrecognized and possibly undermanaged by clinicians.
View details for DOI 10.1378/chest.130.2.455
View details for Web of Science ID 000239886800023
View details for PubMedID 16899845
Critical care medicine update: essentials for the nonintensivist, part 1.
2006; 32 (2): 74-81
The intensive care unit (ICU) can be a challenging environment for health care practitioners who are not trained in critical care medicine. A structured approach to patient care is necessary in order to achieve optimal clinical outcomes. The purpose of this two-part article is to review essential highlights of critical care medicine for the nonintensivist. We provide a structured overview of the management of the critically ill patient and focus on problems commonly encountered in the heterogeneous ICU patient population. In Part 1 we review (a) altered states of consciousness and sedation, (b) respiratory failure and ventilators, (c) cardiovascular monitoring and management, and (d) fluid and electrolyte disorders.
View details for PubMedID 16845149
Critical care medicine update: essentials for the nonintensivist, part 2.
2006; 32 (2): 82-89
In Part 2 of this update on the essentials of critical care medicine for the nonintensivist, we continue our review of common problems encountered in the intensive care unit (ICU). The focus of this part is on renal failure, acid-base disturbances, common ICU complications, nutrition management, endocrine disorders, prognostic indicators and principles of patient- and family-centered care.
View details for PubMedID 16845150
- Normal chest radiograph in terminal respiratory failure due to amyotrophic lateral sclerosis SOUTHERN MEDICAL JOURNAL 2006; 99 (5): 551-552
- Dying patients and palliative sedation JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 2006; 295 (11): 1250-1250
Sildenafil citrate therapy for pulmonary arterial hypertension.
New England journal of medicine
2006; 354 (10): 1091-1093
View details for PubMedID 16528810
Sildenafil citrate therapy for pulmonary arterial hypertension
NEW ENGLAND JOURNAL OF MEDICINE
2006; 354 (10): 1092
View details for Web of Science ID 000235822200029
- Pulmonary artery catheter effectiveness in congestive heart failure JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 2006; 295 (10): 1121-1121
- A 35-year-old man, with fever, dyspnea, and diffuse reticular opacities CHEST 2006; 129 (2): 482-487
- Work-related airways disease Clin Pulm Med 2006; 13: 169-177
- A 24-year-old woman with bilateral pulmonary infiltrates, pericardial effusion, and bilateral pleural effusions CHEST 2005; 128 (6): 4013-4017
- Media Attention to End-of-Life Cases. The virtual mentor : VM 2005; 7 (12)
Accuracy of transbronchial needle aspiration for mediastinal staging of non-small cell lung cancer: a meta-analysis
2005; 60 (11): 949-955
The reported accuracy of transbronchial needle aspiration (TBNA) for mediastinal staging in non-small cell lung cancer (NSCLC) varies widely. We performed a meta-analysis to estimate the accuracy of TBNA for mediastinal staging in NSCLC.Medline, Embase, and the bibliographies of retrieved articles were searched for studies evaluating TBNA accuracy with no language restriction. Meta-analytical methods were used to construct summary receiver-operating characteristic curves and to pool sensitivity and specificity.Thirteen studies met inclusion criteria, including six studies that surgically confirmed all TBNA results and enrolled at least 10 patients with and without mediastinal metastasis (tier 1). Methodological quality varied but did not affect diagnostic accuracy. In tier 1 studies the median prevalence of mediastinal metastasis was 34%. Using a random effects model, the pooled sensitivity and specificity were 39% (95% CI 17 to 61) and 99% (95% CI 96 to 100), respectively. Compared with tier 1 studies, the median prevalence of mediastinal metastasis (81%; p = 0.002) and pooled sensitivity (78%; 95% CI 71 to 84; p = 0.009) were higher in non-tier 1 studies. Sensitivity analysis confirmed that the sensitivity of TBNA depends critically on the prevalence of mediastinal metastasis. The pooled major complication rate was 0.3% (95% CI 0.01 to 4).When properly performed, TBNA is highly specific for identifying mediastinal metastasis in patients with NSCLC, but sensitivity depends critically on the study methods and patient population. In populations with a lower prevalence of mediastinal metastasis, the sensitivity of TBNA is much lower than reported in recent lung cancer guidelines.
View details for DOI 10.1136/thx.2005.041525
View details for Web of Science ID 000232965900014
View details for PubMedID 15994251
View details for PubMedCentralID PMC1747236
- Pulmonary dirofilariasis presenting as multiple pulmonary nodules in a patient with a history of lymphoma AMER COLL CHEST PHYSICIANS. 2005: 481S-482S
- Asthma and invasive pneumococcal disease NEW ENGLAND JOURNAL OF MEDICINE 2005; 353 (7): 738-739
Health-related quality of life in patients with idiopathic pulmonary fibrosis: a systematic review
2005; 60 (7): 588-594
Idiopathic pulmonary fibrosis (IPF) profoundly affects the quality of patients' lives. A systematic review was performed to evaluate critically the published literature and to examine what is known about health-related quality of life (HRQL) in patients with IPF.The MEDLINE, EMBASE, Health and Psychosocial Instruments, and Cochrane Library databases were searched to 1 April 2004. Abstracts and bibliographies of published articles were scanned and contact was made with investigators. Included studies analysed HRQL (or quality of life) in at least 10 patients with IPF. Two reviewers independently selected studies, evaluated their quality according to predetermined criteria, and abstracted data on study design, patients' demographic and clinical characteristics, and quality of life outcome measures.Seven studies met the inclusion criteria. The studies enrolled 512 patients with IPF and used three different instruments to measure HRQL. All studies had important limitations in methodological quality; none measured longitudinal changes in HRQL over time. Patients reported substantially impaired HRQL, especially in domains that measured physical health and level of independence. Patients with IPF appear to have similar impairments in HRQL to those with chronic obstructive pulmonary disease. Measures of dyspnoea were moderately correlated with scores from domains that measured physical health (R2 = 0.03-0.66) and energy/fatigue/pep (R2 = 0.19-0.55), but measures of pulmonary function and gas exchange did not correlate as strongly with these and other domains.Studies of HRQL in patients with IPF suggest that, in addition to the obvious effect on physical health, general health, energy level, respiratory symptoms, and level of independence are also impaired. Variability in HRQL among patients is not fully explained by measures of dyspnoea or pulmonary function, suggesting that HRQL measures provide unique information. More research is needed to identify or design appropriate measurement instruments for patients with IPF and to examine changes in HRQL over time or in response to specific treatments.
View details for DOI 10.1136/thx.2004.035220
View details for Web of Science ID 000230236800017
View details for PubMedID 15994268
View details for PubMedCentralID PMC1747452
Diagnosing occupational lung disease: a practical guide to the occupational pulmonary history for the primary care practitioner.
2005; 31 (1): 2-11
A well-executed occupational pulmonary history should be part of the evaluation of workers presenting with respiratory illnesses or symptoms. In this article, we review the scope of occupational lung disease and detail the essential elements of the occupational pulmonary history.
View details for PubMedID 15793319
Hospital ethics case consultations: practical guidelines.
2005; 31 (4): 279-283
Hospital ethics committees provide education, assist in policymaking, and deliver consultation services. In this article, we describe the structure, operation, and institutional framework within which an ethics committee fulfills its missions, with emphasis on the consultation process.
View details for PubMedID 16407608
Idiopathic pulmonary fibrosis - Challenges and opportunities for the clinician and investigator
2005; 127 (1): 275-283
Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and typically fatal interstitial lung disease. Besides its grave natural history and prognosis, three aspects of IPF challenge clinicians and investigators: (1) recent changes in the conceptual framework and definition of IPF complicate interpretation of prior clinical investigations; (2) while most patients with suspected IPF do not undergo open-lung biopsy, clinical definitions that do not include biopsy criteria have not been validated prospectively; and (3) available treatments have not been shown to be effective. To optimize clinical care and facilitate clinical investigation, a major goal of IPF research should be to develop validated sets of clinical diagnostic and prognostic criteria. Studies have shown the diagnostic value of high-resolution CT scans and identified important prognostic variables; many of these observations await prospective validation. While previous therapeutic studies have been limited by small sample sizes, lack of a placebo control group, and insufficient attention to patient-centered outcomes, the recent study of interferon gamma-1b demonstrated the feasibility of a large-scale, multicenter clinical trial in IPF. In this article, we discuss how overcoming challenges in IPF research will enable future investigators to conduct well-designed observational studies and clinical trials, whose meaningful results will advance our understanding of IPF, its management, and its impact on patients' lives.
View details for Web of Science ID 000226365200046
View details for PubMedID 15653995
Increasing referrals to telephone counseling for smoking cessation.
27th Annual Meeting of the Society-of-General-Internal-Medicine
SPRINGER. 2004: 167–168
View details for Web of Science ID 000221125800607
Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer - A meta-analysis
ANNALS OF INTERNAL MEDICINE
2003; 139 (11): 879-892
To compare the diagnostic accuracy of computed tomography (CT) and positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) for mediastinal staging in patients with non-small-cell lung cancer and to determine whether test results are conditionally dependent (the sensitivity and specificity of FDG-PET depend on the presence or absence of enlarged mediastinal lymph nodes on CT).Computerized search of MEDLINE, EMBASE, BIOSIS, and CancerLit through March 2003 and reference lists of retrieved studies and review articles.Studies in any language that examined FDG-PET for mediastinal staging in patients with known or suspected non-small-cell lung cancer, enrolled at least 10 participants (including at least 5 participants with mediastinal metastasis), and provided enough data to permit calculation of sensitivity and specificity for identifying lymph node involvement.One reviewer (of non-English-language studies) or 2 reviewers (of English-language studies) independently evaluated studies for inclusion, rated methodologic quality, and abstracted relevant data.Thirty-nine studies met inclusion criteria. Methodologic quality varied, but few aspects of study quality affected diagnostic accuracy. The authors constructed summary receiver-operating characteristic curves for CT and FDG-PET. Positron emission tomography with 18-fluorodeoxyglucose was more accurate than CT for identifying lymph node involvement (P < 0.001). For CT, median sensitivity and specificity were 61% (interquartile range, 50% to 71%) and 79% (interquartile range, 66% to 89%), respectively. For FDG-PET, median sensitivity and specificity were 85% (interquartile range, 67% to 91%) and 90% (interquartile range, 82% to 96%), respectively. Fourteen studies provided information about the conditional test performance of CT and FDG-PET. Positron emission tomography with 18-fluorodeoxyglucose was more sensitive but less specific when CT showed enlarged lymph nodes (median sensitivity, 100% [interquartile range, 90% to 100%]; median specificity, 78% [interquartile range, 68% to 100%]) than when CT showed no lymph node enlargement (median sensitivity, 82% [interquartile range, 65% to 100%]; median specificity, 93% [interquartile range, 92% to 100%]; P = 0.002).Positron emission tomography with 18-fluorodeoxyglucose is more accurate than CT for mediastinal staging. Positron emission tomography with 18-fluorodeoxyglucose is more sensitive but less specific when CT shows enlarged mediastinal lymph nodes.
View details for Web of Science ID 000186884800001
View details for PubMedID 14644890
Massive pulmonary pseudotumor
2003; 124 (2): 758-760
The term pulmonary pseudotumor may be used to describe a well-demarcated interlobar pleural effusion. Pseudotumors are located within pulmonary fissures and are commonly associated with congestive heart failure and other processes that cause transudative pleural effusions. Pseudotumors are typically diagnosed presumptively on chest radiographs based on their lenticular configuration. We report a case of a massive pseudotumor opacifying one third of the right hemithorax on a frontal radiograph. CT scan of the chest showed a loculated effusion within the oblique fissure measuring 10 x 5 cm. The Hounsfield unit characteristic of the effusion was similar to that of freely layering liquid in the contralateral hemithorax that was shown to be a transudate. The pseudotumor resolved with medical management over 8 weeks. This case proves that even a massive pulmonary pseudotumor will resolve with conservative management.
View details for Web of Science ID 000184801000052
View details for PubMedID 12907571
Efficacy trial of live, cold-adapted and inactivated influenza virus vaccines in older adults with chronic obstructive pulmonary disease: a VA cooperative study
2003; 21 (17-18): 2133-2144
We assessed whether trivalent live, cold-adapted influenza virus (CAIV-T) vaccine provides added protection when co-administered with trivalent inactivated influenza virus vaccine (TVV) in patients with chronic obstructive pulmonary disease (COPD). Subjects (N=2215) were randomly assigned to receive either TVV intramuscularly (IM) and CAIV-T intranasally (TC), or TVV and placebo (TP). The vaccines were well-tolerated. Efficacy of TC compared to TP was not statistically significant and was 0.16 for any influenza virus strain (95% confidence limit (CL): -0.22, 0.43), 0.26 for A (H3N2) virus (95% CL: -0.17, 0.53), and -0.05 for type B virus (95% CL: -1.13, 0.48). However, there was a possible advantage for TC over TP in reducing respiratory consequences of an influenza season measured by pulmonary function and symptoms at end of study.
View details for DOI 10.1016/S0264-410X(02)00748-X
View details for Web of Science ID 000183100200042
View details for PubMedID 12706704
Occupational lung disease Part 2. Discovering the cause of diffuse parenchymal lung disease
2003; 113 (4): 81-?
Diffuse parenchymal lung disease (also known as interstitial lung disease) and acute irritant reactions are much less commonly managed by primary care physicians than asthma. Acute irritant reactions are typically readily recognized because of the immediate exposure-response relationship. As with asthma, a diagnosis of diffuse parenchymal lung disease should prompt a careful review of the patient's work history. Findings from history taking and radiography provide most of the data needed to establish a diagnosis of asbestosis or silicosis. A pulmonologist should be consulted about lung disease that eludes diagnosis. In cases in which a link between work and illness is strongly suspected, an occupational medicine specialist may be consulted for assistance with preparing reports for a workers' compensation claim as well as characterizing and quantifying impairment. Various government agencies provide extensive information about specific toxic exposures and occupational lung diseases by telephone and on the World Wide Web.
View details for Web of Science ID 000205393800009
View details for PubMedID 12718237
- Occupational medicine A three-article symposium INTRODUCTION POSTGRADUATE MEDICINE 2003; 113 (4): 69
Occupational lung disease Part 1. Identifying work-related asthma and other disorders
2003; 113 (4): 70-?
Lung disease is prevalent among workers. Occupational toxicant exposures have an important role in many cases of lung disease seen in workers. Most occupational lung diseases can be grouped into one of four categories that include asthma and the diffuse parenchymal lung diseases (also known as interstitial lung disease). Asthma is especially prevalent among workers, and occupational factors should be explored in all adults with asthma. A worker's visit to a primary care physician often represents the first opportunity to establish a link between lung disease and the workplace. Therefore, it is important to maintain a high level of suspicion about the potential etiologic role of workplace exposures, especially in new cases of lung disease among workers. Although accumulating absolute proof of work-relatedness may not be possible, a brief occupational history and physical evaluation can provide substantial evidence to effectively rule out, or begin to rule in, a link between work and lung disease.
View details for Web of Science ID 000205393800008
View details for PubMedID 12718236
Lymphoid interstitial pneumonia - A narrative review
2002; 122 (6): 2150-2164
Lymphoid interstitial pneumonia (LIP) is regarded as both a disease and a nonneoplastic, inflammatory pulmonary reaction to various external stimuli or systemic diseases. It is an uncommon condition with incidence and prevalence rates that are largely unknown. Liebow and Carrington originally classified LIP as an idiopathic interstitial pneumonia in 1969. Although LIP had since been removed from that category, the most recent consensus classification sponsored by the American Thoracic Society and the European Respiratory Society recognizes that some cases remain idiopathic in origin, and its clinical, radiographic, and pathologic features warrant the return of LIP to its original classification among the idiopathic interstitial pneumonias. LIP also belongs within a spectrum of pulmonary lymphoproliferative disorders that range in severity from benign, small, airway-centered cellular aggregates to malignant lymphomas. It is characterized by diffuse hyperplasia of bronchus-associated lymphoid tissue. The dominant microscopic feature of LIP is a diffuse, polyclonal lymphoid cell infiltrate surrounding airways and expanding the lung interstitium. Classically, LIP occurs in association with autoimmune diseases, most often Sjögren syndrome. This has led to consideration of an autoimmune etiology for LIP, but its pathogenesis remains poorly understood. Persons who are seropositive for HIV, and children in particular, are at increased risk of acquiring LIP. Some studies suggest causal roles for both HIV and Epstein-Barr virus. The incidence of LIP is approximately twofold greater in women than men. The average age at diagnosis is between 52 years and 56 years. Symptoms of progressive cough and dyspnea predominate. There is great variability in the clinical course of LIP, from resolution without treatment to progressive respiratory failure and death. Although LIP is often regarded as a steroid-responsive condition, and oral corticosteroids continue to be the mainstay of therapy, response is unpredictable. Approximately 33 to 50% of patients die within 5 years of diagnosis, and approximately 5% of cases of LIP transform to lymphoma.
View details for Web of Science ID 000179985600047
View details for PubMedID 12475860
Occupational inhalant exposure and respiratory disorders among never-smokers referred to a hospital pulmonary function laboratory
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
2001; 322 (3): 121-?
Multiple reports have described associations between occupational inhalant exposure and lung disease. Previous occupational lung disease investigations have studied populations consisting of both smokers and nonsmokers. Smoking complicates interpretation of toxicant exposure-response relationships. The objective of this study was to determine whether, among never-smokers, occupational exposure to gases, dusts, or fumes is associated with a history of respiratory disorders and pulmonary function test defined obstructive lung disease.We performed a retrospective analysis of 517 never-smoker patients who underwent pulmonary function testing in our clinical laboratory between 1986 and 1999. We calculated the relative risks of developing adverse respiratory health outcomes given a history of exposure to occupational inhalants.Compared with persons with a negative occupational exposure history, exposed persons had an increased risk of reporting a history of bronchitis [relative risk (RR), 1.59; 95% confidence interval (CI), 1.20-2.12], recurrent lung infections (RR, 2.09; 95% CI, 1.14-3.82), and bronchodilator use (RR, 1.61; 95% CI, 1.26-2.06). There was also a statistically significant association between a history of inhalant exposure and the finding of an obstructive ventilatory defect on pulmonary function testing (RR, 1.79; 95% CI, 1.12-2.85). A history of inhalant exposure was not associated with self-reported asthma (RR, 1.08; 95% CI, 0.83-1.41). The population attributable risk estimates for respiratory disorders due to inhalant exposure were: bronchitis, 23.6%; recurrent lung infection, 36.3%; bronchodilator use, 24.3%; and obstructive lung disease, 29.6%.Occupational inhalant exposure is a strong risk factor for lung disease in this population of never smokers. A significant burden of respiratory disease in this population may be attributable to occupational inhalant exposure.
View details for Web of Science ID 000170971600001
View details for PubMedID 11570775
- Wegener's granulomatosis and the Churg-Strauss syndrome CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY 2001; 21 (1): 17-26
Occupational and environmental causes of bronchogenic carcinoma.
Current opinion in pulmonary medicine
2001; 7 (4): 220-225
Occupational and environmental carcinogens account for an important minority of cases of bronchogenic carcinoma. From a public health perspective, it is important to characterize occupational and environmental carcinogens and to define disease risk to reduce preventable lung cancer. From a clinician's perspective, it is important to distinguish individual cases of occupational lung cancer from nonoccupational cases, because cancer acquired from work may be compensable through worker's compensation claims and litigation. Important carcinogens include asbestos, radon daughters, diesel exhaust, and metals. Epidemiologic investigations identify excess cases of lung cancer in populations exposed to carcinogens. Experimental animal and ex vivo human research provide complementary information supporting causal relationships between exposure and carcinogenesis. Clinical challenges include proving that a given case of lung cancer is due to an occupational exposure. Research challenges include determining safe exposure thresholds. Only a small percentage of all chemicals used in industry have been extensively analyzed for their carcinogenic potential. Scientific and regulatory information about pulmonary occupational and environmental health and safety is available from several important agencies and organizations, including the Occupational Safety and Health Administration, the National Institute for Occupational Safety and Health, the International Agency for Research on Cancer, the American Lung Association, and the Environmental Protection Agency.
View details for PubMedID 11470978
Foreign body aspiration diagnosed by microscopy
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
2001; 322 (1): 44-47
We report a rare case of foreign body aspiration diagnosed by microscopic analysis of a sample of the foreign body. A 50-year-old man presented with a 5-month history of 40 pound weight loss and a nonresolving right lower lobe pneumonia. Medical history, radiographic studies, direct visualization of the foreign body by flexible fiberoptic bronchoscopy, and gross examination of a sample of the foreign body retrieved by a forceps biopsy catheter failed to yield the diagnosis. Moderate bleeding associated with the bronchoscopic "biopsy" procedure contributed to a preliminary misdiagnosis of endobronchial tumor. Microscopic analysis of the "biopsy" specimen demonstrated vegetable matter. The patient underwent rigid bronchoscopy and a peanut was retrieved from the bronchus intermedius. He was maintained on antibiotics for an additional 8 weeks and had complete clinical and radiographic recovery. The epidemiology, presentation, and management strategies of foreign body aspiration in the adult are briefly reviewed.
View details for Web of Science ID 000169860300008
View details for PubMedID 11465246
Improved quality of life among patients completing a pulmonary rehabilitation program: one center's early experience.
2001; 46 (6): 595-600
The conclusion of previous investigations that pulmonary rehabilitation (PR) is an effective intervention for the management of chronic lung disease may not be generalizable to PR programs with limited experience delivering this complex, interdisciplinary service.Determine whether PR is effective for the first group of patients treated in a newly formed interdisciplinary PR program.We conducted a longitudinal analysis of changes in health-related quality of life and 6-minute walk test for the first group of patients completing our newly formed 8-week outpatient PR program. We studied 6 men, age 65-77 years, with stable severe chronic obstructive pulmonary disease. Patients completed the Chronic Respiratory Disease Questionnaire immediately before and 1 year after participation in our PR program.Four patients completed the PR 6-minute walk test both before and after the program. We found improvement in all Chronic Respiratory Disease Questionnaire domains at follow-up (mean +/- SD before and after): dyspnea 1.67 +/- 0.82 vs 4.92 +/- 0.49; emotional function 2.33 +/- 0.82 vs 5.50 +/- 0.55; fatigue 2.00 +/- 0.63 vs 5.00 +/- 0.63; feeling of mastery over disease 1.83 +/- 0.41 vs 5.83 +/- 1.17. The interval improvements in all health-related quality of life domains were statistically significant (p < 0.02 for all comparisons). There was a trend toward improvement in exercise tolerance: 231 +/- 213 ft before PR vs 353 +/- 66 ft at the 1-year follow-up (p = 0.2).PR can result in sustained improvement in the quality of life of patients with severe chronic obstructive pulmonary disease, even when this complex, interdisciplinary service is delivered by a newly formed and inexperienced PR program.
View details for PubMedID 11353548
Risk of coronary artery disease in Veterans Affairs patients with sleep disordered breathing
AMER ACAD SLEEP MEDICINE. 2001: A290–A290
View details for Web of Science ID 000168230900500
- Adjuvant chemotherapy for completely resected non-small-cell lung cancer. The New England journal of medicine 2001; 344 (9): 689-90
Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions - A meta-analysis
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
2001; 285 (7): 914-924
Focal pulmonary lesions are commonly encountered in clinical practice, and positron emission tomography (PET) with the glucose analog 18-fluorodeoxyglucose (FDG) may be an accurate test for identifying malignant lesions.To estimate the diagnostic accuracy of FDG-PET for malignant focal pulmonary lesions.Studies published between January 1966 and September 2000 in the MEDLINE and CANCERLIT databases; reference lists of identified studies; abstracts from recent conference proceedings; and direct contact with investigators.Studies that examined FDG-PET or FDG with a modified gamma camera in coincidence mode for diagnosis of focal pulmonary lesions; enrolled at least 10 participants with pulmonary nodules or masses, including at least 5 participants with malignant lesions; and presented sufficient data to permit calculation of sensitivity and specificity were included in the analysis.Two reviewers independently assessed study quality and abstracted data regarding prevalence of malignancy and sensitivity and specificity of the imaging test. Disagreements were resolved by discussion.We used a meta-analytic method to construct summary receiver operating characteristic curves. Forty studies met inclusion criteria. Study methodological quality was fair. Sample sizes were small and blinding was often incomplete. For 1474 focal pulmonary lesions of any size, the maximum joint sensitivity and specificity (the upper left point on the receiver operating characteristic curve at which sensitivity and specificity are equal) of FDG-PET was 91.2% (95% confidence interval, 89.1%-92.9%). In current practice, FDG-PET operates at a point on the summary receiver operating characteristic curve that corresponds approximately to a sensitivity and specificity of 96.8% and 77.8%, respectively. There was no difference in diagnostic accuracy for pulmonary nodules compared with lesions of any size (P =.43), for semiquantitative methods of image interpretation compared with qualitative methods (P =.52), or for FDG-PET compared with FDG imaging with a modified gamma camera in coincidence mode (P =.19).Positron emission tomography with 18-fluorodeoxyglucose is an accurate noninvasive imaging test for diagnosis of pulmonary nodules and larger mass lesions, although few data exist for nodules smaller than 1 cm in diameter. In current practice, FDG-PET has high sensitivity and intermediate specificity for malignancy.
View details for PubMedID 11180735
- Endobronchial pneumocystis carinii pneumonia J Bronchol 2001; 8: 197-199
- The case of the burping man J Respir Dis 2001; 22: 323-325
Benzocaine-associated methemoglobinemia following bronchoscopy in a healthy research participant.
2000; 45 (8): 953-956
Benzocaine (ethyl aminobenzoate) is a local anesthetic commonly used to achieve topical anesthesia of the skin and mucous membranes prior to endoscopic procedures. Methemoglobinemia, a condition in which hemoglobin cannot bind and deliver oxygen normally, has been associated with benzocaine use in various patient populations. This is the first report of benzocaine-associated methemoglobinemia occurring in a healthy research participant. The research participant developed a methemoglobin level of 27% and marked cyanosis. No adverse sequelae other than cyanosis were identified. This report extends the population in which benzocaine-associated methemoglobinemia has been described. Additionally, this report supports the observation that methemoglobin levels approaching 30% may be tolerated in otherwise healthy individuals, producing few clinically important effects. Finally, this case also indicates that, in obtaining informed consent for a procedure in which benzocaine will be administered, patients and research participants should be specifically informed of the risk of benzocaine-induced methemoglobinemia. This information is especially important in those settings in which the manufacturer-recommended dose of benzocaine may either intentionally or inadvertently be exceeded.
View details for PubMedID 10963319
- Reanalysis of Blanc PD et al, "Use of herbal products, coffee or black tea, and over-the-counter medications as self treatments among adults with asthma" JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2000; 106 (1): 196-196
Massive esophageal variceal hemorrhage triggered by complicated endotracheal intubation
JOURNAL OF EMERGENCY MEDICINE
2000; 18 (3): 317-322
Esophageal variceal hemorrhage is frequently a catastrophic event. The specific events that trigger variceal rupture are not well understood. Acute elevations in systemic blood pressure and increased splanchnic blood flow, however, may lead to increased intravariceal pressure followed by variceal rupture and hemorrhage. This report describes a strong temporal association between complicated endotracheal intubation and abrupt onset of life-threatening variceal hemorrhage. A 52-year-old man with a history of portal hypertension was intubated emergently for airway protection because of respiratory insufficiency due to sepsis. Intubation was complicated by initial inadvertent esophageal intubation and by a peak mean arterial blood pressure of 155 mmHg. At the conclusion of the procedure, the patient sustained large volume hematemesis due to esophageal variceal rupture. This case suggests a risk of triggering variceal hemorrhage as a result of intubation-induced increase in blood pressure. A number of agents, including fentanyl, have been shown to be effective in attenuating the cardiovascular response to intubation. This case report provides strong evidence in support of administering fentanyl, or a suitable alternative adjunctive medication, before intubation of patients with documented portal hypertension and a history of esophageal variceal hemorrhage.
View details for Web of Science ID 000085977500005
View details for PubMedID 10729669
- Pressure to publish in the premedical years JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 2000; 283 (3): 340-340
- Asthma guidelines: An assessment of physician understanding and practice AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2000; 161 (1): 330-330
Fine particulate air pollution (PM2.5) and medical visits for lower respiratory tract illness among children in Santiago, Chile.
LIPPINCOTT WILLIAMS & WILKINS. 2000: 96A
View details for Web of Science ID 000086346600528
- What exactly is flock worker's lung? CHEST 2000; 117 (1): 10-13
Role of systemic beta(2) agonists in treatment of asthma - Response
2000; 107 (1): 23-23
View details for Web of Science ID 000084692500009
Clinical and chest radiographic findings among persons with sputum culture positive for Mycobacterium gordonae - A review of 19 cases
2000; 117 (1): 96-102
To describe the clinical and radiographic findings associated with growth of Mycobacterium gordonae in cultured sputum and to determine the proportion of cases that fulfill criteria for nontuberculous mycobacterial pulmonary disease as established by the American Thoracic Society.A retrospective review of charts and radiographs of all patients from whom M gordonae was isolated from sputum cultures between November 1996 and June 1998.University-affiliated Veterans Affairs hospital.Nineteen patients were identified with sputum culture positive for M gordonae. All patients had a chest radiograph within 1 month of sputum culture.Sixteen patients (84%) had suppressed local and/or general immunity. Sixteen patients (84%) had respiratory symptoms, weight loss, fever, or night sweats as an indication for chest radiography. Seventeen patients (89%) had abnormal chest radiographs; however, no typical radiographic pattern was observed. No patient met diagnostic criteria for nontuberculous mycobacterial pulmonary disease as delineated by the American Thoracic Society. All patients with abnormal chest radiographs and/or respiratory symptoms ultimately had alternative explanations for their pulmonary disease.There is a broad spectrum of chest radiographic findings among persons with sputum culture positive for M gordonae, arguing against the presence of a characteristic chest radiograph in this patient population. M gordonae is usually a nonpathogenic colonizing organism, even among persons with local or general immune suppression and abnormal chest radiograph findings.
View details for Web of Science ID 000084774400020
View details for PubMedID 10631205
From Ware G. Kuschner, MD.
MedGenMed : Medscape general medicine
View details for PubMedID 11104434
From Ware G. Kuschner, MD.
MedGenMed : Medscape general medicine
View details for PubMedID 11104437
Lessons Learned From the Terminally, Critically Ill Patient Who Demands to Live as Long as Possible.
MedGenMed : Medscape general medicine
A 67-year-old man with metastatic pancreatic cancer was admitted to the hospital for terminal care. The patient requested intensive medical support in order "to live as long as possible." Management goals included preserving end-of-life autonomy; therefore, life-extending treatments were delivered as he had adamantly requested. Simultaneously, there was agreement among physicians that futile treatments were unwarranted. Discussions with the power of attorney did not alter medical management. Elements of a "Fair Process Approach to Futility," published in March 1999 by the American Medical Association (AMA) Council on Ethical and Judicial Affairs, were utilized in an attempt to achieve conflict resolution. Medical subspecialist and ethics committee consultations had contributory roles in resolving conflict between the patient and patient surrogate and the patient's physicians. This case offers the following lessons: 1.Potential conflicts in end-of-life care management philosophy should be addressed early in the patient-physician relationship. 2.Patients and surrogates should be made aware that physicians are under no obligation to provide futile care. 3.Futile or medically inappropriate care should not be offered "theoretically" with the expectation that it will be refused. 4.The Advance Directive can guide end-of-life care but does not substitute for physician judgements. 5.A "fair process" end-of-life care management algorithm can provide limited structure to the process of patient-physician deliberation and conflict resolution.
View details for PubMedID 11104417
Ten asthma pearls every primary care physician should know
1999; 106 (3): 99-104
Asthma is often easily identified and effectively treated. However, presenting symptoms are variable, and many cases of asthma may not be obvious or typical. Since asthma affects about 5% of the US population, primary care physicians should be prepared to identify and manage both atypical and classic types. Atypical symptoms include disturbed sleep, chest tightness, and persistent cough without audible wheezing. Occupational factors should be suspected in all cases of adult-onset asthma. The patient's history and results of simple pulmonary function tests are useful in diagnosing, staging, and managing asthma. A beta 2 agonist delivered by metered-dose inhaler (e.g., albuterol) should provide prompt relief of most exacerbations. Inhaled corticosteroid therapy delivered via a spacer helps prevent exacerbations and has an important role in long-term control of moderate and severe asthma. If symptoms do not improve with the use of standard asthma medications, alternative diagnoses should be considered.
View details for Web of Science ID 000082485900013
View details for PubMedID 10494268
Usefulness of positron emission tomography imaging in the management of lung cancer.
Current opinion in pulmonary medicine
1999; 5 (4): 201-207
Positron emission tomography imaging is useful for the characterization of the solitary pulmonary nodule and mediastinal staging. Potential future applications include extrathoracic staging to help to determine the ideal site for possible tissue diagnosis, to guide treatment plans, and to monitor the response to therapy and recurrence. Positron emission tomography may also predict prognosis. This review discusses the uses of positron emission tomography, the current literature, and the clinical guidelines for positron emission tomography imaging.
View details for PubMedID 10407687
Pulse delivered oxygen system and quality of life in COPD
AMER LUNG ASSOC. 1999: A818
View details for Web of Science ID 000082237104562
Quality of life among patients completing a pulmonary rehabilitation program: One center's early experience.
AMER LUNG ASSOC. 1999: A312
View details for Web of Science ID 000082237101690
Occupational asthma - Practical points for diagnosis and management
WESTERN JOURNAL OF MEDICINE
1998; 169 (6): 342-350
Asthma is a common chronic illness characterized by episodes of reversible airflow obstruction. A cornerstone of asthma management is identifying and avoiding agents that cause bronchospasm. The workplace is an important potential source of respirable exposures that can cause or trigger asthma. Identification of an occupational factor in asthma is important: early diagnosis and removal of the worker from the exposure is associated with improved prognosis; the diagnosis of occupational asthma may lead to compensation for work-related impairment and disability; and the diagnosis of occupational asthma is a Sentinel Health Event with implications for public health and prevention. In this article, we review specific causes of occupational asthma and general settings in which an occupational factor should be suspected and explored as part of the management of the worker with asthma. We also review specific and simple elements of history and pulmonary function testing that can be easily assessed by most health care practitioners and may be sufficient to establish a diagnosis of occupational asthma. Finally, we review the medical-legal implications of occupational asthma.
View details for Web of Science ID 000077582000002
View details for PubMedID 9866431
- Nonprescription bronchodilator use in asthma CHEST 1998; 114 (2): 657-658
Tumor necrosis factor-alpha and interleukin-8 release from u937 human mononuclear cells exposed to zinc oxide in vitro - Mechanistic implications for metal fume fever
JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
1998; 40 (5): 454-459
Respiratory exposure to zinc oxide results in metal fume fever, a flu-like illness characterized by dose-dependent increases in pulmonary tumor necrosis factor-alpha (TNF) and interleukin-8 (IL-8). To examine whether mononuclear cells are a source of these proinflammatory cytokines, we exposed U937 cells to zinc oxide in vitro. Cell culture supernatant TNF and IL-8 was measured after 3, 8, and 24 hours of exposure to zinc oxide in varying concentrations. Zinc oxide exposure in vitro led to TNF release in a dose-dependent manner at 3, 8, and 24 hours (analysis of variance [ANOVA] P = 0.0001). IL-8 demonstrated a statistically significant zinc exposure response at 8 hours (ANOVA P = 0.005) and 24 hours (ANOVA P = 0.02). IL-8 at 8 hours correlated with 3-hour TNF levels (r = 0.52, P = 0.04). These data demonstrate that in vitro zinc oxide exposure stimulates U937 mononuclear cells to release TNF and IL-8 consistent with in vivo observations in metal fume fever.
View details for Web of Science ID 000074242300008
View details for PubMedID 9604183
- Neoplasms other than Bronchogenic Carcinoma identified on PET scan. Am J Resp Crit Care Med Suppl 1998:157(3)A320 1998; 157 (3): A320
Use of herbal products, coffee or black tea, and over-the-counter medications as self-treatments among adults with asthma
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
1997; 100 (6): 789-791
There are few data on the use of alternative therapies in adult asthma and their impact on health outcomes.The objective of this study was to study the prevalence and morbidity of asthma self-treatment with herbs, coffee or black tea, and over-the-counter (OTC) medications containing ephedrine or epinephrine.We carried out a cross-sectional analysis of interview data for 601 adults with asthma recruited from a random sample of pulmonary and allergy specialists. We estimated the 12-month prevalence of reported use of herbal products, coffee or black tea, or OTC products to self-treat asthma and their association with emergency department visits and hospitalization.Herbal asthma self-treatment was reported by 46 (8%; 95% confidence interval [CI] 6% to 10%); coffee or black tea self-treatment by 36 (6%; 95% CI 4% to 8%), epinephrine or ephedrine OTC use by 36 (6%; 95% CI 4% to 8%), and any of the three practices by 98 subjects (16%; 95% CI 13% to 19%). Adjusting for demographic and illness covariates, herbal use (odds ratio [OR] 2.5; 95% CI 1.1 to 5.6) and coffee or black tea use (OR 3.1; 95% CI 1.2 to 7.8) were associated with asthma hospitalization; OTC use was not (OR 0.8; 95% CI 0.3 to 2.5).Even among adults with access to specialty care for asthma, self-treatment with nonprescription products was common and was associated with increased risk of reported hospitalization. This association does not appear to be accounted for by illness severity or other disease covariates. It may reflect delay in utilization of more efficacious treatments.
View details for Web of Science ID 000071353600012
View details for PubMedID 9438488
Human pulmonary responses to experimental inhalation of high concentration fine and ultrafine magnesium oxide particles
ENVIRONMENTAL HEALTH PERSPECTIVES
1997; 105 (11): 1234-1237
Exposure to air polluted with particles less than 2.5 micron in size is associated epidemiologically with adverse cardiopulmonary health consequences in humans. The goal of this study was to characterize human pulmonary responses to controlled experimental high-dose exposure to fine and ultrafine magnesium oxide particles. We quantified bronchoalveolar lavage (BAL) cell and cytokine concentrations, pulmonary function, and peripheral blood neutrophil concentrations in six healthy volunteers 18 to 20 hr after inhalation of fine and ultrafine magnesium oxide particles produced from a furnace system model. We compared postexposure studies with control studies from the same six subjects. Mean +/- standard deviation (SD) cumulative magnesium dose was 4,138 +/- 2,163 min x mg/m3. By weight, 28% of fume particles were ultrafine (<0.1 micron in diameter) and over 98% of fume particles were fine (<2.5 micron in diameter). There were no significant differences in BAL inflammatory cell concentrations, BAL interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor, pulmonary function, or peripheral blood neutrophil concentrations postexposure compared with control. Our findings suggest that high-dose fine and ultrafine magnesium oxide particle exposure does not produce a measurable pulmonary inflammatory response. These findings are in marked contrast with the well-described pulmonary inflammatory response following zinc oxide particle inhalation. We conclude that fine and ultrafine particle inhalation does not result in toxicity in a generic manner independent of particle composition. Our findings support the concept that particle chemical composition, in addition to particle size, is an important determinant of respiratory effects.
View details for Web of Science ID 000072815000018
View details for PubMedID 9370520
View details for PubMedCentralID PMC1470327
Nonprescription bronchodilator medication use in asthma
1997; 112 (4): 987-993
Many persons with asthma self-medicate with widely available and potentially hazardous nonprescription medicines. This study assessed the demographic and clinical covariates of self-treatment with over-the-counter asthma medications (OTCs).We conducted an analytical investigation using questionnaires and measures of lung function, comparing OTC and prescription medication users. We recruited adults with asthma by public advertisement.We studied 22 exclusive prescription asthma medication users, 15 exclusive OTC users, and 13 other subjects who combined prescription medication use with self-treatment with asthma OTCs. All but one OTC user self-medicated with a nonselective, sympathomimetic metered-dose inhaler.Taking income, access to care, and self-assessed disease severity into account, male gender was strongly associated with exclusive OTC use alone (odds ratio [OR]=8.9, 95% confidence interval [CI]= 1.3 to 61) and mixed OTC-prescription medication use (OR=9.7, 95% CI=1.1 to 83). The covariates of income, access to care, and self-assessed disease severity provided significant additional explanatory power to the model of exclusive OTC use (model chi2 difference 11.3, 5 df, p<0.05). Pulmonary function was similar among OTC and prescription medication users. However, prescription medication users' self-assessed asthma severity (mild compared to more severe) was associated with postbronchodilator reversibility of FEV1 obstruction (6% vs 18% reversibility, p<0.05) while exclusive OTC users' self-assessed severity showed the reverse pattern (19% vs 8%, p=0.2).Asthma education programs attempting to discourage unregulated bronchodilator use should give consideration to this profile of the "asthmatic-at-risk."
View details for Web of Science ID A1997YA35100022
View details for PubMedID 9377963
Early pulmonary cytokine responses to zinc oxide fume inhalation
1997; 75 (1): 7-11
Zinc oxide inhalation causes metal fume fever, a flu-like syndrome common among welders. Proinflammatory pulmonary cytokines play a role in mediating this occupational illness. The goal of this investigation was to characterize early pulmonary cytokine responses after experimental human exposure to inhaled purified zinc oxide fume. We quantified bronchoalveolar lavage (BAL) cytokine concentrations in 15 healthy volunteers 3 hr after inhalation of zinc oxide fume. We compared postexposure cytokine responses with postsham exposure responses in the same 15 subjects. We also compared cytokine responses with those of 14 "late follow-up" subjects previously studied by BAL 20 hr after zinc oxide fume exposure. Zinc oxide exposure was a statistically significant, dose-dependent predictor of increases in BAL TNF (mean exposure-sham difference +/- SE = 9.5 +/- 3.6 pg/mL, P = 0.02), IL-6 (mean exposure-sham difference +/- SE = 5.5 +/- 1.8 pg/mL, P = 0.009), and IL-8 (mean exposure-sham difference +/- SE = 64.1 +/- 23.9 pg/mL, P = 0.02). The TNF response was significantly greater at 3 hr follow-up compared with 20 hr follow-up, after adjusting for smoking status, zinc dose, and BAL macrophages (P = 0.004). Our findings provide evidence for a pulmonary inflammatory response 3 hr after inhalation of zinc oxide fume characterized by dose-dependent increases in BAL proinflammatory cytokine concentrations. These data indicate that TNF plays an important initial role in mediating metal fume fever.
View details for Web of Science ID A1997YC20300002
View details for PubMedID 9356189
Pulmonary responses after wood chip mulch exposure
JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
1997; 39 (4): 308-314
Organic Dust Toxic Syndrome (ODTS) is a flu-like syndrome that can occur after inhalation of cotton, grain, wood chip dusts, or other organic dusts or aerosols. We investigated whether inflammatory pulmonary responses occur, even after relatively brief, low-level wood chip mulch exposure. Six volunteers were exposed to wood chip mulch dust. Total dust and/or endotoxin levels were measured in five subjects. Pulmonary function and peripheral blood counts were measured before and after exposure in each subject. Bronchoalveolar lavage (BAL) was performed in each subject after exposure, and cell, cytokine, and protein concentrations were measured. Control BAL without previous exposure was also performed on three of the subjects. Three of six subjects had symptoms consistent with ODTS. No clinically relevant or statistically significant changes in pulmonary function tests after exposure were found. Three subjects manifested a marked elevation in neutrophil percentage in their BAL (range, 10 to 57%). When these three subjects underwent control BAL, the postexposure comparison demonstrated an increase in neutrophil levels of 154 +/- 89 x 10(3)/mL (mean +/- standard error; P = 0.22). The mean increase in BAL interleukin-8 levels after exposure, compared with paired control values, was 11.2 +/- SE 2.5 pg/mL (P = 0.047). There was also an increase in BAL interleukin-6 levels that reached borderline significance (6.4 +/- SE 2.0 pg/mL; P = 0.08). Tumor necrosis factor levels were increased in all three subjects' BAL as well (0.4 +/- SE 0.2 pg/mL), but this change was not statistically significant (P = 0.2). Our findings of increased BAL proinflammatory cytokine and neutrophil levels are consistent with the theory that cytokine networking in the lung may mediate ODTS.
View details for Web of Science ID A1997WU65500006
View details for PubMedID 9113600
Dose-dependent cigarette smoking-related inflammatory responses in healthy adults
EUROPEAN RESPIRATORY JOURNAL
1996; 9 (10): 1989-1994
The aim of this study was to determine the dose-response relationship between cigarette smoke exposure and pulmonary cell and cytokine concentrations in bronchoalveolar lavage (BAL). BAL cells and BAL supernatant concentrations of tumour necrosis factor-alpha (TNF alpha), interleukin (IL)-1 beta, IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1 from 14 healthy smokers and 16 healthy nonsmokers were quantified. Statistically greater concentrations of neutrophils, macrophages, IL-1 beta, IL-6, IL-8 and MCP-1 were observed among smokers compared with nonsmokers (p < or = 0.0007 in all cases). Cigarette smoking, categorized ordinally as: less than one pack, one pack, or greater than one pack per day, was predictive of BAL macrophages (p < 0.0001), neutrophils (p = 0.015), IL-1 beta (p < 0.001) and IL-8 (p = 0.02). We conclude that concentrations of macrophages, neutrophils, IL-1 beta and IL-8 are elevated in the pulmonary microenvironment of smokers in a cigarette dose-dependent manner. Based on the present findings, we would caution against simple analyses that treat current smokers as a homogeneous group and which do not account for smoking intensity.
View details for Web of Science ID A1996VL73700005
View details for PubMedID 8902455
Exaggerated responses to chlorine inhalation among persons with nonspecific airway hyperreactivity
1996; 109 (2): 331-337
Although chlorine gas is a common irritant exposure, little is known about airway responses to chlorine inhalation among persons with baseline airway hyperreactivity. We wished to determine whether such persons manifest an exaggerated response to chlorine compared with normal subjects. We studied 10 subjects, five with and five without airway hyperresponsiveness (HR) after exposure to 1.0 ppm chlorine and five persons, all with HR, to 0.4 ppm chlorine. After 1.0 ppm inhalation, there was a significant (p < 0.05) fall (mean +/- SE) in FEV1 immediately following exposure among normal (-180 +/- 37 mL) and HR subjects (-520 +/- 171 mL). The fall was greater among the HR compared with the normal subjects (p = 0.04). Specific airway resistance (Sraw) increased to a greater degree among the HR group compared with normal subjects (p = 0.04). Among all subjects (n = 10), the proportional change in FEV1 after 1.0 ppm chlorine correlated with baseline reactivity (Spearman rank correlation r = 0.64, p < 0.05). At 24-h follow-up, there were no significant chlorine-related pulmonary function deficits. After 0.4 ppm chlorine inhalation, there was no significant pulmonary function effect. These data indicated that persons with hyperreactive airways manifest an exaggerated airway response to chlorine at 1.0 ppm. This suggests that when large numbers of persons are exposed to chlorine, a susceptible subpopulation may acutely respond with a greater decrement in pulmonary function.
View details for Web of Science ID A1996TV42900012
View details for PubMedID 8620701
PULMONARY RESPONSES TO PURIFIED ZINC-OXIDE FUME
JOURNAL OF INVESTIGATIVE MEDICINE
1995; 43 (4): 371-378
Metal fume fever is a flu-like illness caused by zinc oxide fume inhalation and mediated by unknown mechanisms. It is one of a group of work-related febrile inhalational syndromes. We studied bronchoalveolar lavage (BAL) obtained from cigarette smoking and nonsmoking human volunteers after controlled exposure to purified zinc oxide fume to explore the possible roles of proinflammatory cytokines in this condition.We studied 14 volunteers after inhalation exposure to purified zinc oxide fume and after sham exposure to air. The mean cumulative exposure was 537 +/- 232 mg min per cubic meter elemental zinc. Twenty hours after exposure we performed BAL. We analyzed BAL cells and studied BAL supernatant for cytokines including tumor necrosis factor-alpha (TNF alpha), interleukin(IL)-8, and IL-1 by enzyme-linked immunosorbant assay (ELISA).Polymorphonuclear leukocytes (PMNs) were significantly increased in the BAL fluid obtained post-exposure compared to sham (mean difference = 41.3 +/- 16.8 x 10(3) per mL; p < 0.05). Cumulative zinc exposure positively correlated with exposure-sham differences in BAL supernatant concentrations of both TNF (r2 = 0.58; p = .002) and IL-8 (r2 = 0.44, p = 0.01). Exposure-sham concentration differences in BAL supernatant IL-8 and BAL PMNs were also positively correlated (r2 = 0.60; p < 0.001). Cigarette smoking was not associated with exposure-sham differences in BAL TNF or IL-8, but did demonstrate a packs-per-day dependent increase in BAL supernatant IL-1 (t = 2.3, p = 0.04) post-exposure compared to sham, after taking into account the zinc exposure response.Purified zinc oxide fume inhalation causes an exposure-dependent increase in proinflammatory cytokines and PMNs in the lung. This supports a role for cytokine networking in mediating metal fume fever.
View details for Web of Science ID A1995RT74600006
View details for PubMedID 7552586
A SENSITIVE NEW BIOASSAY FOR TUMOR-NECROSIS-FACTOR
JOURNAL OF IMMUNOLOGICAL METHODS
1994; 175 (2): 181-187
Tumor necrosis factor is an important cytokine involved in inflammation and assay of this cytokine in biological fluids may be important in the understanding of several disease processes. This report describes an improved TNF bioassay employing a newly isolated subclone of the cell line NCTC-clone 929 as well as a novel fluorescence indicator system for detecting viability of the target cells. The limit of detection for the TNF hypersensitive cell line with this fluorescence viability assay was 68 +/- 2.5 fg/ml, which is approximately 3 x more sensitive than the parental clone and approximately 10 x more sensitive than that reported by Branch et al. (1991) using the neutral red indicator system. The hypersensitivity of the clone gradually declined over a 45-day period and at regular intervals new cells were cultivated from frozen stocks. Two different serum sources, bovine fetal serum and horse serum, and four different serum concentrations (5, 10, 15, 20%) were evaluated to optimize sensitivity. No difference was found between serum sources but sensitivity was significantly reduced if < 15% serum was used.
View details for Web of Science ID A1994PN07300004
View details for PubMedID 7930647
- QUANTIFYING LYMPHOCYTES IN BRONCHOALVEOLAR LAVAGE FLUID ANNALS OF INTERNAL MEDICINE 1993; 119 (10): 1050-1051