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Publication Record


Per cent emphysema is associated with respiratory and lung cancer mortality in the general population: a cohort study.
Oelsner EC, Carr JJ, Enright PL, Hoffman EA, Folsom AR, Kawut SM, Kronmal RA, Lederer DJ, Lima JA, Lovasi GS, Smith BM, Shea SJ, Barr RG
(2016) Thorax 71: 624-32
MeSH Terms: Aged, Aged, 80 and over, Cause of Death, Female, Humans, Lung Neoplasms, Male, Middle Aged, Prognosis, Pulmonary Emphysema, Respiratory Function Tests, Respiratory Tract Diseases, Risk Factors, Smoking, Tomography, X-Ray Computed
Show Abstract · Added September 29, 2016
BACKGROUND - Emphysema on CT is a risk factor for all-cause mortality in persons with and without airflow obstruction; however, causes of death associated with emphysema remain uncertain, particularly in the general population.
AIMS - To test associations between quantitatively assessed emphysema on CT and cause of death in persons with and without a substantial smoking history.
METHODS - The Multi-Ethnic Study of Atherosclerosis recruited 6814 participants, aged 45-84 years and without clinical cardiovascular disease, in 2000-2002. Per cent emphysema was defined on cardiac CT as per cent of lung voxels less than -950 Hounsfield units; emphysema on CT was defined as per cent emphysema above the upper limit of normal. Cause of death was classified by administrative codes. Proportional-hazards models were adjusted for age, race/ethnicity, gender, body mass index, smoking status, pack-years, coronary artery calcium, site and education. Additional adjustment for lung function was made in a subset with spirometry from 2004 to 2006.
RESULTS - There were 1091 deaths over 12 years median follow-up. Emphysema on CT was strongly associated with increased mortality due to respiratory diseases (adjusted HR 2.94, 95% CI 1.68 to 5.15), particularly chronic lower respiratory diseases (adjusted HR 9.54, 95% CI 4.70 to 19.35), and lung cancer (adjusted HR 1.84, 95% CI 1.09 to 3.12), but not cardiovascular disease. Associations persisted among participants with fewer than 10 pack-years and those without physician-diagnosed respiratory disease, and were similar after adjustment for airflow measures and in persons without airflow limitation.
CONCLUSIONS - Quantitatively assessed emphysema on CT is associated with greater respiratory disease and lung cancer mortality, even among persons without traditional risk factors.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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1 Members
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15 MeSH Terms
Flu-like and Other Systemic Drug Reactions Among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study.
Sterling TR, Moro RN, Borisov AS, Phillips E, Shepherd G, Adkinson NF, Weis S, Ho C, Villarino ME, Tuberculosis Trials Consortium
(2015) Clin Infect Dis 61: 527-35
MeSH Terms: Adolescent, Adult, Antitubercular Agents, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Isoniazid, Latent Tuberculosis, Male, Middle Aged, Prospective Studies, Respiratory Tract Diseases, Rifampin
Show Abstract · Added February 17, 2016
BACKGROUND - Weekly rifapentine plus isoniazid for 3 months (3HP) is as effective as daily isoniazid for 9 months (9H) for latent tuberculosis infection in high-risk persons, but there have been reports of possible flu-like syndrome.
METHODS - We identified clinically significant systemic drug reactions (SDR) and evaluated risk factors in patients who did not complete treatment in the PREVENT Tuberculosis study.
RESULTS - Among 7552 persons who received ≥ 1 dose of study drug, 153 had a SDR: 138/3893 (3.5%) with 3HP vs 15/3659 (0.4%) with 9H (P < .001). In the 3HP arm, 87 (63%) had flu-like syndrome and 23 (17%) had cutaneous reactions; 13/3893 (0.3%) had severe reactions (6 were hypotensive) and 6 reported syncope. Symptoms occurred after a median of 3 doses, and 4 hours after the dose; median time to resolution was 24 hours. There were no deaths. In multivariate logistic regression analysis, factors independently associated with SDR included receipt of 3HP (adjusted odds ratio [aOR] 9.4; 95% confidence interval [CI], 5.5, 16.2), white non-Hispanic race/ethnicity (aOR 3.3; 95% CI, 2.3, 4.7), female sex (aOR 2.0; 95% CI, 1.4, 2.9), age ≥ 35 years (aOR 2.0; 95% CI, 1.4, 2.9), and lower body mass index (body mass index [BMI]; P = .009). In a separate multivariate analysis among persons who received 3HP, severe SDR were associated with white non-Hispanic race/ethnicity (aOR 5.4; 95% CI, 1.8, 16.3), and receipt of concomitant non-study medications (aOR 5.9; 95% CI, 1.3, 27.1).
CONCLUSIONS - SDR were more common with 3HP, and mostly flu-like. Persons of white race, female sex, older age, and lower BMI were at increased risk. Severe reactions were rare and associated with 3HP, concomitant medication, and white race. The underlying mechanism is unclear.
Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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13 MeSH Terms
Burden of total and cause-specific mortality related to tobacco smoking among adults aged ≥ 45 years in Asia: a pooled analysis of 21 cohorts.
Zheng W, McLerran DF, Rolland BA, Fu Z, Boffetta P, He J, Gupta PC, Ramadas K, Tsugane S, Irie F, Tamakoshi A, Gao YT, Koh WP, Shu XO, Ozasa K, Nishino Y, Tsuji I, Tanaka H, Chen CJ, Yuan JM, Ahn YO, Yoo KY, Ahsan H, Pan WH, Qiao YL, Gu D, Pednekar MS, Sauvaget C, Sawada N, Sairenchi T, Yang G, Wang R, Xiang YB, Ohishi W, Kakizaki M, Watanabe T, Oze I, You SL, Sugawara Y, Butler LM, Kim DH, Park SK, Parvez F, Chuang SY, Fan JH, Shen CY, Chen Y, Grant EJ, Lee JE, Sinha R, Matsuo K, Thornquist M, Inoue M, Feng Z, Kang D, Potter JD
(2014) PLoS Med 11: e1001631
MeSH Terms: Adult, Asia, Cardiovascular Diseases, Cost of Illness, Female, Humans, Male, Middle Aged, Neoplasms, Prevalence, Respiratory Tract Diseases, Risk, Risk Factors, Smoking
Show Abstract · Added February 16, 2015
BACKGROUND - Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest.
METHODS AND FINDINGS - We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan-accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37-1.51) and 1.48-fold (1.38-1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%-17.2%) and 3.3% (2.6%-4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000-1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y.
CONCLUSIONS - Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented. Please see later in the article for the Editors' Summary.
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14 MeSH Terms
Update in interventional pulmonology: a prologue to a new review series.
Maldonado F, Edell ES, Barron PJ, Yung RC
(2014) Respirology 19: 471
MeSH Terms: Bronchoscopy, Disease Management, Humans, Inventions, Models, Educational, Needs Assessment, Pulmonary Medicine, Respiratory Tract Diseases
Added July 28, 2015
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8 MeSH Terms
Achieving competency in bronchoscopy: challenges and opportunities.
Fielding DI, Maldonado F, Murgu S
(2014) Respirology 19: 472-82
MeSH Terms: Bronchoscopy, Clinical Competence, Computer Simulation, Education, Medical, Graduate, Educational Measurement, Educational Status, Humans, Problem-Based Learning, Pulmonary Medicine, Respiratory Tract Diseases, United States
Show Abstract · Added July 28, 2015
Bronchoscopy education is undergoing significant changes in step with other medical and surgical specialties that seek to incorporate simulation-based training and objective measurement of procedural skills into training programmes. Low- and high-fidelity simulators are now available and allow learners to gain fundamental bronchoscopy skills in a zero-risk environment. Testing trainees on simulators is currently possible by using validated assessment tools for both essential bronchoscopy and endobronchial ultrasound skills, and more tools are under development for other bronchoscopic techniques. Educational concepts including the 'flipped classroom' model and problem-based learning exercises are increasingly used in bronchoscopy training programmes. These learner-centric teaching modalities require well-trained educators, which is possible thorough the expansion of existing faculty development programmes.
© 2014 Asian Pacific Society of Respirology.
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11 MeSH Terms
Impact of home environment interventions on the risk of influenza-associated ARI in Andean children: observations from a prospective household-based cohort study.
Budge PJ, Griffin MR, Edwards KM, Williams JV, Verastegui H, Hartinger SM, Mäusezahl D, Johnson M, Klemenc JM, Zhu Y, Gil AI, Lanata CF, Grigalva CG, RESPIRA PERU Group
(2014) PLoS One 9: e91247
MeSH Terms: Acute Disease, Cohort Studies, Environment, Female, Housing, Humans, Incidence, Infant, Male, Orthomyxoviridae, Peru, Prospective Studies, Respiratory Tract Diseases, Risk Factors
Show Abstract · Added May 28, 2014
BACKGROUND - The Respiratory Infections in Andean Peruvian Children (RESPIRA-PERU) study enrolled children who participated in a community-cluster randomized trial of improved stoves, solar water disinfection, and kitchen sinks (IHIP trial) and children from additional Andean households. We quantified the burden of influenza-associated acute respiratory illness (ARI) in this household-based cohort.
METHODS - From May 2009 to September 2011, we conducted active weekly ARI surveillance in 892 children age <3 years, of whom 272 (30.5%) had participated in the IHIP trial. We collected nasal swabs during ARI, tested for influenza and other respiratory viruses by RT-PCR, and determined influenza incidence and risk factors using mixed-effects regression models.
RESULTS - The overall incidence of influenza-associated ARI was 36.6/100 child-years; incidence of influenza A, B, and C was 20.5, 8.7, and 5.2/100 child-years, respectively. Influenza C was associated with fewer days of subjective fever (median 1 vs. 2) and malaise (median 0 vs. 2) compared to influenza A. Non-influenza ARI also resulted in fewer days of fever and malaise, and fewer healthcare visits than influenza A-associated ARI. Influenza incidence varied by calendar year (80% occurred in the 2010 season) and IHIP trial participation. Among households that participated in the IHIP trial, influenza-associated ARI incidence was significantly lower in intervention than in control households (RR 0.40, 95% CI: 0.20-0.82).
CONCLUSIONS - Influenza burden is high among Andean children. ARI associated with influenza A and B had longer symptom duration and higher healthcare utilization than influenza C-associated ARI or non-influenza ARI. Environmental community interventions may reduce influenza morbidity.
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14 MeSH Terms
Are respiratory complications common causes of death in inflammatory myopathies? An autopsy study.
Maldonado F, Patel RR, Iyer VN, Yi ES, Ryu JH
(2012) Respirology 17: 455-60
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Autopsy, Cardiovascular Diseases, Cause of Death, Dermatomyositis, Disease Progression, Female, Humans, Male, Middle Aged, Polymyositis, Respiratory Tract Diseases, Retrospective Studies, Young Adult
Show Abstract · Added February 1, 2016
BACKGROUND AND OBJECTIVE - Polymyositis (PM) and dermatomyositis (DM) are idiopathic inflammatory myopathies that are associated with a variety of clinical manifestations including pulmonary complications. The objective of the present study was to determine the causes of deaths in this complex patient population.
METHODS - A computer-assisted search of medical and autopsy records identified a total of 39 patients with either PM or DM who underwent an autopsy at the Mayo Clinic (Rochester, MN, USA) over a 29-year period from 1 January 1981 to 31 December 2009. The immediate causes of death along with contributing causes were determined by reviewing all available clinical data and autopsy findings. We also analysed the discordance between ante-mortem clinical diagnoses provided by clinicians and the final diagnosis by the post-mortem analysis.
RESULTS - Respiratory (33%), infectious (28%) and cardiovascular diseases (26%) accounted for the majority of immediate causes of death. Acute exacerbation of chronic interstitial lung disease (15%) and bronchopneumonia (15%) were the most common specific causes. Immediate cause of death was not suspected in nearly one third of cases and included bronchopneumonia, sepsis, acute myocardial infarction, aspiration pneumonia, pulmonary embolism, aortic stenosis, mycotic aneurysm rupture and acute haemoperitoneum.
CONCLUSIONS - We conclude that pulmonary injury is the immediate cause of death in one third of patients with PM/DM; acute exacerbation of chronic interstitial lung disease and bronchopneumonia were the most common specific causes. Immediate cause of death was not established ante-mortem in nearly one third of cases, and some of these causes were treatable.
© 2011 The Authors. Respirology © 2011 Asian Pacific Society of Respirology.
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17 MeSH Terms
Long-term non-cancer mortality in pediatric and young adult cancer survivors in Finland.
Prasad PK, Signorello LB, Friedman DL, Boice JD, Pukkala E
(2012) Pediatr Blood Cancer 58: 421-7
MeSH Terms: Adolescent, Adult, Cardiovascular Diseases, Cause of Death, Child, Child, Preschool, Female, Finland, Humans, Infant, Infant, Newborn, Male, Mortality, Neoplasms, Respiratory Tract Diseases, Survivors, Young Adult
Show Abstract · Added March 27, 2014
BACKGROUND - Excess late mortality has been reported among pediatric cancer survivors, but there is a need to further establish risk profiles for non-cancer death and to examine cause-specific mortality among survivors of young adult cancers.
PROCEDURES - In a nationwide record linkage study in Finland, we identified 9,245 5-year cancer survivors diagnosed before age 35 and treated between 1966 and 1999, and followed them for mortality endpoints from 1971 to 2008. Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were calculated to compare the observed number of deaths with those expected in the general Finnish population. Primary endpoints included death from cardiovascular and respiratory diseases; death from malignant diseases was excluded.
RESULTS - Non-malignant disease mortality in the cohort was 90% higher (SMR=1.9, 95% CI: 1.7-2.2) than expected, with SMRs for circulatory and respiratory disease similarly elevated (SMR=1.9, 95% CI: 1.5-2.3 and SMR=2.3, 95% CI: 1.3-3.8, respectively). Important differences were noted amongst patient subgroups, with risk greatest for survivors of central nervous system (CNS) cancer, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL). The SMR's for circulatory disease were 6.6 (95% CI: 4.8-8.9) for HL and 4.8 (95% CI: 2.6-8.1) for NHL for the entire population; but these risks remained elevated for survivors diagnosed between 15 and 34 years of age.
CONCLUSIONS - Previous studies have shown that there is an elevated risk of non-cancer mortality in childhood cancer survivors; this is one of the first studies that show an increase in cardiovascular and respiratory mortality in long-term survivors of adolescent and young adult cancers.
Copyright © 2011 Wiley Periodicals, Inc.
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17 MeSH Terms
Real-world comparison of two molecular methods for detection of respiratory viruses.
Ali SA, Gern JE, Hartert TV, Edwards KM, Griffin MR, Miller EK, Gebretsadik T, Pappas T, Lee WM, Williams JV
(2011) Virol J 8: 332
MeSH Terms: Clinical Laboratory Techniques, Female, Humans, Infant, Male, Molecular Diagnostic Techniques, Nasal Mucosa, Pharynx, Respiratory Tract Diseases, Virology, Virus Diseases, Viruses
Show Abstract · Added December 10, 2013
BACKGROUND - Molecular polymerase chain reaction (PCR) based assays are increasingly used to diagnose viral respiratory infections and conduct epidemiology studies. Molecular assays have generally been evaluated by comparing them to conventional direct fluorescent antibody (DFA) or viral culture techniques, with few published direct comparisons between molecular methods or between institutions. We sought to perform a real-world comparison of two molecular respiratory viral diagnostic methods between two experienced respiratory virus research laboratories.
METHODS - We tested nasal and throat swab specimens obtained from 225 infants with respiratory illness for 11 common respiratory viruses using both a multiplex assay (Respiratory MultiCode-PLx Assay [RMA]) and individual real-time RT-PCR (RT-rtPCR).
RESULTS - Both assays detected viruses in more than 70% of specimens, but there was discordance. The RMA assay detected significantly more human metapneumovirus (HMPV) and respiratory syncytial virus (RSV), while RT-rtPCR detected significantly more influenza A. We speculated that primer differences accounted for these discrepancies and redesigned the primers and probes for influenza A in the RMA assay, and for HMPV and RSV in the RT-rtPCR assay. The tests were then repeated and again compared. The new primers led to improved detection of HMPV and RSV by RT-rtPCR assay, but the RMA assay remained similar in terms of influenza detection.
CONCLUSIONS - Given the absence of a gold standard, clinical and research laboratories should regularly correlate the results of molecular assays with other PCR based assays, other laboratories, and with standard virologic methods to ensure consistency and accuracy.
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12 MeSH Terms
Population-based incidence of human metapneumovirus infection among hospitalized children.
Williams JV, Edwards KM, Weinberg GA, Griffin MR, Hall CB, Zhu Y, Szilagyi PG, Wang CK, Yang CF, Silva D, Ye D, Spaete RR, Crowe JE
(2010) J Infect Dis 201: 1890-8
MeSH Terms: Child, Hospitalized, Child, Preschool, Female, Genotype, Humans, Incidence, Infant, Infant, Newborn, Male, Metapneumovirus, Nose, Paramyxoviridae Infections, Pharynx, Prospective Studies, RNA, Viral, Respiratory Tract Diseases, Reverse Transcriptase Polymerase Chain Reaction, United States
Show Abstract · Added December 10, 2013
BACKGROUND - Human metapneumovirus (HMPV) is a leading cause of acute respiratory illness (ARI) in children. Population-based incidence rates and comprehensive clinical characterizations of disease have not been established.
METHODS - We conducted population-based prospective surveillance for 2 years in 2 US counties of HMPV infection among children <5 years old who were hospitalized with ARI or fever. Nasal and throat specimens obtained with swabs were tested for HMPV by real-time reverse-transcription polymerase chain reaction and genotyped.
RESULTS - Forty-two (3.8%) of 1104 children tested positive for HMPV. The overall annual rate of HMPV-associated hospitalizations per 1000 children <5 years old was 1.2 (95% confidence interval [CI], 0.9-1.6). This rate was highest among infants 0-5 months old (4.9 per 1000 [95% CI, 2.9-7.2]), followed by children 6-11 months old (2.9 per 1000 [95% CI, 1.4-4.7]). The annual rate of hospitalization for HMPV infection was less than that for respiratory syncytial virus infection but similar to that for influenza and parainfluenza virus 3 infection in all age groups. The mean age of children hospitalized with HMPV infection was 6 months. Bronchiolitis, pneumonia, and asthma were the most common diagnoses among children with HMPV infection. All 4 HMPV subgroups were detected during both years at both sites. HPMV infection was most prominent from March through May.
CONCLUSION - HMPV was detected in 3.8% of children hospitalized with ARI or fever, with a population incidence similar to that of influenza virus and parainfluenza virus 3.
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18 MeSH Terms