Publications by authors named "Paul D Blanc"

155 Publications

Smoking, occupational exposures, and idiopathic pulmonary fibrosis among Swedish construction workers.

Am J Ind Med 2021 Feb 5. Epub 2021 Feb 5.

Department of Public Health and Clinical Medicine, Sustainable Health, Umeå University, Umeå, Sweden.

Background: Cigarette smoking and occupational exposures each have been reported to increase the risk of idiopathic pulmonary fibrosis (IPF), a disease previously considered of unknown origin. We investigated the risk of IPF mortality associated with combined smoking and occupational exposures.

Methods: A registry study of Swedish construction workers (N = 389,132), linked baseline smoking and occupational data with registry data on cause of death and hospital care diagnoses. Occupation was classified by the likelihood of exposure to vapors, gases, dusts, or fumes using a job-exposure matrix. Those likely exposed to asbestos or silica were excluded from the analysis. Age-adjusted relative risks [RRs] were calculated using Poisson regression. Follow-up observation began at age 40 and ended at age 89.

Results: Heavy smokers at baseline who were exposed to inorganic dusts during their working life had an increased risk of IPF mortality (RR 1.70; 95% confidence interval [CI] 1.11-2.60), while there was no statistically increased risk in the other exposure groups. There were dose-response relationships between smoking at baseline and IPF mortality among both unexposed and dust exposed workers, with similar risk for dust exposed and unexposed, except among baseline heavy smokers, where workers exposed to inorganic dust manifested the highest risk (RR 4.22; 95% CI 2.69-6.60). Excluding workers with chronic obstructive pulmonary disease or emphysema did not affect the results substantively.

Conclusion: A clear dose-response relationship was seen between smoking at baseline and IPF, supporting a causal relationship. Occupational exposure to inorganic dusts, excluding silica and asbestos, was associated with increased risk of IPF in baseline heavy current smokers.
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http://dx.doi.org/10.1002/ajim.23231DOI Listing
February 2021

Smoking practices in relation to exhaled carbon monoxide in an occupational cohort.

BMC Public Health 2020 Dec 9;20(1):1894. Epub 2020 Dec 9.

University of California San Francisco, Suite 609, 350 Parnassus Avenue, San Francisco, CA, 94117, USA.

Background: Exposure to carbon monoxide (CO) remains a leading occupational hazard in firefighters, but cigarette and waterpipe smoking likely contributes to the other sources of CO in such workers. The aim of this study was to estimate the contribution of self-reported active cigarette smoking, waterpipe use, and potential job-related sources of CO to the level of exhaled CO in firefighters.

Methods: We surveyed the personnel of 18 fire stations (N = 842), median age 28 years, who participated at an annual screening not timed to coincide with recent firefighting. We surveyed smoking and waterpipe history, exposure to secondhand smoke (SHS), use of coal for health and biomass for cooking and time since last exposure to firefighting in the workplace. We measured exhaled CO with an instantaneous reading device (piCO Smokerlyzer). We used multivariable regression models to test the association of time since last smoked cigarette (≤12 h) and waterpipe (≤12 h) and time since last fire (≤6 h) with exhaled CO.

Results: In analysis limited to men (93.5% of all surveyed), 42% were daily cigarette; 1% were waterpipe smokers; 94% were exposed to SHS, 29% used coal for heating and 4% used biomass for cooking. The median CO was 4 (interquartile range 3;8) ppm. Age (beta 0.74 per 10 years, p < 0.001), use of biomass fuel for cooking (beta 1.38, p = 0.05), cigarette smoked in the last 12 h (beta 8.22, p < 0.001), waterpipe smoked in the last 12 h (beta 23.10, p < 0.001) were statistically associated with CO, but not time since last fire (≤6 h) (beta 4.12, p = 0.12). There was a significant interaction between older age and firefighting for exhaled CO (p = 0.03).

Conclusions: Cigarette and recent waterpipe smoking are associated with increased exhaled CO in firefighters. Firefighting itself was a less potent contributor to exhaled CO when measured at an annual screening, but an age interaction was manifested.
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http://dx.doi.org/10.1186/s12889-020-09997-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725030PMC
December 2020

Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts.

Ann Am Thorac Soc 2021 02;18(2):238-246

Barcelona Institute of Global Health, Barcelona, Spain.

Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up. To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking. A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV and the FEV/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts. Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.
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http://dx.doi.org/10.1513/AnnalsATS.202002-113OCDOI Listing
February 2021

Occupation environmental factors in hypersensitivity pneumonitis: population attributable fraction.

ERJ Open Res 2020 Oct 5;6(4). Epub 2020 Oct 5.

Division of Pulmonary and Critical Care, Dept of Medicine, University of California, San Francisco, CA, USA.

Background: Despite well-documented case series of hypersensitivity pneumonitis (HP), epidemiological data delineating relative contributions of risk factors are sparse. To address this, we estimated HP risk in a case-referent study of occupational and nonoccupational exposures.

Methods: We recruited cases of HP by ICD-9 codes from an integrated healthcare delivery system (IHCDS) and a tertiary medical care centre. We drew referents, matched for age and sex, from the IHCDS. Participants underwent comprehensive, structured telephone interviews eliciting details of occupational and home environmental exposures. We employed a hierarchical analytic approach for data reduction based on the false discovery rate method within clusters of exposures. We measured lung function and selected biomarkers in a subset of participants. We used multivariate logistic regression to estimate exposure-associated odds ratios (ORs) and population attributable fractions (PAFs) for HP.

Results: We analysed data for 192 HP cases (148 IHCDS; 44 tertiary care) and 229 referents. Occupational exposures combined more than doubled the odds of developing HP (OR 2.67; 95% CI 1.73-4.14) with a PAF of 34% (95% CI 21-46%); nonoccupational bird exposure also doubled the HP odds (OR 2.02; 95% CI 1.13-3.60), with a PAF of 12% (3-21%). Lung function and selected biomarkers did not substantively modify the risk estimates on the basis of questionnaire data alone.

Discussion: In a case-referent approach evaluating HP risk, identifiable exposures accounted, on an epidemiological basis, for approximately two in three cases of disease; conversely, for one in three, the risk factors for disease remained elusive.
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http://dx.doi.org/10.1183/23120541.00374-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533383PMC
October 2020

Cycle Threshold to Test Positivity in COVID-19 for Return to Work Clearance in Health Care Workers.

J Occup Environ Med 2020 11;62(11):889-891

Occupational and Employee Health Section and Infectious Disease Section, Medical Service and Laboratory Medicine Service, San Francisco Veterans Affairs Health Care System (Ms Domeracki, Dr Clapp, Mr Taylor, Dr Lu, Dr Lampiris, Dr Blanc); Occupational and Environmental Health Nursing, Community Health Systems, School of Nursing (Ms Domeracki); Division of Occupational and Environmental Medicine (Dr Clapp, Dr Blanc); Department of Laboratory Medicine (Dr Lu); and Division of Infectious Disease (Dr Lampiris), Department of Medicine, University of California San Francisco, San Francisco, California.

Objective: To ascertain whether reverse transcriptase polymerase chain reaction (RT-PCR) cycle amplifications until detection, the cycle threshold (Ct), could help inform return to work (RTW) strategies for health care workers (HCWs) recovering from COVID-19 infection.

Methods: Sequential Ct data from COVID-19 nasal pharyngeal (NP) RT-PCR testing in all COVID-19 positive HCWs at a single institution. Analysis of Ct in relation to time until negative testing for RTW clearance.

Results: Data for 12 employees showed that time elapsed until RT-PCR test-based RTW clearance ranged from 7 to 57 days (median, 34.5 days). Lower initial Ct correlated with the total time elapsed until clearance (r = -0.80; P = 0.002).

Conclusion: Considering the RT-PCR Ct, which correlates with the estimated viral load, may help inform RTW planning and decision making beyond solely relying on dichotomized positive/negative results.
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http://dx.doi.org/10.1097/JOM.0000000000001996DOI Listing
November 2020

Primary graft dysfunction attenuates improvements in health-related quality of life after lung transplantation, but not disability or depression.

Am J Transplant 2021 02 5;21(2):815-824. Epub 2020 Sep 5.

Division of Pulmonary and Critical Care, Department of Medicine, School of Medicine, University of California, San Francisco, California, USA.

Disability, depressive symptoms, and impaired health-related quality of life (HRQL) are common among patients with life-threatening respiratory compromise. We sought to determine if primary graft dysfunction (PGD), a syndrome of acute lung injury, attenuates improvements in patient-reported outcomes after transplantation. In a single-center prospective cohort, we assessed disability, depressive symptoms, and HRQL before and at 3- to 6-month intervals after lung transplantation. We estimated the magnitude of change in disability, depressive symptoms, and HRQL with hierarchical segmented linear mixed-effects models. Among 251 lung transplant recipients, 50 developed PGD Grade 3. Regardless of PGD severity, participants had improvements in disability and depressive symptoms, as well as generic-physical, generic-mental, respiratory-specific, and health-utility HRQL, exceeding 1- to 4-fold the minimally clinically important difference across all instruments. Participants with PGD Grade 3 had a lower magnitude of improvement in generic-physical HRQL and health-utility than in all other participants. Among participants with PGD Grade 3, prolonged mechanical ventilation was associated with greater attenuation of improvements. PGD remains a threat to the 2 primary aims of lung transplantation, extending survival and improving HRQL. Attenuation of improvement persists long after hospital discharge. Future studies should assess if interventions can mitigate the impact of PGD on patient-reported outcomes.
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http://dx.doi.org/10.1111/ajt.16257DOI Listing
February 2021

Gamma-Butyrolactone Overdose Potentially Complicated by Co-Ingestion of Industrial Solvent N-Methyl-2-pyrrolidone.

J Anal Toxicol 2020 Jul 16. Epub 2020 Jul 16.

Department of Emergency Medicine, Baylor College of Medicine.

Gamma-hydroxybutyrate (GHB) is misused as an intoxicant, either alone or concurrently with other substances. Because GHB is illegal, the precursor chemicals 1,4-butanediol and gamma-butyrolactone are also misused for the same effect, either through pre-ingestion alteration or endogenous metabolism to GHB. We describe a case of a 50-year-old-man with a history of polysubstance misuse who experienced an overdose of GHB from gamma-butyrolactone ingestion. The patient also co-ingested a common industrial solvent, N-methyl-2-pyrrolidone (NMP). This co-ingested substance raised theoretical concern of metabolism to a GHB congener, underscoring that the emergence of new psychoactive substance use patterns requires ongoing vigilance and toxicologic confirmation.
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http://dx.doi.org/10.1093/jat/bkaa076DOI Listing
July 2020

Inhaled Corticosteroids Use and Risk of Invasive Pneumococcal Disease in a Population-based Study.

Ann Am Thorac Soc 2020 12;17(12):1570-1575

School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

The use of inhaled corticosteroids (ICS) is associated with increased pneumonia risk, but the risk of invasive pneumococcal disease (IPD) associated with ICS is not characterized. The aim was to test the hypothesis that the use of ICS increases the risk of IPD. Cases were persons 20-65 years of age included in a Swedish national registry of invasive infection caused by classified as any IPD as well as the subset of IPD with pneumonia. The case index date was the day the infection was diagnosed. Six control subjects for each case (matched for sex, age, and region) were selected from the Swedish National Population Registry and were assigned the index date of their corresponding case. Current and past users of ICS were defined by the last prescriptions dispensed within 60 or 61-365 days of the index date. Nonusers were defined as those with no dispensed prescription the last 365 days. Current users were characterized by use of fluticasone or budesonide. We used conditional logistic analysis, including matching and covariates, to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of IPD, IPD with pneumonia, and IPD without pneumonia associated with current or past use of ICS. Current use of ICS increased the risk for IPD and IPD with pneumonia (OR, 1.71; 95% CI, 1.39-2.10 and OR, 1.94; 95% CI, 1.53-2.47, respectively), but there was no statistical association between current use of ICS and IPD without pneumonia (OR, 1.18; 95% CI 0.78-1.80). Past use of ICS increased the risk for IPD and IPD with pneumonia but not for IPD without pneumonia. Among current ICS users, the odds for IPD were similar for budesonide (OR, 1.34; 95% CI, 1.14-1.57) and fluticasone (OR, 1.41; 95% CI, 1.04-1.90). Among current ICS users, the odds for IPD with pneumonia were slightly higher but of similar magnitude for both budesonide and for fluticasone. ICS use is associated with an increased risk of IPD and IPD with pneumonia. The risk is driven by IPD with pneumonia. We found similar risks for budesonide and fluticasone.
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http://dx.doi.org/10.1513/AnnalsATS.202004-352OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706606PMC
December 2020

Military Deployment and Respiratory Symptoms: Some Answers, Many Questions.

Chest 2020 Jun;157(6):1407-1408

Occupational and Environmental Medicine, San Francisco VA Health Care System, San Francisco, CA; Department of Medicine, University of California San Francisco School of Medicine, San Francisco, CA.

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http://dx.doi.org/10.1016/j.chest.2020.02.023DOI Listing
June 2020

Frailty after lung transplantation is associated with impaired health-related quality of life and mortality.

Thorax 2020 08 6;75(8):669-678. Epub 2020 May 6.

Medicine, University of California San Francisco, San Francisco, California, USA.

Background: Lung transplantation and related medications are associated with pathobiological changes that can induce frailty, a state of decreased physiological reserve. Causes of persistent or emergent frailty after lung transplantation, and whether such transplant-related frailty is associated with key outcomes, are unknown.

Methods: Frailty and health-related quality of life (HRQL) were prospectively measured repeatedly for up to 3 years after lung transplantation. Frailty, quantified by the Short Physical Performance Battery (SPPB), was tested as a time-dependent binary and continuous predictor. The association of transplant-related frailty with HRQL and mortality was evaluated using mixed effects and Cox regression models, respectively, adjusting for age, sex, ethnicity, diagnosis, and for body mass index and lung function as time-dependent covariates. We tested the association between measures of body composition, malnutrition, renal dysfunction and immunosuppressants on the development of frailty using mixed effects models with time-dependent predictors and lagged frailty outcomes.

Results: Among 259 adults (56% male; mean age 55.9±12.3 years), transplant-related frailty was associated with lower HRQL. Frailty was also associated with a 2.5-fold higher mortality risk (HR 2.51; 95% CI 1.21 to 5.23). Further, each 1-point worsening in SPPB was associated, on average, with a 13% higher mortality risk (HR 1.13; 95% CI 1.04 to 1.23). Secondarily, we found that sarcopenia, underweight and obesity, malnutrition, and renal dysfunction were associated with the development of frailty after transplant.

Conclusions: Transplant-related frailty is associated with lower HRQL and higher mortality in lung recipients. Abnormal body composition, malnutrition and renal dysfunction may contribute to the development of frailty after transplant. Confirming the role of these potential contributors and developing interventions to mitigate frailty may improve lung transplant success.
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http://dx.doi.org/10.1136/thoraxjnl-2019-213988DOI Listing
August 2020

Occupational exposure to dust and to fumes, work as a welder and invasive pneumococcal disease risk.

Occup Environ Med 2020 02 17;77(2):57-63. Epub 2019 Dec 17.

Occupational and Environmental medicine, School of Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Objectives: Occupational exposures to metal fumes have been associated with increased pneumonia risk, but the risk of invasive pneumococcal disease (IPD) has not been characterised previously.

Methods: We studied 4438 cases aged 20-65 from a Swedish registry of invasive infection caused by . The case index date was the date the infection was diagnosed. Six controls for each case, matched for gender, age and region of residency, were selected from the Swedish population registry. Each control was assigned the index date of their corresponding case to define the study observation period. We linked cases and controls to the Swedish registries for socioeconomic status (SES), occupational history and hospital discharge. We applied a job-exposure matrix to characterise occupational exposures. We used conditional logistic analyses, adjusted for comorbidities and SES, to estimate the OR of IPD and the subgroup pneumonia-IPD, associated with selected occupations and exposures in the year preceding the index date.

Results: Welders manifested increased risk of IPD (OR 2.99, 95% CI 2.09 to 4.30). Occupational exposures to fumes and silica dust were associated with elevated odds of IPD (OR 1.11, 95% CI 1.01 to 1.21 and OR 1.33, 95% CI 1.11 to 1.58, respectively). Risk associated with IPD with pneumonia followed a similar pattern with the highest occupational odds observed among welders and among silica dust exposed.

Conclusion: Work specifically as a welder, but also occupational exposures more broadly, increase the odds for IPD. Welders, and potentially others with relevant exposures, should be offered pneumococcal vaccination.
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http://dx.doi.org/10.1136/oemed-2019-106175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029234PMC
February 2020

Tacrolimus trough monitoring guided by mass spectrometry without accounting for assay differences is associated with acute kidney injury in lung transplant recipients.

Am J Health Syst Pharm 2019 12;76(24):2019-2027

Division of Pulmonary and Critical Care, Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA.

Purpose: Tacrolimus is a nephrotoxic immunosuppressant historically monitored via enzyme-based immunoassay (IA). After 2011, the 2 largest laboratory companies in the United States implemented tacrolimus quantification by liquid chromatography-mass spectrometry (LC-MS); this method excludes metabolites, potentially resulting in lower quantified drug concentrations. We sought to determine if tacrolimus therapeutic drug monitoring via LC-MS, as performed using trough targets originally derived from IA values, influences clinical outcomes.

Methods: In a single-center retrospective cohort study of lung transplant recipients, risks of acute kidney injury, acute renal failure, and new-onset diabetes after transplantation, as well as chronic lung allograft dysfunction-free survival, were compared in 82 subjects monitored by LC-MS and 102 subjects monitored by IA using Cox proportional hazard models adjusted for age, sex, baseline renal function, and race.

Results: LC-MS-based monitoring was associated with a greater risk of acute kidney injury (adjusted hazard ratio, 1.65; 95% confidence interval, 1.02-2.67). No statistically significant differences in risks of acute renal failure and new-onset diabetes after transplantation were observed.

Conclusion: Although LC-MS provides a more accurate representation of the blood concentration of the parent compound tacrolimus exclusive of metabolite, established cut points for tacrolimus dosing may need to be adjusted to account for the increased risk of renal injury.
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http://dx.doi.org/10.1093/ajhp/zxz243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170730PMC
December 2019

What has been done will be done again.

Authors:
Paul D Blanc

Respirology 2019 12 30;24(12):1125-1126. Epub 2019 Oct 30.

Division of Occupational and Environmental Medicine, University of California San Francisco, San Francisco, CA, USA.

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http://dx.doi.org/10.1111/resp.13724DOI Listing
December 2019

Shoulder Injury Related to Vaccine Administration (SIRVA): An Occupational Case Report.

Workplace Health Saf 2019 Oct 20;67(10):501-505. Epub 2019 Sep 20.

University of California, San Francisco.

Transient shoulder pain is a common complaint following intramuscular vaccine administration into the deltoid. More severe vaccination-associated shoulder complications comprising of weakness and decreased range of motion are categorized under the construct "shoulder injury related to vaccine administration" (SIRVA) that subsumes both subjective and objective findings consistent with injury. We describe the presentation and management of a case of SIRVA in a health care worker following seasonal influenza vaccine administration as part of a hospital-based employee health program and review the relevant biomedical literature. We present a case from a single medical center. All data were collected by professionals in occupational health by interviewing, performing physical examinations, and reviewing medical records associated with the injured worker. Severe pain and limited range of shoulder motion developed following an influenza vaccination that was administered using a poorly positioned, larger than recommended needle. Magnetic resonance imaging (MRI) demonstrated moderate glenohumeral joint effusion and synovitis, with fluid accumulating in the subscapularis recess within 1 week of injury. At 8 months after initial injury, MRI showed persistent mild tenosynovitis of the long head of the biceps tendon, interval accumulation of a large glenohumeral joint effusion, and infraspinatus tendinitis with subjacent reactive bone marrow edema. The affected worker experienced work restrictions but had no complete lost workdays to date due to the injury. Occupationally related SIRVA is a preventable adverse event that should be considered in workplace vaccine administration programs, and appropriate education and training provided to vaccine administrators to address this.
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http://dx.doi.org/10.1177/2165079919875161DOI Listing
October 2019

Respiratory Health after Military Service in Southwest Asia and Afghanistan. An Official American Thoracic Society Workshop Report.

Ann Am Thorac Soc 2019 08;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: ) identifying key studies assessing postdeployment respiratory health, ) describing emerging research, and ) 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.
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http://dx.doi.org/10.1513/AnnalsATS.201904-344WSDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774741PMC
August 2019

The Occupational Burden of Nonmalignant Respiratory Diseases. An Official American Thoracic Society and European Respiratory Society Statement.

Am J Respir Crit Care Med 2019 06;199(11):1312-1334

Workplace inhalational hazards remain common worldwide, even though they are ameliorable. Previous American Thoracic Society documents have assessed the contribution of workplace exposures to asthma and chronic obstructive pulmonary disease on a population level, but not to other chronic respiratory diseases. The goal of this document is to report an in-depth literature review and data synthesis of the occupational contribution to the burden of the major nonmalignant respiratory diseases, including airway diseases; interstitial fibrosis; hypersensitivity pneumonitis; other noninfectious granulomatous lung diseases, including sarcoidosis; and selected respiratory infections. Relevant literature was identified for each respiratory condition. The occupational population attributable fraction (PAF) was estimated for those conditions for which there were sufficient population-based studies to allow pooled estimates. For the other conditions, the occupational burden of disease was estimated on the basis of attribution in case series, incidence rate ratios, or attributable fraction within an exposed group. Workplace exposures contribute substantially to the burden of multiple chronic respiratory diseases, including asthma (PAF, 16%); chronic obstructive pulmonary disease (PAF, 14%); chronic bronchitis (PAF, 13%); idiopathic pulmonary fibrosis (PAF, 26%); hypersensitivity pneumonitis (occupational burden, 19%); other granulomatous diseases, including sarcoidosis (occupational burden, 30%); pulmonary alveolar proteinosis (occupational burden, 29%); tuberculosis (occupational burden, 2.3% in silica-exposed workers and 1% in healthcare workers); and community-acquired pneumonia in working-age adults (PAF, 10%). Workplace exposures contribute to the burden of disease across a range of nonmalignant lung conditions in adults (in addition to the 100% burden for the classic occupational pneumoconioses). This burden has important clinical, research, and policy implications. There is a pressing need to improve clinical recognition and public health awareness of the contribution of occupational factors across a range of nonmalignant respiratory diseases.
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http://dx.doi.org/10.1164/rccm.201904-0717STDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543721PMC
June 2019

Prevalence of Arthritis and Rheumatoid Arthritis in Coal Mining Counties of the United States.

Arthritis Care Res (Hoboken) 2019 09 7;71(9):1209-1215. Epub 2019 Aug 7.

University of California, San Francisco and the San Francisco Veterans Affairs Health Care System, San Francisco, California.

Objective: Exposure to inhaled mineral dust, in particular silica, is associated with increased odds of rheumatoid arthritis (RA) and other autoimmune diseases. We studied the association of RA with work-related coal and silica exposure in the Appalachian region of the US.

Methods: We carried out a random-digit dialed telephone survey in selected counties in Appalachia that had elevated coal workers' pneumoconiosis mortality. Our study cohort included men ages ≥50 with any employment history, and we assessed exposure to coal mining employment, other work-related dust, and ergonomic factors. We ascertained self-reported physician diagnosis of any arthritis and of RA with glucocorticoid treatment. We used multivariable logistic regression analysis to estimate the odds ratios (ORs) and associated population attributable fraction (PAF) estimates.

Results: Among the 973 men who met study entry criteria (mean ± SD ages 66 ± 10 years; 54% ever smokers), 266 (27%) reported coal mining work and 189 (19%) reported other work-related silica exposure. There were 517 men (53%), who reported any arthritis and 112 (12%) whose disease met the study definition of RA. Adjusting for covariates, coal mining was associated with elevated odds of RA (OR 3.6 [95% confidence interval (95% CI) 2.1-6.2]), which accounted for a PAF of 33% (95% CI 26-40%) of the men studied. For any arthritis, the coal mining-associated OR was 2.3 (95% CI 1.6-3.2), with an associated PAF of 20% (95% CI 14-25%).

Conclusion: In this population of older males living in a coal mining region, we estimated that 20% of arthritis and 33% of RA may be attributable to coal mining work.
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http://dx.doi.org/10.1002/acr.23874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717008PMC
September 2019

Gene signatures common to allograft rejection are associated with lymphocytic bronchitis.

Clin Transplant 2019 05 27;33(5):e13515. Epub 2019 Mar 27.

Medical Service, Veterans Affairs Health Care System, San Francisco, California.

Lymphocytic bronchitis (LB) precedes chronic lung allograft dysfunction. The relationships of LB (classified here as Endobronchial or E-grade rejection) to small airway (A- and B-grade) pathologies are unclear. We hypothesized that gene signatures common to allograft rejection would be present in LB. We studied LB in two partially overlapping lung transplant recipient cohorts: Cohort 1 included large airway brushes (6 LB cases and 18 post-transplant referents). Differential expression using DESeq2 was used for pathway analysis and to define an LB-associated metagene. In Cohort 2, eight biopsies for each pathology subtype were matched with pathology-free biopsies from the same subject (totaling 48 samples from 24 subjects). These biopsies were analyzed by multiplexed digital counting of immune transcripts. Metagene score differences were compared by paired t tests. Compared to referents in Cohort 1, LB demonstrated upregulation of allograft rejection pathways, and upregulated genes in these cases characterized an LB-associated metagene. We observed statistically increased expression in Cohort 2 for this LB-associated metagene and four other established allograft rejection metagenes in rejection vs paired non-rejection biopsies for both E-grade and A-grade subtypes, but not B-grade pathology. Gene expression-based categorization of allograft rejection may prove useful in monitoring lung allograft health.
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http://dx.doi.org/10.1111/ctr.13515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545574PMC
May 2019

Occupational exposures and incidence of chronic bronchitis and related symptoms over two decades: the European Community Respiratory Health Survey.

Occup Environ Med 2019 04 30;76(4):222-229. Epub 2019 Jan 30.

Barcelona Institute of Global Health (ISGlobal), Barcelona, Spain.

Objectives: Chronic bronchitis (CB) is an important chronic obstructive pulmonary disease (COPD)-related phenotype, with distinct clinical features and prognostic implications. Occupational exposures have been previously associated with increased risk of CB but few studies have examined this association prospectively using objective exposure assessment. We examined the effect of occupational exposures on CB incidence in the European Community Respiratory Health Survey.

Methods: Population samples aged 20-44 were randomly selected in 1991-1993, and followed up twice over 20 years. Participants without chronic cough or phlegm at baseline were analysed. Coded job histories during follow-up were linked to the ALOHA Job Exposure Matrix, generating occupational exposure estimates to 12 categories of chemical agents. Their association with CB incidence over both follow-ups was examined with Poisson models using generalised estimating equations.

Results: 8794 participants fulfilled the inclusion criteria, contributing 13 185 observations. Only participants exposed to metals had a higher incidence of CB (relative risk (RR) 1.70, 95% CI 1.16 to 2.50) compared with non-exposed to metals. Mineral dust exposure increased the incidence of chronic phlegm (RR 1.72, 95% CI 1.43 to 2.06). Incidence of chronic phlegm was increased in men exposed to gases/fumes and to solvents and in women exposed to pesticides.

Conclusions: Occupational exposures are associated with chronic phlegm and CB, and the evidence is strongest for metals and mineral dust exposure. The observed differences between men and women warrant further investigation.
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http://dx.doi.org/10.1136/oemed-2018-105274DOI Listing
April 2019

Airflow limitation classified with the fixed ratio or the lower limit of normal and cause-specific mortality - A prospective study.

Respir Med 2018 11 4;144:36-41. Epub 2018 Oct 4.

Department of Occupational and Environmental Medicine, Institute of Clinical Medicine and Public Health, University of Umeå, SE-901 87, Umeå, Sweden.

Background: There is controversy as to whether airflow limitation should be defined as forced expiratory volume in 1 s (FEV)/vital capacity (VC) < 0.7 or as FEV/VC< the lower limit of normal (LLN). The aim was to examine whether different definitions of airflow limitation differ in predicting mortality.

Methods: Longitudinal prospective study of a national cohort of Swedish workers (199,408 men; 7988 women), aged 20-64 years with spirometry without bronchodilation at baseline followed from 1979 until death, or censorship at 2010. Airflow limitation (AL) by Global Obstructive Lung Disease criteria, AL, was defined as FEV/VC < 0.7; AL as FEV/VC < LLN. All all-cause, COPD and cardiovascular disease mortality was analyzed among men and women in relation to AL and AL, adjusted for age and smoking.

Results: Among men, all-cause mortality risks were similar by airflow limitation criteria: AL RR = 1.32, 95% CI 1.26-1.38; AL, RR = 1.37, 95% CI 1.31-1.44. The risk estimates were also similar by airflow limitation definition for cardiovascular mortality and for COPD mortality. Among women, all-cause mortality was also similar by airflow limitation criteria, but significantly higher as compared to men: AL RR = 2.10, 95% CI 1.66-2.66; AL, RR = 2.09, 95% CI 1.66-2.62. Also cardiovascular and COPD mortality by airflow limitation criteria was significantly higher among women as compared to men.

Conclusions: Defined either as FEV/VC < 0.7 or as FEV/VC < LLN, airflow limitation predicted excess mortality risk of similar magnitude. Mortality in relation to airflow limitation was higher among women compared to men.
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http://dx.doi.org/10.1016/j.rmed.2018.10.001DOI Listing
November 2018

Occupational Exposures and Computed Tomographic Imaging Characteristics in the SPIROMICS Cohort.

Ann Am Thorac Soc 2018 12;15(12):1411-1419

4 Department of Medicine, Johns Hopkins University, Baltimore, Maryland.

Rationale: Quantitative computed tomographic (CT) imaging can aid in chronic obstructive pulmonary disease (COPD) phenotyping. Few studies have identified whether occupational exposures are associated with distinct CT imaging characteristics.

Objectives: To examine the association between occupational exposures and CT-measured patterns of disease in the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study).

Methods: Participants underwent whole-lung multidetector helical CT at full inspiration and expiration. The association between occupational exposures (self-report of exposure to vapors, gas, dust, or fumes [VGDF] at the longest job) and CT metrics of emphysema (percentage of total voxels < -950 Hounsfield units at total lung capacity), large airways (wall area percent [WAP] and square-root wall area of a single hypothetical airway with an internal perimeter of 10 mm [Pi10]), and small airways (percent air trapping [percent total voxels < -856 Hounsfield units at residual volume] and parametric response mapping of functional small-airway abnormality [PRM fSAD]) were explored by multivariate linear regression, and for central airway measures by generalized estimating equations to account for multiple measurements per individual. Models were adjusted for age, sex, race, current smoking status, pack-years of smoking, body mass index, and site. Airway measurements were additionally adjusted for total lung volume.

Results: A total of 2,736 participants with available occupational exposure data (n = 927 without airflow obstruction and 1,809 with COPD) were included. The mean age was 64 years, 78% were white, and 54% were male. Forty percent reported current smoking, and mean (SD) pack-years was 49.3 (26.9). Mean (SD) post-bronchodilator forced expiratory volume in 1 second (FEV) was 73 (27) % predicted. Forty-nine percent reported VGDF exposure. VGDF exposure was associated with higher emphysema (β = 1.17; 95% confidence interval [CI], 0.44-1.89), greater large-airway disease as measured by WAP (segmental β = 0.487 [95% CI, 0.320-0.654]; subsegmental β = 0.400 [95% CI, 0.275-0.527]) and Pi10 (β = 0.008; 95% CI, 0.002-0.014), and greater small-airway disease was measured by air trapping (β = 2.60; 95% CI, 1.11-4.09) and was nominally associated with an increase in PRM fSAD (β = 1.45; 95% CI, 0.31-2.60). These findings correspond to higher odds of percent emphysema, WAP, and air trapping above the 95th percentile of measurements in nonsmoking control subjects in individuals reporting VGDF exposure.

Conclusions: In an analysis of SPIROMICS participants, we found that VGDF exposure in the longest job was associated with an increase in emphysema, and in large- and small-airway disease, as measured by quantitative CT imaging.
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http://dx.doi.org/10.1513/AnnalsATS.201802-150OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322018PMC
December 2018

Off the Courts: Occupational "Tennis Leg".

Workplace Health Saf 2019 Jan 30;67(1):5-8. Epub 2018 Aug 30.

1 University of California, San Francisco.

Objective: Injury to the gastrocnemius muscle (tennis leg) is a presenting complaint often associated with athletic pursuits. Despite that label, this form of injury is likely to be common to a variety of salaried and nonsalaried pursuits beyond sports.

Method: We describe the presentation and management of two cases of "tennis leg" injury occurring in an occupational rather than athletic setting and review the relevant medical literature.

Results: Partial tears of the medial insertion of the gastrocnemius tendon were documented in both cases, in the first through magnetic resonance imaging and in the second by ultrasound.

Conclusion: Rupture of the tendon to the medial head of the gastrocnemius, the so-called "tennis leg" injury, should be considered as potentially work-related trauma, rather than taken to be solely a sports injury.
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http://dx.doi.org/10.1177/2165079918786294DOI Listing
January 2019

EBUS-TBNA is Sufficient for Successful Diagnosis of Silicosis with Mediastinal Lymphadenopathy.

Lung 2018 08 29;196(4):441-445. Epub 2018 May 29.

Pulmonary Institute, Carmel Medical Center, Haifa, Israel.

Background: Silicosis is an occupational lung disease resulting from inhalation of respirable crystalline silica. Recently, an international silicosis epidemic has been noted among artificial stone workers.

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is currently used for patients with unexplained lymphadenopathy. Since silicosis may present with prominent lymphadenopathy, the diagnostic yield of EBUS-TBNA in diagnosing silicosis was evaluated.

Methods: Twenty-eight patients with suspected silicosis referred for outpatient evaluation in three large tertiary hospitals were evaluated. Patients with mediastinal lymphadenopathy underwent EBUS-TBNA, while others underwent TBB and/or video-assisted thoracoscopic surgery (VATS).

Results: Eleven patients with mediastinal lymphadenopathy (39%) were evaluated using EBUS-TBNA. The diagnosis was accurate in all cases, demonstrating silica particles under polarized light, with no complications. Among the remaining patients, TBB was only 76% diagnostic, therefore requiring VATS.

Conclusions: EBUS-TBNA is a useful and sufficient tool to diagnose silicosis in patients with mediastinal lymphadenopathy along compatible exposure histories.
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http://dx.doi.org/10.1007/s00408-018-0129-3DOI Listing
August 2018

Lung volumes identify an at-risk group in persons with prolonged secondhand tobacco smoke exposure but without overt airflow obstruction.

BMJ Open Respir Res 2018 5;5(1):e000284. Epub 2018 May 5.

Division of Pulmonary, Critical Care, Allergy and Immunology, and Sleep Medicine, Department of Medicine, University of California, San Francisco, California, USA.

Introduction: Exposure to secondhand smoke (SHS) is associated with occult obstructive lung disease as evident by abnormal airflow indices representing small airway disease despite having preserved spirometry (normal forced expiratory volume in 1 s-to-forced vital capacity ratio, FEV/FVC). The significance of lung volumes that reflect air trapping in the presence of preserved spirometry is unclear.

Methods: To investigate whether lung volumes representing air trapping could determine susceptibility to respiratory morbidity in people with SHS exposure but without spirometric chronic obstructive pulmonary disease, we examined a cohort of 256 subjects with prolonged occupational SHS exposure and preserved spirometry. We elicited symptom prevalence by structured questionnaires, examined functional capacity (maximum oxygen uptake, VO) by exercise testing, and estimated associations of those outcomes with air trapping (plethysmography-measured residual volume-to-total lung capacity ratio, RV/TLC), and progressive air trapping with exertion (increase in fraction of tidal breathing that is flow limited on expiration during exercise (per cent of expiratory flow limitation, %EFL)).

Results: RV/TLC was within the predicted normal limits, but was highly variable spanning 22%±13% and 16%±8% across the increments of FEV/FVC and FEV, respectively. Respiratory complaints were prevalent (50.4%) with the most common symptom being ≥2 episodes of cough per year (44.5%). Higher RV/TLC was associated with higher OR of reporting respiratory symptoms (n=256; r=0.03; p=0.011) and lower VO (n=179; r=0.47; p=0.013), and %EFL was negatively associated with VO (n=32; r=0.40; p=0.017).

Conclusions: In those at risk for obstruction due to SHS exposure but with preserved spirometry, higher RV/TLC identifies a subgroup with increased respiratory symptoms and lower exercise capacity.
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http://dx.doi.org/10.1136/bmjresp-2018-000284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942438PMC
May 2018

Occupational exposures and 20-year incidence of COPD: the European Community Respiratory Health Survey.

Thorax 2018 11 24;73(11):1008-1015. Epub 2018 Mar 24.

Barcelona Institute of Global Health (ISGlobal), Barcelona, Spain.

Background: Occupational exposures have been associated with an increased risk of COPD. However, few studies have related objectively assessed occupational exposures to prospectively assessed incidence of COPD, using postbronchodilator lung function tests. Our objective was to examine the effect of occupational exposures on COPD incidence in the European Community Respiratory Health Survey.

Methods: General population samples aged 20-44 were randomly selected in 1991-1993 and followed up 20 years later (2010-2012). Spirometry was performed at baseline and at follow-up, with incident COPD defined using a lower limit of normal criterion for postbronchodilator FEV1/FVC. Only participants without COPD and without current asthma at baseline were included. Coded job histories during follow-up were linked to a Job-Exposure Matrix, generating occupational exposure estimates to 12 categories of agents. Their association with COPD incidence was examined in log-binomial models fitted in a Bayesian framework.

Findings: 3343 participants fulfilled the inclusion criteria; 89 of them had COPD at follow-up (1.4 cases/1000 person-years). Participants exposed to biological dust had a higher incidence of COPD compared with those unexposed (relative risk (RR) 1.6, 95% CI 1.1 to 2.3), as did those exposed to gases and fumes (RR 1.5, 95% CI 1.0 to 2.2) and pesticides (RR 2.2, 95% CI 1.1 to 3.8). The combined population attributable fraction for these exposures was 21.0%.

Interpretation: These results substantially strengthen the evidence base for occupational exposures as an important risk factor for COPD.
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http://dx.doi.org/10.1136/thoraxjnl-2017-211158DOI Listing
November 2018

Improvement in patient-reported outcomes after lung transplantation is not impacted by the use of extracorporeal membrane oxygenation as a bridge to transplantation.

J Thorac Cardiovasc Surg 2018 07 22;156(1):440-448.e2. Epub 2018 Feb 22.

Division of Pulmonary and Critical Care, Department of Medicine, University of California San Francisco School of Medicine, San Francisco, Calif.

Objective: Extracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation. The impact of preoperative ECMO on health-related quality of life (HRQL) and depressive symptoms after lung transplantation remains unknown, however.

Methods: In a single-center prospective cohort study, we assessed HRQL and depressive symptoms before and at 3, 6, and 12 months after lung transplantation using the Short Form 12 Physical and Mental Component Scores (SF12-PCS and SF12-MCS), Airway Questionnaire 20-Revised (AQ20R), EuroQol 5D (EQ5D), and Geriatric Depression Scale (GDS). Changes in HRQL were quantified by segmented linear mixed-effects models controlling for age, sex, diagnosis, preoperative forced expiratory volume in 1 second, 6-minute walk distance, and Lung Allocation Score. We compared changes in HRQL among subjects bridged with ECMO, subjects hospitalized but not on ECMO, and subjects called in for transplantation as outpatients.

Results: Out of 189 subjects, 17 were bridged to transplantation with ECMO. In all groups, improvements in HRQL following lung transplantation exceeded the minimally clinically important difference using the SF12-PCS, AQ20R, EQ5D, and GDS. HRQL defined by SF12-MCS did not change after transplantation. Improvements were generally similar among the groups, except for EQ5D, which showed a trend toward less benefit in the outpatients, possibly due to their better HRQL before lung transplantation.

Conclusions: Subjects ill enough to require ECMO as a bridge to lung transplantation appear to achieve similar improvements in HRQL and depressive symptoms as those who do not. It is reassuring to both providers and patients that lung transplantation provides substantial improvements in HRQL, even for those patients who are critically ill in the run up to transplantation.
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http://dx.doi.org/10.1016/j.jtcvs.2018.01.101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013366PMC
July 2018

Bismuth Subgallate Toxicity in the Age of Online Supplement Use.

Neurologist 2017 Nov;22(6):237-240

Departments of *Neurology †Emergency Medicine §Medicine, Division of Occupational and Environmental Medicine, UCSF ‡California Poison Control System, San Francisco Division, San Francisco, CA.

Introduction: Bismuth salts have been used to treat gastroenterological disorders and are readily available over-the-counter and via the internet. Even though generally considered safe, bismuth compounds can cause a syndrome of subacute, progressive encephalopathy when taken in large quantities.

Case Report: We present the case of woman who developed progressive encephalopathy, aphasia, myoclonus, and gait instability after chronically ingesting large amounts of bismuth subgallate purchased from a major online marketing website to control symptoms of irritable bowel syndrome. After extensive neurological work-up, elevated bismuth levels in her blood, urine, and cerebrospinal fluid confirmed the diagnosis of bismuth-related neurotoxicity. She improved slowly following cessation of exposure.

Conclusion: This case highlights bismuth subgallate as a neurotoxic bismuth formulation and reminds providers of the potential for safety misconceptions of positively reviewed online supplements.
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http://dx.doi.org/10.1097/NRL.0000000000000144DOI Listing
November 2017