Chronic respiratory symptoms following deployment-related occupational and environmental exposures among US veterans.

OBJECTIVES: Characterise inhalational exposures during deployment to Afghanistan and Southwest Asia and associations with postdeployment respiratory symptoms. METHODS: 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). RESULTS: 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). CONCLUSION: Exposures to burn pit smoke and military occupational VGDF during deployment were associated with an increased odds of chronic respiratory symptoms among US Veterans.

Self-report underestimates the frequency of the acute respiratory exacerbations of COPD but is associated with BAL neutrophilia and lymphocytosis: an observational study.

RATIONALE: Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency. OBJECTIVE: Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation. METHODS: We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years). RESULTS: Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohen's Kappa = 0.47 ± 0.07; P < 0.001). Nevertheless, self-reported and EHR-identified m/s-AECOPD events were both associated with higher BAL neutrophils (ß ± SEM: 3.0 ± 1.1 and 1.3 ± 0.5 per 10% neutrophil increase; P ≤ 0.018) and lymphocytes (0.9 ± 0.4 and 0.7 ± 0.3 per 10% lymphocyte increase; P ≤ 0.041). Exacerbation by either measure combined was associated with a larger estimated effect (3.7 ± 1.2 and 1.0 ± 0.5 per 10% increase in neutrophils and lymphocytes, respectively) but was not statistically significantly different compared to the self-report only approach. Among the 184 TEPS participants, there were fewer moderate to very severe respiratory exacerbations by self-report (n = 15 or 8%) or EHR-documentation (n = 9 or 5%), but a similar level of agreement as those with COPD was observed (Cohen's Kappa = 0.38 ± 0.07; P < 0.001). DISCUSSION: While there is modest agreement between self-reported and EHR-identified m/s-AECOPD, events are missed by relying on either method alone. However, m/s-AECOPD quantified by self-report or health records is associated with BAL neutrophilia and lymphocytosis.

Risk of subsequent SARS-CoV-2 infection among vaccinated employees with or without hybrid immunity acquired early in the Omicron-predominant era of the COVID-19 pandemic.

BACKGROUND: Hybrid immunity, from COVID-19 vaccination followed by SARS-CoV-2 infection acquired after its Omicron variant began predominating, has provided greater protection than vaccination alone against subsequent infection over 1-3 months of observation. Its longer-term protection is unknown. METHODS: We conducted a retrospective cohort study of COVID-19 case incidence among healthcare personnel (HCP) mandated to be vaccinated and report on COVID-19-associated symptoms, high-risk exposures, or known-positive test results to an employee health hotline. We compared cases with hybrid immunity, defined as incident COVID-19 during the first 6 weeks of Omicron-variant predominance (run-in period), to those with immunity from vaccination alone during the run-in period. Time until COVID-19 infection over 13 subsequent months (observation period) was analyzed by standard survival analysis. RESULTS: Of 5867 employees, 641 (10.9%, 95% confidence interval [CI]: 10.1%-11.8%) acquired hybrid immunity during the run-in period. Of these, 104 (16.2%, 95% CI: 13.5%-19.3%) experienced new SARS-CoV-2 infection during the 13-month observation period, compared to 2177 (41.7%, 95% CI: 40.3%-43.0%) of the 5226 HCP without hybrid immunity. Time until incident infection was shorter among the latter (hazard ratio: 3.09, 95% CI: 2.54-3.78). CONCLUSIONS: In a cohort of vaccinated employees, Omicron-era acquired SARS-CoV-2 hybrid immunity was associated with significantly lower risk of subsequent infection over more than a year of observation-a time period far longer than previously reported and during which three, progressively more resistant, Omicron subvariants became predominant. These findings can inform institutional policy and planning for future COVID-19 additional vaccine dosing requirements for employees, for surveillance programs, and for risk modification efforts.

Colinet-Caplan Syndrome: History of an Outbreak of Autoimmune Disease in Scouring Powder Workers.

The first modern description linking rheumatoid arthritis to occupational dust exposure is generally attributed to the British physician Anthony Caplan. In 1953, Caplan reported on a "peculiar" nodular pattern on chest radiographs of Welsh coal miners with rheumatoid arthritis that differed from the typical coal workers' pneumoconiosis. However, as early as 1950, the Belgian rheumatologist Émile Colinet described a similar case of rheumatoid arthritis and concomitant pulmonary opacities in a 30-year-old woman with silica exposure. Soon after, he published a second case. Although this condition initially was called Colinet-Caplan syndrome in the Francophone biomedical literature, Colinet's name was later dropped from the eponym. Because Colinet never clearly described the specific occupational context of his cases, Caplan syndrome has been misconstrued as uniquely a disease of coal miners.We attempted to reconstruct the working conditions of Colinet's patients and found that they were packing Vim, a silica-based scouring powder, at the Savonneries Lever Frères factory in Brussels, Belgium. Colinet's cases were only the first 2 in a series of reports of rheumatoid arthritis and other autoimmune diseases, mainly among young women, in those who worked in the production of silica-based scouring powder between the 1930s and 1980s across Europe. The largest outbreak involved 32 cases of autoimmune disease among 50 former workers of a Spanish scouring powder manufacturing facility. After silica in scouring powders was replaced with less hazardous materials later in the 20th century, no further cases have been reported.Although scouring powder disease is a historical phenomenon, autoimmune disorders linked to occupational exposure to silica and coal dust have not disappeared but instead are reemerging among those who work with silica-based artificial stone and in other dusty trades.

Military deployment-related respiratory problems: an update.

PURPOSE OF REVIEW: Military personnel deployed to Southwest Asia and Afghanistan were potentially exposed to high levels of fine particulate matter and other pollutants from multiple sources, including dust storms, burn pit emissions from open-air waste burning, local ambient air pollution, and a range of military service-related activities that can generate airborne exposures. These exposures, individually or in combination, can have adverse respiratory health effects. We review exposures and potential health impacts, providing a framework for evaluation. RECENT FINDINGS: Particulate matter exposures during deployment exceeded U.S. National Ambient Air Quality Standards. Epidemiologic studies and case series suggest that in postdeployment Veterans with respiratory symptoms, asthma is the most commonly diagnosed illness. Small airway abnormalities, most notably particularly constrictive bronchiolitis, have been reported in a small number of deployers, but many are left without an established diagnosis for their respiratory symptoms. The Promise to Address Comprehensive Toxics Act was enacted to provide care for conditions presumed to be related to deployment exposures. Rigorous study of long-term postdeployment health has been limited. SUMMARY: Veterans postdeployment to Southwest Asia and Afghanistan with respiratory symptoms should undergo an exposure assessment and comprehensive medical evaluation. If required, more advanced diagnostic considerations should be utilized in a setting that can provide multidisciplinary expertise and long-term follow-up.

Agent Orange Exposure and Risk of Idiopathic Pulmonary Fibrosis among U.S. Veterans.

Rationale: There is limited literature exploring the relationship between military exposures and idiopathic pulmonary fibrosis (IPF). Objectives: To evaluate whether exposure to Agent Orange is associated with an increased risk of IPF among veterans. Methods: We used Veterans Health Administration data to identify patients diagnosed with IPF between 2010 and 2019. We restricted the cohort to male Vietnam veterans and performed multivariate logistic regression to examine the association between presumptive Agent Orange exposure and IPF. We conducted sensitivity analyses restricting the cohort to army veterans (highest theoretical burden of exposure, surrogate for dose response) and a more specific case definition of IPF. Fine-Gray competing risk models were used to evaluate age to IPF diagnosis. Measurements and Main Results: Among 3.6 million male Vietnam veterans, 948,103 (26%) had presumptive Agent Orange exposure. IPF occurred in 2.2% of veterans with Agent Orange exposure versus 1.9% without exposure (odds ratio, 1.14; 95% confidence interval [CI], 1.12-1.16; P < 0.001). The relationship persisted after adjusting for known IPF risk factors (odds ratio, 1.08; 95% CI, 1.06-1.10; P < 0.001). The attributable risk among exposed veterans was 7% (95% CI, 5.3-8.7%; P < 0.001). Numerically greater risk was observed when restricting the cohort to 1) Vietnam veterans who served in the army and 2) a more specific definition of IPF. After accounting for the competing risk of death, veterans with Agent Orange exposure were still more likely to develop IPF. Conclusions: Presumptive Agent Orange exposure is associated with greater risk of IPF. Future research should validate this association and investigate the biological mechanisms involved.

Depressive symptoms in lung transplant recipients: trajectory and association with mortality and allograft dysfunction.

OBJECTIVE: Most studies observing an association between depressive symptoms following lung transplantation and mortality are limited to depressive symptom measurement at a single time point, unrelated to allograft function. We aimed to test the association of depressive symptoms over multiple assessments with allograft dysfunction and with mortality. METHODS: We assessed depressive symptoms before and serially up to 3 years after lung transplantation in lung transplant recipients. We quantified depressive symptoms with the Geriatric Depression Scale (GDS; range 0-15; minimally important difference (MID): 2). We quantified changes in GDS using linear mixed effects models and tested the association with mortality using Cox proportional hazards models with GDS as a time-dependent predictor. To determine if worsening in GDS preceded declines in lung function, we tested the association of GDS as a time-dependent predictor with the lagged outcome of FEV1 at the following study visit. RESULTS: Among 266 participants, depressive symptoms improved early after transplantation. Worsening in post-transplant GDS by the MID was associated with mortality (HR 1.25, 95% CI 1.05 to 1.50), and in lagged outcome analyses with decreased per cent predicted FEV1 (Δ, -1.62%, 95% CI -2.49 to -0.76). Visual analyses of temporal changes in GDS demonstrated that worsening depressive symptoms could precede chronic lung allograft dysfunction. CONCLUSIONS: Depressive symptoms generally improve after lung transplantation. When they worsen, however, there is an association with declines in lung function and mortality. Depression is one of the few, potentially modifiable, risk factors for chronic lung allograft dysfunction and death.

Dusty trades and associated rheumatoid arthritis in a population-based study in the coal mining counties of Appalachia.

OBJECTIVES: We previously showed increased coal mining-associated risk of rheumatoid arthritis (RA). Using additional survey data, we sought to delineate this risk further. METHODS: We used data from two cross-sectional, random-digit-dial, population-based surveys (males;≥50 years) in selected counties in the Appalachian region of the inland, mid-Atlantic USA with elevated pneumoconiosis mortality. Surveys ascertained age, smoking, coal mining and non-coal silica exposure jobs. In a subset, we surveyed ergonomic exposures, scored by intensity. We queried diagnosis of RA, corticosteroid use, and, in a subset, use of disease modifying antirheumatic drugs (DMARDs). Multivariable logistic regression modelled RA risk (defined by glucocorticoid or DMARDs use) associated with coal mining employment, other silica exposure, smoking status, and age and ergonomic exposures. RESULTS: We analysed data for 2981 survey respondents (mean age 66.6 years; 15% current, 44% ex-smokers). The prevalence of glucocorticoid-treated and DMARD-treated RA was 11% and 4%, respectively. Glucocorticoid-treated RA was associated with coal mining (OR 3.5; 95% CI 2.5 to 4.9) and non-coal mining silica exposure (OR 3.2; 95% CI 2.4 to 4.4). For DMARD-treated RA, the odds associated with coal mining and other silica remained elevated: OR 2.3 (95% CI 1.18, 4.5) and OR 2.7 (95% CI 1.51, 5.0), respectively. In the same model, the highest intensity ergonomic exposure also was associated with increased odds of RA (OR 4.3; 95% CI 1.96 to 9.6). CONCLUSIONS: We observed a strong association between coal mining and other silica-exposing dusty trades and RA. Clinicians and insurers should consider occupational histories in the aetiology of RA.

Fractional exhaled NO in a metalworking occupational cohort.

PURPOSE: Secondary metalworking carries exposure to relatively heavy levels of respirable particulate. We investigated the extent to which metalworking is associated with increased exhaled nitric oxide (FeNO), an established inflammatory biomarker. METHODS: We studied 80 metalworking factory employees in Kazakhstan. Informed by industrial hygiene data, we categorized them into three groups: (1) machine operators (41%); (2) welders or assemblers (33%); and (3) all others, including administrative and ancillary staff (26%). Participants completed questionnaires covering occupational history, smoking, home particulate sources, respiratory symptoms, and comorbidities. We measured exhaled carbon monoxide (CO), exhaled fractional nitric oxide (FeNO), and spirometric function. We used mixed-effects modeling to test the associations of occupational group with FeNO, adjusted for covariates. RESULTS: The median age was 51.5 (interquartile range 20.5) years; 7% were women. Occupational group (p < 0.01), daily current cigarette smoking intensity (p < 0.05), and age (p < 0.05), each was statistically associated with FeNO. Welders, or assemblers (Group 2), who had intermediate particulate exposure, manifested significantly higher exhaled FeNO compared to machinists (Group 1, with the highest particulate exposure) and all others (Groups 3, the lowest particulate): adjusted Group 2 mean 44.8 ppb (95% confidence interval (CI) 33.8-55.9) vs. Group 1 24.6 ppb (95% 20.5-28.7) and Group 3, 24.3 ppb (95% CI 17.7-30.9). Secondhand smoking and height were not associated with FeNO. CONCLUSION: In a metalworking industrial cohort, welders/assemblers manifested significantly higher levels of FeNO. This may reflect respiratory tract inflammation associated with airborne exposures specific to this group.

Cumulative occupational exposure to inorganic dust and fumes and invasive pneumococcal disease with pneumonia.

PURPOSE: Occupational exposure to inorganic dust and fumes in the year preceding disease has been associated with increased pneumococcal pneumonia risk, but the impact of prior cumulative exposure has not been characterized. METHODS: We studied 3184 cases of invasive pneumococcal disease with pneumonia. The case index date was the day the infection was diagnosed. We selected six controls for each case from the Swedish population registry; each control was assigned the index date of their corresponding case. We linked job histories to a job-exposure matrix to calculate a cumulative exposure index, intensity-years, by multiplying the duration (maximum 5 years) of each exposure with the level of exposure (0 for unexposed, 1 for low and 4 for high). We used conditional logistic analyses to estimate the odds ratio (OR) of invasive pneumococcal disease with pneumonia adjusted for comorbidities, educational level, income and other occupational exposures. RESULTS: Taking other occupational exposures into account, greater than 5 intensity-years of exposure to silica dust or to fumes was each associated with increased odds for invasive pneumococcal disease with pneumonia (OR 2.53, 95% CI 1.49-4.32) and (OR 2.24, 95% CI 1.41-3.55), respectively. Five intensity-years or less of exposure to silica dust or fumes manifested lower odds (OR 1.45, 95% CI 1.20-1.76) and (OR 1.05, 95% CI 0.94-1.16), respectively. CONCLUSION: This study adds evidence that the risk of pneumococcal pneumonia increases with increasing cumulative exposure to dust and fumes, indicating the importance of cumulative exposure.

Pneumococcal pneumonia on the job: Uncovering the past story of occupational exposure to metal fumes and dust.

The objectives of this study are to elucidate the early history of risk for pneumococcal pneumonia from occupational exposure to metal fumes and dusts, and to demonstrate the importance of searching older literature when performing reviews. We performed manual searching for articles in the Library of the Surgeon General's Office (the precursor to Index Medicus), in the Hathi Trust database, in PubMed, andby screening reference lists in literature appearing before the introduction of PubMed. An early body of literature, from the 1890s onward, recognized that pneumonia was linked to "Thomas slag," a steel industry byproduct containing iron, manganese, and lime. Researchers, mainly in Germany, showed that workers in metal-dust-exposed occupations, especially using manganese, manifested an increased incidence of pneumococcal pneumonia. An outbreak of pneumococcal pneumonia in the 1930s implicated manganese fume in its etiology. In the immediate post-World War II period, there was a brief flurry of interest in pneumonia from exposure to potassium permanganate that was soon dismissed as a chemical pneumonitis. After a hiatus of two decades, epidemiologic investigations drew attention to the pneumonia risks of welding and related metal fume exposure, bringing renewed interest to the forgotten role of pneumococcal pneumonia as an occupational disease. Occupational or environmental inhalation of manganese, iron, or irritants may be causally related to increased pneumococcal pneumonia risk. In particular, the risk associated with manganese seems to be overlooked in recent literature. An important conclusion is the importance of obtaining additional evidence through a deeper assessment of the literature in a broad historical context.

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

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.

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

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.

Early radiographic pneumoconiosis is associated with impaired exercise gas exchange among coal miners with normal resting spirometry.

RATIONALE: We sought to determine if radiographic pneumoconiosis predicts abnormal gas exchange during exercise in coal mine workers with preserved resting lung function. METHODS: We analyzed data from former coal miners seen between 2006 and 2014 in a single clinic specializing in black lung evaluations. We limited the analysis to those with normal resting spirometry and an A-a gradient at peak exercise ≥10 mmHg. We used multivariable logistic regression to estimate predictors of A-a gradient widened to >150% of the reference value. We focused on chest radiographs consistent with pneumoconiosis, taking into account higher silica exposure mining activities and years underground, and adjusting for cigarette smoking, obesity, and coronary artery disease. RESULTS: Of 5507 miners, we analyzed data for 742 subjects with normal spirometry and all key clinical variables available, of whom 372 (50.1%) had radiographic evidence of pneumoconiosis. All but 21 had small opacity profusion of less than 2/1. The median A-a gradient at peak exercise was 108% of reference value (interquartile range, 81%-141%). In the multivariable analysis, radiographic pneumoconiosis was associated with increased odds of widened A-a gradient (odds ratio [OR], 2.47; 95% confidence interval [CI], 1.7-3.7). Limited to 660 subjects with normal diffusing capacity for carbon monoxide, the odds were similarly increased (OR, 3.20; 95% CI, 1.5-3.6). DISCUSSION: Among coal miners with preserved resting lung function, radiographic evidence of early pneumoconiosis more than doubled the odds of abnormal exercise physiology. Impairment in pneumoconiosis occurs in early disease and may only be evident on exercise testing.

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

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.

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

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 Streptococcus pneumoniae. 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.

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

Rationale: 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. Methods: 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. Results: 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%). Conclusions: 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.

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

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.

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

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.

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

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.