Risk of hypersensitivity pneumonitis and other interstitial lung diseases following organic dust exposure.

BACKGROUND: Organic dust is associated with hypersensitivity pneumonitis, and associations with other types of interstitial lung disease (ILD) have been suggested. We examined the association between occupational organic dust exposure and hypersensitivity pneumonitis and other ILDs in a cohort study. METHODS: The study population included all residents of Denmark born in 1956 or later with at least 1 year of gainful employment since 1976. Incident cases of hypersensitivity pneumonitis and other ILDs were identified in the Danish National Patient Register 1994-2015. Job exposure matrices were used to assign individual annual levels of exposure to organic dust, endotoxin and wood dust from 1976 to 2015. We analysed exposure-response relations by different exposure metrics using a discrete-time hazard model. RESULTS: For organic dust, we observed increasing risk with increasing cumulative exposure with incidence rate ratios (IRR) per 10 unit-years of 1.19 (95% CI 1.12 to 1.27) for hypersensitivity pneumonitis and 1.04 (95% CI 1.02 to 1.06) for other ILDs. We found increasing risk with increasing cumulative endotoxin exposure for hypersensitivity pneumonitis and other ILDs with IRRs per 5000 endotoxin units/m3-years of 1.55 (95% CI 1.38 to 1.73) and 1.09 (95% CI 1.00 to 1.19), respectively. For both exposures, risk also increased with increasing duration of exposure and recent exposure. No increased risks were observed for wood dust exposure. CONCLUSION: Exposure-response relations were observed between organic dust and endotoxin exposure and hypersensitivity pneumonitis and other ILDs, with lower risk estimates for the latter. The findings indicate that organic dust should be considered a possible cause of any ILD. TRIAL REGISTRATION NUMBER: j.no.: 1-16-02-196-17.

Occupational exposure to respirable crystalline silica and incident idiopathic interstitial pneumonias and pulmonary sarcoidosis: a national prospective follow-up study.

BACKGROUND: Respirable crystalline silica is a well-known cause of silicosis but may also be associated with other types of interstitial lung disease. We examined the associations between occupational exposure to respirable crystalline silica and the risk of idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. METHODS: The total Danish working population was followed 1977-2015. Annual individual exposure to respirable crystalline silica was estimated using a quantitative job exposure matrix. Cases were identified in the Danish National Patient Register. We conducted adjusted analyses of exposure-response relations between cumulative silica exposure and other exposure metrics and idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. RESULTS: Mean cumulative exposure was 125 µg/m3-years among exposed workers. We observed increasing incidence rate ratios with increasing cumulative silica exposure for idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. For idiopathic interstitial pneumonias and pulmonary sarcoidosis, trends per 50 µg/m3-years were 1.03 (95% CI 1.02 to 1.03) and 1.06 (95% CI 1.04 to 1.07), respectively. For silicosis, we observed the well-known exposure-response relation with a trend per 50 µg/m3-years of 1.20 (95% CI 1.17 to 1.23). CONCLUSION: This study suggests that silica inhalation may be related to pulmonary sarcoidosis and idiopathic interstitial pneumonias, though these findings may to some extent be explained by diagnostic misclassification. The observed exposure-response relations for silicosis at lower cumulative exposure levels than previously reported need to be corroborated in analyses that address the limitations of this study.

Occupational noise exposure and tinnitus: the HUNT Study.

OBJECTIVE: We aimed to assess the association between occupational noise exposure and tinnitus. Further, to assess whether the association depends on hearing status. DESIGN: In this cross-sectional study, tinnitus (>1 h daily) was regressed on job exposure matrix (JEM)-based or self-reported occupational noise exposure, adjusted for confounders. STUDY SAMPLE: The 14,945 participants (42% men, 20-59 years) attended a population-based study in Norway (HUNT4, 2017-2019). RESULTS: JEM-based noise exposure, assessed as equivalent continuous sound level normalised to 8-h working days (LEX 8 h), over the working career or as minimum 5 years ≥85 dB) was not associated with tinnitus. Years of exposure ≥80 dB (minimum one) was not associated with tinnitus. Self-reported high noise exposure (>15 h weekly ≥5 years) was associated with tinnitus overall and among persons with elevated hearing thresholds (prevalence ratio (PR) 1.3, 1.0-1.7), however not statistically significantly among persons with normal thresholds (PR 1.1, 0.8-1.5). CONCLUSIONS: Our large study showed no association between JEM-based noise exposure and tinnitus. This may to some extent reflect successful use of hearing protection. High self-reported noise exposure was associated with tinnitus, but not among normal hearing persons. This supports that noise-induced tinnitus to a large extent depends on audiometric hearing loss.

Quantitative levels of noise exposure and 20-year hearing decline: findings from a prospective cohort study (the HUNT Study).

OBJECTIVE: We aimed to assess the association between occupational noise exposure and long-term hearing decline. DESIGN: This prospective cohort study used linear regression to investigate the association between occupational noise exposure and 20-year hearing decline, adjusted for important confounders. STUDY SAMPLE: The Norwegian cohort (N = 4,448) participated in two population-based health studies with pure-tone audiometry; HUNT2 1996-1998 and HUNT4 2017-2019. Exposure assessments included a quantitative job exposure matrix (JEM) and questionnaires. RESULTS: The participants (40.2% men, 20-39 years at baseline) had a mean 20-year decline (3-6 kHz) of 11.3 ± 9.8 decibels (dB). There was a positive association between 20-year logarithmic average noise level (JEM-based, LEX,20y) and 20-year hearing decline among men. Compared with no exposure ≥80 dB during follow-up, minimum 5 years of exposure ≥85 dB (JEM-based) predicted 2.6 dB (95% CI: 0.2-5.0) larger 20-year decline for workers aged 30-39 years at baseline, and -0.2 dB (95% CI: -2.2 to 1.7) for workers aged 20-29 years. Combining JEM information with self-reported noise exposure data resulted in stronger associations. CONCLUSION: This large longitudinal study shows an association between JEM-based noise exposure level and increased 20-year hearing decline among men. Contrary to expectations, the associations were weaker among younger workers, which might reflect a latency period.

Associations of Occupational Styrene Exposure With Risk of Encephalopathy and Unspecified Dementia: A Long-Term Follow-up Study of Workers in the Reinforced Plastics Industry.

Exposure to industrial solvents has been associated with encephalopathy. Styrene is a neurotoxic industrial solvent, and we investigated the long-term risk of encephalopathy and unspecified dementia following styrene exposure. We followed 72,465 workers in the reinforced plastics industry in Denmark (1977-2011) and identified incident cases of encephalopathy (n = 228) and unspecified dementia (n = 565) in national registers. Individual styrene exposure levels were modeled from information on occupation, measurements of work place styrene levels, product, process, and years of employment. Adjusted analyses were performed using a discrete survival function. A positive trend for encephalopathy (P < 0.01) and a negative trend for unspecified dementia (P = 0.03) were seen with cumulative styrene exposure accrued during the recent period of up to 15 years. For unspecified dementia and the combination of unspecified dementia and encephalopathy, a positive trend was indicated when applying a 30-year exposure lag (P = 0.13 and P = 0.07). The risk patterns seen following recent exposure probably reflect diagnostic criteria for encephalopathy requiring recent industrial solvent exposure and referral bias rather than association with styrene exposure, while the increasing risk observed for unspecified dementia and the combination of encephalopathy and unspecified dementia following distant exposure indicates an increased risk of dementia following styrene exposure with a long latency period.

A follow-up study of occupational styrene exposure and risk of autoimmune rheumatic diseases.

OBJECTIVES: Increased risk has been suggested for autoimmune rheumatic diseases following solvent exposure. The evidence for specific solvents is limited, and little is known about exposure-response relations. Styrene is an aromatic, organic solvent and the objective of this study was to analyse the association between occupational styrene exposure and autoimmune rheumatic diseases in men and women. METHODS: We followed 72 212 styrene-exposed workers of the Danish reinforced plastics industry from 1979 to 2012. We modelled full work history of styrene exposure from employment history, survey data and historical styrene exposure measurements. We identified cases in the national patient registry and investigated gender-specific exposure-response relations by cumulative styrene exposure for different exposure time windows adjusting for age, calendar year and educational level. RESULTS: During 1 515 126 person-years of follow-up, we identified 718 cases of an autoimmune rheumatic disease, of which 73% were rheumatoid arthritis. When adjusting for potential confounders and comparing the highest with the lowest styrene exposure tertile, we observed a statistically non-significantly increased risk of systemic sclerosis among women (incidence rate ratio (IRR)=2.50; 95% CI 0.50 to 12.50) and men (IRR=1.86; 95 % CI 0.50 to 7.00), based on 9 and 22 cases, respectively. Results were inconsistent for the other autoimmune rheumatic diseases examined. CONCLUSION: This study suggests an association between occupational styrene exposure and systemic sclerosis in men as well as in women but based on few cases. This is a new finding and has to be replicated before conclusions can be drawn.

Styrene Exposure and Risk of Lymphohematopoietic Malignancies in 73,036 Reinforced Plastics Workers.

BACKGROUND: Styrene is an important industrial chemical that the general population is exposed to at low levels. Previous research has suggested increased occurrence of leukemia and lymphoma among reinforced plastics workers exposed at high levels of styrene. METHODS: We followed 73,036 workers of 456 small- and medium-sized Danish reinforced plastics companies from 1968 to 2011 and investigated the exposure-response relation between cumulative styrene exposure and incidence of lymphohematopoietic malignancies. We modeled styrene exposure from employment history, survey data, and historical styrene exposure measurements. We retrieved information on lymphohematopoietic malignancies from national cancer and patient registers. RESULTS: We identified 665 cases overall of 21 different lymphohematopoietic malignancies or combinations thereof, each with at least 20 cases, during 1,581,976 person-years of follow-up. Initial analyses suggested higher age, sex, and calendar year-adjusted incidence rate ratios (RRs) for acute myeloid leukemia, Hodgkin lymphoma, and T-cell lymphoma with higher estimates of cumulative styrene exposure. Accounting for time since exposure showed a trend by cumulative styrene exposure (P = 0.01) and a doubled risk (RR = 2.4; 95% CI, 1.2, 4.6) of acute myeloid leukemia following estimated high compared with estimated low cumulative exposure during the prior 15-29 years. We observed no increased risk following exposure during more recent years and less consistent risk patterns for Hodgkin lymphoma and T-cell lymphoma. CONCLUSIONS: This study, to our knowledge the largest epidemiologic study to date of occupational styrene exposure, suggests increased risk of acute myeloid leukemia following high styrene exposure with a latency period of about 15 years.

Sinonasal adenocarcinoma following styrene exposure in the reinforced plastics industry.

BACKGROUND: Sinonasal adenocarcinoma is a rare disease expected to have rare causes and potential for strong risk factors as reflected by the strong association with occupational wood dust exposure. High level styrene exposure is a rare and suspected carcinogen, and this study examines the exposure-response relation between occupational styrene exposure, sinonasal adenocarcinoma and other subtypes. METHODS: We followed 73 092 styrene-exposed workers from 1968 to 2011 and identified sinonasal cancers in the Danish Cancer Registry. We modelled cumulative styrene exposure and estimated incidence rates and age, sex and wood-industry adjusted ORs. RESULTS: During 1 585 772 person-years, we observed nine cases of adenocarcinoma, corresponding to a fivefold non-significantly increased OR for estimates of high versus low cumulative styrene exposure (OR 5.11, 95% CI 0.58 to 45.12). The increased risk was confined to exposure received during the recent 15 years. The other histological subtypes showed no increased risk. CONCLUSION: This study suggests increased risk of sinonasal adenocarcinoma following styrene exposure. The observations are, however, few, confounding from wood dust exposure cannot be ruled out, and additional studies are needed before firm conclusions can be drawn.

Occupational noise exposure, psychosocial working conditions and the risk of tinnitus.

PURPOSE: The purpose of this study was to evaluate the influence of occupational noise (current and cumulative doses) and psychosocial work factors (psychological demands and decision latitude) on tinnitus occurrence among workers, using objective and non-self-reported exposure measures to prevent reporting bias. METHODS: In a cross-sectional study, we analyzed data from a Danish survey from 2009 to 2010 that included 534 workers from children day care units and 10 manufacturing trades. Associations between risk factors (current noise exposure, cumulative noise exposure and psychosocial working conditions) and tinnitus were analyzed with logistic regression. RESULTS: We found no statistically significant associations between either current [OR 0.95 (95% CI 0.89; 1.01)] or cumulative [OR 0.93 (95% CI 0.81; 1.06)] occupational noise exposure and tinnitus. Likewise, results for psychosocial working conditions showed no statistically significant association between work place decision latitude [OR 1.06 (95% CI 0.94; 1.13)] or psychological demands [OR 1.07 (95% CI 0.90; 1.26)] and tinnitus. CONCLUSIONS: Our results suggest that current Danish occupational noise levels (in combination with relevant noise protection) are not associated with tinnitus. Also, results indicated that the psychosocial working conditions we observed in this cohort of mainly industrial workers were not associated with tinnitus. Therefore, psychosocial working conditions comparable to those observed in this study are probably not relevant to take into account in the evaluation of workers presenting with tinnitus.

Risk of hypersensitivity pneumonitis and interstitial lung diseases among pigeon breeders.

We studied the risk of hypersensitivity pneumonitis and other interstitial lung diseases (ILDs) among pigeon breeders.This is a retrospective follow-up study from 1980 to 2013 of 6920 pigeon breeders identified in the records of the Danish Racing Pigeon Association. They were compared with 276 800 individually matched referents randomly drawn from the Danish population. Hospital based diagnoses of hypersensitivity pneumonitis and other ILDs were identified in the National Patient Registry 1977-2013. Stratified Cox regression analyses estimated the hazard ratios (HR) of hypersensitivity pneumonitis and other ILDs adjusted for occupation, residence and redeemed prescription of medication with ILDs as a possible side-effect. Subjects were censored at death, emigration or a diagnosis of connective tissue disease.The overall incidence rate of ILD was 77.4 per 100 000 person-years among the pigeon breeders and 50.0 among the referents. This difference corresponded to an adjusted HR of 1.56 (95% CI 1.26-1.94). The adjusted HRs of hypersensitivity pneumonitis and other ILDs for pigeon breeders were 14.36 (95% CI 8.10-25.44) and 1.33 (95% CI 1.05-1.69), respectively.This study shows an increased risk of ILD among pigeon breeders compared with the referent population. Protective measures are recommended even though ILD leading to hospital contact remains rare among pigeon breeders.

Atherogenic risk factors and hearing thresholds.

The objective of this study was to evaluate the influence of atherogenic risk factors on hearing thresholds. In a cross-sectional study we analyzed data from a Danish survey in 2009-2010 on physical and psychological working conditions. The study included 576 white- and blue-collar workers from children's day care units, financial services and 10 manufacturing trades. Associations between atherogenic risk factors (blood lipids, glycosylated hemoglobin, smoking habits, body mass index (BMI), and ambulatory blood pressure) and hearing thresholds were analyzed using multiple linear regression models. Adjusted results suggested associations between smoking, high BMI and triglyceride level and low high-density lipoprotein level and increased low-frequency hearing thresholds (average of pure-tone hearing thresholds at 0.25, 0.5 and 1 kHz). Furthermore, an increasing load of atherogenic risk factors seemed associated with increased low-frequency hearing thresholds, but only at a borderline level of statistical significance. Associations were generally strongest with hearing levels of the worst hearing ear. We found no statistically significant associations between atherogenic risk factors and high-frequency hearing thresholds (average of pure-tone hearing thresholds at 4, 6 and 8 kHz).

Supporting the working life exposome: Annotating occupational exposure for enhanced literature search.

An individual's likelihood of developing non-communicable diseases is often influenced by the types, intensities and duration of exposures at work. Job exposure matrices provide exposure estimates associated with different occupations. However, due to their time-consuming expert curation process, job exposure matrices currently cover only a subset of possible workplace exposures and may not be regularly updated. Scientific literature articles describing exposure studies provide important supporting evidence for developing and updating job exposure matrices, since they report on exposures in a variety of occupational scenarios. However, the constant growth of scientific literature is increasing the challenges of efficiently identifying relevant articles and important content within them. Natural language processing methods emulate the human process of reading and understanding texts, but in a fraction of the time. Such methods can increase the efficiency of both finding relevant documents and pinpointing specific information within them, which could streamline the process of developing and updating job exposure matrices. Named entity recognition is a fundamental natural language processing method for language understanding, which automatically identifies mentions of domain-specific concepts (named entities) in documents, e.g., exposures, occupations and job tasks. State-of-the-art machine learning models typically use evidence from an annotated corpus, i.e., a set of documents in which named entities are manually marked up (annotated) by experts, to learn how to detect named entities automatically in new documents. We have developed a novel annotated corpus of scientific articles to support machine learning based named entity recognition relevant to occupational substance exposures. Through incremental refinements to the annotation process, we demonstrate that expert annotators can attain high levels of agreement, and that the corpus can be used to train high-performance named entity recognition models. The corpus thus constitutes an important foundation for the wider development of natural language processing tools to support the study of occupational exposures.

The value of fractional exhaled nitric oxide in occupational diseases - a systematic review.

Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of respiratory tract inflammation, originally designated to identify eosinophilic airway inflammation and to predict steroid response. The main field of application of this biomarker is asthma, but FeNO has also been used for other allergic and non-allergic pulmonary disorders such as chronic obstructive pulmonary disease, hypersensitivity pneumonitis and interstitial lung disease. A substantial part of respiratory diseases are related to work, and FeNO, a safe and easy measure to conduct, is a potential valid examination in an occupational setting.This systematic review assesses the value of measuring FeNO related to three types of airborne exposures: allergens, irritants, and respiratory particles inhaled during occupational activities. The review covers results from longitudinal and observational clinical studies, and highlights the added value of this biomarker in monitoring effects of exposure and in the diagnostic criteria of occupational diseases. This review also covers the possible significance of FeNO as an indicator of the efficacy of interventions to prevent work-related respiratory diseases.Initially, 246 articles were identified in PUBMED and SCOPUS. Duplicates and articles which covered results from the general population, symptoms (not disease) related to work, non-occupational diseases, and case reports were excluded. Finally, 39 articles contributed to this review, which led to the following conclusions:a) For occupational asthma there is no consensus on the significant value of FeNO for diagnosis, or on the magnitude of change needed after specific inhalation test or occupational exposure at the workplace. There is some consensus for the optimal time to measure FeNO after exposure, mainly after 24 h, and FeNO proved to be more sensitive than spirometry in measuring the result of an intervention. b) For other occupational obstructive respiratory diseases, current data suggests performing the measurement after the work shift. c) For interstitial lung disease, the evaluation of the alveolar component of NO is probably the most suitable.

A Quantitative General Population Job Exposure Matrix for Occupational Noise Exposure.

Occupational noise exposure is a known risk factor for hearing loss and also adverse cardiovascular effects have been suggested. A job exposure matrix (JEM) would enable studies of noise and health on a large scale. The objective of this study was to create a quantitative JEM for occupational noise exposure assessment of the general working population. Between 2001-2003 and 2009-2010, we recruited workers from companies within the 10 industries with the highest reporting of noise-induced hearing loss according to the Danish Working Environment Authority and in addition workers of financial services and children day care to optimize the range in exposure levels. We obtained 1343 personal occupational noise dosimeter measurements among 1140 workers representing 100 different jobs according to the Danish version of the International Standard Classification of Occupations 1988 (DISCO 88). Four experts used 35 of these jobs as benchmarks and rated noise levels for the remaining 337 jobs within DISCO 88. To estimate noise levels for all 372 jobs, we included expert ratings together with sex, age, occupational class, and calendar year as fixed effects, while job and worker were included as random effects in a linear mixed regression model. The fixed effects explained 40% of the total variance: 72% of the between-jobs variance, -6% of the between-workers variance and 4% of the within-worker variance. Modelled noise levels showed a monotonic increase with increasing expert score and a 20 dB difference between the highest and lowest exposed jobs. Based on the JEM estimates, metal wheel-grinders were among the highest and finance and sales professionals among the lowest exposed. This JEM of occupational noise exposure can be used to prioritize preventive efforts of occupational noise exposure and to provide quantitative estimates of contemporary exposure levels in epidemiological studies of health effects potentially associated with noise exposure.

Influence of errors in job codes on job exposure matrix-based exposure assessment in the register-based occupational cohort DOC*X.

Objective Job-exposure matrices (JEM) may be efficient for exposure assessment in occupational epidemiological studies, but they rely on valid job information. We evaluated the agreement between JEM-based exposure estimates according to self-reported job titles converted to DISCO-88 codes and according to register-based DISCO-88 codes in the Danish Occupational Cohort with eXposure data (DOC*X). Furthermore, we evaluated the agreement between these two sets of DISCO-88 codes. Methods We used JEM regarding wood dust, lifting, standing/walking, arm elevation >90°, and noise from DOC*X. Participants from previous questionnaire studies were assigned JEM-based exposure estimates using (i) self-reported job titles converted to DISCO-88 codes and (ii) DISCO-88 codes registered in DOC*X, in four time periods (1976-78: N=7707; 1981-83: N=2193; 1991-94: N=2664; 2004: N=11 782). Agreement between the exposure estimates and between the DISCO-88 codes (four-digit levels, 1-4) was evaluated by kappa (κ) statistics. Sensitivities were calculated using the self-reported observation as the gold standard. Results We found substantial agreement (κ>0.60) between exposure estimates for all types of job-exposures and all time periods except for one κ. Low sensitivity (30-65%) was found for the period 1981-83, but for the other time periods the sensitivities varied between 60-91%. For individual 4-digit DISCO-88 codes, the sensitivities varied substantially and overall the sensitivities increased by lower digit level of DISCO-88. Conclusion The validity of the DISCO-88 codes in DOC*X was generally high. Substantial agreement was found for the JEM-based exposure estimates and the DISCO-88 codes per se, although the DISCO-88 code-specific agreement varied across digit levels and time periods.

Recent and long-term occupational noise exposure and salivary cortisol level.

Environmental and occupational noise exposure have been related to increased risk of cardiovascular disease, hypothetically mediated by stress-activation of the hypothalamic-pituitary-adrenal (HPA) axis. The objective of this study was to investigate the relation between recent and long-term occupational noise exposure and cortisol level measured off work to assess a possible sustained HPA-axis effect. We included 501 industrial, finance, and service workers who were followed for 24h during work, leisure, and sleep. Ambient occupational noise exposure levels were recorded every 5s by personal dosimeters and we calculated the full-shift LAEq value and estimated duration and cumulative exposure based on their work histories since 1980. For 332 workers who kept a log-book on the use of hearing protection devices (HPD), we subtracted 10 dB from every noise recording obtained during HPD use and estimated the noise level at the ear. Salivary cortisol concentration was measured at 20.00 h, the following day at awakening, and 30 min after awakening on average 5, 14 and 14.5h after finishing work. The mean ambient noise exposure level was 79.9 dB(A) [range: 55.0-98.9] and the mean estimated level at the ear 77.7 dB(A) [range: 55.0-94.2]. In linear and mixed regression models that adjusted for age, sex, current smoking, heavy alcohol consumption, personal income, BMI, leisure-time noise exposure level, time since occupational noise exposure ceased, awakening time, and time of saliva sampling, we observed no statistically significant exposure response relation between recent, or long-term ambient occupational noise exposure level and any cortisol parameter off work. This was neither the case for recent noise level at the ear. To conclude, neither recent nor long-term occupational noise exposure levels were associated with increased cortisol level off work. Thus, our results do not indicate that a sustained activation of the HPA axis, as measured by cortisol, is involved in the causal pathway between occupational noise exposure and cardiovascular disease.