Relationship between cumulative silica exposure and silicosis: a systematic review and dose-response meta-analysis.

BACKGROUND: Silicosis, a chronic respiratory disease caused by crystalline silica exposure, is a persistent global lung health issue. No systematic review of the relationship between cumulative respirable crystalline silica (RCS) exposure and silicosis exists. UK exposure limits are currently under review. We therefore performed a systematic review and dose-response meta-analysis of this relationship. METHODS: Web of Science, Medline and Embase were searched on 24 February 2023. Studies of radiographic, autopsy or death certificate silicosis, with an estimated average follow-up of over 20 years since first employment, were included. Cumulative silicosis risk methods were compared. The relative risks (RR) of silicosis at increasing cumulative exposures were calculated and used to estimate the absolute risk reduction (ARR). RESULTS: Eight eligible studies, including 10 cohorts, contributed 8792 cases of silicosis among 65 977 participants. Substantial differences in cumulative risk estimates between methodologies exist. Using the same method, we observed higher cumulative silicosis risks among mining compared with non-mining cohorts. A reduction from 4 to 2 mg/m³-years in cumulative RCS exposure corresponded to substantial risk reductions among miners (RR 0.23 (95% CI 0.18 to 0.29, I2=92.9%) with an ARR of 323 (95% CI 298 to 344) per 1000) and non-miners (RR 0.55 (95% CI 0.36 to 0.83, I2=77.0%) with an ARR of 23 (95% CI 9 to 33) per 1000). CONCLUSION: Despite significant heterogeneity, our findings support a reduction in permissible exposure limits from 0.1 mg/m3 to 0.05 mg/m³, particularly among mining populations. Further research is needed among non-miners as only two studies were eligible.

Artificial stone silicosis: a UK case series.

Silicosis due to artificial stone (AS) has emerged over the last decade as an increasing global issue. We report the first eight UK cases. All were men; median age was 34 years (range 27-56) and median stone dust exposure was 12.5 years (range 4-40) but in 4 cases was 4-8 years. One is deceased; two were referred for lung transplant assessment. All cases were dry cutting and polishing AS worktops with inadequate safety measures. Clinical features of silicosis can closely mimic sarcoidosis. UK cases are likely to increase, with urgent action needed to identify cases and enforce regulations.

Occupational interstitial lung diseases.

Millions of workers are exposed to substances known to cause occupational interstitial lung diseases (ILDs), particularly in developing countries. However, the burden of the disease is likely to be underestimated due to under-recognition, under-reporting or both. The diagnosis of occupational ILD requires a high level of suspicion and a thorough occupational history, as occupational and non-occupational ILDs may be clinically, functionally and radiologically indistinguishable, leading to delayed diagnosis and inappropriate management. A potential occupational aetiology should always be considered in the differential diagnosis of ILD, as removal from the workplace exposure, with or without treatment, is a key therapeutic intervention and may lead to significant improvement. In this article, we provide an overview of the 'traditional' inorganic dust-related ILDs but also address idiopathic pulmonary fibrosis and the immunologically mediated chronic beryllium disease, sarcoidosis and hypersensitivity pneumonitis, with emphasis on the importance of surveillance and prevention for reducing the burden of these conditions. To this end, health-care professionals should be specifically trained about the importance of occupational exposures as a potential cause of ILD.

Spirometry parameters used to define small airways obstruction in population-based studies: systematic review.

BACKGROUND: The assessment of small airways obstruction (SAO) using spirometry is practiced in population-based studies. However, it is not clear what are the most used parameters and cut-offs to define abnormal results. METHODS: We searched three databases (Medline, Web of Science, Google Scholar) for population-based studies, published by 1 May 2021, that used spirometry parameters to identify SAO and/or provided criteria for defining SAO. We systematically reviewed these studies and summarised evidence to determine the most widely used spirometry parameter and criteria for defining SAO. In addition, we extracted prevalence estimates and identified associated risk factors. To estimate a pooled prevalence of SAO, we conducted a meta-analysis and explored heterogeneity across studies using meta regression. RESULTS: Twenty-five studies used spirometry to identify SAO. The most widely utilised parameter (15 studies) was FEF25-75, either alone or in combination with other measurements. Ten studies provided criteria for the definition of SAO, of which percent predicted cut-offs were the most common (5 studies). However, there was no agreement on which cut-off value to use. Prevalence of SAO ranged from 7.5% to 45.9%. As a result of high heterogeneity across studies (I2 = 99.3%), explained by choice of spirometry parameter and WHO region, we do not present a pooled prevalence estimate. CONCLUSION: There is a lack of consensus regarding the best spirometry parameter or defining criteria for identification of SAO. The value of continuing to measure SAO using spirometry is unclear without further research using large longitudinal data. PROSPERO registration number CRD42021250206.

Environmental and occupational exposures in interstitial lung disease.

PURPOSE OF REVIEW: We highlight recent advances in the understanding of how environmental and occupational exposures increase the risk of developing interstitial lung disease (ILD), and how to evaluate a patient for potential exposures. RECENT FINDINGS: A review of emerging literature suggests that environmental and occupational exposures can be directly causal, as in the case of the pneumoconioses and smoking-related ILDs, or one of many contributors to disease, as in the case of idiopathic pulmonary fibrosis (IPF). Regardless of the level of association, exposures are clearly prevalent across all ILD subtypes studied. SUMMARY: Inhalational exposures are increasingly recognized as an important component in the development of ILDs, and novel exposure-disease associations continue to be discovered. These exposures represent potential opportunities for further understanding the pathobiology of disease and for the prevention of these often progressive and debilitating disorders. Prospective, comprehensive data collection regarding occupational and environmental exposures are needed in ILD patients to fully elucidate specific antigens and their relationships to disease incidence and outcomes. Systematically collected exposure information will also inform potential interventions to remediate exposures and thus mitigate the course of frequently progressive and fatal diseases.

The Respiratory Microbiome in Chronic Hypersensitivity Pneumonitis Is Distinct from That of Idiopathic Pulmonary Fibrosis.

Rationale: Chronic hypersensitivity pneumonitis (CHP) is a condition that arises after repeated exposure and sensitization to inhaled antigens. The lung microbiome is increasingly implicated in respiratory disease, but, to date, no study has investigated the composition of microbial communities in the lower airways in CHP.Objectives: To characterize and compare the airway microbiome in subjects with CHP, subjects with idiopathic pulmonary fibrosis (IPF), and control subjects.Methods: We prospectively recruited individuals with a CHP diagnosis (n = 110), individuals with an IPF diagnosis (n = 45), and control subjects (n = 28). Subjects underwent BAL and bacterial DNA was isolated, quantified by quantitative PCR and the 16S ribosomal RNA gene was sequenced to characterize the bacterial communities in the lower airways.Measurements and Main Results: Distinct differences in the microbial profiles were evident in the lower airways of subjects with CHP and IPF. At the phylum level, the prevailing microbiota of both subjects with IPF and subjects with CHP included Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. However, in IPF, Firmicutes dominated, whereas the percentage of reads assigned to Proteobacteria in the same group was significantly lower than the percentage found in subjects with CHP. At the genus level, the Staphylococcus burden was increased in CHP, and Actinomyces and Veillonella burdens were increased in IPF. The lower airway bacterial burden in subjects with CHP was higher than that in control subjects but lower than that of those with IPF. In contrast to IPF, there was no association between bacterial burden and survival in CHP.Conclusions: The microbial profile of the lower airways in subjects with CHP is distinct from that of IPF, and, notably, the bacterial burden in individuals with CHP fails to predict survival.

Exacerbation Patterns in Adults with Asthma in England. A Population-based Study.

RATIONALE: Asthma is heterogeneous and knowledge on exacerbation patterns is lacking. Previous studies have had a relatively short follow-up or focused on severe disease. OBJECTIVES: To describe exacerbation patterns over a prolonged follow-up in a population that includes patients of all disease severity. METHODS: We used electronic health care records to identify patients with asthma aged 18-55 years and their exacerbations from 2007 to 2015. A cohort with greater than or equal to 7 years of data was used to describe exacerbation patterns by asthma severity defined by medication use. Effect estimates for risk factors were calculated for sporadic (single year of exacerbations) and recurrent (>1 yr) exacerbation patterns, using logistic regression. In a nested case-control design, the association between a history of exacerbations, spanning 5 years, and a future exacerbation was examined. MEASUREMENTS AND MAIN RESULTS: A total of 51,462 patients were eligible for the 7-year cohort; 64% had no exacerbations. Of those who exacerbated, 51% did so only once; exacerbation frequency increased with disease severity. Only 370 patients (0.7%) were characterized by a frequent-exacerbator phenotype (yearly exacerbations), of whom 58% had mild/moderate asthma. Exacerbation risk factors were not uniquely associated with a particular exacerbation pattern. A past exacerbation increased the risk of a future exacerbation more than all other factors, although this effect dissipated over 5 years. CONCLUSIONS: During 7 years of follow-up, exacerbations occur in around one-third of patients. Of those who exacerbate, half do not do so again; the timing of future exacerbations is largely unpredictable. Just 2% exhibit a frequent-exacerbator phenotype. Past exacerbation patterns are the most informative risk factor for predicting future exacerbations.

Changing prevalence of current asthma and inhaled corticosteroid treatment in the UK: population-based cohort 2006-2016.

Asthma is the most common respiratory disorder in the UK, yet we have incomplete knowledge on the prevalence of current disease, treatment and exacerbations.We used UK electronic healthcare records, 2006-2016, to estimate the prevalence of current asthma by year, sex and age (<5, 5-11, 12-17, 18-24, 25-54 and ≥55 years), and the proportion prescribed inhaled corticosteroids (ICS) and additional asthma therapy, treated for exacerbations and other asthma care markers.Overall current asthma prevalence was 6.5% in 2016 (7.2% in 2006). Prevalence fell in those aged <45 years. The lowest prevalence and largest absolute decrease was in children aged <5 years. In 2016, 80% of current asthma patients were managed on ICS (65% in 2006); this increase occurred in all age groups, primarily due to an increase in low-dose ICS. During this time there was an increase in all age groups in the proportion prescribed additional asthma therapy, treated for an exacerbation within primary care and given an annual asthma review or management plan. Hospitalised exacerbations showed minimal change over time.Asthma remains highly prevalent and a significant healthcare burden. In those with a diagnosis, there was an increase in ICS prescriptions and treatment of exacerbations across all age groups. This may reflect a trend towards more aggressive asthma management within primary care. An apparent decline in prevalence was observed in those aged <45 years, particularly in children aged <5 years.

Laboratory animal allergy is preventable in modern research facilities.

BACKGROUND: Historical data suggest 15% of laboratory animal workers develop IgE sensitisation and 10% symptoms of laboratory animal allergy (LAA), including occupational asthma. Individually ventilated cages (IVCs) are replacing conventional open cages; we sought to evaluate their impact on the development of LAA. METHODS: We surveyed 750 laboratory animal workers and measured airborne Mus m 1 (mouse allergen) levels in seven UK institutions. We compared the prevalence of sensitisation to mouse proteins (by specific IgE assay or skin prick test) and of work-related allergic symptoms in IVC-only and open cage units. RESULTS: Full-shift Mus m 1 levels were lower in IVC than open cage units (geometric mean 1.00 (95% CI 0.73-1.36) versus 8.35 (95% CI 6.97-9.95) ng·m-3; p<0.001), but varied eight-fold across the IVC units (geometric mean range 0.33-4.12 ng·m-3). Primary analyses on data from 216 participants with ≤3 years exposure to mice revealed a lower prevalence of sensitisation in those working in IVC units compared with conventional cage units (2.4% (n=2) versus 9.8% (n=13); p=0.052). Sensitisation in IVC units varied from 0% to 12.5%; the use of fitted respiratory protection was less common in IVC units where prevalence of sensitisation was higher. Work-related allergy symptoms were more frequently reported by mouse-sensitised individuals (46.7% versus 10.9%; p<0.001) and only by those working in open cage units. CONCLUSION: In contemporary practice, LAA is now largely preventable with the use of IVC systems and the judicious use of appropriate respiratory protection.

Biallelic human ITCH variants causing a multisystem disease with dysmorphic features: A second report.

We report a 23 year old female with biallelic truncating variants in the ITCH (Itchy E3 Ubiquitin protein ligase, mouse homolog of; OMIM60649) gene associated with marked short stature, severe early onset chronic lung disease resembling asthma, dysmorphic facial features, and symmetrical camptodactyly of the fingers but normal intellect. The condition has only been reported once previously (Lohr et al., American Journal of Human Genetics, 2010, 86, 447-453) in 10 children from an Old Order Amish family found to have a homozygous frameshift truncating variant in association with failure to thrive, chronic lung disease, motor and cognitive delay, and variable autoimmune diseases including autoimmune hepatitis, enteropathy, hypothyroidism, and diabetes. The condition is listed in OMIM as Autoimmune disease, Multisystem with Facial Dysmorphism (OMIM613385). The clinical course as well as the dysmorphic facial and limb features overlap closely with our patient. We believe the triad of marked syndromic short stature, chronic lung disease, and dysmorphism (with or without cognitive impairment and wider autoimmune involvement) is distinctive.

Small Airways Obstruction and Mortality: Findings From the UK Biobank.

BACKGROUND: Small airways obstruction (SAO) is common in general populations. It has been associated with respiratory symptoms, cardiometabolic diseases, and progression to COPD over time. Whether SAO predicts mortality is largely unknown. RESEARCH QUESTION: Is spirometry-defined SAO associated with increased mortality? METHODS: Data were analyzed from 252,877 adult participants, aged 40 to 69 years at baseline, in the UK Biobank who had provided good-quality spirometry measurements. SAO was defined as the ratio of the forced expiratory volume in 3 s to the forced expiratory volume in 6 s less than the lower limit of normal. SAO was considered to be isolated if present when the FEV1/forced expiratory volume in 6 s ratio was normal (ie, greater than the lower limit of normal). A multivariable Cox regression model was used to assess the association of SAO, and isolated SAO, with all-cause and disease-specific mortality. Sex differences were investigated in these associations, and the primary analysis was repeated, excluding those who ever smoked. All models were adjusted for potential confounders such as sex, BMI, smoking status, smoking pack-years, assessment center, Townsend deprivation index, and ethnicity. RESULTS: A total of 59,744 participants with SAO were identified, of whom 24,004 had isolated SAO. A total of 5,009 deaths were reported over a median of 12.8 years of follow-up. Participants with SAO had increased all-cause (hazard ratio [HR], 1.31; 95% CI, 1.26-1.36), cardiovascular (HR, 1.39; 95% CI, 1.29-1.51), respiratory (HR, 2.20; 95% CI, 1.92-2.51), and neoplasm (HR, 1.23; 95% CI, 1.17-1.29) mortality risk. These associations were not modified by sex. However, in those who never smoked, only respiratory and cardiovascular mortality risk was associated with SAO. Isolated SAO was also associated with an increased mortality risk (HR, 1.14; 95% CI, 1.07-1.20). INTERPRETATION: Individuals with SAO have an increased risk of all-cause and disease-specific mortality. Further studies are needed to determine whether SAO causes mortality or is a marker of underlying disease.

Occupational exposure to particulate matter and staff sickness absence on the London underground.

The London Underground (LU) employs over 19,000 staff, some of whom are exposed to elevated concentrations of particulate matter (PM) within the network. This study quantified the occupational exposure of LU staff to subway PM and investigated the possible association with sickness absence (SA). A job exposure matrix to quantify subway PM2.5 staff exposure was developed by undertaking measurement campaigns across the LU network. The association between exposure and SA was evaluated using zero-inflated mixed-effects negative binomial models. Staff PM2.5 exposure varied by job grade and tasks undertaken. Drivers had the highest exposure over a work shift (mean: 261 µg/m3), but concentrations varied significantly by LU line and time the train spent subway. Office staff work in office buildings separate to the LU network and are unexposed to occupational subway PM2.5. They were found to have lower rates of all-cause and respiratory infection SA compared to non-office staff, those who work across the LU network and are occupational exposed to subway PM2.5. Train drivers on five out of eight lines showed higher rates of all-cause SA, but no dose-response relationship was seen. Only drivers from one line showed higher rates of SAs from respiratory infections (incidence rate ratio: 1.24, 95% confidence interval 1.10-1.39). Lower-grade customer service (CS) staff showed higher rates of all-cause and respiratory infection SA compared to higher grade CS staff. Doctor-certified chronic respiratory and cardiovascular SAs were associated with occupational PM2.5 exposure in CS staff and drivers. While some groups with higher occupational exposure to subway PM reported higher rates of SA, no evidence suggests that subway PM is the main contributing factor to SA. This is the largest subway study on health effects of occupational PM2.5 exposure and may have wider implications for subway workers, contributing to safer working environments.

Scoping review of exposure questionnaires and surveys in interstitial lung disease.

BACKGROUND: Many interstitial lung diseases (ILDs) have clear causal relationships with environmental and occupational exposures. Exposure identification can assist with diagnosis, understanding disease pathogenesis, prognostication and prevention of disease progression and occurrence in others at risk. Despite the importance of exposure identification in ILD, there is no standardised assessment approach. Many questionnaires are in clinical and research use, yet their utility, applicability, relevance and performance characteristics are unknown. OBJECTIVES: This scoping review aimed to summarise the available evidence relating to ILD exposure assessment questionnaires, identify research gaps and inform the content for a future single evidence-based ILD questionnaire. METHODS: A scoping review based on Arksey and O'Malley's methodological framework was conducted. ELIGIBILITY CRITERIA: Any questionnaire that elicited exposures specific to ILD was included. A modified COSMIN Risk of Bias Framework was used to assess quality. SOURCES OF EVIDENCE: Relevant articles were identified from MEDLINE and EMBASE up to 23 July 2023. RESULTS: 22 exposure questionnaires were identified, including 15 generally pertaining to ILD, along with several disease-specific questionnaires for hypersensitivity pneumonitis (n=4), chronic beryllium disease, sarcoidosis and silicosis (1 questionnaire each). For most questionnaires, quality was low, whereby the methods used to determine exposure inclusion and questionnaire validation were not reported or not performed. Collectively the questionnaires covered 158 unique exposures and at-risk occupations, most commonly birds, mould/water damage, wood dust, asbestos, farming, automotive mechanic and miners. Only five questionnaires also provided free-text fields, and 13 queried qualifiers such as temporality or respiratory protection. CONCLUSIONS: Designing a robust ILD-specific questionnaire should include an evidence-based and relevance-based approach to exposure derivation, with clinicians and patients involved in its development and tested to ensure relevance and feasibility.

Mortality risk associated with occupational exposures in people with small airways obstruction.

BACKGROUND: Small airways obstruction (SAO) has been associated with occupational exposures. Whether exposure to harmful occupational agents impacts the survival of people with SAO is unknown. Our aim was to estimate the mortality risk associated with occupational exposures among people with SAO. METHODS: We used data from UK Biobank participants with SAO, defined as a ratio of forced expiratory volume in three seconds to forced expiratory volume in six seconds (FEV3/FEV6) below the lower limit of normal. We assigned lifetime occupational exposures to participants with available occupational histories using the ALOHA+ Job Exposure Matrix. Mortality data were provided by the National Death Registries. We used Cox regression to assess the association of all-cause mortality with lifetime occupational exposures (vapours, gases, dusts, fumes-VGDF; solvents; pesticides; metals), adjusting for potential confounders. RESULTS: The 13,942 participants with SAO had a mean age of 56±7 years, 59% were females and 94.2% were of White ancestry. Overall, there were 457 deaths over a median follow-up of 12.8 years. A greater mortality risk was associated with exposure to VGDF, with hazard ratios of 1.32 (95%CI: 1.04-1.78) for low levels and 1.41 (95%CI: 1.11-1.78) for moderate levels of cumulative exposure. There was no evidence of association for the other occupational exposures. CONCLUSION: Lifetime occupational exposure to VGDF in people with SAO may have a detrimental effect on their survival. Future respiratory health surveillance programmes of people exposed to VGDF should consider assessment for SAO and focus on primary prevention through adequate exposure control.

Silicosis, tuberculosis and silica exposure among artisanal and small-scale miners: A systematic review and modelling paper.

An estimated 44 million artisanal and small-scale miners (ASM), largely based in developing economies, face significant occupational risks for respiratory diseases which have not been reviewed. We therefore aimed to review studies that describe silicosis and tuberculosis prevalence and respirable crystalline silica (RCS) exposures among ASM and use background evidence to better understand the relationship between exposures and disease outcomes. We searched PubMed, Web of Science, Scopus and Embase for studies published before the 24th March 2023. Our primary outcome of interest was silicosis or tuberculosis among ASM. Secondary outcomes included measurements of respirable dust or silica, spirometry and prevalence of respiratory symptoms. A systematic review and narrative synthesis was performed and risk of bias assessed using the Joanna Briggs Prevalence Critical Appraisal Tool. Logistic and Poisson regression models with predefined parameters were used to estimate silicosis prevalence and tuberculosis incidence at different distributions of cumulative silica exposure. We identified 18 eligible studies that included 29,562 miners from 13 distinct populations in 10 countries. Silicosis prevalence ranged from 11 to 37%, despite four of five studies reporting an average median duration of mining of <6 years. Tuberculosis prevalence was high; microbiologically confirmed disease ranged from 1.8 to 6.1% and clinical disease 3.0 to 17%. Average RCS intensity was very high (range 0.19-89.5 mg/m3) and respiratory symptoms were common. Our modelling demonstrated decreases in cumulative RCS are associated with reductions in silicosis and tuberculosis, with greater reductions at higher mean exposures. Despite potential selection and measurement bias, prevalence of silicosis and tuberculosis were high in the studies identified in this review. Our modelling demonstrated the greatest respiratory health benefits of reducing RCS are in those with highest exposures. ASM face a high occupational respiratory disease burden which can be reduced by low-cost and effective reductions in RCS.

Occupational lung disease: when should I think of it and why is it important?

Exposure to toxic inhalants in the workplace has the potential to cause (in susceptible individuals) almost any major type of lung disease, such as asthma, COPD and interstitial lung diseases. Patients with occupational lung disease will often present to or will be managed by respiratory specialists without training in occupational respiratory medicine, and patients (or their clinicians) may not identify a link between their disease and their current or a past job. Without an awareness of the range of different occupational lung diseases that exist, their similarity to their non-occupational counterparts, and without directed questioning, these conditions may go unidentified. Patients with occupational lung diseases are often in lower paid work and are disproportionally affected by health inequality. Both clinical and socioeconomic outcomes generally improve if cases are identified early. This allows appropriate advice to be given about the risks of ongoing exposure, clinical management, occupational mobility and, in some cases, eligibility for legal compensation. As respiratory professionals, it is important that these cases are not missed, and if needed, are discussed with a physician with specialised expertise. Here we describe some of the most common occupational lung diseases and outline the diagnostic and treatment approach.

Occupational exposures and small airway obstruction in the UK Biobank Cohort.

Background: Small airways obstruction (SAO) is a key feature of both COPD and asthma, which have been associated with workplace exposures. Whether SAO, which may occur early in the development of obstructive lung disease and without symptoms, also associates with occupational exposures is unknown. Methods: Using UK Biobank data, we derived measurements of SAO from the 65 145 participants with high-quality spirometry and lifetime occupational histories. The ALOHA+ Job Exposure Matrix was used to assign lifetime occupational exposures to each participant. The association between SAO and lifetime occupational exposures was evaluated using a logistic regression model adjusted for potential confounders. A second logistic regression model was also run to account for potential co-exposures. Results: SAO was present in varying proportions of the population depending on definition used: 5.6% (forced expiratory flow between 25 and 75% of the forced vital capacity (FEF25-75) < lower limit of normal (LLN)) and 21.4% (forced expiratory volume in 3 s (FEV3)/forced expiratory volume in 6 s (FEV6)