Airborne occupational exposures associated with pulmonary sarcoidosis: a systematic review and meta-analysis.

The aetiology and pathophysiology of sarcoidosis is ill defined-current hypotheses centre on complex genetic-immune-environmental interactions in an individual, triggering a granulomatous process. The aim of this systematic review is to define and describe which airborne occupational exposures (aOE) are associated with and precede a diagnosis of pulmonary sarcoidosis. The methodology adopted for the purpose was systematic review and meta-analyses of ORs for specified aOE associated with pulmonary sarcoidosis (DerSimonian Laird random effects model (pooled log estimate of OR)). Standard search terms and dual review at each stage occurred. A compendium of aOE associated with pulmonary sarcoidosis was assembled, including mineralogical studies of sarcoidosis granulomas. N=81 aOE were associated with pulmonary sarcoidosis across all study designs. Occupational silica, pesticide and mould or mildew exposures were associated with increased odds of pulmonary sarcoidosis. Occupational nickel and aluminium exposure were associated with a non-statistically significant increase in the odds of pulmonary sarcoidosis. Silica exposure associated with pulmonary sarcoidosis was reported most frequently in the compendium (n=33 studies) and was the most common mineral identified in granulomas. It was concluded that aOE to silica, pesticides and mould or mildew are associated with increased odds of pulmonary sarcoidosis. Equipoise remains concerning the association and relationship of metal dusts with pulmonary sarcoidosis.

Lung cancer resection in patients with underlying usual interstitial pneumonia: a meta-analysis.

OBJECTIVE: Patients with lung cancer with underlying idiopathic pulmonary fibrosis and usual interstitial pneumonia (UIP) pattern on CT represent a very high-risk group in terms of postoperative UIP acute exacerbations (AEs) and in-hospital mortality. We sought to investigate the outcomes in these patients. METHODS: We carried out a meta-analysis, searching four international databases from 1 January 1947 to 27 April 2022, for studies in any language reporting on the acute postoperative outcomes of patients with lung cancer undergoing surgical resection with underlying UIP (the primary outcome). Random effects meta-analyses (DerSimonian and Laird) were conducted. We analysed the difference in incidence of postoperative AE as well as the difference in long-term overall survival among subpopulations. These were stratified by the extent of surgical resection, with meta-regression testing (uniivariate and multivariate) according to the stage of disease, operative decision making and country of origin. This study was registered with PROSPERO (CRD42022319245). RESULTS: The overall incidence of AE of UIP postoperatively from 10 studies (2202 patients) was 14.6% (random effects model, 95% CI 9.8 to 20.1, I2=74%). Sublobar resection was significantly associated with a reduced odds of postoperative AE (OR 0.521 (fixed effects model), 95% CI 0.339 to 0.803, p=0.0031, I2=0%). The extent of resection was not significantly associated with overall survival following lung cancer resection in UIP patients (HR for sublobar resection 0.978 (random effects model), 95% CI 0.521 to 1.833, p=0.9351, I2=71%). CONCLUSIONS: With appropriate implementation of perioperative measures such as screening for high-risk cases, appropriate use of steroids, antifibrotics and employing sublobar resection in select cases, the risk of local recurrence versus in-hospital mortality from AEUIP can be balanced and long-term survival can be achieved in a super-selected group of patients. Further investigation in the form of a randomised study is warranted.

Novel occupational causes of hypersensitivity pneumonitis.

PURPOSE OF REVIEW: Hypersensitivity pneumonitis (HP) remains a challenging diagnosis, and a cause is not established in up to 50% of cases. This paper aims to update clinicians on traditional and novel occupational causes of HP, and clinical tools for identifying of causative exposures and antigens. RECENT FINDINGS: Metalworking fluid has become the most frequently cited occupational cause of HP, though geographical variations in exposures exist. Occupational HP is usually associated with work-related symptoms. Systematically derived questionnaires and compendia for HP have been developed for use in cryptogenic disease, though have previously lacked validation; these may help identify inciting antigens or relevant occupational exposures. SUMMARY: Clinicians should enquire about job roles and work-relatedness of symptoms when considering a diagnosis of HP. Outbreaks of metalworking fluid associated HP from around the world are well described, so clinicians should remain vigilant. The usual classification for causative antigen includes animal and plant proteins, fungi, bacteria, low-molecular weight chemicals and metals; however novel occupational exposures and work processes are frequently reported.

Screening tools for work-related asthma and their diagnostic accuracy: a systematic review protocol.

INTRODUCTION: Work-related asthma (WRA) refers to asthma caused by exposures at work (occupational asthma) and asthma made worse by work conditions (work-exacerbated asthma). WRA is common among working-age adults with asthma and impacts individual health, work-life and income but is often not detected by healthcare services. Earlier identification can lead to better health and employment outcomes. However, the optimal tool for screening and its effectiveness in practice is not well established. Screening tools may include whole questionnaires, questionnaire items, physiological measurements and/or immunological tests. Since the publication of the most contemporary WRA or occupational asthma-specific guidelines, further studies evaluating tools for identifying WRA have been performed. Our systematic review aims to summarise and compare the performance of screening tools for identifying WRA in both clinical and workplace settings. METHODS AND ANALYSIS: We will conduct a systematic review of observational and experimental studies (1975-2021) using MEDLINE, EMBASE, CINAHL Plus, Web of Science, CDSR, DARE, HTA, CISDOC databases and grey literature. Two independent reviewers will screen the studies using predetermined criteria, extract data according to a schedule and assess study quality using the Quality Assessment of Diagnostic Test Accuracy 2 tool. Screening tools and test accuracy measures will be summarised. Paired forest plots and summary receiver operating characteristic curves of sensitivities and specificities will be evaluated for heterogeneity between studies, using subgroup analyses, where possible. If the studies are sufficiently homogenous, we will use a bivariate random effect model for meta-analysis. A narrative summary and interpretation will be provided if meta-analysis is not appropriate. ETHICS AND DISSEMINATION: As this is a systematic review and does not involve primary data collection, formal ethical review is not required. We will disseminate our findings through open access peer-reviewed publication as well as through other academic and social media. PROSPERO REGISTRATION NUMBER: CRD42021246031.

Pulmonary function test and computed tomography features during follow-up after SARS, MERS and COVID-19: a systematic review and meta-analysis.

Background: The COVID-19 pandemic follows severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus epidemics. Some survivors of COVID-19 infection experience persistent respiratory symptoms, yet their cause and natural history remain unclear. Follow-up after SARS and MERS may provide a model for predicting the long-term pulmonary consequences of COVID-19. Methods: This systematic review and meta-analysis aims to describe and compare the longitudinal pulmonary function test (PFT) and computed tomography (CT) features of patients recovering from SARS, MERS and COVID-19. Meta-analysis of PFT parameters (DerSimonian and Laird random-effects model) and proportion of CT features (Freeman-Tukey transformation random-effects model) were performed. Findings: Persistent reduction in the diffusing capacity for carbon monoxide following SARS and COVID-19 infection is seen at 6 months follow-up, and 12 months after MERS. Other PFT parameters recover in this time. 6 months after SARS and COVID-19, ground-glass opacity, linear opacities and reticulation persist in over 30% of patients; honeycombing and traction dilatation are reported less often. Severe/critical COVID-19 infection leads to greater CT and PFT abnormality compared to mild/moderate infection. Interpretation: Persistent diffusion defects suggestive of parenchymal lung injury occur after SARS, MERS and COVID-19 infection, but improve over time. After COVID-19 infection, CT features are suggestive of persistent parenchymal lung injury, in keeping with a post-COVID-19 interstitial lung syndrome. It is yet to be determined if this is a regressive or progressive disease.

Barriers to identifying occupational asthma among primary healthcare professionals: a qualitative study.

INTRODUCTION: Occupational asthma (OA) accounts for one in six cases of adult-onset asthma and is associated with a large societal cost. Many cases of OA are missed or delayed, leading to ongoing exposure to the causative agent and avoidable lung function loss and poor employment-related outcomes. Enquiry about work-related symptoms and the nature of work by healthcare professionals (HCPs) is limited, evident in primary and secondary care. Potential reasons cited for this are time pressure, lack of expertise and poor access to specialists. AIM: To understand organisational factors and beliefs and behaviours among primary HCPs that may present barriers to identifying OA. METHODS: We employed a qualitative phenomenological methodology and undertook 20-45 min interviews with primary HCPs in West Midlands, UK. We used purposive and snowball sampling to include general practitioners (GPs) and practice nurses with a range of experience, from urban and rural settings. Interviews were recorded digitally and transcribed professionally for analysis. Data were coded by hand, and thematic analysis was undertaken and determined theoretically until themes were saturated. RESULTS: Eleven HCPs participated (eight GPs, three nurses). Four themes were identified that were considered to impact on identification of OA: (1) training and experience, (2) perceptions and beliefs, (3) systems constraints, and (4) variation in individual practice. OA-specific education had been inadequate at every stage of training and practice, and clinical exposure to OA had been generally limited. OA-specific beliefs varied, as did clinical behaviour with working-age individuals with asthma. There was a focus on diagnosis and treatment rather than attributing causation. Identified issues regarding organisation of asthma care were time constraints, lack of continuity, referral pressure, use of guidelines and templates, and external targets. CONCLUSION: Organisation and delivery of primary asthma care, negative OA-related beliefs, lack of formal education, and exposure to OA may all currently inhibit its identification.

An update on hypersensitivity pneumonitis: what a clinician wants to know.

PURPOSE OF REVIEW: A recent international collaboration has updated the clinical definition and diagnostic recommendations for hypersensitivity pneumonitis, focusing on fibrotic and non-fibrotic phenotypes. However, how these transfer to clinical practice and their impact upon clinical management and prognosis of hypersensitivity pneumonitis is unclear. This review will focus on recent advances in the understanding of the clinical aspects of hypersensitivity pneumonitis, predominantly its epidemiology, diagnosis, classification and treatment. RECENT FINDINGS: Hypersensitivity pneumonitis is a rare disease within the general population, with variable geographical incidence because of environmental, cultural and occupational factors. Confidence in diagnosis relies upon the presence of clinical features with a temporal relationship to an associated exposure, radiological and histopathological features, bronchiolo-alveolar lavage lymphocytosis and precipitating antibodies/specific immunoglobulin G to antigens. Although emerging evidence regarding nintedanib use in progressive fibrotic interstitial lung disease is promising, the majority of therapies (corticosteroids and immunosuppressive agents) used traditionally in hypersensitivity pneumonitis lack a robust evidence base. SUMMARY: With a clear definition of fibrotic and nonfibrotic hypersensitivity pneumonitis phenotypes now established, clinical research trials (predominantly randomized controlled trials) should clarify and resolve the discussion regarding antigen avoidance, corticosteroid therapy, immunosuppressive therapy and antifibrotic therapy in fibrotic and nonfibrotic subtypes of hypersensitivity pneumonitis.

Diagnosis of occupational asthma from serial measurements of forced expiratory volume in 1 s (FEV1) using the Area Between Curves (ABC) score from the Oasys plotter.

OBJECTIVES: To identify the changes in serial 2-hourly forced expiratory volume in 1 s (FEV1) measurements required to identify occupational asthma (OA) using the Oasys Area Between Curves (ABC) score. METHODS: The ABC score from 2-hourly measurements of FEV1 was compared between workers with confirmed OA and asthmatics without occupational exposure to identify the optimum separation using receiver operator characteristic (ROC) analysis. Separate analyses were made for plots using clock time and time from waking to allow for use in shift workers. Minimum record criteria were ≥6 readings per day, >4 day shifts and >4 rest days (or >9 days for controls). RESULTS: A retrospective analysis identified 22 workers with OA and 30 control asthmatics whose records reached the quality standards. Median FEV1 diurnal variation was 20.3% (IQR 16.1-32.6) for OA and 19.5% (IQR 14.5-26.1) for asthmatic controls. ROC curve analysis identified that a difference of 0.056 L/hour gave a ROC score of 0.821 for clock time and 0.768 for time from waking with a sensitivity of 73% and a specificity of 93% for the diagnosis of OA. CONCLUSIONS: The diagnosis of OA requires objective confirmation. Unsupervised serial FEV1 measurements are more difficult to obtain reliably than measurements of peak expiratory flow, which are likely to remain the standard for general use. A FEV1 ABC score >0.056 L/hour provides a valid cut-off for those who wish to use FEV1 rather than peak expiratory flow.

Occupational exposures and idiopathic pulmonary fibrosis.

PURPOSE OF REVIEW: A recent meta-analysis of data from international case-control studies reports a population attributable fraction of 16% for occupational factors in the cause of idiopathic pulmonary fibrosis (IPF). Smoking, genetic factors and other prevalent diseases only partly explain IPF, and so this review aims to summarize recent progress in establishing which occupational exposures are important in cause. RECENT FINDINGS: IPF is a rare disease, although it is the commonest idiopathic interstitial pneumonia. Epidemiological study suggests that incidence of IPF is increasing, particularly in older men. There are significant associations with IPF and occupational exposures to organic dust, including livestock, birds and animal feed, metal dust, wood dust and silica/minerals. Estimates of effect vary between studies, and are influenced by the distribution of employment, study design and case definition. Inhalation of asbestos fibres is a known cause of usual interstitial pneumonia (as seen histologically in IPF), though there are significant linear relationships between asbestos consumption, and mortality from both IPF and mesothelioma, leading to the hypothesis that low-level asbestos exposure may cause IPF. SUMMARY: Research must focus on exposure-response relationships between asbestos and other occupational inhaled hazards, and IPF. Funding bodies and policy makers should acknowledge the significant occupational burden on IPF.

Identifying causation in hypersensitivity pneumonitis: a British perspective.

Background: Establishing whether patients are exposed to a 'known cause' is a key element in both the diagnostic assessment and the subsequent management of hypersensitivity pneumonitis (HP). Objective: This study surveyed British interstitial lung disease (ILD) specialists to document current practice and opinion in relation to establishing causation in HP. Methods: British ILD consultants (pulmonologists) were invited by email to take part in a structured questionnaire survey, to provide estimates of demographic data relating to their service and to rate their level of agreement with a series of statements. A priori 'consensus agreement' was defined as at least 70% of participants replying that they 'Strongly agree' or 'Tend to agree'. Results: 54 consultants took part in the survey from 27 ILD multidisciplinary teams. Participants estimated that 20% of the patients in their ILD service have HP, and of these, a cause is identifiable in 32% of cases. For patients with confirmed HP, an estimated 40% have had a bronchoalveolar lavage for differential cell counts, and 10% a surgical biopsy. Consensus agreement was reached for 25 of 33 statements relating to causation and either the assessment of unexplained ILD or management of confirmed HP. Conclusions: This survey has demonstrated that although there is a degree of variation in the diagnostic approach for patients with suspected HP in Britain, there is consensus opinion for some key areas of practice. There are several factors in clinical practice that currently act as potential barriers to identifying the cause for British HP patients.

Characteristics of hypersensitivity pneumonitis diagnosed by interstitial and occupational lung disease multi-disciplinary team consensus.

INTRODUCTION: The causes of hypersensitivity pneumonitis (HP) in the UK are changing as working practices evolve, and metalworking fluid (MWF) is now a frequently reported causative exposure. We aimed to review and describe all cases of HP from our UK regional service, with respect to the causative exposure and diagnostic characteristics. METHODS: In a retrospective, cross-sectional study, we collected patient data for all 206 cases of HP diagnosed within our UK-based regional NHS interstitial and occupational lung disease service, 2002-17. This included demographics, environmental and occupational exposures, clinical features, and diagnostic tests (CT imaging, bronchiolo-alveolar cell count, lung function, histology). We grouped the data by cause (occupational, non-occupational and unknown) and by presence or absence of fibrosis on CT, in order to undertake hypothesis testing. RESULTS: Cases were occupational (n = 50), non-occupational (n = 56) or cryptogenic (n = 100) in aetiology. The commonest causes were birds = 37 (18%) and MWF = 36 (17%). Other occupational causes included humidifiers and household or commercial waste, but only one case of farmers' lung. Cryptogenic cases were associated with significantly older age, female gender, lower lung function parameters, fewer alveolar lymphocyte counts >20%, and fibrosis on CT; exposure information was missing in 22-33% of cryptogenic cases. CONCLUSION: MWF is the commonest occupational cause of HP, where workers usually present with more acute/subacute features and less fibrosis on CT; refuse work is an emerging cause. Cryptogenic HP has a fibrotic phenotype, and a full occupational history should be taken, as historical workplace exposures may be relevant.

Occupational asthma; the limited role of air-fed respiratory protective equipment.

BACKGROUND: Evidence-based reviews have found that evidence for the efficacy of respiratory protective equipment (RPE) in the management of occupational asthma (OA) is lacking. AIMS: To quantify the effectiveness of air-fed RPE in workers with sensitizer-induced OA exposed to metal-working fluid aerosols in a car engine and transmission manufacturing facility. METHODS: All workers from an outbreak of metal-working fluid-induced OA who had continuing peak expiratory flow (PEF) evidence of sensitizer-induced OA after steam cleaning and replacement of all metal-working fluid were included. Workers kept 2-hourly PEF measurements at home and work, before and after a strictly enforced programme of RPE with air-fed respirators with charcoal filters. The area-between-curve (ABC) score from the Oasys plotter was used to assess the effectiveness of the RPE. RESULTS: Twenty workers met the inclusion criteria. Records were kept for a mean of 24.6 day shifts and rest days before and 24.7 after the institution of RPE. The ABC score improved from 26.6 (SD 16.2) to 17.7 (SD 25.4) l/min/h (P > 0.05) post-RPE; however, work-related decline was <15 l/min/h in only 12 of 20 workers, despite increased asthma treatment in 5 workers. CONCLUSIONS: Serial PEF measurements assessed with the ABC score from the Oasys system allowed quantification of the effect of RPE in sensitized workers. The RPE reduced falls in PEF associated with work exposure, but this was rarely complete. This study suggests that RPE use cannot be relied on to replace source control in workers with OA, and that monitoring post-RPE introduction is needed.

Hospital Attendances and Acute Admissions Preceding a Diagnosis of Occupational Asthma.

PURPOSE: Occupational exposures are a common cause of adult-onset asthma; rapid removal from exposure to the causative agent offers the best chance of a good outcome. Despite this, occupational asthma (OA) is widely underdiagnosed. We aimed to see whether chances of diagnosis were missed during acute hospital attendances in the period between symptom onset and the diagnosis of OA. METHODS: Patients diagnosed with OA at the regional occupational lung disease service in Birmingham between 2007 and 2018 whose home address had a Birmingham postcode were included. Emergency department (ED) attendances and acute admission data were retrieved from acute hospitals in the Birmingham conurbation for the period between symptom onset and diagnosis. RESULTS: OA was diagnosed in 406 patients, 147 having a Birmingham postcode. Thirty-four percent (50/147) had acute hospital attendances to a Birmingham conurbation hospital preceding their diagnosis of OA, including 35 (24%) with respiratory illnesses, which resulted in referral for investigation of possible OA in 2/35. The median delay between symptom onset and diagnosis of OA was 30 months (IQR = 13-60) and between first hospital attendance with respiratory illness and diagnosis 12 months (IQR = 12-48, range 3-96 months) CONCLUSIONS: The chance to reduce the delay in the diagnosis of OA was missed in 33/35 patients admitted or seen in ED with respiratory symptoms in the period between symptom onset and diagnosis of OA. The diagnosis of OA was delayed by a median of 12 months by failure to ask about employment and work relationship of symptoms.

The Role of Occupational and Environmental Exposures in the Pathogenesis of Idiopathic Pulmonary Fibrosis: A Narrative Literature Review.

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterised by a progressive and irreversible decline in lung function, which is associated with poor long-term survival. The pathogenesis of IPF is incompletely understood. An accumulating body of evidence, obtained over the past three decades, suggests that occupational and environmental exposures may play a role in the development of IPF. This narrative literature review aims to summarise current understanding and the areas of ongoing research into the role of occupational and environmental exposures in the pathogenesis of IPF.

Respiratory failure caused by lipoid pneumonia from vaping e-cigarettes.

A young female vaper presented with insidious onset cough, progressive dyspnoea on exertion, fever, night sweats and was in respiratory failure when admitted to hospital. Clinical examination was unremarkable. Haematological tests revealed only thrombocytopenia, which was long standing, and her biochemical and inflammatory markers were normal. Chest radiograph and high-resolution CT showed diffuse ground-glass infiltrates with reticulation. She was initially treated with empirical steroids and there was improvement in her oxygenation, which facilitated further tests. Since the bronchoscopy and high-volume lavage was unyielding, a video-assisted thoracoscopicsurgical biopsy was done later and was suggestive of lipoid pneumonia. The only source of lipid was the vegetable glycerine found in e-cigarette (EC). Despite our advice to quit vaping, she continued to use EC with different flavours and there is not much improvement in her clinical and spirometric parameters.

Do laboratory challenge tests for occupational asthma represent what happens in the workplace?

Specific inhalation challenge (SIC) is the diagnostic reference standard for occupational asthma; however, a positive test cannot be considered truly significant unless it can be reproduced by usual work exposures. We have compared the timing and responses during SIC in hospital to Oasys analysis of serial peak expiratory flow (PEF) during usual work exposures.All workers with a positive SIC to occupational agents between 2006 and 2015 were asked to measure PEF every 2 h from waking to sleeping for 4 weeks during usual occupational exposures. Responses were compared between the laboratory challenge and the real-world exposures at work.All 53 workers with positive SIC were included. 49 out of 53 had records suitable for Oasys analysis, 14 required more than one attempt and all confirmed occupational work-related changes in PEF. Immediate SIC reactors and deterioration within the first 2 h of starting work were significantly correlated with early recovery, and late SIC reactors and a delayed start to workplace deterioration were significantly correlated with delayed recovery. Dual SIC reactions had features of immediate or late SIC reactions at work rather than dual reactions.The concordance of timings of reactions during SIC and at work provides further validation for the clinical significance of each test.