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.

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.

Identification of late asthmatic reactions following specific inhalation challenge.

Specific inhalation challenge (SIC) is the reference standard for the diagnosis of occupational asthma. Current guidelines for identifying late asthmatic reactions are not evidence based. OBJECTIVES: To identify the fall in forced expiratory volume in 1 s (FEV1) required following SIC to exceed the 95% CI for control days, factors which influence this and to show how this can be applied in routine practice using a statistical method based on the pooled SD for FEV1 from three control days. METHODS: Fifty consecutive workers being investigated for occupational asthma were asked to self-record FEV1 hourly for 2 days before admission for SIC. These 2 days were added to the in-hospital control day to calculate the pooled SD and 95% CI. RESULTS: 45/50 kept adequate measurements. The pooled 95% CI was 385 mL (SD 126), or 14.2% (SD 6.2) of the baseline FEV1, but was unrelated to the baseline FEV1 (r=0.06, p=0.68), or gender, atopy, smoking, non-specific reactivity or treatment before or during SIC. Thirteen workers had a late asthmatic reaction with ≥2 consecutive FEV1 measurements below the 95% CI for pooled control days, 4/13 had <15% and 9/13 >15% late fall from baseline. The four workers with ≥2 values below the 95% CI all had independent evidence of occupational asthma. CONCLUSION: The pooled SD method for defining late asthmatic reactions has scientific validity, accounts for interpatient spirometric variability and diurnal variation and can identify clinically relevant late asthmatic reactions from smaller exposures. For baseline FEV1 <2.5 L, a 15% fall is within the 95% CI.

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.

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.

Sensitising effects of genetically modified enzymes used in flavour, fragrance, detergence and pharmaceutical production: cross-sectional study.

OBJECTIVES: The use of genetically engineered enzymes in the synthesis of flavourings, fragrances and other applications has increased tremendously. There is, however, a paucity of data on sensitisation and/or allergy to the finished products. We aimed to review the use of genetically modified enzymes and the enormous challenges in human biomonitoring studies with suitable assays of specific IgE to a variety of modified enzyme proteins in occupational settings and measure specific IgE to modified enzymes in exposed workers. METHODS: Specific IgE antibodies against workplace-specific individual enzymes were measured by the specific fluorescence enzyme-labelled immunoassay in 813 exposed workers seen in cross-sectional surveys. RESULTS: Twenty-three per cent of all exposed workers showed type I sensitisation with IgE antibodies directed against respective workplace-specific enzymes. The highest sensitisation frequencies observed were for workers exposed enzymes derived from α-amylase (44%), followed by stainzyme (41%), pancreatinin (35%), savinase (31%), papain (31%), ovozyme (28%), phytase (16%), trypsin (15%) and lipase (4%). The highest individual antibody levels (up to 110 kU/L) were detected in workers exposed to phytase, xylanase and glucanase. In a subgroup comprising 134 workers, detailed clinical diagnostics confirmed work-related symptoms. There was a strong correlation (r=0.75, p<0.0001) between the symptoms and antibody levels. Workers with work-related respiratory symptoms showed a higher prevalence for the presence of specific IgE antibodies against workplace-specific enzymes than asymptomatic exposed workers (likelihood ratio 2.32, sensitivity 0.92, specificity 0.6). CONCLUSIONS: Our data confirm the previous findings showing that genetically engineered enzymes are potent allergens eliciting immediate-type sensitisation. Owing to lack of commercial diagnostic tests, few of those exposed receive regular surveillance including biomonitoring with relevant specific IgE assays.

Hypersensitivity Pneumonitis Due to Metalworking Fluid Aerosols.

PURPOSE OF REVIEW: This review summarises the clinical knowledge of hypersensitivity pneumonitis in workers exposed to aerosols of metalworking fluid, reviewing published outbreaks and clinical cases. RECENT FINDINGS: Metalworking fluid exposure has become the commonest recognised cause of occupational hypersensitivity pneumonitis, having been rare before 2000. There are many possible agents in the metalworking fluid which may be the cause of disease including bacteria, mycobacteria, fungae, biocides, emulsifiers, reodorants and dissolved chrome and cobalt. Causes are likely to be different in different outbreaks. Mycobacteria growing in the metalworking fluid have generated immune responses in some workers, but their role in disease causation is not yet established. Many outbreaks have been identified in large workplaces using common sumps. It is not possible to prevent microbial contamination of metalworking fluids in use. Disease prevention should focus on stopping inhalation of aerosols, particularly by re-engineering to remove recirculation.

Understanding health beliefs and behaviour in workers with suspected occupational asthma.

INTRODUCTION: Long delays from symptom onset to the diagnosis of occupational asthma have been reported in the UK, Europe and Canada and workers are often reluctant to seek medical help or workplace solutions for their symptoms. Reducing this delay could improve workers' quality of life, and reduce the societal cost of occupational asthma. This study aimed to explore reasons behind such delays. METHODS: A purposive sample of 20 individuals diagnosed with, or under investigation for, occupational asthma (median age = 52; 70% male; 80% white British) undertook a single semi-structured interview. Interviews were transcribed verbatim and thematic analysis was undertaken in order to explore health beliefs and identify barriers to diagnosis. RESULTS: Four themes were identified: (1) workers' understanding of symptoms, (2) working relationships, (3) workers' course of action and (4) workers' negotiation with healthcare professionals. Understanding of symptoms varied between individuals, from a lack of insight into the onset, pattern and nature of symptoms, through to misunderstanding of what they represented, or ignorance of the existence of asthma as a disease entity. Workers described reluctance to discuss health issues with managers and peers, through fear of job loss and a perceived lack of ability to find a solution. The evolution of workers' understanding depended upon how actively they looked to define symptoms or seek a solution. Proactive workers were motivated to seek authoritative help and negotiate inadequate healthcare encounters with GPs. CONCLUSION: Understanding workers' health beliefs will enable policy makers and clinicians to develop better workplace interventions that may aid diagnosis and reduce delay in identifying occupational asthma.

Hypersensitivity pneumonitis in workers exposed to metalworking fluids.

BACKGROUND: This study used data from a large UK outbreak investigation, to develop and validate a new case definition for hypersensitivity pneumonitis due to metalworking fluid exposure (MWF-HP). METHODS: The clinical data from all workers with suspected MWF-HP were reviewed by an experienced panel of clinicians. A new MWF-HP Score was then developed to match the "gold standard" clinical opinion as closely as possible, using standard diagnostic criteria that were relatively weighted by their positive predictive value. RESULTS: The new case definition was reproducible, and agreed with expert panel opinion in 30/37 cases. This level of agreement was greater than with any of the three previously utilized case definitions (agreement in 16-24 cases). Where it was possible to calculate, the MWF-HP Score also performed well when applied to 50 unrelated MWF-HP cases. CONCLUSIONS: The MWF-HP Score offers a new case definition for use in future outbreaks.