Occupational asthma in office workers.

BACKGROUND: Office work has a relative perception of safety for the worker. Data from surveillance schemes and population-based epidemiological studies suggest that office work carries a low risk of occupational asthma (OA). Office workers are frequently used as comparators in studies of occupational exposure and respiratory disease. AIMS: We aimed to describe and illustrate our tertiary clinical experience of diagnosing OA in office workers. METHODS: We searched the Birmingham NHS Occupational Lung Disease Service clinical database for cases of occupational respiratory disease diagnosed between 2002 and 2020, caused by office work or in office workers. For patients with OA, we gathered existing data on demographics, diagnostic tests including Occupational Asthma SYStem (OASYS) analysis of serial peak expiratory flow and specific inhalational challenge, and employment outcome. We summarised data and displayed them alongside illustrative cases. RESULTS: There were 47 cases of OA (5% of all asthma) confirmed using OASYS analysis of PEFs in the majority. Sixty percent of cases occurred in healthcare, education and government sectors. The most frequently implicated causative exposures or agents were: indoor air (9), printing, copying and laminating (7), cleaning chemicals (4), mould and damp (4), and acrylic flooring and adhesives (4). Exposures were grouped into internal office environment, office ventilation-related and adjacent environment. CONCLUSIONS: Clinicians should be vigilant for exposures associated with OA in office workers who present with work-related symptoms, where respiratory sensitizing agents may be present. A structured approach to assessment of the workplace is recommended.

Occupational asthma caused by peracetic acid-hydrogen peroxide mixture.

BACKGROUND: Healthcare practice in the UK has moved away from using aldehyde disinfectants for the decontamination of endoscopes, in part due to the risk of respiratory sensitization. Peracetic acid (PAA) in combination with hydrogen peroxide (HP) is a commonly used alternative. AIM: We describe a case of occupational asthma (OA) diagnosed at our specialist occupational lung disease clinic and caused by occupational exposure to PAA-HP mixture, used as a disinfectant in an endoscope washer-disinfector machine. CASE REPORT: A 48-year-old man employed as a mycologist and environmental microbiologist at a Birmingham city hospital, UK, presented following an acute exposure to PAA-HP mixture causing lacrimation, burning optic pain and headache. He had also experienced symptoms suggestive of OA for the preceding 10 months, and the diagnosis was confirmed through OASYS analysis of serial peak expiratory flow measurements. He had been exposed to PAA-HP mixture whilst working in the endoscopy department for 12 months prior to the acute episode, and a subsequent specific inhalation challenge test was positive with a late asthmatic response to PAA-HP mixture. CONCLUSION: This case provides evidence for a sensitization mechanism in OA caused by PAA-HP mixture.

Cleaning agent occupational asthma in the West Midlands, UK: 2000-16.

BACKGROUND: Cleaning agents are now a common cause of occupational asthma (OA) worldwide. Irritant airway and sensitization mechanisms are implicated for a variety of old and new agents. AIMS: To describe the exposures responsible for cleaning agent OA diagnosed within a UK specialist occupational lung disease service between 2000 and 2016. METHODS: The Birmingham NHS Occupational Lung Disease Service clinical database was searched for cases of OA caused by cleaning agents, and data were gathered on age, gender, atopic status, smoking history, symptom onset, diagnostic investigations (including Occupational Asthma SYStem analysis of workplace serial peak expiratory flow measurements and specific inhalational challenge), proposed mechanism, industry, occupation and causative agent. RESULTS: Eighty patients with cleaning agent OA (77% female, 76% arising de novo) were identified. The median annual number of cases was 4 (interquartile range = 2-7). The commonest cleaning agents causing OA were chloramines (31%), glutaraldehyde (26%) and quaternary ammonium compounds (11%) and frequently implicated industries were healthcare (55%), education (18%) and leisure (8%). CONCLUSIONS: Certain cleaning agents in common usage, such as chlorine-releasing agents, quaternary ammonium compounds and aldehydes, are associated with sensitization and asthma. Their use alters over time, and this is particularly evident in UK healthcare where cleaning and decontamination practice and policy have changed. Vigilance for OA in workplaces such as hospitals, nursing homes, leisure centres and swimming pools, where these cleaning agents are regularly used, is therefore essential.

Asbestosis is prevalent in a variety of construction industry trades.

A diagnosis of asbestosis, which is a long-latency, fibrotic lung disease, has implications for the patient in terms of prognosis, treatment and compensation. Identifying and quantifying asbestos exposure is difficult without a detailed occupational history, and the threshold dose of asbestos required to cause asbestosis is not well understood. We reviewed all cases of asbestosis diagnosed between 2001 and 2016 at the Birmingham Regional NHS Occupational Lung Disease Service to determine the industries and occupations most frequently implicated in causation, in order to help clinicians identify where asbestosis might enter the differential diagnosis for a patient with chronic respiratory symptoms. A variety of construction trades were frequently reported including carpenters and joiners, pipe fitters, laggers, labourers, painters and shop fitters. Traditionally heavily exposed occupations such as shipbuilding were not commonly seen.

Occupational asthma caused by acrylic compounds from SHIELD surveillance (1989-2014).

BACKGROUND: Acrylic monomers (acrylates), methacrylates and cyanoacrylates all cause asthma by respiratory sensitization. Occupational inhalation exposures occur across a variety of industries including health care and dental work, beauty, laboratory science, assembly and plastic moulding. AIMS: To examine notifications of occupational asthma caused by acrylic compounds from a UK-based regional surveillance scheme, in order to highlight prevalent exposures and trends in presentation. METHODS: Retrospective review of all cases reported to the SHIELD surveillance scheme for occupational asthma, West Midlands, UK between 1989 and 2014. Patient data were gathered on demographics, employment, asthma symptoms and diagnostic investigations including serum immunological testing, serial peak flow analysis and specific inhalation challenge tests. Descriptive statistics were used to illustrate worker characteristics and evidence for sensitization to acrylic compounds. RESULTS: There were 20 affected patients out of 1790 total cases of occupational asthma (1%); all cases were confirmed by OASYS (Occupational Asthma SYStem) analysis of serial peak flow measurements, with three additional positive specific inhalation challenge tests. Three out of 20 (15%) patients were current smokers and 11/20 (55%) were atopic. A variety of exposures and industries were implicated including: manufacturing, health care, beauty and printing and a novel presentation seen in teachers exposed to floor adhesives. CONCLUSIONS: This is the largest reported series of occupational asthma caused by acrylic compounds, which remain an important aetiological factor in this disease. Exposure occurs in a variety of industries, particularly in manufacturing and is seen with other, perhaps better recognized sensitizing agents such as isocyanates and epoxy resins.

Biopsy-proven hypersensitivity pneumonitis caused by a fluorocarbon waterproofing spray.

BACKGROUND: We present the case of a 35-year-old male who developed a chronic hypersensitivity pneumonitis (HP) following inhalational exposure to a fluorocarbon waterproofing aerosol spray, caused by his work for an upholstery and soft furnishings retailer. This is the first case report from inhalational fluorocarbon exposure with histological evidence of chronic HP. This is then discussed in the context of previous reports of interstitial lung disease and lung injury, caused by similar occupational and non-occupational exposures.

Histologist's original opinion compared with multidisciplinary team in determining diagnosis in interstitial lung disease.

Guidelines recommend that multidisciplinary interstitial lung disease meeting (ILD MDT) decisions become the gold standard for diagnosis, replacing the histologist from this position, and identify this as requiring supportive evidence. We have compared diagnoses from lung biopsy material made by expert histologists with the subsequent consensus opinion from a properly constituted ILD MDT in 71 consecutive patients referred to a regional thoracic unit. MDT changed the original histological diagnoses in 30% (95% CI 19.3% to 41.6%) and strengthened the diagnoses from probable to confident in a further 17% (95% CI 9.1% to 27.7%). The assessment of hypersensitivity pneumonitis, non-necrotising granulomas and organising pneumonia accounted for the majority of the changes.

Can serial PEF measurements separate occupational asthma from allergic alveolitis?

BACKGROUND: Occupational asthma commonly results in work-related changes in serial peak expiratory flow (PEF) measurements. Whether alveolitis can result in similar changes is unknown. AIMS: To identify differences and similarities of serial PEF between workers with occupational alveolitis and asthma seen during an outbreak investigation in a factory with metal-working fluid exposure. METHODS: Workers with respiratory symptoms and rest-day improvement were identified by questionnaire. Each was asked to measure PEF 8 times daily for 4 weeks at home and work. Alveolitis was subsequently diagnosed from a validated scoring system including radiological changes, carbon monoxide diffusing capacity, bronchoalveolar lavage and biopsy results. Occupational asthma was confirmed with a positive Oasys score >2.5 and a mean rest-work PEF >16 l/min from serial 2-hourly PEF measurements. The Oasys PEF plotter calculated differences between rest and workdays for mean PEF, diurnal variation and the scores were used to confirm an occupational effect (Oasys, area between curve and time point). Records were compared between the alveolitis group and the group with occupational asthma without alveolitis. RESULTS: Forty workers with occupational asthma and 16 with alveolitis had indistinguishable PEF changes on workdays in terms of magnitude (median reduction 18.5 and 16.1 l/min, respectively) and diurnal variation. Immediate reactions were more common with occupational asthma and late reactions more common with alveolitis. CONCLUSIONS: PEF responses to metal-working fluid aerosols do not distinguish occupational asthma from alveolitis except in timing. They can be used to identify the workplace as the cause of asthma and also alveolitis.

Twenty years of SHIELD: decreasing incidence of occupational asthma in the West Midlands, UK?

INTRODUCTION: Since 2000 a decline in the incidence of occupational asthma (OA) has been reported in the UK and Europe. We aimed to describe and account for trends in the incidence of OA in the West Midlands, UK using annual notification data from the SHIELD voluntary surveillance scheme over the period 1991-2011. METHODS: All notifications to the SHIELD database between January 1991 and December 2011 were identified, along with patients' demographic data, occupations, causative agents and confirmatory tests. Annual notifications were scaled to give an annual count per million workers, giving a measure of incidence, and also standardised against those of bakers' asthma. Non-parametric analyses were undertaken between annual incidence and time (years) for common causative agents using (1) a negative binomial regression univariate model and (2) a logistic regression model calculating annual reporting ORs. A step-change analysis was used to examine time points at which there were marked reductions in incidence. RESULTS: A decrease in annual incidence of OA was observed over the study period (incident rate ratio=0.945; 95% CI 0.933 to 0.957; p<0.0001), an effect that was lost after standardising for bakers' asthma. Decreases in incidence were seen for most common causative agents, with only cleaning product-related OA increasing over 21 years. Marked fall in incidence was seen in 2004 for isocyanates, and in 1995 for latex. Most notifications came from a regional specialist occupational lung disease unit, with notifications from other sites falling from 16 cases/million workers/annum in 1995 to 0 in 2004. CONCLUSIONS: Reporter fatigue and increasing under-recognition of OA are both factors which contribute to the apparent fall in incidence of OA in the West Midlands. There is a future need for interventions that enable health professionals to identify potential cases of OA in the workplace and in healthcare settings.

Cobalt asthma in metalworkers from an automotive engine valve manufacturer.

BACKGROUND: Cobalt asthma has previously been described in cobalt production workers, diamond polishers and glassware manufacturers. AIMS: To describe a case series of occupational asthma (OA) due to cobalt, identified at the Birmingham Heartlands Occupational Lung Disease Unit, West Midlands, UK. METHODS: Cases of cobalt asthma from a West Midlands' manufacturer of automotive engine valves, diagnosed between 1996 and 2005, were identified from the SHIELD database of OA. Case note data on demographics, employment status, asthma symptoms and diagnostic tests, including spirometry, peak expiratory flow (PEF) measurements, skin prick testing (SPT) and specific inhalational challenge (SIC) tests to cobalt chloride, were gathered, and descriptive statistics used to illustrate the data. RESULTS: The natural history of presentations has been described in detail, as well as a case study of one of the affected workers. Fourteen metalworkers (86% male; mean age 44.9 years) were diagnosed with cobalt asthma between 1996 and 2005. Workers were principally stellite grinders, stellite welders or machine setter-operators. All workers had positive Occupational Asthma SYStem analyses of serial PEF measurements, and sensitization to cobalt chloride was demonstrated in nine workers, by SPT or SIC. CONCLUSIONS: We have described a series of 14 workers with cobalt asthma from the automotive manufacturing industry, with objective evidence for sensitization. Health care workers should remain vigilant for cobalt asthma in the automotive manufacturing industry.

Agents and trends in health care workers' occupational asthma.

BACKGROUND: There is a disproportionately high number of cases of work-related asthma occurring in health care occupations due to agents such as glutaraldehyde, latex and cleaning products. AIMS: To understand the causes and measure trends over time of occupational asthma (OA) in health care workers (HCWs). METHODS: We reviewed OA notifications from the Midland Thoracic Society's Surveillance Scheme of Occupational Asthma (SHIELD) database in the West Midlands, UK, from 1991 to 2011 and gathered data on occupation, causative agent and annual number of notifications. RESULTS: There were 182 cases of OA in HCWs (median annual notifications = 7; interquartile range [IQR] = 5-11), representing 5-19% of annual SHIELD notifications. The modal annual notification was 20 (in 1996); notifications have declined since then, in line with total SHIELD notifications. The majority of cases (136; 75%) occurred in nursing, operating theatre, endoscopy and radiology staff. The most frequently implicated agents were glutaraldehyde (n = 69), latex (n = 47) and cleaning products (n = 27), accounting for 79% of the 182 cases. Cleaning product-related OA was an emerging cause with 22 cases after 2001 and only 5 cases between 1991 and 2000. CONCLUSIONS: Control measures within the UK National Health Service have seen a decline in OA in HCWs due to latex and glutaraldehyde, though OA remains a problem amongst HCWs exposed to cleaning products. Continuing efforts are required to limit the number of cases in this employment sector.

Shift work effects on serial PEF measurements for occupational asthma.

BACKGROUND: Diurnal variation (DV) affects lung function but the changes are thought to be related to sleep patterns rather than time of day. When diagnosing occupational asthma (OA), serial peak expiratory flow (PEF) measurements are the recommended first line investigation, but could be confounded by shift work. AIMS: The aim of the study was to investigate the effects of shift work on PEF measurements used for diagnosing OA. METHODS: PEF records containing more than one shift pattern with ≥ 4 days per shift were identified. OA diagnosis was based on an Oasys-2 score ≥ 2.51 and non-OA on having an alternative clinical diagnosis and Oasys-2 score <2.51. The mean area between curves (ABC) score, mean PEF DV and cross-shift PEF changes were calculated for each shift. RESULTS: Records from 123 workers with OA and 69 without OA satisfied inclusion criteria. In the OA group, PEF declined more on afternoon and night shifts than days (P < 0.001). The ABC score was lower in the OA group on night (P < 0.05) and afternoon shifts (P < 0.05) as compared with days, without significant differences in DV. Among those without OA, cross-shift PEF increased more on day shifts (mean + 25 l/min) than afternoon or night shifts (+1 l/min) (P < 0.001). The sensitivity for the ABC score and DV were good and similar across shifts, but specificity was reduced using DV (DV mean 39%; ABC 98%). CONCLUSIONS: PEF responses between work and rest show small differences according to shift type. The ABC score has a high sensitivity and specificity for all shifts; differences in DV have lower specificity.

An outbreak of occupational asthma due to chromium and cobalt.

BACKGROUND: Five metal turners employed by an aerospace manufacturer presented to the Birmingham Chest Clinic occupational lung disease unit. Four cases of occupational asthma (OA) due to chromium salt (3) and cobalt (1) were diagnosed by serial peak-expiratory flow measurements and specific inhalation challenge testing. AIMS: To measure the extent of the outbreak and to provide epidemiological data to ascertain the aetiology. METHODS: Participants answered a detailed, self-administered questionnaire, designed to detect occupational lung disease. Urine chromium and cobalt excretion, spirometry and exhaled nitric oxide measurements were taken. Those with possible, probable or definite non-OA or OA, after questionnaire, were invited to undertake two-hourly peak flow measurements and received specialist follow-up. RESULTS: A total of 62 workers (95% of workforce) participated. Sixty-one per cent of employees were working in higher metalworking fluid (MWF) exposure areas. Ninety per cent of workers had urinary chromium excretion indicating occupational exposure. Sixty-six per cent of workers reported active respiratory symptoms, although there were no significant differences between exposure groups. Two further workers with probable OA were identified and had significantly higher urinary chromium and cobalt concentration than asymptomatic controls. Eighteen cases of occupational rhinitis (OR) were identified, with significantly raised urinary chromium concentration compared with asymptomatic controls. CONCLUSIONS: Chromium salt and cobalt can be responsible for OA and OR in workers exposed to MWF aerosols. Onset of symptoms in those with positive specific challenges followed change in MWF brand. Workers with OA had increased urinary concentrations of chromium and cobalt, and those with OR had increased urinary concentrations of chromium.

Guidelines for the management of work-related asthma.

Work-related asthma, which includes occupational asthma and work-aggravated asthma, has become one of the most prevalent occupational lung diseases. These guidelines aim to upgrade occupational health standards, contribute importantly to transnational legal harmonisation and reduce the high socio-economic burden caused by this disorder. A systematic literature search related to five key questions was performed: diagnostics; risk factors; outcome of management options; medical screening and surveillance; controlling exposure for primary prevention. Each of the 1,329 retrieved papers was reviewed by two experts, followed by Scottish Intercollegiate Guidelines Network grading, and formulation of statements graded according to the Royal College of General Practitioners' three-star system. Recommendations were made on the basis of the evidence-based statements, which comprise the following major evidence-based strategic points. 1) A comprehensive diagnostic approach considering the individual specific aspects is recommended. 2) Early recognition and diagnosis is necessary for timely and appropriate preventative measures. 3) A stratified medical screening strategy and surveillance programme should be applied to at-risk workers. 4) Whenever possible, removing exposure to the causative agent should be achieved, as it leads to the best health outcome. If this is not possible, reduction is the second best option, whereas respirators are of limited value. 5) Exposure elimination should be the preferred primary prevention approach.

Sensitization and irritant-induced occupational asthma with latency are clinically indistinguishable.

BACKGROUND: Acute irritant exposures at work are well-recognized causes of asthma. In the occupational setting, low-dose exposure to the same agent does not provoke asthma. Occupational asthma (OA) with latency due to irritants is not widely accepted. AIMS: To compare workers with OA with latency likely to be due to irritant exposures with workers with the more usual sensitization-induced OA. METHODS: Following identification of a worker who fulfils all the criteria for irritant-induced OA with latency whose investigation documented lime dust as a cause for his OA, we searched the Shield reporting scheme database between 1989 and 2010 for entries where the OA was more likely to be due to irritant than allergic mechanisms and compared these with the remainder where allergic mechanisms were likely. Outcome measures were latent interval from first exposure to first work-related symptom, non-specific bronchial reactivity, smoking, atopy and the presence of pre-existing asthma. RESULTS: A previously fit lecturer teaching bricklaying had irritant-induced OA with latency without unusual exposures with an immediate asthmatic reaction following exposure to a sand/lime mixture (pH 8). The Shield database identified 127 workers with likely irritant-induced asthma with latency and 1646 with hypersensitivity-induced OA. The two groups were indistinguishable in terms of pre-existing asthma, atopy, age, latent interval, non-specific reactivity and smoking. CONCLUSIONS: Irritant exposure is a cause of OA with latency currently clinically indistinguishable from OA due to sensitization.

Differentiating occupational asthmatics from non-occupational asthmatics and irritant-exposed workers.

BACKGROUND: Serial peak expiratory flow (PEF) records have been recommended as a first-line investigation in workers suspected as having occupational asthma (OA). AIMS: To determine which PEF variability index best differentiates workers with OA from non-occupational asthmatics and unaffected irritant-exposed workers. METHODS: PEF was measured at least four times daily for at least 3 weeks in three groups of subjects: (i) forty healthy grain-exposed farmers and dockers, (ii) forty-two consecutive workers with independently confirmed OA and (iii) forty-eight non-occupational asthmatics. Indices of PEF variability were compared between groups. RESULTS: The difference in mean PEF between rest and work periods best separated the occupational asthmatic workers from the others. The upper 95% confidence limit of this index for grain-exposed workers was 2.8% of predicted PEF (16 l/min) and 3.3% (15 l/min) for non-occupational asthmatics. Sensitivity for diagnosing OA using this index was 70%. An increase in diurnal variation on workdays of >7% had a sensitivity of only 27% for the diagnosis of OA. The difference between maximum PEF on workdays and minimum PEF on rest days had a sensitivity of <10% against non-occupational asthmatic controls. CONCLUSIONS: Difference in mean PEF between workdays and rest days is the best simple index for differentiating subjects with OA from those with non-OA or irritant-exposed healthy subjects. Differences >16 l/min are unlikely to be due to significant irritant exposure in healthy workers.

Occupational asthma caused by heated triglycidyl isocyanurate.

Six workers exposed as bystanders to heated triglycidyl isocyanurate (TGIC) developed occupational asthma confirmed by serial peak expiratory flow measurement and Oasys analysis. Specific inhalation challenge testing resulted in late or dual asthmatic reactions to heated TGIC in four of four tested and was negative in three control asthmatics. One worker tested only with unheated TGIC had a negative specific challenge test. Heated TGIC can cause occupational asthma from bystander exposure.

Recent developments in occupational asthma.

Occupational exposures now account for 20% of adult onset asthma. Overall incidence has not declined, but recognition of the problem and substitutions have resulted in dramatic reductions in some causes of occupational asthma, particularly latex and glutaraldehyde in healthcare workers. Newer at risk workers include cleaners and those exposed to metal-working fluid. Standards of care have now been published, supported by evidence- based reviews of the literature, which are likely to require referral to centres specialising in occupational asthma for compliance. The spectrum of occupational asthma is expanding, with low-dose irritant mechanisms likely to account for some occupational asthma with latency. Eosinophilic and non-eosinophilic phenotypes are also seen, the non-eosinophilic variant having more normal non-specific responsiveness than the eosinophilic subgroup. Physiological confirmation of occupational asthma is required but remains challenging. Specific challenges may be negative in workers confirmed as having occupational asthma from workplace challenges. Serial measurements of peak expiratory flow or FEV1 are feasible in the occupational health and general respiratory clinic settings and provide a method of validation of occupational asthma in those without ready access to specific challenge testing, while minimum data quantity standards are now established which need to be achieved for optimal sensitivity/specificity. New developments in the analysis of serial mea-surements of peak expiratory flow comparing the mean hourly values on work and rest days have shown good specificity and sensitivity from shorter records (but more frequent readings) than needed for the standard Oasys score.

Aclidinium bromide provides long-acting bronchodilation in patients with COPD.

Aclidinium bromide is a novel, long-acting, muscarinic antagonist in phase III development for the maintenance treatment of COPD. This phase IIb study investigated the efficacy and safety of aclidinium for the treatment of moderate to severe COPD to establish the optimal dose for phase III studies. A total of 464 patients with moderate to severe stable COPD were randomised to double-blind, once-daily treatment with aclidinium (25, 50, 100, 200, or 400microg), placebo, or open-label tiotropium (18microg) for 4 weeks. Spirometric measurements were performed at 22-24h after the first dose and then at weekly intervals, and from 0.5 to 6h post-dose on day 1 and day 29. Compared with placebo, aclidinium 200microg and 400microg significantly increased trough FEV(1) on day 29 versus baseline. During the first 6h post-dose, the bronchodilatory effect of aclidinium (all doses) on day 1 was comparable to that on day 29. Time to peak FEV(1) was 3h for aclidinium 100-400microg. Aclidinium was well tolerated, with no dose-dependent effect on ECG, laboratory parameters, or adverse events. The incidence of AEs was generally comparable to placebo. Aclidinium produced sustained bronchodilation over 24h and was well tolerated during this short-term study. Based on these data, aclidinium 200microg was selected as the investigational dose for future clinical trials in COPD.