Epidemiology of occupational hypersensitivity pneumonitis; reports from the SWORD scheme in the UK from 1996 to 2015.

OBJECTIVE: To estimate the reported incidence of occupational hypersensitivity pneumonitis (OHP) in the UK and to consider whether the pattern of attributed causation has changed over time. METHODS: All cases of OHP reported to the SWORD scheme between January 1996 and December 2015 were classified into 1 of 10 categories of the suspected agent. Cases were grouped into four 5-year time periods to examine any changing pattern in incidence or suspected causation. For each time period, the annual incidence was calculated using the estimated number of reported cases and the working population of the UK. RESULTS: Between 1996 and 2015, there were 202 actual cases of OHP reported to SWORD, equating to an estimated 818 cases, when adjusting for the sampling ratio. Over this period, the annual UK incidence was 1.4 per million workers. The mean (SD) age of reported cases was 52 (13) years, and cases were four-times more likely to be men than women. Over the study period, there was a fall in the proportion of cases reported to be due to agricultural exposures (44-12%), and an increase in cases due to metalworking fluids (MWFs, 2-45%). CONCLUSIONS: Over the last 20 years, the incidence of OHP in the UK has been ∼1-2 cases per million workers per year. Working with water-based MWFs is now the most commonly suspected causative exposure for OHP cases reported to the SWORD scheme in the UK.

UK asbestos imports and mortality due to idiopathic pulmonary fibrosis.

BACKGROUND: Previous studies have demonstrated that the rising mortality due to mesothelioma and asbestosis can be predicted from historic asbestos usage. Mortality due to idiopathic pulmonary fibrosis (IPF) is also rising, without any apparent explanation. AIMS: To compare mortality due to these conditions and examine the relationship between mortality and national asbestos imports. METHODS: Mortality data for IPF and asbestosis in England and Wales were available from the Office for National Statistics. Data for mesothelioma deaths in England and Wales and historic UK asbestos import data were available from the Health & Safety Executive. The numbers of annual deaths due to each condition were plotted separately by gender, against UK asbestos imports 48 years earlier. Linear regression models were constructed. RESULTS: For mesothelioma and IPF, there was a significant linear relationship between the number of male and female deaths each year and historic UK asbestos imports. For asbestosis mortality, a similar relationship was found for male but not female deaths. The annual numbers of deaths due to asbestosis in both sexes were lower than for IPF and mesothelioma. CONCLUSIONS: The strength of the association between IPF mortality and historic asbestos imports was similar to that seen in an established asbestos-related disease, i.e. mesothelioma. This finding could in part be explained by diagnostic difficulties in separating asbestosis from IPF and highlights the need for a more accurate method of assessing lifetime occupational asbestos exposure.

Asthma in furniture and wood processing workers: a systematic review.

BACKGROUND: Wood dust is a common cause of occupational asthma. There is potential for high exposure to wood dust during furniture and wood manufacturing processes. AIMS: To evaluate the evidence for non-neoplastic respiratory ill health associated with work in the furniture and wood manufacturing sector. METHODS: A systematic review was performed according to PRISMA guidelines. Articles were graded using SIGN (Scottish Intercollegiate Guideline Network) and MERGE (Methods for Evaluating Research Guidelines and Evidence) criteria, with data grouped by study outcome. RESULTS: Initial searches identified 1328 references, from which 55 articles were included in the review. Fourteen studies were graded A using MERGE or >2++ using SIGN. All but one paper describing airway symptoms reported an increased risk in higher wood dust exposed workers in comparison to lower or non-exposed groups. Five studies reporting asthma examined dose response; three found a positive effect. The relative risk for asthma in exposed workers in the single meta-analysis was 1.5 (95% CI 1.25-1.87). Two studies reported more obstructive lung function (forced expiratory volume in 1 s [FEV1]/forced vital capacity < 0.7) in exposed populations. Excess longitudinal FEV1 decline was reported in female smokers with high wood dust exposures in one study population. Where measured, work-related respiratory symptoms did not clearly relate to specific wood immunoglobulin E positivity. CONCLUSIONS: Work in this sector was associated with a significantly increased risk of respiratory symptoms and asthma. The evidence for wood dust exposure causing impaired lung function is less clearly established. Further study is required to better understand the prevalence, and causes, of respiratory problems within this sector.

Systematic review of respiratory case definitions in metalworking fluid outbreaks.

BACKGROUND: Since the mid-1990s, outbreaks of asthma and extrinsic allergic alveolitis (EAA) have been identified in workers exposed to metalworking fluids (MWFs). The cause of these outbreaks remains to be determined. AIMS: To identify and review all previously published occupational lung disease case definitions and diagnostic criteria that have been utilized during MWF outbreak investigations. METHODS: Respiratory outbreaks due to MWFs were identified by a systematic literature search for articles published between 1990 and October 2011. Investigations reporting the usage of disease case definitions or diagnostic criteria for respiratory disease were reviewed and summarized. RESULTS: The literature search identified 35 papers relating to 27 outbreaks of respiratory disease in MWF-exposed workers. Fourteen case definitions for MWF-related respiratory disease were identified: seven for EAA, five for occupational asthma and one each for humidifier fever and industrial bronchitis. A single paper was identified where any comparison of different disease case definitions (for EAA) had been performed. CONCLUSIONS: A range of case definitions and diagnostic criteria for MWF respiratory disease have been utilized in outbreak investigations, but the majority have been produced for individual outbreak investigations without previous validation. It may be difficult to compare the findings of future workplace studies without a more standardized approach to case identification and diagnosis.

Occupational asthma and rhinitis due to detergent enzymes in healthcare.

BACKGROUND: The use of proteolytic enzymes to improve the cleaning efficacy of washing powders was introduced in the mid 1960s. Many microbial enzymes are known to be potent respiratory sensitizers but previously there has been only one case of occupational asthma associated with workplace exposure in a healthcare worker. AIMS: To report two cases of occupational asthma associated with exposure to biological enzymes in health-care workers and related occupational cases. METHODS: Reporting of clinical case reports from three different work places. RESULTS: One case of occupational asthma and three other cases with work-related asthma or rhinitis occurred in one workplace. A single case of probable occupational asthma presented at a second workplace with another case of work-related asthma at a third workplace. Exposures occurred in areas used for cleaning medical instruments and endoscopy suites. Hygiene measurements confirmed the potential for exposure. Control measures were not in place and recognition of the hazard was missing in these workplaces. CONCLUSIONS: Detergent enzymes when used in healthcare settings should be recognized as potential respiratory sensitizers. Healthcare institutions and professional bodies that recommend the use of detergent enzymes should review their risk assessments to ensure that the most appropriate methods for preventing or reducing exposure are in place.

Work-related symptoms in nail salon technicians.

BACKGROUND: Nail salons are a rapidly expanding small business sector. Environmental health practitioners have raised concerns about potential health and safety issues. AIMS: To establish the extent of work-related health issues reported by nail salon technicians, their knowledge of health and safety regulations and of the products used. METHODS: Nail technicians completed a researcher-administered questionnaire, and responses were compared to those of non-exposed office-based control subjects. RESULTS: In all, 39 of 588 nail salons approached agreed to participate (7%), with all 71 (100%) of the available nail technicians within these salons completing study questionnaires. The majority of the nail technicians (99%) had received training that had included aspects of health and safety and most reported being aware of the Control of Substances Hazardous to Health regulations (59/70, 84%) and risk assessments (65/70, 93%). Compared to the control group, the nail technicians reported statistically significant increased levels of work-related neck (OR 5.0, 95% CI 1.6-15.6), shoulder (15.0, 3.1-71.8), wrist/hand (3.6, 1.2-10.7) and lower back problems (3.5, 1.0-12.5). Work-related nasal symptoms were also significantly more common in nail technicians (6.2, 1.3-30.7). CONCLUSIONS: This study demonstrated a higher prevalence of a range of musculoskeletal problems and respiratory symptoms reported by nail technicians compared to office-based controls. An ergonomic and exposure assessment of work practices in this industry is warranted to identify the working practices associated with these symptoms, in order to inform best practice, supplement industry and regulatory guidance and develop appropriate practical work-based training.

Respiratory symptoms in insect breeders.

BACKGROUND: A number of specialist food suppliers in the UK breed and distribute insects and insect larvae as food for exotic pets, such as reptiles, amphibians and invertebrates. AIMS: To investigate the extent of work-related (WR) symptoms and workplace-specific serum IgE in workers potentially exposed to a variety of biological contaminants, including insect and insect larvae allergens, endotoxin and cereal allergens at a UK specialist insect breeding facility. METHODS: We undertook a study of respiratory symptoms and exposures at the facility, with subsequent detailed clinical assessment of one worker. All 32 workers were assessed clinically using a respiratory questionnaire and lung function. Eighteen workers consented to provide serum for determination of specific IgE to workplace allergens. RESULTS: Thirty-four per cent (11/32) of insect workers reported WR respiratory symptoms. Sensitization, as judged by specific IgE, was found in 29% (4/14) of currently exposed workers. Total inhalable dust levels ranged from 1.2 to 17.9 mg/m(3) [mean 4.3 mg/m(3) (SD 4.4 mg/m(3)), median 2.0 mg/m(3)] and endotoxin levels of up to 29435 EU/m(3) were recorded. CONCLUSIONS: Exposure to organic dusts below the levels for which there are UK workplace exposure limits can result in respiratory symptoms and sensitization. The results should alert those responsible for the health of similarly exposed workers to the potential for respiratory ill-health and the need to provide a suitable health surveillance programme.

Approaches to the diagnosis and management of occupational asthma amongst UK respiratory physicians.

This study aimed to assess the approach to the diagnosis and management of occupational asthma amongst general (non-specialist) respiratory consultants in the UK. A random sample of 100 UK general respiratory physicians were invited to participate, and asked to provide information on their diagnostic approach to a case scenario of a patient with possible occupational asthma relating to flour exposure. Participation rates were 42% for the main part of the study. Less than half of consultants specifically reported they would ask whether symptoms improved away from work, and just over a third mentioned examining the patient. All of those interviewed recommended a chest X-ray, and 98% simple spirometry. Eighty-six per cent suggested measurement of serial peak flows, recorded for between 2 and 8 weeks, with measurements taken half-twelve hourly. Less than half advocated a specific flour allergy test, and almost one-quarter (23%) would not perform any immunological test at all. Once a diagnosis of occupational asthma was confirmed, less than two-thirds of those interviewed commented they would recommend some form of exposure reduction, and only 28% specifically stated they would offer compensation advice. The diagnosis of occupational asthma by general respiratory physicians within the UK lacks standardisation, and in some cases falls short of evidence-based best practise.

Molecular cloning of a novel rat G-protein-coupled receptor gene expressed prominently in lung, adrenal, and liver.

A gene and cDNA (named G10d) encoding a novel member of the G-protein-coupled receptor (GCR) superfamily has been isolated from a rat genomic library and a rat liver cDNA library by tandom polymerase chain reaction (PCR) amplification and hybridization screening. Comparison of the sequence of the encoded protein to other members of the rhodopsin family of the GCR superfamily suggests that this new member is a peptide receptor. The G10d gene is present as a single copy in the rat genome and its translational open reading frame is intronless. Northern analysis demonstrates a wide and uneven distribution of G10d mRNA in the adult rat, with the highest mRNA abundance in lung, liver and adrenal gland extracts.

Human papillomavirus and Epstein-Barr virus in sinonasal Schneiderian papillomas. An in situ hybridization and polymerase chain reaction study.

Using the polymerase chain reaction (PCR), it has been recently reported that the Epstein-Barr virus (EBV) is present in the majority of Schneiderian sinonasal papillomas (SNP) of the inverted type and may play a role in the pathogenesis of these lesions. The reported prevalence rates of human papillomavirus (HPV) in different types of SNP is also controversial and in need of clarification. Twenty-eight SNP from 27 patients were histologically classified and evaluated for evidence of EBV using PCR and 2 different sensitive and specific in situ hybridization (ISH) procedures for EBER1. Similarly, two methods of ISH were also used for the detection of HPV, using biotinylated DNA probes sensitive for 14 different HPV types as well as more sensitive and specific radioactive RNA probes for HPV types 6, 11, and 16. Polymerase chain reaction was successful in 19 papillomas, including 12 of 19 inverted SNP, 1 of 1 inverted SNP with squamous cell carcinoma, 4 of 5 fungiform SNP, and 2 of 3 oncocytic lesions. Southern blot hybridization of PCR products showed the presence of EBV DNA in two lesions, including one inverted SNP and the single inverted SNP with squamous cell carcinoma. By both DNA- and RNA-mRNA ISH, positivity for EBER was detected in rare stomal lymphocytes but not the overlying epithelium in the inverted SNP with SCC. The remaining cases, including the other inverted SNP positive for EBV by PCR, were completely negative by both ISH techniques. Human papillomavirus was detected by ISH in 1 of 19 (5%) inverted, 1 of 1 (100%) inverted with squamous cancer, 5 of 5 (100%) fungiform, and 0 of 3 (0%) oncocytic SNP. Three SNP contained HPV 6 (all fungiform), three SNP labeled for HPV 11 (two fungiform and the inverted SNP with squamous cancer), and one inverted SNP contained HPV 16. Of the five fungiform SNP, four showed foci of koilocytosis. The results indicate that EBV is not present in sinonasal papillomas. The presence of EBV positive stromal lymphocytes in these lesions may account for a proportion of PCR-positive cases. Oncocytic SNP are unassociated with HPV, whereas inverted SNP contain HPV in a minority of cases. In contrast, fungiform SNP are consistently associated with HPV types 6 and 11 and usually show histologic evidence of viral infection.

cDNA cloning of a G-protein-coupled receptor expressed in rat spinal cord and brain related to chemokine receptors.

A series of cDNAs and a genomic clone (named RBS11) were isolated, from a variety of rat brainstem, pituitary and/or spinal cord cDNA libraries and a genomic library by low-stringency hybridization screening with a rat angiotensin receptor cDNA. The RBS11 protein, as conceptualized from these DNAs, is a novel member of the rhodopsin family of the G-protein-coupled receptor (GCR) superfamily. Comparison of RBS11 to other members of the GCR superfamily suggests that the RBS11 protein might be a receptor for a peptide ligand in the chemokine family. The RBS11 protein sequence is unusual in that it is without N-linked glycosylation consensus sequences in the putative exofacial regions. Northern analysis indicates that the mRNA for RBS11 accumulates widely and unevenly in the adult rat, with the mRNA being most prominent in extracts of spinal cord, brain, kidney, gut, uterus and testes.

Using a breastfeeding prevalence survey to identify a population for targeted programs.

Often, efforts to improve overall population health require identifying and targeting programs to specific high-risk populations. Breastfeeding is an example. In order to determine initiation and duration rates among various groups in the City of Toronto, a random sample of 434 mothers with infants at four months of age was surveyed to determine the prevalence of breastfeeding and major impacts on its duration. The study found that, overall, 83% of mothers initiated breastfeeding at birth. The greatest rate of decline occurred during the first month. At four months postpartum, 57% of mothers continued to breastfeed, including 35% who were exclusively breastfeeding and 22% who were supplementing breast milk with formula. Breastfeeding duration was related to a number of factors, including information and support, parity, education, use of formula supplements and country of birth. Specific groups are identified for targeted programs, and a number of strategies are proposed.

Chronic cough - occupational considerations.

Chronic cough is a common symptom in a wide range of respiratory conditions, and may also occur as a result of upper airway or gastro-esophageal problems. Whilst chronic cough of any cause may be exacerbated by work, in some cases it has a direct occupational cause, resulting from a harmful acute or chronic workplace exposure. Such occupational conditions may only be suspected by taking a detailed occupational history, and directly asking employed patients whether their cough improves away from work. Early and accurate diagnosis, linked with tailored drug therapy, modification of workplace exposures, and expert compensation advice is likely to offer the best outcome for this group of patients.

Mutation of N-myristoylation site converts endothelial cell nitric oxide synthase from a membrane to a cytosolic protein.

Endothelial cell nitric oxide synthase (ECNOS) is a membrane-associated enzyme that generates endothelium-derived relaxing factor/nitric oxide (EDRF/NO) from L-arginine. We have suggested, from the cloning of the bovine ECNOS cDNA, that the presence of an N-myristoylation consensus sequence may impart its membrane localization since cytosolic forms of NOS do not contain such domains. To test the hypothesis that N-myristoylation is necessary for particulate ECNOS, we performed site-directed mutagenesis of the myristic acid acceptor site, Gly-2, and changed the glycine codon to alanine by a single nucleotide substitution. Expression of wild-type ECNOS in COS cells resulted in greater than 95% of the enzymatic activity in crude membrane fractions (as measured by the conversion of [3H]L-arginine to [3H]L-citrulline). In contrast, expression of the Gly-2 to Ala-2 mutant (G2A) demonstrated 8% ECNOS activity in membranes and 92% in the cytosol. The back mutation (from Ala-2 to Gly-2, A2G) restored ECNOS activity to the particulate fraction as seen with the wild type. Both wild-type membrane ECNOS and cytosolic G2A ECNOS activities were dependent on NADPH and calcium and were inhibited to the same extent by NG-monomethyl L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME). Moreover, kinetic analysis of these enzymes revealed similar Kms for L-arginine (2-4 microM, n = 3), demonstrating that the mutation did not affect ECNOS function. Thus, N-myristoylation is necessary for the membrane localization of ECNOS and may be of special significance for the basal or flow-induced production of NO by the endothelium.

Differential cytokine mRNA expression by neonatal pulmonary cells.

The purpose of this study was to describe cytokine profiles of human neonatal pulmonary cells isolated by tracheal aspiration (TA) and by deep pulmonary lavage (DPL). We hypothesized that mRNA phenotyping, using the technique of reverse transcriptase polymerase chain reaction (RT-PCR), would reveal differences in cytokine expression patterns between cells from proximal and distal airway compartments. We reasoned that cells derived by DPL may reflect pathogenic pathways indicative for the development of bronchopulmonary dysplasia in the premature infant. Here we have described the detection of mRNA for IL-1 alpha, IL-1 beta, IL-6, IL-8, and tumor necrosis factor-alpha. Fourteen paired TA and DPL samples from six premature infants were collected at 1, 7, or 28 d of age. Two of 14 samples were negative for beta-actin (a ubiquitous mRNA) by RT-PCR and were excluded from further analysis. Each of the remaining 12 samples expressed IL-8. Furthermore, each cytokine could be expressed by TA or DPL cells. Cytokine mRNA phenotype profiles were found to differ between TA and DPL cells in four of five paired samples. Our results show that cells retrieved from these two pulmonary compartments are sources for these cytokines and suggest that RT-PCR of TA/DPL cells can be used to test hypothetical predictive markers for the development of bronchopulmonary dysplasia.

Differential regulation of CENP-A and histone H3 phosphorylation in G2/M.

After DNA replication, cells condense their chromosomes in order to segregate them during mitosis. The condensation process as well as subsequent segregation requires phosphorylation of histone H3 at serine 10. Histone H3 phosphorylation initiates during G2 in pericentric foci prior to H3 phosphorylation in the chromosome arms. Centromere protein A (CENP-A), a histone H3-like protein found uniquely at centromeres, contains a sequence motif similar to that around H3 Ser10, suggesting that CENP-A phosphorylation might be linked to pericentric initiation of histone H3 phosphorylation. To test this hypothesis, we generated peptide antibodies against the putative phosphorylation site of CENP-A. ELISA, western blot and immunocytochemical analyses show that CENP-A is phosphorylated at the shared motif. Simultaneous co-detection demonstrates that phosphorylation of CENP-A and histone H3 are separate events in G2/M. CENP-A phosphorylation occurs after both pericentric initiation and genome-wide stages of histone H3 phosphorylation. Quantitative immunocytochemistry reveals that CENP-A phosphorylation begins in prophase and reaches maximal levels in prometaphase. CENP-A phosphoepitope reactivity is lost during anaphase and becomes undetectable in telophase cells. Duplication of prekinetochores, detected as the doubling of CENP-A foci, occurs prior to complete histone H3 phosphorylation in G2. Mitotic phosphorylation of histone H3-family proteins shows tight spatial and temporal control, occurring in three phases: (1) pericentric H3 phosphorylation, (2) chromosome arm H3 phosphorylation and (3) CENP-A phosphorylation at kinetochores. These observations reveal new cytological landmarks characteristic of G2 progression.