Chronic Obstructive Pulmonary Disease and Work: The Continuing Narrative.

It has long been recognized that harmful inhaled workplace exposures can contribute to the development of chronic obstructive pulmonary disease (COPD). This article, intended for the clinician, summarizes some of this evidence and some areas of controversy. Current estimates based on pooled epidemiological analyses of population-based studies identify that approximately 14% of the burden of COPD (and 13% of the burden of chronic bronchitis) is attributable to such exposures. In addition to these approaches, various studies implicate specific exposures as contributing. Certain of these relating to cadmium, coal, and respirable crystalline silica are discussed in more detail. Despite this amassed evidence to date supporting associations between COPD and workplace exposures, there have been surprisingly few studies that have attempted to assess the attribution by experts of an occupational cause in cases of COPD. One study, using hypothetical cases of COPD, noted that while expert physicians were willing to make such an occupational link, this was only likely in cases with light smoking histories and a priori defined heavy occupational exposures. Relatively recent data relating to computed tomography (CT) scan appearances may give the clinician a further guide. Several studies from populations have now linked potentially harmful occupational exposures specifically with the presence of emphysema on CT scanning. It will be of interest to see if this finding, along with other clinical attributes of cases such as smoking and family histories, exclusion of asthma, genetic data, and the nature of workplace exposures, will increase the future diagnosis by clinicians of occupational COPD. In the interim, while better diagnostic approaches are developed, we suggest that consideration of an occupational cause is an important part of the clinical investigation of cases of COPD. Finally, we suggest that evidence-based workplace preventive strategies for occupational COPD should be informed by knowledge of which exposures are most important to reduce, and whether and when intervention to reduce exposure at an individual worker level is warranted.

What role for asbestos in idiopathic pulmonary fibrosis? Findings from the IPF job exposures case-control study.

BACKGROUND: Asbestos has been hypothesised as the cause of the recent global increase in the incidence of 'idiopathic' pulmonary fibrosis (IPF). Establishing this has important diagnostic and therapeutic implications. The association between occupational asbestos exposure and IPF, and interaction with a common (minor allele frequency of 9% in European populations) genetic variant associated with IPF, MUC5B rs35705950, is unknown. METHODS: Multicentre, incident case-control study. Cases (n=494) were men diagnosed with IPF at 21 UK hospitals. Controls (n=466) were age-matched men who attended a hospital clinic in the same period. Asbestos exposure was assessed at interview using a validated job exposure matrix and a source-receptor model. The primary outcome was the association between asbestos exposure and IPF, estimated using logistic regression adjusted for age, smoking and centre. Interaction with MUC5B rs35705950 was investigated using a genetic dominant model. RESULTS: 327 (66%) cases and 293 (63%) controls ever had a high or medium asbestos exposure risk job; 8% of both cases and controls had cumulative exposure estimates ≥25 fibre ml⁻¹ years. Occupational asbestos exposure was not associated with IPF, adjusted OR 1.1 (95% CI 0.8 to 1.4; p=0.6) and there was no gene-environment interaction (p=0.3). Ever smoking was associated with IPF, OR 1.4 (95% CI 1 to 1.9; p=0.04) and interacted with occupational asbestos exposure, OR 1.9 (95% CI 1 to 3.6; p=0.04). In a further non-specified analysis, when stratifying for genotype there was significant interaction between smoking and work in an exposed job (p<0.01) for carriers of the minor allele of MUC5B rs35705950. CONCLUSION: Occupational asbestos exposure alone, or through interaction with MUC5B rs35705950 genotype, was not associated with IPF. Exposure to asbestos and smoking interact to increase IPF risk in carriers of a common genetic variant, the minor allele of MUC5B rs35705950. TRIAL REGISTRATION NUMBER: NCT03211507.

Chest physician-reported, work-related, long-latency respiratory disease in Great Britain.

Much of the current burden of long-latency respiratory disease (LLRD) in Great Britain is attributed to historical asbestos exposure. However, continuing exposure to other agents, notably silica, also contributes to disease burden. The aim of this study was to investigate the incidence of work-related LLRD reported by chest physicians in Great Britain, including variations by age, gender, occupation and suspected agent.LLRD incidence and incidence rate ratios by occupation were estimated (1996-2014). Mesothelioma cases by occupation were compared with proportional mortality ratios.Cases were predominantly in men (95%) and 92% of all cases were attributed to asbestos. Annual average incidence rates (males) per 100 000 were: benign pleural disease, 7.1 (95% CI 6.0-8.2); mesothelioma, 5.4 (4.8-6.0); pneumoconiosis, 1.9 (1.7-2.2); lung cancer, 0.8 (0.6-1.0); chronic obstructive pulmonary disease (COPD), 0.3 (0.2-0.4). Occupations with a particularly high incidence of LLRD were miners and quarrymen (COPD), plumbers and gas fitters (asbestosis), and shipyard and dock workers (all other categories). There was a clear concordance between cases of SWORD mesothelioma and proportional mortality ratios by occupation.Occupationally caused LLRD continues to contribute to a significant disease burden. Many cases are attributable to past exposure to agents such as asbestos and silica, but the potential for occupational exposures persists.

COPD causation and workplace exposures: an assessment of agreement among expert clinical raters.

BACKGROUND: Although occupational exposure is a known risk factor for Chronic Obstructive Pulmonary Disease (COPD), it is difficult to identify specific occupational contributors to COPD at the individual level to guide COPD prevention or for compensation. The aim of this study was to gain an understanding of how different expert clinicians attribute likely causation in COPD. METHODS: Ten COPD experts and nine occupational lung disease experts assigned occupational contribution ratings to fifteen hypothetical cases of COPD with varying combinations of occupational and smoking exposures. Participants rated the cause of COPD as the percentage contribution to the overall attribution of disease for smoking, occupational exposures and other causes. RESULTS: Increasing pack-years of tobacco smoking was associated with significantly decreased proportional occupational causation ratings. Increasing weighted occupational exposure was associated with increased occupational causation ratings by 0.28% per unit change. Expert background also contributed significantly to the proportion of occupational causation rated, with COPD experts rating on average a 9.4% greater proportion of occupational causation per case. CONCLUSION: Our findings support the notion that respiratory physicians are able to assign attribution to different sources of causation in COPD, taking into account both smoking and occupational histories. The recommendations on whether to continue to work in the same job also differ, the COPD experts being more likely to recommend change of work rather than change of work practice.

Relapsing nitrofurantoin-induced pneumonitis.

Nitrofurantoin has well-described associations with a range of adverse pulmonary effects. We report the case of a 72-year old woman with relapsing pneumonitis secondary to the intermittent use of nitrofurantoin, a pattern of disease not well-represented in the literature. The case is also noteworthy as the diagnosis was initially overlooked due to the circumstances of the patient's medication use. Lung biopsy was avoided by detailed history taking.

Chronic Obstructive Pulmonary Disease and the workplace.

Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disease associated with increasing morbidity and mortality worldwide. Whilst tobacco smoking is the important cause, other causes are recognized. This article discusses the contribution that harmful inhaled occupational exposures make to the overall burden of COPD, and goes on to discuss other aspects of the COPD workplace interface. Prevention is key. All healthcare professionals have a responsibility to consider workplace issues when dealing with their COPD patients.

Adenovirus-derived vectors for prostate cancer gene therapy.

Prostate cancer is a leading cause of death among men in Western countries. Whereas the survival rate approaches 100% for patients with localized cancer, the results of treatment in patients with metastasized prostate cancer at diagnosis are much less successful. The patients are usually presented with a variety of treatment options, but therapeutic interventions in prostate cancer are associated with frequent adverse side effects. Gene therapy and oncolytic virus therapy may constitute new strategies. Already a wide variety of preclinical studies has demonstrated the therapeutic potential of such approaches, with oncolytic prostate-specific adenoviruses as the most prominent vector. The state of the art and future prospects of gene therapy in prostate cancer are reviewed, with a focus on adenoviral vectors. We summarize advances in adenovirus technology for prostate cancer treatment and highlight areas where further developments are necessary.

Clinical adenoviral gene therapy for prostate cancer.

Prostate cancer is at present the most common malignancy in men in the Western world. When localized to the prostate, this disease can be treated by curative therapy such as surgery and radiotherapy. However, a substantial number of patients experience a recurrence, resulting in spreading of tumor cells to other parts of the body. In this advanced stage of the disease only palliative treatment is available. Therefore, there is a clear clinical need for new treatment modalities that can, on the one hand, enhance the cure rate of primary therapy for localized prostate cancer and, on the other hand, improve the treatment of metastasized disease. Gene therapy is now being explored in the clinic as a treatment option for the various stages of prostate cancer. Current clinical experiences are based predominantly on trials with adenoviral vectors. As the first of a trilogy of reviews on the state of the art and future prospects of gene therapy in prostate cancer, this review focuses on the clinical experiences and progress of adenovirus-mediated gene therapy for this disease.

Abuse by care professionals. Part 4: an exploration of available resources.

This fourth article will explore the resources available to those who are abused and also the measures available to prevent abuse by healthcare professionals. It was found that, despite good intentions, available measures, which include training and supervision of those likely to abuse, changes in environment, relying on the victim's own support network and generalist professional support networks, are far from adequate. There are a number of measures available to prevent abuse by care professionals from happening. These include clinical supervision, continuing professional development and training, current research awareness and implementation and vastly improved communication between care providers. The only organization that appears to be working in the field of abuse by healthcare professionals is the London-based voluntary sector organization WITNESS.

Management of simple intratesticular cysts: a single-institution 11-year experience.

OBJECTIVES: To evaluate the clinicoradiologic findings and outcomes of management of simple intratesticular cysts, by review of an 11-year experience. METHODS: From March 1994 to September 2005, 24 men underwent scrotal ultrasound scan and follow-up for simple intratesticular cysts. The median follow-up was 32 months (range, 6 to 124 months). The records were analyzed retrospectively for presentation, radiologic findings, and outcomes of management. RESULTS: All 24 patients with simple intratesticular cysts were managed successfully with radiologic surveillance. No patient underwent orchidectomy or required enucleation of the cyst. CONCLUSIONS: Simple intratesticular cysts can be managed conservatively with regular ultrasound surveillance by an experienced uroradiologist, without the need for surgical intervention.