Karin A. Pacheco

Diagnosis and Management of Work-Related Asthma: American College of Chest Physicians Consensus Statement

BACKGROUND A previous American College of Chest Physicians Consensus Statement on asthma in the workplace was published in 1995. The current Consensus Statement updates the previous one based on additional research that has been published since then, including findings relevant to preventive measures and work-exacerbated asthma (WEA). METHODS A panel of experts, including allergists, pulmonologists, and occupational medicine physicians, was convened to develop this Consensus Document on the diagnosis and management of work-related asthma (WRA), based in part on a systematic review, that was performed by the University of Alberta/Capital Health Evidence-Based Practice and was supplemented by additional published studies to 2007. RESULTS The Consensus Document defined WRA to include occupational asthma (ie, asthma induced by sensitizer or irritant work exposures) and WEA (ie, preexisting or concurrent asthma worsened by work factors). The Consensus Document focuses on the diagnosis and management of WRA (including diagnostic tests, and work and compensation issues), as well as preventive measures. WRA should be considered in all individuals with new-onset or worsening asthma, and a careful occupational history should be obtained. Diagnostic tests such as serial peak flow recordings, methacholine challenge tests, immunologic tests, and specific inhalation challenge tests (if available), can increase diagnostic certainty. Since the prognosis is better with early diagnosis and appropriate intervention, effective preventive measures for other workers with exposure should be addressed. CONCLUSIONS The substantial prevalence of WRA supports consideration of the diagnosis in all who present with new-onset or worsening asthma, followed by appropriate investigations and intervention including consideration of other exposed workers.

Epigenetics mediate environment : gene effects on occupational sensitization.

Purpose of reviewEpigenetics is the study of stable modifications of fixed genomes that direct which genes are expressed and which are silenced. Epigenetic changes are modulated by environmental exposures, making epigenetics the interface between genes and environment. This has particular relevance in understanding the effect of occupational exposures on the expression of allergic disease. The goal of this review is to describe how epigenetic changes affect transcription potential, and to examine more closely the effect of specific environmental and occupational exposures on epigenetic variations that alter allergy gene transcripts and the inflammatory milieu. Recent findingsGene transcription is activated when specific CpG sites are demethylated and histones are acetylated, and, conversely, silenced when sites are methylated and histones deacetylated. The development of Th1 and Th2 phenotypes, and expression of Treg cells, are now known to be modulated by epigenetic mechanisms. Workplace exposures such as tobacco smoke, particulates, diesel exhaust, polyaromatic hydrocarbons, ozone, and endotoxin, among others, suppress Treg development, and enhance expression of inflammatory cytokines and allergic phenotypes by epigenetic means. SummaryEpigenetic manipulation to open and close transcription sites provides flexibility of gene expression in response to changing environmental cues. It may also be the window whereby allergic disease in the workplace can be reduced by targeted environmental interventions.

New insights into laboratory animal exposures and allergic responses.

Purpose of review To update the epidemiology of laboratory animal allergy, identify new exposures in the laboratory animal workplace, discuss complexities in the exposure–response relationship, and review the immunology of symptomatic and allergic responses. Recent findings Laboratory animal allergy remains a common occupational hazard of research scientists, technicians and animal handlers. The epidemiology is typical of a stable workforce: incidence is low, although prevalence is high. Risk factors of atopy, current exposures, and sensitization to cats or dogs incompletely predict disease. Exposures include a complex, potent mixture of allergens, biological adjuvants such as endotoxin and irritants. The dose–response relationship between laboratory animal exposure, sensitization and symptoms is hard to define: cross-sectional studies identify most sensitized workers in moderate laboratory animal exposure, not in the highest exposure. Exposure assessments based on workday averages underestimate exposure peaks that may be significant for symptoms and disease. Although we have assumed that workers without symptoms are not sensitized to laboratory animal allergens, recent data demonstrate that many asymptomatic workers do make laboratory animal-specific immune responses that may be necessary to prevent symptomatic disease. Summary Understanding laboratory animal exposures and disease must include exposures other than allergen, and responses other than allergic disease.

The role of lymphocyte proliferation tests in assessing occupational sensitization and disease.

Purpose of reviewLymphocyte proliferation testing (LPT) is used in diagnosing occupationally acquired delayed-type hypersensitivity. It has been used in beryllium-health effects, and its role is expanding in metal allergy. It may find application in diagnosis of other sensitizers. Recent findingsUse of the beryllium LPT (BeLPT) in medical surveillance identifies beryllium sensitization at low exposure with chronic beryllium disease (CBD) that leads to physiologic impairment and need for immunosuppressive medications. New studies indicate that both beryllium exposure and genetic variation are associated with increased risk of CBD. Borderline positive BeLPTs warrant inclusion into diagnostic algorithms. Furthermore, use of LPTs to diagnose metal allergy is being proposed in diagnosis of chromium allergy and hypersensitivity to surgical implants. New occupational sensitizers continue to be identified including metalworking fluids, the sterilizing agent ortho-phthalaldehyde and the solvent para-chlorobenzotrifluoride. Use of LPT in occupational surveillance to these agents and other known sensitizers may play expanding roles. SummaryLymphocyte proliferation testing serves a valuable role in diagnosing occupational sensitization, as demonstrated with beryllium-health effects, as cases continue to be found at low exposure levels. The use of LPTs in diagnosing contact allergy is expanding, and new applications may be identified in human and animal studies.

RADS and Its Variants Asthma by Another Name

This article describes the different clinical variants of irritant-induced asthma, specifically focusing on high-dose irritant-induced asthma and irritant-induced work-exacerbated asthma, as well as reviews known causes, addresses the often adverse medical and socioeconomic outcomes of this complex condition, and considers issues of causation from an occupational and environmental medicine perspective.

Allergy to Surgical Implants

Surgical implants are essential elements of repair procedures to correct worn out joints, damaged spinal components, heart and vascular disease, and chronic pain. However, many of the materials that provide stability, flexibility, and durability to the implants are also immunogenic. Fortunately, allergic responses to surgical implants are infrequent. When they do occur, however, the associated pain, swelling, inflammation, and decreased range of motion can significantly impair the implant function. Given the high numbers of joint replacements performed in the developed world, allergic reactions to orthopedic implants form the largest category of allergic responses. The most important allergens in this category include nickel, cobalt, chromium, and bone cement. These allergens are also the most important in reactions to spinal surgeries. Multiple cardiac and neurostimulatory devices are constructed of metals and adhesives that can be sensitizing in some individuals. Implantable pulse generators, important in cardiac pacemakers, gastric stimulators, and neurostimulators, may include components made of stainless steel, titanium alloy, platinum and iridium, epoxy resins, poly methyl methacrylates, and isocyanates, all of which are immunogenic in some patients. Cardiac stents and patches are often made of Nitinol, a composite of nickel and titanium. More surgical procedures are closed using skin glues, which are also capable of triggering a blistering contact dermatitis. Patch testing is the gold standard to determine sensitization, and this review provides a list of standard allergens to test for different implants. The patients most appropriate for testing include (1) pre-operative joint replacement patients with a prior history of skin reactions to metal jewelry, jean snaps, watch bands, metal glass frames, artificial nails, or skin glue; (2) post-operative joint replacement failure patients needing revision without an obvious cause such as infection or mechanical incompatibility; and (3) post-operative cardiac or neurological patients with localized rash, pain, swelling, or inflammation near or over the implant.