Stuart M. Brooks

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.

Relationship between numbers of beta adrenergic receptors in lymphocytes and disease severity in asthma.

Abstract In order to assess the status of beta adrenergic receptors in bronchial asthma, binding studies using (−) [ 3 H] dihydroalprenolol (DHA) were performed on lymphocytes of 10 control subjects and 11 stable asthmatic patients. Specific DHA binding was generally lower at all DHA concentrations in asthmatics. At 12 nM DHA concentration, specific DHA binding was 391 ± 40 fM/mg protein in controls and 263 ± 35 fM/mg protein for asthmatic subjects (p

Occupational asthma induced by inhalation and ingestion of garlic

Repeated exposure to garlic dust induced severe asthma in an atopic patient. Subsequently, the patient also developed marked adverse responses after ingestion of garlic. Immunologic investigations carried out in an asymptomatic period revealed significant skin reactivity and bronchospasm after challenge with both garlic dust and extract. The results of a controlled oral challenge test to garlic dust were also positive. The patients serum contained unusually high quantities of garlic-specific IgE. Cross allergenicity between garlic and other members of the Liliaceae family were documented by the RAST inhibition technique.

The diversity of reaginic immune responses to platinum and palladium metallic salts

As part of a National Institute for Occupational Safety and Health health hazards evaluation, workers employed in a precious metal refinery exposed to platinum (Pt), palladium (Pd), and other group VIII metallic salts were evaluated for direct skin test sensitivity to Pt. Current (107) and former (30) workers who quit or were discharged because of Pt-related health problems were prick tested with ammonium hexachloroplatinate ([NH4]2 PtCl6). Of the 107 currently exposed workers, 15 (14%) exhibited positive skin tests, as indexed by immediate reactivity at a dose of 10(-3) gm/ml or less. Eight (27%) of the 30 former workers no longer exposed to Pt also demonstrated positive Pt skin tests. Sera obtained from the workers were assessed for transferable antibodies to Pt and Pd salts by monkey passive cutaneous anaphylaxis. In addition, Pt-specific antibodies were evaluated by RAST. Results of these studies suggested that short- and long-term passive cutaneous anaphylaxis immune responses occur after exposure to both Pt and Pd compounds. Results of RAST analysis for Pt-specific antibodies indicated that significantly higher (p less than 0.001) levels were present in the sera of skin test-positive workers as compared to control sera from Pt-exposed, skin test-negative workers or nonexposed control subjects. Evidence was also obtained that Pt or Pt-protein adducts present in the sera of exposed workers may compete for IgE-binding sites in the RAST assay. The specificity of the Pt-specific RAST system was proved by inhibition experiments.

Assessment of airway hyperresponsiveness in chronic stable asthma

Airway reactivity and disease severity were investigated in 24 subjects with stable chronic bronchial asthma. Disease severity was determined by assigning a disease severity score (DSS) representing six clinical and therapeutic parameters. Airway hyperresponsiveness was assessed in two ways: airway reactivity score (ARS) based on the number of positive responses to a question concerning exposure to 22 nonspecific inhaled irritants and methacholine challenge testing and determining the cumulative dose causing a 20% reduction in FEV2 (CMD20). A significant correlation between DDS and CMD20 (r = 0.57; p less than 0.003) and DSS and ARS (r = 0.67; p less than 0.0003) attested to the important influence of airway hyperresponsiveness on disease severity. Significant correlations for ARS with CMD20 (r = -0.60; p less than 0.002) suggested the consistency with which the ARS estimated methacholine hyperresponsiveness. We found no statistically significant correlations between DSS, ARS, or CMD20 and the age of subject, duration of asthma, or other host characteristics. There was not a significant correlation between the degree of airway obstruction and DSS or ARS noted. The results of this investigation demonstrate the value of the use of clinical information for assessing airway hyperresponsiveness and disease severity in patients with chronic stable asthma. Both ARS and DSS are useful clinical tools for estimating methacholine reactivity.

Platelet thrombopathy in asthmatic patients with elevated immunoglobulin E

Abnormalities of second-wave platelet aggregation were demonstrated in 17 of 33 asthmatic patients in whom drug and diet intake were controlled in the hospital. Mean abnormal responses were significantly greater after epinephrine- (p less than 0.001), adenosine diphosphate-(less than 0.001), collagen- (p = 0.01), and thrombin- (p less than 0.001) induced platelet aggregation in patients with immunologically mediated asthma and serum IgE levels greater than 250 U/ml as compared to patients without immunologic factors and/or normal controls. Mean pollen-specific radioallergosorbent (RAST) binding was also significantly higher in patients with abnormal aggregation as compared to normal platelet responders (p = 0.02). Release of serotonin generally reflected abnormal aggregation patterns in asthmatic patients. Platelet factor 4 release was significantly decreased in the same groups of patients. These results suggest that the allergic state may affect platelet membrane responsiveness to multiple aggregating agents.

Diverse profiles of immunoreactivity in toluene diisocyanate (TDI) asthma.

Possible immunoreactivity to chemically well-characterized mono- and diisocyanate protein conjugates was reevaluated in 15 workers with TDI asthma and 17 normal (nonexposed) volunteers. Lymphocytes of nine sensitive workers were incubated with TDI human serum albumin (HSA) conjugates. Leucocyte inhibitory factor (LIF) was produced. Leucocyte inhibitory factor was also induced by hexamethylene diisocyanate (HDI) protein conjugates in four of these workers who had no prior history of exposure to HDI. Disappearance of TDI- and HDI-induced LIF was noted in several sensitive workers who were removed from further TDI exposure. Three LIF-positive workers also demonstrated positive intracutaneous reactivity to TDI-HSA. One workers had a markedly positive RAST (25.5% binding) to a monofunctional (p-tolyl isocyanate) protein reagent. These studies suggest that isocyanates have the potential for eliciting heterogeneous immune responses in certain subpopulations of exposed workers. Continued contact with isocyanates may be necessary for maintenance of specific immunity. Possible cross reactivity between TDI and HDI may be determined by new antigenic sites created by isocyanate protein interactions.

Reactive Airways Dysfunction Syndrome (RADS) and Irritant-Induced Asthma

Irritant-induced asthma signifies nonallergic asthma without latency or immunological sensitization. The acute sudden-onset type that appears within 24-h after a single, massive irritant gas, vapor, or fume exposure is coined Reactive Airways Dysfunction Syndrome (RADS). Almost all cases are accidental and arise without warning such as with an unanticipated explosion, accidental release of irritant(s) held under pressure, activities taking place in a confined space and/or emissions of smoke and irritant gases accompanying a fire. Presumably in some poorly understood manner, the massive irritant exposure leads to persistent airway inflammation, altered airway remodeling, sustained airway hyperresponsiveness and asthmatic symptoms. A second type of irritant-induced asthma emerges not as suddenly as RADS. Individuals are repeatedly exposed to non-massive levels of irritants over a few days, weeks, or months and eventually develop clinical asthma. Ostensibly, this type of asthma is associated with a preexisting susceptibility including asthma in clinical remission or stability. The long-term outcome of subjects with irritant-induced asthma is similar to subjects with allergic occupational asthma. The treatment of irritant-induced asthma is similar to the treatment afforded patients suffering with other types of adult-onset asthma.

Delayed anaphylactoid reaction in a worker exposed to chromium

A 29-year-old male welder reported systemic reactions after exposure to chromium. Inhalation challenge testing to 29 micrograms/m3 of sodium chromate aerosol resulted in late appearing systemic urticaria, angioedema, and severe bronchospasm that occurred at the same time as a threefold rise in plasma histamine. A direct leukocyte inhibitory factor test to 5.5 X 10(-6)mol/L Na2CrO4 was positive. Although the mechanism of this reaction is unknown, the positive leukocyte inhibitory factor and the general acceptance of hexavalent chromium as a contact skin sensitizer suggest that cell-mediated mechanisms could be involved.

Irritant-Induced Airway Disorders

Thousands of persons experience accidental high-level irritant exposures each year but most recover and few die. Irritants function differently than allergens because their actions proceed nonspecifically and by nonimmunologic mechanisms. For some individuals, the consequence of a single massive exposure to an irritant, gas, vapor or fume is persistent airway hyperresponsiveness and the clinical picture of asthma, referred to as reactive airways dysfunction syndrome (RADS). Repeated irritant exposures may lead to chronic cough and continual airway hyperresponsiveness. Cases of asthma attributed to repeated irritant-exposures may be the result of genetic and/or host factors.