Kam S. Tse

Specific IgE antibodies in workers with occupational asthma due to western red cedar

The presence of specific IgE antibodies in the serum of patients with occupational asthma resulting from exposure to western red cedar (RCA) was studied by a radioallergosorbent test (RAST). The antigen matrix used in the RAST was either a conjugate of Sepharose particles with antigens in a crude cedar extract or with plicatic acid, the major haptenic component of cedar antigens. Of eighteen patients with clinical RCA and positive reaction to antigenic bronchoprovocation, eight were found to have abnormal RAST values. By appropriate absorption experiments, the serum RAST activity was shown to represent cedar antigen‐specific IgE antibodies. No significant RAST activity was detected in the serum specimens from sixteen control subjects or from ten patients with negative bronchoprovocation‐reaction to antigenic challenge. These results suggest that IgE antibody‐mediated allergic reaction may be an important pathogenetic factor in RCA.

Baker's asthma. Clinical and immunological studies.

Seven bakers with respiratory symptoms were evaluated by skin tests, RAST assay for specific IgE antibodies to rye and wheat, inhalation challenge with methacholine for the determination of non‐specific bronchial reactivity, and bronchoprovocation with rye and wheat extracts for the determination of antigen‐specific bronchial reactivity. An immediate asthmatic response to antigen challenge was observed in four subjects and all of them had a high level of flour‐specific IgE antibodies. The serum RAST values provided a more accurate predictive value than the degree of cutaneous sensitivity determined by skin testing with respect to the bronchial response to antigenic challenge. Among those who reacted positively to antigenic bronchoprovocation, a much lower antigen dose was required to elicit a positive reaction if the subject also had an increased degree of non‐specific bronchial reactivity. An elevated RAST value was not found in thirty‐eight asymptomatic bakers or in ten asthmatics who had no occupational exposure to flour. Thus, bakers asthma appears to he a form of allergic asthma to cereal flours mediated by specific IgF antibodies. Both the level of serum IgE antibodies and the degree of non‐specific bronchial reactivity are important factors which may influence a bakers bronchial response upon inhalation of cereal flours.

The release of platelet-activating factor into plasma during allergen-induced bronchoconstriction

Plasma histamine and platelet-activating factor (PAF) were measured in six subjects with mild seasonal asthma before and after allergen-induced bronchoconstriction, and in six other patients with asthma before and after methacholine-induced bronchoconstriction. A significant increase in plasma histamine and PAF levels was found in patients with mild seasonal asthma after allergen-induced bronchoconstriction but not in patients with asthma after bronchoconstriction induced by methacholine. There was a significant correlation between the baseline plasma PAF levels and the degree of bronchial hyperresponsiveness to methacholine. These findings suggests that PAF may be an important mediator in the pathogenesis of asthma and bronchial hyperresponsiveness.

Histamine and leukotrienes release in bronchoalveolar fluid during plicatic acid-induced bronchoconstriction

Bronchoalveolar lavage (BAL) was performed before and 10 minutes after inhalation challenge with plicatic acid in five patients with red cedar asthma. There was a significant release of histamine and leukotriene E4 into the BAL fluid in all the patients after challenge. Inhalation challenge with methacholine in six patients with nonoccupational asthma and inhalation challenge with plicatic acid in two subjects without asthma did not result in the release of mediators in the BAL fluid. These studies provide direct evidence that plicatic acid-induced bronchoconstriction was accompanied by increased levels of histamine and leukotriene E4 release, whereas a nonimmunologic induction of bronchoconstriction did not induce such local mediator release. BAL may provide a useful means of studying the pathogenesis of occupational asthma caused by exposure to low-molecular-weight compounds.

Differences in mediator release between allergic rhinitis and asthma

To determine why patients with allergic rhinitis alone differ in their airway response to inhaled allergen compared to patients with allergic asthma, bronchial lavage was performed in 10 subjects with allergic asthma and in five subjects with allergic rhinitis, before and after inhalation challenge with antigen to produce an immediate asthmatic reaction. Before antigen challenge, the subjects with asthma had higher absolute neutrophil counts in the lavage fluid. After antigen challenge, the subjects with asthma released significant amounts of bronchoconstrictive mediators, such as histamine and thromboxane B2 into the lavage fluid, whereas subjects with rhinitis alone did not. There was also a significant increase in prostaglandin E2 in the subjects with asthma after antigen challenge. Nonimmunologic bronchoconstriction with methacholine inhalation challenge in six other subjects with asthma did not demonstrate an increase in any of the lavage fluid mediator levels that were measured. A positive correlation was found between methacholine provocative concentration causing a 20% drop in FEV1 and the concentration of prostaglandin E2 in the lavage fluid before challenge. The significance of this observation has yet to be determined. The results suggest that subjects with allergic asthma differ from subjects with rhinitis alone in their capacity to release more mediators into the airways on antigen challenge. It is not known whether this increase in mediators is due to increase in the number of mast cells in the airways or due to increase in mediator releasability from the mast cells of subjects with asthma.

Occupational asthma caused by eastern white cedar (Thuja occidentalis) with demonstration that plicatic acid is present in this wood dust and is the causal agent.

A worker developed symptoms of work-related asthma a few weeks after starting to work in a sawmill where eastern white cedar (Thuja occidentalis) was transformed into shingles. The diagnosis of occupational asthma was confirmed by monitoring of peak expiratory flow rates and bronchial responsiveness to histamine off work and at work, and specific inhalation challenges in the laboratory that demonstrated an isolated late asthmatic reaction after exposure for 4 hours to the wood dust. Specific inhalation challenges with western red cedar (thuja plicata) for 2 hours and plicatic acid (PA) for 7 minutes also caused an isolated late asthmatic reaction. Elevated specific IgE levels to PA were present. Antiserum was produced in rabbits that were immunized with PA conjugated to human serum albumin. With this antiserum in inhibition experiments, cross-reactivity between western red cedar and eastern white cedar, both belonging to the family of arborvitae, was found. It is estimated that eastern white cedar contains approximately half the amount of PA present in western red cedar.

Baker's asthma. Studies of the cross-antigenicity between different cereal grains

Specific IgE antibodies were demonstrated in the sera of six bakers with respiratory symptoms of asthma or bronchitis by the radioallergosorbent (RAST) assay. The specificity of the antibodies was found to be directed not only against the common flours (rye, wheat) used in the bakeries but also against triticale, barley, oat. corn and rice in some of the bakers. By using the RAST inhibition tests, cross‐antigenicity was shown to exist between different cereal grains. The degree of cross‐reactivity closely paralleled their taxonomic relationship and appeared to be in the following order of decreasing closeness: wheat, triticale, rye. barley, oat. rice and corn. The allergenic activity in the rye and wheat extracts was found to be distributed among various fractions of different molecular weights.

Lymphocyte sub-populations in patients with allergic and non-allergic asthma

The subpopulations of peripheral blood lymphocytes were identified using monoclonal antibodies specific for T lymphocytes (T11 antibodies), B lymphocytes (B1 antibodies), helper/inducer T cells (T4 antibodies) and suppressor/cytotoxic cells (T8 antibodies). Ninety‐six subjects, including twenty‐five patients with allergic asthma, nineteen patients with non‐allergic asthma and fifty‐two controls without asthma, were studied. There was no significant difference in the lymphocyte subsets between the allergic and non‐allergic asthmatics. When comparing patients with asthma as a group with the controls, a decrease in the number of T8‐positive suppressor cells and therefore, an increase in the helper/suppressor cell ratio were demonstrated in the asthamtics. A relative deficiency of suppressor T cells may represent another immunological marker of bronchial asthma.

A study of serum antibody activity in workers with occupational exposure to diphenylmethane diisocyanate.

The prevalence of sensitization was studied in a group of 76 foundry workers with occupational exposure to diphenylmethane diisocyanate (MDI). Ten workers had clinical evidence of asthma, 40 had non‐asthmatic respiratory symptoms, and 26 were asymptomatic. Specific IgE antibodies to MDI were found in two workers (2.6%) and specific IgG antibodies, in five workers (6.6%). The prevalence of IgE and IgG antibodies was higher in the 10 subjects with asthma than in the non‐asthmatic group. The prevalence of anti‐paratolyl‐monoisocyanate antibodies was not significantly different from that of anti‐MDI antibodies, and both haptenic determinants displayed a high degree of cross‐reactivity in the RAST inhibition test. The role of humoral immunological mechanisms in MDI‐induced asthma is unclear in view of the rather low prevalence of these serum antibodies in this group of workers.

Lymphocyte Subpopulations in Patients with Allergic Rhinitis

The lymphocyte subpopulations were classified using monoclonal antibodies specific for B lymphocytes (B1 antibodies), T lymphocytes (T11 and OKT3 antibodies). Helper/inducer T cells (T4 antibodies) and suppressor/cytotoxic T cells (T8 antibodies). Three groups of subjects were studied: 20 normal controls, 29 patients with allergic rhinitis and a subgroup of nine patients who had received immunotherapy. The proportion of B Lymphocytes, total T cells and T4 positive (helper/inducer) cells were not significantly different between the groups, but allergic patients were found to have a decreased proportion of suppressor T8 positive (suppressor/cytotoxic) cells and hence a high helper/suppressor cell ratio. These received immunotherapy. These results imply that a suppressor cell deficiency may be an underlying mechanism of allergic disease, and that immunotherapy could correct the suppressor cell deficiency.