Page 697 - Clinical Immunology_ Principles and Practice ( PDFDrive )

670 ParT fivE Allergic Diseases

TABLE 49.1 Summary of the Most frequently Encountered Occupational agents Causing
Occupational asthma (Oa)
agents Occupation/industry
High-Molecular-Weight agents
Immunoglobulin E (IgE)–Dependent Causes
Cereals, flour Flour mills, bakers, pastry makers
Animal-derived allergens: laboratory animals Laboratory workers, farmers
Enzymes: α-amylase, maxatase, alcalase, papain, bromelain, Baking product production, bakers, detergent production, pharmaceutical
pancreatin industry, food industry
Seafood Seafood processing
Latex Health care workers, laboratory technicians
Low-Molecular-Weight agents
IgE-Dependent Causes
Acid anhydrides, phthalic, trimellitic, tetrachlorophthalic anhydrides Epoxy resin workers
Platinum salts Platinum refining
Other Potential immunological Mechanisms
Diisocyanates: toluene diisocyanate (TDI), methylene diphenyl- Polyurethane production, plastic industry, insulation, molding, spray painting
diisocyanate (MDI), hexamethylene diisocyanate (HDI)
Wood dusts: western red cedar, iroko, obeche, oak, and others Sawmill workers, carpenters, cabinet and furniture makers
Amines and epoxy resins Rubber industry, cosmetics, hair dye manufacturing, fur industry, rubber
additives
Colophony Electronic industry (flux)
Acrylates: cyanoacrylates, methacrylates, di- and triacrylates Adhesives, dental and orthopedic materials, sculptured fingernails, printing
inks, paints and coatings
Pharmaceutical products Pharmaceutical industry
Formaldehyde, glutaraldehyde, biocides Health care workers, cleaners
Persulfate salts: hair bleach Hairdressers
Reactive dyes: reactive black 5, pyrazolone derivatives, vinyl sulfones, Textile workers, food industry workers
carmine
Metals: chromium, nickel, cobalt Metal refinery, metal alloy production, electroplating, welding

isocyanate-induced asthma. Murine models of toluene diisocya- inhibitory factor [MIF], monocyte chemoattractant protein-1
nate “asthma” have shown a dependence of airway hyperrespon- [MCP-1]). Furthermore, repetitive antigenic stimulation of
siveness (AHR) and Th2-type inflammation on both CD4 and peripheral blood mononuclear cells from patients with diiso-
CD8 cells, but primarily the former. IL-4 and IL-13 are major cyanate asthma induced the synthesis of tumor necrosis factor
determinants of the pathobiology. Recent studies have suggested (TNF)-α and MCP-1, but not IL-4 or IL-5. The bioactive lipid
a role for innate lymphoid (lineage negative) cells to contribute lysophosphatidic acid is released from lung epithelial cells by
to type 2 cytokine production in the airways in response to allergen or isocyanate and has the potential to contribute to the
nonallergenic stimuli. Although few in number, these type 2 pathogenesis of asthma through a number of biological effects.
innate lymphoid cells can produce significant quantities of IL-5 Table 49.1 summarizes the most frequent agents responsible
and IL-13. IL-13 is a pleiotropic cytokine affecting the epithelium, for occupational asthma.
smooth muscle, and immune cells and possibly drives asthma
that is induced by allergens or irritants. The potent oxidant ozone
induces AHR in the mouse through activation of inducible natural NATURAL HISTORY OF OCCUPATIONAL ASTHMA
killer (NK) cells, so similar mechanisms may apply in human AND RISK FACTORS
subjects exposed to molecules that cause oxidative stress.
Neutrophils are also likely to be involved in isocyanate-induced Natural History of the Development of the Disease
asthma, as shown by an increase in myeloperoxidase and IL-8 Studies performed in apprentices shed light on the natural history
after exposure to toluene diisocyanate (TDI). A mixed Th1/Th2 of occupational asthma and risk factors for developing occupa-
pattern of cytokine production has been observed in subjects tional asthma. Epidemiological studies give some indication of
with red cedar–induced asthma. Furthermore, a specific inha- the course of the disease. Atopy and exposure levels have been
lational challenge test induced a mixed Th1/Th2 response in shown to predict sensitization to laboratory animals; sensitization
which CD8 T cells were the main producers of interferon (IFN)-γ. has been shown to precede the occurrence of rhinitis and asthma
However, histopathological changes in the airways in isocyanate- at the workplace. 7
induced asthma are similar to those found in atopic asthma that
is not associated with occupational sensitization. Risk Factors
There is evidence that isocyanates can stimulate human innate The occurrence of OA is the result of an interaction
immune responses by upregulating immune pattern recognition between environmental and host factors (Fig. 49.1). Several host
receptors on monocytes and increasing the chemokines that factors have been shown to increase the risk of developing OA
regulate monocyte/macrophage trafficking (macrophage migration (Table 49.2).