Acid Anhydrides and Asthma

Abstract

We have studied asthma caused by inhaled acid anhydrides as a model of hapten-induced airway hyperresponsiveness. Inhalation tests with the relevant anhydride in sensitised individuals reproducibly provoked a significant increase in non-specific airway responsiveness identifiable 3 h after the test and prior to the development of the late asthmatic reaction. Seven cases of asthma caused by tetrachlorophthalic anhydride (TCPA) had specific IgE in their serum to a TCPA-human serum albumin conjugate. RAST inhibition studies showed the anhydride to be involved in the antibody-combining site. Survey of the factory population where these 7 cases worked allowed investigation of the determinants of the specific IgE response: its presence was associated with intensity of exposure and current cigarette smoking; in addition smoking interacted with atopy to increase the prevalence of specific IgE. During a 5-year period of avoidance of exposure to TCPA specific IgE declined exponentially with a half-life of one year, suggesting continuing IgE secretion. Five years after avoidance of exposure, airway hyperresponsiveness remained increased in several cases.

Characterization in mice of the immunological properties of five allergenic acid anhydrides

“…Many of the acid anhydrides display sensitizing properties and have been associated with occupational asthma. [1][2][3][4] Among those that have been implicated most commonly in allergic sensitization of the respiratory tract, rhinitis and asthma are trimellitic anhydride (TMA), [5][6][7][8] phthalic anhydride (PA), [9][10][11] maleic anhydride (MA), 7,12 hexahydrophthalic anhydride (HHPA) [13][14][15] and tetrahydrophthalic anhydride or methyltetrahydrophthalic anhydride (MTHPA). [16][17][18][19][20] There is considerable, and as yet unresolved, debate regarding the mechanisms through which chemicals may cause respiratory sensitization and occupational asthma and the requirements or otherwise for specific IgE antibody.…”

Dose‐response and time course of specific IgE and IgG after single and repeated topical skin exposure to dry trimellitic anhydride powder in a Brown Norway rat model

“…The pathogenesis of immunologically‐induced asthma can be divided into two phases, a primary antigen/hapten exposure leading to antibody production (sensitization) and subsequent aerosol exposures eliciting asthmatic symptoms. The route of exposure leading to OAA sensitization is commonly thought to be inhalation in the workplace (10–13). Allergic sensitization might also result from antigen exposure by other routes, notably dermal contact.…”

Laboratory Animal Allergy

“…Epithelial cells (furs, hairs and dander) have long been recognised as important allergens (18,19) but more recent studies stress the importance of urine as a primary source of allergenic protein derived from mice, rats and guinea pigs. The presence of allergens in the saliva of rats and in particular of guinea pigs has also been highlighted (19,30,31,32).…”