Bronchial asthmatic reactivity

Persons who have developed a bronchial asthmatic reactivity to one isocyanate may show bronchial asthmatic reactivity to other isocyanates according to studies reported by O Brien et al. (16). 

The mechanism for the development of the bronchial asthmatic reactivity from exposure to isocyanates has not been clearly defined, although there has been and continues to be considerable research on this effect. Bruchner (V7)> Scheel Q8), Nava et. 

The primary respiratory irritancy and bronchial asthmatic reactivity discussed above are generally accepted as occupational health problems that can occur from excessive exposure to isocyanates either as vapor or as inhalable particles in workplace air. 

In summary, the major potential occupational health problem from excessive exposure to isocyanates is primary respiratory irritation. A fraction of workers exposed may develop a bronchial asthmatic reaction to isocyanates and there appears to be some cross reactivity. The most extensive study, including preexposure baseline respiratory function measurements, has provided data indicating that keeping exposures to TDI below 0.02 ppm (0.14 ug/ m3) appears to prevent decrement in respiratory function. There are less data on exposures and respiratory function of workers using other isocyanates. Isocyanates such as MDI are less volatile than TDI. There is less potential for exposure to vapors of the lower volatility isocyanates, but exposures to vapor and to particulates can occur and exposures to all isocyanates do need to be controlled in order to protect workers. 

Hypersensitivity to the irritant effects of inhaled sulfur dioxide is well recognized and is a usual feature of asthma. As little as 1.0 ppm of the inhaled gas can produce significant broncho-constriction in groups of asthmatics (Koenig et ai, 1980 Koenig et ai, 1982), and the symptomatic severity of asthma can be correlated with atmospheric SO2 pollution (Boushey, 1982). Hypersensitivity appears to be due to an exaggerated reflex response to chemical irritation on the background of the bronchial hyper-reactivity which characterizes the asthmatic state (Boushey, 1982). 

The significance of this mechanism has been recognized only relatively recently. Since bronchial hyper-reactivity is usual in asthma, it is likely that most asthmatics will react to large enough ingested doses of sulfiting agents. Further work needs to be done to establish the extent of this problem. 

Corticosteroids have been used to treat asthma since 1950 and are presumed to act by their broad anti-inflammatory efficacy, mediated in part by inhibition of production of inflammatory cytokines (see Chapter 39). They do not relax airway smooth muscle directly but reduce bronchial reactivity and reduce the frequency of asthma exacerbations if taken regularly. Their effect on airway obstruction may be due in part to their contraction of engorged vessels in the bronchial mucosa and their potentiation of the effects of 13-receptor agonists, but their most important action is inhibition of the infiltration of asthmatic airways by lymphocytes, eosinophils, and mast cells. 

Cromolyn sodium (disodium cromoglycate) and nedocromil sodium are stable but extremely insoluble salts (see structures below). When used as aerosols (by nebulizer or metered-dose inhaler), they effectively inhibit both antigen- and exercise-induced asthma, and chronic use (four times daily) slightly reduces the overall level of bronchial reactivity. However, these drugs have no effect on airway smooth muscle tone and are ineffective in reversing asthmatic bronchospasm they are only of value when taken prophylactically. 

On contact with moist membranes, S02 forms sulfurous acid, which is responsible for its severe irritant effects on the eyes, mucous membranes, and skin. Approximately 90% of inhaled S02 is absorbed in the upper respiratory tract, the site of its principal effect. The inhalation of S02 causes bronchial constriction parasympathetic reflexes and altered smooth muscle tone appear to be involved. Exposure to 5 ppm S02 for 10 minutes leads to increased resistance to airflow in most humans. Exposures of 5-10 ppm are reported to cause severe bronchospasm 10-20% of the healthy young adult population is estimated to be reactive to even lower concentrations. The phenomenon of adaptation to irritating concentrations has been reported in workers. However, current studies have not confirmed this phenomenon. Asthmatic individuals are especially sensitive to S02. 

Harving H, Korsgaard J, Pedersen OF, et al. 1990. Pulmonary function and bronchial reactivity in asthmatics during low-level formaldehyde exposure. Lung 168 15-21. 

Hopp RJ, Bewtra AK, Biven R, et al Bronchial reactivity pattern in nonasthmatic parents of asthmatics. Ann Allergy 1988 61 184—186. (Ill)... 

In addition to airway inflammation, asthmatics commonly exhibit bronchial hyperreactivity. The concentration of a bronchial spasmogen (e.g., methacholine or histamine) needed to produce a 20% increase in airway resistance in asthmatics is often only 1-2% of the equally effective concentration in healthy control subjects. This bronchial hyperreactivity most often is nonspecific such that the airways are also inordinately reactive to stimuli such as strong odors, cold air, and pollutants. 

Munn A (1965) Hazards of isocyanates. Ann Occup Hyg 8 163-169 Newman-Taylor AJ, Davies RJ, Hendrick DJ, Pepys J (1979) Recurrent nocturnal asthmatic reactions to bronchial provocation tests. Clin Allergy 9 213-220 O Brien IM, Harries MG, Burge PS, Pepys J (1979 a) Toluene di-isocyanate-induced asthma. 1 Reactions to TDI, MDI, HDI, and histamine. Chn Allergy 9 1-6 O Brien IM, Newman-Taylor AJ, Burge PS, Harries MG, Fawcett IW, Pepys J (1979b) Toluene di-isocyanate-induced asthma. 2 Inhalation challenge tests and bronchial reactivity studies. Clin Allergy 9 7-15... 

Pasargiklian M, Bianco S, Allegra L, Moavero NE, Petrigni C, Robuschi M, Grugni A (1977) Aspects of bronchial reactivity to prostaglandins and aspirin in asthmatic patients. Respiration 34 79-91... 

Lam S, Tkn F, Chan H, Chan-Yeung M 1983 Relationship between types of asthmatic reaction nonspecific bronchial reactivity and specific immunoglobin E antibodies in patients with red cedar Thuja plicata asthma. J Allerg Clin Immunol 72 134-139... 

Lebowitz MD, Bronnimann S, CamiUi AE. Asthmatic risk factors and bronchial reactivity in non-diagnosed asthmatic adults. Eur J Epidemiol 1995 11(5) 541-548. 

---