The fact that a moderate-level irritant exposure could initiate asthma requires consideration of mechanisms other than airway damage alone to induce the asthmatic attack. Preexisting host susceptibility, such as asthma or atopy, with its associated inherent biochemical and pathologic consequences is one possibility. There was no greater prevalence of allergy/atopy among subjects with RADS. However, 88% of individuals with not-so-sudden onset (p<0.01) exhibited an allergy/atopy status and 30% of subjects with new-onset irritant-induced asthma were really manifesting an exacerbation of a preexisting asthmatic state. Therefore, allergy/atopy status and preexisting asthma are important risk factors for developing asthma from irritant exposures and there may be other risk factors for irritant-induced asthma not addressed by this investigation. risk factors
As to other possible mechanisms to initiate irritant-induced asthma in an atopic individual, it is possible that atopic persons have a unique response to irritants. Atopic individuals are known to be at an increased risk for developing asthma, show accelerated declines in lung function, and display exaggerated responses to irritants. Furthermore, IgE, a hallmark of atopy, has been linked to bronchial hyperresponsiveness.
Bronchial epithelial cells of atopies might react differently to irritant exposures because high-affinity IgE is bound to their surfaces. Another possibility is that a preceding irritant exposure enhances bronchial mucosal permeability that has been demonstrated to increase bronchial sensitization. Such enhanced bronchial mucosal permeability leads to greater penetration of the airway mucosa by common airborne environmental aeroallergens. In an atopic person previously sensitized to these aeroallergens, the increased allergen penetration might cause more pronounced allergenic response and mediator release, eventuating into clinically new-onset asthma. An irritant exposure may lead to mediator release from various airway cells (eg, mast cells, bronchial epithelial cells) inducing airway inflammation and hyperresponsiveness. Alternatively, airway sensitivity to an allergen may be augmented by an irritant exposure, supported by the findings of Molfino et al and Jorres and colleagues whose investigations demonstrated enhanced specific bronchial airway responsiveness to aeroallergens after preexposure to low levels of ozone.
The present investigation defined the clinical features of irritant-induced asthma and described some cases that were not so sudden in onset. A preexisting allergic diathesis was identified as a host factor consequential to the development of not-so-sudden irritant-induced asthma. This resembles the findings of adult-onset asthma after a viral respiratory infection. The present study suggests that an irritant exposure of a susceptible person may initiate the onset of asthma in a manner similar to a viral respiratory infection in an atopic individual or a large allergen load in a sensitized person. The importance of not-so-sudden, irritant-induced asthma as a public health issue is that it underscores a critical interaction between environmental and host factors in initiating the onset of asthma. Not-so-sudden, irritant-induced asthma must be differentiated from occupational asthma due to workplace sensitizers and sudden-onset asthma (RADS) from massive workplace irritant exposures.