Late asthmatic responses.

Abstract

Late asthmatic responses provoked in the clinical laboratory under controlled conditions occur commonly in sensitized subjects following inhalation challenge with allergens (1-5) or occupational agents (6-8). Allergen provocation tests generally involve exposure of the subject to increasing allergen concentrations at 10 to 15 rain intervals until an immediate or early response occurs. The early response is maximal at 15 to 30 min and resolves within 2 to 3 h. A proportion of subjects develop a delayed phase of airflow limitation after several hours, the late asthmatic response. Late responses are generally maximal at 6 to 12 h and resolve within 24 h, although an increase in 'morning dipping' a manifestation of increased airway responsiveness, may persist for several days (9). Late responses occurring in the absence of a preceding early response have been observed following occupational type challenge tests for many years (6). However, recent information suggests that these isolated late responses may also occur frequently following exposure to common allergens at low concentrations, insufficient to provoke an immediate asthmatic response (10). The traditional view has been that late asthmatic responses occur as an 'all or nothing' event although this concept was based on the somewhat arbitrary definition of a late response, generally less than or equal to a 15% fall in FEV~ several hours after challenge. It is now accepted that late asthmatic responses occur as a spectrum from 'no late response' to 'severe late responses' and, probably, independently of the size of the early response. Furthermore, although it is not possible to predict accurately the occurrence of late response in individual patients, they occur as dosedependent phenomena (10,11) in relation to the dose of allergen administered and the level of allergen sensitivity of the subject (12-14). The development of late responses after allergens has been regarded as a manifestation of genuine 'allergic' IgE-mediated hypersensitivity to the agent tested, as opposed to an immediate 'irritant' or nonspecific response which might occur in either allergic or nonallergic asthmatic subjects following exposure to many noxious agents or chemicals. Late asthmatic responses have recently been described in other circumstances, including experimental provocation with exercise (l 5-17) and following the inhalation of ultrasonically nebulized distilled water ('fog' challenge) (18). Exercise-induced late responses are generally less severe than following allergen provocation, and appear to be more common in children (15, 16). Indeed, their occurrence in adults has been questioned on methodological grounds (19). In contrast to allergen provocation, the development of exercise-induced late response has not been associated with an increase in nonspecific airway responsiveness following challenge (20). For these reasons the clinical importance of late responses following exercise remains unclear and further studies are required.