Aerosol airway constriction

Taken together, toxicological studies with brevetoxins indicate that the intrinsic potency of bre-vetoxin (PbTx-3) is approximately 5 ng/g and accountable largely by afhnity for binding to the volt-age-gated sodium channel. Integrated toxicity by bath application to hsh or interperitoneal injection to mice yields a reduction in potency of 3- and 40-fold, respectively, likely reflective of differences in uptake and disposition of the toxin. Specialized exposures indicate that PbTx-2 is several-fold less potent orally than interperitoneal in mice and highly potent for localized action on airway constriction by aerosolized exposure to sheep but not for systemic effects in mice or rats. 

Suzuki T, Wang W, Lin JT, Shirato K, Mitsuhashi H, Inoue H. Aerosolized human neutrophil elastase induces airway constriction and hyperresponsiveness with protection by intravenous pretreatment with half-length secretory leukoprotease inhibitor. Am J Respir Crit Care Med 1996 153 1405-1411. 

Within 30 minutes of their administration, 6 -adrenergic drugs often reverse most of the functional deficit in Monday morning byssinotics. As there is no mucous secretion, airway smooth muscle contraction is considered the primary response. Exposure of man to histamine aerosols produces pulmonary function changes similar to those seen after exposure to dust extract. However, exposure to histamine aerosol invariably initiates constriction of smooth muscle more rapidly than exposure to cotton dust ( <15 minutes), and dissipates within minutes, while the acute effects of inhalation of cotton dust and dust extracts lasts for hours. The slowly developing and prolonged effects of dust and extracts suggest that mediators other than histamine are involved. 

In diseased lungs, the airways are often more constricted relative to healthy lungs, so one might expect significant differences in lung deposition fraction and deposition pattern (101). The impact of constriction on aerosol deposition is discussed below. We present deposition data based on models of constricted airways as well as experimentally derived data, taken from healthy subjects in which constriction was induced by methacholine provocation, and from patients who are constricted in their baseline state. 

The impact of constricted airways on aerosol deposition appears to be as follows ... 

---