title: Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection.
abstract: Inhalation of histamine diphosphate aerosol (1.6 per cent, 10 breaths) produced a 218 +/- 54.6 per cent (mean +/- SE) increase in airway resistance in 16 normal subjects with colds compared with a 30.5 +/- 5.5 per cent increase in 11 healthy control subjects (P less than 0.01). There was no significant difference in mean baseline airway resistance between the two groups. Inhalation of saline produced no significant change in airway resistance in either group. Isoproterenol hydrochloride (0.5 per cent, 1 breath) or atropine sulfate aerosol (0.2 per cent, 20 breaths) each reversed and prevented the increase in airway resistance by histamine, indicating that the bronchoconstriction was caused by smooth muscle contraction and that post-ganglionic, cholinergic pathways were involved in the mechanism. In 6 subjects with colds, citric acid aerosol (10 per cent, 5 breaths) caused bronchoconstriction that lasted up to 30 sec after inhalation, a significantly greater effect than that observed in control subjects or in the same subjects after recovery (P less than 0.05). Prior inhalation of atropine aerosol (0.2 per cent, 20 breaths) prevented the bronchoconstriction after citric acid aerosol in all 6 subjects. The threshold concentration of citric acid that produced cough in 7 subjects with colds was significantly lower than that in control subjects or in the 7 subjects after recovery (P less than 0.05), suggesting that the exaggerated cholinergic response was due to a decreased threshold for stimulation of the rapidly adapting sensory receptors in the airways. We have provided evidence that respiratory viral infections that produce airway epithelial damage temporarily cause these subjects to develop more bronchoconstriction after inhaling smaller doses of histamine than do healthy subjects. The fact that atropine prevents this response and that the threshold to cough is temporarily decreased is compatible with our hypothesis that airway epithelial damage by infection exposes and, thus, "sensitizes" the rapidly adapting airway receptors to inhaled irritants, causing increased bronchoconstriction via a vagal reflex. Damage to the airway epithelium may occur as a result of mechanical factors, inhaled chemicals, and pollutants, such as ozone, infections, or perhaps as a result of the action of materials released endogenously (e.g., from mast cells, white blood cells, or platelets). "Sensitization" of rapidly adapting sensory receptors in the airways may be an important factor in asthma and in other diseases of airways.
mesh_terms: D000336:Aerosols; D000403:Airway Resistance; D001249:Asthma / Q000139:chemically induced; D001285:Atropine; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology*; D001982:Bronchial Diseases / Q000139:chemically induced; D002951:Citrates / Q000009:adverse effects; D006632:Histamine / Q000009:adverse effects; D006801:Humans; D008168:Lung / Q000187:drug effects; D012141:Respiratory Tract Infections / Q000503:physiopathology*; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000336:Aerosols; D002951:Citrates; D012965:Sodium Chloride; D001285:Atropine; D006632:Histamine