The effects of tobacco smoke on the central and peripheral airways were assessed in humans and rats by direct and indirect methods. In both species tobacco smoke affected the central and peripheral airways. In humans there were apparent decreases in the 1-second forced expiratory volume, peak expiratory flow rate and significant increases in closing volume and closing capacity (P < 0.001). In rats significant changes were seen in specific airway resistance from the 6th week of exposure onwards. Similarly, airway luminal diameter decreased markedly in tobacco-exposed animals to subthreshold concentrations of acetylcholine (10^-8M), This decrease was also exposure time dependent. The increased responsiveness of the respiratory system has been attributed to inter alia: (1) increased vagal activity; (2) increased mucus production leading to decreased airway lumen; (3) mucosal swelling due to changed ionic constellation; (4) disturbance of the lungs’ defense mechanism; (5) imbalance in and easy accessibility to the adrenoceptors.

Evidence is presented from in vitro experiments in over 1,100 animals that the long accepted hypothesis of a continuous tracheobronchial mucus blanket is untenable, since mucus is transported in the form of flakes, plaques and continuous streams. It is proposed that a liquid of low viscosity lies between the cilia and covers their tips. This liquid is either not transported or very slowly so. Mucus flakes and plaques are transported by the tips of the cilia over this interciliary liquid. Prostaglandin E₁ (PGE₁) in low concentrations caused lysis of stagnant flakes and plaques. In addition, it caused a marked increase in the quantity of the tracheobronchial fluid and no clear-cut effect on the rate of ciliary frequency. The possible involvement of adenyl cyclase in the response to PGE₁ is discussed.

The effect of mucolytic and expectorant substances on ciliary beat frequency, mucus transport velocity and mucus production, was investigated in normal and bronchitic rats. The results showed that: (i) N-acetylcysteine and S-carboxymethylcysteine were midly cilioexcitatory at low and ciliodepressive at higher concentrations in both normal and bronchitic rats. A similar pattern was seen in mucus transport velocity, (ii) Bisolvon® enhanced all aspects of mucoeiliary activity in both groups of animals. Sobrepin was less effective than Bisolvon and more effective than Tachoquilin®. (iii) Geleomyrtol, Ozothin and prostaglandin E₁ were all cilioexcitatory in rats with bronchitis. Mucus transport velocity was similarly stimulated by both Geleomyrtol and Ozothin. (iv) Ammonium chloride and potassium iodide enhanced mucoeiliary activity in normal and bronchitic rats, (v) All substances stimulated mucus production, however, the most potent was prostaglandin E₁. The mechanisms for increased mucoeiliary activity involve inter alia the probable cleaving of disulfide bridges, decreased mucosal swelling, altered rheological characteristics and stimulation of adenylate cyclase.

The response of the airways to adrenergic agonists and antagonists was studied in 3-day- to 2-year-old and bronchitic rats. The results showed that the α-adrenoceptors are not functional at birth but become so by 8 weeks. In contrast, the β-adrenoceptor effects are demonstrable on the third day after birth. The mean decrease in airway luminal diameter after β-adrenergic blockade was greater in bronchitic than in healthy animals and was interpreted to be due to the increased sensitivity of the β-adrenoceptors in bronchitis.

No abstract