Granulocyte recruitment to airways exposed to endotoxin aerosols.

Guinea pigs were exposed to aerosols of 0.1 mg of Salmonella typhosa endotoxin per ml for 2 or 4 hours, and white cells in blood and in bronchopulmonary lavage were counted at 2, 4, and 6 hours. The lungs of a second group of guinea pigs and hamsters exposed in the same manner were fixed in inflation with osmium tetroxide in fluorocarbon, which retains cells on luminal surfaces of airways. The polymorphonuclear leukocyte counts in cardiac blood were significantly increased, and lymphocyte counts were decreased at 6 hours (P less than 0.05). The number of cells obtained by bronchopulmonary lavage, which were mostly polymorphonuclear leukocytes, increased at 4 hours to 28 million, and at 6 hours, was 26.5 million (P less than 0.01), compared to 5 million cells at the same times in air and in water aerosol control preparations. The polymorphonuclear cell counts on airway cross sections, i.e., (polymorphonuclear cells/epithelial cells) x 100, showed a mean +/- SD peak of 53.9 +/- 10.9 after 4 hours in guinea pigs and a peak of 99.7 +/- 11.0 after 6 hours in hamsters. Alveoli showed no cell recruitment. Platelets were aggregated on surfaces of arterioles facing bronchioles, although counts in blood were unchanged. Neither leukocytes nor airway cells showed damage to their ultrastructure. The time course for airway recruitment and leukocytosis matches that for symptoms after exposure of workers to dusts from natural fodder or fibers. This suggests that leukocyte recruitment to airways by inhaled endotoxin may be part of the mechanism for the fever and chest tightness in occupational disorders.

Responses to cotton dust.

Twelve cotton textile workers were studied: (1) to compare standard measures of volume and expiratory flow, maximal expiratory flow volume (MEFV) curves, closing volume (CV), and closing capacity (CC) in detection of airway narrowing with cotton dust exposure; (2) to evaluate the response of arterial blood gases to exposure; (3) to measure changes in leukocytes in peripheral blood and airway secretions; and (4) to assess the temporal relationships and correlations between measures. Change in expiratory flow (FEV) most consistently and significantly discriminated between the control and cotton dust exposures. Vmax50%FVC was a more sensitive indicator, but variance was increased proportionately. CV and CC changed inconsistently with relatively large variances. The PaO-2 decreased overall and two subjects had large decrements. Peripheral blood and polymorphonuclear cell counts increased with exposure to cotton dust and polymorphonuclear leukocytes were recruited to the nasal mucosa. Chest tightness and decreased flow were temporally correlated with leukocyte recruitment that may be important in respiratory disease among cotton textile workers and therefore deserves further investigation.

Cephalexin concentrations in sputum during acute respiratory infections.

In 20 patients with acute pulmonary infections, sputum purulence, sputum volume, and concentration and excretion of cephalexin in the sputum significantly decreased concurrently during therapy. The concentration of cephalexin in the serum remained unchanged. Significant correlations were observed between drug concentrations in sputum and serum and between drug excretion in sputum and concentration in serum. These observations may be explained by decreased integrity of the "blood-bronchus barrier" during inflammation, with diffusion of serum into bronchial mucus, without the necessity of postulating active transport.