Interaction of hypoxia and hypercapnia on respiratory drive in patients with COPD.

The objective of this study was to compare the response of respiratory drive to progressive hypoxia under eucapnic and hypercapnic conditions in patients with severe COPD. Twenty-five patients with severe COPD and 13 nonsmoking young men were studied. The pressure in the occluded airway measured 0.1 second after the onset of inspiration was used as an index of respiratory drive. The occlusion pressure was measured at levels of SaO2 between 97 and 85 percent while eucapnic. The PETCO2 was then increased 10 mm Hg and the study repeated. The response of respiratory drive to hypoxia as measured by the slope of the regression line relating occlusion pressure to SaO2 was weak and variable in eucapnic hypoxia, and some subjects had no demonstrable response. When mild respiratory acidosis was created by increasing the PETCO2, the response to hypoxia was much greater and occurred in all subjects studied. Respiratory acidosis resulting from acute elevation of the PaCO2 greatly potentiates the increase in respiratory drive in response to hypoxia in normal subjects and in patients with severe COPD. Increase in occlusion pressure may occur with slight degrees of hypoxia when acute hypercapnia is present. These observations suggest that patients with acute respiratory failure complicating COPD, treated with controlled oxygen administration with only partial correction of hypoxia and continued respiratory acidosis, will have high respiratory drive.

Effect of nicotine chewing gum on plasma nicotine levels of cigarette smokers.

This study was designed to determine whether the use of nicotine chewing gum modifies the inhalation and absorption of nicotine by cigarette smokers. Our subjects, 12 subjects who smoked cigarettes regularly, were studied for 4 days. On the first day, they smoked as usual, and on the second, third, and fourth days they also chewed a placebo gum, 2-mg nicotine gum, or 4-mg nicotine gum. They were instructed to smoke as usual throughout the study. Mean plasma nicotine concentration was 29.5 ng/ml with the placebo gum, 30.9 ng/ml with the 2-mg gum, and 40.7 ng/ml with the 4-mg gum. Peak carbon monoxide level was lower with nicotine gum than with placebo gum. Data indicate self-regulation of blood nicotine levels. The subjects appear to have compensated almost completely for the increased intake of nicotine from the 2-mg nicotine gum by decreasing the inhalation of tobacco smoke. Nicotine compensation provided by the 4-mg nicotine gum is only partial.

Amount of nicotine and carbon monoxide inhaled by smokers of low-tar, low-nicotine cigarettes.

In 76 smokers, correlations between plasma nicotine and alveolar carbon monoxide levels of the individual smoker and the nicotine and CO yields of his cigarette were very poor. In 24 smokers of low-nicotine, low-tar cigarettes, mean alveolar CO levels did not differ from those of smokers of regular cigarettes. Mean plasma nicotine levels were lower in smokers of low-nicotine cigarettes, but a wide overlap of individual values occurred. The implication that an individual shifting to ultra-low-tar cigarettes reduces risks of cardiopulmonary disease is unwarranted.

Plasma nicotine levels produced by chewing nicotine gum.

Nicotine chewing gum is designed to maintain plasma nicotine levels during a smoking cessation effort while the individual copes with the loss of the repetitive behavioral components of smoking. The plasma nicotine levels obtained with hourly gum chewing were compared with levels obtained with cigarette smoking in nine patients with lung disease. Chewing 2- and 4-mg nicotine gum hourly produced mean steady-state plasma nicotine levels of 11.8 and 23.2 ng/mL, respectively. This compares with a mean plasma nicotine trough level during usual smoking of 15.7 ng/mL and a mean trough level of 18.3 ng/mL with hourly smoking of a cigarette with a nicotine yield of 1.1 mg. Few side effects were seen with the use of either the 2- or 4-mg gum. In a short-term study, nicotine gum proved an acceptable source of nicotine for aiding smoking cessation.

Mucus secretion by the epithelium of the bronchioles of cigarette smokers.

Pieces of tissue were obtained from lungs removed surgically from patients who were long-term cigarette smokers. The lung tissue was placed in culture medium containing 35SO4 or 3H glucosamine and exposed to 95% O2 and 5% CO2 at 37 degree C for varying periods of time. The tissue was then fixed and autoradiographs prepared. Autoradiographs performed after four hours' incubation with the radio-isotope demonstrated a large number of grains in the lumen of the bronchioles with a lesser number of grains over the epithelial cells. Pulse chase studies showed migration of the labelled material from a paranuclear location to the lumen during the four-hour period of incubation. The study provides evidence for mucus secretion by the epithelium of the bronchioles of cigarette smokers.

Small airways of the lung. The importance of understanding and assessing the function of pulmonary bronchioles.

Recent findings have emphasized the importance of the bronchiole to the function of the lung. The surface of the bronchiole differs from that of the alveolus. Rather than being covered by a thin coat of phospholipid, the surface is covered with cilia that are surrounded by a low-viscosity fluid. This permits the removal of foreign particles. Surface forces are important to the function of the bronchiole. The diameter of the bronchiole is a function of the volume of the lung. When the lung is partially collapsed, the bronchiole acts as a capillary tube and is readily obstructed by fluid. In chronic bronchitis, obstruction is related to narrowing by fibrosis and inflammation, alteration in the secretion, and loss of traction on the walls. Obstruction of the bronchiole by fluid in edema of the lung contributes to hypoxemia. Positive end expiratory pressure may prevent obstruction by increasing the bronchiolar diameter.

Study of the surface secretion of the bronchiole using radioautography.

The purpose of the present study was to obtain further information regarding the chemical nature and cell of origin of the surface secretion of the bronchiole using radioautography after the injection of labeled leucine, glucosamine, galactose. Rat lungs were perfused with mammalian Ringer's solution with added albumin. A 10-min pulse of L-leucine labeled with hydrogen-3 was administered, followed by perfusion with nonradioactive solution for 15 min to 4 hours. Similar studies were performed with [3H] glucosamine and [3H] galactose. Heavy labeling of the Clara cells of bronchioles was obtained after injection of [3H] L-leucine. Labeling of alveolar wall cells was also obtained. Labeling of the surface of the bronchiole was much heavier than the labeling of the surface of the alveoli. No specific labeling of bronchiolar cells was obtained with [3H] glucosamine and [3H] galactose. The results provide added evidence for the protein nature of the surface layer of the bronchiole and for the Clara cell as its cell of origin.

Observation of the secretion on the surface of the bronchioles with the scanning electron microscope.

The secretion covering the surface of the bronchioles can be demonstrated with the scanning electron microscope if fixative is introduced into the pulmonary artery or directly into the lung rather than through the trachea. Buffered glutaraldehyde, ethanol, or an ethanol-ether mixture can be used as a fixative. With this method of preparation the surface secretion appears as a smooth coating covering the cilia and cells. The secretion is insoluble in ethanol ether or chloroform methanol, suggesting that there is little lipid contained in it. Reasons are cited for believing that the major component of the secretion is a protein that arises from the Clara cell.

The bronchiolar epithelium in cigarette smokers. Observations with the scanning electron microscope.

Observations with the scanning electron microscope were made on the bronchiolar epithelium of 25 lungs removed at surgery. In all but 3 cases, the lungs were removed for a malignant tumor. Abundant ciliated cells were present in all lung specimens. In lungs obtained from nonsmokers, numerous Clara cells were present in the small bronchioles, whereas goblet cells were seen, and in most cases, the Clara cells were infrequent or absent. The evidence for the secretory nature of the Clara cells is discussed as is the possible effect on lung function of alteration in the type of secretory cell in the bronchioles.