Alveolar Carbon Monoxide Research Articles

Carbon monoxide transfer coefficient KCO (TL/VA): a flawed index L

To the Editor: In their recent “Perspective”, Hughes and Pride 1 described the carbon monoxide (CO) transfer factor ( T L,CO) as the product of two primary measurements: alveolar volume ( V A) and CO transfer coefficient K CO ( T L/ V A). V A is primary in that it has a physiological identity. However, Forster 2 has pointed out that in the context of the measurement of transfer factor, the volume is merely that of the gas exchanger; it has no more physiological significance than can be attached to the volume ( V A+ V bag) that is used for the rebreathing method. Forster 2 also warned against interpreting K CO as a separate index. Its status as a primary index would have been different if Krogh 3 had been right in her belief …

How science happened to me.

The paper I choose to discuss is “Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in the human lung, with special reference to true diffusing capacity of pulmonary membrane and volume of blood in the lung capillaries” ( J. Appl. Physiol. 1957;11:290– 302), by F. J. W. Roughton and me, the culminating article in a group of four, which described the separation of the resistance of carbon monoxide (CO) or oxygen (O 2 ) to diffusion in the pulmonary capillary blood from the resistance through the pulmonary alveolar membrane, as well as the measurement of pulmonary capillary blood volume, all in vivo . I was a medical house officer at the Peter Brent Brigham Hospital in Boston under George Thorn in 1944 when Dr. (Col.) John H. Talbott, commanding officer of the Quartermaster Corps Climatic Research Laboratory, located in the environmental chambers of the Pacific Mills in Lawrence, Mass., called to tell George that Clifford Barger, then at the Climatic Research Laboratory, had contracted tuberculosis so he needed a replacement, and did George know of anyone. Thus, in December of 1944 I found myself in an old New England mill town investigating heat loss from the extremities, temperature regulation, and the effectiveness of footwear and handwear in protecting soldiers under cold conditions. We had published some papers on peripheral blood flow and heat exchange by the end of World War II when I was discharged. I then used the GI Bill to study mathematics (of the baby type), physical chemistry, and physics at Harvard for a year before returning to take up a residency at the Peter Bent Brigham Hospital. After this I spent two years supported by a Life Insurance Fund, now defunct, as a post-doctoral fellow with Eugene Landis at the Harvard Department of Physiology, still working on temperature regulation, but by the hypothalamus in cats. I looked around for a faculty position in internal medicine, interviewed at Hopkins, where they thought I was applying for admission to medical school, when surprisingly I was offered a faculty position in the Graduate School of Medicine at Penn by Robert Dripps, director of anesthesiology, then in the Department of Surgery of the School of Medicine, and Julius Comroe, in the Department of Physiology and Pharmacology. The salary was handsome for the time, $6000, and Landis thought it indecently large, but I accepted. This changed my area of research from temperature regulation to respiration, through no intellectual initiative of my own. When I moved to Philadelphia, the Department of Physiology and Pharmacology of the Graduate School of Medicine was housed in a basement that flooded when it rained, but it had, or shortly gained, a remarkable faculty. Julius Comroe, Seymour Kety, Ward Fowler, Arthur DuBois and George Koelle were a few of the names, and there was a great excitement about the place. The philosophy was to apply the respiratory physiology that had been learned in the air and sea during World War II to the diagnosis and treatment of pulmonary diseases. Wallace Fenn had a similar philosophy for the founding of the Journal of Applied Physiology . I was assigned a small basement lab in the original School of Medicine building, with a new mass spectrometer and carbon monoxide (CO) analyzer, both of which had been ordered by Comroe with advice from Seymour Kety and John Lilly. The mass spectrometer was built to order from a low mass resolution (1 / 80) Instrument made by Consolidated Engineering Corporation to detect leaks in large capacity vacuum equipment. The CO meter was an infrared instrument, built to order by Max Liston, on a principle used by the Germans during World War II. Julius suggested that I repeat an experiment of Marie Krogh in 1914 that measured the diffusion capacity of the lung: the ability of the lung to exchange gases with capillary blood. In order to investigate the possibility of O 2 secretion in the lungs, she had measured the rate of disappearance of CO from the lungs during breath holding by inspiring a gas mixture containing a small amount of CO, immediately and rapidly breathing out an alveolar sample, holding the remaining lung gas for an additional 10 s, and then delivering a second alveolar sample into a rubber bag. The proportional drop in alveolar CO in 10 s plus the alveolar volume permitted her to calculate the pulmonary diffusing capacity for CO (D LCO ), a measure of the efficiency of the lungs in exchanging gas, defined as

The A-B-C's of smoking cessation: Using behavioral strategies to help undergraduates stop smoking.

Despite reports claiming cigarette smoking remains the most preventable cause of premature death in the United States, cigarette use by college students is increasing on campuses nationwide. We investigated the effectiveness of a brief multicomponent smoking cessation program provided for a 21year-old female (Sue) and an 18-year-old male (Tom) undergraduate student from a midwestern university. The treatment program consisted of self-report functional assessment methodology, schedule-reduced smoking, and functionally derived self-management strategies. The use of a functional assessment device provided descriptions of antecedent-behavior-consequence relationships, thereby engendering idiographic self-management cessation strategies, and a schedule-reduced smoking component was included in order to facilitate the programmed reduction in nicotine intake. Dependent measures included self-report of daily smoking frequency and alveolar carbon monoxide levels. Treatment included four weekly sessions lasting approximately 45 minutes. Though neither participant achieved complete cessation, Sue achieved a 70% reduction in smoking at 6-months followup. Tom achieved a 60% reduction in smoking at 14-day follow-up, but reported returning to above pre-treatment smoking frequency at 6-months follow-up. Treating college smokers with a rapid multicomponent program targeting the both the behavioral and pharmacological aspects of smoking behavior may offer reductions in smoking. Approximately one quarter of U.S.

Dependence on Smoking and the Acoustic Startle Response in Healthy Smokers

Recent data from nicotine-dependent rats [14]and healthy smokers [18]would suggest that nicotine withdrawal modulates the acoustic startle reflex in a way similar to that of fear [5, 20]. We examined this directly using nonsmokers and healthy smokers who had no deprivation, brief deprivation (2–3 h), or prolonged deprivation (15 h). Groups differences in heart rate (HR), alveolar carbon monoxide (CO) levels, and desire and craving for cigarettes confirmed the presence of smoking withdrawal. However, there were no significant differences in the magnitude of the baseline startle response among the differently deprived smokers or between the smokers and the nonsmokers. Subsequent startle tests were carried out in the smokers during repeated sequences of preparing a cigarette for smoking (smoking cues) and then smoking. Whereas we did find statistically significant interactions of smoking deprivation with smoking cues and with renewed smoking, there was only weak confirmation of a priori predictions of motivational effects of smoking cues or of smoking. We conclude that smoking dependence may not affect the acoustic startle response itself; modulation seems to occur, but only after experience with the test situation. Discussed were possible mechanisms of this modulation in both humans and animals and further application of the startle response for providing interdisciplinary assessments of the motivational effects of nicotine withdrawal.

The role of carbon monoxide in lucigenin-dependent chemiluminescence of rat alveolar macrophages

We have investigated the role of carbon monoxide (CO) in lucigenin-dependent chemiluminescence of alveolar macrophages from rat lungs. CO (10 nM to 1 μM) decreased chemiluminescence of alveolar macrophages in a concentration-dependent fashion. At a concentration of 1 μM, Co significantly increased intracellular cyclic GMP levels from a control value of 175 ± 25 fmol/2 × 10 6 cells to 431 ± 49 fmol/2 × 10 6 cells. Pretreatment of alveolar macrophages with N G-monomethyl-L- arginine (100 μM) failed to inhibit CO (1 μM)-induced decreases in chemiluminescence of alveolar macrophages (3.7 ± 0.7 cpm × 10 3 in the presence of N G-monomethyl-L-arginine and 3.4 ± 0.6 cpm × 10 3 in the absence of N G-monomethyl-L-arginine) and CO (1 μM)-induced increases in intracellular cyclic GMP levels (452 ± 65 fmol/2 × 10 6 cells in the presence of N G-monomethyl-L-arginine and 419 ± 58 fmol/2 × 10 6 cells in the absence of N G-monomethyl-L-arginine). Decreases in chemiluminescence of alveolar macrophages induced by CO (1 μM) were concentration-dependently inhibited by methylene blue (from 0.1 μM to 10 μM). Dibutyryl cyclic GMP (db cyclic GMP) (1 mM) also reduced chemiluminescence of alveolar macrophages (1.5 ± 0.3 cpm × 10 3 in the presence of db cyclic GMP and 3.6 ± 0.6 cpm × 10 3 in the absence of db cyclic GMP). In contrast to CO and db cyclic GMP, zinc protoporphyrin-9 (10 nM to 1 μM), an inhibitor of heme oxygenase potentiated chemiluminescence of alveolar macrophages in a concentration-dependent fashion. Northern blot analysis revealed that alveolar macrophages expressed mRNA of heme oxygenase-1. These results suggest that an endogenous CO-like factor inhibits chemiluminescence of alveolar macrophages via activating guanylate cyclase.

Sampler for Measurement of Alveolar Carbon Monoxide

A simple sampler for measurement of alveolar carbon monoxide (CO) has been developed. The alveolar CO sampler consists of a mouthpiece, an alveolar air trap system using two one-way valves, and an adsorbent tube. The alveolar CO sampler can collect alveolar CO without subjective discard of dead space air in the subject respiratory system. The small size of the alveolar CO sampler could make the measurement of alveolar CO less laborious. Accuracy and precision of the alveolar CO sampler were evaluated with a pseudo-expired test air at a relative humidity of 80% and at a relative humidity of 100%. The alveolar CO sampler can measure alveolar CO ranged from 3 to 70 ppm without relative humidity effect

Carbon monoxide and nitrogen dioxide exposures in indoor ice skating rinks

Exposures to carbon monoxide (CO) and nitrogen dioxide (NO2) were determined in seven enclosed ice skating rinks and an outdoor rink. The uptake of CO was also determined by the difference in alveolar CO concentration of the non-smoking hockey players before and after games. Carbon monoxide concentrations in enclosed rinks ranged from 4 to 117 ppm and NO2 concentrations from 342 to 2729 ppb for 2 h hockey games. The CO uptakes were linearly related to the ambient CO concentrations. Alveolar CO of the hockey players increased on average by 0.53 ppm per 1 ppm CO exposure over 2 h. Considering the CO and NO2 levels currently measured in enclosed ice skating rinks, indoor air quality guidelines or standards should be established. It is recommended that 1 h maximum allowable limits of 20 ppm CO and 250 ppb NO2 be established.

Use of alveolar carbon monoxide measurements to assess red blood cell survival in hemodialysis patients.

We recently described a simple technique for measuring RBC survival based on measurements of the concentration of carbon monoxide (CO) in alveolar air, corrected for environmental CO using a device that equilibrates with atmospheric CO at the same rate as does the patient. The purpose of the present report is to demonstrate the clinical utility of this method via measurements of RBC turnover in hemodialysis patients. Prior to dialysis, the mean RBC survival of 9 chronic dialysis patients was 70 +/- 9 days, about 50% shorter than that of 32 healthy subjects. During the dialysis, the endogenous PCO increased by 14% (P < 0.05) while subjects not undergoing dialysis had a 6% fall in endogenous PCO over this same time period. Thus, this technique demonstrated that the hemodialysis procedure resulted in about a 20% increase in RBC destruction. This increased RBC destruction has not been detectable with previous methodologies (including conventional measurements of CO production) due to the insensitivity and lack of reproducibility of conventional techniques. We conclude that the simple, non-invasive measurement of endogenous PCO provides the most accurate available means of assessing the influence of a variety of acute manipulations on RBC survival.

Can a Mass-Media Campaign Modify Tobacco Smoking in a Large Organization? Evaluation of the Great American Smokeout in an Urban Hospital

The Great American Smokeout's effect on smoking in a large urban hospital was evaluated by unobtrusive observations of people in a hospital cafeteria and collection of expired alveolar carbon monoxide (CO) levels from volunteers at a hospital information booth. Number of people observed sitting in the smoking section of the cafeteria, number of people observed smoking, and mean expired CO levels taken from volunteers were reduced only on the day of the Smokeout as compared to data collected during a baseline period during the month prior to the Smokeout, but returned to their previous levels the day after the Smokeout. These results provide empirical support that a mass-media based campaign such as the Smokeout may reduce smoking temporarily, but additional strategies for maintenance of smoking reduction and cessation are needed.

The relation of affective processing measures and smoking motivation indices among college-age smokers

Two studies examined the relation among affective processing measures as assessed by the Affective Information Processing Questionnaire (AIPQ) and smoking indices. The AIPQ assesses attributional style, expectations regarding the strength, frequency, and duration of affective reactions, and expectations regarding the controllability of affective reactions both by smoking and by other means in response to a series of vignettes depicting stressful situations. In the first study, 195 undergraduates completed the AIPQ along with measures of affect and smoking. Results indicated satisfactory reliability for the AIPQ scales. A subsample of Study 1 subjects ( n=49) were exposed to a laboratory stressor in Study 2. Results indicated that the affect control expectations measures predicted post-stressor measures of negative affect, urge to smoke, negative reinforcement from smoking, and alveolar carbon monoxide value. Attributional style and expectations regarding affective reactions did not consistently predict post-stressor measures. The relation of affective processing to smoking motivation and relapse is discussed.

Evaluation of a New Solid Sorbent Sampler for Alveolar Methylene Chloride Used in Tandem with a Bag for Sampling Alveolar Carbon Monoxide

Abstract A method for sampling and analysis of methylene chloride and carbon monoxide in alveolar air is described. The method employs a three-section bed of charcoal cloth sorbent for the determination of methylene chloride concentrations and a bag downstream of the solid sorbent sampler for determination of carbon monoxide concentrations. The method was evaluated in a study to assess the level of exposure to and uptake of methylene chloride by 14 furniture strippers. Alveolar breath samples obtained from these workers were analyzed for methylene chloride and carbon monoxide. Venous blood samples also were obtained from the furniture strippers and analyzed for methylene chloride and carboxyhemoglobin. All methylene chloride samples were analyzed by gas chromatography with flame ionization detection. Breath carbon monoxide was analyzed using an electrochemical detector (Ecolyzer). Blood carboxyhemoglobin levels were determined with a CO-Oximeter. The accuracy of the breath sampling and analytical procedure was assessed by comparing the alveolar breath methylene chloride and carbon monoxide concentrations to venous blood concentrations of methylene chloride and carboxyhemoglobin, respectively. Linear regression analysis showed that the blood and breath concentrations of methylene chloride were reasonably correlated (r = 0.87), with a standard error of estimation of 1.37 mg/L (even including two extreme outliers in the data analysis). An in vivo blood:gas partition coefficient of 16.7 for methylene chloride was computed from the blood:breath concentration data (excluding the two extreme outliers). Breath carbon monoxide measurements were not as well correlated with blood carboxyhemoglobin (r = 0.84) as historically expected, primarily due to two outlying data points. The standard error of the estimate was also relatively large—1.89 percent carboxyhemoglobin. However, the slope of the linear regression equation relating blood carboxyhemoglobin to breath carbon monoxide was comparable to previously reported results. This study has demonstrated that monitoring of these analytes in alveolar breath may be a useful alternative to monitoring them in blood. Recommendations for improvements to the breath and blood sampling and analytical procedures are also given.

Effects of individually motivating smoking cessation in male blue collar workers.

Adverse demonstrable health effects linked to the individual's smoking were shown to 2,689 American workers to motivate cessation during routine examinations to detect asbestosis. This intervention was evaluated six to 25 months later by a mailed questionnaire and by telephone to non-responders. Results were compared to yearly quit rates of 2.5 percent to 5 percent for 736 workers who were ex-smokers at the initial examination. Of the 504 men who responded by mail, 29.8 percent had quit smoking, 35.9 percent had cut down from a mean of 28 to 13 cigarettes per day, and 34.3 percent were smoking as before. Subsequent follow-up at one year showed that 25.6 percent remained quit, and that 23 percent of those who cut down had quit, for an overall quit rate of 34 percent. Of 101 non-responders contacted by telephone, 17 percent had quit and 53 percent had reduced smoking. In both samples, those who quit were more likely to have had lower alveolar carbon monoxide (COa) levels, to be older, and to have had asbestosis. Responders by mail were the same age as non-responders but had smoked longer, had higher prevalences of asbestosis, emphysema, chronic bronchitis and higher COa. Demonstration of the adverse personal effects of smoking appear to have contributed to the quit rates or reduced smoking rates in 65 percent of the responding workers.

Carbon monoxide in indoor ice skating rinks: evaluation of absorption by adult hockey players.

We evaluated alveolar carbon monoxide (CO) levels of 122 male, adult hockey players active in recreational leagues of the Quebec City region (Canada), before and after 10 weekly 90-minute games in 10 different rinks. We also determined exposure by quantifying the average CO level in the rink during the games. Other variables documented included age, pulmonary function, aerobic capacity, and smoking status. Environmental concentrations varied from 1.6 to 131.5 parts per million (ppm). We examined the absorption/exposure relationship using a simple linear regression model. In low CO exposure levels, physical exercise lowered the alveolar CO concentration. However, we noted that for each 10 ppm of CO in the ambient air, the players had adsorbed enough CO to raise their carboxyhemoglobin (COHb) levels by 1 percent. This relationship was true both for smokers and non-smokers. We suggest that an average environmental concentration of 20 ppm of CO for the duration of a hockey game (90 minutes) should be reference limit not to be exceeded in indoor skating rinks.

Fire Fighters' Exposure to Carbon Monoxide during Australian Bushfires

Fatal entrapments of Australian bushfire fighters have led to suggestions that carbon monoxide (CO) poisoning could have contributed to these accidents by impairing the fire fighters' judgement. Carboxyhemoglobin saturation (COHb%) levels were assessed from alveolar CO levels in 24 fire fighters working with handtools and in 12 accompanying scientific observers, before and after fire fighting (duration 37-187 min) on 15 experimental bushfires. Carboxyhemoglobin levels increased on average by 0.7% per hour in the fire fighters and by 0.3% per hour in the observers. Nonsmoking fire fighters had lower COHb% after fires than the smokers had before fires. Estimates of environmental CO concentrations (including cigarette smoke) during the fires averaged 31 parts per million (ppm) for the smokers, 17 ppm for the nonsmoking crew members, and 11 ppm for the observers, none of whom smoked. The highest estimates of environmental CO arising solely from bushfire smoke were 40 to 50 ppm. Smokers were exposed to as much CO from their cigarettes as from bushfire smoke. Carboxyhemoglobin levels at the end of 8-hr fire fighting shifts, predicted from these levels of environmental CO, averaged about 5% (maximum 11%) in smokers and about 3% (maximum 7%) in nonsmokers. Acute levels of COHb% of this degree are not considered to have significant effects on health or performance. These results indicate that bushfire fighters are generally unlikely to experience hazardous levels of CO exposure.

Effects of cigarette smoking on subjective and brain evoked responses to electrical pain stimulation

The effects of smoking two cigarettes on brain evoked potentials (EP) and subjective ratings (SR) of pain intensity to 3 levels of electrical skin stimulation were investigated in 14 female habitual smokers. Smoking increased EP amplitudes to all stimulus intensities, but did not alter SRs. Changes in SRs to intensities in the pain range, but not in the prepain range, were found to be negatively correlated with smoke inhalation as measured by expired alveolar carbon monoxide (CO) elevation. No significant EP-smoking inhalation correlations were observed.

On the measurement of tobacco use by adolescents. Validity of self-reports of smokeless tobacco use and validity of cotinine as an indicator of cigarette smoking.

This study assessed the validity of self-reports of smokeless tobacco use by adolescents and the validity of cotinine as a measure of adolescent cigarette smoking. For a sample of 1,854 persons aged 12-14 years living in the southeastern United States in 1985, a combination of three biochemical measures (salivary cotinine, salivary thiocyanate, and alveolar carbon monoxide) and self-reports of cigarette smoking were used to identify subjects who used only smokeless tobacco and subjects who did not use smokeless tobacco. The sensitivity and specificity of self-reports of smokeless tobacco use were 40.8% and 97.9%, respectively. It was determined that of the 175 subjects who ordinarily would be considered smokers because they had salivary cotinine levels greater than or equal to 10 ng/ml, 43.4% used only smokeless tobacco.

Measuring the heaviness of smoking: using self-reported time to the first cigarette of the day and number of cigarettes smoked per day.

Two simple self-report measures have been used to assess the heaviness of smoking, 'number of cigarettes per day' (CPD) and 'time to the first cigarette of the day' (TTF). Little attention, however, has been given to the precise method of scoring this information. Using biochemical indicators of heaviness of smoking (alveolar carbon monoxide and cotinine), we explore the optimum data transformations for regression analysis and categorical analysis. We suggest a four category scoring scheme for both time to the first cigarette of the day (less than or equal to 5, 6-30, 31-60 and 61+ min) and average daily consumption of cigarettes (1-10, 11-20, 21-30, 31+ cigarettes) as the most powerful and practical categorical scoring of these variables. Due to possible ceiling effects on biochemical measures, we suggest using logarithmic transformations of CPD or TTF for regression or correlation analyses.

Long-term effects of switching to cigarettes with lower tar and nicotine yields

On switching to cigarettes with lower tar and nicotine yields, most individuals smoke more intensively, but it is not clear if this effect persists over a long period. Smoking behaviour was monitored in 10 male and 18 female volunteers at five monthly visits, smoking commercially available cigarettes (tar yield greater than 10 mg), then for six more visits at 6-week intervals after switching (mean reduction of 5.9 mg tar and 0.45 mg nicotine). Puffing behaviour was monitored with a flow sensing holder, and measurements were made before and after smoking of plasma cotinine, carboxyhaemglobin and alveolar carbon monoxide. After switching, cotinine levels only fell 40% of that predicted from the fall in nicotine yields, and there were no systematic trends for the rest of the study. Puff volumes rose (reflecting perhaps the reduced draw resistance of the lower yield cigarettes), and remained higher thereafter. The number of puffs per cigarette appeared to rise on switching, but then decreased again. In conclusion, most effects of switching to lower yield cigarettes appeared to persist for at least 36 weeks, suggesting that the strategy of reducing exposure to cigarette smoke by lowering tar and nicotine yields may be of limited value.

Acute effect of smoking on rebreathing carbon monoxide, breath-hold carbon monoxide and alveolar oxygen.

1. The rise ('boost') in carboxyhaemoglobin (HbCO) on smoking has been studied with alveolar carbon monoxide measurements before and after smoking a cigarette. We re-examined this in 28 subjects with HbCO values compared with rebreathing carbon monoxide [FACO(Rb)] and breath-hold alveolar carbon monoxide and oxygen concentrations, obtained after a 20 s breath-hold [FACO(Bh) and FAO2(Bh), respectively]. Tests were done in the order FACO(Bh) and FAO2(Bh), FACO(Rb), FACO(Bh) and FAO2(Bh) before and after smoking a single cigarette, with HbCO being measured 1 min before and after smoking. 2. The changes were expressed as the relative boost: (Post value-pre value)/(Pre value + post value)/2 X 100 For HbCO the average value was 23.7%, but the FACO(Rb) boost was only 9.8%. The first post-smoking FACO(Bh) boost was 3.9% (5.0 min after smoking), rising to 8.5% 9.4 min later. 3. The FAO2(Bh) values fell from a mean of 15.4% before smoking to 14.3% (5.0 min after smoking) then recovered to 15.4% 9.4 min later, suggesting a transient effect on pulmonary gas exchange. Correction of the first post-smoke FACO(Bh) data for this effect increased the relative boost to 11.5%. Routine FAO2(Bh) measurements may be useful in further smoking studies. 4. We conclude that none of the alveolar sampling techniques gives a reliable measurement of the acute HbCO changes associated with smoking.

The alveolar carbon monoxide uptake fraction: a simple, alternative measure of carbon monoxide transfer

The measurement and interpretation of "diffusing capacity" by either single-breath or steady-state methods are complicated by both technical and conceptual difficulties. The CO uptake fraction is less complex but, as originally described, it is unacceptably sensitive to dead-space ventilation. A modification (the "alveolar CO uptake fraction", UA) largely removes this factor. We have measured UA in thirteen healthy subjects and 100 patients with a variety of pulmonary disorders. It is reproducible and appears sensitive to clinical abnormality. Its technical and interpretative simplicity suggest its use as an alternative to other measures of CO transfer.