Bronchodilator response in the lung health study over 11 yrs.

Long-term changes in bronchodilator response in people with mild chronic obstructive pulmonary disease were assessed in this study. Changes in forced expiratory volume in one second (FEV1) in response to isoproterenol was measured in 4,194 participants in the Lung Health Study annually for 5 yrs, and again 11 yrs after study entry. Responses were quantitated in terms of mL (absolute), as per cent of the pre-bronchodilator value (relative), and as a per cent of the predicted normal value (% predicted). At baseline, the mean pre-bronchodilator FEV1 was 75.4% predicted, and responses were small. Relative and percentage predicted responses were similar in males and females; and correlated positively with methacholine reactivity, and negatively with smoking intensity and age. Baseline bronchodilator responses did not correlate with subsequent decline in FEV1. There was a substantial increase in response over the first year of the study, largely due to smoking cessation, with larger increases in those who stopped smoking. After the first year absolute responses changed little in those who maintained smoking cessation, but increased in those who did not. Mean relative and percentage predicted responses increased in all participants throughout the study. There was substantial annual variability of absolute response, and it was poorly reproducible in individual participants. In conclusion, smoking cessation increased bronchodilator response, and response did not predict the rate of decline of forced expiratory volume in one second.

Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease: results from the lung health study.

We analyzed Lung Health Study (LHS) data to assess the effect of self-reported lower respiratory illnesses resulting in physician visits (LRI) on lung function. Participants were 5,887 smokers aged 35-60 yr, FEV(1)/FVC < 0.70 and FEV(1) of 55-90% predicted. Two-thirds were randomized into an intensive smoking cessation program (SI); one-third were advised only to stop smoking (UC). For 5 yr participants had annual spirometry and questioning regarding LRI. SI had greater rates of smoking cessation than usual care (UC) with fewer LRI (p = 0.0008). Sustained quitters had fewer LRI than continuing smokers (p = 0.0003). In the year LRI occurred, FEV(1) did not change in sustained quitters, but decreased significantly in smokers (p = 0.0001) with some recovery the following year if no LRI occurred. Over 5 yr, LRI had a significant effect on rate of decline of FEV(1) only in smokers. In smokers averaging one LRI/yr over 5 yr there were additional declines in FEV(1) of 7 ml /yr (p = 0.001). Smokers with more than one LRI/yr had greater declines. Chronic bronchitis was associated with increased frequencies of LRI, but did not affect their influence on lung function. Smoking and LRI had an interactive effect on FEV(1) in people with mild COPD, and in smokers frequent LRI may influence the long-term course of the disease.

Acute exposure to environmental tobacco smoke and heart rate variability.

Environmental tobacco smoke (ETS) has been associated with cardiovascular mortality. Pathophysiologic pathways leading from ETS exposure to cardiopulmonary disease are still being explored. Reduced cardiac autonomic function, as measured by heart rate variability (HRV), has been associated with cardiac vulnerability and may represent an important pathophysiologic mechanism linking ETS and risk of cardiac mortality. In this study we evaluated acute ETS exposure in a commercial airport with changes in HRV in 16 adult nonsmokers. We conducted ambulatory electrocardiographic (ECG) monitoring for 8-hr periods while participants alternated 2 hr in nonsmoking and smoking areas. Nicotine and respirable suspended particle concentrations and participants' blood oxygen saturation were also monitored. We calculated time and frequency domain measures of HRV for periods in and out of the smoking area, and we evaluated associations with ETS using comparative statistics and regression modeling. ETS exposure was negatively associated with all measures of HRV. During exposure periods, we observed an average decrement of approximately 12% in the standard deviation of all normal-to-normal heart beat intervals (an estimate of overall HRV). ETS exposures were not associated with mean heart rate or blood oxygen saturation. Altered cardiac autonomic function, assessed by decrements in HRV, is associated with acute exposure to ETS and may be part of the pathophysiologic mechanisms linking ETS exposure and increased cardiac vulnerability.

Heart rate variability associated with particulate air pollution.

BACKGROUND: Epidemiologic studies have linked fine particulate air pollution with cardiopulmonary mortality, yet underlying biologic mechanisms remain unknown. Changes in heart rate variability (HRV) may reflect changes in cardiac autonomic function and risk of sudden cardiac death. This study evaluated changes in mean heart rate and HRV in human beings associated with changes in exposure to particulate air pollution. METHODS: Repeated ambulatory electrocardiographic monitoring was conducted on 7 subjects for a total of 29 person-days before, during, and after episodes of elevated pollution. Mean HR, the standard deviation of normal-to-normal (NN) intervals (SDNN), the standard deviation of the averages of NN intervals in all 5-minute segments of the recording (SDANN), and the square root of the mean of squared differences between adjacent NN intervals (r-MSSD) were calculated for 24-hour and 6-hour time segments. Associations of HRV with particulate pollution levels were evaluated with fixed-effects regression models. RESULTS: After controlling for differences across patients, elevated particulate levels were associated with (1) increased mean HR, (2) decreased SDNN, a measure of overall HRV, (3) decreased SDANN, a measure that corresponds to ultralow frequency variability, and (4) increased r-MSSD, a measure that corresponds to high-frequency variability. The associations between HRV and particulates were small but persisted even after controlling for mean HR. CONCLUSIONS: This study suggests that changes in cardiac autonomic function reflected by changes in mean HR and HRV may be part of the pathophysiologic mechanisms or pathways linking cardiovascular mortality and particulate air pollution.

Effects of randomized assignment to a smoking cessation intervention and changes in smoking habits on respiratory symptoms in smokers with early chronic obstructive pulmonary disease: the Lung Health Study.

PURPOSE: To evaluate the effects of randomly assigning smokers who have early chronic obstructive pulmonary disease (COPD) to a smoking-cessation intervention on the symptoms of chronic cough, chronic phlegm production, wheezing and shortness of breath, and to determine the effects of quitting smoking on these symptoms. SUBJECTS AND METHODS: A total of 5,887 male and female smokers 35 to 60 years of age with early COPD [defined as a forced expiratory volume in the first second (FEV1) of 55% to 90% of predicted and FEV1/forced vital capacity (FVC) <0.70] were enrolled in a 5-year clinical trial. Two-thirds of participants were randomly assigned to smoking-intervention groups and one-third to a usual-care group. The intervention groups attended 12 intensive smoking-cessation sessions that included behavior modification techniques and the use of nicotine chewing gum. One intervention group was treated with ipratropium bromide by inhaler; the other intervention group received placebo inhalers. The usual-care group was advised to stop smoking. All participants were followed annually. Smoking status was biochemically validated by salivary cotinine measurements or exhaled carbon monoxide values. RESULTS: Validated 5-year sustained smoking cessation occurred in 22% of participants in the intervention compared with only 5% of participants in the usual-care group. At the end of the study, the prevalence of each of the four symptoms in the two intervention groups was significantly less than in the usual-care group (P <0.0001). For example, among participants who did not report cough at baseline, 15% of those in the intervention groups had cough at least 3 months during the year, compared with 23% of those in usual care. Sustained quitters had the lowest prevalence of all four symptoms, whereas continuous smokers had the greatest prevalence of these symptoms. Changes in symptoms occurred primarily in the first year after smoking cessation. Respiratory symptoms were associated with greater declines in FEV1 during the study (P <0.001). Ipratropium bromide had no long-term effects on respiratory symptoms. CONCLUSIONS: In this prospective randomized trial using an intention-to-treat analysis, smokers with early COPD who were assigned to a smoking-cessation intervention had fewer respiratory symptoms after 5 years of follow-up.

Daily changes in oxygen saturation and pulse rate associated with particulate air pollution and barometric pressure.

Epidemiologic studies have linked fine particulate air pollution with increases in morbidity and mortality rates from cardiopulmonary complications. Although the underlying biologic mechanisms responsible for this increase remain largely unknown, potential pathways include transient declines in blood oxygenation and changes in pulse rate following exposures to particulate air pollution episodes. This study evaluated potential associations between daily measures of respirable particulate matter (PM) with pulse rate and oxygen saturation of the blood. Pulse rate and oxygen saturation (Spo2) using pulse oximetry were measured daily in 90 elderly subjects living near air pollution monitors during the winter of 1995-96 in Utah Valley. We also evaluated potential associations of oxygen saturation and pulse rate with barometric pressure. Small but statistically significant positive associations between day-to-day changes in Spo2 and barometric pressure were observed. Pulse rate was inversely associated with barometric pressure. Exposure to particulate pollution was not significantly associated with Spo2 except in male participants 80 years of age or older. Increased daily pulse rate, as well as the odds of having a pulse rate 5 or 10 beats per minute (bpm) above normal (normal is defined as the individual's mean pulse rate throughout the study period), were significantly associated with exposure to particulate pollution on the previous 1 to 5 days. The medical or biologic relevance of these increases in pulse rate following exposure to particulate air pollution requires further study.

Oxygen saturation, pulse rate, and particulate air pollution: A daily time-series panel study.

Although epidemiological studies have linked particulate air pollution with cardiopulmonary mortality, underlying biological mechanisms remain largely unknown. Unexplored pathophysiological pathways include transient declines in blood oxygenation and/or changes in cardiac rhythm following particulate exposure. In this study, blood oxygen saturation using pulse oximetry (SpO2) and pulse rate were measured daily on a panel of 90 elderly subjects during the winter of 1995-1996 in Utah Valley. Associations of SpO2 and pulse rate with respirable particulate pollution (particles with an aerodynamic diameter

Effect of weight gain on pulmonary function after smoking cessation in the Lung Health Study.

The objective of this study was to determine if the weight gain that accompanies smoking cessation is independently associated with reductions in FEV1 and FVC, using a multicenter randomized intervention trial of smoking cessation in 10 communities in the United States and Canada. Enrollees were currently smoking women and men 35 to 60 yr of age with mild-to-moderate airway obstruction. Participants were randomized to one of three study groups: an intensive smoking cessation program with an inhaled bronchodilator (or a placebo), and usual care. Changes in absolute and percent predicted FEV1 and FVC between baseline and fifth annual follow-up visit were monitored in relation to changes in body weight during the interval. At the baseline examination, percent predicted FEV1 was maximal at 90 to 100% ideal body weight (IBW) and was lower as body weight deviated from this range. The FVC decreased linearly when IBW exceeded 100%. Weight gain was greatest during the first 12 mo after smoking cessation. Weight gain was associated with lower fifth-year FEV1 and FVC in all smoking categories: continuous smokers, intermittent smokers, and sustained quitters. The FVC was affected by weight gain more than was the FEV1, and the FEV1 was affected by smoking cessation more than FVC. Men showed more impairment of FVC with weight gain than did women, possibly because of differential patterns of fat deposition. In sustained quitters, after adjustment for baseline factors, the estimated reduction of FVC was 17.4 ml/kg weight gain for men and 10.6 ml/kg for women. The estimated loss of FEV1 was 11.1 ml/kg weight gain for men and 5.6 ml/kg for women. Lung function after smoking cessation is significantly influenced by weight gain and affects men more than women. The deleterious effects of weight gain are small, however, in comparison with the beneficial effects of smoking cessation.

Early intervention in COPD.

Much has been learned in the 35 years since the Dutch Hypothesis proposed early identification and intervention in those at risk for COPD. More has been accomplished in identification than in therapy. This is due in part to the powerful addiction of cigarette smoking and the continued search for effective pharmacologic means to prevent the accelerated loss in lung function. The Dutch Hypothesis states that airways hyperresponsiveness predicts future acceleration of the rate of lung function decline, particularly in susceptible smokers. In the Lung Health Study, heightened bronchoconstrictor response to methacholine did, indeed, strongly predict an adverse longitudinal decline in lung function. Further, airway hyperresponsiveness was more common than previously suspected, particularly in women. In this subgroup of cigarette smokers, selected because of early COPD, the incidence of hyperresponsiveness was 62% in men and 87% in women, rather than the anticipated 20%. In addition, in the Lung Health Study data recently released, female continuous smokers with the greatest degree of airway hyperresponsiveness exhibited the fastest rate of decline in lung function. However, cigarette smoking had a greater negative impact than hyperresponsiveness. Those with the greatest responsiveness who quit smoking declined more slowly than those with the least responsiveness who continued to smoke. The evidence continues to mount that smoking cessation should be the first and single most important intervention to prevent COPD. Many studies have demonstrated the beneficial effect of smoking cessation on declining lung function. In the comparison of the randomized groups, the Lung Health Study gives the strongest evidence to date that smoking cessation results in substantial benefit to lung function; the benefit continued to increase during the five year study. There was no evidence in the Lung Health Study that bronchodilator usage prevents the relentless decline in lung function in COPD. The increase of FEV1 among users of ipratroprium (even among the most-compliant) was not sustained when the bronchodilator was discontinued at the end of the study.

Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease. The Lung Health Study Research Group.

As part of a clinical trial of early intervention in chronic obstructive pulmonary disease (COPD) (the Lung Health Study), 5,733 smokers with mild to moderate airflow obstruction underwent methacholine challenge tests at baseline. All participants were randomized to receive either usual care (no intervention) or special intervention, consisting of intensive smoking cessation counseling and the prescription of a metered-dose inhaler containing either ipratropium bromide or placebo (two inhalations three times daily). For this report, we analyzed the relationship between baseline methacholine reactivity and subsequent change in lung function. Methacholine reactivity was expressed as a logarithmic function of the two-point slope of percent decline in FEV1 over the concentration of methacholine (LMCR). Using a random effects linear model, LMCR was found to be a strong predictor of change in FEV1% predicted, after controlling for baseline lung function, age, sex, baseline smoking history, and changes in smoking status. Significant interactions were found between reactivity and smoking behavior. In the first year, participants who quit smoking showed improvement in FEV1, whereas continuing smokers showed worsening, and between Years 1 and 5, lung function declined to a greater extent in continuing smokers than in sustained quitters. For both time periods, these quitter/smoker differences increased as a function of airway reactivity. These findings indicate that methacholine reactivity is an important predictor of progression of airway obstruction in continuing smokers with early COPD, independent of the baseline level of obstruct.

Early intervention in chronic obstructive pulmonary disease. A review of the Lung Health Study results.

The major findings of the LHS that have been reported thus far are that an effective smoking cessation program can be developed that can produce more than a 20% success rate in getting smokers to give up the habit permanently, and that by stopping smoking, individuals with early COPD benefit by having an initial improvement in lung function and a slowing of the annual loss of their FEV1. The use of a bronchodilator has a short-term effect in improving the FEV1, but it does not affect long-term changes in lung function. AHR is common in patients with mild-to-moderate COPD. The reward for a smoker to give up the habit is an initial gain in FEV1 and a subsequent close to normal annual rate of decline of this pulmonary function parameter. These results should provide a positive incentive for smokers to quit and thereby decrease the morbidity and mortality caused by the use of tobacco.

Spirometry in the Lung Health Study: II. Determinants of short-term intraindividual variability.

The Lung Health Study (LHS) is a randomized clinical trial designed to determine whether a smoking intervention program and use of an inhaled bronchodilator (BD) can reduce the rate of decline of FEV1 in cigarette smokers with airflow limitation. During recruitment, spirometry was performed at second and third screening visits, a mean of 21 d apart. A total of 5,887 smokers, 35 to 60 yr of age and of whom 63% were men, met the study eligibility requirements. Smokers taking physician-prescribed BDs or with an FEV1 < 50% or > 90% predicted were excluded, as were those whose FEV1/FVC ratio was greater than 70%. Two inhalations of isoproterenol were given to determine BD response during the second visit. A serial dilution methacholine challenge test was done during the third visit to determine nonspecific airway reactivity. Ninety-five percent of the differences between FEV1 measured at the two visits were within 240 ml for women and within 320 ml for men (coefficients of repeatability). The best independent predictors of the mean short-term (between visit) intraindividual FEV1 variability were factors indicating intrinsic airway reactivity of the participants: bronchodilator response, methacholine reactivity, and the presence of wheezing; as well as factors influenced by the quality of spirometry testing: the difference between the highest and second highest FEV1s and peak flows during baseline spirometry, and the time to reach peak flow (PEFT).

Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study.

OBJECTIVE: To determine whether a program incorporating smoking intervention and use of an inhaled bronchodilator can slow the rate of decline in forced expiratory volume in 1 second (FEV1) in smokers aged 35 to 60 years who have mild obstructive pulmonary disease. DESIGN: Randomized clinical trial. Participants randomized with equal probability to one of the following groups: (1) smoking intervention plus bronchodilator, (2) smoking intervention plus placebo, or (3) no intervention. SETTING: Ten clinical centers in the United States and Canada. PARTICIPANTS: A total of 5887 male and female smokers, aged 35 to 60 years, with spirometric signs of early chronic obstructive pulmonary disease. INTERVENTIONS: Smoking intervention: intensive 12-session smoking cessation program combining behavior modification and use of nicotine gum, with continuing 5-year maintenance program to minimize relapse. Bronchodilator: ipratropium bromide prescribed three times daily (two puffs per time) from a metered-dose inhaler. MAIN OUTCOME MEASURES: Rate of change and cumulative change in FEV1 over a 5-year period. RESULTS: Participants in the two smoking intervention groups showed significantly smaller declines in FEV1 than did those in the control group. Most of this difference occurred during the first year following entry into the study and was attributable to smoking cessation, with those who achieved sustained smoking cessation experiencing the largest benefit. The small noncumulative benefit associated with use of the active bronchodilator vanished after the bronchodilator was discontinued at the end of the study. CONCLUSIONS: An aggressive smoking intervention program significantly reduces the age-related decline in FEV1 in middle-aged smokers with mild airways obstruction. Use of an inhaled anticholinergic bronchodilator results in a relatively small improvement in FEV1 that appears to be reversed after the drug is discontinued. Use of the bronchodilator did not influence the long-term decline of FEV1.

Gender difference in airway hyperresponsiveness in smokers with mild COPD. The Lung Health Study.

Methacholine bronchoprovocation challenge testing was successfully completed in 5,662 participants (3,556 men and 2,106 women) at the time they were randomized into the Lung Health Study, a multicenter trial designed to evaluate early intervention in chronic obstructive pulmonary disease (COPD). All participants were smokers between the ages of 35 and 60 yr who had mild COPD. The male:female prevalence of a positive challenge (PC20FEV1) was 25%:48% and 63%:87% at a PC20FEV1 of < or = 5 mg/ml (AHR5) and < or = 25 mg/ml (AHR25), respectively. This analysis explores these marked gender differences in airway hyperresponsiveness (AHR). Relative risks (RR) for predictors of AHR and the 95% confidence intervals (95% CI) were estimated using semiparametric Cox proportional-hazards models. The initial model controlled for age, gender, smoking history, height, and weight. The RR (95% CI) for female gender was 1.75 (1.60, 1.92). When the measured baseline FEV1 was added to the model as a surrogate for airway caliber, the RR for female gender decreased to 1.06 (0.96, 1.18). Thus, in this population of middle-aged smokers with mild COPD, the high prevalence of AHR appears to be associated with a decrease in airway caliber. The higher prevalence of AHR noted in women is due to their having a smaller airway caliber than their male counterparts.

Acute effects of PM10 pollution on pulmonary function of smokers with mild to moderate chronic obstructive pulmonary disease.

This study assessed the association between respirable particulate air pollution (PM10) and changes in the pulmonary function (FEV1, FEV1/FVC, and FVC) of smokers with mild to moderate airflow limitation. Spirometric data of Salt Lake City participants in The Lung Health Study were used from two screening visits 10 to 90 days apart after an initial screening visit, which included spirometry. We analyzed differences in pulmonary function (delta FEV1, delta FEV1/FVC, and delta FVC) for participants between the two spirometry visits. Significant associations between changes in pulmonary function and PM10 were observed. delta FEV1 and delta FEV1/FVC were inversely associated with changes in PM10. Although these associations were small, explaining only about 2 to 3% of the variance in delta FEV1, they were consistently negative and statistically significant (p < or = 0.01). On average, an increase in PM10 equal to 100 micrograms/m3 was associated with a marginal decline in FEV1 equal to approximately 2%. Associations between delta FVC and PM10 were consistently negative, but they were not statistically significant. No consistent or statistically significant associations between delta FEV1, delta FEV1/FVC, or delta FVC with changes in daily temperatures were observed. The effect of PM10 was greater for men than for women. The effect was nearly the same for those with nonspecific airway hyperresponsiveness (AHR), based on methacholine inhalation challenge testing, versus those without AHR. We conclude that in current smokers PM10 possibly has a small transient negative effect on lung function that is not entirely obscured by their smoking habit.

Chronic Obstructive Pulmonary Disease Early Intervention Trial (Lung Health Study). Baseline characteristics of randomized participants.

The Chronic Obstructive Pulmonary Disease Early Intervention Trial, or Lung Health Study, is a multicenter randomized clinical trial sponsored by the Division of Lung Diseases of the National Heart, Lung, and Blood Institute. The hypothesis being tested is that over a 5-year period, a comprehensive intervention program can reduce both the rate of decline in pulmonary function and the rates of respiratory morbidity and mortality in middle-aged smokers with mild to moderate airflow obstruction. The primary outcome variable of the trial is the annual rate of decline of maximum postbronchodilator FEV1. Secondary outcomes are the development of respiratory and nonrespiratory morbidity and mortality. After screening 73,694 cigarette smokers, aged 35 to 60 years, 5,887 participants were randomized into three equal groups: usual care, smoking intervention with daily use of a metered-dose inhaler with ipratropium bromide, and smoking intervention with inhalation of placebo. Eligible participants had a ratio of FEV1 to forced vital capacity (FVC) of 70 percent or less, were free of known life-limiting conditions, expressed willingness to enter the intervention program if so randomized, and gave written informed consent prior to entry into the trial. Spirometry, methacholine challenge, and questionnaires were strictly standardized within and across centers. The purpose of this report is to describe the characteristics of randomized participants at the time of entry into the study. For both sexes, three measures of lung function--average cross-sectional FEV1/FVC ratio, FEV1, and FEV1 percentage of predicted normal--showed slight downward trends for each successively older 5-year age cohort. The increase in FEV1 after isoproterenol was 15 percent or more in only 2.4 percent of men and 2.8 percent of women. A positive response to methacholine (defined as a fall in FEV1 of > 20 percent from baseline at concentrations up to 25 mg/ml) occurred in 63 percent of men and 87 percent of women. The cross-sectional prevalences of cough, phlegm, wheeze on most days or nights, and shortness of breath were 49 percent, 43 percent, 32 percent, and 43 percent, respectively. Respiratory symptoms were reported by a higher proportion of participants in the younger age groups than in the older age groups. Participants who reported cough, phlegm, and/or wheeze averaged lower FEV1 percent predicted and higher probability of positive response to methacholine than participants who did not. Shortness of breath appeared to be significantly associated with lower lung function and higher reactivity in men but not in women.(ABSTRACT TRUNCATED AT 400 WORDS)

The lung health study: airway responsiveness to inhaled methacholine in smokers with mild to moderate airflow limitation. The Lung Health Study Research Group.

As part of a multicenter clinical trial (Lung Health Study), methacholine inhalation challenge testing was performed in 5,877 current cigarette smokers, ages 35 to 59 yr (mean 48.5 +/- 6.8 yr), with borderline to moderate airflow limitation (FEV1/FVC ratio 63.0 +/- 5.5). The test was successfully completed in 96.4% of subjects, of whom 63% were male and 95.9% were white. Symptomatic reactions to methacholine were rarely severe enough to require evaluation by a trial physician. Nonspecific airways hyperresponsiveness (AHR) was defined as a greater than or equal to 20% decline in FEV1 from the post-diluent control value after inhalation of less than or equal to 25 mg/ml methacholine. AHR was noted in a significantly higher percentage of women (85.1%) than men (58.9%). Moreover, nearly twice as many women as men (46.6 and 23.9%, respectively) responded to less than or equal to 5 mg/ml of methacholine. In both men and women, baseline degree of airways obstruction and clinical center were strongly associated with AHR (p less than 0.001), whereas age was not. Additional associations with AHR were analyzed in men and women separately using logistic regression after adjustment for baseline lung function, age, and center-to-center differences. In men, AHR was significantly related to symptoms of wheeze, chronic cough and/or sputum, and a history of asthma or hay fever (p less than 0.004), but not to current or lifetime tobacco use. By contrast, among women, AHR was not significantly associated with chronic cough and/or phlegm (p greater than 0.05) or a past history of asthma or hay fever (p greater than 0.1) and was only weakly related to wheeze and current asthma (p = 0.04), as well as to cigarette pack-years (p = 0.044). These results indicate that most continuing smokers with functional evidence of early chronic obstructive pulmonary disease have nonspecific AHR that is strongly related to gender and baseline lung function and, to a lesser extent, to respiratory symptoms. The reason for the striking effect of gender on AHR in early chronic obstructive pulmonary disease is unclear but cannot be attributed to male-female differences in age, cigarette use, presence of asthma, or baseline degree of airflow obstruction.

Adjustment of DLCO for varying COHb, and alveolar PO2 using a theoretical adjustment equation.

The diffusing capacity of the lung for carbon monoxide (DL) is affected by changes in alveolar partial pressure of oxygen (PAO2), hemoglobin concentration (Hb), and carboxyhemoglobin concentration (COHb). A number of investigators have derived empiric adjustment equations to account for changes in these variables. We evaluated an adjustment of DL for changes in COHb and PAO2 using a single equation derived from Roughton and Forster's original definitions (J. Appl. Physiol., 1957). Unadjusted DL values declined significantly with rising COHb (-0.938%/percent COHb increase, P less than 0.0001) and rising PAO2 (-0.343%/mm Hg PAO2 increase, P less than 0.0001). Adjusted measured DL using the derived equation showed no significant change with changing COHb and PAO2 levels and provides an acceptable method for adjustment of DL for the effects of varying COHb and PAO2 levels from the standard conditions of COHb% = 0, and PAO2 = 110 mm Hg. Since a similar equation has previously been used to adjust for changes in DL due to anemia, we propose to use a single equation which is theoretically derived and empirically verified to adjust DL measurements for changes in COHb, PAO2 and hemoglobin.