PubMed Health⌕ Search

Biomedical subjects

Karlman Wasserman

Publications and source records attributed to Karlman Wasserman.

At least 19 recordsLinked to original sources

Ethnic- and sex-free formulae for detection of airway obstruction.

RATIONALE: Spirometric detection of airway obstruction in adults requires separate predictive formulae for each ethnicity and sex for percentage of FEV(1)/FVC (%FEV(1)/FVC) and percentage of FEV(3)/FVC (%FEV(3)/FVC), the major measurements for defining airway obstruction. OBJECTIVES: To eliminate the need for multiple formulae for black, Latin, and white men and women by developing single formulae with less variance than current formulae for %FEV(1)/FVC and %FEV(3)/FVC. METHODS: Data from nearly 6,000 healthy never-smokers 20.0-79.9 yr of age in the Third National Health and Nutrition Examination Survey were reevaluated mathematically and graphically based on the preliminary hypothesis that predictive normal FEV(1)/FVC and FEV(3)/FVC ratios could be calculated from the age and FVC alone, without considering ethnicity, sex, or height. Current and new formulae were evaluated, first considering the population as consisting of 36 equally weighted subgroups (6 decades x 3 ethnicities x 2 sexes) and then weighting each individual equally. MEASUREMENTS AND RESULTS: For each year of age, the slope of %FEV(1)/FVC versus FVC approximated -1.8%/l/yr; the slope of %FEV(3)/FVC versus FVC approximated -0.8%/l/yr. After trial and error iterations, the optimal formulae were %FEV(1)/FVC = 98.8 - 0.25 x years - 1.79 x FVC and %FEV(3)/FVC = 105.4 - 0.20 x years - 0.75 x FVC. CONCLUSIONS: These two new predicting formulae for %FEV(1)/FVC and %FEV(3)/FVC, which require only age and FVC as variables, approximate actual values closer than previously published separate formulae for each ethnicity and sex. With 95% confidence limits, they should allow better discrimination between normality and airway obstruction in adults of at least these three ethnicities.

Adult↗

Discriminating measures and normal values for expiratory obstruction.

OBJECTIVES: To develop mean and 95% confidence limits for the lower limit of normal (LLN) values for forced expiratory volume in 3 s (FEV3)/FVC ratio for Latin, black, and white adults; to ascertain comparative variability of the FEV1/FVC ratio, the FEV3/FVC ratio, and forced expiratory flow, midexpiratory phase (FEF(25-75)) in never-smoking adults; to evaluate their utility in measuring the effect of smoking on airflow limitation; and to develop and use the fraction of the FVC that had not been expired during the first 3 s of the FVC (1 - FEV3/FVC) to identify the growing fraction of long-time-constant lung units. DESIGN: Analysis of the Third National Health and Nutrition Examination Survey (NHANES III) database of never-smokers and current smokers. PARTICIPANTS: A total of 5,938 adult never-smokers and 3,570 current smokers from NHANES III with spirometric data meeting American Thoracic Society standards. MEASUREMENTS AND RESULTS: After establishing new databases for never-smokers and current smokers, we quantified the mean and LLN values of FEV3/FVC in never-smokers, and identified spirometric abnormalities in current smokers. When associated with older age, FEV3/FVC decreases and 1 - FEV3/FVC increases as FEV1/FVC decreases. On average, using these measurements, the condition of current smokers worsened about 20 years faster than that of never-smokers by middle age. If < 80% of the mean predicted FEF(25-75) was used to identify abnormality, over one quarter of all never-smokers would have been falsely identified as being abnormal. Using 95% confidence limits, 42% of 683 smokers with reduced FEV1/FVC and/or FEV3/FVC would have been judged as normal by FEF(25-75). CONCLUSIONS: FEV1/FVC, FEV3/FVC, and 1 - FEV3/FVC characterize expiratory obstruction well. In contrast, FEF(25-75) measurements can be misleading and can cause an unacceptably large number of probable false-negative results and probable false-positive results.

Adult↗

Cardiopulmonary exercise testing and six-minute walk correlations in pulmonary arterial hypertension.

In a clinical trial of 178 patients with pulmonary arterial hypertension, treatment improved the 6-minute walk (6MW) distance but not the peak VO2. To clarify this discrepancy, we examined the exercise data from all study sites. Patients received either the endothelin receptor antagonist sitaxsentan or placebo and underwent serial 6MW and cardiopulmonary exercise testing (CPET). In 518 pairs of body weight-adjusted and unadjusted 6MW and CPET data, the correlation between 6MW and peak VO2 was 0.48. In the 4 sites with the highest overall correlation at baseline (r = 0.62 compared with 0.46 for the other 19 sites, p = 0.04), the correlations at baseline (0.66) and at week 12 (0.65) were similar (p = 0.90). However, the correlation increased significantly from baseline (0.34) to week 12 (0.54, p = 0.0005) for the other 19 sites. The correlations between weight-adjusted 6MW distance and peak VO2 for all centers (0.76) were significantly higher than the unadjusted correlations (0.48, p < 0.0001). Improvement in the correlations over time between the 6MW and CPET data at less-experienced sites was most consistent with improved technical skill with increasing experience. Weight adjustment of the 6MW improved its correlation with peak VO2. In conclusion, in future multicenter trials, CPET expertise should be validated at all sites before subject enrollment.

Adolescent↗

Work-rate affects cardiopulmonary exercise test results in heart failure.

AIMS: Cardiopulmonary exercise test (CPET) is used to evaluate patients with chronic heart failure (HF) usually by means of a personalized ramp exercise protocol. Our aim was to evaluate if exercise duration or ramp rate influences the results. METHODS AND RESULTS: Ninety HF patients were studied (peak V (O(2)): >20 ml/min/kg, n=28, 15-20 ml/min/kg, n=39 and <15 ml/min/kg, n=23). Each patient did four CPET studies. The initial study was used to separate the subjects into three groups, according to their exercise capacity. In the remaining studies, work-rate was increased at three different rates designed to have the subjects reach peak exercise in 5, 10 and 15 min from the start of the ramp increase in work-rate, respectively. The order was randomized. The work-rate applied for the total population averaged 22.7+/-8.0, 11.6+/-3.7, 7.5+/-2.9 W/min with effective loaded exercise duration of 5 min and 16 s+/-29 s, 9 min and 43 s+/-49 s and 14 min and 32 s+/-1 min and 12 s for the 5-, 10- and 15-min tests, respectively. Peak V (O(2)) averaged 16.9+/-4.3*, 18.0+/-4.4 and 18.0+/-5.4 ml/min/kg for the 5-, 10- and 15-min tests, (*=p<0.001 vs. 10 min). The shortest test had the lowest peak heart rate and ventilation and highest peak work-rate. Peak V (O(2)) and heart rate were lowest in 5-min tests regardless of HF severity. The DeltaV (O(2))/Deltawork-rate was lowest in 5-min tests and highest in 15-min tests. At all ramp rates, DeltaV (O(2))/Deltawork-rate was lower for the subjects with the lower peak V (O(2)). The V (e)/V (CO(2)) slope and V (O(2)) at anaerobic threshold were not affected by the protocol for any grade of HF. CONCLUSIONS: In chronic HF, exercise protocol has a small effect on peak V (O(2)) and DeltaV (O(2))/Deltawork but does not affect V (O(2)) at anaerobic threshold and V (e)/V (CO(2)) slope.

Anaerobic Threshold↗

End-tidal PCO2 abnormality and exercise limitation in patients with primary pulmonary hypertension.

OBJECTIVES: Primary pulmonary hypertension (PPH) is a pulmonary vasculopathy resulting in exercise intolerance, usually due to dyspnea. We hypothesized that ventilation is increased during exercise in PPH relative to normal because the ventilated lung is underperfused, cardiac output increase is restricted, and arterial hypoxemia may develop. Our aim was to determine the size of the reduction in end-tidal Pco(2) (Petco(2)) as a reflection of the abnormality in ventilatory efficiency and ventilatory drive in PPH patients. METHODS: We performed cardiopulmonary exercise testing (CPET) in 52 PPH patients. All had hemodynamic measurements to confirm the diagnosis of PPH. A subgroup of 29 patients who underwent right-heart catheterization within 50 days of CPET were studied to compare their CPET responses to resting hemodynamics. Nine healthy volunteers matched for age and gender served as CPET control subjects. RESULTS: In PPH patients, the percentage of predicted peak oxygen uptake (Vo(2)) correlated significantly with mean pulmonary artery pressure (mPAP) [r = - 0.59, p = 0.0007, n = 29]. Petco(2) values at rest, anaerobic threshold (AT), and peak Vo(2) were proportionately reduced as percentage of predicted peak Vo(2) decreased (r = 0.66 to 0.72, p < 0.0001, n = 52). Petco(2) values at rest, AT, and peak Vo(2) were also reduced as mPAP increased (r = - 0.51 to - 0.53, p < 0.005, n = 29). In contrast to normal subjects in whom Petco(2) increased from rest to AT, Petco(2) decreased in PPH patients, except for two patients with mild PPH in whom there was no change. Also, Petco(2) increased rather than decreased further at the start of recovery, in contrast to normal. Although usually normal at rest, oxyhemoglobin saturation decreased during exercise in most PPH patients. CONCLUSIONS: In patients with PPH, Petco(2) at rest and exercise is significantly reduced in proportion to physiologic disease severity. The range of values is unusually low. Furthermore, the directional changes of Petco(2) during exercise and early recovery are in the opposite direction of normal.

Adult↗

Non-linear cardiac output dynamics during ramp-incremental cycle ergometry.

Published literature asserts that cardiac output (Q(.) = V(.) >O(2)x1/C((a-v))O(2)) increases as a linear function of oxygen uptake with a slope of approximately 5-6 during constant work rate exercise. However, we have previously demonstrated that C((a-v))O(2) has a linear relationship as a function of V(.)O(2) during progressively increasing work rate incremental exercise. Therefore, we hypothesized that Q(.) may indeed have a non-linear relationship with respect to V(.)O(2) during incremental, non-steady state exercise. To investigate this hypothesis, we performed five maximal progressive work rate exercise studies in healthy human subjects. Q(.) was determined every minute during exercise using measured breath-by-breath V(.) >O(2), and arterial and pulmonary artery measurements of PO(2), hemoglobin saturation, and content. Q(.) was plotted as a function of V(.) >O(2) and the linear and non-linear (first order exponential and hyperbolic) fits determined for each subject. Tests for linearity were performed by assessing the significance of the quadratic terms added to the linear relation using least squares estimation in linear regression. Linearity was inadequate in all cases (group P<0.0001). We conclude that cardiac output is a non-linear function of V(.)O(2 )during ramp-incremental exercise; the pattern of non-linearity suggests that while the kinetics of Q(.) > are faster than those of V(.) >O(2) they progressively slow as work rate (and V(.) >O(2)) increases.

Adult↗

Gas exchange responses to constant work-rate exercise in patients with glycogenosis type V and VII.

During constant work-rate exercise above the lactic acidosis threshold, oxygen consumption fails to plateau by 3 minutes, but continues to rise slowly. This slow component correlates closely with the rise in lactate in normal subjects. We investigated if oxygen consumption during constant work-rate exercise could rise after 3 minutes in the absence of a rise in lactate. We studied five patients with McArdle's disease, one patient with phosphofructokinase deficiency and six normal subjects. Subjects performed two 6-minute duration constant work-rate exercise tests at 40 and 70% of peak oxygen consumption. During low-intensity exercise, oxygen consumption reached steady state by 3 minutes in both groups. Lactate rose slightly in control subjects but not in patients. During high-intensity exercise, oxygen consumption rose from the third to the sixth minute by 144 (21-607) ml/minute (median and range) in control subjects and by 142 (73-306) ml/minute in patients (p = not significant, Mann-Whitney U test). Over the same period, lactate (geometric mean and range) rose from 2.68 (1.10-5.00) to 5.39 (2.70-10.00) mmol/L in control subjects, but did not rise in patients (1.20 [0.64-1.60] to 0.70 [0.57-1.20] mmol/L). We conclude that the slow component of oxygen consumption during heavy exercise is not dependent on lactic acidosis.

Acidosis, Lactic↗

Altered exercise gas exchange as related to microalbuminuria in type 2 diabetic patients.

STUDY OBJECTIVE: Microalbuminuria in diabetes mellitus is a risk factor for cardiovascular disease. We hypothesized that microalbuminuria in type 2 diabetic patients is related to impaired cardiopulmonary function during exercise, and that the severity of impairment is correlated with the degree of microalbuminuria. DESIGN: Twenty of each of the following categories of subjects performed symptom-limited cardiopulmonary exercise testing on a cycle ergometer: (1) type 2 diabetic patients with normoalbuminuria (daily urinary albumin excretion [UAE] < 30 mg/d); (2) type 2 diabetic patients with microalbuminuria (daily UAE, 30 to 300 mg/d); and (3) normal control subjects. MEASUREMENTS AND RESULTS: Oxygen consumption (VO(2)) of patients with microalbuminuria was lower than that of control subjects at anaerobic threshold (AT) [p < 0.001], and was lower than both control subjects (p < 0.001) and patients with normoalbuminuria (p = 0.015) at peak exercise. There was a progressive worsening in gas exchange efficiency at the lungs, as measured by minute ventilation (VE)/carbon dioxide production (VCO(2)) at AT or DeltaVE/DeltaVCO(2) slope, (p = 0.006 and p = 0.019, respectively) going from control subjects to patients with normoalbuminuria and then to patients with microalbuminuria. Left ventricular ejection fractions and BP were similar in patients with normoalbuminuria and microalbuminuria. More patients with microalbuminuria (n = 9) than with normoalbuminuria (n = 2) demonstrated diastolic dysfunction (p = 0.013). These 11 patients had lower peak VO(2) values (p = 0.001) and higher daily UAE (p = 0.028). An inverse linear relationship was found between peak VO(2) and log(10) daily UAE (r = - 0.57, r(2) = 0.29, p < 0.001). CONCLUSIONS: Abnormalities reflecting reduced oxygen transport and impaired gas exchange efficiency were found during exercise, and were especially profound in patients with microalbuminuria. These changes could be secondary to pulmonary microangiopathy and myocardial interstitial changes. Increases in capillary permeability to proteins may take place in the myocardium as they do in the kidneys, and contribute to impaired myocardial distensibility and hence diastolic dysfunction.

Albuminuria↗

Reproducibility of cardiopulmonary exercise measurements in patients with pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVES: As part of a recent study, cardiopulmonary exercise tests (CPETs) were used to evaluate and follow up patients with pulmonary arterial hypertension (PAH). These patients were more impaired than those in other published series evaluating CPET reproducibility. We used these patient tests to assess patient performance variability and evaluate reading variability. To achieve this end, six independent evaluators graded key CPET measurements in patients with PAH who underwent duplicate CPETs within 3 days of each other. SETTING AND PATIENTS: Over a 15-month period at two tertiary-care teaching hospitals, 42 patients with PAH underwent repeated, paired CPETs using cycle ergometry. INTERVENTIONS AND MEASUREMENTS: Each patient underwent one to six pairs of cycle ergometry tests to maximal tolerance. Each pair of tests was separated by 3 months, with each test in the pair separated by 1 to 3 days. Specific guidelines were given to the independent evaluators for the key measurements assessed from each CPET study: peak O(2) uptake (Vo(2)), peak heart rate, peak O(2) pulse, anaerobic threshold (AT), and end-tidal Po(2), end-tidal Pco(2), and the ventilatory equivalent for CO(2) at the AT (Ve/Vco(2)@AT). RESULTS: There were no fatalities or complications occurring among the 242 tests performed on 42 patients. The mean peak Vo(2) was 722 mL/min or 41% of predicted; 34 patients were Weber class C or D. Using the specific guidelines to measure the variability of measurements made by the six independent evaluators, the coefficients of variation were < 2.2% for peak Vo(2), peak heart rate, peak O(2) pulse, end-tidal values at the AT, and Ve/Vco(2)@AT, while for the AT, it was 8.5%. There were no significant differences in these measurements between the first and second tests of any pair or between the earlier and later sets of pairs. CONCLUSIONS: Using specific guidelines, key CPET measurements can be safely, reliably, and reproducibly assessed even in patients with severe exercise intolerance.

Adolescent↗

Exercise-induced pulmonary edema in heart failure.

BACKGROUND: In heart failure (HF) patients, exercise may increase pulmonary capillary hydrostatic pressure and thereby generate pulmonary edema. If pulmonary edema developed, alveolar-capillary membrane conductance (Dm), measured immediately after exercise, would decrease. To test this hypothesis, we measured Dm before and at 2 and 60 minutes after exercise. METHODS AND RESULTS: We studied 10 HF patients with exercise-induced periodic breathing, 10 with peak o2 < or =15 mL x min(-1) x kg(-1) (severe HF), 10 with o2=15 to 20 mL x min(-1) x kg(-1) (moderate HF), and 10 normal subjects (control). Using the Roughton-Forster technique, we measured carbon monoxide diffusion capacity (DLco) and its components, capillary blood volume (Vc) and Dm, at rest and 2 and 60 minutes after exercise. At rest, DLco and Dm were lowest in periodic breathing and highest in control subjects. Dm decreased in periodic breathing, severe HF, and moderate HF (-7.83+/-3.98, -5.57+/-2.03, and -3.85+/-3.53 mL x min(-1) x mm Hg(-1), respectively; P<0.01) at 2 minutes after exercise but not in control subjects. Vc increased in all groups at 2 minutes and remained elevated at 60 minutes only in periodic breathing. Dm/Vc was decreased in periodic breathing, severe HF, and moderate HF at 2 minutes but not in control subjects. Dm and Dm/Vc remained low at 60 minutes only in periodic breathing. CONCLUSIONS: Dm decreases after exercise in HF patients but not in control subjects, which suggests a decrease in conductance across the alveolar-capillary barrier, as with pulmonary edema. The reductions were most marked in HF patients with periodic breathing and less reduced in less severe HF.

Aged↗

Beraprost therapy for pulmonary arterial hypertension.

OBJECTIVES: The purpose of this study was to assess the safety and efficacy of the oral prostacyclin analogue beraprost sodium during a 12-month double-blind, randomized, placebo-controlled trial in patients with pulmonary arterial hypertension (PAH). BACKGROUND: Pulmonary arterial hypertension is a progressive disease that ultimately causes right heart failure and death. Despite the risks from its delivery system, continuous intravenous epoprostenol remains the most efficacious treatment currently available. METHODS: A total of 116 patients with World Health Organization (WHO) functional class II or III primary pulmonary hypertension or PAH related to either collagen vascular diseases or congenital systemic to pulmonary shunts were enrolled. Patients were randomized to receive the maximal tolerated dose of beraprost sodium (median dose 120 microg four times a day) or placebo for 12 months. The primary end point was disease progression; i.e., death, transplantation, epoprostenol rescue, or >25% decrease in peak oxygen consumption (VO(2)). Secondary end points included exercise capacity assessed by 6-min walk test and peak VO(2), Borg dyspnea score, hemodynamics, symptoms of PAH, and quality of life. RESULTS: Patients treated with beraprost exhibited less evidence of disease progression at six months (p = 0.002), but this effect was not evident at either shorter or longer follow-up intervals. Similarly, beraprost-treated patients had improved 6-min walk distance at 3 months by 22 m from baseline and at 6 months by 31 m (p = 0.010 and 0.016, respectively) compared with placebo, but not at either 9 or 12 months. Drug-related adverse events were common and were related to the disease and/or expected prostacyclin adverse events. CONCLUSIONS: These data suggest that beneficial effects may occur during early phases of treatment with beraprost in WHO functional class II or III patients but that this effect attenuates with time.

Administration, Oral↗

Pulmonary function in primary pulmonary hypertension.

OBJECTIVES: The study was done to ascertain the degree to which abnormalities in resting lung function correlate with the disease severity of patients with primary pulmonary hypertension (PPH). BACKGROUND: Patients with PPH are often difficult to diagnose until several years after the onset of symptoms. Despite the seriousness of the disorder, the diagnosis of PPH is often delayed because it is unsuspected and requires invasive measurements. Although PPH often causes abnormalities in resting lung function, these abnormalities have not been shown to be statistically significant when correlated with other measures of PPH severity. METHODS: Resting lung mechanics and diffusing capacity for carbon monoxide DL(CO) were assessed in 79 patients whose findings conformed to the classical diagnostic criteria of PPH and who had no evidence of secondary causes of pulmonary hypertension. These findings were correlated with severity of disease as assessed by cardiac catheterization, New York Heart Association (NYHA) class, and cardiopulmonary exercise testing. RESULTS: When PPH patients were first evaluated at our referral clinic, the DL(CO) and lung volumes were decreased in approximately three-quarters and one-half, respectively. The decreases in DL(CO), and to a lesser extent lung volumes, correlated significantly with decreases in peak oxygen uptake (reflecting maximum cardiac output), peak oxygen pulse (reflecting maximum stroke volume), and anaerobic threshold (reflecting sustainable exercise capacity) and higher NYHA class. CONCLUSIONS: Patients with PPH commonly have abnormalities in lung mechanics and DL(CO) levels that correlate significantly with disease severity. These measurements can be useful in evaluating patients with unexplained dyspnea and fatigue.

Adult↗

Exercise anaerobic threshold and ventilatory efficiency identify heart failure patients for high risk of early death.

BACKGROUND: The maximal oxygen uptake (peak VO2) is used in risk stratification of patients with chronic heart failure (CHF). Peak VO2 might be lower than maximally possible if exercise is stopped early because of lack of patient motivation or premature cessation by the investigator. In contrast, the anaerobic threshold (VO2AT) and the ventilatory efficiency (VE versus VCO2 slope) are less subject to these influences. Thus, we compared these parameters with peak VO2 in identifying patients with CHF at increased risk for death within 6 months after evaluation. METHODS AND RESULTS: We performed cardiopulmonary exercise tests with gas exchange measurements in 223 consecutive patients with CHF (114 coronary artery disease, 92 dilated cardiomyopathy, 17 others) at the Herzzentrum Ludwigshafen between 1995 and 1998. We measured peak VO2, VO2AT and VE versus VCO2 slope. We selected peak VO2 of < or =14 mL/kg per minute, VO2AT of <11 mL/kg per minute, and VE versus VCO2 slope of >34 as threshold values for high risk of death. The median follow-up time was 644 days. Patients with peak VO2 of < or =14 mL/kg per minute had a >3-fold-increased risk (OR=3.4; CI, 1.3 to 9.1), with VO2AT <11 mL/min per kg or VE versus VCO2 slope >34 a 5-fold increased risk for early death (OR=5.3; CI, 1.5 to 19.0; OR=4.8; CI, 1.7 to 13.8, respectively). In patients with both VO2AT <11 mL/kg per minute and VE versus VCO2 slope >34, the risk of early death was 10-fold higher (OR=9.6; CI, 2.1 to 44.7). After correction for age, sex, left ventricular ejection fraction, and New York Heart Association class in a multivariate analysis, the combination of VO2AT <11 mL/kg per minute and VE versus VCO2 slope >34 was the best predictor of 6-month mortality (RR=5.1, P=0.001). CONCLUSIONS: VO2AT of <11 mL/kg per minute and slope of VE versus VCO2 >34, combined, better identified patients at high risk for early death from CHF than did peak VO2 and should therefore be considered when prioritizing patients for heart transplantation.

Age Factors↗

Ventilatory efficiency during exercise in healthy subjects.

When evaluating dyspnea in patients with heart or lung disease it is useful to measure the quantity of ventilation needed to eliminate metabolically produced CO2 (i.e., the ventilatory efficiency). Mathematically, the relationship between ventilation (VE) and CO2 output is determined by the arterial CO2 pressure and the physiologic dead space-tidal volume ratio. We decided to determine how age, sex, size, fitness, and the type of ergometer influenced ventilatory efficiency in normal subjects. Three methods were compared for expressing this relationship: (1) the VE versus CO2 output slope below the ventilatory compensation point, commonly used by cardiologists for estimating the severity of heart failure; (2) the VE/CO2 output ratio at the anaerobic threshold, commonly used by pulmonologists; and (3) the lowest VE/CO2 output ratio during exercise, the latter parameter not previously reported. We studied 474 healthy adults, between 17 and 78 years of age during incremental cycle and treadmill cardiopulmonary exercise tests at three test sites, correcting the total VE for the equipment dead space. The lowest VE/CO2 output ratio was insignificantly different from the ratio at the anaerobic threshold, less variable than that for the slope relationship, and unaffected by the site, ergometer, and gas exchange measurement systems. The regression equation for the lowest VE/CO2 output ratio was 27.94 + 0.108 x age + (0.97 = F, 0.0 = M) - 0.0376 x height, where age is in years and height is in centimeters. We conclude that the lowest VE/CO2 output ratio is the preferred noninvasive method to estimate ventilatory inefficiency.

Adult↗