Pain phenotyping and investigation of outcomes in physical therapy: An exploratory study in patients with low back pain.

Phenotypes have been proposed as a method of characterizing subgroups based on biopsychosocial factors to identify responders to analgesic treatments. This study aimed to, first, confirm phenotypes in patients with low back pain receiving physical therapy based on an a priori set of factors used to derive subgroups in other pain populations. Second, an exploratory analysis examined if phenotypes differentiated pain and disability outcomes at four weeks of physical therapy. Fifty-five participants completed psychological questionnaires and pressure pain threshold (PPT). Somatization, anxiety, and depression domains of the Symptom-Checklist-90-Revised, and PPT, were entered into a hierarchical agglomerative cluster analysis with Ward's method to identify phenotypes. Repeated measures ANOVAs assessed pain ratings and disability by phenotype at four weeks. Three clusters emerged: 1) high emotional distress and pain sensitivity (n = 10), 2) low emotional distress (n = 34), 3) low pain sensitivity (n = 11). As an exploratory study, clusters did not differentiate pain ratings or disability after four weeks of physical therapy (p's>0.05). However, trends were observed as magnitude of change for pain varied by phenotype. This supports the characterization of homogenous subgroups based on a protocol conducted in the clinical setting with varying effect sizes noted by phenotype for short-term changes in pain. As an exploratory study, future studies should aim to repeat this trial in a larger sample of patients.

Lactate threshold at the same fat-free mass and age is larger in men than women.

The lactate threshold (LT) represents the onset of a metabolic acidosis during graded exercise testing (GXT). It is typically measured as an oxygen uptake (VO(2)) but then ratio scaled by body mass or VO(2) peak to make comparisons among subjects. Theoretical considerations and empirical evidence suggest that this type of ratio scaling is not valid. A method that allows a dependent variable to be compared between groups at that same value of one or more covariates is analysis of covariance (ANCOVA). Our purpose was to compare the LT, estimated non-invasively by gas exchange (LT(GE)), at the same fat-free mass (FFM) and age in 203 sedentary subjects (102 men) aged 20-70 years. Each subject underwent cycle ergometer GXT with LT(GE) measured by the V-slope method. In model development, we discovered an interaction term between sex and age. As dimensional analysis predicts a log-linear relationship between LT(GE) and FFM, two of the model terms were ln LT(GE) and ln FFM. The ANCOVA model was then as follows: dependent variable = ln LT(GE), fixed factor = sex, covariates = ln FFM, age, and sex x age. Sex made a significant contribution to the model (F = 30.7, P < 0.001). At the mean FFM (56.32 kg) and age (44.01 years) of both sexes combined, the LT(GE) was 29% larger in males (1,307 ml min(-1) versus 1,011 ml min(-1)). The model's interaction term resulted in larger differences at younger ages and smaller differences at older ages. We conclude that LT(GE) at the same FFM and age is larger in sedentary men compared to sedentary women.

Comparison of three methods for detection of the lactate threshold.

The lactate threshold (LT) represents the onset of a metabolic acidosis during graded exercise testing (GXT). It is a valuable measurement in clinical exercise testing and correlates well with endurance performance. Our purpose was to compare three LT detection methods, namely, Inspection (work rate at onset of a systematic increase in blood lactate concentration determined by inspection of blood lactate versus work rate plot), 0.5 mM (work rate which just precedes a rise in blood lactate concentration of >0.5 mM) and log-log (work rate at the intersection of two linear lines in plot of log lactate versus log work rate where the residual sum of squares for both lines added together is minimized). Fourteen subjects underwent cycle ergometer GXT with blood samples obtained at the end of each 3-min work rate increment and analysed for lactate concentration. The mean +/- 95% confidence limits of work rates at LT for the Inspection, 0.5 mM and log-log methods were 104.5 +/- 28.0, 103.2 +/- 28.1 and 105.1 +/- 27.3 W, respectively. Repeated-measures analysis of variance yielded a non-significant F ratio. The Bland-Altman bias +/- 95% limits of agreement for Inspection versus 0.5 mM, Inspection versus log-log and 0.5 mM versus log-log were 1.3 +/- 20.6, -0.6 +/- 12.5 and -1.9 +/- 20.5 W, respectively. The intraclass correlation coefficients for Inspection versus 0.5 mM, Inspection versus log-log and 0.5 mM versus log-log were 0.978, 0.992 and 0.977, respectively. The results of this study suggest that all three methods detect the LT at the same work rate.

Scaling of lactate threshold by peak oxygen uptake and by fat-free mass 0 x 67.

The lactate threshold (LT) represents the onset of metabolic acidosis during cardiopulmonary exercise testing (CPET). It is measured as a O(2) in the units of ml min(-1). In order to make comparisons among subjects, LT is often scaled or normalized by O(2) peak resulting in the LT/O(2) peak ratio. Ratio variables have underlying assumptions. One assumption is that the relationship between the numerator and denominator is linear with a zero y-intercept. If the relationship has a positive y-intercept, then the ratio will decrease with increasing values of the scaling variable thereby penalizing subjects with larger values of the scaling variable. Our purpose was to examine the validity of scaling LT by O(2) peak and by fat-free mass raised to 0 x 67 power (FFM(0 x 67)) as dimensional analysis predicts that LT is proportional to FFM(0 x 67). Cycle ergometer CPET was administered to 204 healthy, sedentary subjects (103 males) to the limit of tolerance. Lactate threshold was estimated noninvasively using the V-slope technique. Fat-free mass was assessed by skinfolds. The relationship of LT versus O(2) peak was linear with a positive y-intercept for both sexes. Consequently, the LT/O(2) peak ratio decreased as O(2) peak increased for both sexes. The relationship of LT versus FFM(0 x 67)was linear with a zero y-intercept for both sexes. Consequently, the plot of the LT/FFM(0 x 67) ratio versus FFM resulted in a straight line with a slope of zero for both sexes. The results of this study support the conclusion that FFM(0 x 67), but not O(2) peak, is a valid scaling variable for LT.

Effect of plasma volume loss during graded exercise testing on blood lactate concentration.

Previous studies have shown that plasma volume (PV) loss can be a confounding variable in the interpretation of changes in blood constituents. We examined the effect of PV loss on three features of the blood lactate versus work-rate relationship, namely, slight blood lactate increase during the early stages of graded exercise testing (GXT); work rate at the onset of a systematic increase in blood lactate, i.e., lactate threshold (LT); and work rate at a blood lactate concentration of 4 mM, i.e., onset of blood lactate accumulation (OBLA). Fourteen subjects underwent cycle ergometer GXT. Blood samples were obtained at rest and at the end of each 3-min work-rate increment and analyzed for hematocrit and lactate concentration. For exercise levels up to and including LT, PV loss was relatively stable at approximately 2.8%. Beyond LT, PV loss accelerated. From the first work rate to LT, blood lactate concentration uncorrected for PV loss increased 0.24 +/- 0.07 mM (P < 0.05). After correction for PV loss, the increase was 0.21 +/- 0.08 mM (P < 0.05). These mean increases were not significantly different from each other. For the four exercise levels above LT common to most subjects, PV-corrected lactate values were significantly lower than uncorrected values. Correction of lactate values for PV loss did not alter LT for any subject, but it did result in a significant increase in OBLA. Thus, PV loss has the potential to be a confounding variable for the interpretation of blood lactate parameters that are determined at exercise levels above LT.

Reliability and validity of the lung volume measurement made by the BOD POD body composition system.

The BOD POD Body Composition System uses air-displacement plethysmography to measure body volume. To correct the body volume measurement for the subject's lung volume, the BOD POD utilizes pulmonary plethysmography to measure functional residual capacity (FRC) at mid-exhalation as that is the subject's lung volume during the body volume measurement. Normally, FRC is measured at end-exhalation. The BOD POD FRC measurement can be corrected to an end-exhalation volume by subtracting approximately one-half of the measured tidal volume. Our purpose was to determine the reliability and validity of the BOD POD FRC measurement at end-exhalation. Ninety-two healthy adults (half female) underwent duplicate FRC measurements by the BOD POD and one FRC measurement by a traditional gas dilution technique. The latter method was used as the reference method for the validity component of the study. The order of the FRC measurements by the two methods was randomized. The test-retest correlation coefficients for the duplicate BOD POD FRC measurements for the male and female subjects were 0.966 and 0.948, respectively. The mean differences between the BOD POD FRC trial #1 measurement and gas dilution FRC measurement for the male and female subjects were -32 and -23 ml, respectively. Neither difference was statistically significant. The correlation coefficients for these two measurements in the male and female subjects were 0.925 and 0.917, respectively. Based on these results, we conclude that the BOD POD FRC measurement in healthy males and females is both reliable and valid.

Test-retest reliability for two indices of ventilatory efficiency measured during cardiopulmonary exercise testing in healthy men and women.

The level of ventilation (VE)) at a given carbon dioxide output (CO2) determines ventilatory efficiency. During cardiopulmonary exercise testing (CPET), ventilatory efficiency can be measured as the slope of the (VE) versus VCO2 relationship or the lowest VE/VCO2. We evaluated the test-retest reliability of these two ventilatory efficiency indices in 29 healthy subjects (14 males). Each subject performed duplicate cycle ergometer tests on different days. Ventilation and the gas fractions for oxygen and CO2 were measured with a Vacumed metabolic cart. Linear regression analysis of the VE versus VCO2 slope for the duplicate tests in the males, females, and both sexes combined yielded correlation coefficients of 0.822, 0.942, and 0.910, respectively. The corresponding correlation coefficients for the lowest VE/VCO2 were 0.745, 0.929, and 0.884. A comparison of the test-retest correlation coefficients between the two ventilatory efficiency measures for the men, women, and both sexes combined revealed that they were not significantly different and, for a given index, there were no sex differences. The bias (mean of difference scores between tests) and 95% limits of agreement for the VE versus VCO2 slope in the males, females, and both sexes combined were -0.05 +/- 2.41, -0.57 +/- 1.92, and -0.32 +/- 2.20, respectively. The bias and 95% limits of agreement for the lowest VE/VCO2 were very similar with values of 0.06 +/- 2.45, -0.22 +/- 2.03, and -0.10 +/- 2.27. We conclude that the test-retest reliability for the VE versus VCO2 slope and the lowest VE/VCO2 is the same and that there is no sex difference in reliability for either index of ventilatory efficiency.

Is ventilatory efficiency dependent on the speed of the exercise test protocol in healthy men and women?

Indices of ventilatory efficiency have proven useful in assessing patients with heart and lung disease. One of these indices is the slope of the ventilation (V(E)) versus carbon dioxide output (VCO(2)) relationship during cardiopulmonary exercise testing (CPET) for work rates where the relationship is linear. However, this relationship is defined not only by the slope but also by the y-intercept. To examine whether this relationship is dependent on the speed of the CPET protocol, 30 healthy subjects (16 males) were administered a rapid CPET with 1-min increment duration (1-min CPET) to the limit of tolerance and a slow CPET with 4-min increment duration (4-min CPET) to the lactate threshold. Ventilation and the gas fractions for oxygen and CO(2) were measured with a Vacumed metabolic cart. The average increment size of both protocols for both sexes was not significantly different (P>0.05). For the males, the mean (SD) slope for the 1- and 4-min CPET was 20.12 (2.61) and 20.37 (2.41), respectively. The corresponding values for the y-intercept were 4..89 (2.08) and 5..10 (2.00) l min(-1). For the females, the mean (SD) slope for the 1- and 4-min CPET was 23.90 (2.38) and 24.16 (2.55), respectively. The corresponding values for the y-intercept were 3.93 (0.39) and 3.77 (0.71) l min(-1). Paired t-test analysis demonstrated for both sexes that the slopes and y-intercepts were not different for the two protocols (P>0.05). The results of this study demonstrate that the V(E) versus VCO(2) relationship is not dependent on the speed of the CPET protocol.

Exercise test mode dependency for ventilatory efficiency in women but not men.

Ventilatory efficiency is commonly defined as the level of ventilation V(E) at a given carbon dioxide output (V(CO(2) )). The slope of the V(E) versus V(CO(2) ) relationship and the lowest V(E)/V(CO(2) ) are two ventilatory efficiency indices that can be measured during cardiopulmonary exercise testing (CPET). A possible CPET mode dependency for these indices was evaluated in healthy men and women. Also evaluated was the relationship between these two indices as, in theory, V(E)/V(CO(2) ) falls hyperbolically towards an asymptote that numerically equals the V(E) versus V(CO(2) ) slope at exercise levels below the ones that cause respiratory compensation for metabolic acidosis. Twenty-eight healthy subjects (14 men) underwent treadmill and cycle ergometer CPET on different days. Ventilation and the gas fractions for oxygen and CO(2) were measured with a vacumed metabolic cart. In men, paired t-test analysis failed to find a mode difference for either ventilatory efficiency index but the opposite was true in the women as each woman had higher values for both indices on the treadmill. For men, the lowest V(E)/V(CO(2) ) was larger than the V(E) versus V(CO(2) ) slope by 1.3 on the treadmill and 0.8 on the cycle ergometer. The corresponding values for women were 1.7 and 1.4. We conclude that in healthy subjects, women, but not men, demonstrate a mode dependency for the two ventilatory efficiency indices investigated in this study. Furthermore, our results are consistent with the theoretical expectation that the lowest V(E)/V(CO(2) ) has a numerical value just above the asymptote of the V(E)/V(CO(2) ) versus V(CO(2) ) relationship.

Maximal oxygen uptake at the same fat-free mass is greater in men than women.

Maximal oxygen uptake (VO(2max)) is commonly divided by body mass or fat-free mass (body mass minus fat mass) in order to make it size independent so that comparisons among persons of different size can be made. However, numerous studies have shown that the ratio created is not size-independent. Analysis of covariance (ANCOVA) allows a dependent variable to be compared between groups at a common value of a covariate. The purpose of this study was to compare VO(2max) at the same fat-free mass (FFM) in 230 sedentary subjects (half men) who ranged in age from 20 to 70 years. The subjects underwent maximal cardiopulmonary exercise testing on a cycle ergometer as ventilation and the expired gas fractions were being measured. Two ANCOVA models were evaluated. The dependent variable, fixed factor and covariate(s) in the linear model were VO(2max), sex and FFM, respectively. The corresponding terms in the log-linear model were ln VO(2max), sex, and ln FFM and age. Sex made a significant contribution to both models. In the linear model, the mean VO(2max) at the same FFM was 27% higher in men (2,444 versus 1,929 ml min(-1); P<0.001). In the log-linear model, the corresponding value at the same FFM and age was 32% higher in men (2,368 versus 1,794 ml min(-1); P<0.001). The goodness of fit indices of squared multiple correlation coefficient and standard error of estimate were significantly better for the log-linear model. We conclude that VO(2max) at the same FFM is considerably higher in men than in women who have a sedentary lifestyle.

Comparison of stroke volume estimation for non-steady-state and steady-state graded exercise testing.

The stroke volume (SV) during exercise is an important index of the heart's functional capacity. A new method has been developed for the non-invasive estimation of exercise SV (SVex). It requires the determination of the slope for the oxygen uptake versus heart rate relationship in the steady state of graded exercise testing (GXT). The product of the slope and a constant (reciprocal of an assumed value of the arterial oxygen content) equals an estimated value for SVex. It was validated in a previous study using invasive measurements while subjects were performing steady-state GXT. However, currently the most commonly used GXT protocols are non-steady state, e.g. protocols with 1-min increment durations. We tested the hypothesis that SVex is the same for steady-state and non-steady-state GXT. A total of 30 subjects (15 males and 15 females) served as subjects for the study. Each subject performed two GXTs on different days with different increment durations - 1 and 4 min. Ventilation and gas exchange were measured with the Vacumed metabolic cart. For the male subjects, the mean (SD) SVex values for the 1- and 4-min GXTs were 155.4 (39.5) and 134.6 (27.5) ml, respectively. The corresponding values for the female subjects were 151.6 (37.6) and 134.3 (36.4) ml. Paired t-test analysis demonstrated that for both genders the mean SVex for the 1-min GXT was significantly larger than the 4-min GXT mean value (P<0.05). Hence, the commonly used 1-min GXT does not yield the same values for SVex as the steady-state GXT.

Lower reference limit for maximal oxygen uptake in men and women.

Maximal oxygen uptake (VO2max) is an important measure of exercise tolerance and low values may have clinical significance. Our purpose was to develop the necessary statistics--prediction equations and standard errors of estimate (SEE)--so that the lower reference limit for VO2max can be predicted for men and women. The subjects were healthy, non-smoking, sedentary men (n = 115) and women (n = 115) aged 20-70 years who performed 15 W min-1 cycle ergometer exercise tests. Three equations were developed for each gender using multiple linear regression with the non-exercise predictor variables of age and height, age and mass, and age and fat-free mass (FFM). The assumptions of regression analysis were examined and the predicted residual sum of squares (PRESS) method was used to cross-validate each equation. Healthy and diseased individual subject data from the literature were used to externally validate our lower reference limit statistics. The equations developed meet the assumptions of regression analysis and have an accuracy similar to the non-exercise prediction equations in the literature with R2 values of approximately 0.581. The PRESS method revealed that the equations are generalizable, i.e. may be used in future studies without a significant loss of accuracy. The lower reference limit predictions for the healthy and diseased individual subject data from the literature produced few miscategorizations unless the subjects were obese and mass was used as a predictor variable. In conclusion, the equations and SEE generated in this study can be used to predict an accurate and valid VO2max lower reference limit for a given subject.