Diffusing capacity of the lung for CO and pulmonary blood flow during incremental and intermittent exercise.

The aims of this study were to evaluate the feasibility of successive diffusing capacity of the lung for carbon monoxide (DLCO) measurements during two different exercise tests (upright cycling), and to compare the relationships between DLCO and pulmonary blood flow (Qc). Eight healthy subjects performed an incremental test (1-min step) and a strenuous 30-min intermittent-work exercise test (4 min at low and 2 min at high workload). Intrabreath DLCO and Qc were calculated by assessing the uptake of CO and C2H2 during exhalation. DLCO could be measured reliably up to 73-90% of peak oxygen consumption (VO2) during the incremental test, and up to 85-95% of peak VO2 during the intermittent test. The coefficients of variation of DLCO and Qc measured during two successive constant-load exercise tests were 5-6% and 7-11%, respectively. The highest values of DLCO, Qc and VO2 measured during the incremental and intermittent tests were similar (56 and 51 mL/mmHg/min for DLCO, 18.7 and 18.3 L/min, for Qc and 2.4 and 2.3 L/min for VO2, respectively). The main observed result was that the linear relationships between DLCO and Qc were similar whatever the exercise type. This allows DLCO comparisons, with regards to Qc, during different exercise protocols.

Prognostic factors in COPD patients receiving long-term oxygen therapy. Importance of pulmonary artery pressure.

Prognostic factors in COPD patients receiving long-term oxygen (LTO) therapy were recently analyzed, but very few studies considered the prognostic value of pulmonary artery pressure (PAP) in these patients. We investigated 84 patients who had undergone a right heart catheterization just before the onset of LTO. There were 75 men and 9 women, with a mean age of 63.0 +/- 9.9 (SD) years, at the onset of LTO. When PaO2 was persistently less than 55 mm Hg, LTO was initiated. This therapy was started in some patients with PaO2 in the range of 55 to 60 mm Hg if they had signs of cor pulmonale or a resting PAP of 25 mm Hg or greater at right heart catheterization. The daily duration of LTO was 16 h/d or more. Oxygen flow was adapted to achieve a PaO2 of 65 mm Hg or more. The patients were subdivided into subgroups according to the median value of age (cutoff value = 63 years); vital capacity (2,250 mL); FEV1 (800 mL); residual volume-total lung capacity ratio (58%); PaO2 value (52 mm Hg), PaCO2 level (45 mm Hg); and PAP (25 mm Hg). The cumulative 5-year survival rate was 48% for the group as a whole. Actuarial survival curves were plotted for the two subgroups of patients subdivided according to the initial median value of the variables just listed. There was no significant difference in survival rate between subgroups except when taking into account the level of PAP and age. In patients with an initial PAP of 25 mm Hg or less (n = 44), the 5-year survival was of 62.2 vs 36.3% in the remainder (n = 40) [p < 0.001]. We performed a multivariate analysis of survival using Cox's model of the proportional hazards regression including sex and the variables with the same categorization in the stepwise procedure: PAP and age were the only variables included in the final model. We conclude that the best prognostic factor in COPD patients receiving LTO is not the FEV1, nor the degree of hypoxemia or hypercapnia, but the level of PAP.

Measurements of respiratory system resistance by the interrupter technique in healthy and asthmatic children.

We studied respiratory system resistance by the interrupter technique (Rint) in healthy and asthmatic children, paying special attention to the effect of cheek compliance and the effects of supporting the cheeks, the influence of lung volume at which interruption was performed, the effect of direction of flow before occlusion (inspiration vs. expiration), and short-term reproducibility of this method. One hundred and thirty-two children (36 controls and 96 asthmatics) were included in the study (mean, 9.0 +/- SD 3.6 years). Rint was calculated from the ratio of the alveolar pressure (estimated from moth pressure during occlusion) to the flow prior to interruption. We observed that 1) underestimation of airway resistance due to upper airway compliance can be minimized by supporting the cheeks; Rint was significantly lower when measured without supporting the cheeks than with support of the cheeks in controls (3.9 +/- 0.9 vs. 4.7 +/- 1.2 cmH2O.L-1.s, respectively) and asthmatics (5.2 +/- 1.6 vs 6.9 +/- 2.0 cmH2O.L-1.s); the quantitative differences of Rint with and without cheek support was larger in small children and in the most obstructed children; 2) performing occlusion at mid-tidal volume accurately reflected the respiratory system resistance of the whole respiratory cycle since we observed no difference in Rint when performing occlusion at different volumes during quiet respiration or at the middle of tidal volume; 3) Rint measured during expiration was higher than Rint obtained during inspiration in controls and in asthmatics; moreover, the effect of direction of flow before occlusion was greater in the small children; 4) Rint was closely correlated to height in controls (r = -0.82; P < 0.001); and 5) short-term reproducibility (at 15 min intervals) was satisfactory in controls and asthmatics (coefficients of variation were 9% and 7%, respectively).

Interrupter technique versus plethysmography for measurement of respiratory resistance in children with asthma or cystic fibrosis.

The purpose of the present study was to compare measurements of respiratory system resistance by the interrupter method (Rrsint) with those of airway resistance by plethysmography (Raw) in nonobstructed children with asthma or cystic fibrosis (ratio of forced expiratory volume in 1 sec to vital capacity, FEV(1)/VC >/=80% with a forced expiratory flow rate between 25-75% of forced vital capacity, FEF(25-75) >/=75% of normal values) and in obstructed children with the same diseases (FEV(1)/VC <80% and/or FEF(25-75) <75% of normal values). Eighty-one children (47 asthmatics and 34 suffering from cystic fibrosis) aged 5-18 years (mean 11.2 +/- SD 3.4 years) were included in the study. For the overall group, we observed generally lower values for Raw (4.7 +/- 2. 8 cmH(2)O.L(-).s) than for Rrsint20 (extrapolation of the mouth pressure during occlusion to 40 ms after interruption) (5.6 +/- 1.7 cmH(2)O.L(-1).s) (P < 0.02), or for Rrsint40 (extrapolation of the mouth pressure during occlusion to 60 ms after interruption) (6.6 +/- 2.2 cmH(2)O.L(-1).s) (P < 0.001), but there was no difference between Rrsint20 and Raw in the obstructed subgroup. Moreover, we observed a correlation between the difference (Rrsint20 - Raw) expressed in percentage of predicted values and the degree of obstruction estimated by FEV(1)/VC (r = 0.56, P < 0.001). The differences between the specific resistances (sRrsint20 - sRaw, sRrsint40 - sRaw) were also correlated with the severity of the obstruction (r = 0.65, P < 0.001 and r = 0.57, P < 0.001, respectively). We observed also that the tendency to underestimate resistance by Rrsint in obstructed children was not the same in children with asthma and cystic fibrosis. We conclude that the tendency of Rrsint, as measured with our method, to underestimate airway obstruction appears to increase in proportion to the severity of the airway obstruction.

[Cystic fibrosis and bronchial hyper-reactivity]. / Mucoviscidose et hyperréactivité bronchique.

An increased airway responsiveness to inhaled nonspecific stimuli has been often observed in cystic fibrosis patients. But bronchial hyperreactivity in such patients is due, in most cases, to damaged bronchial mucosa rather than to coexistent asthma, and it remains under question whether or not bronchodilators are of help in cystic fibrosis. Indeed some authors reported adverse effects after inhalation of beta-mimetic drugs. This behavior seems to be due to an "instability" of the bronchial walls in cystic fibrosis. Nevertheless other studies showed that bronchodilators could be of help when administered in some cases and during definite periods in the evolution of the disease. Indeed, variability in responsiveness to bronchodilator drugs is one of the features of cystic fibrosis and therapy must be adjusted to this variability in every patient. In any way, pulmonary functional tests must be performed before and after administration of a bronchodilator drug and before beginning such therapy.

[Hypoxia and pulmonary circulation. The importance of hypoxia in pulmonary arterial hypertension of chronic obstructive bronchopneumopathies]. / Hypoxie et circulation pulmonaire. Importance de l'hypoxie dans l'hypertension artérielle pulmonaire des bronchopneumopathies chroniques obstructives.

In chronic airflow obstruction (CAO), there are grounds for distinguishing between the effects of acute alveolar hypoxia and those of chronic hypoxia. Acute hypoxia leads, in healthy subjects, to pulmonary vasoconstriction. In patients with CAO, there is however a great variability in the pulmonary vascular response to hypoxia. Chronic hypoxia leads in the long term to structural modifications in the pulmonary vessels (arteriolar muscularization, hypertrophy of the small arterial muscles, and intimal fibrosis), which are similar enough to those seen in residents at high altitude and which lead to an elevation of the pulmonary vascular resistance. These structural changes are potentially reversible but one does not know up to which point they are. This potential reversibility represents one of the justifications of long term oxygen therapy in these patients. The pulmonary arterial hypertension of CAO is generally moderated; it evolves slowly over years and years in the majority of cases; it certainly doesn't merit to be treated at any cost. Up to the present, pulmonary vasodilators have given rather disappointing results. Prolonged oxygen therapy (for greater than 16 hours in 24), which improves in other respects the expectation of life in patients is currently the most logical treatment for pulmonary hypertension in CAO.

[M-mode echocardiography in the diagnosis of pulmonary arterial hypertension in chronic respiratory disorders]. / Apport de l'échocardiographie de mode M au diagnostic de l'hypertension artérielle pulmonaire dans les affections respiratoires chroniques.

Right heart catheterisation (reference method) and M-mode echocardiography were performed in 90 patients with chronic respiratory failure (73 BPCO-chronic airflow obstruction and 17 non-BPCO). The aim of this study was to assess the place of echo-cardiography in the diagnosis and assessment of pulmonary arterial hypertension (HTAP) and/or right ventricular hypertrophy (HVD). The results are somewhat deceptive; first as reliable measurements were impossible in 20% of cases (due to airways distension), then because the sensibility of the method is only 75% (only 62.2% in the group with moderate HTAP with a mean pulmonary artery pressure (PAP) between 21 and 30 mmHg, where as the specificity was satisfactory (87.5%). The best coefficient of linear correlation was observed between the PAP and the end-diastolic diameter of the right ventricle (DTDVD) (r = 0.52; p less than 0.001). Such a correlation does not allow for a prediction of an exact level of PAP in individual cases. The combination of 3 non-invasive methods (ECG, Echo-cardiography and myocardial scintigraphy) allows for an excellent overall sensibility (91.7%) but to the detriment of the specificity (66.6% only).

A comparison of four algorithms for the measurement of interrupter respiratory resistance in adults.

The aim of our study was to compare four algorithms for the measurement of respiratory resistance in adults using the interrupter technique. Four methods to estimate alveolar pressure from the mouth pressure during occlusion were assessed in 122 normal adults (57 males, 65 females, aged 18-79 yr, mean 41.2 +/- 15.6): taking the mean oscillation pressure (Rint), performing a linear back extrapolation (RintL) or a linear regression for the whole curve (RintRL), taking the end-occlusion pressure (RintE). Mean values for Rint, RintL and RintRL in males were respectively 0.23 +/- 0.04, 0.22 +/- 0.04 and 0.22 +/- 0.04 kPa s L(-1), not statistically different. In females values were respectively 0.27 +/- 0.05, 0.26 +/- 0.05 and 0.26 +/- 0.05 kPa s L(-1), not statistically different. RintE was higher than the remainder and was the only measure correlating weakly with morphometric variables: RintE = 1.152 - (0.00152 x age (yr)) - (0.00382 x height (cm)), r = 0.31 (p < 0.05) in females; RintE = 0.227 - (0.00122 x age (yr)) + (0.00830 x body mass index (kg m(-2))) with r = 0.34 (p < 0.05) in males. We conclude that it is equivalent to estimate alveolar pressure from or extrapolating it to the beginning of occlusion in healthy adults but when taking the end-occlusion pressure, resistance is higher and depends in part on morphometric parameters.

Pulmonary hemodynamics in chronic obstructive pulmonary disease of the emphysematous type.

Pulmonary hemodynamics have been extensively investigated in patients with chronic bronchitis or in 'mixed' patients (chronic bronchitis + emphysema) but rarely in patients with markedly predominant emphysema. We have investigated a large series (n = 151) of such patients, emphysema having been assessed on radiological, clinical and functional grounds. The mean age was 58 +/- 10 years; vital capacity (VC, % of predicted) = 81 +/- 19; forced expiratory volume in 1 s (FEV1) = 1,198 +/- 589 ml; FEV1/VC = 38 +/- 12%; PaO2 = 72 +/- 11 mm Hg; PaCO2 = 37.5 mm Hg. Pulmonary hypertension (PH), defined by a resting pulmonary artery pressure (PAP) of greater than or equal to 20 mm Hg, was present in only 31 of 151 patients. During steady-state exercise (40 W or less) an abnormally high PAP (greater than or equal to 30 mm Hg) was observed in 99 of 151 patients. Resting and exercising PAP were poorly correlated with resting PaO2 and PaCO2, but were better correlated with the amplitude of the respiratory pressure swings, FEV1, the transfer factor and exercising PaO2. Patients with PH (n = 31) showed significantly more obstruction and pulmonary distension than the remainder, but they did not differ from the non-PH patients with regard to resting PaO2. It is concluded that: (1) resting PH is not the rule in diffuse emphysema but exercising hypertension is frequent (2 of 3 patients), and (2) hypoxemia is not a determining factor of hemodynamic abnormalities in emphysema.

AaDO2 as a predictor of pulmonary hypertension resulting from pulmonary emboli.

The authors examined the records of all patients referred for right heart catheterization between 1963-84 because of persistent dyspnoea after one or more episodes of pulmonary emboli. Patients with a history of congestive heart failure, angina, restrictive or obstructive pulmonary disease that could explain their symptoms were excluded. Catheterization was performed 15.8 +/- 24 months after the first suspected episode of pulmonary embolism. Seven of the 29 patients included had resting pulmonary hypertension (PH). All of these had an alveolo-arterial oxygen difference (AaDO2) greater than 25 mmHg. Twenty patients of the group, taken as a whole, had an AaDO2 greater than 25 mmHg. Information was available from 1 month to 5 years later in 6/9 patients with an AaDO2 less than 25 mmHg. In all of them dyspnoea improved or resolved. Information was available in 15/20 patients with AaDO2 greater than 25 mmHg. Three of 8 patients without PH but with an increased AaDO2 on the initial catheterization developed PH within 2 years. Dyspnoea increased in 1 of the remaining five. Four patients who initially had PH developed right heart failure 6 months-3 years later. In the remaining 3, dyspnoea was stable in 1, increased in 1 and one patient died with autopsy evidence of multiple pulmonary emboli. Abnormal oxygenation predicts the presence or subsequent development of PH in patients who are chronically dyspnoeic after pulmonary embolism.

Non-invasive diagnosis of pulmonary hypertension in chronic obstructive pulmonary disease. Comparison of ECG, radiological measurements, echocardiography and myocardial scintigraphy.

The respective value of four non-invasive methods for the diagnosis of pulmonary arterial hypertension (PAH) was investigated in 63 COPD patients, using right heart catheterization as the reference method: 22 patients had no resting PAH (pulmonary artery mean pressure (PAP) less than or equal to 20 mmHg); 26 patients had mild PAH (PAP = 21-30 mmHg); and 15 patients had moderate to severe PAH (PAP greater than 30 mmHg). The specificity of ECG was 86% and the sensitivity 51% (only 38% in mild PAH). The specificity of radiological measurements was 63% and the sensitivity 46% (38% in mild PAH). Echocardiography (echo) had the best results with a specificity of 75% and a sensitivity of 78% (73% in mild PAH), but reliable echo measurements were available in only 52 out of 63 patients. Myocardial scintigraphy had a specificity of 68% and a sensitivity of 66% (58% in mild PAH). A stepwise regression analysis (including one echo, one ECG, one radiological and one functional variable) explained only 43% of the variance of PAP (multiple r = 0.66). These results suggest that no individual method is sufficiently reliable for predicting the presence of PAH, and particularly mild PAH, but the combination of echo + myocardial scintigraphy allows the prediction of PAH with a good probability. The precise level of PAH cannot be estimated, even when using multiple regression equations.

Effect of lung volume reduction surgery on gas exchange and pulmonary hemodynamics at rest and during exercise.

Lung volume reduction surgery (LVRS) has become an extended surgery for emphysema in order to improve the dyspnea of severely affected patients. Because resection of lung areas may reduce the vascular bed, which is an important factor of pulmonary hypertension in emphysematous patients, especially during exercise, the aim of our study was to assess the outcome of pulmonary hemodynamics and gas exchange at rest and during exercise after LVRS. Nine patients had right heart catheterization before and 3 to 12 mo (mean, 4.5 mo) after LVRS. FEV1 increased from 705 to 1,005 ml (p < 0.05) after LVRS. PaO2, PaCO2 and mean pulmonary artery pressure (Ppa) did not change after LVRS, either at rest or during exercise. However, a significant overall decrease of the respiratory swings of the pulmonary artery diastolic pressure (DeltaPd) at rest (median value, from 12 to 8 mm Hg, p < 0.01) and during exercise (from 20 to 15 mm Hg, p < 0.05) was observed. There was a significant correlation between the change in resting Ppa (Ppa before minus Ppa after LVRS) and the change in resting DeltaPd (r = 0.73, p < 0.03), and also between the change in exercising Ppa and the change in resting DeltaPd (r = 0.80, p < 0.02). Significant correlations were also found between the change in exercising Ppa and the change in exercising PaO2 (r = -0.70, p < 0.05), and between the change in exercising Ppa and the change in exercising PaCO2 (r = 0.76, p < 0. 03). We conclude that pulmonary hemodynamics in most cases are not impaired by LVRS either at rest or during exercise. The possible mechanisms influencing hemodynamics after a lung volume reduction procedure are discussed.

"Natural history" of pulmonary hypertension in a series of 131 patients with chronic obstructive lung disease.

The prognostic value and the evolution of pulmonary hypertension (PH) in patients with markedly hypoxemic chronic obstructive pulmonary disease (COPD), treated or not with long-term oxygen therapy (LTOT), has been extensively investigated. However, little is known in patients with mildly or moderately hypoxemic COPD not requiring LTOT. Therefore, we assessed the evolution of pulmonary hemodynamics in 131 patients with stable COPD by performing two right heart catheterizations at a mean (+/- SD) time interval of 6.8 +/- 2.9 yr. At inclusion (T0), no patient had PH (i.e., the mean pulmonary artery pressure [Ppa] at rest was < 20 mm Hg). Group 1 included 55 patients without exercising PH and group 2 included 76 patients with exercising PH, defined by a pulmonary arterial pressure (Ppa) > 30 mm Hg during a steady-state 40-W exercise. Group 2 patients compared with group 1 patients had a significantly higher resting Ppa (16 +/- 3 mm Hg versus 14 +/- 2 mm Hg, p = 0.001). At the second catheterization, 33 (25%) patients (9 of 55 in group 1, 24 of 76 in group 2, p = 0.048) showed a resting Ppa > 20 mm Hg, but PH was generally mild, ranging from 20 to 42.5 mm Hg. The mean Ppa at second evaluation was 16 +/- 5 mm Hg in group 1 and 19 +/- 7 mm Hg in group 2 (p = 0.01). The patients who developed resting PH at the second catheterization (T1) had higher resting and exercising Ppa (p = 0.001 and p = 0.002, respectively), and significantly lower resting and exercising Pa(O(2)) (p = 0.005 and p = 0.012, respectively) at T0. Logistic regression analysis showed that resting and exercising Ppa were independent predictors (at T0) for the subsequent development of PH (p = 0.029 and p = 0.027, respectively). The patients who developed resting PH (T1) had a significantly worsening of Pa(O(2)) (from 63.5 mm Hg at T0 to 60 mm Hg at T1, p = 0.047), whereas the Pa(O(2)) as a mean was stable in the remainder (69.5 mm Hg at T0 and T1). These results show the following. The progression of Ppa over time in patients with COPD with mild to moderate hypoxemia is rather slow, the average change for the group as a whole being of + 0.4 mm Hg/yr. Only about 25% of patients with COPD with mild to moderate hypoxemia and without resting PH at the onset will develop PH during a 6-yr follow-up. The patients with exercising PH at the onset have a significantly increased risk of developing PH over time. Only resting and exercising Ppa at the onset are independently related to the subsequent development of PH. However, in individual cases, the models of linear or logistic regression do not allow a pertinent prediction of the level of Ppa or the presence of PH at the second right heart catheterization.

A new impedance cardiograph device for the non-invasive evaluation of cardiac output at rest and during exercise: comparison with the "direct" Fick method.

The objectives of this study were to evaluate the reliability and accuracy of a new impedance cardiograph device, the Physio Flow, at rest and during a steady-state dynamic leg exercise (work intensity ranging from 10 to 50 W) performed in the supine position. We compared cardiac output determined simultaneously by two methods, the Physio Flow (QcPF) and the direct Fick (QcFick) methods. Forty patients referred for right cardiac catheterisation, 14 with sleep apnoea syndrome and 26 with chronic obstructive pulmonary disease, took part in this study. The subjects' oxygen consumption values ranged from 0.14 to 1.19 l x min(-1). The mean difference between the two methods (QcFick - QcPF) was 0.04 l x min(-1) at rest and 0.29 l x min(-1) during exercise. The limits of agreement, defined as mean difference +/- 2SD, were -1.34, +1.41 l x min(-1)] at rest and -2.34, +2.92 l x min(-1) during exercise. The difference between the two methods exceeded 20% in only 2.5% of the cases at rest, and 9.3% of the cases during exercise. Thoracic hyperinflation did not alter QcPF. We conclude that the Physio Flow provides a clinically acceptable and non-invasive evaluation of cardiac output under these conditions. This new impedance cardiograph device deserves further study using other populations and situations.

Non-invasive cardiac output evaluation during a maximal progressive exercise test, using a new impedance cardiograph device.

One of the greatest challenges in exercise physiology is to develop a valid, reliable, non-invasive and affordable measurement of cardiac output (CO). The purpose of this study was to evaluate the reproducibility and accuracy of a new impedance cardiograph device, the Physio Flow, during a 1-min step incremental exercise test from rest to maximal peak effort. A group of 12 subjects was evaluated to determine the reproducibility of the method as follows: (1) each subject performed two comparable tests while their CO was measured by impedance cardiography using the new device (COImp1, COImp2), and (2) in a subgroup of 7 subjects CO was also determined by the direct Fick method (COFick) during the second test. The mean difference between the values obtained by impedance (i.e. COImp1-COImp2) was -0.009 l.min-1 (95% confidence interval: -4.2 l.min-1, 4.2 l.min-1), and CO ranged from 3.55 l.min-1 to 26.75 l.min-1 (n = 146). When expressed as a percentage, the difference (COImp1-COImp2) did not vary with increasing CO. The correlation coefficient between the values of COImp and COFick obtained during the second exercise test was r = 0.94 (P < 0.01, n = 50). The mean difference expressed as percentage was -2.78% (95% confidence interval: -27.44%, 21.78%). We conclude that COImp provides a clinically acceptable evaluation of CO in healthy subjects during an incremental exercise.