Hervé Guénard

Determination of lung capillary blood volume and membrane diffusing capacity in man by the measurements of NO and CO transfer

NO and CO lung transfer values (TL) were measured separately in 14 healthy subjects (7 men, 7 women), using the single breath technique. Five repetitive maneuvers were performed by each subject for TLNO and TLCO determinations. The inspired mixture contained either 8 ppm NO or 0.25% CO, with 2% He, 21% O2 in N2. In order to measure an appreciable fraction of NO in the alveolar gas it was necessary to shorten the breath holding time to 3 sec. TLNO was about five times greater than TLCO. This result suggests that the specific conductance of blood (theta) for NO is very high and that the second term of the second member of the equation 1/TLNO = 1/DmNO + 1/(theta NO.Qc) is therefore negligible. DmCO and Qc values can thus be computed from TLNO and TLCO measurements. The results obtained with this method are very close to those reported in the literature; for men DmCO = 79.0 +/- 14.3 ml.min-1.Torr-1, Qc = 78.0 +/- 13.2 ml and for women DmCO = 59.0 +/- 10.1 ml.min-1.Torr-1, Qc = 59.5 +/- 11.6 ml.

European reference equations for CO and NO lung transfer

The aim of the present study was to calculate reference equations for carbon monoxide and nitric oxide transfer, measured in two distinct populations. The transfer factor of the lung for nitric oxide (TL,NO) and carbon monoxide (TL,CO) were measured in 303 people aged 18–94 yrs. Measurements were similarly made in two distant cities, using the single-breath technique. Capillary lung volume (Vc) and membrane conductance, the diffusing capacity of the membrane (Dm), for carbon monoxide (Dm,CO) were derived. The transfer of both gases appeared to depend upon age, height, sex and localisation. The rate of decrease in both transfers increased after the age of 59 yrs. TL,NO/alveolar volume (VA) and TL,CO/VA were only age-dependent. The mean TL,NO/TL,CO was 4.75 and the mean Dm/Vc was 6.17 min−1·kPa−1; these parameters were independent of any covariate. Vc and Dm,CO calculations depend upon the choice of coefficients included in the Roughton–Forster equation. Values of 1.97 for Dm,NO/Dm,CO ratio and 12.86 min·kPa−1 for 1/red cell CO conductance are recommended. The scatter of transfer reference values in the literature, including the current study, is wide. The present results suggest that differences might be due to the populations themselves and not the methods alone.

Pulmonary diffusion limitation after prolonged strenuous exercise

To determine the effect of strenuous prolonged exercise on alveolo-capillary membrane diffusing capacity, 11 marathon runners aged 37 +/- 7 years (mean +/- SD) were studied before and during early recovery (28 +/- 14 min) from a marathon race. Lung capillary blood volume (Vc) and the alveolo-capillary diffusing capacity (Dm) were determined in a one-step maneuver by simultaneous measurements of CO and NO lung transfer (DLCO and DLNO, respectively) using the single breath, breath-holding method. After the race, both DLCO and DLNO were significantly decreased in all subjects (-10.9 +/- 4.8%, P less than 10(-4) and -29.0 +/- 11.1%, P less than 10(-4), respectively). The mean value of the derived DmCO decreased by -29.3 +/- 11.1%, whereas Vc had not entirely returned to control resting value. Although these results do not indicate the detailed mechanism involved, interstitial lung fluid was suspected to accumulate, particularly in alveoli, during the race. We concluded that the high overall work load and the extended duration of the exercise both contributed to a transient change in the structure of the alveolo-capillary membrane thereby affecting the diffusing capacity of the alveolo-capillary membrane.

Intrapulmonary percussive ventilation in acute exacerbations of COPD patients with mild respiratory acidosis: a randomized controlled trial [ISRCTN17802078]

IntroductionWe hypothesized that the use of intrapulmonary percussive ventilation (IPV), a technique designed to improve mucus clearance, could prove effective in avoiding further deterioration in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) with mild respiratory acidosis.MethodsThe study was performed in a medical intensive care unit of a university hospital. Thirty-three patients with exacerbations of COPD with a respiratory frequency ≥ 25/min, a PaCO2 > 45 Torr and 7.35 ≤ pH ≤ 7.38 were included in the study. Patients were randomly assigned to receive either standard treatment (control group) or standard treatment plus IPV (IPV group). The IPV group underwent two daily sessions of 30 minutes performed by a chest physiotherapist through a full face mask. The therapy was considered successful when both worsening of the exacerbation and a decrease in pH to under 7.35, which would have required non-invasive ventilation, were avoided.ResultsThirty minutes of IPV led to a significant decrease in respiratory rate, an increase in PaO2 and a decrease in PaCO2 (p < 0.05). Exacerbation worsened in 6 out of 17 patients in the control group versus 0 out of 16 in the IPV group (p < 0.05). The hospital stay was significantly shorter in the IPV group than in the control group (6.8 ± 1.0 vs. 7.9 ± 1.3 days, p < 0.05).ConclusionIPV is a safe technique and may prevent further deterioration in patients with acute exacerbations of COPD with mild respiratory acidosis.

Deciphering the nitric oxide to carbon monoxide lung transfer ratio: physiological implications.

Using simultaneous nitric oxide and carbon monoxide lung transfer measurements (TLNO and TLCO), the membrane transfer capacity (Dm) and capillary lung volume (Vc) as well as the dimensionless ratio TLNO/TLCO can be calculated. The significance of this ratio is yet unclear. Theoretically, the TLNO/TLCO ratio should be inversely related to the product of  both lung alveolar capillary membrane (μ) and blood sheet thicknesses (K). NO and CO transfers were measured in healthy subjects in various conditions likely to be associated with changes in K and/or μ. Experimentally, deflation of the lung from 7.4 to 4.8 l decreased the TLNO/TLCO ratio from 4.9 to 4.2 (n= 25) which was consistent mainly with a thickening of the blood sheet. Compared with continuous negative pressure breathing, continuous positive pressure breathing increased this ratio suggesting a thinning of the capillary sheet. It was also observed with 12 healthy subjects that slight haemodilution that may thicken the blood sheet decreased the TLNO/TLCO ratio from 4.85 to 4.52. In conclusion, the TLNO/TLCO ratio is related to the thickness of the alveolar blood barrier. This ratio provides novel information for the analysis of the diffusion properties.

Echocardiographic and Tissue Doppler Imaging of Cardiac Adaptation to High Altitude in Native Highlanders Versus Acclimatized Lowlanders

High-altitude exposure is a cause of pulmonary hypertension and decreased exercise capacity, but associated changes in cardiac function remain incompletely understood. The aim of this study was to investigate right ventricular (RV) and left ventricular function in acclimatized Caucasian lowlanders compared with native Bolivian highlanders at high altitudes. Standard echocardiography and tissue Doppler imaging studies were performed in 15 healthy lowlanders at sea level; <24 hours after arrival in La Paz, Bolivia, at 3,750 m; and after 10 days of acclimatization and ascent to Huayna Potosi, at 4,850 m, and the results were compared with those obtained in 15 age- and body size-matched inhabitants of Oruro, Bolivia, at 4,000 m. Acute exposure to high altitude in lowlanders caused an increase in mean pulmonary arterial pressure, to 20 to 25 mm Hg, and altered RV and left ventricular diastolic function, with prolonged isovolumic relaxation time, an increased RV Tei index, and maintained RV systolic function as estimated by tricuspid annular plane excursion and the tricuspid annular S wave. This profile was essentially unchanged after acclimatization and ascent to 4,850 m, except for higher pulmonary arterial pressure. The native highlanders presented with relatively lower pulmonary arterial pressures but more pronounced alterations in diastolic function, decreased tricuspid annular plane excursion and tricuspid annular S waves, and increased RV Tei indexes. In conclusion, cardiac adaptation to high altitude was qualitatively similar in acclimatized Caucasian lowlanders and in Bolivian native highlanders. However, lifelong exposure to high altitude may be associated with different cardiac adaptation to milder hypoxic pulmonary hypertension.

Exercise Pathophysiology in Patients With Chronic Mountain Sickness

BACKGROUND Chronic mountain sickness (CMS) is characterized by a combination of excessive erythrocytosis,severe hypoxemia, and pulmonary hypertension, all of which affect exercise capacity. METHODS Thirteen patients with CMS and 15 healthy highlander and 15 newcomer lowlander control subjects were investigated at an altitude of 4,350 m (Cerro de Pasco, Peru). All of them underwent measurements of diffusing capacity of lung for nitric oxide and carbon monoxide at rest, echocardiography for estimation of mean pulmonary arterial pressure and cardiac output at rest and at exercise, and an incremental cycle ergometer cardiopulmonary exercise test. RESULTS The patients with CMS, the healthy highlanders, and the newcomer lowlanders reached a similar maximal oxygen uptake at 32 1, 32 2, and 33 2 mL/min/kg, respectively, mean SE( P 5 .8), with ventilatory equivalents for C O 2 vs end-tidal P CO 2 , measured at the anaerobic threshold,of 0.9 0.1, 1.2 0.1, and 1.4 0.1 mm Hg, respectively ( P , .001); arterial oxygen content of 26 1, 21 2, and 16 1 mL/dL, respectively ( P , .001); diffusing capacity for carbon monoxide corrected for alveolar volume of 155% 4%, 150% 5%, and 120% 3% predicted, respectively( P , .001), with diffusing capacity for nitric oxide and carbon monoxide ratios of 4.7 0.1 at sea level decreased to 3.6 0.1, 3.7 0.1, and 3.9 0.1, respectively ( P , .05) and a maximal exercise mean pulmonary arterial pressure at 56 4, 42 3, and 31 2 mm Hg, respectively ( P , .001). CONCLUSIONS The aerobic exercise capacity of patients with CMS is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of the blood and lung diffusion, the latter being predominantly due to an increased capillary blood volume.

Responsiveness to histamine in human sensitized airway smooth muscle

Passive sensitization of human isolated airway smooth muscle increases contractile responses to histamine. We looked to see whether this increase was due to an alteration in the relative role of histamine H1 and H2 receptors. Human bronchial spiral strips obtained at thoracotomy were passively sensitized by incubation in serum from atopic asthmatic patients to Dermatophagoïdes pteronyssinus and control strips were incubated in serum from healthy non-allergic non-atopic subjects. We also studied spiral strips dissected from two spontaneously sensitized human lung specimens. Cumulative concentration-response curves (CCRC) to Ca2+ (10(-5) -3 x 10(-2) M) were constructed either in the presence of 10(-5) M histamine alone or in that of the combination histamine and the H2 antagonist cimetidine (10(-5) M). Unlike in the absence of histamine, Ca2+ CCRC in the presence of histamine alone were significantly shifted to the left in the passively sensitized tissues (mean EC50: 5.7 x 10(-4) M) compared to control ones (mean EC50: 9.3 x 10(-4) M, n = 6, P < 0.05). Addition of cimetidine to histamine did not alter the Ca2+ CCRC either in the control or in passively or spontaneously sensitized airway smooth muscle. These results suggest that (i) passive sensitization increases contractile response to Ca2+ of human bronchial smooth muscle in the presence of histamine; (ii) this increase is not due to a difference in the H1- vs H2-mediated response; and (iii) H2-mediated effects do not play a significant role in spontaneously sensitized human lung as both in the non-sensitized and passively sensitized lung.

Helium-oxygen mixture in respiratory distress syndrome: A double-blind study

In a randomized, controlled trial, the lungs of infants with respiratory distress syndrome were ventilated with either a helium-oxygen mixture or a nitrogen-oxygen mixture. In the helium-oxygen group, infants required a lower inspired oxygen concentration and a shorter duration of ventilation. There were also fewer deaths and fewer cases of bronchopulmonary dysplasia in the helium-oxygen group.

Nitric oxide and carbon monoxide lung transfer in patients with advanced liver cirrhosis

In advanced cirrhosis, decreased lung transfer for carbon monoxide (TLCO) and increased alveolar-arterial oxygen tension difference (PA-aO(2) >or=15 mmHg while breathing ambient air) are frequently detected. Pulmonary membrane diffusion capacity for CO (DmCO) and pulmonary capillary blood volume (Vcap) can be derived from the simultaneous measurement of TLCO and lung transfer for nitric oxide (TLNO). Measurements of single-breath TLNO and TLCO were performed in 49 cirrhotic patients with advanced liver cirrhosis and in 35 healthy controls to derive Vcap, DmCO, and TLNO:TLCO ratio. Twenty-five patients had increased PA-aO(2), of whom 11 had hepatopulmonary syndrome (HPS). Compared with controls, non-HPS patients with normal PA-aO(2) had a significant approximately 10% decrease in TLCO, DmCO, and Vcap but similar TLNO:TLCO ratios. Compared with non-HPS patients with normal PA-aO(2), non-HPS patients with increased PA-aO(2) had lower Vcap and higher TLNO:TLCO ratio but similar DmCO. HPS patients had lower Vcap and higher TLNO:TLCO ratios than both subgroups of non-HPS patients. In cirrhotic patients, TLNO:TLCO ratios correlated positively, and TLCO (percentage of the predicted value) and Vcap (percentage of the predicted value) correlated negatively with PA-aO(2) (r(2) = 0.25, P = 0.0003, r(2) = 0.48, P < 0.0001 and r(2) = 0.57, P < 0.0001, respectively). We concluded that, in cirrhotic patients, lower TLCO and increased PA-aO(2) are associated with lower Vcap. In addition, high TLNO:TLCO ratios in patients with increased PA-aO(2) suggest a decreased thickness of the capillary blood layer in these patients.