Effects of Endurance Training Intensity on Pulmonary Diffusing Capacity at Rest and after Maximal Aerobic Exercise in Young Athletes.

This study compared the effects of varying aerobic training programs on pulmonary diffusing capacity (TLCO), pulmonary diffusing capacity for nitric oxide (TLNO), lung capillary blood volume (Vc) and alveolar-capillary membrane diffusing capacity (DM) of gases at rest and just after maximal exercise in young athletes. Sixteen healthy young runners (16-18 years) were randomly assigned to an intense endurance training program (IET, n = 8) or to a moderate endurance training program (MET, n = 8). The training volume was similar in IET and MET but with different work intensities, and each lasted for 8 weeks. Participants performed a maximal graded cycle bicycle ergometer test to measure maximal oxygen consumption (VO2max) and maximal aerobic power (MAP) before and after the training programs. Moreover, TLCO, TLNO and Vc were measured during a single breath maneuver. After eight weeks of training, all pulmonary parameters with the exception of alveolar volume (VA) and inspiratory volume (VI) (0.104 < p < 0889; 0.001 < ES < 0.091), measured at rest and at the end of maximal exercise, showed significant group × time interactions (p < 0.05, 0.2 < ES < 4.0). Post hoc analyses revealed significant pre-to-post decreases for maximal heart rates (p < 0.0001, ES = 3.1) and improvements for VO2max (p = 0.006, ES = 2.22) in the IET group. Moreover, post hoc analyses revealed significant pre-to-post improvements in the IET for DM, TLNO, TLCO and Vc (0.001 < p < 0.0022; 2.68 < ES < 6.45). In addition, there were increases in Vc at rest, VO2max, TLNO and DM in the IET but not in the MET participants after eight weeks of training with varying exercise intensities. Our findings suggest that the intensity of training may represent the most important factor in increasing pulmonary vascular function in young athletes.

Pulmonary diffusing capacity measured by NO/CO transfer in Tunisian boys.

BACKGROUND: The diffusing capacity, which measures gas-exchange, uses reference values based on data from American or European studies. There are currently no reference values of pulmonary diffusing capacity (TL) and its components, such as the conductance of the membrane (Dm) and capillary lung volume (Vc) for healthy North African children. OBJECTIVES: We determined the prediction equations-reference values for TL, Dm, Vc and the alveolar volume (VA) in healthy Tunisian boys. METHODS: Values of Vc, Dm, TL, and VA were measured by the NO/CO transfer method, using a single breath maneuver in 118 Tunisian boys (8-14 years old) at rest. We performed linear regression analysis of the pulmonary parameters and independent variables, such as height, weight, and age. RESULTS: The reference equations for pulmonary diffusing capacity for carbon monoxide (TLCO ) was 0.201 × weight (kg) + 8.979; for TLNO was 0.76 × height (cm)-24.383; for Dm was 0.388 × height (cm)- 12.555 and for VA was 0.34 × height (cm)-3.951. Vc increased significantly with weight (P < .05) but not with age (P > .05). CONCLUSIONS: References norms for TLCO and TL for nitric oxide and its components in young Tunisian boys are similar to data from other countries. The prediction equations we developed can be extended to clinical practice in Tunisia and can be considered for use in neighboring North African countries.

Changes in dynamic lung mechanics after lung volume reduction coil treatment of severe emphysema.

We assessed the relationships between changes in lung compliance, lung volumes and dynamic hyperinflation in patients with emphysema who underwent bronchoscopic treatment with nitinol coils (coil treatment) (n=11) or received usual care (UC) (n=11). Compared with UC, coil treatment resulted in decreased dynamic lung compliance (CLdyn) (p=0.03) and increased endurance time (p=0.010). The change in CLdyn was associated with significant improvement in FEV1 and FVC, with reduction in residual volume and intrinsic positive end-expiratory pressure, and with increased inspiratory capacity at rest/and at exercise. The increase in end-expiratory lung volume (EELV) during exercise (EELVdyn-ch=EELVisotime EELVrest) demonstrated significant attenuation after coil treatment (p=0.02).

Persistent respiratory effort after adenotonsillectomy in children with sleep-disordered breathing.

OBJECTIVES: Adenotonsillectomy (AT) markedly improves but does not necessarily normalize polysomnographic findings in children with adenotonsillar hypertrophy and related sleep-disordered breathing (SDB). Adenotonsillectomy efficacy should be evaluated by follow-up polysomnography (PSG), but this method may underestimate persistent respiratory effort (RE). Mandibular movement (MMas) monitoring is an innovative measurement that readily identifies RE during upper airway obstruction. We hypothesized that MMas indices would decrease in parallel of PSG indices and that children with persistent RE more reliably could be identified with MMas. METHODS: Twenty-five children (3-12 years of age) with SDB were enrolled in this individual prospective-cohort study. Polysomnography was supplemented with a midsagittal movement magnetic sensor that measured MMas during each respiratory cycle before and > 3 months after AT. RESULTS: Adenotonsillectomy significantly improved PSG indices, except for RE-related arousals (RERA). Mandibular movement index changes after AT significantly were correlated with corresponding decreases in sleep apnea-hypopnea index (AHI) and O2 desaturation index (ODI) (Spearman's rho = 0.978 and 0.922, respectively), whereas changes in MMas duration significantly were associated with both RERA duration (rho = 0.475, P = 0.017) and index (rho = 0.564, P = 0.003). Conditional multivariate analysis showed that both AHI and RERA significantly contributed to the variance of MMas index after AT (P = 0.0003 and 0.0005, respectively), whereas MMas duration consistently was related to the duration of RERA regardless of AT. CONCLUSION: Adenotonsillectomy significantly reduced AHI. However, persistent RERA were apparent in a significant proportion of children, and this was reflected by the remaining abnormal MMas pattern. Follow-up of children after AT can be recommended and readily achieved by monitoring MMas to identify persistent RE. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1230-1237, 2018.

No compensatory lung growth after resection in a one-year follow-up cohort of patients with lung cancer.

BACKGROUND: As compensatory lung growth after lung resection has been studied in animals of various ages and in one case report in a young adult, it has not been studied in a cohort of adults operated for lung cancer. METHODS: A prospective study including patients with lung cancer was conducted over two years. Parenchymal mass was calculated using computed tomography before (M0) and at 3 and 12 months (M3 and M12) after surgery. Respiratory function was estimated by plethysmography and CO/NO lung transfer (DLCO and DLNO). Pulmonary capillary blood volume (Vc) and membrane conductance for CO (DmCO) were calculated. Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) plasma concentrations were measured simultaneously. RESULTS: Forty-nine patients underwent a pneumonectomy (N=12) or a lobectomy (N=37) thirty two completed the protocol. Among all patients, from M3 to M12 the masses of the operated lungs (239±58 to 238±72 g in the lobectomy group) and of the non-operated lungs (393±84 to 377±68 g) did not change. Adjusted by the alveolar volume (VA), DLNO/VA decreased transiently by 7% at M3, returning towards the M0 value at M12. Both Vc and DmCO increased slightly between M3 and M12. IGF-1 and IGFBP-3 concentrations did not change at M3, IGF-1 decreased significantly from M3 to M12. CONCLUSIONS: Compensatory lung growth did not occur over one year after lung surgery. The lung function data could suggest a slight recruitment or distension of capillaries owing to the likely hemodynamic alterations. An angiogenesis process is unlikely.

Mandibular Movements As Accurate Reporters of Respiratory Effort during Sleep: Validation against Diaphragmatic Electromyography.

CONTEXT: Mandibular movements (MM) are considered as reliable reporters of respiratory effort (RE) during sleep and sleep disordered breathing (SDB), but MM accuracy has never been validated against the gold standard diaphragmatic electromyography (EMG-d). OBJECTIVES: To assess the degree of agreement between MM and EMG-d signals during different sleep stages and abnormal respiratory events. METHODS: Twenty-five consecutive adult patients with SDB were studied by polysomnography (PSG) that also included multipair esophageal diaphragm electromyography and a magnetometer to record MM. EMG-d activity (microvolt) and MM (millimeter) amplitudes were extracted by envelope processing. Agreement between signals amplitudes was evaluated by mixed linear regression and cross-correlation function and in segments of PSG including event-free and SDB periods. RESULTS: The average total sleep time was 370 ± 18 min and the apnea hypopnea index was 24.8 ± 5.2 events/h. MM and EMG-d amplitudes were significantly cross-correlated: median r (95% CI): 0.67 (0.23-0.96). A mixed linear model showed that for each 10 µV of increase in EMG-d activity, MM amplitude increased by 0.28 mm. The variations in MM amplitudes (median range: 0.11-0.84 mm) between normal breathing, respiratory effort-related arousal, obstructive, mixed, and central apnea periods closely corresponded to those observed with EMG-d activity (median range: 2.11-8.23 µV). CONCLUSION: MM amplitudes change proportionally to diaphragmatic EMG activity and accurately identify variations of RE during normal sleep and SDB.

Monitoring mandibular movements to detect Cheyne-Stokes Breathing.

BACKGROUND: The patterns of mandibular movements (MM) during sleep can be used to identify increased respiratory effort periodic large-amplitude MM (LPM), and cortical arousals associated with "sharp" large-amplitude MM (SPM). We hypothesized that Cheyne Stokes breathing (CSB) may be identified by periodic abnormal MM patterns. The present study aims to evaluate prospectively the concordance between CSB detected by periodic MM and polysomnography (PSG) as gold-standard. The present study aims to evaluate prospectively the concordance between CSB detected by periodic MM and polysomnography (PSG) as gold-standard. METHODS: In 573 consecutive patients attending an in-laboratory PSG for suspected sleep disordered breathing (SDB), MM signals were acquired using magnetometry and scored manually while blinded from the PSG signal. Data analysis aimed to verify the concordance between the CSB identified by PSG and the presence of LPM or SPM. The data were randomly divided into training and validation sets (985 5-min segments/set) and concordance was evaluated using 2 classification models. RESULTS: In PSG, 22 patients (mean age ± SD: 65.9 ± 15.0 with a sex ratio M/F of 17/5) had CSB (mean central apnea hourly indice ± SD: 17.5 ± 6.2) from a total of 573 patients with suspected SDB. When tested on independent subset, the classification of CSB based on LPM and SPM is highly accurate (Balanced-accuracy = 0.922, sensitivity = 0.922, specificity = 0.921 and error-rate = 0.078). Logistic models based odds-ratios for CSB in presence of SPM or LPM were 172.43 (95% CI: 88.23-365.04; p < 0.001) and 186.79 (95% CI: 100.48-379.93; p < 0.001), respectively. CONCLUSION: CSB in patients with sleep disordered breathing could be accurately identified by a simple magnetometer device recording mandibular movements.

The blood transfer conductance for CO and NO.

Nitric oxide was introduced over 30 years ago as a test gas for alveolar capillary diffusion. As for CO its transfer has been interpreted according to the Roughton Forster relationship: 1/DL=1/DM+1/θVc. There has been disagreement, since the first measurements of DLNO, over whether θNO is infinite and thus DLNO=DMNO. There is overwhelming in vitro evidence that θNO is finite yet several groups (Coffman et al., 2017; Tamhane et al., 2001) use an infinite value in vivo. They also assume that DMNO is greater than twice DMCO, making DMCO less than that predicted by the physical laws of diffusion. Finally some (Coffman et al., 2017) recommend use of Reeve and Park's value for θCO (Reeves and Park, 1992; Coffman et al., 2017) rather than Forster's (Forster, 1987). Their grounds for doing so are that the combination of an infinite theta NO, an empirical value for DMNO/DMCO (>2.0) and Reeve and Park's θCO gives a value of DMCO (using a combined DLNO-DLCO analysis) which agrees with the DMCO value calculated separately by the classical two-stage oxygen technique of Roughton and Forster. In this paper we examine whether there are physiological reasons for assuming that DMNO is over twice DMCO in vivo. We are critical of Reeves and Park's estimate for the 1/θCO-PO2 relationship. We review in vitro estimates of θCO in the light of Guenard et al.'s recent in vivo estimate.

Standardisation and application of the single-breath determination of nitric oxide uptake in the lung.

Diffusing capacity of the lung for nitric oxide (DLNO), otherwise known as the transfer factor, was first measured in 1983. This document standardises the technique and application of single-breath DLNO This panel agrees that 1) pulmonary function systems should allow for mixing and measurement of both nitric oxide (NO) and carbon monoxide (CO) gases directly from an inspiratory reservoir just before use, with expired concentrations measured from an alveolar "collection" or continuously sampled via rapid gas analysers; 2) breath-hold time should be 10 s with chemiluminescence NO analysers, or 4-6 s to accommodate the smaller detection range of the NO electrochemical cell; 3) inspired NO and oxygen concentrations should be 40-60 ppm and close to 21%, respectively; 4) the alveolar oxygen tension (PAO2 ) should be measured by sampling the expired gas; 5) a finite specific conductance in the blood for NO (θNO) should be assumed as 4.5 mL·min-1·mmHg-1·mL-1 of blood; 6) the equation for 1/θCO should be (0.0062·PAO2 +1.16)·(ideal haemoglobin/measured haemoglobin) based on breath-holding PAO2 and adjusted to an average haemoglobin concentration (male 14.6 g·dL-1, female 13.4 g·dL-1); 7) a membrane diffusing capacity ratio (DMNO/DMCO) should be 1.97, based on tissue diffusivity.

Mandibular position and movements: Suitability for diagnosis of sleep apnoea.

BACKGROUND AND OBJECTIVE: Mandibular movements (MMs) and position during sleep reflect respiratory efforts related to increases in upper airway resistance and micro-arousals. The study objective was to assess whether MM identifies sleep-disordered breathing (SDB) in patients with moderate to high pre-test probability. METHODS: This was a prospective study of 87 consecutive patients referred for an in-laboratory sleep test. Magnetometer-derived MM signals were incorporated into standard polysomnography (PSG). Respiratory events detected with MM analysis were compared with PSG for respiratory disturbance index (RDI) with a blinded scoring. All records were scored manually according to American Academy of Sleep Medicine rules. Primary outcome was to rule-in obstructive sleep apnoea syndrome (OSAS) defined as RDI cut-off value ≥5 or 15/h total sleep time (TST). RESULTS: High concordance emerged between MM and PSG-derived RDI with high temporal coincidence between events (R2 = 0.906; P < 0.001). The mean diagnostic accuracy of MM for OSAS using RDI MM cut-off values of 5.9 and 13.5 was 0.935 (0.86-0.97) and 0.913 (0.84-0.95), with a mean positive likelihood ratio (LLR+) of 3.73 (2.7-20.4) and 8.46 (2.3-31.5), respectively. Receiver operating characteristic (ROC) curves at PSG cut-off values of 5 and 15/h TST had areas under the curve (AUC) of 0.96 (95% CI: 0.89-0.99) and 0.97 (95% CI: 0.91-0.99) (P < 0.001), respectively. MM analysis accurately identified SDB at different levels of severity. CONCLUSION: RDI assessed by MM is highly concordant with PSG, suggesting a role of ambulatory MM recordings to screen for SDB in patients with moderate to high pre-test probability.

Nitrogen monoxide and carbon monoxide transfer interpretation: state of the art.

Just a few clinicians routinely measure the subcomponents of the lung diffusing capacity for Carbone monoxide (DLCO ). This is because the measurement of membrane and blood conductances for CO (DmCO and DbCO  = Î¸CO  × Vc , respectively) by the classic Roughton and Forster method is complicated and time consuming. In addition, it mistakenly assumes a close relationship between alveolar oxygen partial pressure (PAO2 ) and mean intracapillary oxygen partial pressure (PcapO2 ) which is the true determinant of specific conductance of haemoglobin for CO (θCO ). Besides that, the critical multistep oxygenation method along with different linear equations relating 1/θCO to PcapO2 gave highly scattered DmCO and Vc values. The Dm and Vc can also be derived from a simultaneous measurement of DLNO and DLCO with the blood resistance for NO assumed to be negligible. However, recent in vitro and in vivo experiments point towards a finite value of θNO (about 4·5 mlNO  × mlblood-1  × min-1  × mmHg-1 ). Putting together the arguments and our clinical data allows us to report here the state of the art in partitioning the CO diffusing capacity into its constitutive components, with the goal to encourage further studies examining the sensitivity of DmCO and Vc to alterations observed in parenchymal diseases.

Feasibility of intercostal blood flow measurement by echo-Doppler technique in healthy subjects.

Intercostal artery blood flow supplies the external and internal intercostal muscles, which are inspiratory and expiratory muscles. Intercostal blood flow measured by the echo-Doppler (ED) technique has not previously been reported in humans. This study describes the feasibility of this measurement during free and loaded breathing in healthy subjects. Systolic, diastolic and mean blood flows were measured in the eighth dorsal intercostal space during free and loaded breathing using the ED technique. Flows were calculated as the product of the artery intraluminal surface and blood velocity. Ten healthy subjects (42 ± 13·6 years) were included. Integrated electromyogram (iEMG), arterial pressure, cardiac frequency and breathing pattern were also recorded. Mean blood flows were 3·5 ± 1·2 ml min-1 at rest, 6 ± 2·6 ml min-1 while breathing through a combined inspiratory and expiratory resistance and 4·0 ± 1·3 ml min-1 1 min after unloading. Diastolic blood flow was about one-third the systolic blood flow. The changes in blood flows were consistent with those in iEMG. No change in mean blood flow was observed between inspiration and expiration, suggesting a balance in the perfusion of external and internal muscles during breathing. In conclusion, ED is a feasible technique for non-invasive, real-time measurement of intercostal blood flow in humans. In healthy subjects, mean blood flow appeared tightly matched to iEMG activity. This technique may provide a way to assess the vascular adaptations induced by diseases in which respiratory work is increased or cardiac blood flow altered.

The history of the pulmonary diffusing capacity for nitric oxide DL,NO.

The DL,NO (TL,NO) had its unexpected origins in the Paris "events" of 1968 and the unsuccessful efforts of the UK tobacco industry in the 1970's to create a "safer cigarette". Adoption of the technique has been slow due to the instability of NO in air, lack of standardisation of the technique and lack of agreement as to whether DL,NO is equal to or merely reflects membrane diffusing capacity (DM). With the availability of inexpensive analysers, standardisation of the technique and publication of reference equations we believe that its worldwide use will increase.

In vivo estimates of NO and CO conductance for haemoglobin and for lung transfer in humans.

Membrane conductance (Dm) and capillary lung volume (Vc) derived from NO and CO lung transfer measurements in humans depend on the blood conductance (θ) values of both gases. Many θ values have been proposed in the literature. In the present study, measurements of CO and NO transfer while breathing 15% or 21% O2 allowed the estimation of θNO and the calculation of the optimal equation relating 1/θCO to pulmonary capillary oxygen pressure (PcapO2). In 10 healthy subjects, the mean calculated θNO value was similar to the θNO value previously reported in the literature (4.5mmHgmin(-1)) provided that one among three θCO equations from the literature was chosen. Setting 1/θCO=a·PcapO2+b, optimal values of a and b could be chosen using two methods: 1) by minimizing the difference between Dm/Vc ratios for any PcapO2, 2) by establishing a linear equation relating a and b. Using these methods, we are proposing the equation 1/θCO=0.0062·PcapO2+1.16, which is similar to two equations previously reported in the literature. With this set of θ values, DmCO reached the morphometric range.

Mandibular movements identify respiratory effort in pediatric obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea-hypopnea (OAH) diagnosis in children is based on the quantification of flow and respiratory effort (RE). Pulse transit time (PTT) is one validated tool to recognize RE. Pattern analysis of mandibular movements (MM) might be an alternative method to detect RE. We compared several patterns of MM to concomittant changes in PTT during OAH in children with adenotonsillar hypertrophy. PARTICIPANTS: 33 consecutive children with snoring and symptoms/signs of OAH. MEASUREMENTS: MMs were measured during polysomnography with a magnetometer device (Brizzy Nomics, Liege, Belgium) placed on the chin and forehead. Patterns of MM were evaluated representing peak to peak fluctuations > 0.3 mm in mandibular excursion (MML), mandibular opening (MMO), and sharp MM (MMS), which closed the mouth on cortical arousal (CAr). RESULTS: The median (95% CI) hourly rate of at least 1 MM (MML, or MMO, or MMS) was 18.1 (13.2-36.3) and strongly correlated with OAHI (p = 0.003) but not with central apnea-hypopnea index (CAHI; p = 0.292). The durations when the MM amplitude was > 0.4 mm and PTT > 15 ms were strongly correlated (p < 0.001). The mean (SD) of MM peak to peak amplitude was larger during OAH than CAH (0.9 ± 0.7 mm and 0.2 ± 0.3 mm; p < 0.001, respectively). MMS at the termination of OAH had larger amplitude compared to MMS with CAH (1.5 ± 0.9 mm and 0.5 ± 0.7 mm, respectively, p < 0.001). CONCLUSIONS: MM > 0.4 mm occurred frequently during periods of OAH and were frequently terminated by MMS corresponding to mouth closure on CAr. The MM findings strongly correlated with changes in PTT. MM analysis could be a simple and accurate promising tool for RE characterization and optimization of OAH diagnosis in children.

Pulmonary circulation and gas exchange at exercise in Sherpas at high altitude.

Tibetans have been reported to present with a unique phenotypic adaptation to high altitude characterized by higher resting ventilation and arterial oxygen saturation, no excessive polycythemia, and lower pulmonary arterial pressures (Ppa) compared with other high-altitude populations. How this affects exercise capacity is not exactly known. We measured aerobic exercise capacity during an incremental cardiopulmonary exercise test, lung diffusing capacity for carbon monoxide (DL(CO)) and nitric oxide (DL(NO)) at rest, and mean Ppa (mPpa) and cardiac output by echocardiography at rest and at exercise in 13 Sherpas and in 13 acclimatized lowlander controls at the altitude of 5,050 m in Nepal. In Sherpas vs. lowlanders, arterial oxygen saturation was 86 ± 1 vs. 83 ± 2% (mean ± SE; P = nonsignificant), mPpa at rest 19 ± 1 vs. 23 ± 1 mmHg (P < 0.05), DL(CO) corrected for hemoglobin 61 ± 4 vs. 37 ± 2 ml · min(-1) · mmHg(-1) (P < 0.001), DL(NO) 226 ± 18 vs. 153 ± 9 ml · min(-1) · mmHg(-1) (P < 0.001), maximum oxygen uptake 32 ± 3 vs. 28 ± 1 ml · kg(-1) · min(-1) (P = nonsignificant), and ventilatory equivalent for carbon dioxide at anaerobic threshold 40 ± 2 vs. 48 ± 2 (P < 0.001). Maximum oxygen uptake was correlated directly to DL(CO) and inversely to the slope of mPpa-cardiac index relationships in both Sherpas and acclimatized lowlanders. We conclude that Sherpas compared with acclimatized lowlanders have an unremarkable aerobic exercise capacity, but with less pronounced pulmonary hypertension, lower ventilatory responses, and higher lung diffusing capacity.

Lung membrane conductance and capillary volume derived from the NO and CO transfer in high-altitude newcomers.

Acute exposure to high altitude may induce changes in carbon monoxide (CO) membrane conductance (DmCO) and capillary lung volume (Vc). Measurements were performed in 25 lowlanders at Brussels (D0), at 4,300 m after a 2- or 3-day exposure (D2,3) without preceding climbing, and 5 days later (D7,8), before and after an exercise test, under a trial with two arterial pulmonary vasodilators or a placebo. The nitric oxide (NO)/CO transfer method was used, assuming both infinite and finite values to the NO blood conductance (θNO). Doppler echocardiography provided hemodynamic data. Compared with sea level, lung diffusing capacity for CO increased by 24% at D2,3 and is returned to control at D7,8. The acute increase in lung diffusing capacity for CO resulted from increases in DmCO and Vc with finite and infinite θNO assumptions. The alveolar volume increased by 16% at D2,3 and normalized at D7,8. The mean increase in systolic arterial pulmonary pressure at rest at D2,3 was minimal. In conclusion, the acute increase in Vc may be related to the increase in alveolar volume and to the increase in capillary pressure. Compared with the infinite θNO value, the use of a finite θNO value led to about a twofold increase in DmCO value and to a persistent increase in DmCO at D7,8 compared with D0. After exercise, DmCO decreased slightly less in subjects treated by the vasodilators, suggesting a beneficial effect on interstitial edema.

Pulmonary vascular reserve and exercise capacity at sea level and at high altitude.

It has been suggested that increased pulmonary vascular reserve, as defined by reduced pulmonary vascular resistance (PVR) and increased pulmonary transit of agitated contrast measured by echocardiography, might be associated with increased exercise capacity. Thus, at altitude, where PVR is increased because of hypoxic vasoconstriction, a reduced pulmonary vascular reserve could contribute to reduced exercise capacity. Furthermore, a lower PVR could be associated with higher capillary blood volume and an increased lung diffusing capacity. We reviewed echocardiographic estimates of PVR and measurements of lung diffusing capacity for nitric oxide (DL(NO)) and for carbon monoxide (DL(CO)) at rest, and incremental cardiopulmonary exercise tests in 64 healthy subjects at sea level and during 4 different medical expeditions at altitudes around 5000 m. Altitude exposure was associated with a decrease in maximum oxygen uptake (VO2max), from 42±10 to 32±8 mL/min/kg and increases in PVR, ventilatory equivalents for CO2 (V(E)/VCO2), DL(NO), and DL(CO). By univariate linear regression VO2max at sea level and at altitude was associated with V(E)/VCO2 (p<0.001), mean pulmonary artery pressure (mPpa, p<0.05), stroke volume index (SVI, p<0.05), DL(NO) (p<0.02), and DL(CO) (p=0.05). By multivariable analysis, VO2max at sea level and at altitude was associated with V(E)/VCO2, mPpa, SVI, and DL(NO). The multivariable analysis also showed that the altitude-related decrease in VO2max was associated with increased PVR and V(E)/VCO2. These results suggest that pulmonary vascular reserve, defined by a combination of decreased PVR and increased DL(NO), allows for superior aerobic exercise capacity at a lower ventilatory cost, at sea level and at high altitude.

Inhaled magnesium sulphate in the treatment of bronchial hyperresponsiveness.

UNLABELLED: Magnesium sulphate (MgSO(4)) is one of numerous treatment options available during acute asthma exacerbation. A significant, bronchodilating effect of intravenous MgSO(4) has been demonstrated in previous studies, but its inhaled use is less well-defined. OBJECTIVE: To investigate the effects of inhaled MgSO(4) alone and in association with a ß(2-)agonist in the treatment of bronchial hyperresponsiveness. Methods. We conducted a placebo-controlled, double-blind clinical trial with seventy six adult patients with bronchial hyperresponsiveness. Subjects were randomized into four groups receiving four inhaled products at the end of methacholine (Mech) challenge: NaCl 0.9%, MgSO(4)alone, ß(2-)agonist alone, and the combination of MgSO(4)+ ß(2-)agonist. Repeated measures of the forced expiratory volume at 1s (FEV(1)) were performed at 0, 5, 10, and 20 minutes after the end of the inhalations. In the MgSO(4)and MgSO(4)+ ß(2-)agonist groups, a blood sample was taken before and after inhalation to determine serum magnesium levels. Results. (1) Inhaled MgSO(4) led to a significant improvement of the FEV(1) from the 15(th) minute after its inhalation. (2) ß(2-)agonist significantly increased FEV(1) from the 5(th)minute (3) inhaled MgSO(4) + ß(2-)agonist led to a significantly greater FEV(1) from the 5(th)minute than inhaled MgSO(4)alone or inhaled ß(2-)agonist alone (p<0.05) (4) There is a correlation between low serum magnesium level and the increase in FEV(1)after inhalation of MgSO(4) + ß(2-)agonist (p<0.001). Conclusion Inhaled MgSO(4), in combination with ß(2-)agonist, appears to have benefits in the treatment of bronchial hyperresponsiveness, especially when associated with hypomagnesemia.