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Background: Pulmonary hypertension (PH) is a well-recognized complication of COPD. The impact of PH on exercise tolerance is largely unknown. We evaluated and compared the circulatory and ventilatory profiles during exercise in patients with COPD without PH, with moderate PH, and with severe PH.Methods: Forty-seven patients, GOLD (Global Initiative for Chronic Obstructive Lung Disease)stages II to IV, underwent cardiopulmonary exercise testing and right-sided heart catheterization at rest and during exercise. Patients were divided into three groups based on mean pulmonary artery pressure (mPAP) at rest: no PH (mPAP, < 25 mm Hg), moderate PH (mPAP, 25-39 mm Hg),and severe PH (mPAP, ≥ 40 mm Hg). Mixed venous oxygen saturation (S VO 2 ) was used for evaluating the circulatory reserve. Pa CO 2 and the calculated breathing reserve were used for evaluation of the ventilatory reserve.Results: Patients without PH (n = 24) had an end-exercise S VO 2 of 48%± 9%, an increasing Pa CO 2 with exercise, and a breathing reserve of 22% ± 20%. Patients with moderate PH (n = 14) had an exercise S VO 2 of 40% ± 8%, an increasing Pa CO 2 , and a breathing reserve of 26% ± 15%. Patients with severe PH (n =9) had a significantly lower end-exercise S VO 2 (30% ± 6%), a breathing reserve of 37% ± 11%, and an absence of Pa CO 2 accumulation.Conclusion: Patients with severe PH showed an exhausted circulatory reserve at the end of exercise.A profile of circulatory reserve in combination with ventilatory impairments was found inpatients with COPD and moderate or no PH. The results suggest that pulmonary vasodilation might only improve exercise tolerance in patients with COPD and severe PH. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND:: The 6-min walk distance (6MWD) predicts survival in pulmonary hypertension (PH). The peak oxygen consumption (V O2peak) measured during a cardiopulmonary exercise test (CPET) also relates to survival in PH, and it is unknown how the prognostic information from measurements of ventilatory responses and gas exchange during CPET compares to the prognostic information obtained by the 6MWD alone. The aims of our study were to compare prognostic values of different exercise parameters in PH and to assess whether CPET adds prognostic value to the information from the 6MWD. METHODS:: After baseline right-heart catheterization and exercise testing, survival was assessed in a cohort of 115 PH patients. RESULTS:: During the 4 yr of follow-up, 18 patients died. At baseline, pulmonary arterial pressure was 49 +/- 17 mm Hg, the slope relating minute ventilation to carbon dioxide output (V E/V CO2slope) = 45 +/- 11, V O2peak = 15 +/- 6 mL.kg.min, increase in O2 pulse from rest to peak exercise (DeltaO2 pulse) = 5 +/- 2 mL.beat, and 6MWD = 445 +/- 128 m. For the prediction of mortality, the areas under the receiver operating curves were very similar for the different parameters and ranged from 0.69 to 0.74. Patients with a V E/V CO2slope < 48, V O2peak > 13.2 mL.kg.min, DeltaO2 pulse > 3.3 mL.beat, or a 6MWD > 399 m had a higher cumulative survival (P < 0.05). Multivariable Cox regression with a forward selection procedure showed that only DeltaO2 pulse improved the univariate 6MWD prediction model significantly (P < 0.05). CONCLUSION:: CPET parameters predict survival in PH patients and add marginally to the prognostic value of the 6MWD. [ABSTRACT FROM AUTHOR]

Abstract Background To assess a pulmonary function change over time the mass flow sensor and the pneumotachograph are widely used in commercially available instruments. However, the smallest detectable change for both devices has never been compared. Therefore, the aim of this study is to determine the smallest detectable change in vital capacity (VC) and single-breath diffusion parameters measured by mass flow sensor and or pneumotachograph. Method In 28 healthy pulmonary function technicians VC, transfer factor for carbon monoxide (DLCO) and alveolar volume (VA) was repeatedly (10×) measured. The smallest detectable change was calculated by 1.96 x Standard Error of Measurement ×√2. Findings The mean (range) of the smallest detectable change measured by mass flow sensor and pneumotachograph respectively, were for VC (in Liter): 0.53 (0.46-0.65); 0.25 (0.17-0.36) (p = 0.04), DLCO (in mmol*kPa-1*min-1): 1.53 (1.26-1.7); 1.18 (0.84-1.39) (p = 0.07), VA (in Liter): 0.66. (0.53-0.82); 0.43 (0.34-0.53) (p = 0.04) and DLCO/VA (in mmol*kPa-1*min-1*L-1): 0.22 (0.19-0.28); 0.19 (0.14-0.22) (p = 0.79). Conclusions Smallest detectable significant change in VC and VA as measured by pneumotachograph are smaller than by mass flow sensor. Therefore, the pneumotachograph is the preferred instrument to estimate lung volume change over time in individual patients.

Abstract Background There is no optimal screening tool for the assessment of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). A decreasing transfer factor of the lung for CO (TLCO) is associated with the development of PAH in SSc. TLCO can be partitioned into the diffusion of the alveolar capillary membrane (Dm) and the capillary blood volume (Vc). The use of the partitioned diffusion to detect PAH in SSc is not well established yet. This study evaluates whether Dm and Vc could be candidates for further study of the use for screening for PAH in SSc. Methods Eleven SSc patients with PAH (SScPAH+), 13 SSc patients without PAH (SScPAH-) and 10 healthy control subjects were included. Pulmonary function testing took place at diagnosis of PAH. TLCO was partitioned according to Roughton and Forster. As pulmonary fibrosis in SSc influences values of the (partitioned) TLCO, these were adjusted for fibrosis score as assessed on HRCT. Results TLCO as percentage of predicted (%) was lower in SScPAH+ than in SScPAH- (41 ± 7% vs. 63 ± 12%, p < 0.0001, respectively). Dm% in SScPAH+ was decreased as compared with SScPAH- (22 ± 6% vs. 39 ± 12%, p < 0.0001, respectively), also after adjustment for total fibrosis score (before adjustment: B = 17.5, 95% CI 9.0–25.9, p = < 0.0001; after adjustment: B = 14.3, 95% CI 6.0–21.7, p = 0.008). No difference was found in Vc%. There were no correlations between pulmonary hemodynamic parameters and Dm% in the PAH groups. Conclusion SScPAH+ patients have lower Dm% than SScPAH- patients. There are no correlations between Dm% and hemodynamic parameters of PAH in SScPAH+. These findings do not support further study of the role of partitioning TLCO in the diagnostic work- up for PAH in SSc.

Background: There is no optimal screening tool for the assessment of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). A decreasing transfer factor of the lung for CO (TLCO) is associated with the development of PAH in SSc. TLCO can be partitioned into the diffusion of the alveolar capillary membrane (Dm) and the capillary blood volume (Vc). The use of the partitioned diffusion to detect PAH in SSc is not well established yet. This study evaluates whether Dm and Vc could be candidates for further study of the use for screening for PAH in SSc. Methods: Eleven SSc patients with PAH (SScPAH+), 13 SSc patients without PAH (SScPAH-) and 10 healthy control subjects were included. Pulmonary function testing took place at diagnosis of PAH. TLCO was partitioned according to Roughton and Forster. As pulmonary fibrosis in SSc influences values of the (partitioned) TLCO, these were adjusted for fibrosis score as assessed on HRCT. Results: TLCO as percentage of predicted (%) was lower in SScPAH+ than in SScPAH- (41 ± 7% vs. 63 ± 12%, p < 0.0001, respectively). Dm% in SScPAH+ was decreased as compared with SScPAH- (22 ± 6% vs. 39 ± 12%, p < 0.0001, respectively), also after adjustment for total fibrosis score (before adjustment: B = 17.5, 95% CI 9.0-25.9, p = < 0.0001; after adjustment: B = 14.3, 95% CI 6.0-21.7, p = 0.008). No difference was found in Vc%. There were no correlations between pulmonary hemodynamic parameters and Dm% in the PAH groups. Conclusion: SScPAH+ patients have lower Dm% than SScPAH- patients. There are no correlations between Dm% and hemodynamic parameters of PAH in SScPAH+. These findings do not support further study of the role of partitioning TLCO in the diagnostic work- up for PAH in SSc. [ABSTRACT FROM AUTHOR]

Objectives: Avoiding inadvertent hypothermia during surgery is important. Intravenous fluid warmers used intraoperatively are critical for maintaining euthermia. We sought to prospectively evaluate the performance of the parylene-coated enFlow™ intravenous fluid warmer in patients undergoing surgery., Methods: This was a prospective two-center observational clinical trial performed in inpatient surgical services of two large academic hospital systems. After written informed consent, patients were enrolled in the trial. All patients were adults scheduled for a surgery that was expected to last for at least 1 h with the administration of at least 1 L of fluid warmed prior to infusion. Patient temperature was recorded in the preoperative unit, at the induction of anesthesia, and then every 15 or 30 min until the end of surgery. Temperature monitoring continued in the recovery unit. The parylene-coated enFlow™ intravenous fluid warmer was used in addition to the usual patient warming techniques. The primary outcome was the average core temperature, and secondary analyses assessed individual temperature measurements, temperature measurements during specific time periods, and rate of hypothermic events., Results: In all, 50 patients (29 males) with a mean age of 64 years were included in the analysis. The mean surgical time was 195 min and patients received an average of 1142 mL of fluids. Core temperature dropped by only 0.3°C approximately 60 min after induction and recovered back to the baseline level approximately 60 min later. There was no correlation between flow rate and measured core body temperature., Conclusions: The parylene-coated enFlow intravenous fluid warmer was able to warm fluids at all flow rates during prolonged surgery. The results showed that enFlow performed as expected., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ML, SM, KR, JJ, and VK have no competing interests. The actual research including case extraction and data analysis were performed by an outside clinical research organization, Clinius Oy (VK). DB, ER, HG, and AW are affiliated with Vyaire Medical. SC is an independent consultant. This manuscript and all attached tables and figures were reviewed and approved by all authors., (© The Author(s) 2023.)

Objective: In the delivery of intravenous fluids, in-line warming devices frequently transfer heat using a metal heating plate, which if uncoated can risk elution. This bench study examined extractable elements detected following long-term use of the parylene-coated enFlow ® Disposable IV/Blood Warmer., Methods: We tested 16 clinically relevant challenge fluids typical of the surgical setting, including commercially available single donor blood and blood products as well as intravenous saline and electrolyte solutions. After 72 h of warming at 40°C (104°F) via the enFlow, analytical chemistry identified and quantified the most clinically significant extractable elements (arsenic, barium, cadmium, copper, and lead) to estimate chemical exposure. We also measured the extracted concentrations of these five elements following simulated use of the device with three solutions (Sterofundin ISO, Plasma-Lyte 148, and whole blood) that were pumped through the warmed device at two different flow rates (0.2 and 5.5 mL min -1 )., Results: Across all scenarios of acute and long-term exposures for different populations, the enFlow demonstrated low toxicological risks as measured by the calculation of tolerable exposure for extracted arsenic, barium, cadmium, copper, and lead., Conclusion: The results suggest biological safety for the use of parylene-coated enFlow with a variety of intravenous solutions and in different therapeutic scenarios., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.B., H.G., and A.D.W. are the employees of Vyaire Medical. M.P. is an employee and medical director of Vyaire Medical. E.R. is an independent consultant retained by Vyaire Medical for this project., (© The Author(s) 2022.)

Background: Perioperative hypothermia is a common occurrence, particularly with the elderly and pediatric age groups. Hypothermia is associated with an increased risk of perioperative complications. One method of preventing hypothermia is warming the infused fluids given during surgery. The enFlow™ intravenous fluid warmer has recently been reintroduced with a parylene coating on its heating blocks. In this paper, we evaluated the impact of the parylene coating on the new enFlow's fluid warming capacity., Methods: Six coated and six uncoated enFlow cartridges were used. A solution of 10% propylene glycol and 90% distilled H 2 O was infused into each heating cartridge at flow rates of 2, 10, 50, 150, and 200 ml/min. The infused fluid temperature was set at 4 °C, 20 °C, and 37 °C. Output temperature was recorded at each level. Data for analysis was derived from 18 runs at each flow rate (six cartridges at three temperatures)., Results: The parylene coated fluid warming cartridge delivered very stable output of 40 °C temperatures at flow rates of 2, 10, and 50 ml/min regardless of the temperature of the infusate. At higher flow rates, the cartridges were not able to achieve the target temperature with the colder fluid. Both cartridges performed with similar efficacy across all flow rates at all temperatures., Conclusions: At low flow rates, the parylene coated enFlow cartridges was comparable to the original uncoated cartridges. At higher flow rates, the coated and uncoated cartridges were not able to achieve the target temperature. The parylene coating on the aluminum heating blocks of the new enFlow intravenous fluid warmer does not negatively affect its performance compared to the uncoated model., (© 2022. The Author(s).)

Purpose: Human respiratory aerosols may have important implications for transmission of pathogens. The study of aerosol production during vigorous breathing activities such as exercise is limited. In particular, data on aerosol production during cardiopulmonary exercise testing (CPET) are lacking., Methods: In this pilot project, we used a high-powered, pulsed Nd:YAG laser to illuminate a region of interest in front of two healthy adult subjects during CPET. Subjects exercised to the point of respiratory compensation. Images were captured with a high-speed, high-resolution camera to determine net exhaled particle (NEP) counts at different phases of CPET, including resting breathing, submaximal exercise, peak exercise, and active recovery. Experiments were performed with the room ventilation activated., Results: Net exhaled particle counts remained relatively constant until late/peak exercise when they decreased prior to rebounding into recovery. NEP counts at resting breathing were higher than those reported using other methods of measurement. Exhaled particles were in the submicron size range., Conclusion: Our method of aerosol particle quantification enables measurement of significant quantities of ultrafine particles and dynamic assessment of aerosol production during CPET. The unique pattern of aerosol production observed during submaximal and peak exercise suggests that extension of results from resting breathing to CPET may not be appropriate., Competing Interests: Conflict of interestCMV, KJK, MJP, HG, and KDP are employees of Vyaire Medical, Mettawa, IL.; CG is an employee of LaVision Inc., Ypsilanti, MI., (© Taiwanese Society of Biomedical Engineering 2021.)

Hyperventilation is common in pulmonary arterial hypertension and may be related to autonomic imbalance. Patients underwent exercise testing and hyperoxic breathing before and after bisoprolol treatment. We found that neither beta blocker treatment nor hyperoxic breathing in patients reduced hyperventilation at rest and during exercise, although it reduced heart rate., Competing Interests: The author(s) declare that there is no conflict of interest., (© The Author(s).)

Introduction: Metabolic simulators (MS) produce simulated human breaths for the purpose of verification of cardiopulmonary exercise test (CPET) equipment. MS should produce consistent identical breaths with known CO 2 and O 2 gas concentrations over a range of breath rates and tidal volumes. Reliability of a CPET metabolic cart depends on ongoing quality control and maintenance of the device, including intermittent verification with a MS. We compared two MS devices against two standard CPET systems., Methods: The Vacumed 17056 (Vacumetrics, Ventura, CA) and Relitech (Relitech Systems BV, Nijkerk, The Netherlands) were used with two standard metabolic carts (Vyntus CPX and Vyntus ONE, both Vyaire Medical, Mettawa, IL, United States). Tidal volume (VT) was set at 2 and 3 L and breathing frequency ranged from 20 to 80 breaths per minute for each MS. At each set point, we measured three sets of 40 breaths. Primary outcome parameters collected were VT, oxygen consumption ( v . O 2 ), carbon dioxide production ( v . CO 2 ), and respiratory exchange ratio (RER)., Results: VT, RER, v . O 2 , and v . CO 2 results as obtained from both MS were all within the limits of acceptability, at both tidal volume settings, and all ventilatory rates. No significant trends were identified for either MS device. The Relitech MS produced tidal volumes that were closer to the target VT for both CPET carts at both VT and all rates, but the results of both MS were within acceptable ranges., Conclusion: Verification of CPET equipment using either the VM or RT metabolic simulator, producing highly accurate and predictable simulated breaths of known composition, enabling CPET laboratory managers to rely on subject test data obtained during cardiopulmonary exercise testing., Competing Interests: TS and ER are paid consultants for Vyaire Medical, Mettawa, IL, United States. HG is an employee of Vyaire Medical, Mettawa, IL, United States. Financial support for this project came from Vyaire Medical, Mettawa, IL, United States., (Copyright © 2021 Souren, Rose and Groepenhoff.)

Objectives: To provide sex, age, and race specific reference values for ramp cycle ergometer cardiopulmonary exercise test (CPET) in children in the US., Study Design: Retrospective review was conducted of all cardiopulmonary CPET data from our Exercise Physiology Laboratory on healthy children and adolescents (6-18 years) with body mass index between the 5th and 95th percentiles and structurally normal hearts who performed a ramp cycle ergometry stress test between 1999 and 2015. Twenty-eight exercise variables were included: peak oxygen consumption, oxygen consumption at ventilatory anaerobic threshold, peak work rate, resting and peak heart rate and blood pressure, resting pulmonary function testing, and ventilatory responses to progressive exercise using breath-by-breath gas exchange. Owing to the nonlinear association between CPET results and age, fractional polynomials were used in the mixed-effects regression models to describe the sex- and age-specific normative values with 95% CIs, after adjusting for race and body mass index., Results: We analyzed data on 1829 children (average age, 13.6 ± 2.6 years; 52% male). After 12 years of age, males generally had higher peak values for aerobic capacity and work rate. There were progressive increases with age for both sexes in resting pulmonary function and ventilatory response to exercise, peak aerobic and work rate, and oxygen pulse. Notably, there was an age-related decrease in ventilatory equivalents of oxygen and carbon dioxide at the ventilatory anaerobic threshold., Conclusions: Future research using prospective, inclusive, and statistically planned cohorts with standardized laboratory approaches and confirmed interoperability should be considered as a focus for validating normative pediatric CPET values in the future., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Unlabelled: In patients with idiopathic pulmonary arterial hypertension (iPAH), iron deficiency is common and has been associated with reduced exercise capacity and worse survival. Previous studies have shown beneficial effects of intravenous iron administration. In this study, we investigated the use of intravenous iron therapy in iron-deficient iPAH patients in terms of safety and effects on exercise capacity, and we studied whether altered exercise capacity resulted from changes in right ventricular (RV) function and skeletal muscle oxygen handling. Fifteen patients with iPAH and iron deficiency were included. Patients underwent a 6-minute walk test, cardiopulmonary exercise tests, cardiac magnetic resonance imaging, and a quadriceps muscle biopsy and completed a quality-of-life questionnaire before and 12 weeks after receiving a high dose of intravenous iron. The primary end point, 6-minute walk distance, was not significantly changed after 12 weeks (409 ± 110 m before vs. 428 ± 94 m after; P = 0.07). Secondary end points showed that intravenous iron administration was well tolerated and increased body iron stores in all patients. In addition, exercise endurance time (P < 0.001) and aerobic capacity (P < 0.001) increased significantly after iron therapy. This coincided with improved oxygen handling in quadriceps muscle cells, although cardiac function at rest and maximal [Formula: see text] were unchanged. Furthermore, iron treatment was associated with improved quality of life (P < 0.05). In conclusion, intravenous iron therapy in iron-deficient iPAH patients improves exercise endurance capacity. This could not be explained by improved RV function; however, increased quadriceps muscle oxygen handling may play a role. (, Trial Registration: ClinicalTrials.gov identifier NCT01288651).

Aims: The pathophysiology underlying aortic valve stenosis (AVS)-induced cardiac dysfunction and reduced exercise capacity is unclear. We hypothesize that improvement of myocardial external efficiency (MEE)--the ratio between external work and myocardial oxygen consumption (MVO2)--underlies functional improvement of AVS patients after aortic valve replacement (AVR). Therefore, the aim of this proof-of-concept study was to investigate whether myocardial efficiency is reduced in patients with cardiac hypertrophy caused by AVS and to assess the effect of AVR on myocardial efficiency in relation to exercise capacity., Methods and Results: Echocardiography, cardiopulmonary exercise test, [(11)C]-acetate positron emission tomography and cardiovascular magnetic resonance imaging were performed in 10 AVS patients prior to (pre-AVR) and 4 months after AVR (post-AVR). Fourteen healthy individuals served as control group. MEE was significantly lower in pre-AVR patients (32 ± 7%) than in controls (49 ± 6%). AVR significantly decreased left ventricle mass and MVO2. Also, external work significantly decreased post-AVR reaching similar values as in controls. AVR significantly improved MEE from 32 ± 7 to 37 ± 5% (P = 0.02). Moreover, significant correlations were present between the AVR-induced increase in MEE and changes in both exercise work (r = 0.74, P = 0.01) and peak VO2 (r = 0.67, P = 0.03). However, four AVS patients did not show improved MEE, which was associated with no or minimal improvement in exercise parameters., Conclusion: MEE is significantly reduced in patients with AVS-induced hypertrophy. Improved MEE is an important predictor of AVR-induced improvement of exercise capacity in AVS patients. Future investigation is needed to confirm our observations in a large prospective, multicenter clinical trial., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Rationale: Exercise tolerance is decreased in patients with pulmonary hypertension (PH). It is unknown whether exercise intolerance in PH coincides with an impaired rest-to-exercise response in right ventricular (RV) contractility., Objectives: To investigate in patients with PH the RV exertional contractile reserve, defined as the rest-to-exercise response in end-systolic elastance (ΔEes), and the effects of exercise on the matching of Ees and RV afterload (Ea) (i.e., RV-arterial coupling; Ees/Ea). In addition, we compared ΔEes with a recently proposed surrogate, the rest-to-exercise change in pulmonary artery pressure (ΔPAP)., Methods: We prospectively included 17 patients with precapillary PH and 7 control subjects without PH who performed a submaximal invasive cardiopulmonary exercise test between January 2013 and July 2014. Ees and Ees/Ea were assessed using single-beat pressure-volume loop analysis., Measurements and Main Results: Exercise data in 16 patients with PH and 5 control subjects were of sufficient quality for analysis. Ees significantly increased from rest to exercise in control subjects but not in patients with PH. Ea significantly increased in both groups. As a result, exercise led to a decrease in Ees/Ea in patients with PH, whereas Ees/Ea was unaffected in control subjects (Pinteraction = 0.009). In patients with PH, ΔPAP was not related to ΔEes but significantly correlated to the rest-to-exercise change in heart rate., Conclusions: In contrast to control subjects, patients with PH were unable to increase Ees during submaximal exercise. Failure to compensate for the further increase in Ea during exercise led to deterioration in Ees/Ea. Furthermore, ΔPAP did not reflect ΔEes but rather the change in heart rate.

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.

A subgroup of patients with idiopathic pulmonary arterial hypertension (IPAH) has severely reduced diffusing capacity of the lung for carbon monoxide (DLCO) and poor prognosis. Their characteristics are currently unknown. The aim of this study is to contrast clinical characteristics and treatment responses of IPAH-patients with a severely reduced and more preserved DLCO. Retrospectively, 166 IPAH patients were included and grouped based on a DLCO cut-off value of 45% pred (IPAH(<45%) and IPAH(≥45%)). Clinical characteristics, treatment responses and survival were compared. IPAH(<45%) were older, more often male, had a more frequent history of coronary disease and a higher tobacco exposure. Forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity, total lung capacity and alveolar volume values were slightly lower and computed tomography scan abnormalities more prevalent in patients with a low DLCO. Age and number of pack years were independently associated with DLCO < 45% pred. IPAH(<45%) showed no different haemodynamic profile, yet worse exercise performance and a worse survival rate, which were both related to age, sex and the presence of coronary disease. To conclude, a severely reduced DLCO in IPAH is associated with advanced age and a greater tobacco exposure. These patients have a worse exercise performance despite a similar hemodynamic profile. We confirm the decreased survival in this patient group and now show that this poor outcome is related to age, sex and the presence of coronary disease.

Introduction: Exercise variables determined in patients with pulmonary arterial hypertension (PAH) at the time of diagnosis, predict survival. It is unknown whether upon treatment, subsequent changes in these exercise variables reflect improvements in survival. The aim of this study was to determine changes in exercise variables in PAH patients and to relate these changes to survival., Methods: Baseline cardiopulmonary exercise test (CPET) variables and six-minute-walk-distance (6MWD) were available from 65 idiopathic PAH patients (50 females; mean age 45±2yrs). The same variables were determined after treatment (13months) in a sub group of 43 patients. To estimate the association between changes in exercise variables and changes in cardiac function, right-ventricle ejection fraction (RVEF) was measured by cardiac MRI at baseline and after treatment in 34 patients. Mean follow-up time after the second CPET was 53 (range: 4-111) months. Kaplan-Meier analysis was used to relate survival to baseline and treatment-associated changes in exercise variables., Results: Survivors showed a significantly greater change in maximal oxygen uptake than non-survivors and this change in aerobic capacity was significantly related to changes in RVEF. From baseline until the end of the study period, two patients underwent a lung transplantation and 19 patients died. Survival analysis showed that baseline 6MWD (p<0.0001), maximal heart rate (p<0.0001) and the slope relating ventilation with carbon dioxide production (p≤0.05) were significant predictors of survival, whereas baseline oxygen uptake and oxygen pulse held no predictive value. Treatment associated changes in 6MWD (p<0.01), maximal heart rate (p<0.05), oxygen uptake (p<0.001) and oxygen pulse predicted survival (p<0.05), whereas changes in the slope relating ventilation with carbon dioxide production did not., Conclusion: Exercise variables with prognostic significance when determined at baseline, retain their prognostic relevance after treatment. However, when changes in exercise variables upon treatment are considered, a different set of variables provides prognostic information.

Introduction: It is generally known that positive pressure ventilation is associated with impaired venous return and decreased right ventricular output, in particular in patients with a low right atrial pressure and relative hypovolaemia. Altered lung mechanics have been suggested to impair right ventricular output in COPD, but this relation has never been firmly established in spontaneously breathing patients at rest or during exercise, nor has it been determined whether these cardiopulmonary interactions are influenced by right atrial pressure., Methods: Twenty-one patients with COPD underwent simultaneous measurements of intrathoracic, right atrial and pulmonary artery pressures during spontaneous breathing at rest and during exercise. Intrathoracic pressure and right atrial pressure were used to calculate right atrial filling pressure. Dynamic changes in pulmonary artery pulse pressure during expiration were examined to evaluate changes in right ventricular output., Results: Pulmonary artery pulse pressure decreased up to 40% during expiration reflecting a decrease in stroke volume. The decline in pulse pressure was most prominent in patients with a low right atrial filling pressure. During exercise, a similar decline in pulmonary artery pressure was observed. This could be explained by similar increases in intrathoracic pressure and right atrial pressure during exercise, resulting in an unchanged right atrial filling pressure., Conclusions: We show that in spontaneously breathing COPD patients the pulmonary artery pulse pressure decreases during expiration and that the magnitude of the decline in pulmonary artery pulse pressure is not just a function of intrathoracic pressure, but also depends on right atrial pressure.

Background: To assess a pulmonary function change over time the mass flow sensor and the pneumotachograph are widely used in commercially available instruments. However, the smallest detectable change for both devices has never been compared. Therefore, the aim of this study is to determine the smallest detectable change in vital capacity (VC) and single-breath diffusion parameters measured by mass flow sensor and or pneumotachograph., Method: In 28 healthy pulmonary function technicians VC, transfer factor for carbon monoxide (DLCO) and alveolar volume (VA) was repeatedly (10×) measured. The smallest detectable change was calculated by 1.96 x Standard Error of Measurement ×√2., Findings: The mean (range) of the smallest detectable change measured by mass flow sensor and pneumotachograph respectively, were for VC (in Liter): 0.53 (0.46-0.65); 0.25 (0.17-0.36) (p = 0.04), DLCO (in mmol*kPa-1*min-1): 1.53 (1.26-1.7); 1.18 (0.84-1.39) (p = 0.07), VA (in Liter): 0.66. (0.53-0.82); 0.43 (0.34-0.53) (p = 0.04) and DLCO/VA (in mmol*kPa-1*min-1*L-1): 0.22 (0.19-0.28); 0.19 (0.14-0.22) (p = 0.79)., Conclusions: Smallest detectable significant change in VC and VA as measured by pneumotachograph are smaller than by mass flow sensor. Therefore, the pneumotachograph is the preferred instrument to estimate lung volume change over time in individual patients.

Aims: In pulmonary arterial hypertension (PAH), the exercise-induced increase in stroke volume (SV) is limited by the increase in pulmonary artery pressure. In left heart failure (LHF), systemic arterial pressure increases little during exercise, and the SV increase is limited by the left ventricle itself. These differences might be reflected by a dissimilar SV and heart rate (HR) response to exercise, which could have important therapeutic implications, for example in beta-blocker therapy. Therefore, we tested the hypothesis that SV and HR responses during exercise are different between PAH and LHF patients., Methods and Results: We included 28 PAH and 18 LHF patients (recruited from the heart failure unit) matched on a maximal oxygen uptake of <15 mL/kg/min, who were referred to our Pulmonary Function Department between 2000 and 2008 for a maximal cardio-pulmonary exercise test. Only patients who had not been exposed to beta-blockers were included. Pulmonary arterial hypertension and LHF patient groups had equally impaired exercise tolerance (about 42% of predicted) with a maximal oxygen uptake of 0.80 +/- 0.29 and 0.86 +/- 0.19 L/min. The peak SV response to exercise was significantly lower in PAH patients (-14 mL, P = 0.01); this was compensated by a steeper slope of HR relating to oxygen uptake (0.03 beats/mL, P = 0.001)., Conclusion: We conclude that PAH patients have a smaller SV response, but a larger HR response than LHF patients.

The intra-breath technique to measure acetylene absorption offers the possibility to determine augmentation of the pulmonary blood flow per heart beat (Q(C)) as an estimate of the stroke volume response during exercise. However, this method has not been compared with a validated test until now. Therefore, the aim of this study was to compare Q(C) with stroke volume (SV(MRI)) determined by magnetic resonance imaging (MRI) at rest and during exercise in healthy subjects and patients. For this purpose, ten healthy subjects and ten patients with idiopathic pulmonary arterial hypertension (iPAH) with expected impaired stoke volume response during exercise were measured by both methods. Exercise-induced changes in Q(C) and SV(MRI) were correlated in healthy controls (r = 0.75, p < 0.05). Compared to healthy controls, Q(C) increased less during exercise in iPAH patients (11 +/- 17 ml versus 33 +/- 12 ml, p < 0.05). A similar difference in stroke volume response to exercise between the two groups was measured by MRI (-0.6 +/- 8 ml versus 23 +/- 12 ml, p < 0.05, respectively). Hence, intra-breath and MRI measurements showed similar differences in exercise-induced changes in stroke volume between controls and patients. From these results it can be concluded that the intra-breath measurement of acetylene absorption might be of value as a non-invasive tool to estimate stroke volume augmentation during exercise and can detect differences in stroke volume responses between iPAH patients and healthy subjects.