Pulmonary Capillary Blood Volume Research Articles

Chronic e-cigarette use in young adults is associated with reduced cardiopulmonary function at rest and during exercise

E-cigarette aerosols produce contaminant particles that have the potential to impair cardiopulmonary function. However, the current understanding of the impact of e-cigarette use on cardiopulmonary function remains inconclusive. Exercise represents a stress on the cardiopulmonary system and may help identify cardiopulmonary dysfunction in chronic e-cigarette users. Consequently, the purpose of this study was to investigate if e-cigarette users exhibit cardiopulmonary abnormalities under physiological stress of exercise. To further investigate pulmonary vascular responses, the secondary purpose of the study was to examine how diffusing capacity (DLCO), pulmonary capillary blood volume (VC), and membrane diffusing capacity (DM) respond to positional changes, as the transition from the upright to supine position should increase DLCO, VC, and DM, secondarily to increased perfusion pressure. We hypothesized that e-cigarette users would exhibit impaired cardiopulmonary function during exercise and reduced pulmonary vascular responsiveness to postural changes. Six chronic e-cigarette (e-cig) users (age: 24±5yrs, 5±2 years of e-cigarette use) with <5 pack years of traditional cigarette smoking history and six non-smoking controls who were age-, height-, and sex-matched completed two experimental trials. Day 1: Pulmonary function test and cardiopulmonary exercise test. Day 2: multiple fraction of inspired oxygen DLCO technique to quantify DLCO, VC, and DM at rest in the upright and supine positions. Resting pulmonary function was not significantly different between groups. The change in DLCO from upright to supine was significantly lower in e-cig users compared to controls (Control: 7.61±2.32 ml/min/mmHg vs. E-cig: 3.17±2.09 ml/min/mmHg; p=0.01), due to a smaller change in VC ( p=0.03), which suggests reduced pulmonary vascular distention in e-cig users. V̇O2peak was significantly lower in e-cig users compared to controls (Control: 4.4±1.2 L/min vs. E-cig: 2.6 ±0.7 L/min; p=0.01). E-cig users exhibited significantly elevated V̇E/ V̇CO2nadir ( p=0.02) indicating worse ventilatory effciency, and greater dyspnea relative to power output ( p=0.02) compared to controls. Preliminary findings suggest that e-cigarette use is associated with normal resting lung function but reduced pulmonary vascular distensibility. Further, e-cigarette users demonstrate ventilatory ineffciency and greater exertional dyspnea along with exercise intolerance. Canadian Institutes of Health Research. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pulmonary diffusing capacity for carbon monoxide and nitric oxide after COVID-19: A prospective cohort study (the SECURe study).

Many patients exhibit persistently reduced pulmonary diffusing capacity after coronavirus disease 2019 (COVID-19). In this study, dual test gas diffusing capacity for carbon monoxide and nitric oxide (DL,CO,NO) metrics and their relationship to disease severity and physical performance were examined in patients who previously had COVID-19. An initial cohort of 148 patients diagnosed with COVID-19 of all severities between March 2020 and March 2021 had a DL,CO,NO measurement performed using the single-breath method at 5.7months follow-up. All patients with at least one abnormal DL,CO,NO metric (n=87) were revaluated at 12.5months follow-up. The DL,CO,NO was used to provide the pulmonary diffusing capacity for nitric oxide (DL,NO), the pulmonary diffusing capacity for carbon monoxide (DL,CO,5s), the alveolar-capillary membrane diffusing capacity and the pulmonary capillary blood volume. At both 5.7 and 12.5months, physical performance was assessed using a 30 s sit-to-stand test and the 6min walk test. Approximately 60% of patients exhibited a severity-dependent decline in at least one DL,CO,NO metric at 5.7months follow-up. At 12.5months, both DL,NO and DL,CO,5s had returned towards normal but still remained abnormal in two-thirds of the patients. Concurrently, improvements in physical performance were observed, but with no apparent relationship to any DL,CO,NO metric. The severity-dependent decline in DL,NO and DL,CO observed at 5.7months after COVID-19 appears to be reduced consistently at 12.5months follow-up in the majority of patients, despite marked improvements in physical performance.

Pulmonary Capillary Recruitment Is Attenuated Post Left Ventricular Assist Device Implantation

There is limited knowledge of pulmonary physiology and pulmonary function after continuous flow-left ventricular assist device (CF-LVAD) implantation. Therefore, this study investigated whether CF-LVAD influenced pulmonary circulation by assessing pulmonary capillary blood volume and alveolar-capillary conductance in addition to pulmonary function in patients with heart failure. Seventeen patients with severe heart failure who were scheduled for CF-LVAD implantation (HeartMate II, III, Abbott, Abbott Park, IL or Heart Ware, Medtronic, Minneapolis, MN) participated in the study. They underwent pulmonary function testing (measures of lung volumes and flow rates) and unique measures of pulmonary physiology using a rebreathe technique that quantified the diffusing capacity of the lungs for carbon monoxide (DLCO) and diffusing capacity of the lungs for nitric oxide before and 3months after CF-LVAD implantation. After CF-LVAD, pulmonary function was not significantly changed (p >0.05). For lung diffusing capacity, alveolar volume (VA) was not changed (p=0.47), but DLCO was significantly reduced (p=0.04). After correcting for VA, DLCO/VA showed a trend toward reduction (p=0.08). For the alveolar-capillary component, capillary blood volume (Vc) was significantly reduced (p=0.04), and alveolar-capillary membrane conductance trended toward a reduction (p=0.06). However, alveolar-capillary membrane conductance/Vc was not altered (p=0.92). In conclusion, soon after CF-LVAD implantation, Vc is reduced likely because of pulmonary capillary derecruitment, which contributes to the decrease in lung diffusing capacity.

Influence of rapidly oscillating inspired O2 and N2 concentrations on pulmonary vascular function and lung fluid balance in healthy adults.

Introduction: Aircrew may experience rapidly oscillating inspired O2/N2 ratios owing to fluctuations in the on-board oxygen delivery systems (OBOG). Recent investigations suggest these oscillations may contribute to the constellation of physiologic events in aircrew of high-performance aircraft. Therefore, the purpose of this study was to determine whether these "operationally-relevant" environmental challenges may cause decrements in measures of pulmonary vascular physiology. Methods: Thirty healthy participants (Age: 29 ± 5years) were recruited and assigned to one of the three exposures. Participants were instrumented for physiologic monitoring and underwent baseline cardiopulmonary physiology testing (ground level) consisting of a rebreathe method for quantifying pulmonary blood flow (Qc), pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (Dm). Ultrasound was used to quantify "comet tails" (measure of lung fluid balance). After baseline testing, the participants had two 45min exposures to an altitude of 8,000ft where they breathed from gas mixtures alternating between 80/20 and 30/70 O2/N2 ratios at the required frequency (30s, 60s, or 120s), separated by repeat baseline measure. Immediately and 45min after the second exposure, baseline measures were repeated. Results: We observed no changes in Qc, Dm or Vc during the 60s exposures. In response to the 30s oscillation exposure, there was a significantly reduced Qc and Vc at the post-testing period (p = 0.03). Additionally, exposure to the 120s oscillations resulted in a significant decrease in Vc at the recovery testing period and an increase in the Dm/Vc ratio at both the post and recovery period (p < 0.01). Additionally, we observed no changes in the number of comet tails. Conclusion: These data suggest "operationally-relevant" changes in inspired gas concentrations may cause an acute, albeit mild pulmonary vascular derecruitment, reduced distention and/or mild pulmonary-capillary vasoconstriction, without significant changes in lung fluid balance or respiratory gas exchange. The operational relevance remains less clear, particularly in the setting of additional environmental stressors common during flight (e.g., g forces).

A single breath of nitric oxide does not alter pulmonary perfusion pressure.

What is the central question of this study? Is the amount of inhaled nitric oxide (NO) used during a diffusing capacity for inhaled NO manoeuvre sufficient to reduce pulmonary artery systolic pressure (PASP)? What is the main finding and its importance? These findings suggest that a single breath of inhaled NO does not change PASP, and combined with previous correlational work, further validates the use of the diffusing capacity for NO manoeuvre as a technique to determine pulmonary capillary blood volume and membrane diffusing capacity. The measurement of diffusing capacity is an important pulmonary function test to evaluate gas exchange. Using both carbon monoxide and nitric oxide (NO), the diffusing capacity for nitric oxide (DL,NO ) technique allows for the partitioning of capillary blood volume and membrane diffusing capacity. However, inhaled NO is known to dilate pulmonary arterioles in both health and disease and therefore could alter the outcomes that the DL,NO technique aims to quantify. The purpose of the study was to determine if a DL,NO manoeuvre alters pulmonary perfusion pressure. Nine participants completed 12 simulated 10-s breath-hold DL,NO manoeuvres (n=6 placebo inhalations and n=6 with 40ppm NO; order randomized) during which tricuspid regurgitant jet velocity was recorded continuously using Doppler ultrasound to estimate pulmonary artery systolic pressure (PASP) as a surrogate for pulmonary perfusion pressure. The PASP was not different between the placebo and NO conditions (P=0.742). These data indicate that a single DL,NO manoeuvre does not alter PASP and therefore would not be expected to acutely alter pulmonary capillary blood volume or membrane diffusing capacity.

Sex-specific Physiological Responses To Ultramarathon

PURPOSE. Despite a growing body of literature on the physiological response to ultra-marathon, there is a paucity of data in female athletes. This study assessed the female physiological response to ultra-marathon and compared perturbations to a group of race- and performance-matched males. METHODS. Data were examined from a cohort of 53 individuals who contested an ultra-marathon trail race at the Ultra Trail du Mont-Blanc (UTMB®) in 2018/19. Before and within 2-h of the finish, subjects underwent physiological assessments including: Blood sampling (creatine kinase, CK-MB; cardiac troponin I, cTnI; brain natriuretic peptide, BNP, creatinine, Cr); pulmonary function testing (spirometric indices, exhaled NO, diffusing capacities, mouth pressures); and transthoracic ultrasound (lung comet tails, cardiac function). Data from eight female finishers (age = 36.6 ± 6.9 y; finish time = 30:57 ± 11:36 hh:mm) were compared to a group of eight time-matched males (age = 40.3 ± 8.3 y; finish time = 30:46 ± 10:32 hh:mm). RESULTS. Females exhibited significant post-race hematological changes in BNP (25.8 ± 14.6 vs. 140.9 ± 102.7 pg/mL; p = 0.017) and CK-MB (3.3 ± 2.4 vs. 74.6 ± 49.6 IU/L; p = 0.005), whereas males exhibited significant post-race hematological changes in BNP (26.6 ± 17.5 vs. 96.4 ± 51.9 pg/mL; p = 0.007), CK-MB (7.2 ± 3.9 vs. 108.8 ± 37.4 IU/L; p < 0.001), cTnI (0.01 ± 0.01 vs. 0.05 ± 0.05 ng/mL; p = 0.033), and Cr (1.06 ± 0.19 vs. 1.23 ± 0.24 mg/dL; p = 0.014). Post-race peak expiratory flows decreased in both groups; however, only males exhibited reductions in lung diffusing capacities (DLCO = 34.4 ± 5.7 vs. 29.2 ± 6.9 mL/min/mmHg, p = 0.002; DLNO = 179.1 ± 26.2 vs. 152.8 ± 33.4 mL/min/mmHg, p = 0.001) and pulmonary capillary blood volume (77.4 ± 16.7 vs. 57.3 ± 16.1 mL; p < 0.001). Males, but not females, exhibited a significant post-race increase in the number of lung comet tails (2.4 ± 2.2 vs. 8.3 ± 2.7; p = 0.001). CONCLUSION. Participation in an ultra-marathon negatively affects numerous aspects of physiological function but evokes more extensive perturbations in males compared to females with similar race performances.

Right ventricular-pulmonary arterial coupling impairment and exercise capacity in obese adults.

BackgroundObesity-related exercise intolerance may be associated with pulmonary vascular and right ventricular dysfunction. This study tested the hypothesis that decreased pulmonary vascular reserve and right ventricular (RV)-pulmonary arterial (PA) uncoupling contributes to exercise limitation in subjects with obesity.MethodsSeventeen subjects with obesity were matched to normo-weighted healthy controls. All subjects underwent; exercise echocardiography, lung diffusing capacity (DL) for nitric oxide (NO) and carbon monoxide (CO) and an incremental cardiopulmonary exercise test. Cardiac output (Q), PA pressure (PAP) and tricuspid annular plane systolic excursion (TAPSE) were recorded at increasing exercise intensities. Pulmonary vascular reserve was assessed by multipoint mean PAP (mPAP)/Q relationships with more reserve defined by lesser increase in mPAP at increased Q, and RV-PA coupling was assessed by the TAPSE/systolic PAP (sPAP) ratio.ResultsAt rest, subjects with obesity displayed lower TAPSE/sPAP ratios (1.00 ± 0.26 vs. 1.19 ± 0.22 ml/mmHg, P < 0.05), DLCO and pulmonary capillary blood volume (52 ± 11 vs. 64 ± 13 ml, P < 0.01) compared to controls. Exercise was associated with steeper mPAP-Q slopes, decreased TAPSE/sPAP and lower peak O2 uptake (VO2peak). The changes in TAPSE/sPAP at exercise were correlated to the body fat mass (R = 0.39, P = 0.01) and VO2peak (R = 0.44, P < 0.01).ConclusionObesity is associated with a decreased pulmonary vascular and RV-PA coupling reserve which may impair exercise capacity.

Perspectives on the Structure and Function of the Avian Respiratory System: Functional Efficiency Built on Structural Complexity

Among the air-breathing vertebrates, regarding respiratory efficiency, the avian respiratory system rests at the evolutionary zenith. Structurally, it is separated into a lung that serves as a gas exchanger and air sacs that mechanically ventilate the lung continuously and unidirectionally in a caudocranial direction. Largely avascular, the air sacs are delicate, transparent, compliant and capacious air-filled spaces that are not meaningfully involved in gas exchange. The avian lungs are deeply and firmly attached to the vertebrae and the ribs on the dorsolateral aspects, rendering them practically rigid and inflexible. The attachment of the lung to the body wall allowed extreme subdivision of the exchange tissue into minuscule and stable terminal respiratory units, the air capillaries. The process generated a large respiratory surface area in small lungs with low volume density of gas exchange tissue. For the respiratory structures, invariably, thin blood-gas barrier, large respiratory surface area and large pulmonary capillary blood volume are the foremost adaptive structural features that confer large total pulmonary morphometric diffusing capacities of O2. At parabronchial level, the construction and the arrangement of the airway- and the vascular components of the avian lung determine the delivery, the presentation and the exposure of inspired air to capillary blood across the blood-gas barrier. In the avian lung, crosscurrent-, countercurrent- and multicapillary serial arterialization systems that stem from the organization of the structural parts of the lung promote gas exchange. The exceptional respiratory efficiency of the avian respiratory system stems from synergy of morphological properties and physiological processes, means by which O2uptake is optimized and high metabolic states and capacities supported. Given that among the extant animal taxa insects, birds and bats (which accomplished volancy chronologically in that order) possess structurally much different respiratory systems, the avian respiratory system was by no means a prerequisite for evolution of powered flight but was but one of the adaptive solutions to realization of an exceptionally efficient mode of locomotion.

Pulmonary Capillary Recruitment Is Attenuated Post Left Ventricular Assist Device Implantation

Intoduction There is limited knowledge of pulmonary physiology and pulmonary function following continuous flow-left ventricular assist device (CF-LVAD) implantation. Therefore, the present study investigated if CF-LVAD influenced the pulmonary circulation by assessing pulmonary capillary blood volume and alveolar- capillary conductance as well as pulmonary function in heart failure patients. Methods 17 patients with severe HF who were scheduled for CF-LVAD (Heart Mate II® or Heart Ware®) implantation participated in the study. They underwent pulmonary function testing (measures of lung volumes and flow rates) and more unique measures of pulmonary physiology using a rebreathe-technique that quantified the diffusing capacity of the lungs for carbon monoxide and nitric oxide (DLCO and DLNO, respectively) pre and 3 months post CF-LVAD implantation. Results After CF-LVAD, pulmonary function was not significantly changed (p>0.05). For lung diffusing capacity, DLCO was significantly reduced (p=0.04), however, alveolar volume (VA) was not changed (p=0.47). After DLCO was corrected by VA, DLCO/VA demonstrated a trend towards reduction (p=0.08). For the alveolar-capillary component, capillary blood volume (Vc) and alveolar membrane conductance (Dm) were significantly or trended towards a reduction (p<0.04, p=0.06, respectively). However, Dm/Vc was not altered (p=0.92). Conclusions Early post CF LVAD implantation, Vc is reduced likely as a result of pulmonary capillary de-recruitment which contributes to the fall in lung diffusing capacity. There is limited knowledge of pulmonary physiology and pulmonary function following continuous flow-left ventricular assist device (CF-LVAD) implantation. Therefore, the present study investigated if CF-LVAD influenced the pulmonary circulation by assessing pulmonary capillary blood volume and alveolar- capillary conductance as well as pulmonary function in heart failure patients. 17 patients with severe HF who were scheduled for CF-LVAD (Heart Mate II® or Heart Ware®) implantation participated in the study. They underwent pulmonary function testing (measures of lung volumes and flow rates) and more unique measures of pulmonary physiology using a rebreathe-technique that quantified the diffusing capacity of the lungs for carbon monoxide and nitric oxide (DLCO and DLNO, respectively) pre and 3 months post CF-LVAD implantation. After CF-LVAD, pulmonary function was not significantly changed (p>0.05). For lung diffusing capacity, DLCO was significantly reduced (p=0.04), however, alveolar volume (VA) was not changed (p=0.47). After DLCO was corrected by VA, DLCO/VA demonstrated a trend towards reduction (p=0.08). For the alveolar-capillary component, capillary blood volume (Vc) and alveolar membrane conductance (Dm) were significantly or trended towards a reduction (p<0.04, p=0.06, respectively). However, Dm/Vc was not altered (p=0.92). Early post CF LVAD implantation, Vc is reduced likely as a result of pulmonary capillary de-recruitment which contributes to the fall in lung diffusing capacity.

Development of lung diffusion to adulthood following extremely preterm birth.

BackgroundGas exchange in extremely preterm (EP) infants must take place in fetal lungs. Childhood lung diffusing capacity of the lung for carbon monoxide (DLCO) is reduced; however, longitudinal development has not been investigated. We describe the growth of DLCO and its subcomponents to adulthood in EP compared with term-born subjects.MethodsTwo area-based cohorts born at gestational age ≤28 weeks or birthweight ≤1000 g in 1982–1985 (n=48) and 1991–1992 (n=35) were examined twice, at ages 18 and 25 years and 10 and 18 years, respectively, and compared with matched term-born controls. Single-breath DLCO was measured at two oxygen pressures, with subcomponents (membrane diffusion (DM) and pulmonary capillary blood volume (VC)) calculated using the Roughton–Forster equation.ResultsAge-, sex- and height-standardised transfer coefficients for carbon monoxide (KCO) and DLCO were reduced in EP compared with term-born subjects, and remained so during puberty and early adulthood (p-values for all time-points and both cohorts ≤0.04), whereas alveolar volume (VA) was similar. Development occurred in parallel to term-born controls, with no signs of pubertal catch-up growth nor decline at age 25 years (p-values for lack of parallelism within cohorts 0.99, 0.65, 0.71, 0.94 and 0.44 for z-DLCO, z-VA, z-KCO, DM and VC, respectively). Split by membrane and blood volume components, findings were less clear; however, membrane diffusion seemed most affected.ConclusionsPulmonary diffusing capacity was reduced in EP compared with term-born subjects, and development from childhood to adulthood tracked in parallel to term-born subjects, with no signs of catch-up growth nor decline at age 25 years.

Exercise hyperventilation and pulmonary gas exchange in chronic thromboembolic pulmonary hypertension: Effects of balloon pulmonary angioplasty

Excessive ventilation (V̇E) and abnormal gas exchange during exercise are features of chronic thromboembolic pulmonary hypertension (CTEPH). In selected CTEPH patients, balloon pulmonary angioplasty (BPA) improves symptoms and exercise capacity. How BPA affects exercise hyperventilation and gas exchange is poorly understood. In this longitudinal observational study, symptom-limited cardiopulmonary exercise tests and carbon monoxide lung diffusion (DLCO) were performed before and after BPA (interval, mean (SD): 3.1 (2.4) months) in 36 CTEPH patients without significant cardiac and/or pulmonary comorbidities. Peak work rate improved by 20% after BPA whilst V̇E at peak did not change despite improved ventilatory efficiency (lower V̇E with respect to CO2 output [V̇CO2]). At the highest identical work rate pre- and post-BPA (75 (30) watts), V̇E and alveolar-arterial oxygen gradient (P(Ai-a)O2) decreased by 17% and 19% after BPA, respectively. The physiological dead space fraction of tidal volume (VD/VT), calculated from measurements of arterial and mixed expired CO2, decreased by 20%. In the meantime, DLCO did not change. The best correlates of P(Ai-a)O2 measured at peak exercise were physiological VD/VT before BPA and DLCO after BPA. Ventilatory efficiency, physiological VD/VT, and pulmonary gas exchange improved after BPA. The fact that DLCO did not change suggests that the pulmonary capillary blood volume and probably the true alveolar dead space were unaffected by BPA. The correlation between DLCO measured before BPA and P(Ai-a)O2 measured after BPA suggests that DLCO may provide an easily accessible marker to predict the response to BPA in terms of pulmonary gas exchange.

Week to week variability of pulmonary capillary blood volume and alveolar membrane diffusing capacity in patients with heart failure

BackgroundAlveolar-capillary membrane diffusing capacity for carbon monoxide (DMCO) and pulmonary capillary volume (Vcap) can be estimated by the multi-step Roughton and Foster (RF, original method from 1957) or the single-step NO–CO double diffusion technique (developed in the 1980s). The latter method implies inherent assumptions. We sought to determine which combination of the alveolar membrane diffusing capacity for nitric oxide (DMNO) to DMCO ratio, an specific conductance of the blood for NO (θNO) and CO (θCO) gave the lowest week-to-week variability in patients with heart failure. Methods44 heart failure patients underwent DMCO and Vcap measurements on three occasions over a ten-week period using both RF and double dilution NO-CO techniques. ResultsWhen using the double diffusing method and applying θNO = infinity, the smallest week-to-week coefficient of variation for DMCO was 10 %. Conversely, the RF method derived DMCO had a much greater week-to-week variability (2x higher coefficient of variation) than the DMCO derived via the NO-CO double dilution technique. The DMCO derived from the double diffusion technique most closely matched the DMCO from the RF method when θNO = infinity and DMCO = DLNO/2.42. The Vcap measured week-to-week was unreliable regardless of the method or constants used. ConclusionsIn heart failure patients, the week-to-week DMCO variability was lowest when using the single-step NO-CO technique. DMCO obtained from double diffusion most closely matched the RF DMCO when DMCO/2.42 and θNO = infinity. Vcap estimation was unreliable with either method.

Relationship Between Lung Diffusion And Exercise Capacity In Heart Failure With Preserved Ejection Fraction

PURPOSE: Patients with heart failure with preserved ejection fraction (HFpEF) have impaired lung diffusion (DL) at rest and during exercise which may contribute to a reduced exercise capacity. However, it is unclear whether these impairments are solely due to alterations in pulmonary hemodynamics or related to other cardiopulmonary factors which may impair oxygen uptake such as the inability to recruit lung surface area. Therefore this study examined simultaneous measurements of DL for carbon monoxide (DLCO) and nitric oxide (DLNO), which allows for partitioning of DL into its alveolar-capillary membrane (Dm) and pulmonary capillary blood volume (Vc) components, to better understand the relationship between exertional changes in lung diffusion and exercise capacity. METHODS: HFpEF patients (N=17, age=62±9y, BMI=36±8kg/m2) undergoing exercise right heart catheterization performed simultaneous rebreathe DLCO/NO tests at rest and during each stage of incremental supine cycling exercise, and membrane conductance (Dm) and pulmonary capillary blood volume (Vc) were calculated. Breath-by-breath pulmonary gas exchange was recorded throughout rest and exercise. RESULTS: All patients were hemodynamically diagnosed with HFpEF (pulmonary capillary wedge pressure >15 at rest and/or >25 mmHg during exercise). Overall lung and alveolar-capillary membrane diffusion increased from rest to peak exercise (DLCO: 11.8±4.0 to 16.2±7.4 ml/min/mmHg, DLNO: 33.1±11.5 to 48.4±21.9 ml/min/mmHg, Dm: 18.9±7.2 to 28.3±13.1 ml/min/mmHg; p’s<0.01). The change in DL was related to exercise capacity (change in DLCO vs. peak VO2: R=0.69, p<0.01, change in DLNO vs. peak VO2: R=0.65, p<0.01) and this was primarily driven by changes in Dm (change in Dm vs. peak VO2: R=0.63, p<0.01) but not Vc (change in Vc vs. peak VO2: R=0.15, p=0.582). CONCLUSIONS: These data highlight that a limited increase in lung diffusion and alveolar-capillary membrane conductance during exercise are associated with a lower VO2 peak in HFpEF patients. In addition to hemodynamic constraints previously reported in HFpEF, an inability to recruit lung surface area during exercise may also contribute to the reduced exercise capacity in these patients.

Pulmonary Capillary Blood Volume And Membrane Conductance In Iraq And Afghanistan Veterans With Deployment-related Exposures

Pulmonary Capillary Blood Volume And Membrane Conductance In Iraq And Afghanistan Veterans With Deployment-related Exposures

The supine position improves but does not normalize the blunted pulmonary capillary blood volume response to exercise in mild COPD.

Patients with mild chronic obstructive pulmonary disease (COPD) demonstrate resting pulmonary vascular dysfunction as well as a blunted pulmonary diffusing capacity (DLCO) and pulmonary capillary blood volume (VC) response to exercise. The transition from the upright to supine position increases central blood volume and perfusion pressure, which may overcome microvascular dysfunction in an otherwise intact alveolar-capillary interface. The present study examined whether the supine position normalized DLCO and VC responses to exercise in mild COPD. Sixteen mild COPD participants and 13 age-, gender-, and height-matched controls completed DLCO maneuvers at rest and during exercise in the upright and supine position. The multiple -DLCO method was used to determine DLCO, VC, and membrane diffusion capacity (DM). All three variables were adjusted for alveolar volume (DLCOAdj, VCAdj, and DMAdj). The supine position reduced alveolar volume similarly in both groups, but oxygen consumption and cardiac output were unaffected. DLCOAdj, DMAdj, and VCAdj were all lower in COPD. These same variables all increased with upright and supine exercise in both groups. DLCOAdj was unaffected by the supine position. VCAdj increased in the supine position similarly in both groups. DMAdj was reduced in the supine position in both groups. While the supine position increased exercise VCAdj in COPD, the increase was of similar magnitude to healthy controls; therefore, exercise VC remained blunted in COPD. The persistent reduction in exercise DLCO and VC when supine suggests that pulmonary vascular destruction is a contributing factor to the blunted DLCO and VC response to exercise in mild COPD.NEW & NOTEWORTHY Patients with mild chronic obstructive pulmonary disease demonstrate a combination of reversible pulmonary microvascular dysfunction and irreversible pulmonary microvascular destruction.

Differences in alveolo-capillary equilibration in healthy subjects on facing O2 demand

Oxygen diffusion across the air-blood barrier in the lung is commensurate with metabolic needs and ideally allows full equilibration between alveolar and blood partial oxygen pressures. We estimated the alveolo-capillary O2 equilibration in 18 healthy subjects at sea level at rest and after exposure to increased O2 demand, including work at sea level and on hypobaric hypoxia exposure at 3840 m (PA ~ 50 mmHg). For each subject we estimated O2 diffusion capacity (DO2), pulmonary capillary blood volume (Vc) and cardiac output (dot{Q}). We derived blood capillary transit time {boldsymbol{(}}{boldsymbol{T}}{boldsymbol{t}}{boldsymbol{=}}frac{{boldsymbol{V}}{boldsymbol{c}}}{dot{{boldsymbol{Q}}}}{boldsymbol{)}} and the time constant of the equilibration process ({boldsymbol{tau }}{boldsymbol{=}}frac{{boldsymbol{beta }}{boldsymbol{V}}{boldsymbol{c}}}{{boldsymbol{D}}{{boldsymbol{O}}}_{{boldsymbol{2}}}}, β being the slope of the hemoglobin dissociation curve). O2 equilibration at the arterial end of the pulmonary capillary was defined as {{bf{L}}}_{{bf{e}}{bf{q}}}{boldsymbol{=}}{{bf{e}}}^{{boldsymbol{-}}frac{{bf{T}}t}{{boldsymbol{tau }}}}. Leq greately differed among subjects in the most demanding O2 condition (work in hypoxia): lack of full equilibration was found to range from 5 to 42% of the alveolo-capillary PO2 gradient at the venous end. The present analysis proves to be sensible enough to highlight inter-individual differences in alveolo-capillary equilibration among healthy subjects.

Early and late effects of remote ischemic preconditioning on spirometry and gas exchange in healthy volunteers

PurposeRemote ischemic preconditioning (RIP) may protect remote organs from ischemia-reperfusion-injury (IRI) in surgical and non-surgical patients. There are few data available on RIP and lung function, especially not in healthy volunteers. The null-hypothesis was tested that RIP does not have an effect on pulmonary function when applied on healthy volunteers that were breathing spontaneously and did not experience any intervention. After approval of the Ethics Committee and informed consent of the study subjects, 28 healthy non-smoking volunteers were included and randomized in either the RIP group (n = 13) or the control group (n = 15). In the RIP group, lower limb ischemia was induced by inflation of a blood pressure cuff to a pressure 20 mmHg above the systolic blood pressure. After five minutes the blood pressure cuff was released for five minutes rest. The procedure was repeated three times resulting in 40 min ischemia and reperfusion. Capillary blood samples were taken, and lung function tests were performed at baseline (T1) and 60 min (T2) and 24 h (T3) after RIP. The control group was treated in the same fashion, but the RIP procedure was replaced by a sham protocol. Results60 min after RIP capillary pO2 decreased significantly and returned to baseline level after 24 h in the RIP group. This did not occur in the control group. Capillary pCO2, variables of lung function tests and pulmonary capillary blood volume remained unchanged throughout the experiment in both groups. ConclusionOxygenation is impaired early after RIP which is possibly induced by transient ventilation-perfusion inequality. No late effects of RIP were observed. The null hypothesis has to be rejected that RIP has no effect on respiratory variables in healthy volunteers.

Pulmonary capillary blood volume response to exercise is diminished in mild chronic obstructive pulmonary disease.

Previous work suggests that mild chronic obstructive pulmonary disease (COPD) patients have greater lung dysfunction than previously appreciated from spirometry alone. There is evidence of pulmonary microvascular dysfunction in mild COPD, which may reduce diffusing capacity (DLCO) and increase ventilatory inefficiency during exercise. The purpose of this study was to determine if DLCO, pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) are diminished during exercise in mild COPD, and whether this is related to ventilatory inefficiency and dyspnea. Seventeen mild COPD patients (FEV1/FVC: 64 ± 4%, FEV1 = 94 ± 11%pred) and 17 age- and sex-matched controls were recruited. Ten moderate COPD patients were also tested for comparison (FEV1 = 66 ± 7%pred). DLCO, Vc, and Dm were determined using the multiple-fraction of inspired oxygen (FIO2) DLCO method at baseline and during steady-state cycle exercise at 40W, 50%, and 80% of V˙O2peak. Using expired gas data, ventilatory inefficiency was assessed by V˙E/V˙CO2. Compared to controls, mild COPD had lower DLCO at baseline and during exercise secondary to diminished Vc (P < 0.05). No difference in Dm was observed between controls and mild COPD at rest or during exercise. Patients with high V˙E/V˙CO2 (i.e. ≥34) had lower Vc and greater dyspnea ratings compared to control at 40W. Moderate COPD patients were unable to increase Vc with increasing exercise intensity, suggesting further pulmonary vascular impairment with increased obstruction severity. Despite relatively minor airflow obstruction, mild COPD patients exhibit a diminished DLCO and capillary blood volume response to exercise, which appears to contribute to ventilatory inefficiency and greater dyspnea.

Age-dependent effects of thoracic and capillary blood volume distribution on pulmonary artery pressure and lungdiffusing capacity.

Aging is associated with pulmonary vascular remodeling and reduced distensibility. We investigated the influence of aging on changes in cardiac output (Q), mean pulmonary artery pressure (mPAP), and lung diffusing capacity in response to alterations in thoracic blood volume. The role of pulmonary smooth muscle tone was also interrogated via pulmonary vasodilation. Nine younger (27 ± 4 years) and nine older (71 ± 4 years) healthy adults reached steady‐state in a Supine (0°), Upright (+20°), or Head‐down (−20°) position in order to alter thoracic blood volume. In each position, echocardiography was performed to calculate mPAP and Q, and lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO) was assessed. Next, 100 mg sildenafil was administered to reduce pulmonary smooth muscle tone, after which the protocol was repeated. mPAP (P ≤ 0.029) and Q (P ≤ 0.032) were lower in the Upright versus Supine and Head‐down positions, and mPAP was reduced following sildenafil administration (P = 0.019), in older adults only. SV was lower in the Upright versus Supine and Head‐down positions in both younger (P ≤ 0.008) and older (P ≤ 0.003) adults. DLCO and DLNO were not greatly altered by position changes or sildenafil administration. However, the DLNO/DLCO ratio was lower in the Supine and/or Head‐down positions (P ≤ 0.05), but higher following sildenafil administration (P ≤ 0.007), in both younger and older adults. In conclusion, older adults experience greater cardiopulmonary alterations following thoracic blood volume changes, and pulmonary smooth muscle tone plays a role in resting mPAP in older adults only. Furthermore, mPAP is an important determinant of pulmonary capillary blood volume distribution (DLNO/DLCO), regardless of age.

Acute effects of combined exercise and oscillatory positive expiratory pressure therapy on sputum properties and lung diffusing capacity in cystic fibrosis: a randomized, controlled, crossover trial

BackgroundRegular airway clearance by chest physiotherapy and/or exercise is critical to lung health in cystic fibrosis (CF). Combination of cycling exercise and chest physiotherapy using the Flutter® device on sputum properties has not yet been investigated.MethodsThis prospective, randomized crossover study compared a single bout of continuous cycling exercise at moderate intensity (experiment A, control condition) vs a combination of interval cycling exercise plus Flutter® (experiment B). Sputum properties (viscoelasticity, yield stress, solids content, spinnability, and ease of sputum expectoration), pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) were assessed at rest, directly and 45 min post-exercise (recovery) at 2 consecutive visits. Primary outcome was change in sputum viscoelasticity (G’, storage modulus; G”, loss modulus) over a broad frequency range (0.1–100 rad.s− 1).Results15 adults with CF (FEV1range 24–94% predicted) completed all experiments. No consistent differences between experiments were observed for G’ and G” and other sputum properties, except for ease of sputum expectoration during recovery favoring experiment A. DLNO, DLCO, alveolar volume (VA) and pulmonary capillary blood volume (Vcap) increased during experiment A, while DLCO and Vcap increased during experiment B (all P < 0.05). We found no differences in absolute changes in pulmonary diffusing capacity and its components between experiments, except a higher VA immediately post-exercise favoring experiment A (P = 0.032).ConclusionsThe additional use of the Flutter® to moderate intensity interval cycling exercise has no measurable effect on the viscoelastic properties of sputum compared to moderate intensity continuous cycling alone. Elevations in diffusing capacity represent an acute exercise-induced effect not sustained post-exercise.Trial registrationClinicalTrials.gov; No.: NCT02750722; URL: clinical.trials.gov; Registration date: April 25th, 2016.