Johnson, Bruce D.

Introduction Ultra-marathon races present a prolonged cardiopulmonary physiological stress but the magnitude, persistence, and impact of race environment on respiratory function are incompletely understood. The aim of this study is to observe the effect of ultra-marathon trail races on both lung function and airway impedance. Methods Fifty-seven individuals (49/8, M/F) participated in either the Courmayeur-Champex-Chamonix (CCC ® , 101.5km), Ultra Trail du Mont-Blanc (UMTB ® , 171.5 km), or the Hong Kong 100 (HK, 100 km) races. Participant demographics were measured pre-race and included: age (40.7±10.3 yrs); height (175.5±7.1 cm), body mass (69.7±8.3 kg). Spirometry, airway impedance (via forced oscillation technique, FOT), maximal inspiratory (MIP) and expiratory pressure (MEP), and exhaled nitric oxide (ExNO) were assessed before, immediately (18–4 hours after), and 188–24 hours post-race. Mixed effects analysis with Dunnett’s post-hoc correction were conducted to evaluate the effects of race and time. Results Results demonstrated significant effects of time for: forced vital capacity (FVC), forced expiratory flow over one second (FEV 1 ), peak expiratory flow (PEF), forced expiratory flow between 25-75% (FEF25-75), forced expiratory flow at 25% and at 50% (FEF 25 and FEF 50 , respectively), MIP, MEP, airway reactance (X) at all frequencies from FOT (X 5 , X 11 , X 19 ), respiratory rate, and ExNO (all p <0.05). A significant effect of race was also observed for ExNO ( p =0.002). Discussion Findings indicate declines in lung function and airway impedance immediately after ultra-marathon races, some of which, persisted up to 24 hours post-race. Further investigations are required to better understand the etiology of changes in lung function following ultra-endurance events.

Abstract Brief inhalation of carbon dioxide (CO 2 ) has been proposed to counteract transient hypocapnia by enhancing oxygen unloading, vasodilation, and sympathetic modulation. Despite these potential ergogenic mechanisms, CO 2 has rarely been investigated in the exercise context. The present study investigated whether brief CO 2 inhalation (iCO 2 ) influences performance and recovery during high‐intensity interval exercise. Nine healthy adults completed two randomized, single‐blinded crossover trials of repeated cycling intervals at 85% peak work rate until volitional exhaustion or cadence dropped below 60 rpm, with a minimum 2‐min interval duration required and 3‐min active recovery between bouts. Participants inhaled 5% CO 2 or room air (15 breaths) before and after each exercise bout. Gas exchange, cardiovascular responses, and perceived exertion were assessed. Total exercise time was similar between trials; however, participants completed more intervals with iCO 2 . During the first interval, iCO 2 increased exercise duration and VO 2 . At matched exercise time, perceived exertion and dyspnea were lower with iCO 2 . During recovery, systolic blood pressure was lower and heart rate was higher following iCO 2 . Brief iCO 2 improved first‐interval performance, altered cardiovascular recovery, and reduced perceptual strain but did not extend overall exercise duration. These findings suggest iCO 2 may transiently modulate tolerance and autonomic‐vascular responses during high‐intensity interval exercise.

Background: Exhaled volatile organic compounds (VOCs) can provide insight into various physiological and metabolic processes. Aim: The purpose of this study was to determine if exhaled VOCs would differ across disease severity in heart failure (HF) patients. Methods: We recruited 62 individuals who were classified as healthy control (CTL), admissions with fluid overload (DHF), NYHA class I-II or NYHA class II-III. Breath samples were collected using the ReCIVA Breath Sampler (Owlstone Medical Ltd) and analyzed using mass spectrometry and gas chromatography. Typical clinical characteristics were documented at the time of exhaled breath collection. Results: Data were obtained on 16 CTL, 21 DHF, 15 NYHA I-II and 10 NYHA II-III (characteristics shown in Table). For the HF groups, DHF, NYHA I-II and NYHA II-III, the %HPEFF were 32, 63 and 63% respectively. Regarding exhaled VOCs, we observed a stepwise increase in VOCs potentially linked to lipid peroxidation or fatty acid metabolism, such as pent-3-en-2-one, 2-pentanone, and 4-heptanone, as disease severity worsened. A similar trend was seen for sulphur containing compounds (methyl propyl sulfide, allyl methyl sulfide and 1(methyl thiol)-1 propene)), potentially providing insight into impaired hepatic or renal clearance in more advanced HF. The level of methyl pyruvate on breath also rose with increasing disease severity, which may reflect altered energy metabolism. Finally, gut microbiome-related VOCs (acetoin, 2,3-butanediol, and butyric anhydride) increased across severity groups, potentially reflecting dysbiosis in advanced disease. Conclusions: In a small pilot study aiming to identify potential exhaled breath biomarkers in HF, we observed significant differences in VOCs across disease severity. These compounds have been linked to lipid peroxidation, energy metabolism, liver and kidney function as well as microbial fermentation and short-chain fatty acid metabolism. Collectively, these data demonstrate the ability of breath omics to potentially stratify disease severity and provide additional biological insights into HF pathophysiology. Larger studies are needed to determine whether a breath biomarker panel could be established to quantify disease severity and predict decompensation risk in HF.

Abstract Rationale: Volatile organic compounds (VOCs) in exhaled breath change significantly after ultramarathons and could help monitor athletes’ physiological status to optimize training. While VOCs can reflect metabolic changes, the connection between VOCs and clinical blood and respiratory data remains unknown. In this study, we investigated how breath VOCs are linked to clinical variables that reflect the cardiovascular and respiratory system. Methods: Correlation analysis was performed between respiratory data collected in pre- and post-race samples from 24 runners who participated in the 2019 Ultra-Trail du Mont Blanc (UTMB®) ultra-marathon. Correlation analysis was then performed between these clinical data and previously published breath VOC data collected from the same individuals. Results: Clinical data indicated a slight decrease in runner's lung function post-race. Interestingly, in post-race samples, respiratory parameters vital capacity (VC) and forced expiratory volume in one second (FEV1) formed a moderate positive correlation with 2,3-butanediol (r = 0.53, r = 0.63, respectively), a compound produced by bacterial metabolism. We hypothesize that production of 2,3-butanediol results from the effect of exhaustive exercise on the gut microbiome, which may provide protection to ameliorate lung injury. Additionally, a strengthened correlation from moderate (r = 0.5 – 0.7) to strong (r > 0.7) between VC and FEV1 (r = 0.67 to r = 0.84), forced vital capacity (FVC) and maximal expiratory pressure (MEP) (r = 0.57 to r = 0.75), was observed from pre-race to post-race samples. Finally, FEV1 and MEP shifted from no correlation (r < 0.5) in pre-race to a strong correlation (r = 0.73) in post-race. Conclusion: The strengthened correlation between respiratory data in post-race samples suggests that the gut microbiome, under the effect of exercise, may have an indirect impact on both lung function and respiratory muscle function changes. Our findings support the notion that there is an intricate relationship between exhaustive exercise, altered gut microbiome activity, and lung function, and together they can influence athlete performance.

Abstract Rationale: Heart failure (HF) is often characterized by elevated left ventricular filling pressures (LVFP) and pulmonary congestion. However, LVFP may not always predict congestion. Pulmonary congestion can be quantified by computed tomography (CT) imaging. We hypothesized that extravascular lung water quantified by CT may differ in HF groups such as HF with preserved ejection fraction (HFpEF) vs HF with reduced ejection fraction (HFrEF), inpatients with acute decompensated heart failure (ADHF) vs stable and this would be related to echocardiography (echo) derived estimates of LVFP. Methods: We enrolled and studied 83 patients with HF who were either admitted or had a clinic visit at Mayo Clinic, Rochester, MN from May 2018 through March 2019. All subjects underwent comprehensive echo and supine thoracic CT scans. CT lung fluid was quantified and reported as proportion (%) of total lung volume. CT attenuation in lung tissue was also measured. LVFP was evaluated according to standardized echo diagnostic algorithms. Patients were stratified based on clinical diagnosis of HF as inpatients with HFpEF (n=26, 75.6±8.5yrs, M=50%, BMI=36.2±8.9kg/m2) inpatients with HFrEF (n=33, 75.6±14yrs, M=79%, BMI=31.1±9.1kg/m2), inpatients with ADHF (n=14, 72.6±14.5yrs, m=64.2%, BMI= 32.2±7.6Kg/m2) and stable outpatient HF controls (n=10, 65±13 yrs, m=90%, BMI= 29.5±5.2Kg/m2). All four groups were compared using one-way ANOVA followed by a post-hoc analysis. A correlation between lung fluid % and LVFP was performed using Spearman's correlation test. Results: When HF groups were compared according to CT % lung fluid, significant differences were found between HF groups (p=0.004). Post-hoc analysis revealed a significant difference in % lung fluid as HFrEF group had higher mean value in % lung fluid compared to HF control group (p=0.004). Similarly, ADHF group had higher mean % lung fluid compared to HF control group (p= 0.007). However, we found no correlation between LVFP and % lung fluid. The rightward shift in CT attenuation for HFpEF, HFrEF, and ADHF subjects, as displayed in figure 1, suggests greater levels of % lung water in these subjects compared to controls. Conclusion: These data suggest that CT measures of lung water differ in subgroups of HF patients and may not correlate with LVFP.

AbstractAimWe investigated whether a commercial bi‐level positive airway pressure (BPAP) device, would improve peripheral oxygen saturation (SpO2) during recreational aviation up to 12,500 feet without supplemental oxygen. Ten adults with recreational flight experience (age:47 ± 14; female = 5) completed a standardized flight profile in an unpressurised aircraft, involving randomized crossover design at 8,000 feet and 12,500 feet with BPAP or control. SpO2, middle cerebral artery velocity (MCAv), heart rate (HR), respiratory rate (RR), and relative tidal volume (TV) index were measured continuously. Psychomotor vigilance test (3‐min) assessed reaction time halfway through taxi and altitude stages. Altitude significantly (p < 0.05) decreased mean SpO2, MCAv, and RR, and increased TV index and HR. There was no effect of altitude (p > 0.05) on reaction time. BPAP increased mean SpO2 at 8,000 feet [Control: 92 ± 1%; BPAP: 94 ± 2%; mean difference (MD) = 2 ± 2%; p = 0.002] and 12,500 feet [Control: 86 ± 4%; BPAP: 89 ± 4%; MD = 2 ± 3%; p = 0.013]. BPAP lowered MCAv at 8,000 feet [Control: 53 ± 10 cm/s; BPAP: 50 ± 9 cm/s; MD = ‐3 ± 2 cm/s; p = 0.001] and 12,500 feet [Control: 52 ± 10 cm/s; BPAP: 50 ± 8 cm/s; MD = ‐2 ± 3 cm/s; p = 0.041]. BPAP increased TV index at 8,000 feet (Control: 6.6 ± 1.3; BPAP:8.1 ± 1.8; MD = 1.9 ± 0.8; p < 0.001) but not 12,500 feet, without effect on RR or reaction time. This study provides preliminary results that BPAP may improve mean SpO2 for recreational aviators up to 12,500 feet without supplemental oxygen.

ABSTRACT Introduction Endurance exercise at altitude can increase cardiac output and pulmonary vascular pressure to levels that may exceed the stress tolerability of the alveolar–capillary unit. This study examined the effect of ultramarathon trail racing at different altitudes (ranging from <1000 m to between 1500 and 2700 m) on alveolar–capillary recruitment and lung diffusion. Methods Cardiac and lung function were examined before and after an ultramarathon in 67 runners (age: 41 ± 9 yr, body mass index: 23 ± 2 kg·m −2 , 10 females), and following 12–24 h of recovery in a subset ( n = 27). Cardiac biomarkers (cTnI and BNP) were assessed from whole blood, whereas lung fluid accumulation (comet tails), stroke volume (SV), and cardiac output ( Q ) were quantified via echocardiography. Lung diffusing capacity for carbon monoxide (DLco) and its components, alveolar membrane conductance (Dm) and capillary blood volume (Vc), were determined via a single-breath method at rest and during three stages of submaximal semirecumbent cycling (20, 30, and 40 W). Results Average race time was 25 ± 12 h. From pre- to post-race, there was an increase in cardiac biomarkers (cTnI: 0.04 ± 0.02 vs 0.13 ± 0.03 ng·mL −1 , BNP: 20 ± 2 vs 112 ± 21 pg·mL −1 ; P < 0.01) and lung comet tails (2 ± 1 vs 7 ± 6, P < 0.01), a decrease in resting and exercise SV (76 ± 2 vs 69 ± 2 mL, 40 W: 93 ± 2 vs 88 ± 2 mL; P < 0.01), and an elevation in Q at rest (4.1 ± 0.1 vs 4.6 ± 0.2 L·min −1 , P < 0.01; 40 W: 7.3 ± 0.2 vs 7.4 ± 0.3 L·min −1 , P = 0.899). Resting DLco and Vc decreased after the race ( P < 0.01), whereas Dm was unchanged ( P = 0.465); however, during the three stages of exercise, DLco, Vc, and Dm were all reduced from pre- to post-race (40 W: 36.3 ± 0.9 vs 33.0 ± 0.8 mL·min −1 ·mm Hg −1 , 83 ± 3 vs 73 ± 2 mL, 186 ± 6 vs 170 ± 7 mL·min −1 ·mm Hg −1 , respectively; P < 0.01). When corrected for alveolar volume and Q , DLco decreased from pre- to post-race ( P < 0.01), and changes in DLco were similar for all ultramarathon events ( P > 0.05). Conclusions Competing in an ultramarathon leads to a transient increase in cardiac injury biomarkers, mild lung-fluid accumulation, and impairments in lung diffusion. Reductions in DLco are predominantly caused by a reduced Vc and possible pulmonary capillary de-recruitment at rest. However, impairments in alveolar–capillary recruitment and Dm both contribute to a fall in exertional DLco following an ultramarathon. Perturbations in lung diffusion were evident across a range of event distances and varying environmental exposures.

Introduction: Patients with coronary artery disease (CAD) are at increased risk of cognitive decline. A proposed mechanism is cerebral hypoperfusion related to vascular dysfunction and impaired cerebral blood flow regulation Hypothesis: Patients with CAD will have lower cerebrovascular function than age- and sex-matched controls, assessed as reactivity to a vasodilatory carbon dioxide (CO 2 ) stimulus. Methods: Adults 40-70years old with CAD were recruited on enrollment to a cardiac rehabilitation program following a cardiac event or hospitalization. Age and sex-matched adults without known disease or cardiovascular risk factors were recruited as healthy controls. Cognitive function was assessed by the Fluid Composite of the NIH Cognition Toolbox. Following a familiarization visit, participants underwent a stepped CO 2 protocol (room air, 2% CO 2 , 4% CO 2 , 6% CO 2 ) while continuously measuring middle cerebral artery velocity (MCAv) using transcranial doppler ultrasound, mean arterial pressure (MAP), ventilation (VE), and end-tidal CO 2 . Cerebrovascular conductance (CVCi) was calculated as MCAv/MAP. Cerebrovascular reactivity was calculated as the linear regression slope of CVCi against the change in end-tidal CO 2 . The reactivity of MAP and VE (or chemosensitivity) were also calculated. Results: 19 patients with CAD and 10 healthy controls were recruited ( Table 1 ). Compared with controls, patients with CAD had a 2-fold lower cerebrovascular reactivity (p=0.003), higher MAP reactivity (p<0.05), and a trend towards higher chemosensitivity (p<0.1) ( Table 2 ). There were no group differences in resting CVCi or cognition ( Table 2 ). After adjustment for age and sex, lower cerebrovascular reactivity was associated with lower peak oxygen uptake, diabetes, and smoking history ( Table 3 ). Conclusions: Compared with healthy controls, we report that patients with CAD have significantly lower cerebrovascular function, with no differences in cognitive function.