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In order to inform the Athlete Biological Passport (ABP), this study determined whether the elevation in hemoglobin (Hb) following intracellular or extracellular dehydration would trigger an atypical passport finding (ATPF). Seven male and three female volunteers (age: 23 ± 4 y; height: 170 ± 8 cm; body mass: 78 ± 12 kg) were carefully euhydrated (EUH) to determine baseline Hb levels. Volunteers then completed both an exercise-induced sweating dehydration (SW) protocol and a diuretic-induced dehydration (DI) protocol. Dehydration was assessed via body mass changes and Hb was measured via a bench-top automated hematology analyzer. Using the ABP module, the expected baseline range for each individual was determined using EUH trials, and the impact of each dehydration protocol was then assessed in comparison with these thresholds. Volunteers lost on average 3.1% and 3.7% body mass in the SW and DI trials, respectively. While only one subject exceeded the upper threshold following DI dehydration, six additional subjects demonstrated highly unusual ABP profiles; this was not the case for SW. Sweating is not a feasible explanation for elevated Hb during ABP testing; however, recent illness such as secretory diarrhea, which is mimicked by diuretic administration, may be capable of producing elevated Hb in athletes' biological passports.

Coffman, KE, Luippold, AJ, Salgado, RM, Heavens, KR, Caruso, EM, Fulco, CS, and Kenefick, RW. Aerobic exercise performance during load carriage and acute altitude exposure. J Strength Cond Res 34(4): 946-951, 2020-This study quantified the impact of combined load carriage and acute altitude exposure on 5-km running time-trial (TT) performance and self-selected pacing strategy. Furthermore, this study developed a velocity prediction tool (nomogram) for similar aerobic exercise tasks performed under various combinations of altitude and load stress. Nine volunteers (6M/3F, age: 24 ± 7 years, height: 171 ± 6 cm, body mass: 72 ± 7 kg, and V[Combining Dot Above]O2peak: 50.5 ± 5.2 ml·min·kg) completed a randomized, repeated-measures design protocol. Volunteers performed 3 familiarization (FAM) trials at sea level (SL; 250 m) with no-load carriage. Experimental testing included 3 self-paced, blinded 5-km running TT on a treadmill while carrying a 30% body mass external load at SL, moderate altitude (MA; 2000 m), and high altitude (HA; 3000 m). At SL, load carriage resulted in a 36% decrement in 5-km exercise performance in comparison with FAM trials (43 ± 7 vs. 32 ± 3 minutes; p < 0.001). Time required to complete the 5-km distance while carrying an external load was increased by 11% when performed at HA vs. SL (48 ± 7 vs. 43 ± 7 minutes; p = 0.001). TT pace was not different among experimental conditions (load carriage at SL, MA, and HA) until after 1 km of the running distance had been completed. Heart rate was not different among experimental conditions throughout the entire TT (170 ± 17 b·min). These data quantify the anticipated reduction in aerobic exercise performance under various combinations of acute altitude exposure and load carriage conditions. The self-paced running TT approach used presently allowed for development of an altitude-load nomogram for use in recreational, occupational, or military settings.

Acetazolamide (AZ) is a medication commonly used to prevent acute mountain sickness (AMS) during rapid ascent to high altitude. However, it is unclear whether AZ use impairs exercise performance; previous literature regarding this topic is equivocal. The purpose of this study was to evaluate the impact of AZ on time-trial (TT) performance during a 30-h exposure to hypobaric hypoxia equivalent to 3,500-m altitude. Ten men [sea-level peak oxygen consumption (VO2peak): 50.8 ± 6.5 mL·kg−1·min−1; body fat %: 20.6 ± 5.2%] completed 2 30-h exposures at 3,500 m. In a crossover study design, subjects were given 500 mg/day of either AZ or a placebo. Exercise testing was completed 2 h and 24 h after ascent and consisted of 15-min steady-state treadmill walking at 40%–45% sea-level VO2peak, followed by a 2-mile self-paced treadmill TT. AMS was assessed after ~12 h and 22 h at 3,500 m. The incidence of AMS decreased from 40% with placebo to 0% with AZ. Oxygen saturation was higher ( P < 0.05) in AZ versus placebo trials at the end of the TT after 2 h (85 ± 3% vs. 79 ± 3%) and 24 h (86 ± 3% vs. 81 ± 4%). There was no difference in time to complete 2 miles between AZ and PL after 2 h (20.7 ± 3.2 vs. 22.7 ± 5.0 min, P > 0.05) or 24 h (21.5 ± 3.4 vs. 21.1 ± 2.9 min, P > 0.05) of exposure to altitude. Our results suggest that AZ (500 mg/day) does not negatively impact endurance exercise performance at 3,500 m. NEW & NOTEWORTHY To our knowledge, this is the first study to examine the impact of acetazolamide (500 mg/day) versus placebo on self-paced, peak-effort exercise performance using a short-duration exercise test in a hypobaric hypoxic environment with a repeated-measures design. In the present study, acetazolamide did not impact exercise performance after 2-h or 24-h exposure to 3,500-m simulated altitude.

Heat and hypobaric hypoxia independently compromise exercise performance; however, their combined impact on exercise performance has yet to be quantified. This study examined the effects of heat, hypobaric hypoxia, and the combination of these environments on self-paced cycling time trial (TT) performance. Twelve subjects [2 female, 10 male; sea level (SL) peak oxygen consumption (V̇o2peak), 41.5 ± 4.4 mL·kg−1·min−1, mean ± SD] completed 30 min of steady-state cycling exercise (50% SL V̇o2peak), followed by a 15-min self-paced TT in four environmental conditions: SL thermoneutral [SLTN; 250 m, 20°C, 30–50% relative humidity (rh)], SL hot (SLH; 250 m, 35°C, 30% rh), hypobaric hypoxia thermoneutral (HTN; 3,000 m, 20°C, 30–50% rh), and hypobaric hypoxia hot (HH; 3,000 m, 35°C, 30% rh). Performance was assessed by the total work (kJ) completed. TT performance was lower ( P < 0.05) in SLH, HTN, and HH relative to SLTN (−15.4 ± 9.7, −24.1 ± 16.2, and −33.1 ± 13.4 kJ, respectively). Additionally, the total work completed in HTN and HH was lower ( P < 0.05) than that in SLH. In SLH, HTN, and HH, work rate was reduced versus SLTN ( P < 0.05) within the first 3 min of exercise and was consistent for the remainder of the bout. No differences ( P > 0.05) existed for heart rate or Ratings of Perceived Exertion at the end of exercise among conditions. The decrease in self-paced TT performance in the heat and/or hypobaric hypoxia conditions compared with SLTN conditions resulted from a nearly immediate reduction in work rate that may have been regulated by environmentally induced changes in physiological strain and perception of effort in response to TT exercise. NEW & NOTEWORTHY This is the first known study to examine the combined effects of heat and hypobaric hypoxia on short-duration self-paced cycling time trial performance. Regardless of environmental condition, subjects utilized an even work rate for the entire duration of the time trial. The presence of both environmental stressors led to a greater performance impairment than heat or hypobaric hypoxia alone, and the performance decrement stemmed from an early reduction of work rate.

Resting measures of ventilation and gas exchange are impacted by a variety of physiological stressors, such as those resulting from a research intervention or an extreme environment. However, the biological variation of these parameters, an important statistical consideration for identifying a meaningful physiological change, has not been quantified. We performed a retrospective analysis of 21 studies completed by the U.S. Army Research Institute of Environmental Medicine (USARIEM) from 1985 to present, totaling 411 healthy volunteers. First, we determined the intraindividual, interindividual, and analytic coefficients of variation (CVI, CVG, and CVA, respectively) and subsequently the index of individuality and heterogeneity (II and IH, respectively). Second, when deemed appropriate via these outcomes, we defined the accompanying static and dynamic thresholds, beyond which a significant deviation from normal is indicated. End-tidal partial pressure of oxygen (PETO2) and the respiratory exchange ratio (RER) approached the II threshold required to be considered useful in the static assessment of physiological deviations from normal. PETO2 and peripheral oxygen saturation (SpO2) approached the IH threshold required to be considered useful in the dynamic assessment of physiological deviations from normal. This analysis identifies RER and PETO2 as parameters that might be most useful when aiming to identify a meaningful ventilatory change following a research intervention or stressor. Alternatively, other parameters of ventilation and gas exchange, such as PETCO2 and VE, may be less useful for observing an anticipated physiological change.

Extravascular lung water (EVLW) increases in healthy adults upon exposure to high altitude, likely due to increased pulmonary vascular resistance (PVR). Older individuals experience increased PVR during exercise, which may be exacerbated by trekking at high altitude. This study aimed to determine whether EVLW development is greater in older versus younger adults during graded altitude exposure. Fourteen younger (32 ± 6y) and 12 older (58 ± 5y) healthy adults completed an 11-day trek of Mount Kilimanjaro. EVLW was assessed at rest via comet tails prior to the trek in Moshi (950 m), at Shira Camp (3505 m), at Barafu Camp (4837 m), and post-descent. An increase in altitude from Baseline to Barafu tended to increase the proportion of participants with mild EVLW (p = 0.06). A higher proportion of older versus younger individuals tended to show mild EVLW at Barafu (56 vs. 14%, p = 0.06). In conclusion, EVLW formation may be more common in older adults trekking at high altitude. However, the presence of EVLW in older adults was subclinical.

Selecting the most appropriate performance test is critical in detecting the effect of an intervention. In this investigation we 1) used time-trial (TT) performance data to estimate sample size requirements for test selection and 2) demonstrated the differences in statistical power between a repeated-measures ANOVA (RM-ANOVA) and analysis of covariance (ANCOVA) for detecting an effect in parallel group design. A retrospective analysis of six altitude studies was completed, totaling 105 volunteers. We quantified the test-retest reliability [i.e., intraclass correlation coefficient (ICC) and standard error of measurement (SEM)] and then calculated the standardized effect size for a 5–20% change in TT performance. With these outcomes, a power analysis was performed and required sample sizes were compared among performance tests. Relative to TT duration, the 11.2-km run had the lowest between-subject variance, and thus greatest statistical power (i.e., required smallest sample size) to detect a given percent change in performance. However, the 3.2-km run was the most reliable test (ICC: 0.89, SEM: 81 s) and thus better suited to detect the smallest absolute (i.e., seconds) change in performance. When TT durations were similar, a running modality (11.2-km run; ICC: 0.83, SEM: 422 s) was far more reliable than cycling (720-kJ cycle; ICC: 0.77, SEM: 480 s). In all scenarios, the ANCOVA provided greater statistical power than the RM-ANOVA. Our results suggest that running tests (3.2 km and 11.2 km) using ANCOVA analysis provide the greatest likelihood of detecting a significant change in performance response to an intervention, particularly in populations unaccustomed to cycling. NEW & NOTEWORTHY This is the first investigation to utilize time-trial (TT) data from previous studies in simulations to estimate statistical power. We developed an easy-to-use decision aid detailing the required sample size needed to detect a given change in TT performance for the purpose of test selection. Furthermore, our detailed methods can be applied to any scenario in which there is an impact of a stressor and the desire to detect a treatment effect.

Exercise-heat acclimation (EHA) induces adaptations that improve tolerance to heat exposure. Whether adaptations from EHA can also alter responses to hypobaric hypoxia (HH) conditions remains unclear. This study assessed whether EHA can alter time-trial performance and/or incidence of acute mountain sickness (AMS) during HH exposure. Thirteen sea-level (SL) resident men [SL peak oxygen consumption (V̇o2peak) 3.19 ± 0.43 L/min] completed steady-state exercise, followed by a 15-min cycle time trial and assessment of AMS before (HH1; 3,500 m) and after (HH2) an 8-day EHA protocol [120 min; 5 km/h; 2% incline; 40°C and 40% relative humidity (RH)]. EHA induced lower heart rate (HR) and core temperature and plasma volume expansion. Time-trial performance was not different between HH1 and HH2 after 2 h (106.3 ± 23.8 vs. 101.4 ± 23.0 kJ, P = 0.71) or 24 h (107.3 ± 23.4 vs. 106.3 ± 20.8 kJ, P > 0.9). From HH1 to HH2, HR and oxygen saturation, at the end of steady-state exercise and time-trial tests at 2 h and 24 h, were not different ( P > 0.05). Three of 13 volunteers developed AMS during HH1 but not during HH2, whereas a fourth volunteer only developed AMS during HH2. Heat shock protein 70 was not different from HH1 to HH2 at SL [1.9 ± 0.7 vs. 1.8 ± 0.6 normalized integrated intensities (NII), P = 0.97] or after 23 h (1.8 ± 0.4 vs. 1.7 ± 0.5 NII, P = 0.78) at HH. Our results indicate that this EHA protocol had little to no effect—neither beneficial nor detrimental—on exercise performance in HH. EHA may reduce AMS in those who initially developed AMS; however, studies at higher elevations, having higher incidence rates, are needed to confirm our findings.

Summerfield, Douglas T., Kirsten E. Coffman, Bryan J. Taylor, Amine N. Issa, and Bruce D. Johnson. Exhaled nitric oxide changes during acclimatization to high altitude: a descriptive study. High Alt Med Biol. 19:215-220, 2018.This study describes differences in the partial pressures of exhaled nitric oxide (PeNO) between subjects fully acclimatized (ACC) to 5300 m and those who have just arrived to high altitude.PeNO was determined in eight subjects newly exposed and nonacclimatized (non-ACC) to high altitude and compared with that in nine subjects who had ACC to high altitude for 1 month. In addition, systolic pulmonary artery pressure (sPAP) and arterial oxygen saturation (SaOPeNO levels on day 1 were significantly higher in the non-ACC versus ACC cohort (8.7 ± 3.5 vs. 3.9 ± 2.2 nmHg, p = 0.004). As the non-ACC group remained at altitude, PeNO levels fell and were not different when compared with those of the ACC group by day 9 (5.9 ± 2.4 vs. 3.9 ± 2.2 nmHg, p = 0.095). Higher sPAP was correlated with lower PeNO levels in all participants (R = -0.50, p = 0.043). PeNO levels were not correlated with SaOAs individuals acclimatized to high altitude, PeNO levels decreased. Even after acclimatization, PeNO levels continued to play a role in pulmonary vascular tone.

Introduction Pulmonary congestion is a common finding of heart failure (HF), but it remains unclear how pulmonary and heart blood volumes (Vp and Vh, respectively) and extravascular lung water (EVLW) change in stable HF and affect lung function. Methods Fourteen patients with HF (age 68 ± 11 y, LVEF 33 ± 8%) and 12 control subjects (age 65 ± 9 y) were recruited. A pulmonary function test, thoracic computerized tomographic (CT) scan, and contrast perfusion scan were performed. From the thoracic scan, a histogram of CT attenuation of lung tissue was generated and skew, kurtosis, and full-width half-max (FWHM) calculated as surrogates of EVLW. Blood volumes were calculated from the transit time of the contrast through the great vessels of the heart. Results Patients with HF had greater Vp and Vh (Vp 0.55 ± 0.21 L vs 0.41 ± 0.13 L; Vh 0.53 ± 0.33 L vs 0.40 ± 0.15 L) and EVLW (skew 3.2 ± 0.5 vs 3.7 ± 0.7; kurtosis 19.4 ± 6.6 vs 25.9 ± 9.4; FWHM 73 ± 13 HU vs 59 ± 9 HU). Spirometric measures were decreased in HF (percentage of predicted: forced vital capacity 86 ± 17% vs 104 ± 9%; forced expiratory volume in 1 second 83 ± 20% vs 105 ± 11%; maximal mid-expiratory flow 82 ± 42% vs 115 ± 43%). Vp was associated with decreased expiratory flows, and EVLW was associated with decreased lung volumes. Conclusions Congestion in stable patients with HF includes expanded Vp and Vh and increased EVLW associated with reductions in lung volumes and expiratory flows.

High-altitude ascent induces left (LV) and right (RV) ventricular adaptations secondary to hypoxia-related hemodynamic and myocardial alterations. Since cardiopulmonary decrements observed with aging (e.g., decreased LV compliance and increased pulmonary vascular resistance) may limit cardiac plasticity, this study examined myocardial adaptability throughout an 11 day sojourn to 5893 m in young and older-aged trekkers.Echocardiography was performed on 14 young (8 men; 32 ± 5 years) and 13 older-aged (8 men; 59 ± 5 years) subjects on non-trekking days (Day 0: 880 m; Day 3: 3100 m; Day 8: 4800 m; Day 12/post-climb: 880 m). RV systolic pressure (mmHg) was systematically higher in older-aged subjects (p 0.01) with similar progressive increases observed during ascent for young and older subjects, respectively (Day 0: 18 ± 1 vs 20 ± 2; Day 3: 25 ± 2 vs 29 ± 3; Day 8: 30 ± 2 vs 35 ± 2). Estimates of LV filling pressure (E/E') were systematically higher in older subjects (p 0.01) with similar progressive decreases observed during ascent for young and older-aged subjects, respectively (Day 0: 5.6 ± 0.3 vs 6.7 ± 0.5; Day 3: 5.1 ± 0.2 vs 6.1 ± 0.3; Day 8: 4.7 ± 0.3 vs 5.4 ± 0.3). Overall, RV end-diastolic and end-systolic area increased at altitude (p 0.01), while LV end-diastolic and end-systolic volume decreased (p 0.01). However, all RV and LV morphological measures were similar on Day 3 and Day 8 (p 0.05), and returned to baseline post-climb (p 0.05). Excluding mild LV dilatation in some older-aged trekkers on Day 8/Day 12 (p 0.01), altitude-induced morphological and functional adaptations were similar for all trekkers (p 0.05).Altitude-induced myocardial adaptations are chamber specific, secondary to RV and LV hemodynamic alterations. Despite progressive hemodynamic alterations during ascent, morphological and functional cardiac perturbations plateaued, suggesting rapid myocardial adaptation which was mostly comparable in young and older-aged individuals.

Resting measures of ventilation and gas exchange are impacted by a variety of physiological stressors, such as those resulting from a research intervention or an extreme environment. However, the biological variation of these parameters, an important statistical consideration for identifying a meaningful physiological change, has not been quantified.We performed a retrospective analysis of 21 studies completed by the U.S. Army Research Institute of Environmental Medicine (USARIEM) from 1985 to present, totaling 411 healthy volunteers. First, we determined the intraindividual, interindividual, and analytic coefficients of variation (CVEnd-tidal partial pressure of oxygen (PThis analysis identifies RER and P

Alveolar-capillary membrane conductance (D(M,CO)) and pulmonary-capillary blood volume (V(C)) are calculated via lung diffusing capacity for carbon monoxide (DL(CO)) and nitric oxide (DL(NO)) using the single breath, single oxygen tension (single-FiO2) method. However, two calculation parameters, the reaction rate of carbon monoxide with blood (θ(CO)) and the D(M,NO)/D(M,CO) ratio (α-ratio), are controversial. This study systematically determined optimal θ(CO) and α-ratio values to be used in the single-FiO2 method that yielded the most similar D(M,CO) and V(C) values compared to the 'gold-standard' multiple-FiO2 method. Eleven healthy subjects performed single breath DL(CO)/DL(NO) maneuvers at rest and during exercise. D(M,CO) and V(C) were calculated via the single-FiO2 and multiple-FiO2 methods by implementing seven θ(CO) equations and a range of previously reported α-ratios. The RP θ(CO) equation (Reeves, R.B., Park, H.K., 1992. Respiration Physiology 88 1-21) and an α-ratio of 4.0-4.4 yielded DM,CO and VC values that were most similar between methods. The RP θ(CO) equation and an experimental α-ratio should be used in future studies.

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.

The single breath hold maneuver for measuring lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO) incorporates multiple sources of variability. This study examined how changes in intrathoracic pressure, inhalation time, and breath hold time affect DLCO, DLNO, alveolar-capillary membrane conductance (DmCO) and pulmonary capillary blood volume (Vc) at rest and during submaximal exercise. Thirteen healthy subjects (mean ± SD; age = 26 ± 3y) performed duplicate tests at rest and during submaximal exercise. DLCO and Vc were lower with a positive versus negative intrathoracic pressure during the breath hold at rest (DLCO: 22.2 ± 5.5 vs. 22.7 ± 5.5 ml/min/mmHg, p = 0.028; Vc: 46.5 ± 11.6 vs. 48.2 ± 11.7 ml, p = 0.018). However, during exercise, DLCO and Vc were higher with positive versus negative pressure (DLCO: 26.7 ± 5.5 vs. 25.7 ± 5.7 ml/min/mmHg, p = 0.014; Vc: 56.2 ± 12.6 vs. 53.9 ± 13.1 ml, p = 0.039). The inhalation time did not significantly affect DLCO, DLNO, DmCO or Vc. Short breath hold times (4s) may yield high DLNO/DLCO ratios and non-physiologic DmCO values. The single breath hold maneuver is useful for evaluating gas transfer at rest and during exercise, however intrathoracic pressure, inhalation time, and breath hold time should be kept consistent between repeated tests.

Alveolar‐capillary surface area for pulmonary gas exchange falls with aging, causing a reduction in lung diffusing capacity for carbon monoxide (DLCO). However, during exercise additional factors may influence DLCO, including pulmonary blood flow and pulmonary vascular pressures. First, we sought to determine the age‐dependent effect of incremental exercise on pulmonary vascular pressures and DLCO. We also aimed to investigate the dependence of DLCO on pulmonary vascular pressures during exercise via sildenafil administration to reduce pulmonary smooth muscle tone. Nine younger (27 ± 4 years) and nine older (70 ± 3 years) healthy subjects performed seven 5‐min exercise stages at rest, 0 (unloaded), 10, 15, 30, 50, and 70% of peak workload before and after sildenafil. DLCO, cardiac output (Q), and pulmonary artery and wedge pressure (mPAP and mPCWP; subset of participants) were collected at each stage. mPAP was higher (P = 0.029) and DLCO was lower (P = 0.009) throughout exercise in older adults; however, the rate of rise in mPAP and DLCO with increasing Q was not different. A reduction in pulmonary smooth muscle tone via sildenafil administration reduced mPAP, mPCWP, and the transpulmonary gradient (TPG = mPAP–mPCWP) in younger and older subjects (P

In the era of individualized medicine, gaps in knowledge remain about sex-specific risk factors, diagnostic and treatment options that might reduce mortality from cardiovascular disease (CVD) and improve outcomes for both women and men. In this review, contributions of biological mechanisms involving the sex chromosomes and the sex hormones on the cardiovascular system will be discussed in relationship to the female-specific risk factors for CVD: hypertensive disorders of pregnancy, menopause and use of hormonal therapies for contraception and menopausal symptoms. Additionally, sex-specific factors to consider in the differential diagnosis and treatment of four prevalent CVDs (hypertension, stroke, coronary artery disease and congestive heart failure) will be reviewed with emphasis on areas where additional research is needed.

Whether the specific blood transfer conductance for nitric oxide (NO) with hemoglobin (θNO) is finite or infinite is controversial but important in the calculation of alveolar capillary membrane conductance (DmCO) and pulmonary capillary blood volume (VC) from values of lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO). In this review, we discuss the background associated with θNO, explore the resulting values of DmCO and VC when applying either assumption, and investigate the mathematical underpinnings of DmCO and VC calculations. In general, both assumptions yield reasonable rest and exercise DmCO and VC values. However, the finite θNO assumption demonstrates increasing VC, but not DmCO, with submaximal exercise. At relatively high, but physiologic, DLNO/DLCO ratios both assumptions can result in asymptotic behavior for VC values, and under the finite θNO assumption, DmCO values. In conclusion, we feel that the assumptions associated with a finite θNO require further in vivo validation against an established method before widespread research and clinical use.

Aging is associated with deterioration in the structure and function of the pulmonary circulation. We characterized the lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO), and pulmonary-capillary blood volume (Vc) response to discontinuous incremental exercise at 25, 50, 75, and 90% of peak work (Wpeak) in four groups: 1) Young [27 ± 3 yr, maximal oxygen consumption (V̇o2max): 110 ± 18% age predicted]; 2) Young Highly Fit (27 ± 3 yr, V̇o2max: 147 ± 8% age predicted); 3) Old (69 ± 5 yr, V̇o2max: 116 ± 13% age predicted); and 4) Old Highly Fit (65 ± 5 yr, V̇o2max: 162 ± 18% age predicted). At rest and at 90% Wpeak, DLCO, DmCO, and Vc were decreased with age. At 90% Wpeak, DLCO, DmCO, and Vc were greater in Old Highly Fit vs. Old adults. The slope of the DLCO-cardiac output (Q̇) relationship from rest to end exercise at 90% Wpeak was not different between Young, Young Highly Fit, Old, and Old Highly Fit (1.35 vs. 1.44 vs. 1.10 vs. 1.35 mlCO·mmHg−1·liter blood−1, P = 0.388), with no evidence of a plateau in this relationship during exercise; this was also true for DmCO-Q̇ and Vc-Q̇. V̇o2max was positively correlated with 1) DLCO, DmCO, and Vc at rest; and 2) the rest to end exercise change in DLCO, DmCO, and Vc. In conclusion, these data suggest that despite the age-associated deterioration in the structure and function of the pulmonary circulation, expansion of the pulmonary capillary network does not become limited during exercise in healthy individuals regardless of age or cardiorespiratory fitness level. NEW & NOTEWORTHY Healthy aging is a crucial area of research. This article details how differences in age and cardiorespiratory fitness level affect lung diffusing capacity, particularly during high-intensity exercise. We conclude that highly fit older adults do not experience a limit in lung diffusing capacity during high-intensity exercise. Interestingly, however, we found that highly fit older individuals demonstrate greater values of lung diffusing capacity during high-intensity exercise than their less fit age-matched counterparts.

The purpose of this report was to illustrate how thoracic gas compression (TGC) artifact, and differences in air density, may together conflate the interpretation of changes in the forced expiratory flows (FEFs) at high altitude (>2400 m). Twenty‐four adults (10 women; 44 ± 15 year) with normal baseline pulmonary function (>90% predicted) completed a 12‐day sojourn at Mt. Kilimanjaro. Participants were assessed at Moshi (Day 0, 853 m) and at Barafu Camp (Day 9, 4837 m). Typical maximal expiratory flow‐volume (MEFV) curves were obtained in accordance with ATS/ERS guidelines, and were either: (1) left unadjusted; (2) adjusted for TGC by constructing a “maximal perimeter” MEFV curve; or (3) adjusted for both TGC and differences in air density between altitudes. Forced vital capacity (FVC) was lower at Barafu compared with Moshi camp (5.19 ± 1.29 L vs. 5.40 ± 1.45 L, P

Purpose We determined whether well-acclimatized humans have a reserve to recruit pulmonary capillaries in response to exercise at high altitude. Methods At sea level, lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO), and pulmonary capillary blood volume (Vc) were measured at rest before maximal oxygen consumption (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}{\text{O}}_{2\hbox{max} }$$\end{document}V˙O2max) was determined in seven adults. Then, DLCO, DmCO and Vc were measured pre- and post-exhaustive incremental exercise at 5150 m after ~40 days of acclimatization. Results Immediately after exercise at high altitude, there was an increase in group mean DmCO (14 ± 10 %, P = 0.040) with no pre- to post-exercise change in group mean DLCO (46.9 ± 5.8 vs. 50.6 ± 9.6 ml/min/mmHg, P = 0.213) or Vc (151 ± 28 vs. 158 ± 37 ml, P = 0.693). There was, however, a ~20 % increase in DLCO from pre- to post-exercise at high altitude (51.2 ± 0.2 vs. 61.1 ± 0.2 ml/min/mmHg) with a concomitant increase in DmCO (123 ± 2 vs. 156 ± 4 ml/min/mmHg) and Vc (157 ± 3 vs. 180 ± 8 ml) in 2 of the 7 participants. There was a significant positive relationship between the decrease in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}{\text{O}}_{2\hbox{max} }$$\end{document}V˙O2max from sea level to high altitude and the change in DLCO and lung diffusing capacity for nitric oxide (DLNO) from rest to end-exercise at high altitude. Conclusion These data suggest that recruitment of the pulmonary capillaries in response to exercise at high altitude is limited in most well-acclimatized humans but that any such a reserve may be associated with better exercise capacity.