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Background: The purpose of this study was to determine the influence of changes in cardiac size on total lung volume in patients with chronic heart failure compared to control subjects. Methods: Forty-four patients and age-, gender-, and height-matched control participants were recruited. All participants underwent posteroanterior and lateral chest radiography for volumetric estimations of the total thoracic cavity (TTC), diaphragm, heart, and lungs. To assess the relationship between chronic heart failure severity and cardiac enlargement, patients with chronic heart failure were classified into groups based on New York Heart Association class, as follows: class I and II, n = 26 (group A); class III and IV, n = 18 (group B). Results: There was no difference between the groups for TTC volume (TTCV) [p = 0.56]. Cardiac volumes were significantly different between all groups for both the absolute volumes (p < 0.001) were calculated as a percentage of TTCV (p < 0.001), with the largest cardiac volumes in group B (twice the volume of healthy control subjects). When expressed as a percentage of TTCV, there also was a clear reduction in lung volumes as a function of disease severity (p < 0.001). Conclusions: The present study demonstrates a close relationship between the severity of heart failure and cardiac size. These changes in cardiac size within a closed thoracic cavity may pose significant constraints on the lungs, resulting in reductions in lung volumes that likely play a major role in the restrictive breathing patterns often reported in patients with chronic heart failure. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the limits for repeatability of FEV1, FVC, and PEF during spirometry test sessions in adult outpatients. A retrospective chart review of 18,000 consecutive patients, aged 20 to 90 years, referred to a large outpatient pulmonary function laboratory for testing was performed. Measurements included the differences between the highest and second-highest FVC (dFVC), FEV1 (dFEV1), and PEF (dPEF), from prebronchodilator spirometry, and anthropometric factors. Ninety percent of the patients were able to reproduce FEV1 within 120 ml (6.1%), FVC within 150 ml (5.3%), and PEF within 0.80 L (12%). Patient characteristics, such as sex, age, height, smoking status, and FEV1 (% predicted), had very little effect on repeatability, explaining only 2 to 4% of the variation in repeatability (expressed in milliliters). We conclude that the ability of patients to meet or exceed spirometry repeatability goals does not depend on patient characteristics when testing is performed by experienced personnel. The current American Thoracic Society repeatability goal of 200 ml for FEV1 and FVC may be too lenient. [ABSTRACT FROM AUTHOR]

Study Objective: The impact of stable, chronic heart failure on baseline pulmonary function remains controversial. Confounding influences include previous coronary artery bypass or valve surgery (CABG), history of obesity, stability of disease, and smoking history.Design: To control for some of the variables affecting pulmonary function in patients with chronic heart failure, we analyzed data in four patient groups, all with left ventricular (LV) dysfunction (LV ejection fraction [LVEF] < or =35%): (1) chronic heart failure, nonsmokers, no CABG (n = 78); (2) chronic heart failure, nonsmokers, CABG (n = 46); (3) chronic heart failure, smokers, no CABG (n = 40); and (4) chronic heart failure, smokers, CABG (n = 48). Comparisons were made with age- and gender-matched patients with a history of coronary disease but no LV dysfunction or smoking history (control subjects, n = 112) and to age-predicted norms.Results: Relative to control subjects and percent-predicted values, all groups with chronic heart failure had reduced lung volumes (total lung capacity [TLC] and vital capacity [VC]) and expiratory flows (p < 0.05). CABG had no influence on lung volumes and expiratory flows in smokers, but resulted in a tendency toward a reduced TLC and VC in nonsmokers. Smokers with chronic heart failure had reduced expiratory flows compared to nonsmokers (p < 0.05), indicating an additive effect of smoking. Diffusion capacity of the lung for carbon monoxide (DLCO) was reduced in smokers and in subjects who underwent CABG, but not in patients with chronic heart failure alone. There was no relationship between LV size and pulmonary function in this population, although LV function (cardiac index and stroke volume) was weakly associated with lung volumes and DLCO.Conclusions: We conclude that patients with chronic heart failure have primarily restrictive lung changes with smoking causing a further reduction in expiratory flows. [ABSTRACT FROM AUTHOR]

This study used rich individual-level registry data covering the entire Norwegian population to identify students aged 17-21 who either failed a high-stakes exit exam or who received the lowest passing grade from 2006 to 2018. Propensity score matching on high-quality observed characteristics was utilized to allow meaningful comparisons (N = 18,052, 64% boys). Results showed a 21% increase in odds of receiving a psychological diagnosis among students who failed the exam. Adolescents were at 57% reduced odds of graduating and 44% reduction in odds of enrolling in tertiary education 5 years following the exam. Results suggest that failing a high-stakes exam is associated with mental health issues and therefore may impact adolescents more broadly than captured in educational outcomes., (© 2023 The Authors. Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

Introduction: Poly-tobacco use (PTU), or the concomitant use of two or more nicotine and tobacco products, are a growing public health concern. Adults reporting increased psychological distress (PD) experience profound nicotine and tobacco health-related disparities. Sexual minority (SM) adults report more PTU and higher levels of PD than heterosexuals, yet little is known about patterns of nicotine and tobacco use and its relationship to PD in SM populations., Aims and Methods: The purpose of this study was to investigate sexual identity differences in PD and PTU. Data were drawn from the 2016-2018 National Health Interview Survey (N = 83 017), an annual cross-sectional survey of a nationally representative sample of U.S. adults. PD was assessed using the Kessler Psychological Distress Scale (K6). We fit sex-stratified, weighted, adjusted logistic models to compare PTU and PD by sexual identity., Results: PTU was more prevalent in adults with higher K6 scores. Female adults and SM adults had significantly higher K6 scores and were significantly more likely to experience serious PD when compared to their male and heterosexual counterparts., Conclusions: The current study provides a snapshot of trends in PTU in relation to PD, gender, and sexual identity. Findings suggest higher rates of both PD and PTU in SM adults. Further research examining the mechanisms underlying this disparity is critical to the development of effective intervention and prevention strategies., Implications: Little is known about sex and sexual identity differences in the relations between patterns of tobacco product use and PD. This study is the first to examine the effect of gender and sexual identity on both PD and PTU. SMs reported higher rates of PD and were more likely to be poly-tobacco users. As new ways of engaging nicotine/tobacco continue to proliferate, health risks will endure especially for marginalized populations. An increased understanding of the psychological and social correlates of PTU in SMs is warranted., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: In this study, we aim to analyse the relationship between educational attainment and all-cause mortality of adults in the high-income Asia Pacific region., Design: This study is a comprehensive systematic review and meta-analysis with no language restrictions on searches. Included articles were assessed for study quality and risk of bias using the Joanna Briggs Institute critical appraisal checklists. A random-effects meta-analysis was conducted to evaluate the overall effect of individual level educational attainment on all-cause mortality., Setting: The high-income Asia Pacific Region consisting of Japan, South Korea, Singapore and Brunei Darussalam., Participants: Articles reporting adult all-cause mortality by individual-level education were obtained through searches conducted from 25 November 2019 to 6 December 2019 of the following databases: PubMed, Web of Science, Scopus, EMBASE, Global Health (CAB), EconLit and Sociology Source Ultimate., Primary and Secondary Outcome Measures: Adult all-cause mortality was the primary outcome of interest., Results: Literature searches resulted in 15 345 sources screened for inclusion. A total of 30 articles meeting inclusion criteria with data from the region were included for this review. Individual-level data from 7 studies covering 222 241 individuals were included in the meta-analyses. Results from the meta-analyses showed an overall risk ratio of 2.40 (95% CI 1.74 to 3.31) for primary education and an estimate of 1.29 (95% CI 1.08 to 1.54) for secondary education compared with tertiary education., Conclusion: The results indicate that lower educational attainment is associated with an increase in the risk of all-cause mortality for adults in the high-income Asia Pacific region. This study offers empirical support for the development of policies to reduce health disparities across the educational gradient and universal access to all levels of education., Prospero Registration Number: CRD42020183923., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Racial disparities in New York City (NYC) breast cancer incidence and mortality rates have previously been demonstrated. Disease stage at diagnosis and mortality-to-incidence ratio (MIR) may present better measures of differences in screening and treatment access. Racial/ethnic trends in NYC MIR have not previously been assessed., Methods: Mammogram rates were compared using the NYC Community Health Survey, 2002-2014. Breast cancer diagnosis, stage, and mortality were from the New York State Cancer Registry, 2000-2016. Primary outcomes were MIR, the ratio of age-adjusted mortality to incidence rates, and stage at diagnosis. Joinpoint regression analysis identified significant trends., Results: Mammogram rates in 2002-2014 among Black and Latina women ages 40 and older (79.9% and 78.4%, respectively) were stable and higher than among White (73.6%) and Asian/Pacific-Islander women (70.4%) (P < .0001). There were 82 733 incident cases of breast cancer and 16 225 deaths in 2000-2016. White women had the highest incidence, however, rates among Black, Latina, and Asian/Pacific Islander women significantly increased. Black and Latina women presented with local disease (Stage I) less frequently (53.2%, 57.6%, respectively) than White (62.5%) and Asian/Pacific-Islander women (63.0%). Black women presented with distant disease (Stage IV) more frequently than all other groups (Black 8.7%, Latina 5.8%, White 6.0%, and Asian 4.2%). Black women had the highest breast cancer mortality rate and MIR (Black 0.25, Latina 0.18, White 0.17, and Asian women 0.11)., Conclusions: More advanced disease at diagnosis coupled with a slower decrease in breast cancer mortality among Black and Latina women may partially explain persistent disparities in MIR especially prominent among Black women. Assessment of racial/ethnic differences in screening quality and access to high-quality treatment may help identify areas for targeted interventions to improve equity in breast cancer outcomes., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA. Cancer Medicine published by John Wiley & Sons Ltd.)

Colorectal cancer (CRC) incidence rates are rising in younger Americans and mortality rates are increasing among younger white Americans. We used New York State Cancer Registry data to examine New York City CRC incidence and mortality trends among adults ages 20-54 years by race from 1976 to 2015. Annual percent change (APC) was considered statistically significant at P less than .05 using a two-sided test. CRC incidence increased among those ages 20-49 years, yet blacks had the largest APC of 2.2% (1993-2015; 95% confidence interval [CI] = 1.4% to 3.1%) compared with 0.5% in whites (1976-2015; 95% CI = 0.2% to 0.7%). Among those aged 50-54 years, incidence increased among blacks by 0.8% annually (1976-2015; 95% CI = 0.4% to 1.1%), but not among whites. CRC mortality decreased among both age and race groups. These findings emphasize the value of local registry data to understand trends locally, the importance of timely screening, and the need for clinicians to consider CRC among all patients with compatible signs and symptoms.

Introduction: Burn trauma damages resting cardiac function; however, it is currently unknown if the cardiovascular response to exercise is likewise impaired. We tested the hypothesis that, in children, burn injury lowers cardiac output (Q˙) and stroke volume (SV) during submaximal exercise., Methods: Five children with 49% ± 4% total body surface area (BSA) burned (two female, 11.7 ± 1 yr, 40.4 ± 18 kg, 141.1 ± 9 cm) and eight similar nonburned controls (five female, 12.5 ± 2 yr, 58.0 ± 17 kg, 147.3 ± 12 cm) with comparable exercise capacity (peak oxygen consumption [peak V˙O2]: 31.9 ± 11 vs 36.8 ± 8 mL O2·kg·min, P = 0.39) participated. The exercise protocol entailed a preexercise (pre-EX) rest period followed by 3-min exercise stages at 20 W and 50 W. V˙O2, HR, Q˙ (via nonrebreathing), SV (Q˙/HR), and arteriovenous O2 difference ([a-v]O2diff, Q˙/ V˙O2) were the primary outcome variables., Results: Using a 2-way factorial ANOVA (group [G] × exercise [EX]), we found that Q˙ was approximately 27% lower in the burned than the nonburned group at 20 W of exercise (burned 5.7 ± 1.0 vs nonburned: 7.9 ± 1.8 L·min) and 50 W of exercise (burned 6.9 ± 1.6 vs nonburned 9.2 ± 3.2 L·min) (G-EX interaction, P = 0.012). SV did not change from rest to exercise in burned children but increased by approximately 24% in the nonburned group (main effect for EX, P = 0.046). Neither [a-v] O2diff nor V˙O2 differed between groups at rest or exercise, but HR response to exercise was reduced in the burn group (G-EX interaction, P = 0.004). When normalized to BSA, SV (index) was similar between groups; however, Q˙ (index) remained attenuated in the burned group (G-EX interaction, P < 0.008)., Conclusions: Burned children have an attenuated cardiovascular response to submaximal exercise. Further investigation of hemodynamic function during exercise will provide insights important for cardiovascular rehabilitation in burned children.

It is generally recommended that an esophageal balloon-catheter possess an adequate frequency response up to 15 Hz, such that parameters of respiratory mechanics may be quantified with precision. In our experience, however, we have observed that some commercially available systems do not display an ideal frequency response (<8-10 Hz). We therefore investigated whether the poor frequency response of a commercially available esophageal catheter may be adequately compensated using two numerical techniques: 1) an exponential model correction, and 2) Wiener deconvolution. These two numerical techniques were performed on a commercial balloon-catheter interfaced with 0, 1, and 2 lengths of extension tubing (90 cm each), referred to as configurations L0, L90, and L180, respectively. The frequency response of the balloon-catheter in these configurations was assessed by empirical transfer function analysis, and its "working" range was defined as the frequency beyond which more than 5% amplitude and/or phase distortion was observed. The working frequency range of the uncorrected balloon-catheter extended up to only 10 Hz for L0, and progressively worsened with additional tubing length (L90 = 3 Hz, L180 = 2 Hz). Although both numerical methods of correction adequately enhanced the working frequency range of the balloon-catheter to beyond 25 Hz for all length configurations (L0, L90, and L180), Wiener deconvolution consistently provided more accurate corrections. Our data indicate that Wiener deconvolution provides a superior correction of the balloon-catheter's dynamic response, and is relatively more robust to extensions in catheter tube length compared with the exponential correction method., (Copyright © 2016 the American Physiological Society.)

Heart failure (HF) is often associated with pulmonary congestion, reduced lung function, abnormal gas exchange, and dyspnea. We tested whether pulmonary congestion is associated with expanded vascular beds or an actual increase in extravascular lung water (EVLW) and how airway caliber is affected in stable HF Subsequently we assessed the influence of an inhaled short acting beta agonist (SABA). Thirty-one HF (7F; age, 62 ± 11 years; ht. 175 ± 9 cm; wt. 91 ± 17 kg; LVEF, 28 ± 15%) and 29 controls (11F; age; 56 ± 11 years; ht. 174 ± 8 cm; wt. 77 ± 14 kg) completed the study. Subjects performed PFTs and a chest computed tomography (CT) scan before and after SABA CT measures of attenuation, skew, and kurtosis were obtained from areas of lung tissue to assess EVLW Airway luminal areas and wall thicknesses were also measured : CT tissue density suggested increased EVLW in HF without differences in the ratio of airway wall thickness to luminal area or luminal area to TLC (skew: 2.85 ± 1.08 vs. 2.11 ± 0.79, P < 0.01; Kurtosis: 15.5 ± 9.5 vs. 9.3 ± 5.5 P < 0.01; control vs. HF). PFTs were decreased in HF at baseline (% predicted FVC:101 ± 15% vs. 83 ± 18%, P < 0.01;FEV1:103 ± 15% vs. 82 ± 19%, P < 0.01;FEF25-75: 118 ± 36% vs. 86 ± 36%, P < 0.01; control vs. HF). Airway luminal areas, but not CT measures, were correlated with PFTs at baseline. The SABA cleared EVLW and decreased airway wall thickness but did not change luminal area. Patients with HF had evidence of increased EVLW, but not an expanded bronchial circulation. Airway caliber was maintained relative to controls, despite reductions in lung volume and flow rates. SABA improved lung function, primarily by reducing EVLW., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Functional values of LogSD of the ventilation distribution (σ(V)) have been reported previously, but functional values of LogSD of the perfusion distribution (σ(q)) and the coefficient of correlation between ventilation and perfusion (ρ) have not been measured in humans. Here, we report values for σ(V), σ(q), and ρ obtained from wash-in data for three gases, helium and two soluble gases, acetylene and dimethyl ether. Normal subjects inspired gas containing the test gases, and the concentrations of the gases at end-expiration during the first 10 breaths were measured with the subjects at rest and at increasing levels of exercise. The regional distribution of ventilation and perfusion was described by a bivariate log-normal distribution with parameters σ(V), σ(q), and ρ, and these parameters were evaluated by matching the values of expired gas concentrations calculated for this distribution to the measured values. Values of cardiac output and LogSD ventilation/perfusion (Va/Q) were obtained. At rest, σ(q) is high (1.08 ± 0.12). With the onset of ventilation, σ(q) decreases to 0.85 ± 0.09 but remains higher than σ(V) (0.43 ± 0.09) at all exercise levels. Rho increases to 0.87 ± 0.07, and the value of LogSD Va/Q for light and moderate exercise is primarily the result of the difference between the magnitudes of σ(q) and σ(V). With known values for the parameters, the bivariate distribution describes the comprehensive distribution of ventilation and perfusion that underlies the distribution of the Va/Q ratio.

Patients with heart failure (HF) display numerous derangements in ventilatory function, which together serve to increase the work of breathing (W(b)) during exercise. However, the extent to which the resistive and elastic properties of the respiratory system contribute to the higher W(b) in these patients is unknown. We quantified the resistive and elastic W(b) in patients with stable HF (n = 9; New York Heart Association functional class I-II) and healthy control subjects (n = 9) at standardised levels of minute ventilation (V'(E)) during graded exercise. Dynamic lung compliance was systematically lower for a given level of V'(E) in HF patients than controls (p<0.05). HF patients displayed slightly higher levels of inspiratory elastic W(b) with greater amounts of ventilatory constraint and resistive W(b) than control subjects during exercise (p<0.05). Our data indicates that the higher W(b) in HF patients is primarily due to a greater resistive, rather than elastic, load to breathing. The greater resistive W(b) in these patients probably reflects an increased hysteresivity of the airways and lung tissues. The marginally higher inspiratory elastic W(b) observed in HF patients appears related to a combined decrease in the compliances of the lungs and chest wall. The clinical and physiological implications of our findings are discussed.

Aim: Recent findings have challenged the belief that the cardiac output (CO) and oxygen consumption (VO(2) ) relationship is linear from rest to maximal exercise. The purpose of this study was to determine the CO and stroke volume (SV) response to a range of exercise intensities, 40-100% of VO(2max), during cycling., Methods: Ten well-trained cyclists performed a series of discontinuous exercise bouts to determine the CO and SV vs. VO(2) responses., Results: The rate of increase in CO, relative to VO(2) , during exercise from 40 to 70% of VO(2max) was 4.4 ± 1.4 L L(-1). During exercise at 70-100% of VO(2max) , the rate of increase in CO was reduced to 2.1 ± 0.9 L L(-1) (P = 0.01). Stroke volume during exercise at 80-100% of VO(2max) was reduced by 7% when compared to exercise at 50-70% of VO(2max) (134 ± 5 vs. 143 ± 5 mL per beat, P = 0.02). Whole body arterial-venous O(2) difference increased significantly as intensity increased., Conclusion: The observation that the rate of increase in CO is reduced as exercise intensity increases suggests that cardiovascular performance displays signs of compromised function before maximal VO(2) is reached., (© 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.)

The impact of acute altitude exposure on pulmonary function is variable. A large inter-individual variability in the changes in forced expiratory flows (FEFs) is reported with acute exposure to altitude, which is suggested to represent an interaction between several factors influencing bronchial tone such as changes in gas density, catecholamine stimulation, and mild interstitial edema. This study examined the association between FEF variability, acute mountain sickness (AMS) and various blood markers affecting bronchial tone (endothelin-1, vascular endothelial growth factor (VEGF), catecholamines, angiotensin II) in 102 individuals rapidly transported to the South Pole (2835 m). The mean FEF between 25 and 75% (FEF(25-75)) and blood markers were recorded at sea level and after the second night at altitude. AMS was assessed using Lake Louise questionnaires. FEF(25-75) increased by an average of 12% with changes ranging from -26 to +59% from sea level to altitude. On the second day, AMS incidence was 36% and was higher in individuals with increases in FEF(25-75) (41 vs. 22%, P = 0.05). Ascent to altitude induced an increase in endothelin-1 levels, with greater levels observed in individuals with decreased FEF(25-75). Epinephrine levels increased with ascent to altitude and the response was six times larger in individuals with decreased FEF(25-75). Greater levels of endothelin-1 in individuals with decreased FEF(25-75) suggest a response consistent with pulmonary hypertension and/or mild interstitial edema, while epinephrine may be upregulated in these individuals to clear lung fluid through stimulation of β(2)-adrenergic receptors.

Introduction: Each year, the US Antarctic Program rapidly transports scientists and support personnel from sea level (SL) to the South Pole (SP, 2835 m) providing a unique natural laboratory to quantify the incidence of acute mountain sickness (AMS), patterns of altitude related symptoms and the field effectiveness of acetazolamide in a highly controlled setting. We hypothesized that the combination of rapid ascent (3 hr), accentuated hypobarism (relative to altitude), cold, and immediate exertion would increase altitude illness risk., Methods: Medically screened adults (N = 246, age = 37 ± 11 yr, 30% female, BMI = 26 ± 4 kg/m(2)) were recruited. All underwent SL and SP physiological evaluation, completed Lake Louise symptom questionnaires (LLSQ, to define AMS), and answered additional symptom related questions (eg, exertional dyspnea, mental status, cough, edema and general health), during the 1st week at altitude. Acetazolamide, while not mandatory, was used by 40% of participants., Results: At SP, the barometric pressure resulted in physiological altitudes that approached 3400 m, while T °C averaged -42, humidity 0.03%. Arterial oxygen saturation averaged 89% ± 3%. Overall, 52% developed LLSQ defined AMS. The most common symptoms reported were exertional dyspnea-(87%), sleeping difficulty-(74%), headache-(66%), fatigue-(65%), and dizziness/lightheadedness-(46%). Symptom severity peaked on days 1-2, yet in >20% exertional dyspnea, fatigue and sleep problems persisted through day 7. AMS incidence was similar between those using acetazolamide and those abstaining (51 vs. 52%, P = 0.87). Those who used acetazolamide tended to be older, have less altitude experience, worse symptoms on previous exposures, and less SP experience., Conclusion: The incidence of AMS at SP tended to be higher than previously reports in other geographic locations at similar altitudes. Thus, the SP constitutes a more intense altitude exposure than might be expected considering physical altitude alone. Many symptoms persist, possibly due to extremely cold, arid conditions and the benefits of acetazolamide appeared negligible, though it may have prevented more severe symptoms in higher risk subjects.

Key elements for determining alveolar-capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) from the lung diffusing capacity (Dl) for carbon monoxide (DlCO) or for nitric oxide (DlNO) are the reaction rate of carbon monoxide with hemoglobin (thetaCO) and the DmCO/DlNO relationship (alpha-ratio). Although a range of values have been reported, currently there is no consensus regarding these parameters. The study purpose was to define optimal parameters (thetaCO, alpha-ratio) that would experimentally substantiate calculations of Dm and Vc from the single-inspired O2 tension [inspired fraction of O2 (FiO2)] method relative to the multiple-FiO2 method. Eight healthy men were studied at rest and during moderate exercise (80-W cycle). Dm and Vc were determined by the multiple-FiO2 and single-FiO2 methods (rebreathe technique) and were tabulated by applying previously reported thetaCO equations (both methods) and by varying the alpha-ratio (single-FiO2 method) from 1.90 to 2.50. Values were then compared between methods throughout the examined alpha-ratios. Dm and Vc were critically dependent on the applied thetaCO equation. For the multiple-FiO2 method, Dm was highly variable between thetaCO equations (rest and exercise); the range of Vc was less widespread. For the single-FiO2 method, the thetaCO equation by Reeves and Park (1992) combined with an alpha-ratio between 2.08 and 2.26 gave values for Dm and Vc that most closely matched those from the multiple-FiO2 method and were also physiologically plausible compared with predicted values. We conclude that the parameters used to calculate Dm and Vc values from the single-FiO2 method (using DlCO and DlNO) can significantly influence results and should be evaluated within individual laboratories to obtain optimal values.

The purpose of this study was to compare the repeatability (2.77 multiplied by the within-subject SD)between two different rebreathing protocols on cardiac output ( ˙Q ), pulmonary diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO), and pulmonary capillary blood volume (Vc). This study compared two bag volume protocols [Fixed Bag Volume (FBV) = bag volume fixed at 60% of forced vital capacity; Dynamic Bag Volume (DBV) = bag volume matched to tidal volume at each stage of exercise].Ten females (age = 27±8 yrs; ˙VO2, (peak)=2.5±0.6 L/min had measurements at rest (12%), 52%, 88%, and 100% of ˙VO2, (peak) on two study days. Neither the slope nor intercept of ˙Q vs. ˙VO2 were different between either bag volume protocols. The slope of DLCO vs. ˙Q was the same but the intercept was higher for the FBV protocol. The bag volume affected the slope and the intercept between DLNO vs. ˙Q (p < 0.05).The mean repeatability was similar between both protocols for ˙Q (2.0 vs. 2.3 L/min) and DLCO (3.8 vs.5.9 mL/min/mmHg), regardless of exercise intensity. Increasing exercise intensity made the measurement error worse for Vc and DLNO (p ≤ 0.06). Measurement error was lower for Vc when using the FBV protocol (p = 0.02). Also, the pattern of bag volume used during rebreathing maneuvers affected the relation between DLNO vs. ˙Q more than it affected DLCO vs. ˙Q , or Vc vs. ˙Q. Additionally, the FBV protocol provided less measurement error for Vc compared to the DBV protocol [corrected]., (Copyright 2010 Elsevier B.V. All rights reserved.)

We evaluated the influence of age and sex on the relationship between central and peripheral vasodilatory capacity. Healthy men (19 younger, 12 older) and women (17 younger, 17 older) performed treadmill and knee extensor exercise to fatigue on separate days while maximal cardiac output (Q, acetylene uptake) and peak femoral blood flow (FBF, Doppler ultrasound) were measured, respectively. Maximal Q was reduced with age similarly in men (Y: 23.6 +/- 2.7 vs. O: 17.4 +/- 3.5 l/min; P < 0.05) and women (Y: 17.7 +/- 1.9 vs. O: 12.3 +/- 1.6 l/min; P < 0.05). Peak FBF was similar between younger (Y) and older (O) men (Y: 2.1 +/- 0.5 vs. O: 2.2 +/- 0.7 l/min) but was lower in older women compared with younger women (Y: 1.9 +/- 0.4 vs. O: 1.4 +/- 0.4 l/min; P < 0.05). Maximal Q was positively correlated with peak FBF in men (Y: r = 0.55, O: r = 0.74; P < 0.05) but not in women (Y: r = 0.34, O: r = 0.10). Normalization of cardiac output to appendicular muscle mass and peak FBF to quadriceps mass reduced the correlation between these variables in younger men (r = 0.30), but the significant association remained in older men (r = 0.68; P < 0.05), with no change in women. These data suggest that 1) aerobic capacity is associated with peripheral vascular reserve in men but not women, and 2) aging is accompanied by a more pronounced sex difference in this relationship.

Circulation time (the transit time for a bolus of blood through the circulatory system) is a potential index of cardiac dysfunction in chronic heart failure (HF). In healthy subjects, circulation time falls as cardiac output (Q) rises during exercise, however little is known about this index in HF. In this study we examined the relationship between lung-to-lung circulation time (LLCT) during exercise in ten HF (53 +/- 14 year, resting ejection fraction = 23 +/- 8%) and control subjects (51 +/- 18 year). We hypothesized that HF patients would have slower LLCT times during exercise when compared to control subjects. Each subject completed two identical incremental exercise tests during which LLCT was measured in one test and Q measured in the other. Q was measured using the open circuit C(2)H(2) washin technique and circulation time measured using an inert gas technique. In HF patients and control subjects, LLCT decreased and Q increased from rest (HF:LLCT = 53.6 +/- 8.2 s, Q = 4.3 +/- 1.1 l min(-1); control: LLCT = 55.3 +/- 10.9 s, Q = 4.5 +/- 0.5 l min(-1)) to peak exercise (HF:LLCT = 20.6 +/- 3.9* s, Q = 8.8 +/- 2.5* l min(-1); control:LLCT = 14.9 +/- 2.4 s, Q = 16.5 +/- 1.2 l min(-1); *P < 0.05 vs control). LLCT was significantly (P < 0.05) slower for the HF group when compared to the control group during submaximal exercise and at peak exercise. However, at a fixed Q the HF subjects had a faster LLCT. We hypothesize that the faster LLCT at a fixed Q for HF patients, may be the result of a more intensive peripheral vasoconstriction of non-active beds and a better redistribution of blood flow.

This study examined the relationship between airway blood flow (Q(aw)), ventilation (V(E)) and cardiac output (Q(tot)) during exercise in healthy humans (n=12, mean age 34+/-11 yr). Q(aw) was estimated from the uptake of the soluble gas dimethyl ether while V(E) and Q(tot) were measured using open circuit spirometry. Measurements were made prior to and during exercise at 34+/-5 W (Load 1) and 68+/-10 W (Load 2) and following the cessation of exercise (recovery). Q(aw) increased in a stepwise fashion (P<0.05) from rest (52.8+/-19.5 microl min(-1) ml(-1)) to exercise at Load 1 (67.0+/-20.3 microl min(-1) ml(-1)) and Load 2 (84.0+/-22.9 microl min(-1) ml(-1)) before returning to pre-exercise levels in recovery (51.7+/-13.2 microl min(-1) ml(-1)). Q(aw) was positively correlated with both Q(tot) (r=0.58, P<0.01) and V(E) (r=0.50, P<0.01). These results demonstrate that the increase in Q(aw) is linked to an exercise related increase in both Q(tot) and V(E) and may be necessary to prevent excessive airway cooling and drying.

Background: Peak exercise capacity (VO2peak) is a measure of the severity of chronic heart failure (CHF); however, few indices of resting cardiopulmonary function have been shown to predict VO2peak. A prolonged circulation time has been suggested as an index of increased severity of CHF. The aim of this study was to investigate the relationship between resting lung-to-lung circulation time (LLCT) and VO2peak in CHF., Methods and Results: Thirty CHF patients (59 +/- 13 years, New York Heart Association: 1.9 +/- 1.0) undertook the study. Each subject completed resting pulmonary and echocardiography measures and an incremental exercise test. LLCT was measured using the reappearance of end-tidal acetylene (P(ET),C2H2) after a single inhalation. Univariate and multivariate stepwise linear regression was used to determine the predictors of VO2peak. Univariate correlates of VO2peak (group mean 1.53 +/- 0.44 L/min(-1)) included LLCT (r = -0.75), inspiratory capacity (r = 0.41), ejection fraction (r = 0.33), peak early flow velocity (r = -0.39), and the ratio of early to late flow velocity (r = -0.31). LLCT was the only independent predictor where VO(2peak) = 3.923-0.045 (LLCT); r2 = 54%., Conclusions: These results suggest that resting LLCT determined using the soluble inert gas technique represents a simple, noninvasive method that provides additional information regarding exercise capacity in CHF.

The beta2-adrenergic receptors (beta2AR) play an important role in lung fluid regulation. Previous research has suggested that subjects homozygous for arginine at amino acid 16 of the beta2AR (Arg16) may have attenuated receptor function relative to subjects homozygous for glycine at the same amino acid (Gly16). We sought to determine if the Arg16Gly polymorphism of the beta2AR influenced lung fluid balance in response to rapid saline infusion. We hypothesized that subjects homozygous for Arg at amino acid 16 (n=14) would have greater lung fluid accumulation compared with those homozygous for Gly (n=15) following a rapid intravenous infusion of isotonic saline (30 ml/kg over 17 min). Changes in lung fluid were determined using measures of lung density and tissue volume (computerized tomography imaging) and measures of pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (DM, determined from the simultaneous assessment of the diffusing capacities of the lungs for carbon monoxide and nitric oxide). The saline infusion resulted in elevated catecholamines in both genotype groups (Arg16 283+/-117% vs. Gly16 252+/-118%, P>0.05). The Arg16 group had a larger decrease in DM and increase in lung tissue volume and lung water after saline infusion relative to the Gly16 group (DM -13+/-14 vs. 0+/-26%, P<0.05; lung tissue volume 13+/-11 vs. 3+/-11% and lung water +90+/-66 vs. +48+/-144 ml, P=0.10, P<0.05, for Arg vs. Gly16, respectively, means+/-SD). These data suggest that subjects homozygous for Arg at amino acid 16 of the beta2AR have a greater susceptibility for lung fluid accumulation relative to subjects homozygous for Gly at this position.

Xenon computed tomography (Xe-CT) is used to estimate regional ventilation by measuring regional attenuation changes over multiple breaths while rebreathing a constant Xe concentration ([Xe]). Xe-CT has potential human applications, although anesthetic properties limit [Xe] to

Background: This study examined the influence of increased cardiac size on maximal lung volumes, forced expiratory airflows, and the diffusing capacity of the lungs in heart failure (HF) patients compared with controls., Methods and Results: Forty-one HF patients of New York Heart Association (NYHA) class: Group A = class I/II (n = 26) and Group B = class III/IV (n = 15) and an equal number matched controls (CTL) were recruited. Participants underwent echocardiography, spirometry, and posteroanterior and lateral chest radiographic evaluation (RAD) for volumetric estimation of the total thoracic cavity (TTC), diaphragm, heart, and lungs. Analysis of variance demonstrated no difference between groups for TTC volume (P = .63). RAD cardiac volumes (% TTC volume) were significantly different among all groups (P < .001). Echocardiograms determined left ventricular mass was elevated in the HF groups compared with the CTL group (P < .001) with no difference between HF groups. Lung volume (% TTC volume) was reduced as a function of disease severity (P < .001). RAD measures of cardiac volume demonstrated the strongest relationship with restrictive lung alterations (t-statistic = -5.627, P < .001 and t-statistic = -4.378, P < .001 for forced vital capacity and forced expiratory volume in 1 second, respectively)., Conclusions: These results suggest cardiac size may pose significant constraints on the lungs and likely plays a major role in the restrictive breathing patterns often reported in HF patients.

Background: Patients with heart failure (HF) display a number of breathing abnormalities including periodic breathing (PB) at rest. Although the mechanism(s) contributing to PB remain unclear, we examined whether changes in pulmonary wedge pressure (PWP) and pulmonary vascular resistance (PVR) alter PB in patients with established HF., Methods: We studied 12 male patients with HF (age, 50 +/- 11 years; ejection fraction, 18.3 +/- 3.8 %; New York Heart Association class, 3.2 +/- 0.4), with PB at rest, who are undergoing right heart catheterization with infusion of nitroprusside., Results: At baseline, patients with HF displayed minute ventilation (V(E)) oscillations with amplitude of 5.5 +/- 2.7 L/min (57 +/- 34% of the average V(E)) and cycle length of 61 +/- 18 seconds. Cardiac index (CI), PVR, and mean PWP averaged 2.0 +/- 0.4 L min(-1) m(-2), 281.9 +/- 214.9 dyne/s per cm(-5), and 28.3 +/- 5.4 mm Hg, respectively. During nitroprusside infusion, CI increased to 3.1 +/- 0.6 L min(-1) m(-2), PVR decreased to 163.9 +/- 85.2 dyne/s per cm(-5), and PWP fell to 10.0 +/- 4.2 mm Hg. Nitroprusside reduced the amplitude (2.6 +/- 2.4 L/min, 23 +/- 21% of average V(E); P < .01) and cycle length (41.4 +/- 28.8 seconds; P < .01) of V(E) oscillations while abolishing oscillations in 3 patients. Although average V(E) and PaCO2 remained unchanged, there was a significant increase in the ratio of tidal volume to inspiratory time (V(T)/T(I); P < .01), suggesting an increase in ventilatory drive. The change in the amplitude of V(E) oscillations was positively correlated with the change in PWP (r = 0.75; P < .01), negatively correlated with the change in PVR (r = 0.63; P < .05), and not correlated with the change in CI., Conclusions: These data suggest that PWP (left atrial pressure) may play a direct role in the PB observed in HF at rest.

Hypoxia and hypoxic exercise increase pulmonary arterial pressure, cause pulmonary capillary recruitment, and may influence the ability of the lungs to regulate fluid. To examine the influence of hypoxia, alone and combined with exercise, on lung fluid balance, we studied 25 healthy subjects after 17-h exposure to 12.5% inspired oxygen (barometric pressure = 732 mmHg) and sequentially after exercise to exhaustion on a cycle ergometer with 12.5% inspired oxygen. We also studied subjects after a rapid saline infusion (30 ml/kg over 15 min) to demonstrate the sensitivity of our techniques to detect changes in lung water. Pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (D(M)) were determined by measuring the diffusing capacity of the lungs for carbon monoxide and nitric oxide. Lung tissue volume and density were assessed using computed tomography. Lung water was estimated by subtracting measures of Vc from computed tomography lung tissue volume. Pulmonary function [forced vital capacity (FVC), forced expiratory volume after 1 s (FEV(1)), and forced expiratory flow at 50% of vital capacity (FEF(50))] was also assessed. Saline infusion caused an increase in Vc (42%), tissue volume (9%), and lung water (11%), and a decrease in D(M) (11%) and pulmonary function (FVC = -12 +/- 9%, FEV(1) = -17 +/- 10%, FEF(50) = -20 +/- 13%). Hypoxia and hypoxic exercise resulted in increases in Vc (43 +/- 19 and 51 +/- 16%), D(M) (7 +/- 4 and 19 +/- 6%), and pulmonary function (FVC = 9 +/- 6 and 4 +/- 3%, FEV(1) = 5 +/- 2 and 4 +/- 3%, FEF(50) = 4 +/- 2 and 12 +/- 5%) and decreases in lung density and lung water (-84 +/- 24 and -103 +/- 20 ml vs. baseline). These data suggest that 17 h of hypoxic exposure at rest or with exercise resulted in a decrease in lung water in healthy humans.

ECG-triggered computed tomography (CT) was used during passage of iodinated contrast to determine regional pulmonary blood flow (PBF) in anesthetized prone/supine dogs. PBF was evaluated as a function of height within the lung (supine and prone) as a function of various normalization methods: raw unit volume data (PBFraw) or PBF normalized to regional fraction air (PBFair), fractional non-air (PBFgm), or relative number of alveoli (PBFalv). The coefficient of variation of PBFraw, PBFair, PBFalv, and PBFgm ranged between 30 and 50% in both lungs and both body postures. The position of maximal flow along the height of the lung (MFP) was calculated for PBFraw, PBFair, PBFalv, and PBFgm. Only PBFgm showed a significantly different MFP height supine vs. prone (whole lung: 2.60 +/- 1.08 cm supine vs. 5.08 +/- 1.61 cm prone, P < 0.01). Mean slopes (ml/min/gm water content/cm) of PBFgm were steeper supine vs. prone in the right (RL) but not left lung (LL) (RL: -0.65 +/- 0.29 supine vs. -0.26 +/- 0.25 prone, P < 0.02; LL: -0.47 +/- 0.21 supine vs. -0.32 +/- 0.26 prone, P > 0.10). Mean slopes of PBFgm vs. vertical lung height were not different prone vs. supine above this vertical height of MFP (VMFP), but PBFgm slopes were steeper in the supine position below the VMFP in the RL. We conclude that PBFgm distribution was posture dependent in RL but not LL. Support of the heart may play a role. We demonstrate that normalization factors can lead to differing attributions of gravitational effects on PBF heterogeneity.

Introduction: The standard technique for assessing pulmonary diffusing capacity of the lungs (DL) for carbon monoxide (CO) is the single breath (SB) technique. SB&#95;DLco in children can be problematic because it requires a vital capacity >1.5 L. We have developed an open-circuit technique (OC), which uses the wash-in of CO over a series of 8-10 normal breaths that does not require rebreathing. In this study, we compared the SB&#95;DLco against the OC&#95;DLco., Methods: Nineteen healthy children between 7 and 18 years performed SB&#95;DLco and OC&#95;DLco tests. The mean SB&#95;DLco was significantly larger than the mean OC&#95;DLco. The mean difference OC&#95;DLco minus SB&#95; DLco was: -2.92 +/- 4.21 ml/min/mm Hg, though the difference was negatively correlated with the mean of the two (r = 0.73). The lower mean OC&#95;DLco was in part due to lower lung volume (as measured by alveolar volume (VA)) during the maneuver. In both groups there was a positive correlation between VA and DLco, and the mean VA was -2.17 +/- 1.07 L lower using OC compared to SB. The difference was again negatively correlated with the mean (r = 0.82). The mean OC minus SB difference in DLco/VA was: 6.06 +/- 1.98 ml/min/mm Hg/L, though this difference was positively correlated with the mean, r = 0.76., Conclusions: We found a good correlation between both techniques for DLco, VA, and DLco/VA. The OC offers the advantage of minimal subject cooperation, and may be preferable to use in children.

The relationship between cardiac output (CardOut) and oxygen consumption (VO2) during exercise has generally been assumed to be linear. To test this assumption, we studied 72 healthy subjects using a graded, 2-min cycle-ergometry exercise test to maximum while measuring gas exchange continuously and CardOut at the end of each stage, the latter using an open-circuit gas technique. Data for VO2 and CardOut at each stage were fit to a quadratic expression y = a + (b.VO2) + (c.VO2(2)), and statistical significance of the quadratic c term was determined in each subject. Subjects were then divided into two groups: those with statistically significant negative quadratic term ("negative curvature group," n = 25) and those with either nonsignificant quadratic term or c significantly > 0 ("non-negative curvature group," n = 47, 2 with c significantly > 0). We found the negative curvature group had significantly higher maximal VO2/kg (median 37.9 vs. 32.4 ml x min(-1) x kg(-1); P = 0.03) higher resting stroke volume (SV; median 77 vs. 60 ml; P = 0.04), lower resting heart rate (HR; median 72 vs. 82 beats/min, P = 0.04), and higher tissue oxygen extraction at maximal exercise (17.1 +/- 2.2 vs 15.5 +/- 2.1 ml/100 ml; P < 0.01), with tendencies for higher maximal CardOut and SV. We also found the HR vs. VO2 relationship to be negatively curved, with negative curvature in HR associated with the negative curvature in CardOut (P < 0.05), suggesting the curvature in the CardOut vs. VO2 relationship was secondary to curvature in HR vs. VO2. We conclude that the CardOut vs. VO2 relationship is not always linear, and negative curvature in the relationship is associated with higher fitness levels in normal, non-elite-athletic subjects.

Background: Patients with chronic heart failure (CHF) have reduced pulmonary diffusing capacity for carbon monoxide (DLCO). Acute pulmonary congestion also causes reduction of DLCO, which is reversible. We hypothesized for patients with CHF that the rate of rise of exercise DLCO is reduced compared to healthy controls and falls near end-exercise consistent with progressive interstitial edema., Methods and Results: DLCO and pulmonary blood flow (QC)) were measured by a rebreathe technique in CHF subjects (n = 11) and controls (n = 8) at rest, during constant workload exercise, and after exercise. DLCO of CHF subjects was less than controls at rest (16.5 +/- 1 vs. 21.9 +/- 2 mL/min/mm Hg, P < .01). CHF subjects exercised 11 +/- 2 minutes to 90% peak VO2, whereas controls exercised 17 +/- 2 minutes, reaching 88% peak VO2. In CHF subjects, DLCO increased to 19 +/- 2 mL/min/mm Hg and for controls to 38 +/- 3 mL/min/mm Hg. During the final 3 minutes of exercise, DLCO increased 5% in controls while decreasing 5% in CHF subjects (DLCO/Q(C)) was lower in CHF subjects at rest and progressively lower throughout exercise (P < .01)., Conclusion: In patients with CHF, DLCO has reduced rate of rise with exercise and falls near end-exercise consistent with limitation of alveolar-capillary recruitment and progressive interstitial edema.

Background: The International Olympic Committee Medical Commission required a medical justification for athletes to inhale a beta2-agonist before an event at the Summer Games in Athens in 2004., Objective: We sought to establish the percentage of athletes applying to use an inhaled beta2-agonist on the basis of the results of objective tests to establish a diagnosis of asthma or exercise-induced bronchoconstriction. We also sought to compare this percentage with the percentage of athletes simply notifying the intention to use a beta2-agonist at the previous Summer Games in Sydney in 2000., Methods: An analysis was made of tests that measured the change in FEV1 in response to a bronchodilator or in response to a provoking stimulus, such as exercise, eucapnic voluntary hyperpnea, hypertonic saline, or methacholine., Results: Ten thousand six hundred fifty-three athletes competed in Athens; 4.2% were approved to use a beta2-agonist, and 0.4% were rejected. This approval rate was 26% less than the notifications in 2000 in Sydney (5.7%). Compared with Sydney 2000, there was a significant reduction of submissions and approvals for athletes from the United States, New Zealand, Australia, and Canada and in triathlon and swimming sports., Conclusion: The need to provide objective testing has resulted in a reduction in the number of athletes seeking approval to use an inhaled beta2-agonist. Objective evidence has provided information for the doctor that is likely to improve the health of the athlete because many athletes appeared to be undertreated at the time of testing., Clinical Implications: We show that documentation of airway narrowing in athletes, particularly in response to exercise or surrogate stimuli for exercise, aids in the diagnosis and management of asthma by providing evidence of bronchial hyperresponsiveness that will respond to treatment with inhaled corticosteroids and is usually associated with a reduction in respiratory symptoms on exercise.

Background: In humans, beta(2)-adrenergic receptors (beta(2)ARs) influence airway tone. There are known functional polymorphisms of the beta(2)AR, such as substitution of glycine for arginine at codon 16. We sought to determine if this variation in genotype differentially influences airway function during exercise., Methods: Healthy subjects without asthma who were either homozygous for Arg16 (n = 16; mean age, 29 +/- 2 years [+/- SD]; mean maximum oxygen uptake [Vo(2)], 32 +/- 2 mL/kg/min) or the Gly16 allele (n = 26; mean age, 30 +/- 1 years; mean maximum Vo(2), 33 +/- 1 mL/kg/min) participated in the study. Baseline testing included spirometry and maximal symptom-limited exercise. On a separate day, an arterial cannula was placed to measure catecholamine levels. Subjects then performed exercise at two work levels (40% and 75% of peak work) for 9 min each and performed spirometry at 3-min intervals for assessment of airway function., Results: There were no statistically significant differences between groups in maximum Vo(2) or baseline spirometry (p > 0.05). With both light and heavy exercise, the groups had similar increases in the forced expiratory flow at 50% of vital capacity (FEF(50)). FEF(50) increased by 14 +/- 4% and 15 +/- 3% in arginine and glycine groups, respectively, by end exercise (p > 0.05). During recovery (5 min and 10 min after), the Gly16 homozygotes demonstrated persistent bronchodilation (10 min after FEF(50) = + 7 +/- 2% over pre-exercise) while the Arg16 subjects had a rapid return to baseline (10 min after FEF(50) = - 3 +/- 3%, p = 0.007 between groups). No differences were observed in the catecholamine responses between genotypes, although the increase in epinephrine in the arginine group tended to be higher (p = 0.07)., Conclusions: These data suggest that the Arg16Gly polymorphism of the beta(2)AR does not influence airway function during short-duration low- and high-intensity exercise. However, during recovery, the Arg16 genotype is associated with a reduced bronchodilation, possibly due to increased catecholamine desensitization.

In humans, subjects homozygous for arginine (ArgArg) at codon 16 of the beta2-adrenergic receptor (beta2AR) have been shown to have greater agonist-mediated desensitization than subjects homozygous for glycine (GlyGly). We sought to determine if this substitution differentially influenced cardiovascular function during short duration (9 min) low and high intensity exercise (40 and 75% of peak work). Healthy Caucasian ArgArg (n = 16), GlyGly (n = 31) and ArgGly (n = 17) subjects matched for age, sex and peak oxygen uptake were studied. There were no differences in adrenaline (ADR) at rest or with heavy exercise, but the ArgArg group had lower ADR with light exercise (P = 0.04). Resting heart rate (HR) was higher in ArgArg (P < 0.01), while cardiac output (Q), stroke volume (SV), and mean arterial pressure (MAP) were lower than the other groups (HR = 86+/-2, 78+/-2, 80+/-1 beats min(-1); Q = 5.7+/-0.81, 6.1+/-0.18, 6.7+/-0.22 l min(-1); SV = 68+/-3, 82+/-3, 89+/-4 ml beat(-1); MAP = 92+/-1, 103+/-2, 98+/-1 mmHg-- for ArgArg, ArgGly and GlyGly, respectively, means +/-s.e.m., P < 0.01), however, no differences were observed in systemic vascular resistance (SVR). With low intensity exercise and high intensity exercise the ArgArg group continued to have a lower , SV and MAP compared to the other groups (P < 0.05), with no differences observed in SVR. During recovery, the ArgArg subjects continued to have a lower MAP but there were no differences in HR, , or SVR. These data suggest that subjects homozygous for Arg at codon 16 of the beta2AR have reduced and MAP at rest that persist during exercise with no evidence for differential changes over the course of exercise despite large changes in catecholamines. This may suggest possible genotype-related differences in baseline receptor function or density which causes phenotypic differences at rest that are sustained during short-term exercise.

Airway responses were compared following 6-minute eucapnic voluntary hyperventilation and 6-minute exercise challenges by examining resting and post-challenge impulse oscillometry and spirometry variables. Twenty-two physically active individuals with probable exercise-induced bronchoconstriction took part in this study. Impulse oscillometry and spirometry were performed at baseline and for 20 minutes post-challenge at 5-minute intervals. High correlation was found between the two measures of change in airway function for both methods of challenge. Impulse oscillometry detected a difference in degree of response to the challenges, whereas spirometry indicated no difference, suggesting that impulse oscillometry is a more sensitive measure of change in airway function.

To avoid limitations associated with the use of single-breath and rebreathe methods for assessing the lung diffusing capacity for carbon monoxide (D(L)CO) during exercise, we developed an open-circuit technique. This method does not require rebreathing or alterations in breathing pattern and can be performed with little cognition on the part of the patient. To determine how this technique compared with the traditional rebreathe (D(L)CO,RB) method, we performed both the open-circuit (D(L)CO,OC) and the D(L)CO,RB methods at rest and during exercise (25, 50, and 75% of peak work) in 11 healthy subjects [mean age = 34 yr (SD 11)]. Both D(L)CO,OC and D(L)CO,RB increased linearly with cardiac output and external work. There was a good correlation between D(L)CO,OC and D(L)CO,RB for rest and exercise (mean of individual r2 = 0.88, overall r2 = 0.69, slope = 0.97). D(L)CO,OC and D(L)CO,RB were similar at rest and during exercise [e.g., rest = 27.2 (SD 5.8) vs. 29.3 (SD 5.2), and 75% peak work = 44.0 (SD 7.0) vs. 41.2 ml.min(-1).mmHg(-1) (SD 6.7) for D(L)CO,OC vs. D(L)CO,RB]. The coefficient of variation for repeat measurements of D(L)CO,OC was 7.9% at rest and averaged 3.9% during exercise. These data suggest that the D(L)CO,OC method is a reproducible, well-tolerated alternative for determining D(L)CO, particularly during exercise. The method is linearly associated with cardiac output, suggesting increased alveolar-capillary recruitment, and values were similar to the traditional rebreathe method.

We used the direct Fick measurements to validate a method for estimating cardiac output by iteratively fitting VCO(2) at the mouth to lung model values. This model was run using a series of 50, 30 and 10 breaths to test sensitivity to number of breaths used for fitting. The lung was treated as a catenary two-compartment lung model consisting of a dead space compartment connected with a single alveolar space compartment, perfused with constant pulmonary blood flow. The implemented mathematical modeling described variations in O(2) and CO(2) compartmental fractions and alveolar volume. This model also included pulmonary capillary gas exchange. Experimental data were collected from measurements performed on six healthy subjects at rest and during 20, 40, 60 and 85-90% of peak V(O)(2). The correlation between the two methods was highest and the average agreement between the methods was best using 50 breaths R = 095; P < 0.0001; Q(model) = 1.1Q(Fick) - 2.3). The mean difference and lower to upper limits of agreement between measured and estimated data were 0.7 l/min (-2.7 to 4.1 l/min) for cardiac output; -0.9 ml/100 ml (-1.3 to -0.5 ml/100 ml) for arterial O(2) content; -0.8 ml/100 ml (-3.8 to 2.2 ml/100 ml) for mixed venous O(2) content and -0.1 ml/100 ml (-2.9 to 2.7 ml/100 ml) for arteriovenous difference O(2) content. The cardiac output estimated by the lung model was in good agreement with the direct Fick measurements in young healthy subjects.

Study Objective: The efficacy of using impulse oscillometry (IOS) as an indirect measure of airflow obstruction compared to spirometry after exercise challenges in the evaluation of exercise-induced bronchoconstriction (EIB) has not been fully appreciated. The objective was to compare airway responses following room temperature and cold temperature exercise challenges, and to compare whether IOS variables relate to spirometry variables., Design: Spirometry and IOS were performed at baseline and for 20 min after challenge at 5-min intervals., Setting: Two 6-min exercise challenges, inhaling either room temperature (22.0 degrees C) or cold temperature (- 1 degrees C) dry medical-grade bottled air. At least 48 h was observed between these randomly assigned challenges., Participants: Twenty-two physically active individuals (12 women and 10 men) with probable EIB., Interventions: Subjects performed 6 min of stationary cycle ergometry while breathing either cold or room temperature medical-grade dry bottled air. Subjects were instructed to exercise at the highest intensity sustainable for the duration of the challenge. Heart rate and kilojoules of work performed were documented to verify exercise intensity., Measurements and Results: Strong correlations were observed within testing modalities for post-room temperature and post-cold temperature exercise spirometry and IOS values. Spirometry revealed no differences in postexercise peak falls in lung function between conditions; however, IOS identified significant differences in respiratory resistance (p < 0.05), with room temperature-inspired air being more potent than cold temperature-inspired air., Conclusions: Correlations were found between spirometric and IOS measures of change in airway function for both exercise challenges, indicating close equivalency of the methods. The challenges appeared to elicit the EIB response by a similar mechanism of water loss, and cold temperature did not have an additive effect. IOS detected a difference in degree of response between the temperatures, whereas spirometry indicated no difference, suggesting that IOS is a more sensitive measure of change in airway function.

Unlabelled: Xenon-enhanced computed tomography (Xe-CT) has been used to measure regional ventilation by determining the wash-in (WI) and wash-out (WO) rates of stable Xe. We tested the common assumption that WI and WO rates are equal by measuring WO-WI in different anatomic lung regions of six anesthetized, supine sheep scanned using multi-detector-row computed tomography (MDCT). We further investigated the effect of tidal volume, image gating (end-expiratory EE versus end-inspiratory EI), local perfusion, and inspired Xe concentration on this phenomenon., Results: WO time constant was greater than WI in all lung regions, with the greatest differences observed in dependent base regions. WO-WI time constant difference was greater during EE imaging, smaller tidal volumes, and with higher Xe concentrations. Regional perfusion did not correlate with WI-WO. We conclude that Xe-WI rate can be significantly different from the WO rate, and the data suggest that this effect may be due to a combination of anatomic and fluid mechanical factors such as Rayleigh-Taylor instabilities set up at interfaces between two gases of different densities.

Objective: A major goal of maxillary antrostomy is to increase sinus ventilation. Limited data exist regarding the effect of maxillary antrostomy size on sinus ventilation. We sought to quantify the effect of uncinectomy, small antrostomy, and large antrostomy on maxillary sinus ventilation using xenon-enhanced CT in the sheep model. MATERIALS, STUDY DESIGN, AND METHODS: A xenon-oxygen-air mixture was delivered to 8 fresh cadaveric sheep heads while repeated CT scans were performed through the maxillary sinuses. Baseline and postoperative studies were performed after an endoscopic uncinectomy, small antrostomy, or large antrostomy was created. Images were analyzed to measure the density of the xenon gas in the maxillary sinus as a function of time, generating a time constant., Results: The time constants for both small antrostomy and large antrostomy were significantly different compared to baseline ( P = 0.003 for both). The time constant comparison between small antrostomy and large antrostomy was not significant ( P = 0.948)., Conclusions: A small antrostomy produces a statistically significant increase in maxillary sinus ventilation over baseline. No significant further ventilation increase is obtained by creating a large antrostomy in the sheep model. This lends credence to the use of small antrostomies to improve maxillary sinus ventilation in human sinus surgery.