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Nitric oxide (NO) can temporally and spatially match microvascular oxygen (O(2)) delivery (Qo(2mv)) to O(2) uptake (Vo(2)) in the skeletal muscle, a crucial adjustment-to-exercise tolerance that is impaired in chronic heart failure (CHF). To investigate the effects of NO bioavailability induced by sildenafil intake on muscle Qo(2mv)-to-O(2) utilization matching and Vo(2) kinetics, 10 males with CHF (ejection fraction = 27 ± 6%) undertook constant work-rate exercise (70-80% peak). Breath-by-breath Vo(2), fractional O(2)extraction in the vastus lateralis {∼deoxygenated hemoglobin + myoglobin ([deoxy-Hb + Mb]) by near-infrared spectroscopy}, and cardiac output (CO) were evaluated after sildenafil (50 mg) or placebo. Sildenafil increased exercise tolerance compared with placebo by ∼20%, an effect that was related to faster on- and off-exercise Vo(2) kinetics (P < 0.05). Active treatment, however, failed to accelerate CO dynamics (P > 0.05). On-exercise [deoxy-Hb + Mb] kinetics were slowed by sildenafil (∼25%), and a subsequent response "overshoot" (n = 8) was significantly lessened or even abolished. In contrast, [deoxy-Hb + Mb] recovery was faster with sildenafil (∼15%). Improvements in muscle oxygenation with sildenafil were related to faster on-exercise Vo(2) kinetics, blunted oscillations in ventilation (n = 9), and greater exercise capacity (P < 0.05). Sildenafil intake enhanced intramuscular Qo(2mv)-to-Vo(2) matching with beneficial effects on Vo(2) kinetics and exercise tolerance in CHF. The lack of effect on CO suggests that improvement in blood flow to and within skeletal muscles underlies these effects.

Background: Expiratory positive airway pressure (EPAP) is a form of noninvasive positive-pressure ventilatory support that, in spite of not unloading respiratory muscles during inspiration, may reduce the inspiratory threshold load and attenuate expiratory dynamic airway compression, contributing to reduced expiratory air-flow limitation in patients with COPD. We sought to determine the effects of EPAP on operational lung volumes during exercise in COPD patients., Methods: This was a nonrandomized, experimental comparison of 2 exercise conditions (with and without EPAP); subjects completed a treadmill exercise test and performed, before and immediately after exercise, lung volume measurements. Those who overtly developed dynamic hyperinflation (DH), as defined by at least a 15% reduction from pre-exercise inspiratory capacity (IC), were invited for an additional research visit to repeat the same exercise protocol while receiving EPAP through a spring loaded resistor face mask. The primary outcome was IC variance (pre-post exercise) comparison under the 2 exercise conditions., Results: Forty-six subjects (32 males), a mean 65.0 ± 8.2 years of age, and with moderate to severe COPD (FEV(1) = 38 ± 16% predicted) were initially enrolled. From this initial sample, 17 (37%) presented overt DH, as previously defined. No significant difference was found between these subjects and the rest of the initial sample. Comparing before and after exercise, there was significantly less reduction in IC observed when EPAP was used (-0.18 ± 0.35 L vs -0.57 ± 0.45 L, P = .02), allowing greater IC final values (1.45 ± 0.50 L vs 1.13 ± 0.52 L, P = .02)., Conclusions: The application of EPAP reduced DH, as shown by lower operational lung volumes after submaximal exercise in COPD patients who previously manifested exercise DH., (Copyright 2012 Daedalus Enterprises)

Background: Ventilator-associated pneumonia (VAP) is a common infectious disease in intensive care units (ICUs). The best diagnostic approach to resolve this condition remains uncertain., Objectives: To evaluate whether quantitative cultures of respiratory secretions are effective in reducing mortality in immunocompetent patients with VAP, compared with qualitative cultures. We also considered changes in antibiotic use, length of ICU stay and mechanical ventilation., Search Methods: We searched The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2011, which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to June Week 4, 2011), EMBASE (1974 to June 2011) and LILACS (1982 to June 2011)., Selection Criteria: Randomised controlled trials (RCTs) comparing respiratory samples processed quantitatively or qualitatively, obtained by invasive or non-invasive methods from immunocompetent patients with VAP and which analysed the impact of these methods on antibiotic use and mortality rates., Data Collection and Analysis: Two review authors independently reviewed and trials identified in the search results and assessed studies for suitability, methodology and quality. We analysed data using Review Manager software. We pooled the included studies to yield the risk ratio (RR) for mortality and antibiotic change with 95% confidence intervals (CI)., Main Results: Of the 4459 references identified from the electronic databases, five RCTs (1367 patients) met the inclusion criteria. Three studies compared invasive methods using quantitative cultures versus non-invasive methods using qualitative cultures, and were used to answer the main objective of this review. The other two studies compared invasive versus non-invasive methods, both using quantitative cultures. We combined all five studies to compare invasive versus non-invasive interventions for diagnosing VAP. The studies that compared quantitative and qualitative cultures (1240 patients) showed no statistically significant differences in mortality rates (RR 0.91; 95% CI 0.75 to 1.11). The analysis of all five RCTs showed there was no evidence of reduction in mortality in the invasive group versus the non-invasive group (RR 0.93; 95% CI 0.78 to 1.11). There were no significant differences between the interventions with respect to the number of days on mechanical ventilation, length of ICU stay or antibiotic change., Authors' Conclusions: There is no evidence that the use of quantitative cultures of respiratory secretions results in reduced mortality, reduced time in ICU and on mechanical ventilation, or higher rates of antibiotic change when compared to qualitative cultures in patients with VAP. Similar results were observed when invasive strategies were compared with non-invasive strategies.

Objective: To characterize the presence, extent, and patterns of dynamic hyperinflation (DH) during treadmill exercise testing in patients with moderate to severe COPD., Methods: This was a cross-sectional study involving 30 non-hypoxemic patients (FEV1= 43 ± 14% of predicted) who were submitted to a cardiopulmonary exercise test on a treadmill at a constant speed (70-80% of maximum speed) to the tolerance limit (Tlim). Serial inspiratory capacity (IC) maneuvers were used in order to assess DH., Results: Of the 30 patients studied, 19 (63.3%) presented with DH (DH+ group), having greater pulmonary function impairment at rest than did those without DH (DH- group). None of the variables studied correlated with exercise tolerance in the DH- group, whereas Tlim, IC, and perception of dyspnea during exercise did so correlate in the DH+ group (p < 0.05). In the DH+ group, 7 and 12 patients, respectively, presented with a progressive and a stable pattern of DH (ΔIC Tlim,2min = -0.28 ± 0.11 L vs. 0.04 ± 0.10 L; p < 0.01). Patients with a progressive pattern of DH presented with higher perception of dyspnea/Tlim rate and lower exercise tolerance than did those with a stable pattern (354 ± 118 s and 465 ± 178 s, respectively; p < 0.05)., Conclusions: The presence of DH is not a universal phenomenon during walking in COPD patients, even in those with moderate to severe airflow limitation. In the patients who presented DH, a progressive pattern of DH had a greater impact on exercise tolerance than did a stable pattern of DH.

Background and Objective: Proportional assist ventilation (PAV) has been proposed as a more physiological modality of non-invasive ventilation, thereby reducing the potential for deleterious cardio-circulatory effects during exercise, in patients with COPD. We therefore evaluated whether PAV modulates the kinetic and 'steady-state' haemodynamic responses to exercise in patients with moderate-to-severe COPD., Methods: Twenty patients underwent constant-load (75-80% peak work rate) cycle ergometer exercise testing to the limit of tolerance (T(lim)), while receiving PAV or breathing spontaneously. Stroke volume (SV), heart rate (HR) and cardiac output (CO) were monitored by impedance cardiography., Results: Compared with unassisted breathing, PAV increased T(lim) in 8/20 patients (median improvement 113% (range 8 to 212) vs -20% (range -40 to -9)). PAV had no significant effects on 'steady-state' haemodynamic responses either in patients with or those without increased T(lim) (P > 0.05). However, at the onset of exercise, SV kinetics were slowed with PAV, in 13/15 patients with analysable data. HR dynamics remained unaltered or failed to accelerate sufficiently in nine of these patients, thereby slowing CO kinetics (T(1/2) 61 s (range 81-30) vs 89 s (range 100-47)). These deleterious effects were not, however, associated with PAV-induced changes in T(lim) (P > 0.05)., Conclusions: PAV slowed the SV and CO kinetics at the onset of high-intensity exercise in selected patients with moderate-to-severe COPD. However, these adverse effects of PAV disappeared during the stable phase of exercise, and were not related to the ergogenic potential of PAV in this patient population., (© 2010 The Authors; Respirology © 2010 Asian Pacific Society of Respirology.)

Background: It is currently unclear whether the additive effects of a long-acting beta(2)-agonist (LABA) and the antimuscarinic tiotropium bromide (TIO) on resting lung function are translated into lower operating lung volumes and improved exercise tolerance in patients with chronic obstructive pulmonary disease (COPD)., Methods: On a double-blind and cross-over study, 33 patients (FEV(1) = 47.4 +/- 12.9% predicted) were randomly allocated to 2-wk formoterol fumarate 12 microg twice-daily (FOR) plus TIO 18 microg once-daily or FOR plus placebo (PLA). Inspiratory capacity (IC) was obtained on constant-speed treadmill tests to the limit of tolerance (Tlim)., Results: FOR-TIO was superior to FOR-PLA in increasing post-treatment FEV(1) and Tlim (1.34 +/- 0.42 L vs. 1.25 +/- 0.39 L and 124 +/- 27% vs. 68 +/- 14%, respectively; p < 0.05). FOR-TIO slowed the rate of decrement in exercise IC compared to FOR-PLA (Deltaisotime-rest = -0.27 +/- 0.40 L vs. -0.45 +/- 0.36 L, p < 0.05). In addition, end-expiratory lung volume (% total lung capacity) was further reduced with FOR-TIO (p < 0.05). Of note, patients showing greater increases in Tlim with FOR-TIO (16/26, 61.6%) had more severe airways obstruction and lower exercise capacity at baseline. Improvement in Tlim with FOR-TIO was also related to larger increases in FEV(1) (p < 0.05)., Conclusions: Compared to FOR monotherapy, FOR-TIO further improved effort-induced dynamic hyperinflation and exercise endurance in patients with moderate-to-severe COPD. These beneficial consequences were more likely to be found in severely-disabled patients with larger resting functional responses to the combination therapy., Trial Registration: Clinicaltrials.gov Identifier: NCT00680056 [ClinicalTrials.gov].

Inspiratory pressure support (IPS) plus positive end-expiratory pressure (PEEP) ventilation might potentially interfere with the "central" hemodynamic adjustments to exercise in patients with chronic obstructive pulmonary disease (COPD). Twenty-one non- or mildly-hypoxemic males (FEV(1) = 40.1 +/- 10.7% predicted) were randomly assigned to IPS (16 cmH(2)O) + PEEP (5 cmH(2)O) or spontaneous ventilation during constant-work rate (70-80% peak) exercise tests to the limit of tolerance (T (lim)). Heart rate (HR), stroke volume (SV), and cardiac output (CO) were monitored by transthoracic cardioimpedance (Physioflow, Manatec, France). Oxyhemoglobin saturation was assessed by pulse oximetry (SpO(2)). At similar SpO(2), IPS(16) + PEEP(5) was associated with heterogeneous cardiovascular effects compared with the control trial. Therefore, 11 patients (Group A) showed stable or increased Delta "isotime" - rest SV [5 (0-29) mL], lower DeltaHR but similar DeltaCO. On the other hand, DeltaSV [-10 (-15 to -3) mL] and DeltaHR were both lower with IPS(16) + PEEP(5) in Group B (N = 10), thereby reducing DeltaCO (p < 0.05). Group B showed higher resting lung volumes, and T (lim) improved with IPS(16) + PEEP(5) only in Group A [51 (-60 to 486) vs. 115 (-210 to 909) s, respectively; p < 0.05]. We conclude that IPS(16) + PEEP(5) may improve SV and exercise tolerance in selected patients with advanced COPD. Impaired SV and CO responses, associated with a lack of enhancement in exercise capacity, were found in a sub-group of patients who were particularly hyperinflated at rest.

Background: Ventilator-associated pneumonia (VAP) is a common infectious disease in intensive care units (ICUs). The best diagnostic approach to resolve this condition remains uncertain., Objectives: To evaluate whether quantitative cultures of respiratory secretions are effective in reducing mortality in immunocompetent patients with VAP, compared with qualitative cultures. We also considered changes in antibiotic use, length of ICU stay and mechanical ventilation., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, issue 4), which contains the Acute Respiratory Infections Group's Specialized Register; MEDLINE (1966 to December 2007); EMBASE (1974 to December 2007); and LILACS (1982 to December 2007)., Selection Criteria: Randomized controlled trials (RCTs) comparing respiratory samples processed quantitatively or qualitatively, obtained by invasive or non-invasive methods from immunocompetent patients with VAP, and which analyzed the impact of these methods on antibiotic use and mortality rates., Data Collection and Analysis: Two review authors independently reviewed and selected trials from the search results, and assessed studies for suitability, methodology and quality. We analyzed data using Review Manager software. We pooled the included studies to yield the risk ratio (RR) for mortality and antibiotic change with 95% confidence intervals (CI)., Main Results: Of the 3931 references identified from the electronic databases, five RCTs (1367 patients) met the inclusion criteria. Three studies compared invasive methods using quantitative cultures versus non-invasive methods using qualitative cultures, and were used to answer the main objective of this review. The other two studies compared invasive versus non-invasive methods, both using quantitative cultures. All five studies were combined to compare invasive versus non-invasive interventions for diagnosing VAP. The studies that compared quantitative and qualitative cultures (1240 patients) showed no statistically significant differences in mortality rates (RR = 0.91, 95% CI 0.75 to 1.11). The analysis of all five RCTs showed there was no evidence of mortality reduction in the invasive group versus the non-invasive group (RR = 0.93, 95% CI 0.78 to 1.11). There were no significant differences between the interventions with respect to the number of days on mechanical ventilation, length of ICU stay or antibiotic change., Authors' Conclusions: There is no evidence that the use of quantitative cultures of respiratory secretions results in reduced mortality, reduced time in ICU and on mechanical ventilation, or higher rates of antibiotic change when compared to qualitative cultures in patients with VAP. Similar results were observed when invasive strategies were compared with non-invasive strategies.

Background: Respiratory muscle unloading during exercise could improve locomotor muscle oxygenation by increasing oxygen delivery (higher cardiac output and/or arterial oxygen content) in patients with chronic obstructive pulmonary disease (COPD)., Methods: Sixteen non-hypoxaemic men (forced expiratory volume in 1 s 42.2 (13.9)% predicted) undertook, on different days, two constant work rate (70-80% peak) exercise tests receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (Delta%) in deoxyhaemoglobin (HHb), oxyhaemoglobin (O(2)Hb), tissue oxygenation index (TOI) and total haemoglobin (Hb(tot)) in the vastus lateralis muscle were measured by near-infrared spectroscopy. In order to estimate oxygen delivery (Do(2)est, l/min), cardiac output and oxygen saturation (Spo(2)) were continuously monitored by impedance cardiography and pulse oximetry, respectively., Results: Exercise tolerance (Tlim) and oxygen uptake were increased with PAV compared with sham ventilation. In contrast, end-exercise blood lactate/Tlim and leg effort/Tlim ratios were lower with PAV (p<0.05). There were no between-treatment differences in cardiac output and Spo(2) either at submaximal exercise or at Tlim (ie, Do(2)est remained unchanged with PAV; p>0.05). Leg muscle oxygenation, however, was significantly enhanced with PAV as the exercise-related decrease in Delta(O(2)Hb)% was lessened and TOI was improved; moreover, Delta(Hb(tot))%, an index of local blood volume, was increased compared with sham ventilation (p<0.01)., Conclusions: Respiratory muscle unloading during high-intensity exercise can improve peripheral muscle oxygenation despite unaltered systemic Do(2 )in patients with advanced COPD. These findings might indicate that a fraction of the available cardiac output had been redirected from ventilatory to appendicular muscles as a consequence of respiratory muscle unloading.

Blood flow requirements of the respiratory muscles (RM) increase markedly during exercise in chronic heart failure (CHF). We reasoned that if the RM could subtract a fraction of the limited cardiac output (QT) from the peripheral muscles, RM unloading would improve locomotor muscle perfusion. Nine patients with CHF (left ventricle ejection fraction = 26 +/- 7%) undertook constant-work rate tests (70-80% peak) receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (Delta%) in deoxy-hemoglobyn, oxi-Hb ([O2Hb]), tissue oxygenation index, and total Hb ([HbTOT], an index of local blood volume) in the vastus lateralis were measured by near infrared spectroscopy. In addition, QT was monitored by impedance cardiography and arterial O2 saturation by pulse oximetry (SpO2). There were significant improvements in exercise tolerance (Tlim) with PAV. Blood lactate, leg effort/Tlim and dyspnea/Tlim were lower with PAV compared with sham ventilation (P < 0.05). There were no significant effects of RM unloading on systemic O2 delivery as QT and SpO2 at submaximal exercise and at Tlim did not differ between PAV and sham ventilation (P > 0.05). Unloaded breathing, however, was related to enhanced leg muscle oxygenation and local blood volume compared with sham, i.e., higher Delta[O2Hb]% and Delta[HbTOT]%, respectively (P < 0.05). We conclude that RM unloading had beneficial effects on the oxygenation status and blood volume of the exercising muscles at similar systemic O2 delivery in patients with advanced CHF. These data suggest that blood flow was redistributed from respiratory to locomotor muscles during unloaded breathing.

Introduction: The six-minute walking test distance, despite being considered the main parameter, does not consider body weight which is known to influence exercise capacity. A body of evidence shows the degree of airflow obstruction does not correlate to walking distance and the body weight affects the work/energy required to perform the walk., Objective: To verify if the degree of airflow obstruction correlates to six-minute walk work obtained by weight-walking distance product., Patient and Methods: A total of 60 patients with chronic obstructive pulmonary disease were evaluated. The physiological and functional variables were correlated to distance and body weight walking distance product (WxW)., Results: There were no correlations between six- minute walk work and the degree of airflow obstruction. A positive and significant correlation were observed between the distance and Carbon Monoxide Diffusing Capacity (DLCO) (r=0.6; p<0.01) and between the distance and final SatO 2 (r= 0.3 ; p <0.05). Correlation between distance and Borg scale was negative and significant (r= -0.3; p<0.05). The six-minute walk work was positive and significantly correlated to DLCO (r= 0.7; p<0.01) and negative but significantly correlated to Borg scale in the initial (r= - 0.3; p<0.01) and final of the test (r= -0.4; p<0.05)., Conclusion: Based on this data, there was no correlation between the degree of airflow obstruction and six-minute walk work test. The DLCO was the only respiratory functional parameter significantly correlated to the distance and to the six- minute walk work.