Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial.

BACKGROUND: Short-acting ß2-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity. This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD. METHODS: The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily umeclidinium/vilanterol 62.5/25 µg, once-daily umeclidinium 62.5 µg or twice-daily salmeterol 50 µg for 24 weeks. Pre-specified subgroup analyses stratified patients by median baseline SABA use (low, < 1.5 puffs/day; high, ≥1.5 puffs/day) to examine change from baseline in trough forced expiratory volume in 1 s (FEV1), change in symptoms (Transition Dyspnoea Index [TDI], Evaluating Respiratory Symptoms-COPD [E-RS]), daily SABA use and exacerbation risk. A post hoc analysis used fractional polynomial modelling with continuous transformations of baseline SABA use covariates. RESULTS: At baseline, patients in the high SABA use subgroup (mean: 3.91 puffs/day, n = 1212) had more severe airflow limitation, were more symptomatic and had worse health status versus patients in the low SABA use subgroup (0.39 puffs/day, n = 1206). Patients treated with umeclidinium/vilanterol versus umeclidinium demonstrated statistically significant improvements in trough FEV1 at Week 24 in both SABA subgroups (59-74 mL; p < 0.001); however, only low SABA users demonstrated significant improvements in TDI (high: 0.27 [p = 0.241]; low: 0.49 [p = 0.025]) and E-RS (high: 0.48 [p = 0.138]; low: 0.60 [p = 0.034]) scores. By contrast, significant reductions in mean SABA puffs/day with umeclidinium/vilanterol versus umeclidinium were observed only in high SABA users (high: - 0.56 [p < 0.001]; low: - 0.10 [p = 0.132]). Similar findings were observed when comparing umeclidinium/vilanterol and salmeterol. Fractional polynomial modelling showed baseline SABA use ≥4 puffs/day resulted in smaller incremental symptom improvements with umeclidinium/vilanterol versus umeclidinium compared with baseline SABA use < 4 puffs/day. CONCLUSIONS: In high SABA users, there may be a smaller difference in treatment response between dual- and mono-bronchodilator therapy; the reasons for this require further investigation. SABA use may be a confounding factor in bronchodilator trials and in high SABA users; changes in SABA use may be considered a robust symptom outcome. FUNDING: GlaxoSmithKline (study number 201749 [NCT03034915]).

Characteristics of COPD in never-smokers and ever-smokers in the general population: results from the CanCOLD study.

BACKGROUND: There is limited data on the risk factors and phenotypical characteristics associated with spirometrically confirmed COPD in never-smokers in the general population. AIMS: To compare the characteristics associated with COPD by gender and by severity of airway obstruction in never-smokers and in ever-smokers. METHOD: We analysed the data from 5176 adults aged 40 years and older who participated in the initial cross-sectional phase of the population-based, prospective, multisite Canadian Cohort of Obstructive Lung Disease study. Never-smokers were defined as those with a lifetime exposure of <1/20 pack year. Logistic regressions were constructed to evaluate associations for 'mild' and 'moderate-severe' COPD defined by FEV1/FVC <5th centile (lower limits of normal). Analyses were performed using SAS V.9.1 (SAS Institute, Cary, North Carolina, USA). RESULTS: The prevalence of COPD (FEV1/FVC

Exacerbation-like respiratory symptoms in individuals without chronic obstructive pulmonary disease: results from a population-based study.

RATIONALE: Exacerbations of COPD are defined clinically by worsening of chronic respiratory symptoms. Chronic respiratory symptoms are common in the general population. There are no data on the frequency of exacerbation-like events in individuals without spirometric evidence of COPD. AIMS: To determine the occurrence of 'exacerbation-like' events in individuals without airflow limitation, their associated risk factors, healthcare utilisation and social impacts. METHOD: We analysed the cross-sectional data from 5176 people aged 40 years and older who participated in a multisite, population-based study on lung health. The study cohort was stratified into spirometrically defined COPD (post-bronchodilator FEV1/FVC < 0.7) and non-COPD (post bronchodilator FEV1/FVC ≥ 0.7 and without self-reported doctor diagnosis of airway diseases) subgroups and then into those with and without respiratory 'exacerbation-like' events in the past year. RESULTS: Individuals without COPD had half the frequency of 'exacerbation-like' events compared with those with COPD. In the non-COPD group, the independent associations with 'exacerbations' included female gender, presence of wheezing, the use of respiratory medications and self-perceived poor health. In the non-COPD group, those with exacerbations were more likely than those without exacerbations to have poorer health-related quality of life (12-item Short-Form Health Survey), miss social activities (58.5% vs 18.8%), miss work for income (41.5% vs 17.3%) and miss housework (55.6% vs 16.5%), p<0.01 to <0.0001. CONCLUSIONS: Events similar to exacerbations of COPD can occur in individuals without COPD or asthma and are associated with significant health and socioeconomic outcomes. They increase the respiratory burden in the community and may contribute to the false-positive diagnosis of asthma or COPD.

Tiotropium improves walking endurance in COPD.

The primary objective of this study was to evaluate the effects of a 3-week treatment with tiotropium on walking capacity in chronic obstructive pulmonary disease (COPD). After familiarisation with study procedures, 36 patients were randomised to receive tiotropium 18 µg once daily or a matching placebo in a double-blind, parallel-group study. Pre- (trough) and 2-h post-dose pulmonary function was measured. An endurance shuttle walk was then completed. The same procedures were repeated after 3 weeks of treatment. Ventilatory parameters were monitored during exercise. At 3 weeks, tiotropium significantly improved walking endurance time in comparison with placebo, with a mean±sd between-group difference of 128±141 s (p=0.017). At 3 weeks, trough values for forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were significantly improved with tiotropium in comparison with placebo. The post-dose response to tiotropium was statistically superior to placebo after the first dose and after 3 weeks of treatment for FEV(1), FVC and inspiratory capacity. Ventilation and tidal volume at the end of walking were significantly improved with tiotropium. 3 weeks of tiotropium resulted in a greater walking endurance in patients with COPD. Improvements in FEV(1), maximal ventilation and tidal volume may contribute to this enhanced exercise capacity.

Trajectories of endurance activity following pulmonary rehabilitation in COPD patients.

Maintenance of physical activity following pulmonary rehabilitation remains a challenge for patients with chronic obstructive pulmonary disease (COPD). The objectives of this study were to identify patterns of endurance activity after completion of pulmonary rehabilitation and to characterise people who succeed and those who have difficulty maintaining endurance activity. In a longitudinal study embedded within a randomised clinical trial, 206 individuals with COPD underwent a 3-month pulmonary rehabilitation programme. Weekly duration of endurance activity was assessed at 4, 6, 8 and 12 months after the start of rehabilitation. Trajectory modelling was used to determine the most common patterns of activity during the post-rehabilitation phase from 4-12 months. Three distinct patterns were identified, two of which indicated difficulty in maintaining endurance activity: 61 individuals reported a high activity level at 4 months (2.7 h·week(-1)) and stayed high; 114 individuals started at a low activity level (mean 1.0 h·week(-1)) and stayed low; and 31 individuals started high (3.0 h·week(-1)) and declined. The low activity group was characterised by more severe disease and greater respiratory impairment. The high and declined group had less severe disease and respiratory impairment, but reported greater barriers to exercise. Pulmonary rehabilitation should include interventions aimed at minimising barriers, in order to induce long-term behaviour change.

Reliability of ventilatory parameters during cycle ergometry in multicentre trials in COPD.

We studied the distribution profiles and repeatability of key exercise performance parameters in the first large multicentre trials to include these measurements in chronic obstructive pulmonary disease (COPD). After a screening visit, 463 subjects with COPD (mean+/-SD forced expiratory volume in 1 s 43+/-13% predicted) completed two run-in visits before treatment randomisation. At the run-in visits, measurements were conducted at rest, at a standardised time near end-exercise (isotime) and at peak exercise during constant work rate (CWR) cycle tests at 75% of each individual's maximum work capacity. The intraclass correlation coefficient was used to evaluate the test-retest repeatability of measurements of endurance time (ET), inspiratory capacity (IC), ventilation and dyspnoea intensity (Borg scale) during exercise. IC, ventilation and dyspnoea ratings were normally distributed; ET showed rightward skew (median or = 0.87). Ventilation was repeatable over the same time-points (R > or = 0.92), as was dyspnoea intensity at isotime (R = 0.79) and at peak exercise (R = 0.81). In conclusion, key perceptual and ventilatory parameters can be reliably measured during CWR cycle exercise in multicentre clinical trials in moderate to very severe COPD.

Pulmonary rehabilitation in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and an important worldwide cause of disability and handicap. Centered around exercise training, pulmonary rehabilitation is a global, multidisciplinary, individualized and comprehensive approach acting on the patient as a whole and not only on the pulmonary component of the disease. Pulmonary rehabilitation is now well recognized as an effective and key intervention in the management of several respiratory diseases particularly in COPD. Modern and effective pulmonary rehabilitation programs are global, multidisciplinary, individualized and use comprehensive approach acting on the patient as a whole and not only on the pulmonary component of the disease. In the last two decades interest for pulmonary rehabilitation is on the rise and a growing literature including several guidelines is now available. This review addresses the recent developments in the broad area of pulmonary rehabilitation as well as new methods to consider in the development of future and better programs. Modern literature for rationale, physiopathological basis, structure, exercise training as well challenges for pulmonary rehabilitation programs are addressed. Among the main challenges of pulmonary rehabilitation, efforts have to be devoted to improve accessibility to early rehabilitation strategies, not only to patients with COPD but to those with other chronic respiratory diseases.

Assessing the impact of pulmonary rehabilitation on functional status in COPD.

BACKGROUND: The optimal way of assessing the impact of pulmonary rehabilitation on functional status in chronic obstructive pulmonary disease (COPD) is currently unknown. The minimal clinically important difference for the constant work rate cycling exercise test also needs to be investigated to facilitate its interpretation. A study was undertaken to evaluate the changes in the 6-min walking test and in the constant work rate cycle endurance test immediately following and 1 year after pulmonary rehabilitation, together with the importance of these changes in terms of health status in patients with COPD. METHODS: Patients with COPD of mean (SD) age 65 (8) years and mean (SD) forced expiratory volume in 1 s (FEV1) 45 (15)% predicted were recruited from a multicentre prospective cohort study and evaluated at baseline, immediately after a pulmonary rehabilitation programme (n = 157) and at 1 year (n = 106). The 6-min walking test and the cycle endurance test were performed at each evaluation. Health status was evaluated with the St George Respiratory Questionnaire. RESULTS: Following pulmonary rehabilitation, cycle endurance time increased (198 (352) s, p<0.001) and stayed over baseline values at 1 year (p<0.001). The 6-min walking distance also showed improvements following rehabilitation (25 (52) m, p<0.001) but returned to baseline values at the 1-year follow-up. Changes in cycle endurance time were more closely associated with changes in health status than with the 6-min walking test. An improvement of 100-200 s in the cycle endurance time was associated with clinically meaningful changes in the St George Respiratory Questionnaire scores. CONCLUSIONS: The cycle endurance test was more responsive than the 6-min walking test in detecting improvement in exercise tolerance following pulmonary rehabilitation, and was also better correlated with improvements in health status. An improvement in the cycle endurance time of 100-200 s appeared to be clinically meaningful.

Counting, analysing and reporting exacerbations of COPD in randomised controlled trials.

BACKGROUND: Clinical trials measure exacerbations of chronic obstructive pulmonary disease (COPD) inconsistently. A study was undertaken to determine if different methods for ascertaining and analysing COPD exacerbations lead to biased estimates of treatment effects. METHODS: Information on the methods used to count, analyse and report COPD exacerbation rates was abstracted from clinical trials of long-acting bronchodilators or long-acting bronchodilator/inhaled steroid combination products published between 2000 and 2006. Data from the Canadian Optimal Therapy of COPD Trial was used to illustrate how different analytical approaches can affect the estimate of exacerbation rates and their confidence intervals. RESULTS: 22 trials (17,156 patients) met the inclusion criteria and were reviewed. None of the trials adjudicated exacerbations or determined independence of events. 14/22 studies (64%) introduced selection bias by not analysing outcome data for subjects who prematurely stopped study medications. Only 31% of trials used time-weighted analyses to calculate the mean number of exacerbations/patient-year and only 15% accounted for between-subject variation. In the Canadian Optimal Therapy of COPD Trial the rate ratio for exacerbations/patient-year was 0.85 when all data were included in a time-weighted analysis, but was overestimated as 0.79 when data for those who prematurely stopped study medications were excluded and was further overestimated as 0.46 when a time-weighted analysis was not conducted; p values ranged from 0.03 to 0.24 depending on how exacerbations were determined and analysed. CONCLUSIONS: Clinical trials have used widely different methods to define and analyse COPD exacerbations and this can lead to biased estimates of treatment effects. Future trials should strive to include blinded adjudication and assessment of the independence of exacerbation events, and trials should report time-weighted intention-to-treat analyses with adjustments for between-subject variation in COPD exacerbations.

Endurance shuttle walking test: responsiveness to salmeterol in COPD.

Few studies have shown that the endurance shuttle walking test (ESWT) is responsive to treatment in patients with chronic obstructive pulmonary disease (COPD). This exercise test needs to be further investigated because of its relevance for activity of daily living. The aim of the present study was to evaluate, in patients with COPD, the responsiveness of the ESWT in detecting improvement in walking performance after a single dose of salmeterol. In a randomised, double-blind, placebo-controlled crossover trial, 20 patients with COPD performed two ESWT at 80% of peak capacity 2.5 h after inhaling either a placebo or 50 microg of salmeterol. Cardiorespiratory parameters were monitored during each walking test. Inspiratory capacities and Borg ratings for dyspnoea were obtained every other minute throughout the tests. Compared with placebo, salmeterol produced a significant change in lung function and a significant improvement in walking performance (mean+/-sd difference in time: 117+/-20 s; difference in distance: 160+/-277 m). At isotime (the latest exercise time that was reached on both ESWT), a significant reduction in dyspnoea was observed after bronchodilation. Bronchodilation with salmeterol reduced dyspnoea during walking and improved walking capacity in patients with chronic obstructive pulmonary disease. These findings provide further support for the use of the endurance shuttle walking test as an evaluative tool in chronic obstructive pulmonary disease.

[Cardiovascular manifestations in patients with COPD]. / Les manifestations cardiovasculaires chez les patients atteints d'une BPCO.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterized mainly by airway obstruction due to chronic bronchitis and/or emphysema. In addition, COPD is frequently associated with other health problems with serious systemic manifestations. In particular, COPD patients are at increased risk of cardiovascular disease. BACKGROUND: Current knowledge about cardiovascular disease in patients with COPD mainly concerns the high prevalence of cardiac arrhythmias in this population. Systemic hypertension, cardiovascular disease, heart failure and cerebro-vascular disease are also frequently encountered. This review discusses the cardiovascular manifestations associated with COPD, excluding right heart failure due to pulmonary hypertension. VIEWPOINTS AND CONCLUSION: Non pulmonary health problems in patients with COPD, such as cardiovascular disease, are arousing increasing interest in the medical community. More studies are needed to increase our knowledge of cardiovascular disease in COPD and allow better medical management of patients.

A randomized, double-blind, placebo-controlled study of lorazepam as premedication for bronchoscopy.

To our knowledge, no study has clearly demonstrated the advantage of sedative premedication for bronchoscopy. In a double-blind study, we evaluated the efficacy of oral lorazepam as premedication for bronchoscopy. One hundred patients were randomly assigned to receive placebo (group A) or lorazepam (2 mg) (group B) approximately 1.5 h before bronchoscopy. Immediately after the procedure and the following day, a questionnaire addressing the patient's perception of the procedure was administered. Specifically, subjects were asked to grade the bronchoscopy as very easy, easy, difficult, or very difficult to tolerate and if they would agree to a second bronchoscopy if believed necessary. In addition, their recollection of the procedure was graded as clear, indistinct, or not at all. No difference was found between the two groups for age, duration of the bronchoscopy, and the answers to the questionnaire administered immediately after the procedure. Most patients from both groups found their level of sedation adequate. On the following day, however, group B reported with lower frequency that the technique was difficult or very difficult (38.0% vs 65.3% for group A; p < 0.005) and that they would be less reluctant to a repeated bronchoscopy (30.0% vs 57.1% for group A; p < 0.015). Moreover, their recollection of the procedure was now less precise than for those who had received the placebo (p < 0.005). This suggests that the difference observed between the two groups at 24 h was related to the amnesic effect of lorazepam. We conclude that lorazepam, by improving patient's perception of the bronchoscopy, is a useful premedication and may facilitate patient's investigation when a second bronchoscopy becomes necessary.

Blood hypereosinophilia in the course of posttraumatic pleural effusion.

We report four cases of posttraumatic pleural effusion associated with blood hypereosinophilia. Three men and one woman were examined at our institution for pleural effusion between 21 and 50 days after a minor thoracic trauma. At their initial examination, the pleural fluid analysis showed, for each subject, a high eosinophilic count (54, 45, 25, and 45 percent, respectively). Blood analysis taken at that time revealed a concomitant increase in the number of peripheral eosinophils (1,078, 3,894, 900, and 2,128 eosinophils per cubic millimeter, respectively). For each subject, there was no evidence of past or current allergy or of systemic disease that could be associated with hypereosinophilia. We observed a parallel regression of the pleural effusion and of the number of blood eosinophils in each case. Only when the pleural effusion completely cleared did the blood eosinophilia return to normal. We conclude that posttraumatic pleural effusion may cause a striking blood eosinophilia and that a persistently elevated number of blood eosinophils suggests the nonresolution of the pleural effusion.

Respiratory mechanics in status asthmaticus. Effects of inhalational anesthesia.

The incidence and severity of bronchial asthma has increased considerably in recent years. As a result, the number of patients requiring mechanical ventilation and more intensive medical therapy for treatment of refractory asthma has also increased. Despite this, available information concerning the quantitative changes in respiratory mechanics and the response to treatment that occur in such patients is limited. The present study describes the abnormalities in respiratory mechanics and the response to isoflurane anesthesia observed in three adults mechanically ventilated for treatment of status asthmaticus. Airway pressure, flow, and volume were measured during controlled mechanical ventilation in which the airway was periodically occluded in order to determine respiratory system mechanics. In two patients, the volume of hyperinflation and expiratory volume-flow relationship were also obtained. Inspiratory and expiratory indices of respiratory resistance were markedly abnormal. These abnormalities were associated with significant dynamic hyperinflation and high levels of intrinsic PEEP. Expiratory flow limitation was also identified in two patients by failure of low levels of applied positive end-expiratory pressure (PEEP) to alter the expiratory volume-flow relationship. Indices of respiratory resistance as well as the magnitude of dynamic hyperinflation and intrinsic PEEP improved considerably with isoflurane administration, after having been refractory to intensive conventional bronchodilator therapy. In summary, these results demonstrate the severity of abnormalities in respiratory mechanics present in ventilated patients with status asthmaticus and the potential therapeutic efficacy of inhalational anesthesia in this setting.

Incidence and predictors of ARDS after cardiac surgery.

BACKGROUND: Severe pulmonary injury with the development of ARDS is a potential complication of cardiac surgery and cardiopulmonary bypass (CPB). STUDY OBJECTIVES: This retrospective, case-control study was designed to determine the incidence and mortality of ARDS after cardiac surgery and CPB, as well as to identify preoperative and perioperative predisposing factors of this complication. METHODS: Of 3,278 patients who underwent cardiac surgery and CPB between January 1995 and December 1998, 13 patients developed ARDS during the postoperative period. Each patient was matched with four or five control subjects who had the same type of surgery on the same day but did not develop postoperative respiratory complications. RESULTS: The incidence of ARDS was 0.4%, with an ARDS mortality of 15%. In the ARDS group, 38% had previous cardiac surgery, as compared to 3.5% in the control group (p < 0.002). During the postoperative period, ARDS patients received more blood products (4 +/- 5 vs 2 +/- 3; p < 0.01) and developed shock more frequently (31% vs 5%; p < 0.02) than patients in the control group. Multivariate regression analysis identified previous cardiac surgery, shock, and the number of transfused blood products as significant independent predictors for ARDS, with odds ratios of 31.5 (p = 0.015), 10.8 (p = 0.03), and 1.6 (p = 0.03), respectively. CONCLUSIONS: ARDS following cardiac surgery and CPB was a rare complication that carried a 15% mortality rate. Previous cardiac surgery, shock, and number of blood products received are important predicting factors for this complication.

Changes in upper airway resistance during progressive normocapnic hypoxia in normal men.

The effects of normocapnic progressive hypoxia on nasal and pharyngeal resistances were evaluated in nine normal men. To calculate resistances, upper airway pressures were measured with two low-bias flow catheters; one was placed at the tip of the epiglottis and the other in the posterior nasopharynx, and we measured flow with a Fleish no. 3 pneumotachograph connected to a tightly fitting mask. Both resistances were obtained during a baseline period and during progressive normocapnic hypoxia achieved by a rebreathing method. We collected the breath-by-breath values of upper airway resistances, minute ventilation, O2 and CO2 fractions, arterial O2 saturation (SaO2), and changes in functional residual capacity (inductance vest). The central respiratory drive was evaluated by the mouth occlusion pressure 0.1 s after the onset of inspiration (P0.1), and breath-by-breath P0.1 values were estimated by intrapolation from the linear relationship between P0.1 and SaO2. In each subject both resistances decreased during the hypoxic test. The slope of the decrease in resistance with decreasing SaO2 (%baseline/%SaO2) was steeper for pharyngeal resistance than for nasal resistance [2.67 +/- 0.29 and 1.61 +/- 0.25 (SE), respectively; P less than 0.05]. The slope of the decrease in resistance with increasing P0.1 (%baseline/cmH2O) was -0.24 +/- 0.05 for nasal resistance and -0.39 +/- 0.07 for pharyngeal resistance (P less than 0.05). Functional residual capacity progressively increased during the test, but the decrease in resistance was greater than expected from an isolated increase in lung volume. We conclude that nasal and pharyngeal resistances decrease during progressive normocapnic hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of static and dynamic measurements of intrinsic PEEP in anesthetized cats.

Dynamic measurements of intrinsic positive end-expiratory pressure (PEEPi,dyn) considerably underestimate values obtained under static conditions (PEEPi,stat) in patients with severe airway obstruction. This may be related to regional differences in respiratory system mechanical properties and/or viscoelastic behavior. To evaluate this concept, PEEPi,stat and PEEPi,dyn were compared in six anesthetized paralyzed cats during dynamic hyperinflation produced by inverse ratio ventilation (IRV) and aerosolized methacholine (MCh). PEEPi,stat did not differ between IRV and MCh, averaging 2.70 +/- 0.33 (SE) and 2.70 +/- 0.25 cmH2O, respectively. PEEPi,dyn was significantly less with MCh (0.25 +/- 0.05 cmH2O) than IRV (2.05 +/- 0.28 cmH2O) (P < 0.0001), resulting in a lower PEEPi,dyn/PEEPi,stat ratio for MCh (0.10 +/- 0.02) than for IRV (0.76 +/- 0.03) (P < 0.0001). Compared with control values (33.5 +/- 3.7 cmH2O.l-1.s), maximum resistance (Rmax) was unchanged during IRV (29.1 +/- 2.1 cmH2O.l-1.s) but increased considerably with MCh (288.8 +/- 18.4 cmH2O.l-1.s) (P < 0.0001). Similar changes in minimum resistance (Rmin) and delta R (Rmax-Rmin) were noted. There was a strong inverse relationship between delta P, an index of time constant inequalities and viscoelastic pressure losses and PEEPi,dyn/PEEPi,stat ratio. No correlation was found between this ratio and Rmax, Rmin, delta R, or compliance. In conclusion, PEEPi,dyn considerably underestimates PEEPi,stat in acute nonhomogeneous airway obstruction with MCh in contrast to IRV, where the magnitude and distribution of mechanical properties remain unaltered. These findings support the concept that the difference between PEEPi,dyn and PEEPi,stat is related to regional time constant inequalities and/or increased viscoelastic pressure losses.

Influence of site of tracheal pressure measurement on in situ estimation of endotracheal tube resistance.

In situ measurement of distal tracheal pressure (Ptr) via an intraluminal side-hole catheter (IC) has been used to determine endotracheal tube (Rett) and intrinsic patient (Rpt) resistances in intubated subjects. Because of differences in cross-sectional area between the endotracheal tube (ETT) and trachea, fluid dynamic principles predict that IC position should critically influence these results. Accordingly, the aim of this study was to determine the effect of IC position on Rett. Ptr was recorded in vitro through an IC from 2 cm inside, at the tip of, or 2 cm outside an ETT (7, 8, and 9 mm ID) situated within an artificial trachea (13, 18, and 22 mm ID). A reference value of Rett was also obtained. Results were unaffected by IC position during inspiration, overestimating Rett by 7.9 +/- 0.7% (SE). In contrast, during expiration, Rett fell as IC position changed from outside to inside the ETT and was underestimated by 41.3 +/- 3.6% with Ptr recorded inside the ETT. Varying ETT or tracheal size had little effect on the relative error in Rett. The IC itself did increase Rett due to a reduction in effective cross-sectional area, the change varying directly with IC size and inversely with ETT caliber. In vivo values in 11 intubated patients were comparable to in vitro results. In summary, IC position and size can have important consequences on in situ measurements of Ptr and should be considered when clinically monitoring Rett or Rpt.

Limitation of lower limb VO(2) during cycling exercise in COPD patients.

Patients with chronic obstructive pulmonary disease (COPD) usually stop exercise before reaching physiological limits in terms of O(2) delivery and extraction. A plateau in lower limb O(2) uptake (VO(2)) and blood flow occurs despite progression of the imposed workload during cycling in some patients with COPD, suggesting that maximal capacity to transport O(2) had been reached and that it had been extracted in the peripheral exercising muscles. This study addresses this observation. Symptom-limited incremental cycle exercise was performed by 14 men [62 +/- 11 (SD) yr] with severe COPD (forced expiratory volume in 1 s = 35 +/- 7% of predicted value). Leg blood flow was measured at each exercise step with a thermodilution catheter inserted in the femoral vein. This value was multiplied by two to account for both working legs (Q(LEGS)). Arterial and femoral venous blood was sampled at each exercise step to measure blood gases. Leg O(2) consumption (VO(2LEGS)) was calculated according to the Fick equation. Total body VO(2) (VO(2TOT)) was measured from expired gas analysis, and tidal volume (VT) and minute ventilation (VE) were derived from the flow signal. In eight patients, VO(2LEGS) kept increasing in parallel with VO(2TOT) as external work rate was increasing. In six subjects, a plateau in VO(2LEGS) and Q(LEGS) occurred during exercise (increment of <3% between 2 consecutive increasing workloads) despite the increase in workload and VO(2TOT) [corresponding mean was 110 +/- 38 ml (11 +/- 4%)]. These six patients also exhibited a plateau in O(2) extraction during exercise. Peak exercise work rate was higher in the eight patients without a plateau than in the six with a plateau (51 +/- 10 vs. 40 +/- 13 W, P = 0.043). VT, VE, and dyspnea were significantly greater at submaximal exercise in patients of the plateau group compared with those of the nonplateau group. These results show that, in some patients with COPD, blood flow directed to peripheral muscles and O(2) extraction during exercise may be limited. We speculate that redistribution of cardiac output and O(2) from the lower limb exercising muscles to the ventilatory muscles is a possible mechanism.

Metabolic and hemodynamic responses of lower limb during exercise in patients with COPD.

Premature lactic acidosis during exercise in patients with chronic obstructive pulmonary disease (COPD) may play a role in exercise intolerance. In this study, we evaluated whether the early exercise-induced lactic acidosis in these individuals can be explained by changes in peripheral O2 delivery (O2). Measurements of leg blood flow by thermodilution and of arterial and femoral venous blood gases, pH, and lactate were obtained during a standard incremental exercise test to capacity in eight patients with severe COPD and in eight age-matched controls. No significant difference was found between the two groups in leg blood flow at rest or during exercise at the same power outputs. Blood lactate concentrations and lactate release from the lower limb were greater in COPD patients at all submaximal exercise levels (all P < 0.05). Leg D02 at a given power output was not significantly different between the two groups, and no significant correlation was found between this parameter and blood lactate concentrations. COPD patients had lower arterial and venous pH at submaximal exercise, and there was a significant positive correlation between venous pH at 40 W and the peak O2 uptake (r = 0.91, P < 0.0001). The correlation between venous pH and peak O2 uptake suggests that early muscle acidosis may be involved in early exercise termination in COPD patients. The early lactate release from the lower limb during exercise could not be accounted for by changes in peripheral O2. The present results point to skeletal muscle dysfunction as being responsible for the early onset of lactic acidosis in COPD.