Modifying track layout from straight to circular has a modest effect on the 6-min walk distance

BACKGROUND: The protocol used for the 6-min walk test (6MWT) influences its results. The only study to examine the effect of modifying track layout performed a retrospective analysis and concluded that institutions using continuous tracks yield greater distances than those using straight tracks. Agreement between the distances measured on different tracks could not be examined. We evaluated the effect of modifying track layout on walk distance and examined the agreement and repeatability of distances measured on different tracks. METHODS: In a prospective, randomized, cross-over study, 27 COPD subjects (FEV(1), 38 +/- 14% [mean +/- SD]; 15 men) attended three separate test sessions, completing six 6MWTs. To familiarize all subjects with both tracks, the first two sessions comprised two 6MWTs on either a circular or straight track. During the final session, each subject was tested once on the straight and once on the circular track. RESULTS: The distance walked on the circular track exceeded the straight track by 13 +/- 17 m (p < 0.001). The limit of agreement between tracks was 33 m. Coefficient of repeatability values when the test was completed on different days for the straight and circular tracks were 51 m and 65 m, respectively. CONCLUSIONS: When evaluating changes in 6-min walk distance in groups of patients, track layout should be standardized. However, the effect of modifying track layout on an individual's walking distance is small compared to their daily variability in walk distance. Therefore, standardizing track layout for any given individual may be inconsequential when evaluating the change in distances from tests performed on different days.     

Effects of a walking aid in COPD patients receiving oxygen therapy

STUDY OBJECTIVES: To elucidate whether a simple walking aid may improve physical performance in COPD patients with chronic respiratory insufficiency who usually carry their own heavy oxygen canister. DESIGN: Randomized crossover trial. SETTING: Physiopathology laboratory of three rehabilitation centers. PATIENTS AND INTERVENTIONS: We studied 60 stable COPD patients (mean age, 70.6 +/- 7.9 years; FEV(1), 44.8 +/- 14.3% of predicted [+/- SD]) with chronic respiratory insufficiency who randomly performed, on 2 consecutive days, a standardized 6-min walking test using two different modalities: a full-weight oxygen canister transported using a small wheeled cart and pulled by the patient (Aid modality) or full-weight oxygen canister carried on the patient's shoulder (No-Aid modality). MEASUREMENTS AND RESULTS: The distance walked, peak effort dyspnea, and leg fatigue scores as primary outcomes, and other cardiorespiratory parameters as secondary outcomes were recorded during both tests. A significant difference (p < 0.05) between the two tests occurred for all the measured outcomes in favor of the Aid modality. Most importantly, significant changes for distance (+ 43 m, p < 0.001), peak effort dyspnea (- 2.0 points, p < 0.001), leg fatigue (- 1.4 points, p < 0.001), as well as for mean and nadir oxygen saturation and heart rate with the Aid modality (but not with the No-Aid modality) were recorded in the subgroup of patients walking < 300 m at baseline. CONCLUSIONS: This study suggests that a simple walking aid may be helpful in COPD patients receiving long-term oxygen therapy, particularly in those with lower residual exercise capacity.     

Six-minute walking-induced systemic inflammation and oxidative stress in muscle-wasted COPD patients

BACKGROUND: Systemic inflammation and oxidative stress are potential mechanisms for muscle wasting in COPD patients. Six-minute walking testing (6MWT) has been suggested as simple and valid exercise test in COPD that is well tolerated, and reflective of activities of daily living. The present study investigated physiologic and systemic immunologic responses to a 6MWT in muscle-wasted patients with COPD and compared them with maximal cardiopulmonary exercise testing (CPET). METHODS: Ten patients with muscle-wasted COPD were included (fat-free mass index [FFMI]: men, < 16 kg/m2; women, < 15 kg/m2). 6MWT and CPET were performed in random order. The physiologic response was followed by a mobile oxycon. Arterial blood was obtained at rest and after exercise to measure blood gases and markers of systemic inflammation and oxidative stress. RESULTS: In these patients (FEV1 55 +/- 4% of predicted [mean +/- SE]), the 6MWT was a submaximal, albeit intense, exercise as reflected by oxygen uptake (VO2), minute ventilation, heart rate, and lactate values. Leukocytosis was less intense after 6MWT compared to CPET. Contrary, the increase in interleukin-6, free radical release by neutrophils, oxidation of proteins and lipids, and the reduction in antioxidant capacity were similar after both exercises. FFMI was inversely related to 6MWT-induced increases in protein and lipid peroxidation. CONCLUSIONS: This study shows that a 6MWT induces a systemic immunologic response in muscle-wasted patients with COPD, which is comparable to CPET-induced responses. The correlation between systemic oxidative stress and the degree of muscle wasting supports a possible causal relation between systemic inflammation, oxidative stress, and muscle wasting.     

Six-minute walk test for the evaluation of pulmonary disease severity in scleroderma patients

BACKGROUND: Pulmonary involvement is the leading cause of systemic sclerosis (SSc)-related deaths. A simple test to evaluate exercise capacity is the 6-min walk test (6MWT), and the walk distance is used as a primary outcome in clinical trials. Hemoglobin desaturation during a 6MWT is predictive of mortality in patients with primary pulmonary hypertension. Our objectives were to evaluate the walk distance and resting oxygen saturation - oxygen saturation after the 6-min period (DeltaSat) during the 6MWT in patients with SSc, and to establish correlations between the 6MWT results and other clinical variables. METHODS: We analyzed 110 SSc patients. DeltaSat was defined as a fall of end-of-test saturation >or= 4%. Clinical and demographic data were collected. All the patients were submitted to chest radiographs and high-resolution CT (HRCT) and underwent pulmonary function testing and echocardiography, and the presence of autoantibodies was determined. RESULTS: The variables associated with a walk distance < 400 m (p < 0.05) were age, dyspnea index, fibrosis on radiography, pulmonary arterial systolic pressure (PASP) >or= 30 mm Hg, and desaturation. The variables associated with DeltaSat (p < 0.05) were age, positive anti-Scl-70 autoantibody, dyspnea index, fibrosis on radiography, FVC < 80% of predicted, PASP >or= 30 mm Hg, and ground-glass or reticular opacities on HRCT. In the multivariate logistic regression analysis, three variables were significant when tested with walk distance: age, race, and dyspnea index; four variables were significant when tested with DeltaSat: age, dyspnea index, positive anti-Scl-70 autoantibody, and FVC < 80% of predicted. CONCLUSIONS: Desaturation during a 6MWT provides additional information regarding severity of disease in scleroderma patients with pulmonary manifestations.     

Double-blind, randomized trial of dexmethylphenidate hydrochloride for the treatment of sarcoidosis-associated fatigue

BACKGROUND: Fatigue is a common complaint in patients with sarcoidosis. We studied the effectiveness of dexmethylphenidate hydrochloride (d-MPH) in treating sarcoidosis-associated fatigue. METHODS: This was a double-blind, randomized, placebo-controlled, crossover trial of d-MPH. Patients were seen weekly and completed Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Fatigue Assessment Score (FAS) instruments. After a 1-week wash-in period, patients received either d-MPH or placebo. After 8 weeks, the medications were stopped. Following a 2-week wash-out period, patients were crossed over to 8 weeks of the other treatment. FVC and 6-min walk distance (6MWD) were determined initially and after each treatment arm. RESULTS: Ten patients with sarcoidosis were enrolled: 8 women and 5 African Americans. All were receiving systemic sarcoidosis therapy. Significant improvement in fatigue was reported by patients when receiving d-MPH (FACIT-F, p < 0.001; FAS, p < 0.02). FVC was higher at the end of 8 weeks of d-MPH compared to the baseline values (baseline median, 2.38 L; range, 1.17 to 4.53 L; placebo median, 2.41 L; range, 1.50 to 4.65 L; d-MPH median, 2.56 L; range, 1.50 to 4.96 L; p < 0.01). There was no significant difference in the 6MWD (baseline median, 330 m; range, 60 to 460 m; placebo median, 350 m; range, 180 to 460 m; d-MPH median, 390 m; range, 200 to 460 m). d-MPH was well tolerated. CONCLUSIONS: Treatment with d-MPH was associated with a significant improvement in sarcoidosis-associated fatigue. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00361387.     

Granulocyte chemotactic activity in exhaled breath condensate of healthy subjects and patients with COPD

BACKGROUND: Several chemoattractants have been measured in exhaled breath condensate (EBC) from patients with COPD. The aim of this study was to compare the eosinophil and neutrophil chemotactic activity contained in EBC from healthy subjects and patients with COPD. METHODS: EBC collected using a commercially available condenser (EcoScreen; Erich Jaeger Viasys; Hoechberg, Germany) was compared in 45 COPD patients and 65 healthy subjects. EBC chemotactic activity for eosinophils and neutrophils was assessed using microchambers (Boyden; Neuro Probe; Cabin John, MD). Chemotactic index (CI) was used to evaluate cell migration. RESULTS: EBC from patients with COPD (CI, 2.21 +/- 0.16 [mean +/- SEM]) and healthy subjects (CI, 1.67 +/- 0.11) displayed significant neutrophil chemotactic activity (p < 0.0001 for both), which was however higher in patients with COPD (p < 0.001). Healthy smokers had a significantly raised CI for neutrophils by comparison with healthy nonsmokers (p < 0.01) and ex-smokers (p < 0.05). Likewise, current COPD smokers tended to have greater neutrophil CI than COPD who stopped smoking (p = 0.08). COPD ex-smokers had raised chemotactic activity by comparison with healthy ex-smokers (p < 0.05). Anti-interleukin-8 (10(-6) g/mL) antibodies reduced neutrophil chemotactic activity by 35.2% (p < 0.05). EBC also contained significant eosinophil chemotactic activity in healthy subjects (CI, 1.68 +/- 0.09; p < 0.0001) and patients with COPD (CI, 1.23 +/- 0.07; p < 0.01), with a significantly lower CI in patients with COPD as compared to healthy subjects (p < 0.001). Smoking did not influence eosinophil chemotactic activity in healthy subjects or patients with COPD. CONCLUSIONS: Current smoking favors neutrophil chemotactic activity. As compared to healthy subjects, EBC from patients with COPD displays a skewed chemotactic activity toward neutrophils vs eosinophils.     

Quadriceps weakness is related to exercise capacity in idiopathic pulmonary fibrosis

STUDY OBJECTIVE: In COPD, it has been shown that peripheral muscle dysfunction is a factor determining exercise intolerance. We examined the hypothesis that exercise capacity of patients with idiopathic pulmonary fibrosis (IPF) is, at least in part, determined by peripheral muscle dysfunction. METHODS: Maximum oxygen uptake (V(O2)max) was evaluated in 41 consecutive patients with IPF, along with potential determinants of exercise capacity, both in the lungs and in the peripheral muscles. RESULTS: Patients had reduced V(O2)max (893 +/- 314 mL, 46.0% predicted) and reduced quadriceps force (QF) [65% predicted]. Significant correlates of V(O2)max reduction were vital capacity (VC) [r = 0.79], total lung capacity (r = 0.64), diffusion capacity (r = 0.64), QF (r = 0.62), maximum expiratory pressure (r = 0.48), and Pa(O2) at rest (r = 0.33). In stepwise multiple regression analysis, VC and QF were independent predictors of V(O2)max. Furthermore, in subgroup analysis, QF was a significant contributing factor for V(O2)max in patients who discontinued exercise because of dyspnea and/or leg fatigue. CONCLUSIONS: We conclude that QF is a predictor of exercise capacity in IPF. Measures that improve muscle function might improve exercise tolerance.     

Air travel hypoxemia vs. the hypoxia inhalation test in passengers with COPD

BACKGROUND: Limited data are available comparing air travel with the hypoxia inhalation test (HIT) in passengers with COPD. The aim of this study was to assess the predictive capability of the HIT to in-flight hypoxemia in passengers with COPD. METHODS: Thirteen passengers (seven female passengers) with COPD (mean [+/- SD], FEV(1)/FVC ratio, 44 +/- 17%) volunteered for this study. Respiratory function tests were performed preflight. Pulse oximetry, cabin pressure, and dyspnea were recorded in flight. The HIT and a 6-min walk test were performed postflight. The in-flight oxygenation response was compared to the HIT results and respiratory function parameters. RESULTS: All subjects flew without the use of oxygen, and no adverse events were recorded in-flight (mean cabin altitude, 2,165 m; altitude range, 1,892 to 2,365 m). Air travel caused significant desaturation (mean preflight oxygen saturation, 95 +/- 1%; mean in-flight oxygen saturation, 86 +/- 4%), which was worsened by activity (nadir pulse oximetric saturation [Spo(2)], 78 +/- 6%). The HIT caused mean desaturation that was comparable to that of air travel (84 +/- 4%). The mean in-flight partial pressure of inspired oxygen (Pio(2)) was higher than the HIT Pio(2) (113 +/- 3 mm Hg vs 107 +/- 1 mm Hg, respectively; p < 0.001). The HIT Spo(2) showed the strongest correlation with in-flight Spo(2) (r = 0.84; p < 0.001). CONCLUSION: Significant in-flight desaturation can be expected in passengers with COPD. The HIT results compared favorably with the air travel data, with differences explainable by Pio(2) and physical activity. The HIT is the best widely available laboratory test to predict in-flight hypoxemia.     

C-reactive protein levels and survival in patients with moderate to very severe COPD

BACKGROUND: Serum levels of C-reactive protein (CRP) are increased in patients with COPD and correlate modestly with variables predictive of outcomes. In epidemiologic studies, CRP level is associated with all-cause mortality in patients with mild-to-moderate disease. OBJECTIVE: To determine if CRP levels are associated with survival in patients with moderate to very severe COPD in comparison with other well-known prognostic parameters of the disease. METHODS: In 218 stable patients with COPD, we measured baseline serum CRP level, BODE (body mass index, obstruction, dyspnea, and exercise capacity) index and its components, arterial oxygenation (Pao(2)), inspiratory capacity (IC) to total lung capacity (TLC) ratio, and Charlson comorbidity score. We followed up the patients over time and evaluated the strength of the association between the variables and all-cause mortality. RESULTS: During the follow-up time (median, 36 months; 25th to 75th percentiles, 24 to 50 months), 54 patients (25%) died. CRP levels were similar between survivors and the deceased (median, 3.8 mg/L; 95% confidence interval, 1.9 to 8.1; vs median, 4.5 mg/L; 95% confidence interval, 2.1 to 11.5; p = 0.22) and was not significantly associated with survival. CONCLUSIONS: In this population of patients with clinically moderate to very severe COPD, the level of CRP level was not associated with survival compared with other prognostic clinical tools such as the BODE index, modified Medical Research Council scale, 6-min walk distance, percentage of predicted FEV(1), IC/TLC ratio < 0.25, and Pao(2). Other long-term studies of well-characterized patients with COPD could help determine the exact role of CRP levels as a biomarker in patients with clinical COPD.     

Impact of COPD exacerbations on patient-centered outcomes

BACKGROUND: Frequent exacerbations are associated with a faster decline in FEV(1), impaired health status, and worse survival. Their impact and temporal relationship with other outcomes such as functional status, dyspnea, and the multidimensional body mass index, obstruction, dyspnea, exercise capacity (BODE) index remain unknown. HYPOTHESIS: We reasoned that exacerbations affect the BODE index and its components, and that changes in the BODE index could be used to monitor the effect of exacerbations on the host. STUDY DESIGN: Prospective observational study in a Veterans Affairs medical center. METHODS: We studied 205 patients with COPD (mean [+/- SD] FEV(1), 43 +/- 15% predicted), and recorded the body mass index, FEV(1) percent predicted, modified Medical Research Council dyspnea scale, 6-min walk distance, and the BODE index at baseline, during the exacerbation, and at 6, 12, and 24 months following the first episode, and documented all exacerbations for 2 years after the first acute exacerbation. RESULTS: From the cohort, 130 patients (63%) experienced 352 exacerbations or (0.85 exacerbations per patient per year); 48 patients (23%), experienced one episode, 82 patients (40%) experienced 2 or more exacerbations, and 50 patients required hospitalization. At study entry, exacerbators had a worse mean baseline BODE index score (4.2 +/- 2.1 vs 3.57 +/- 2.3, respectively; p < 0.03). The BODE index score worsened by 1.38 points during the exacerbation, and remained 0.8 and 1.1 points above baseline at 1 and 2 years, respectively. There was little change in BODE index score at 2 years in nonexacerbators. CONCLUSION: COPD exacerbations negatively impact on the BODE index and its components. The BODE index is a sensitive tool used to assess the impact of exacerbations and to monitor COPD disease progression.     

Atrial septostomy decreases sympathetic overactivity in pulmonary arterial hypertension

BACKGROUND: We have reported previously that the sympathetic nervous system is activated in patients with pulmonary arterial hypertension (PAH), and that this is only partly explained by a decrease in arterial oxygenation. Possible causes for increased muscle sympathetic nerve activity (MSNA) in patients with PAH include right atrial distension and decreased cardiac output. Both may be improved by atrial septostomy, but this intervention also further decreases arterial oxygenation. In the present study, we wanted to investigate the effect of atrial septostomy on MSNA in patients with PAH. METHODS: We recorded BP, heart rate (HR), arterial O2 saturation (SaO2), and MSNA before and after atrial septostomy in PAH patients (mean [+/- SE] age, 48 +/- 5 years) and in closely matched control subjects. Measurements were also performed after septostomy, while SaO2 was brought to the preprocedure level by supplemental O2 therapy. RESULTS: Compared to the control subjects (n = 10), the PAH patients (n = 11) had a lower mean BP (75 +/- 2 vs 96 +/- 3 mm Hg, respectively; p < 0.001), lower mean SaO2 (92 +/- 1% vs 97 +/- 0%, respectively; p < 0.001), increased mean HR (84 +/- 4 vs 68 +/- 3 beats/min; p < 0.01), and markedly increased mean MSNA (76 +/- 5 vs 29 +/- 2 bursts per minute; p < 0.001). Atrial septostomy decreased mean SaO2 (to 85 +/- 2%; p < 0.001) and mean MSNA (to 69 +/- 4 bursts per minute; p < 0.01), but did not affect HR or BP. Therapy with supplemental O2 did not affect MSNA, BP, or HR. The decrease in MSNA was correlated to the decrease in right atrial pressure (r = 0.62; p < 0.05). CONCLUSIONS: Atrial septostomy in PAH patients decreases sympathetic hyperactivity despite an associated decrease in arterial oxygenation, and this appears to be related to decreased right atrial distension.     

Tiotropium and simplified detection of dynamic hyperinflation

STUDY OBJECTIVE: To detect dynamic hyperinflation (DH) by evaluating reduction in inspiratory capacity (IC) during metronome-paced hyperventilation (MPH) in patients with moderate-to-severe COPD, studied before and after treatment with tiotropium. METHODS: IC and FEV(1) were measured before and immediately after MPH at two times resting the respiratory rate for 20 s in 60 COPD patients (28 men; mean age, 66 +/- 10 years [+/- SD]) before and after 30 days of treatment with tiotropium bromide, 18 mug. Patients were encouraged to maintain a constant tidal volume during MPH. RESULTS: At baseline, mean FEV(1) was 1.5 +/- 0.1 L (+/- SE) [57 +/- 1.6% of predicted], mean FVC was 2.6 +/- 0.1L (77 +/- 1.8% of predicted), and mean FEV(1)/FVC was 56 +/- 1%. After 180 mug of aerosolized albuterol sulfate, mean FEV(1) was 1.7 +/- 0.1 L (63 +/- 1.5% of predicted) [p < 0.001] and mean FEV(1)/FVC was 58 +/- 1%. Compared to baseline, after 30 days and 1.5 h after tiotropium there was an increase in IC of 0.18 +/- 0.04L (p < 0.0001); FEV(1) of 0.13 +/- 0.03 L (5.6 +/- 0.8% of predicted; p = 0.0002); FVC of 0.22 +/- 0.05 L (6.5 +/- 1.3% of predicted; p < 0.001); and decrease in end-expiratory lung volume (EELV)/total lung capacity (TLC) of - 3.1 +/- 0.6% (p = 0.0001); a decrease in end-inspiratory lung volume (EILV)/TLC of - 2.9 +/- 1.3% (p = 0.03); and no change in TLC (- 0.06 +/- 0.05 L). Results following MPH-induced DH at baseline and after 30 days of tiotropium were similar, with decreases in IC (- 0.35 +/- 0.03 L; p < 0.001); FEV(1) (- 0.05 +/- 0.04 L; p = 0.2); and FVC (- 0.22 +/- 0.03 L; p < 0.0001); no change in TLC; and increases in EELV/TLC (11.8 +/- 1.0% of predicted; p < 0.0001) and EILV/TLC (4.0 +/- 1.3% of predicted, p < 0.003). CONCLUSION: In patients with moderate-to-severe COPD, tiotropium did not reduce MPH-induced DH and reduction in IC, compared to baseline. However, because tiotropium induced bronchodilation and increased baseline IC, lower operational lung volumes may blunt the effect of MPH-induced DH. The noninvasive simplicity of MPH-induced DH provides a clinically useful screening surrogate to monitor changes in IC following treatment with tiotropium.     

Importance of noninvasively measured respiratory muscle overload among the causes of hospital readmission of COPD patients

AIM: To evaluate the influence of respiratory muscle overload and right cardiac overload among the possible risk factors of hospital readmission in a 1-year follow-up of a cohort of patients with moderate-to-severe COPD. METHODS: A total of 112 COPD patients who were admitted consecutively to the hospital for acute exacerbation. At hospital discharge, we evaluated the conventional clinical and functional determinations in addition to the pressure-time index (PTI), which is obtained using the equation PTI = (Pawo/Pimax) x (Ti/Ttot) x 100, where Pawo represents the mean airway pressure measured at the mouth during spontaneous breathing, Pimax is the maximal inspiratory pressure, Ti is the inspiratory time, and Ttot is the total breathing cycle time. A cardiac echo-Doppler examination was carried out when patients were in stable condition and presented clinical signs of right cardiac overload prior to inclusion in the study. RESULTS: Multivariate analysis showed that the use of long-term oxygen therapy (LTOT) and high PTI (> 0.25) were independently related to the risk of hospital readmission. Patients receiving LTOT had higher Paco(2) (p < 0.05), FEV(1) percent predicted (p < 0.05), FVC percent predicted (p < 0.05), and Pao(2) (p < 0.05), and had higher Paco(2) (p < 0.05). An elevated systolic pulmonary arterial pressure (> 40 mm Hg) was also independently related, but only 28 patients had echo-Doppler data that could be used. CONCLUSIONS: At hospital discharge, noninvasively measured respiratory muscle overload as well as the use of LTOT were associated with an increased risk of hospital readmission for exacerbation in patients with moderate-to-severe COPD.     

Predictors of survival in COPD patients with chronic hypercapnic respiratory failure receiving noninvasive home ventilation

BACKGROUND: Patients with COPD and chronic hypercapnic respiratory failure (CHRF) are at high risk, and noninvasive ventilation at home is increasingly being used. Knowledge of prognostic parameters under these conditions is limited but may be clinically helpful and highlight the role of noninvasive ventilation. METHODS: In 188 patients with COPD (mean +/- SD FEV1, 31.0 +/- 9.6% of predicted; PaCo2, 56.3 +/- 9.4 mm Hg) discharged from the hospital receiving NIV between July 1994 and July 2004, the prognostic value of body mass index (BMI), lung function, laboratory parameters, and blood gas levels was assessed by univariate and multivariate Cox regression analyses. Moreover, the impact of changes in risk factors on mortality assessed 6.7 +/- 2.8 months after the initiation of noninvasive ventilation was evaluated. RESULTS: Overall, the mortality rate during follow-up (duration, 32.2 +/- 24.3 months) was 44.7%, with 1-year, 2-year, and 5-year survival rates of 84.0%, 65.3%, and 26.4%. Deaths resulted predominantly from respiratory causes (73.8%). Univariate regression analyses revealed age, BMI, hemoglobin, FEV1, specific airway resistance, residual volume (RV)/total lung capacity (TLC), pH, and base excess (BE) to be associated with prognosis (p < 0.01 each), whereas multivariate analysis identified only age, BMI, RV/TLC, and BE as independent predictors (p < 0.05). In patients at risk (BMI < 25 km/m2, RV/TLC >or= 73%, or BE >or= 9 mmol/L), changes in these predictors were also associated with survival. CONCLUSIONS: In patients with COPD and CHRF, nutritional status, hyperinflation, and BE, which turned out to be reliable and consistent markers in CHRF, were independent prognostic factors for mortality. These data favor a multidimensional approach in these patients, including the use of noninvasive ventilation.     

Inspiratory muscle unloading by neurally adjusted ventilatory assist during maximal inspiratory efforts in healthy subjects

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation in which the ventilator is controlled by the electrical activity of the diaphragm (EAdi). During maximal inspirations, the pressure delivered can theoretically reach extreme levels that may cause harm to the lungs. The aims of this study were to evaluate whether NAVA could efficiently unload the respiratory muscles during maximal inspiratory efforts, and if a high level of NAVA would suppress EAdi without increasing lung-distending pressures. METHOD: In awake healthy subjects (n = 9), NAVA was applied at increasing levels in a stepwise fashion during quiet breathing and maximal inspirations. EAdi and airway pressure (Paw), esophageal pressure (Pes), and gastric pressure, flow, and volume were measured. RESULTS: During maximal inspirations with a high NAVA level, peak Paw was 37.1 +/- 11.0 cm H(2)O (mean +/- SD). This reduced Pes deflections from - 14.2 +/- 2.7 to 2.3 +/- 2.3 cm H(2)O (p < 0.001) and EAdi to 43 +/- 7% (p < 0.001), compared to maximal inspirations with no assist. At high NAVA levels, inspiratory capacity showed a modest increase of 11 +/- 11% (p = 0.024). CONCLUSION: In healthy subjects, NAVA can safely and efficiently unload the respiratory muscles during maximal inspiratory maneuvers, without failing to cycle-off ventilatory assist and without causing excessive lung distention. Despite maximal unloading of the diaphragm at high levels of NAVA, EAdi is still present and able to control the ventilator.     

Sildenafil improves walk distance in idiopathic pulmonary fibrosis

Pulmonary hypertension is a common finding in patients with idiopathic pulmonary fibrosis (IPF), and is associated with increased morbidity and mortality. Therapy with sildenafil has been shown to decrease pulmonary vascular resistance in patients with pulmonary fibrosis and may improve functional status. Patients with IPF and documented pulmonary hypertension were followed up in an open-label study of sildenafil. The 6-min walk test distance (6MWD) was obtained before and after 3 months of sildenafil therapy. Fourteen patients were followed up in the study; 11 patients completed both 6-min walk tests. The mean improvement in walk distance was 49.0 m (90% confidence interval, 17.5 to 84.0 m). When all 14 patients were dichotomized into groups of "responders" (ie, >/= 20% improvement in 6MWD) or "nonresponders" (ie, < 20% change or unable to complete), 57% were classified as responders. Sildenafil is a promising and well-tolerated therapeutic agent for use in patients with IPF and pulmonary hypertension, and should be studied in a large, well-controlled trial.     

Limitations of transcutaneous carbon dioxide measurements for assessing long-term mechanical ventilation

STUDY OBJECTIVES: Transcutaneous CO(2) pressure (Ptcco(2)) and transcutaneous O(2) pressure (Ptco(2)) measurements are routinely used in pediatric ICUs in order to avoid serial arterial punctures. The aim of this study was to determine the value of Ptcco(2) assessment during the evaluation of home ventilation in 12 adult patients with COPD or restrictive respiratory failure in the stable state (mean [+/- SD] basal Paco(2), 48.8 +/- 8.3 mm Hg) who were treated by mask or tracheotomy-mediated ventilation. METHODS: After radial catheter insertion, patients were instructed to breathe spontaneously for 40 min and then to receive ventilation for 40 min according to their individual home ventilation modalities. An in vivo calibration was performed in the initial stage of the study in order to optimize the arterial Pco(2) and Ptcco(2) values. Every 5 min, transcutaneous measurements were performed and simultaneously compared with arterial values. MEASUREMENTS AND RESULTS: Ptcco(2) and Ptco(2) were correlated with arterial values (p < 0.0001) except for Paco(2) values of > 56 mm Hg and Pao(2) values of > 115 mm Hg. During ventilation, Paco(2) decreased >or= 4 mm Hg in seven patients. Ptcco(2) variations recorded during consecutive 5-min periods while the patient received mechanical ventilation were well correlated with the arterial variations (p = 0.0033), with a delay of < 5 min. CONCLUSION: Ptcco(2) values and variations accurately reflected Paco(2) values and variations during mechanical ventilation. However, the accuracy of these data seems to be restricted to patients with Paco(2) values of < 56 mm Hg.     

CXCR3 and CCR5 chemokines in induced sputum from patients with COPD

BACKGROUND: COPD is associated with increased numbers of CD4(+) and CD8(+) lymphocytes and macrophages in the small airways and lung parenchyma. The chemokines regulating T-cell recruitment into the lung are unknown but may involve CXCR3 and CCR5 chemoattractants. The aims of this study were to determine the concentrations of CXCR3 chemokines CXCL9, CXCL10, CXCL11, and the CCR5 chemokine CCL5 in induced sputum from patients with COPD, smokers, and nonsmokers, and to examine the relationship between chemokine expression, inflammatory cells, and airway obstruction. METHODS: Differential cell counts were performed and concentrations of CXCL9, CXCL10, CXCL11, and CCL5 were measured in induced sputum from nonsmokers (n = 18), smokers (n = 20), and COPD patients (n = 35) using an enzyme-linked immunosorbent assay. RESULTS: Concentrations of CXCL9, CXCL10, CXCL11, and CCL5 were significantly increased in the sputum of patients with COPD when compared with nonsmokers but not smokers without obstruction: CXCL9 (median, 14.3 pg/mL; interquartile range [IQR], 6.5 to 99.3; vs median, 1.4 pg/mL; IQR, 0 to 10.4 [p < 0.001]; vs 8.5 pg/mL; IQR, 0 to 16.0, respectively); CXCL10 (16.9 pg/mL; IQR, 6.2 to 148.8; vs 3.7 pg/mL; IQR, 0 to 18.8 [p < 0.05]; vs 11.3 pg/mL; IQR, 3.7 to 46.7); CXCL11 (58.1 pg/mL; IQR, 34.5 to 85.3; vs 33.5 pg/mL; IQR, 23.2 to 49.7 [p < 0.05]; vs 49.8 pg/mL; IQR, 32.6 to 105.6); and CCL5 (59.9 pg/mL; IQR, 57.1 to 67.8; vs 33.5 pg/mL; IQR, 31.6 to 36.9 [p < 0.001]). CCL5 in sputum from smokers was also significantly increased compared with that from nonsmokers (median, 63.0 pg/mL; IQR, 60.8 to70.2; p < 0.001). There was a negative correlation between FEV(1) percentage of predicted, FEV(1)/FVC ratio, and percentage of macrophages, and all the chemokines analyzed. Neutrophil numbers correlated positively with the concentrations of chemokines. CONCLUSIONS: CXCR3 chemokines and CCL5 are increased in sputum from COPD patients compared with nonsmokers, and may be important in COPD pathogenesis.     

Copeptin, C-reactive protein, and procalcitonin as prognostic biomarkers in acute exacerbation of COPD

BACKGROUND: A novel approach to estimate the severity of COPD exacerbation and predict its outcome is the use of biomarkers. We assessed circulating levels of copeptin, the precursor of vasopressin, C-reactive protein (CRP), and procalcitonin as potential prognostic parameters for in-hospital and long-term outcomes in patients with acute exacerbation of COPD (AECOPD) requiring hospitalization. METHODS: Data of 167 patients (mean age, 70 years; mean FEV(1), 39.9 +/- 16.9 of predicted [+/- SD]) presenting to the emergency department due to AECOPD were analyzed. Patients were evaluated based on clinical, laboratory, and lung function parameters on hospital admission, at 14 days, and at 6 months. RESULTS: Plasma levels of all three biomarkers were elevated during the acute exacerbation (p < 0.001), but levels at 14 days and 6 months were similar (p = not significant). CRP was significantly higher in patients presenting with Anthonisen type I exacerbation (p = 0.003). In contrast to CRP and procalcitonin, copeptin on hospital admission was associated with a prolonged hospital stay (p = 0.002) and long-term clinical failure (p < 0.0001). Only copeptin was predictive for long-term clinical failure independent of age, comorbidity, hypoxemia, and lung functional impairment in multivariate analysis (p = 0.005). The combination of copeptin and previous hospitalization for COPD increased the risk of poor outcome (p < 0.0001). Long-term clinical failure was observed in 11% of cases with copeptin < 40 pmol/L and no history of hospitalization, as compared to 73% of patients with copeptin >/= 40 pmol/L and a history of hospitalization (p < 0.0001). CONCLUSIONS: We suggest copeptin as a prognostic marker for short-term and long-term prognoses in patients with AECOPD requiring hospitalization.     

The early phase of the minute ventilation recovery curve predicts extubation failure better than the minute ventilation recovery time

STUDY OBJECTIVES: To determine, in patients who had successful outcomes in spontaneous breathing trials (SBTs), whether the analysis of the minute ventilation (Ve) recovery time obtained by minute-by-minute sequential monitoring after placing the patient back on mechanical ventilation (MV) may be useful in predicting extubation outcome. DESIGN: Twelve-month prospective observational study. SETTING: Medical-surgical ICU of a university hospital. PATIENTS: Ninety-three patients receiving > 48 h of MV. INTERVENTIONS: Baseline respiratory parameters (ie, respiratory rate, tidal volume, and Ve) were measured under pressure support ventilation prior to the SBT. After tolerating the SBT, patients again received MV with their pre-SBT ventilator settings, and respiratory parameters were recorded minute by minute. MEASUREMENTS AND RESULTS: Seventy-four patients (80%) were successfully extubated, and 19 patients (20%) were reintubated. Reintubated patients were similar to non-reintubated patients in baseline respiratory parameters and baseline variables, except for age and COPD diagnosis. The recovery time needed to reduce Ve to half the difference between the Ve measured at the end of a successful SBT and basal Ve (RT50%DeltaVe) was lower in patients who had undergone successful extubation than in those who had failed extubation (mean [+/- SD] time, 2.7 +/- 1.2 vs 10.8 +/- 8.4 min, respectively; p < 0.001). Multiple logistic regression adjusted for age, sex, comorbid status, diagnosis (ie, neurocritical vs other), and severity of illness revealed that neurocritical disease (odds ratio [OR], 7.6; p < 0.02) and RT50%DeltaVe (OR, 1.7; p < 0.01) were independent predictors of extubation outcome. The area under the receiver operating characteristic curve for the predictive model was 0.89 (95% confidence interval, 0.81 to 0.96). CONCLUSION: Determination of the RT50%DeltaVe at the bedside may be a useful adjunct in the decision to extubate, with better results found in nonneurocritical patients.