A randomized, placebo-controlled trial of bronchodilators for bronchoscopy in patients with COPD

BACKGROUND: In contrast to asthma, the indication for bronchodilators prior to bronchoscopy in patients with COPD has not been properly investigated. We therefore performed a randomized, double-blind, placebo-controlled trial to determine whether use of a short-acting bronchodilator provides a protective effect in patients with COPD undergoing bronchoscopy. METHODS: One hundred twenty patients undergoing bronchoscopy were included. Patients with COPD were randomized to receive either 200 mug of salbutamol (n = 40) or placebo (n = 40) before bronchoscopy. Control patients (n = 40) did not receive any inhaled medication. Spirometry was performed before and 2 h after bronchoscopy in all patients. Sedative drug requirements and hemodynamic parameters were recorded. RESULTS: Hemodynamic findings before, during, and after bronchoscopy were similar in patients with COPD randomized to either salbutamol or placebo (p = not significant for all). Compared to prebronchoscopy values, postbronchoscopy percentage of predicted FEV(1) decreased significantly in all three groups: salbutamol (median, - 4.7%; interquartile range [IQR], - 13.3 to 6.6); placebo (median, - 4.8%; IQR, - 19.9 to 8.4); and control subjects (median, - 10.0%; IQR, - 20.2 to - 3.3) [p = 0.023]. The decrease in FEV(1) was similar in all three patient groups (p = 0.432). The relative change in FEV(1) was inversely correlated to the increasing severity of COPD as expressed by Global Initiative for Chronic Obstructive Lung Disease stages (p = 0.01). CONCLUSIONS: Premedication with an inhaled short-acting beta-agonist cannot be recommended in patients with COPD undergoing bronchoscopy.     

Safety of sputum induction during exacerbations of COPD

Sputum induction (SI) is considered to be a safe tool for assessing airway inflammation in stable patients with COPD, but little is known about its safety during exacerbations. We therefore assessed the safety of SI during COPD exacerbations. SI data from 44 COPD patients were assessed both in the stable phase and during exacerbation. The median FEV1 for the stable phase and exacerbation were 61% predicted (interquartile range [IQR], 49 to 74% predicted) and 51% predicted (IQR, 45 to 60% predicted), respectively. The median decrease in FEV(1) with SI during an exacerbation was 0.27 L (IQR, 0.17 to 0.40 L) vs 0.28 L (IQR, 0.22 to 0.44 L) during the stable phase (p = 0.03). The patients experienced the associated dyspnea well; no other adverse events occurred. All FEV1 values returned to within 90% of their initial value within 30 min. A larger decrease in FEV1 due to SI during an exacerbation was associated with the following parameters in the stable phase of disease: lower total sputum cell count (r = -0.37; p = 0.01); higher percentage of eosinophils (r = 0.33; p = 0.04); and a larger decrease in FEV1 after SI (r = 0.39; p = 0.03). In a multivariate analysis, the only independent association was with the larger decrease in FEV1 in the stable phase. We concluded that SI can be safely carried out in patients with mild-to-moderate COPD who experience an exacerbation, and this occurs with no greater risk than in stable patients with COPD.     

Contemporary management of acute exacerbations of COPD: a systematic review and metaanalysis

BACKGROUND: Systemic corticosteroids, antibiotics, and noninvasive positive pressure ventilation (NPPV) are recommended for patients with acute exacerbation of COPD. However, their clinical benefits in various settings are uncertain. We undertook a systematic review and metaanalysis to systematically evaluate the effectiveness of these therapies. METHODS: MEDLINE and EMBASE were searched to identify relevant randomized controlled clinical trials published from January 1968 to November 2006. We identified additional studies by searching bibliographies of retrieved articles. RESULTS: Compared with placebo, systemic corticosteroids reduced treatment failure by 46% (95% confidence interval [CI], 0.41 to 0.71), length of hospital stay by 1.4 days (95% CI, 0.7 to 2.2), and improved FEV(1) by 0.13 L after 3 days of therapy (95% CI, 0.04 to 0.21). Meanwhile, the risk of hyperglycemia significantly increased (relative risk, 5.88; 95% CI, 2.40 to 14.41). Compared with placebo, antibiotics reduced treatment failure by 46% (95% CI, 0.32 to 0.92) and in-hospital mortality by 78% (95% CI, 0.08 to 0.62). Compared with standard therapy, NPPV reduced the risk of intubation by 65% (95% CI, 0.26 to 0.47), in-hospital mortality by 55% (95% CI, 0.30 to 0.66), and the length of hospitalization by 1.9 days (95% CI, 0.0 to 3.9). CONCLUSIONS: For acute COPD exacerbations, systemic corticosteroids are effective in reducing treatment failures, while antibiotics reduce mortality and treatment failures in those requiring hospitalization and NPPV reduces the risk of intubation and in-hospital mortality, especially in those who demonstrate respiratory acidosis.     

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.     

A 1-year prospective study of the infectious etiology in patients hospitalized with acute exacerbations of COPD

INTRODUCTION: Infection is a major cause of acute exacerbations of COPD (AECOPDs). We aimed to study the infectious etiology related to AECOPD. METHODS: Patients admitted to an acute care hospital in Hong Kong with an AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005. Sputum samples, nasopharyngeal aspirate (NPA) samples, and paired serology specimens were collected. Spirometry was performed with patients in the stable phase 2 to 3 months after hospital discharge. RESULTS: There were 643 episodes of AECOPD among 373 patients. Their mean age was 75.3 years (SD, 7.9 years) with 307 male patients. The mean FEV(1) was 40.4% predicted (SD, 18.7% predicted), and the mean FEV(1)/FVC ratio was 58.4% (SD, 16.0%). Among sputum samples from the 530 episodes of AECOPD hospital admissions that were saved, 13.0%, 6.0%, and 5.5%, respectively, had positive growth of Haemophilus influenzae, Pseudomonas aeruginosa, and Streptococcus pneumoniae. Among the 505 hospital admissions with patients who had NPA samples saved, 5.7%, 2.3%, 0.8%, and 0.8%, respectively, had influenza A, respiratory syncytial virus (RSV), influenza B, and parainfluenza 3 isolated from viral cultures. Paired serology test results revealed a fourfold rise in viral titers in 5.2%, 2.2%, and 1.4% of patients, respectively, for influenza A, RSV, and influenza B. Very severe airflow obstruction (stable-state spirometry) was associated with a higher chance of a positive sputum culture (FEV(1) >/= 30% predicted, 28.2%; FEV(1) < 30% predicted, 40.4%; p = 0.006). CONCLUSION: H influenzae and influenza A were the most common etiologic agents in patients who were hospitalized with AECOPDs. More severe airflow obstruction was associated with a higher chance of a positive sputum culture finding.     

The effects of helium-hyperoxia on 6-min walking distance in COPD: a randomized, controlled trial

BACKGROUND: We hypothesized that breathing helium-hyperoxia (HeO2) would significantly improve 6-min walking test (6MWT) distance in COPD subjects. METHODS: This was a blinded, randomized crossover study. At visit 1, we assessed pulmonary function, exercise capacity, and 6MWT distance. Visits 2 and 3 consisted of four 6MWTs in which the following different inspired gases were used: room air (RA) by mask; 100% O2 by mask (mask O2); 100% O2 by nasal prongs (nasal O2); and 70% He/30% O2 by mask (HeO2). Walking distance, shortness of breath, leg fatigue, O2 saturation, and heart rate (HR) were assessed. RESULTS: Sixteen COPD subjects participated (mean FEV(1)/FVC ratio [+/- SD], 48 +/- 8%; mean FEV1, 55 +/- 13% predicted). Subjects walked farther when breathing HeO2 (564 m) compared to RA (497 m; p < 0.001), mask O2 (520 m; p < 0.001), or nasal O2 (528 m; p < 0.001). Despite the increased distance walked while breathing HeO2, there was no increase in shortness of breath or leg fatigue. There was desaturation when breathing RA (8%; p < 0.001) and nasal O2 (5%; p < 0.001), which was reduced when breathing HeO2 (3%; difference not significant) and mask O(2) (0%; difference not significant). There were no significant differences in HR in the four 6MWTs. CONCLUSIONS: The use of HeO2 increased 6MWT distance in COPD subjects more than either mask O2 or nasal O2 compared to RA. The increased walking distance was not associated with increased shortness of breath or leg fatigue. The results suggest that clinical benefit would be obtained by administering HeO2 during exercise, which may have significant clinical implications for the management of COPD patients.     

Use of B-type natriuretic peptide in the risk stratification of acute exacerbations of COPD

BACKGROUND: In patients with COPD, prognosis might be determined at least in part by the extent of cardiac stress induced by hypoxia and pulmonary arterial hypertension. METHODS: B-type natriuretic peptide (BNP), a quantitative marker of cardiac stress, was determined in 208 consecutive patients presenting to the emergency department with an acute exacerbation of COPD (AECOPD). The accuracy of BNP to predict death at a 2-year follow-up was evaluated as the primary end point. The need for intensive care and in-hospital mortality were determined as secondary end points. RESULTS: BNP levels were significantly elevated during the acute exacerbation compared to recovery (65 pg/mL; interquartile range [IQR], 34 to 189 pg/mL; vs 45 pg/mL; IQR, 25 to 85 pg/mL; p < 0.001), particularly in those patients requiring ICU treatment (105 pg/mL; IQR, 66 to 553 pg/mL; vs 60 pg/mL; IQR, 31 to 169 pg/mL; p = 0.007). In multivariate Cox regression analysis, BNP accurately predicted the need for ICU care (hazard ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.24 for an increase in BNP of 100 pg/mL; p = 0.008). In a receiver operating characteristic analysis to evaluate the potential of BNP levels to predict short-term and long-term mortality rates, areas under the curve were 0.55 (SD, 0.71; 95% CI, 0.41 to 0.68) and 0.56 (SD, 0.53; 95% CI, 0.45 to 0.66, respectively). CONCLUSIONS: In patients with AECOPD, BNP levels independently predict the need for intensive care. However, BNP levels failed to adequately predict short-term and long-term mortality rates in AECOPD patients.     

Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial

OBJECTIVE: To determine the effects of low-dose prolonged methylprednisolone infusion on lung function in patients with early severe ARDS. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: ICUs of five hospitals in Memphis. PARTICIPANTS: Ninety-one patients with severe early ARDS (相似文献   

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.     

Risk indexes for exacerbations and hospitalizations due to COPD

OBJECTIVE: The ability to predict exacerbations in patients with COPD might permit more rational use of preventive interventions. Our objective was to develop risk indexes for exacerbations and hospitalizations due to exacerbations that might be applied to the individual patient. METHODS: Spirometry, demographics, and medical history were obtained at baseline in 1,829 patients with moderate-to-very severe COPD who entered a trial of inhaled tiotropium. Information about exacerbations and hospitalizations due to exacerbation was collected during the 6-month follow-up period. Analyses of first outcomes were modeled using univariable and multivariable Cox proportional hazards regressions. RESULTS: During follow-up, 551 patients had at least one exacerbation and 151 patients had at least one hospitalization due to exacerbation. In the multivariable model for exacerbation, older age, percentage of predicted FEV(1), duration of COPD, a productive cough, antibiotic or systemic corticosteroid use for COPD in the prior year, hospitalization for COPD in the prior year, and theophylline use at baseline predicted a higher risk. In the multivariable model for hospitalization, older age, percentage of predicted FEV(1), unscheduled clinic/emergency department visits for COPD in the prior year, any cardiovascular comorbidity, and prednisone use at baseline were associated with greater risk. Both the exacerbation and the hospitalization models provided moderately good discrimination, the validated concordance indexes being 0.66 and 0.73, respectively. Methods for calculating risk in individual patients are provided. CONCLUSIONS: Spirometry along with a few questions directed to the patient are strongly predictive of exacerbations and related hospitalizations over the ensuing 6 months.     

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.     

A single dose of dexamethasone to prevent postbronchoscopy fever in children: a randomized placebo-controlled trial

STUDY OBJECTIVE: To assess the effectiveness of one dose of dexamethasone (0.5 mg/kg; maximum, 10 mg) to prevent fever after bronchoscopy with BAL. DESIGN: Randomized, placebo-controlled study. PATIENTS: Immunocompetent nonfebrile children undergoing fiberoptic bronchoscopy with BAL. MEASUREMENTS AND RESULTS: Sixty-nine children were included in the study. Thirty-eight children received saline solution, and 31 children received dexamethasone. The two groups were similar regarding the number of children < 2 years old, the percentage of abnormal bronchoscopic findings, the number of positive BAL culture findings, and the index of lipid-laden macrophages. Twenty-six children (68%) in the saline solution group (SG) had fever, compared to 3 children (9.6%) in the dexamethasone group (DG) [p < 0.001]. Fever after the procedure appeared later (12.3 +/- 5.5 h) in the DG compared to 5.4 +/- 2.7 h in the SG. CONCLUSIONS: One dose of dexamethasone administered prior to performing bronchoscopy with BAL may prevent fever subsequent to the procedure. Further studies are necessary in order to determine the optimal dosing regimen for dexamethasone when used for this purpose.     

Reported and unreported exacerbations of COPD: analysis by diary cards

BACKGROUND: Exacerbations of COPD are a major cause of morbidity and mortality; however, it has been reported that nearly half of such episodes based on symptoms are classified as "unreported" (no change in treatment), although the reasons are unknown. METHOD: We used a symptom-based diary card to study 155 symptom-defined episodes (74 episodes in which treatment was not changed) in 19 patients with alpha(1)-antitrypsin deficiency. RESULTS: The average length for the untreated episodes (time to resolution of all symptoms) was shorter than treated episodes (mean +/- SE, 8.3 +/- 1.0 days vs 16.1 +/- 1.6 days; p < 0.001). Of most importance, the patients documented feeling less well than usual for an average of only 1.9 +/- 0.4 days for untreated episodes, vs 11.7 +/- 1.7 days for treated episodes (p < 0.001). We developed a scoring system based on the symptoms of breathlessness, well-being, sputum color, and volume to quantify the episodes. The scores were higher for the first day of the treated episodes than untreated episodes (33.5 +/- 0.6 vs 28.4 +/- 0.5, respectively; p < 0.001), and the treated episodes had total scores that exceeded the baseline more than the untreated episodes (160.5 +/- 20.0 vs 43.4 +/- 6.6; p < 0.001). Antibiotics or steroids were started 4.4 +/- 0.5 days and 4.9 +/- 1.8 days on average, respectively, after symptoms changed, suggesting that the early return of well-being to normal is central to the episodes described as unreported (untreated) by others. CONCLUSION: The diary card analysis described here provides a tool to document therapies that influence health-care-dependent exacerbations of COPD.     

FEV1 performance among patients with acute asthma: results from a multicenter clinical trial

OBJECTIVE: To determine the ability of patients seen for acute asthma exacerbations in the emergency department (ED) to perform good-quality FEV(1) measurements. METHODS: Investigators from 20 EDs were trained to perform spirometry testing as part of a clinical trial that included standardized equipment with special software-directed prompts. Spirometry was done on ED arrival and 30 min, 1 h, 2 h, and 4 h later, and during follow-up outpatient visits. MEASUREMENTS: Study performance criteria differed from American Thoracic Society (ATS) guidelines because of the population acuity and severity of illness as follows: ability to obtain acceptable FEV(1) measures (defined as two or more efforts with forced expiratory times >/= 2 s and time to peak flow < 120 ms or back-extrapolated volume < 5% of the FVC) and reproducibility criteria (two highest acceptable FEV(1) values within 10% of each other). RESULTS: Of the 620 patients (age range, 12 to 65 years), > 90% met study acceptability criteria on ED arrival and 74% met study reproducibility criteria. Mean initial FEV(1) was 38% of predicted. Spirometry quality improved over time; by 1 h, 90% of patients met study acceptability and reproducibility criteria. Patients with severe airway obstruction (FEV(1) < 25% of predicted) were initially less likely to meet quality goals, but this improved with time. The site was also an independent predictor of quality. CONCLUSION: When staff are well trained and prompt feedback regarding adequacy of efforts is given, modified ATS performance goals for FEV(1) tests can be met from most acutely ill adolescent and adult asthmatics, even within the first hour of evaluation and treatment for an asthma exacerbation.     

The effects of 1-year treatment with a herbst mandibular advancement splint on obstructive sleep apnea, oxidative stress, and endothelial function

BACKGROUND: Obstructive sleep apnea (OSA) is associated with endothelial dysfunction. In the current study, we assessed the effect of long-term modified Herbst mandibular advancement splint (MAS) treatment on OSA, oxidative stress markers, and on endothelial function (EF). METHODS: A total of 16 subjects participated (11 men and 5 women; mean [+/- SD] age, 54.0 +/- 8.3 years; mean body mass index, 28.0 +/- 3.1 kg/m(2)), 12 of whom completed the 1-year evaluation. Apnea severity, levels of oxidative stress markers, and EF were assessed after 3 months and 1 year of receiving treatment. For comparison, 6 untreated patients underwent two evaluations 9 months apart, and 10 non-OSA individuals were assessed once as a reference group. The results are presented as the mean +/- SD. RESULTS: The mean apnea-hypopnea index (AHI) decreased significantly from 29.7 +/- 18.5 events/h before treatment to 17.7 +/- 11.1 events/h after 3 months of treatment and 19.6 +/- 11.5 events/h after 1 year of treatment (p < 0.005 for both). The mean Epworth sleepiness scale score decreased significantly from 12.4 +/- 6.0 before treatment to 10.2 +/- 6.6 after 3 months of treatment and 7.8 +/- 3.8 after 1 year of treatment (p < 0.001 for both). The mean EF improved significantly from 1.77 +/- 0.4 before treatment to 2.1 +/- 0.4 after 3 months of treatment (p < 0.05) and 2.0 +/- 0.3 after 1 year of treatment (p = 0.055), which were similar to the values of the reference group. Thiobarbituric acid-reactive substance (TBARS) levels decreased from 18.8 +/- 6.2 nmol malondialdehyde (MDA)/mL before treatment to 15.8 +/- 3.9 MDA/mL after 3 months of treatment (p = 0.09) and 15.5 +/- 3.2 nmol MDA/mL after 1 year of treatment (p < 0.05). There was a correlation between the improvement in AHI and in EF or TBARS levels (r = 0.55; p = 0.05). The untreated control group remained unchanged. CONCLUSIONS: The Herbst MAS may be a moderately effective long-term treatment for patients with OSA. EF improved to levels that were not significantly different than reference levels, even though apneic events were not completely eliminated. We think that these data are encouraging and that they justify the performance of larger randomized controlled studies.