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1.
Clin Transl Sci ; 9(2): 105-13, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26945929

ABSTRACT

The propellant-free Combivent Respimat Soft Mist Inhaler (CVT-R) was developed to replace the chlorofluorocarbon-propelled Combivent metered-dose inhaler (CVT-MDI). This steady-state pharmacokinetic (PK) substudy evaluated drug lung-delivery efficiency, using data from two phase III safety and efficacy trials. PK parameters were obtained from well-controlled population PK analyses. Area under the plasma concentration-time curve (AUC), maximum observed plasma concentration (C(max)), and minimum observed plasma concentration (C(min)) showed systemic exposure to ipratropium bromide and albuterol delivered via the CVT-R was proportional to ex-mouthpiece delivered dose. Although the labeled dose of ipratropium bromide in the CVT-R was half that in the CVT-MDI, the systemic exposure was comparable. No PK interaction for the ipratropium bromide and albuterol Respimat drug components was demonstrated. Ipratropium bromide alone resulted in similar exposure to the combination of ipratropium bromide and albuterol. These results show that CVT-R delivers drug more efficiently to the lung than CVT-MDI.


Subject(s)
Albuterol/administration & dosage , Chlorofluorocarbons/administration & dosage , Ipratropium/administration & dosage , Lung/drug effects , Metered Dose Inhalers , Administration, Inhalation , Albuterol/blood , Albuterol/pharmacokinetics , Confidence Intervals , Female , Humans , Ipratropium/blood , Ipratropium/pharmacokinetics , Male , Treatment Outcome
2.
Chron Respir Dis ; 12(4): 299-304, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26033837

ABSTRACT

Although sleep disturbance is common in chronic obstructive pulmonary disease (COPD), relatively little is known on the effect of the exacerbation on sleep quality. Accordingly, we longitudinally assessed sleep variables during exacerbations and clinical stability. This is a sub-study of a larger observational analysis. Inclusion criteria were clinically stable COPD and two or more clinical exacerbations in the preceding 12 months. Patients were followed for approximately 6 months and during this time the following were recorded daily: (1) COPD exacerbations, which were determined in two ways, clinically and symptom defined using the exacerbations of chronic pulmonary disease tool (EXACT); (2) daytime sleepiness, which was measured using the Stanford Sleepiness Scale; (3) subjective awakenings, which was measured from a sleep diary; and (4) sleep duration, efficiency, and objective awakenings, which was measured from actigraphy. These variables for exacerbation and non-exacerbation days were compared. Seventeen patients (9 male, age 63 ± 12 years, forced expiratory volume in 1 second 52 ± 20%) entered data over 135 ± 18 days. During this time, 15 patients had 27 symptom-defined exacerbations and 8 had 9 clinically reported exacerbations. Symptom-defined exacerbation days were 26% of the total study days. More daytime sleepiness, decreased total sleep time (TST), and decreased sleep efficiency (SE) were present during exacerbations compared with clinical stability (p < 0.001). These disturbances tended to be greater during clinically reported exacerbations than during unreported events (p < 0.05). Increased daytime sleepiness, less TST, and poorer SE are present during COPD exacerbations.


Subject(s)
Pulmonary Disease, Chronic Obstructive/physiopathology , Sleep Wake Disorders/physiopathology , Sleep/physiology , Actigraphy , Age Factors , Aged , Disease Progression , Female , Forced Expiratory Volume , Humans , Linear Models , Longitudinal Studies , Male , Middle Aged , Severity of Illness Index
3.
Eur J Phys Rehabil Med ; 47(3): 465-74, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21946404

ABSTRACT

The optimal therapy of an individual with chronic respiratory disease usually requires a combination of pharmacologic and non-pharmacologic therapies. A case of a 68-year-old man with advanced chronic obstructive pulmonary disease is given to illustrate this point. He is a recent ex-smoker with severe chronic obstructive pulmonary disease by spirometric criteria, frequent exacerbations of this disease, considerable recent health care utilization, dyspnea with minimal activities, severe functional status limitation, prominent systemic effects of the disease (e.g., weight loss) and substantial comorbidities. The primary respiratory disease cannot be isolated from and treated independently of these important factors. Pulmonary rehabilitation is an important therapeutic option in situations like this, providing a mode of integrating care, complementing otherwise standard medical therapy, and producing significant gains across multiple outcome areas of importance to the patient. Pulmonary rehabilitation has been defined by the American Thoracic Society and European Respiratory Society as: "an evidence-based, multidisciplinary, and comprehensive intervention for patients with chronic respiratory diseases who are symptomatic and often have decreased daily life activities. Integrated into the individualized treatment of the patient, pulmonary rehabilitation is designed to reduce symptoms, optimize functional status, increase participation, and reduce health care costs through stabilizing or reversing systemic manifestations of the disease". Its components include comprehensive assessment, education, exercise training, and psychosocial intervention. Outcomes assessment is usually performed for quality assessment. Pulmonary rehabilitation produces the greatest improvements of any available therapy in dyspnea, exercise capacity, and health-related quality of life. These gains are realized despite the fact that pulmonary rehabilitation has no direct effect on lung function. It works primarily through reducing the impact of the systemic manifestations of the disease and frequent comorbidity. Pulmonary rehabilitation also leads to substantial reductions in subsequent health care utilization, possibly through collaborative self-management strategies emphasized in the program. Although pulmonary rehabilitation has been utilized by astute clinicians for many years, its science has been developed over the past two decades.


Subject(s)
Lung Diseases/rehabilitation , Activities of Daily Living , Chronic Disease , Evidence-Based Medicine , Humans , Lung Diseases/physiopathology , Precision Medicine , Quality of Life
4.
Respir Med ; 104(8): 1179-88, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20172704

ABSTRACT

We compared the efficacy and safety of ipratropium bromide/albuterol delivered via Respimat inhaler, a novel propellant-free inhaler, versus chlorofluorocarbon (CFC)-metered dose inhaler (MDI) and ipratropium Respimat inhaler in patients with COPD. This was a multinational, randomized, double-blind, double-dummy, 12-week, parallel-group, active-controlled study. Patients with moderate to severe COPD were randomized to ipratropium bromide/albuterol (20/100mcg) Respimat inhaler, ipratropium bromide/albuterol MDI [36mcg/206mcg (Combivent Inhalation Aerosol MDI)], or ipratropium bromide (20mcg) Respimat inhaler. Each medication was administered four times daily. Serial spirometry was performed over 6h (0.15min, then hourly) on 4 test days. The primary efficacy variable was forced expiratory volume in 1s (FEV(1)) change from test day baseline at 12 weeks. A total of 1209 of 1480 randomized, treated patients completed the study; the majority were male (65%) with a mean age of 64 yrs and a mean screening pre-bronchodilator FEV(1) (percent predicted) of 41%. Ipratropium bromide/albuterol Respimat inhaler had comparable efficacy to ipratropium bromide/albuterol MDI for FEV(1) area under the curve at 0-6h (AUC(0-6)), superior efficacy to ipratropium Respimat inhaler for FEV(1) AUC(0-4) and comparable efficacy to ipratropium Respimat inhaler for FEV(1) AUC(4-6). All active treatments were well tolerated. This study demonstrates that ipratropium bromide/albuterol 20/100mcg inhaler administered four times daily for 12 weeks had equivalent bronchodilator efficacy and comparable safety to ipratropium bromide/albuterol 36mcg/206mcg MDI, and significantly improved lung function compared with the mono-component ipratropium bromide 20 mcg Respimat inhaler. [Clinical Trial Identifier Number: NCT00400153].


Subject(s)
Albuterol/administration & dosage , Bronchodilator Agents/administration & dosage , Ipratropium/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Administration, Inhalation , Albuterol, Ipratropium Drug Combination , Double-Blind Method , Female , Forced Expiratory Volume/drug effects , Forced Expiratory Volume/physiology , Humans , Male , Middle Aged , Nebulizers and Vaporizers , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Function Tests/methods , Treatment Outcome
5.
Chron Respir Dis ; 6(4): 217-24, 2009.
Article in English | MEDLINE | ID: mdl-19858351

ABSTRACT

BACKGROUND: The purpose of this study was to determine whether a commercially available pedometer could detect changes in home-based walking activity among chronic obstructive pulmonary disease (COPD) patients completing pulmonary rehabilitation (PR). METHODS: Patients with COPD referred to outpatient PR wore a pedometer to count steps for 1 week at the beginning and 1 week at the end of PR. Patients also completed the 6-min walk test (6MWT), the Medical Research Council (MRC) dyspnea scale and the self-administered chronic respiratory disease questionnaire (CRQ) at the beginning and the end of PR. Paired t tests were used to compare pre- and post-PR changes in outcome variables. RESULTS: 45 patients with severe COPD (forced expiratory volume in 1 second [FEV(1)] 45% +/- 18% of predicted) participated in a total of 17.4 +/- 4.6 PR sessions. Significant improvements in 6MWT (49 +/- 59 m; p < .0001), MRC dyspnea score (-0.64 +/- 0.96 units; p = .003) and CRQ score (10 +/- 18 units; p = .0007) were noted following PR. Patients whose pedometer-measured steps were within 20% of observed counted steps were included in the analysis. Pedometer counts increased by 33 +/- 149 steps per hour worn after, as compared with before PR (p = .14). There was a significant inverse relationship between baseline pedometer counts and change in pedometer counts per hour post-PR (r = -.46; p = .001). Patients with low baseline activity levels had significant increases in pedometer activity (88 +/- 30 counts per hour worn) and a greater reduction in MRC dyspnea score (-0.94 vs -0.29; p = .04) following PR, whereas those with higher baseline activity levels had a decrease in pedometer activity (-19 +/- 29 counts/hour; p = .015). CONCLUSIONS: A standard pedometer worn at the waist did not detect changes in lower extremity activity following PR. This negative finding occurred despite demonstrated improvements in dyspnea, exercise tolerance and quality of life measures. Although pedometers are inexpensive and easy to use, they may not be sensitive enough to be used routinely as an outcome measure for PR.


Subject(s)
Exercise Therapy/methods , Monitoring, Physiologic/instrumentation , Motor Activity/physiology , Pulmonary Disease, Chronic Obstructive/rehabilitation , Walking/physiology , Aged , Dyspnea/etiology , Dyspnea/physiopathology , Dyspnea/rehabilitation , Equipment Design , Female , Follow-Up Studies , Forced Expiratory Volume/physiology , Humans , Male , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/physiopathology , Treatment Outcome
6.
Chron Respir Dis ; 5(4): 205-9, 2008.
Article in English | MEDLINE | ID: mdl-19029231

ABSTRACT

Although obesity is increasing in prevalence, relatively little attention has been given to its impact on outcomes in patients with chronic obstructive pulmonary disease (COPD) completing pulmonary rehabilitation. We conducted a retrospective chart review of 114 patients with COPD who completed outpatient pulmonary rehabilitation at our center. Body habitus categories were determined based on body mass index (BMI). Underweight patients (BMIA 30A kg/m(2)) were compared with non-obese patients in the following areas: forced expiratory volume in 1A s (FEV(1)) percent predicted, the 6-min walk distance (6MWD), health status, the number of unsupported arm lifts per minute, and functional performance. Health status was determined using the Self-Reported Chronic Respiratory Questionnaire (CRQ-SR), which has dimensions of dyspnea, fatigue, emotion, and mastery. Functional performance was determined using the Pulmonary Functional Status Scale Daily Activities subscore. Compared with non-obese patients, obese patients had a higher FEV(1) percent-predicted (44A +/-A 15% vs 52A +/-A 16%; PA =A 0.01), yet had lower 6MWD (269A +/-A 11 vs 203A +/-A 13; PA =A 0.0002), lower functional status, and greater fatigue at initial evaluation. However, the two groups had similar walk-work, which adjusts for differences in weight. Despite the baseline differences, both groups improved similarly following pulmonary rehabilitation (change in 6MWD was 52A +/-A 7A m in the non-obese patients versus 47A +/-A 9 in the obese patients; PA =A 0.65). Our study suggests that obese COPD patients are referred to pulmonary rehabilitation at an earlier spirometric stage of their disease, but have a poorer exercise performance, a greater degree of functional impairment and greater fatigue levels. This is probably, largely because of the effect of an increased weight burden. However, obesity did not seem to adversely affect the pulmonary rehabilitation outcomes.


Subject(s)
Obesity/complications , Pulmonary Disease, Chronic Obstructive/rehabilitation , Aged , Body Mass Index , Case-Control Studies , Exercise Tolerance , Female , Health Status Indicators , Humans , Male , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Function Tests , Retrospective Studies , Surveys and Questionnaires , Treatment Outcome
8.
Chron Respir Dis ; 3(1): 11-8, 2006.
Article in English | MEDLINE | ID: mdl-16509173

ABSTRACT

Although pulmonary rehabilitation has proven effectiveness in multiple outcome areas, the optimum duration of this intervention is not clear. We evaluated in an observational study the trajectory of change in upper and lower extremity exercise performance, exertional dyspnea and health status over the course of 12 weeks (24 sessions) of pulmonary rehabilitation in individuals with chronic obstructive pulmonary disease. Demonstrating a plateau in response in these areas might be of practical use for pulmonary rehabilitation programs. We measured outcomes at baseline and at four-session (two week) intervals over the course of our comprehensive outpatient pulmonary rehabilitation program. These included treadmill endurance time at approximately 85% of initial maximal workrate, the number of arm lifts per minute, dyspnea at isotime during treadmill walking and the Chronic Respiratory Disease Questionnaire (CRQ) total score. Thirteen patients with chronic obstructure pulmonary disease (COPD) (five male, eight female) were studied; their age was 66 +/- 8 years and their FEV1 was 34 +/- 11% of predicted. Improvement was noted in all four outcome areas very early in the course of pulmonary rehabilitation. Treadmill endurance time and arm lifts increased significantly over baseline by the fourth and eighth session, respectively, and both increased in a near-linear fashion throughout pulmonary rehabilitation. Exertional dyspnea and CRQ also improved very early, with each showing a significant change from baseline by the fourth session. Their improvement, however, appeared to plateau relatively early during the course of pulmonary rehabilitation. Although the numbers studied are small and the applicability of these results to other programs is undetermined, this study does suggest that 20 or more sessions are needed for optimal acute changes in exercise performance, but improvement in dyspnea and quality of life may occur earlier.


Subject(s)
Exercise Tolerance/physiology , Physical Endurance/physiology , Pulmonary Disease, Chronic Obstructive/rehabilitation , Aged , Dyspnea/physiopathology , Exercise Test , Extremities/physiopathology , Female , Health Status , Humans , Male , Outpatient Clinics, Hospital , Prospective Studies , Pulmonary Disease, Chronic Obstructive/physiopathology , Quality of Life , Surveys and Questionnaires
9.
Chron Respir Dis ; 1(3): 143-9, 2004.
Article in English | MEDLINE | ID: mdl-16281656

ABSTRACT

BACKGROUND: Exercise training is considered a necessary component of comprehensive pulmonary rehabilitation. However, to date, there is no consensus on an exercise training strategy for pulmonary rehabilitation, and this has resulted in varied approaches to this intervention in its literature. As in healthy individuals, the effect of exercise training on patients with chronic lung disease is dose dependent, with higher intensities resulting in greater physiological adaptations than lower intensities. RESULTS: It is not clear from our review of the literature that these enhanced physiological effects from higher levels of exercise training translate into a reduced burden of symptoms, hence a better quality of life. Indeed, there is some evidence that pulmonary rehabilitation approaches incorporating lower intensities of exercise training are at least as good in improving questionnaire rated symptoms of health status. This provides food for thought, since the prominent goal of pulmonary rehabilitation should be to reduce bothersome symptoms or enhance health status, not simply increase endurance time on a cycle ergometer.


Subject(s)
Exercise Therapy/methods , Pulmonary Disease, Chronic Obstructive/rehabilitation , Health Status , Humans , Pulmonary Disease, Chronic Obstructive/psychology , Quality of Life
10.
Monaldi Arch Chest Dis ; 59(3): 230-3, 2003.
Article in English | MEDLINE | ID: mdl-15065323

ABSTRACT

A limitation in functional status is an important factor in the handicap caused by advanced chronic lung disease such as COPD. Indicators of functional status in these patients include exercise performance levels common to everyday activity (such as the six minute walk distance) and scores on self-completed questionnaires rating interference with daily activities (such as the Functional Activities component of the PFSS). Both a longer timed walk distance and a higher functional performance score were highly predictive of survival in independent studies of pulmonary rehabilitation patients. This probably reflects the ability of measures of functional status to quantify non-pulmonary as well as morbidity, both of which contribute to the overall mortality in individuals with advanced lung disease.


Subject(s)
Lung/physiopathology , Pulmonary Disease, Chronic Obstructive/physiopathology , Quality of Life , Humans , Karnofsky Performance Status , Survival Analysis , Time Factors
11.
Eur Respir J ; 19(2): 217-24, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11866001

ABSTRACT

Currently available inhaled bronchodilators used as therapy for chronic obstructive pulmonary disease (COPD) necessitate multiple daily dosing. The present study evaluates the long-term safety and efficacy of tiotropium, a new once-daily anticholinergic in COPD. Patients with stable COPD (age 65.2+/-8.7 yrs (mean+/-SD), n=921) were enrolled in two identical randomized double-blind placebo-controlled 1-yr studies. Patients inhaled tiotropium 18 microg or placebo (mean screening forced expiratory volume in one second (FEV1) 1.01 versus 0.99 L, 39.1 and 38.1% of the predicted value) once daily as a dry powder. The primary spirometric outcome was trough FEV1 (i.e. FEV1 prior to dosing). Changes in dyspnoea were measured using the Transition Dyspnea Index, and health status with the disease-specific St. George's Respiratory Questionnaire and the generic Short Form 36. Medication use and adverse events were recorded. Tiotropium provided significantly superior bronchodilation relative to placebo for trough FEV1 response (approximately 12% over baseline) (p<0.01) and mean response during the 3 h following dosing (approximately 22% over baseline) (p<0.001) over the 12-month period. Tiotropium recipients showed less dyspnoea (p<0.001), superior health status scores, and fewer COPD exacerbations and hospitalizations (p<0.05). Adverse events were comparable with placebo, except for dry mouth incidence (tiotropium 16.0% versus placebo 2.7%, p<0.05). Tiotropium is an effective, once-daily bronchodilator that reduces dyspnoea and chronic obstructive pulmonary disease exacerbation frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic obstructive pulmonary disease therapy.


Subject(s)
Bronchodilator Agents/administration & dosage , Cholinergic Antagonists/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Scopolamine Derivatives/administration & dosage , Administration, Inhalation , Aged , Bronchodilator Agents/adverse effects , Cholinergic Antagonists/adverse effects , Double-Blind Method , Drug Administration Schedule , Female , Health Status , Humans , Male , Peak Expiratory Flow Rate , Pulmonary Disease, Chronic Obstructive/physiopathology , Scopolamine Derivatives/adverse effects , Spirometry , Tiotropium Bromide
12.
J Cardiopulm Rehabil ; 21(5): 288-95, 2001.
Article in English | MEDLINE | ID: mdl-11591043

ABSTRACT

Nutritional depletion is prevalent in patients with advanced chronic obstructive pulmonary disease (COPD). These nutritional abnormalities are pronounced in patients with the "emphysematous" form of COPD on chronic corticosteroid therapy. The pathophysiologic mechanisms for the involuntary weight loss appear to be multifactorial. Clinical research has revealed that nutritional depletion in advanced COPD is associated with an increased morbidity and mortality. This review will address the implications of nutritional depletion in addition to potential therapeutic options.


Subject(s)
Nutrition Disorders/complications , Pulmonary Disease, Chronic Obstructive/complications , Body Composition/physiology , Body Mass Index , Health Status , Humans , Nutrition Assessment , Nutrition Disorders/diet therapy , Nutrition Disorders/physiopathology , Nutritional Status , Prevalence , Pulmonary Disease, Chronic Obstructive/diet therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , United States/epidemiology , Weight Loss/physiology
13.
Monaldi Arch Chest Dis ; 56(1): 17-22, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11407202

ABSTRACT

Therapy of patients with chronic respiratory failure is mainly directed at minimizing symptoms in order to improve, or at least to prevent a deterioration of, patients' well-being. Under such circumstances, the perceived effect of therapies on patients' well-being and daily life represents the most important subjective outcome of treatment. Therefore, there is a need to provide a global estimate of health in patients on long term oxygen therapy or overnight home mechanical ventilation. The Maugeri Foundation Respiratory Failure Questionnaire (MRF28) is the first health status ("quality of life") questionnaire specifically developed for use in CRF and its items were selected to be applicable to patients with both obstructive and restrictive diseases. The Quality of Life Evaluation and Survival Study (QuESS) is a multinational study with the aim of re-evaluating the natural history of chronic respiratory failure in about 300 patients. To the authors knowledge, the Quality of Life Evaluation and Survival Study is the first study to evaluate the natural history of chronic respiratory failure in such a large number of subjects and with a complete set of data. In fact, both pathophysiologic and health status assessments will be made. Moreover, by collecting data on mortality, disease exacerbations and hospitalization, it will also be possible to verify the predictive ability of health status versus pathophysiology in terms of mortality and healthcare utilization.


Subject(s)
Quality of Life , Respiratory Insufficiency/mortality , Respiratory Insufficiency/physiopathology , Chronic Disease , Delivery of Health Care , Follow-Up Studies , Health Status , Health Status Indicators , Humans , Prognosis , Prospective Studies , Reproducibility of Results , Survival Rate
14.
Chest ; 119(6): 1661-70, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11399688

ABSTRACT

BACKGROUND: Patients with COPD often require multiple therapies to improve lung function and decrease symptoms and exacerbations. Salmeterol and theophylline are indicated for the treatment of COPD, but the use of these agents in combination has not been extensively studied. OBJECTIVES: To compare the efficacy and safety of salmeterol plus theophylline vs either agent alone in COPD. METHODS: Randomized, double-blind, double-dummy, parallel-group trial in 943 patients with COPD. After an open-label theophylline titration period (serum levels, 10 to 20 microg/mL), patients were randomly assigned to receive salmeterol (42 microg bid) plus theophylline, salmeterol (42 microg bid), or theophylline for 12 weeks. Serial pulmonary function tests were completed on day 1 and treatment week 12. Patients kept diary cards and noted their peak flow rates, symptom scores, and albuterol use, and periodically completed quality-of-life and dyspnea questionnaires. RESULTS: All three groups significantly improved compared with baseline. Combination treatment with salmeterol plus theophylline provided significantly (p < or = 0.045) greater improvements in pulmonary function; significantly (p < or = 0.048) greater decreases in symptoms, dyspnea, and albuterol use; and significantly fewer COPD exacerbations (p = 0.023 vs theophylline). In general, treatment with salmeterol provided greater improvement in lung function and satisfaction with treatment compared with theophylline. Salmeterol treatment was also associated with significantly fewer drug-related adverse events (p < or = 0.042) than either treatment that included theophylline. The safety profile (adverse events, vital signs, and ECG findings) of the two treatments that included theophylline were similar. CONCLUSION: Patients with COPD may benefit from combination treatment with salmeterol plus theophylline, without a resulting increase in adverse events or other adverse sequelae.


Subject(s)
Adrenergic beta-Agonists/administration & dosage , Albuterol/analogs & derivatives , Albuterol/administration & dosage , Bronchodilator Agents/administration & dosage , Lung Diseases, Obstructive/drug therapy , Theophylline/administration & dosage , Aged , Aged, 80 and over , Albuterol/adverse effects , Albuterol/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Female , Hemodynamics/drug effects , Humans , Lung Diseases, Obstructive/physiopathology , Male , Middle Aged , Salmeterol Xinafoate , Theophylline/adverse effects , Theophylline/blood
15.
Am J Respir Crit Care Med ; 163(5): 1087-92, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11316640

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a condition in which continuous bronchodilation may have clinical advantages. This study evaluated salmeterol, a beta-agonist bronchodilator with a duration of action substantially longer than that of short-acting beta-agonists, compared with ipratropium, an anticholinergic bronchodilator, and placebo in patients with COPD. Four hundred and five patients with COPD received either salmeterol 42 microg twice daily, ipratropium bromide 36 microg four times daily, or placebo for 12 wk in this randomized, double-blind, parallel-group study. Patients were stratified on the basis of bronchodilator response to albuterol (> 12% and > 200-ml improvement) and were randomized within each stratum. Bronchodilator response was measured over 12 h four times during the treatment period. Salmeterol provided similar maximal bronchodilatation to ipratropium but had a longer duration of action and a more constant bronchodilatory effect with no evidence of bronchodilator tolerance. Both active treatments were well tolerated. Salmeterol was an effective bronchodilator with a consistent effect over this 12-wk study in patients with COPD, including those "unresponsive" to albuterol. The long duration of action of salmeterol offers the advantage of twice daily dosing compared with the required four times a day dosing with ipratropium.


Subject(s)
Adrenergic beta-Agonists/therapeutic use , Albuterol/analogs & derivatives , Albuterol/therapeutic use , Bronchodilator Agents/therapeutic use , Lung Diseases, Obstructive/drug therapy , Adrenergic beta-Agonists/pharmacology , Albuterol/pharmacology , Analysis of Variance , Bronchodilator Agents/pharmacology , Cholinergic Antagonists/pharmacology , Cholinergic Antagonists/therapeutic use , Double-Blind Method , Female , Forced Expiratory Volume/drug effects , Humans , Ipratropium/pharmacology , Ipratropium/therapeutic use , Male , Middle Aged , Quality of Life , Salmeterol Xinafoate , Vital Capacity/drug effects
16.
Monaldi Arch Chest Dis ; 56(4): 331-5, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11770216

ABSTRACT

Patients referred to pulmonary rehabilitation usually have advanced chronic obstructive lung disease (COPD). This disease is a common cause of death in developed countries, ranking fourth as a cause of death in the United States, behind heart disease, cancer, and stroke. The three-year survival following outpatient pulmonary rehabilitation is approximately 80%. Clearly, markers of disease severity such as the degree of airways obstruction, arterial blood gas abnormality, degree of pulmonary hypertension, and the need for hospitalizations predict mortality in this disease. However, because of substantial co-morbidity, patients with COPD often die with their disease rather than from their disease. Thus, only 45 to 63% of deaths in patients with advanced lung disease are directly due to the disease itself. Factors other than primary disease severity that predict mortality in COPD include nutritional depletion, exercise endurance, functional performance, and even social factors such as marital status. Thus, once the chronic lung disease progresses to the point where referral is made to pulmonary rehabilitation, non-pulmonary factors are also important predictors of survival. This underscores the importance of a holistic approach to the patient with advanced lung disease, and the need for a comprehensive severity grading system that includes more than the forced expiratory volume in 1 sec (FEV1).


Subject(s)
Cause of Death , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Disease, Chronic Obstructive/rehabilitation , Quality of Life , Respiratory Therapy/methods , Female , Humans , Male , Predictive Value of Tests , Respiratory Function Tests , Risk Assessment , Risk Factors , Severity of Illness Index , Survival Analysis
17.
Chest ; 118(3): 697-703, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10988191

ABSTRACT

BACKGROUND: Functional exercise capacity has been shown to be a strong predictor of survival following pulmonary rehabilitation. This study evaluated whether questionnaire-rated functional status is also predictive of survival. PATIENTS AND METHODS: Following pulmonary rehabilitation, patients with advanced chronic lung disease were evaluated for survival, 6-min walk distance, and questionnaire-rated functional status. The latter was measured using the pulmonary functional status scale, which has subscores of functional activities, psychological status, and dyspnea. Information on survival was available on 149 patients. RESULTS: The mean age was 69 years, and 45% of patients were male. Eighty-nine percent had a diagnosis of COPD, and their FEV(1) was 37+/-18% of predicted. Ninety-one (61%) were married. The 3-year survival for the group was 85%. Age, gender, body mass index, and primary diagnosis were not related to survival. Variables strongly associated with increased survival following pulmonary rehabilitation included a higher postrehabilitation Functional Activities score, a longer postrehabilitation 6-min walk distance, and being married (vs widowed, single, or divorced). Disease severity variables associated with survival included an initial referral to outpatient pulmonary rehabilitation, no supplemental oxygen requirement, and a higher percent-predicted FEV(1). CONCLUSION: Indicators of functional status are strong predictors of survival in patients with advanced lung disease.


Subject(s)
Health Status Indicators , Lung Diseases, Obstructive/rehabilitation , Aged , Body Mass Index , Connecticut/epidemiology , Exercise Test , Female , Humans , Lung Diseases, Obstructive/mortality , Lung Diseases, Obstructive/physiopathology , Male , Prognosis , Proportional Hazards Models , Respiratory Function Tests , Retrospective Studies , Risk Factors , Surveys and Questionnaires , Survival Rate
18.
Chest ; 118(2): 303-12, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10936117

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of fluticasone propionate administered as a once-daily or twice-daily regimen over a period of 1 year to patients with moderate asthma. DESIGN: Double-blind, randomized, parallel group, and placebo-controlled phase (12 weeks) and an open-label phase (54 weeks). SETTING: Multicenter study in an outpatient setting. PARTICIPANTS: Patients (n = 253; age, > or = 12 years) with a mean FEV(1) of 67% predicted normal were stratified according to baseline therapy of maintenance inhaled corticosteroids vs beta(2)-agonists alone. MEASUREMENTS AND INTERVENTIONS: Fluticasone propionate (250 microg bid or 500 microg qd) or placebo (bid) was administered via the Diskus multidose powder inhaler (Glaxo Wellcome; Research Triangle Park, NC) for 12 weeks. During open-label treatment, patients were re-randomized to once-daily or twice-daily fluticasone propionate. RESULTS: Compared to placebo, fluticasone propionate administered qd or bid significantly improved FEV(1) (p < 0.001), morning (p < 0.001) and evening peak expiratory flow (PEF; p < 0.001), asthma symptom scores (p < or = 0.001), and albuterol use (p

Subject(s)
Androstadienes/administration & dosage , Anti-Asthmatic Agents/administration & dosage , Asthma/drug therapy , Administration, Inhalation , Adolescent , Adrenergic beta-Agonists/administration & dosage , Adult , Aged , Albuterol/administration & dosage , Asthma/physiopathology , Child , Circadian Rhythm , Double-Blind Method , Drug Administration Schedule , Female , Fluticasone , Follow-Up Studies , Forced Expiratory Volume/drug effects , Humans , Male , Middle Aged , Nebulizers and Vaporizers , Powders , Safety , Severity of Illness Index
19.
Psychosom Med ; 62(1): 61-8, 2000.
Article in English | MEDLINE | ID: mdl-10705912

ABSTRACT

OBJECTIVE: This study examined the within-person relations between transitory changes in mood, asthma symptoms, and peak expiratory flow rate (PEFR). METHODS: Thrice-daily for 21 consecutive days, 48 adults with moderate to severe asthma entered information in palm-top computers about their mood and asthma symptoms. A multidimensional model of mood, ie, the mood circumplex, informed the assessment of mood arousal and mood pleasantness. At each observation, participants also recorded their PEFR with peak flow meters that stored blinded data. Albuterol doses were also monitored electronically. Before and after the 21-day study, spirometric measures of airways obstruction were taken under controlled conditions. RESULTS: Random effects regression models revealed a significant, but weak, within-person relation between symptoms and PEFR. Changes in mood vectors with an arousal component were significantly related to PEFR changes, whereas changes in mood vectors with a pleasantness component tracked changes in asthma symptom reports, even after adjustment for contemporaneous PEFR and after controlling for time of day and albuterol dosing. Comparison of spirometric assessments with unsupervised PEFR suggested that part of the relation between mood arousal and PEFR may be attributable to the "effort-dependence" of peak flow self-monitoring. CONCLUSIONS: Different dimensions of mood were associated with transitory changes in asthma symptoms and PEFR. This may be one reason why individuals with asthma misperceive the severity of their symptoms in relation to underlying airways obstruction.


Subject(s)
Affect/physiology , Asthma/diagnosis , Asthma/psychology , Adult , Albuterol/therapeutic use , Arousal/physiology , Asthma/drug therapy , Bronchodilator Agents/therapeutic use , Electronic Data Processing/methods , Female , Humans , Interpersonal Relations , Male , Middle Aged , Peak Expiratory Flow Rate/physiology , Severity of Illness Index
20.
Monaldi Arch Chest Dis ; 54(2): 189-92, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10394839

ABSTRACT

The beneficial effects of pulmonary rehabilitation programmes on the overall quality of life in patients with chronic obstructive pulmonary disease (COPD) has been well documented. However, there has been a paucity of studies demonstrating the long-term benefits of short-stay inpatient pulmonary rehabilitation (SSIPR) programmes in patients with severe COPD (forced expiratory volume in one second (FEV1) < 40% of predicted). The authors have previously reported that their multidisciplinary SSIPR programme improved outcome measurements immediately post-rehabilitation in 38 patients with severe COPD. The purpose of this study was to evaluate the long-term (1-yr follow-up) benefits of SSIPR in these patients. The outcome measurements used were: timed 12-min walking distance, Borg dyspnoea scale, annual days of acute care hospitalization, and Pulmonary Functional Status Scale. All outcome measurements were significantly improved at 1 yr post-SSIPR as compared to pre-SSIPR values. The 12-min walking distance was significantly improved in patients 1 yr post-SSIPR (251 m) as compared to either pre-SSIPR (133 m, p < 0.0001) or immediately post-SSIPR (224 m, p < 0.01). The number of annual days of acute care hospitalization was reduced from 15.4 pre-SSIPR to 3.8 (p < 0.0001) 1 yr post-SSIPR. The Borg dyspnoea scale measurement showed improvement, both at rest and after 12 min walking at 1 yr post-SSIPR. Also, the Pulmonary Functional Status Scale analysis showed significant (p < 0.001) sustained improvement at 1 yr post-SSIPR as compared to pre-SSIPR. In conclusion, it has been demonstrated that long-term sustained outcome benefits can be achieved from a comprehensive short-stay inpatient pulmonary rehabilitation programme for patients with severe chronic obstructive pulmonary disease.


Subject(s)
Length of Stay , Lung Diseases, Obstructive/rehabilitation , Aged , Connecticut , Female , Humans , Inpatients , Lung Diseases, Obstructive/diagnosis , Lung Diseases, Obstructive/physiopathology , Male , Middle Aged , Patient Satisfaction , Physical Therapy Modalities/methods , Prognosis , Respiratory Function Tests , Severity of Illness Index , Treatment Outcome
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