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Biomedical subjects

Donald A Mahler

Publications and source records attributed to Donald A Mahler.

18 recordsLinked to original sources
PubMed2007

Responsiveness of patient-reported breathlessness during exercise in persistent asthma.

BACKGROUND: The purpose of the study was to examine the responsiveness of a computerized system whereby the patient reports spontaneously any change in the intensity of breathlessness during exercise. The hypotheses were that hypercapnia would increase and hyperoxia would decrease the slope of power production-breathlessness ratings compared with a control condition during cycle ergometry. METHODS: Thirty adult subjects (15 women and 15 men) with persistent asthma (mean [+/- SD] FEV(1)/FVC ratio, 57 +/- 10%) completed an initial familiarization visit and three study visits. All subjects inhaled two puffs of albuterol (180 microg) in order to standardize lung function prior to exercise. At visits 2 to 4, subjects breathed one of the three gas mixtures administered in a random order while performing a ramp exercise test. The experimental conditions were as follows: hypercapnia (5% carbon dioxide); hyperoxia (40% oxygen); and control (room air). RESULTS: Lung function was the same before and after exercise with the three experimental conditions. With hypercapnia, peak ventilation was increased, peak oxygen consumption, and power production were reduced, the slope of power-breathlessness was increased, and 25 patients (83%) reported breathlessness as the limiting symptom. With hyperoxia, peak ventilation was decreased, peak power production and the slope of power-breathlessness were unchanged, and 16 patients (53%) reported leg discomfort as the limiting symptom. CONCLUSIONS: Breathing 5% carbon dioxide altered physiologic responses and the slope of power production-breathlessness during exercise. The responses to hyperoxia were inconsistent. The continuous method for patient-reported breathlessness was responsive to hypercapnia, but not to hyperoxia, during incremental exercise.

Adult↗
PubMed2006

Continuous ratings of breathlessness during exercise by children and young adults with asthma and healthy controls.

Although it is recommended and common practise for adults with respiratory disease to rate symptoms (e.g., dyspnea and/or leg discomfort) during exercise testing, there are no reports on whether children can rate their perception of breathlessness during exercise. Our aims were to evaluate the ability of children and young adults with asthma to continuously rate breathlessness on the 0-10 category-ratio (CR-10) scale with a computerized system during cycle ergometry, and to compare their results with those of healthy subjects. At an initial visit, subjects were familiarized with equipment and exercise protocol, and practised rating breathlessness while cycling. At a follow-up visit (2-4 days later), subjects performed incremental exercise and rated breathlessness using a computer system, mouse, and monitor. Changing the position of the mouse caused movement of a vertical bar located adjacent to the CR-10 scale to indicate the severity of breathlessness. Baseline characteristics of the 14 subjects with asthma (age, 15 +/- 3 years) and 33 healthy subjects (age, 16 +/- 2 years) were similar. The two groups had comparable levels of fitness as measured by peak oxygen consumption (VO(2)). Correlations between exercise physiologic variables (power production, VO(2), and minute ventilation) and breathlessness ratings were >0.90. Subjects reported progressively more ratings of breathlessness with increasing exercise intensities. There were no differences between groups for slopes, x-intercepts, and absolute thresholds relating physiologic variables and breathlessness. In conclusion, children and young adults with asthma as well as healthy individuals of comparable age successfully used the computerized system to rate breathlessness continuously during cycle ergometry. Both groups reported more ratings of breathlessness with this technique as exercise progressed.

Adolescent↗
PubMed2006

Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD.

STUDY OBJECTIVE: To examine the effect of fluticasone propionate, 250 microg/salmeterol, 50 microg combination (FSC 250/50) twice daily on lung hyperinflation and associated measures of exercise performance in patients with COPD. DESIGN: This was a randomized, double-blind, parallel-group study. PATIENTS: Eligible patients were > or = 40 years old with a diagnosis of COPD, prealbuterol FEV(1) < 70% of predicted, FEV1/FVC ratio > or = 0.70, and functional residual capacity (FRC) > or = 120% of predicted normal. INTERVENTIONS: Patients were randomized to FSC 250/50; salmeterol, 50 microg; or placebo twice daily for 8 weeks. Predose and postdose spirometry, plethysmography, and constant-load cycle cardiopulmonary exercise test evaluations were compared. The primary comparison was FSC 250/50 with placebo. The salmeterol group was included for exploratory comparisons with FSC 250/50. RESULTS: A total of 185 patients (mean baseline FEV1 of 41% predicted) were enrolled. At rest, FSC 250/50 significantly reduced postdose FRC and increased inspiratory capacity (IC) compared with placebo (differences of - 0.35 +/- 0.12 L and 0.33 +/- 0.06 L [mean +/- SE], respectively, at week 8; p > or = 0.003) and increased exercise endurance time (difference, 132 +/- 45 s; p = 0.004). At a standardized time during exercise (isotime), FSC 250/50 increased postdose IC by 0.20 +/- 0.05 L over placebo with associated improvements in tidal volume and minute ventilation (p < 0.05 vs placebo at week 8). Improvement in exercise time was significantly correlated with the increase in IC (r = 0.45, p < 0.001) but not FEV1 (r = 0.23, p = 0.08). Predose comparisons of FSC 250/50 with salmeterol and placebo favored FSC 250/50. CONCLUSION: We conclude that FSC 250/50 decreases lung hyperinflation at rest and during exercise with an associated increase in exercise endurance time when compared with placebo.

Adrenergic beta-Agonists↗
PubMed2006

Mechanisms and measurement of dyspnea in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) describe their breathlessness as related to the work and effort associated with breathing. Current evidence suggests that the perception of dyspnea is due to a "mismatch" between the outgoing motor command from the central nervous system and the corresponding afferent information from chemoreceptors and/or mechanoreceptors. To measure the severity of dyspnea the principles of psychophysics (stimulus --> response relationship) can be applied. One approach is to consider activities of daily living as a putative stimulus. Although this method relies on patient recall and description of daily tasks, ability to function, as well as time and effort to complete an activity, select clinical instruments have demonstrated appropriate measurement criteria in randomized clinical trials involving patients with COPD. Another approach is for a patient to report the intensity of dyspnea during exercise, and current practice is to provide ratings each minute "on cue" during the exercise test. A computerized system has been developed whereby the person can report ratings spontaneously and continuously by moving a computer mouse that adjusts a vertical bar adjacent to 0-10 category-ratio scale positioned on a monitor. With this continuous method the patient reports twice the number of dyspnea ratings during exercise compared with discrete ratings each minute. Patient-reported dyspnea based on activities of daily living and exercise testing provides distinct but complimentary information.

Dyspnea↗
PubMed2005

Measuring the effects of COPD on the patient.

Evaluation of the effectiveness of treatment for chronic obstructive pulmonary disease (COPD) requires the assessment of both clinical and physiological measures. Parameters such as the forced expiratory volume in 1 s are well established in providing an indication of the degree of airflow limitation. However, additional measurements, such as dyspnoea, functional status and health status, are required to provide a complete picture of COPD. Indeed, dyspnoea is the predominant symptom of COPD experienced by the patient, which treatment is designed to reduce. Methods of assessing dyspnoea have developed over the previous five decades. The most widely used instruments for assessing the impact of dyspnoea are the baseline dyspnoea index, the transition dyspnoea index and the Medical Research Council Questionnaire. A more comprehensive approach to the assessment of disability caused by dyspnoea and fatigue is provided by assessments of functional status, such as the pulmonary functional status and dyspnoea questionnaire. Respiratory-specific health status questionnaires, such as the St. George's Respiratory Questionnaire, attempt to capture the wide range of effects of COPD into a single score that reflects the overall impact of the disease. Developing the means to measure the effects of COPD is important, both in terms of understanding disease pathophysiology for research purposes, and in terms of accurately assessing the effects of treatment on the patient. Future developments will include computerising these methodologies to permit faster and more individual patient-centred measurements.

Dyspnea↗
PubMed2005

The MCID of the transition dyspnea index is a total score of one unit.

The Baseline (BDI) and Transition (TDI) Dyspnea Indexes provide interview-based measurements of breathlessness related to activities of daily living. The BDI is a discriminative instrument that includes specific criteria for each of three components at a single point in time. The TDI is an evaluative instrument that includes specific criteria for each of three components to measure changes from a baseline state. Observational studies have shown that patients with COPD generally experience a gradual progression of breathing difficulty as measured by the TDI over time. Randomized controlled trials have demonstrated excellent measurement characteristics of the TDI; these include responsiveness (ability to detect change) and construct validity (a change in the TDI correlates with changes in other variables). Supporting evidence for one unit as the minimal clinically important difference (MCID) of the TDI is based on: expert preference; use of the physician's global evaluation score as an anchor; and distribution estimates (standard error of measurement and 0.5 of the standard deviation). As an alternative to the interview process, self-administered computerized (SAC) versions of the BDI/TDI have been developed to provide direct patient-reported ratings of dyspnea. To further establish the MCID of the interview-administered and/or the SAC TDI, we recommend that a patient's report of global ratings of change by used as an independent standard or anchor.

Activities of Daily Living↗
PubMed2005

Responsiveness of continuous ratings of dyspnea during exercise in patients with COPD.

PURPOSE: To examine the responsiveness of a new computerized method for patients to provide continuous ratings of dyspnea during exercise in patients with chronic obstructive pulmonary disease (COPD). METHODS: In this randomized, double-blind study the effects of an inhaled bronchodilator (BD), albuterol/ipratropium bromide solution, were compared with normal saline (NS) in 30 patients with COPD (age, 66+/-9 yr; forced expiratory volume in 1 s, 48+/-14% pred). At visit 1, patients were familiarized with the cycle ergometer and computer, monitor, and mouse system to provide continuous ratings of dyspnea during exercise. At subsequent visits 2-3 d apart, patients performed pulmonary function tests followed by incremental ramp (15 W.min-1) and, 1 h later, constant work (at 55% of maximal work capacity) exercise tests. RESULTS: During incremental exercise the slopes of VO2:dyspnea and VE:dyspnea regressions were significantly lower, and patients exercised longer (Delta=0.4 min; P=0.003) with BD therapy compared with NS. During constant work exercise there was a significant reduction in dyspnea at the same exercise duration (5.0+/-2.8 vs 6.2+/-2.8 units on the 0-10 category-ratio scale; P=0.02) and patients exercised longer (Delta=0.9 min; P=0.04) with BD therapy. Changes in lung function at rest did not correlate significantly with changes in dyspnea ratings during exercise. CONCLUSIONS: Continuous ratings of dyspnea were responsive to inhaled bronchodilator therapy during both incremental and constant work exercise tests in patients with symptomatic COPD.

Aged↗
PubMed2004

Development of self-administered versions of modified baseline and transition dyspnea indexes in COPD.

In this study we developed self-administered versions of modified baseline and transition dyspnea indexes and compared the scores obtained by this method with the mean value obtained by two trained interviewers. Twenty-five patients (14 males/11 females) with chronic obstructive disease who had a chief complaint of "breathlessness" were tested. Age was 66+/-11 years; forced expiratory volume in one second was 48+/-23% predicted. The baseline total scores were 5.0+/-1.8 for the interviewers and 5.4+/-2.0 for the self-administered method. For the baseline dyspnea scores the correlations were 0.83 (p<0.0001) between self-administration and the mean value of two interviewers and 0.75 (p<0.0001) between the two interviewers. The transition total scores, obtained an average of 102 days (range, 7-377 days) later, were - 0.1+/-3.0 for the interviewers and - 0.4+/-3.0 for the self-administered method. For the transition dyspnea scores the correlations were 0.94 (p<0.0001) between self-administration and the mean value of two interviewers and 0.83 (p<0.0001) between the two interviewers. The self-administered dyspnea scores had similar correlations with measures of lung function as did the interview dyspnea scores. We conclude that self-administered versions of the modified baseline and transition dyspnea indexes provide comparable scores as those obtained by trained and experienced interviewers. The advantages of the self-administered versions include standardized methodology and computerized scoring.

Aged↗
PubMed2004

Comparison of continuous and discrete measurements of dyspnea during exercise in patients with COPD and normal subjects.

STUDY OBJECTIVES: The objectives of this study were as follows: (1) to compare results of the discrete and the continuous methods for measuring breathlessness; (2) to examine test-retest reliability; (3) and to test the hypothesis that patients with COPD have higher slopes and lower x-intercepts and absolute thresholds for power production, oxygen consumption (O(2)), and minute ventilation as independent variables and breathlessness ratings as the dependent variable, as compared with healthy subjects. DESIGN: Visit 1 (familiarization) and visit 2 and visit 3 (2 days apart) with randomized assignment of the discrete and continuous methods for subjects rating breathlessness during cycle ergometry. SETTING: Cardiopulmonary exercise laboratory in a university medical center. PARTICIPANTS: Twenty-four patients with COPD (mean age, 66 +/- 8 years [+/- SD]) and 24 healthy subjects (mean age, 66 +/- 10 years). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Ratings of breathlessness on the Borg scale on cue with subjects moving and pressing the computer mouse button to indicate a rating (discrete method) or by moving the position of the mouse to adjust a vertical bar to indicate a change in breathlessness (continuous method). There were no significant differences in results between visit 2 and visit 3. Although peak exercise variables were similar with the discrete and continuous methods, both groups provided significantly more ratings of breathlessness with the continuous method. Patients with COPD exhibited higher slopes, lower x-intercepts, and lower absolute thresholds (breathlessness rating >/==" BORDER="0"> 0.5 ["just noticeable"] on the Borg scale) for power production and O(2)-breathlessness compared with healthy subjects (p < 0.05). CONCLUSIONS: Elderly patients with COPD and healthy subjects are able to use the continuous method successfully. Reliability is excellent for both methods. The continuous method provides a greater number of breathlessness ratings over the course of exercise, and allows the clinician to calculate an absolute threshold and just-noticeable differences. Regression parameters and absolute thresholds discriminate between patients with COPD and healthy subjects.

Aged↗
PubMed2004

Efficacy and safety of a monoclonal antibody recognizing interleukin-8 in COPD: a pilot study.

STUDY OBJECTIVE: To investigate the efficacy and safety of a fully human monoclonal antibody recognizing the chemokine interleukin (IL)-8 in patients with COPD. DESIGN: Randomized, double-blind, parallel-group, placebo-controlled trial. SETTING: Eighteen clinics/hospitals in the United States. PATIENTS: One hundred nine patients with stable COPD. INTERVENTIONS: Three IV infusions of either monoclonal antibody recognizing IL-8 (800-mg loading dose; 400-mg subsequent doses) or active buffer solution administered monthly over a 3-month period. MEASUREMENTS AND RESULTS: The differences in the transition dyspnea index (TDI) total score, the primary outcome measure, between fully human monoclonal IgG(2) antibody directed against IL-8 and placebo were 0.8, 1.0, 0.8, and 0.3 at week 2 (p = 0.046) and months 1 to 3, respectively. At all time points, the proportion of patients achieving >/= 1 point improvement in the TDI was greater for the monoclonal antibody group compared with the placebo group: 28% vs 11% at week 2 (p = 0.028). There were no significant differences observed for lung function, health status, 6-min walking distance, and adverse events between groups. CONCLUSIONS: The results of this phase 2 study suggest that neutralization of IL-8 with monoclonal antibody therapy may improve dyspnea in patients with COPD. These results support the further investigation of monoclonal antibody therapy targeting IL-8 for the treatment of this disease.

Aged↗
PubMed2003

Evaluation of dyspnea in the elderly.

The word "dyspnea" encompasses many different features. It can be considered to be a sensation, a symptom, or an illness. From a practical perspective many physicians and nurses use dyspnea to refer to difficult or labored breathing or an uncomfortable awareness of breathing. The American Thoracic Society recently defined dyspnea as a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.

Aged↗
PubMed2003

Meaningful effect size and patterns of response of the transition dyspnea index.

Ths object of this study was to examine validity, meaningful effect sizes, and patterns of response of the Transition Dyspnea Index (TDI) in a clinical trial cohort of chronic obstructive pulmonary disease (COPD) patients. The design was a retrospective analysis of data from a randomized, double-blind placebo-controlled clinical trial. We analyzed fifty clinical investigation sites in United States. There were 921 patients with stable COPD. Tiotropium 18 microg dry powder or matching placebo was used. Patients were allowed to remain on usual care less ipratropium bromide. Construct validity was demonstrated by significant correlations (P <.05) between Baseline Dyspnea Index (BDI) and other baseline measures, as well as between TDI and changes in other measures at the end of 1 year. Concurrent validity was observed by the significant correlation between TDI and dyspnea diary responses. Changes in TDI focal score were in the range of one unit when the group was stratified by a minimal change in the physician's global evaluation. Significantly less (P <.05) supplemental albuterol was observed in the group of responders defined by a one-unit improvement in TDI. Responders also had few exacerbations and better health status. The validity of the TDI is supported in a large clinical trial setting. A one-unit change in the TDI focal score represented the minimal important difference.

Adult↗
PubMed2003

Stability of dyspnea ratings after exercise training in patients with COPD.

PURPOSE: The purpose of this study was to examine whether patients with chronic obstructive pulmonary disease (COPD) would report similar ratings of dyspnea at the same relative exercise intensity after participation in pulmonary rehabilitation. METHODS: Forty-two patients with COPD performed incremental cardiopulmonary exercise testing before and after completion of a 6-wk exercise-training program. Subjects rated dyspnea on the 0-10 category-ratio (CR-10) scale each minute of the exercise test. RESULTS: Both responders (21 patients who exhibited an increase in [OV0312]O(2peak) after pulmonary rehabilitation) and nonresponders (21 patients who had no increase in [OV0312]O(2peak)) reported slightly lower ratings of dyspnea ( approximately 0.5 on the CR-10 scale) at the same relative (50% and 75% of [OV0312]O(2peak)) exercise intensities. These changes in dyspnea ratings after pulmonary rehabilitation were not significantly different between responders and nonresponders. CONCLUSION: The study suggests that patients with COPD can use the same ratings of dyspnea to monitor training at the same relative exercise intensity whether they achieve a physiological training response or not.

Aged↗
PubMed2002

Effectiveness of fluticasone propionate and salmeterol combination delivered via the Diskus device in the treatment of chronic obstructive pulmonary disease.

This randomized controlled trial examined the benefits of combining an inhaled corticosteroid, fluticasone propionate (F), with an inhaled long-acting beta(2)-agonist, salmeterol (S), to treat the inflammatory and bronchoconstrictive components of chronic obstructive pulmonary disease (COPD). A total of 691 patients with COPD received the combination of F and S (FSC), S (50 mcg), F (500 mcg), or placebo twice daily via the Diskus device for 24 weeks. A significantly greater increase in predose FEV(1) at the endpoint was observed after FSC (156 ml) compared with S (107 ml, p = 0.012) and placebo (-4 ml, p < 0.0001). A significantly greater increase in 2-hour postdose FEV(1) at the endpoint was observed after treatment with FSC (261 ml) compared with F (138 ml, p < 0.001) and placebo (28 ml, p < 0.001). There were greater improvements in the Transition Dyspnea Index with FSC (2.1) compared with F (1.3, p = 0.033), S (0.9, p < 0.001), and placebo (0.4, p < 0.0001). The incidence of adverse effects (except for an increase in oral candidiasis with FSC and F) was similar among the treatment groups. We conclude that FSC improved lung function and reduced the severity of dyspnea compared with individual components and placebo.

Administration, Inhalation↗
PubMed2002

The effect of inhaled beta2-agonists on clinical outcomes in chronic obstructive pulmonary disease.

The major clinical outcomes measured in evaluating the responses to pharmacotherapy in patients with chronic obstructive pulmonary disease (COPD) include the severity of dyspnea, exercise capacity, exacerbations, and health status. Various studies have demonstrated that testing for acute bronchodilator reversibility in the pulmonary function laboratory does not predict the clinical responses to a trial of bronchodilator therapy in patients with COPD. Separate studies have shown that inhaled albuterol, both a single dose (300 microg) and 2 weeks of therapy (200 microg/4x/day), reduces dyspnea. There is more published information available about the effects of long-acting (>/=12 hours' duration of action) inhaled beta(2)-agonists because of greater interest in considering clinical outcomes at the time of drug testing. In one randomized clinical trial, formoterol reduced symptoms (as recorded in a home diary) and improved health status. Nine clinical studies have examined the effects of salmeterol on clinical outcomes. Salmeterol reduced the perception of breathlessness (in 6 of 9 studies) and improved health status (in 3 of 4 studies). These results collectively demonstrate that long-acting inhaled beta(2)-agonists not only relax bronchial smooth muscle but also provide important clinical benefits in symptomatic patients with COPD.

Administration, Inhalation↗