Severe Chronic Airflow Limitation Research Articles

Exploration of the Value of Health-Related Quality-of-Life Information From Clinical Research and Into Clinical Practice

Quality-of-life (QOL) instruments used in clinical research can provide important evidence to inform decisions about alternative treatments. This is particularly true when patients, such as those with cancer who are contemplating toxic chemotherapy, face tradeoffs between quantity of life and QOL or when the primary goal of therapy is to improve how patients feel. Surrogate measures (cardiac function, exercise capacity, bone density, tumor size) are inadequate substitutes for direct measurement of QOL. Quality-of-life measures will be most valuable when they comprehensively measure aspects of QOL that are both important to patients and likely to be influenced by therapy, when the QOL measurement instruments are valid (measuring what is intended) and responsive (able to detect all important changes, even if small), and when the results are readily interpretable (determining whether treatment-related changes are trivial, small but important, or large). Researchers are finding new, imaginative ways to help clinicians understand the magnitude of treatment impact on QOL. Additionally, QOL measures may be useful in clinical practice. Recent results from well-designed randomized controlled trials suggest that information on patient QOL provided to clinicians might, in some circumstances, result in benefits for these patients. Further investigation is warranted to confirm these observations and to define the particular combination of methods and settings most likely to yield important benefits.

Generic and Specific Measurement of Health-Related Quality of Life in a Clinical Trial of Respiratory Rehabilitation

The purpose of this study was to compare the performance of measures of health-related quality of life in a randomized controlled trial of respiratory rehabilitation versus conventional community care for patients with chronic airflow limitation. The study included 89 stable patients with moderate to severe chronic airflow limitation with measurement of health status at 12, 18, and 24 weeks. Outcomes included two disease-specific (the Oxygen Cost Diagram and the Chronic Respiratory Questionnaire [CRQ]) measures, a generic health profile (the Sickness Impact Profile [SIP]), and two utility measures (the Standard Gamble and the Quality of Well-Being index [QWB]). Of the measures, only the four domains of the CRQ (dyspnea, fatigue, mastery, and emotional function) showed statistically significant differences (P ≤ 0.05) between treatment and control groups. Correlation between change in the CRQ and change in other relevant measures, including the 6-minute walk test and global ratings of change in dyspnea, fatigue, and emotional function were generally weak to moderate (from 0.19 to 0.51). All correlations between change in the QWB, SIP, and Standard Gamble and other measures were very weak or weak (up to 0.30). Correlation between change in the three generic measures were all very weak (<0.15). The results suggest that unless investigators include responsive and valid disease-specific measures of health-related quality of life in controlled trials in chronic diseases, they risk misleading conclusions about the effect of treatments on health status.

Acute Exacerbations of Chronic Bronchitis: An International Comparison

The prevalence of chronic bronchitis is between 3% and 17% in most developed countries. However, higher rates in the range of 13 to 27% are encountered in less developed areas of the world. Acute exacerbations of chronic bronchitis (AECB) have usually been defined as the presence of increases in cough/sputum, sputum purulence, and dyspnea. However, recent investigations suggest that the severity of AECB may be divided into three stages based on the history of the patient: (1) previously healthy individuals; (2) patients with chronic cough and sputum and infrequent exacerbations; and (3) persons with frequent exacerbations or more severe chronic airflow limitation. Therapy for patients with less severe AECB include older and less expensive broad-spectrum antibiotics, while newer agents are indicated for patients with the most severe stage of AECB.

Qualitative aspects of exertional breathlessness in chronic airflow limitation: pathophysiologic mechanisms.

We compared qualitative aspects of the sensory experience of exertional breathlessness in normal subjects and in patients with chronic airflow limitation (CAL) and sought a physiologic rationale for these. Twelve patients (66 +/- 2 yr of age, mean +/- SEM) with severe CAL (FEV1 = 37 +/- 5% predicted) and 12 age-matched normal subjects (FEV1 = 103 +/- 5% predicted) were studied. Perceived inspiratory difficulty (BorgIN), inspiratory effort (esophageal pressure expressed as a fraction of maximal esophageal pressure at isovolume [Pes/PImax]), breathing pattern, and operational lung volumes (end-expiratory/inspiratory lung volumes [EELV/EILV]) were measured during symptom-limited incremental cycle exercise testing and compared at a standard VO2 of 50% predicted maximum in normal subjects and in patients with CAL. Qualitative descriptors of breathlessness were selected immediately after exercise. Breathlessness was qualitatively different between normal subjects and patients with CAL. Both normal subjects and patients with CAL chose descriptors of increased "work/effort" and "heaviness" of breathing; however, only patients with CAL consistently chose descriptors denoting "increased inspiratory difficulty" (75%), "unsatisfied inspiratory effort" (75%), and "shallow breathing" (50%). Stepwise regression analysis identified the ratio of Pes/PImax to VT/predicted VC as the strongest correlate of standardized BorgIN (n = 24, r = 0.86, p < 0.001). This latter measurement, which reflects the relationship between effort and ventilatory output, correlated strongly with dynamic EELV/TLC at isotime (r = 0.78, p < 0.001). In conclusion, the qualitatively discrete respiratory sensations of exertional inspiratory difficulty peculiar to patients with CAL may have their origins in thoracic hyperinflation and the resultant disparity between inspiratory effort and ventilatory output.

The Impact of Exercise Reconditioning on Breathlessness in Severe Chronic Airflow Limitation

The Impact of Exercise Reconditioning on Breathlessness in Severe Chronic Airflow Limitation

The Impact of Exercise Reconditioning on Breathlessness in Severe Chronic Airflow Limitation.

The Impact of Exercise Reconditioning on Breathlessness in Severe Chronic Airflow Limitation.

The impact of exercise reconditioning on breathlessness in severe chronic airflow limitation.

Exercise in chronic airflow limitation (CAL) is often limited by symptoms before the physiologic boundaries of maximal ventilatory or cardiovascular capacities are attained. Symptom amelioration should translate directly into improved exercise performance. We studied the impact of a 6-wk supervised multimodality endurance exercise program (EXT) on perceived breathlessness (B) and leg effort (LE) and sought a physiologic rationale for symptom improvement. Thirty patients with CAL (FEV1/FVC = 42 +/- 2%, mean +/- SEM) were tested before and after EXT. Their responses were compared with those of a matched control group (n = 30; FEV1/FVC = 44 +/- 2%) after a nonintervention period. Testing included pulmonary function tests, chronic dyspnea evaluation (Baseline/Transition Dyspnea Index [BDI/TDI]), and graded cycle exercise with cardioventilatory monitoring and Borg scaling of B and LE. Spirometry did not change (delta) post-EXT. EXT significantly (p < 0.001) reduced chronic breathlessness (TDI = +2.8 +/- 0.3) compared with control (TDI = 0.0 +/- 0.3). Exertional symptoms of B and LE also fell (p < 0.01) after EXT (slopes of B and LE relative to VO2 fell by 14 and 23%, respectively; delta B/VO2 was associated with delta LE/VO2, r = 0.52, p < 0.01). Post-EXT slopes of B over ventilation (VE) also decreased by 10% (p < 0.025). Total cycle work increased 142 +/- 70% (p < 0.001) post-EXT and correlated primarily with delta B/VO2 (r = -0.64, p < 0.001). The best correlate of delta B/VO2 was delta VE/VO2 (r = 0.47, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Exertional breathlessness in patients with chronic airflow limitation. The role of lung hyperinflation.

There is considerable intersubject variability in the perceived intensity of breathlessness for a given level of activity among patients with chronic airflow limitation (CAL). To examine possible factors contributing to this variability we compared breathing pattern parameters, dynamic operational lung volumes, and Borg dyspnea ratings in 23 patients with severe CAL and in 10 healthy age-matched normal subjects during cycle ergometry to symptom-limitation. Patients with CAL had significantly (p < 0.01) higher levels of ventilation (% maximal voluntary ventilation) for a given work rate (slope of VE(%MVV)/WR(% pred max) = 1.51 +/- 0.18 versus 0.63 +/- 0.10; mean +/- SEM) and greater dynamic lung hyperinflation (DH) (change [delta] in end-expiratory lung volume [EELVdyn] = +0.31 +/- 0.11 L versus -0.16 +/- 0.22 L). Compared with normal subjects at a standardized VE (30 L/min), the CAL group was more breathless Borg = 4 +/- 1 versus 2 +/- 1, p < 0.01) and hyperinflated (EELVdyn = 75 +/- 3 versus 46 +/- 6% TLC, p < 0.001; end-inspiratory lung volume [EILVdyn] = 85 +/- 3 versus 67 +/- 5% TLC, p < 0.01). Within the CAL group, change in Borg ratings correlated with delta VE(%MVV) (r = 0.77, p < 0.001) and with slope of VE(%MVV)/WR(% pred max) (r = 0.48, p < 0.01). Regression analysis selected delta EILVdyn (or delta inspiratory reserve volume [delta IRVdyn]) from various dynamic ventilatory parameters as the strongest predictor of delta Borg (r = 0.63, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Breathlessness in Patients With Severe Chronic Airflow Limitation

Breathlessness in Patients With Severe Chronic Airflow Limitation

Theophylline. Current thoughts on the risks and benefits of its use in asthma.

Theophylline and its derivatives have been used in the treatment of asthma for over 50 years, but since the advent of more potent bronchodilators their use has become cloaked in controversy. Their continued existence results from their undoubted usefulness in severe acute asthma, nocturnal asthma, childhood asthma and moderate to severe chronic airflow limitation, and because of habitual use by physicians in other situations. The precise mechanism of action of theophylline remains uncertain. The role of phosphodiesterase inhibition and adenosine antagonism has been reviewed and the clinical significance of the anti-inflammatory action of theophylline discussed. Theophylline has unpredictable metabolism when first administered, and continued monitoring of drug concentrations is essential. Commonly encountered adverse effects may occur at therapeutic serum concentrations, frequently necessitating drug withdrawal. The overlapping therapeutic and toxic theophylline serum ranges can lead to life-threatening adverse effects at the upper end of the therapeutic range, especially in the elderly in whom special precaution is required.

Breathlessness in Patients with Severe Chronic Airflow Limitation: Physiologic Correlations

We wished to identify the physiologic abnormalities that distinguish severely breathless (SB) patients with chronic airflow limitation (CAL) from mildly breathless (MB) patients. Thirty-seven patients with stable, advanced CAL (FEV1 = 38 +/- 10 percent predicted, mean +/- SD) were separated into two distinct groups, SB and MB, solely on the basis of their baseline dyspnea index (BDI). BDI ratings in SB (n = 17) and MB (n = 20) patients were 2.5 +/- 1.5 and 8.5 +/- 1.5 (mean +/- SD), respectively (p less than 0.001). Groups were compared with respect to pulmonary function, breathing pattern parameters, arterial blood gases (ABGs), and responses to progressive exercise. Steady-state gas-exchange parameters were measured in a subgroup of 16 patients during exercise. There were no significant intergroup differences in dynamic flows, plethysmographic lung volumes, ABGs, resting ventilation, or breathing pattern parameters. However, the SB group had significantly lower single-breath diffusing capacities for carbon monoxide (Dco) (by an average of 50 percent, p less than 0.001), together with significantly higher resting ventilatory equivalents for carbon dioxide (VE/VCO2) (by 17 percent, p less than 0.01) and dead space to tidal volume ratios (by 11 percent, p less than 0.05). Ventilatory responses for a given metabolic load were, on average, 33 percent higher (p less than 0.05) in the SB group reflecting greater ventilation-perfusion inhomogeneity and wasted ventilation. The SB subgroup (n = 7), in contrast to the MB subgroup (n = 9), demonstrated significantly (p less than 0.01) greater O2 desaturation during exercise; PaO2 decreased in SB and MB at peak exercise by -13 +/- 7 mm Hg and -4 +/- 2 mm Hg (mean +/- SD), respectively. Stepwise regression analysis selected DCO and VE/VCO2 as the only predictors of breathlessness in this group, accounting for 52 percent of the variance in BDI (F-ratio = 18.49, p less than 0.001). Although the origin of breathlessness is multifactorial, variation in its intensity among patients with comparable levels of airflow limitation can be accounted for, in part, by underlying pathophysiologic differences. Severely breathless patients were characterized by lower resting diffusing capacities and accelerated ventilatory responses to exercise.

An evaluation of three elements of pulmonary rehabilitation

In this study of 39 patients with severe chronic airflow limitation, an independent group design examined the effect on exercise performance of a six-week program of leg muscle training, inspiratory muscle training and postural drainage. Exercise performance was reassessed at three months after the completion of the training program. MANOVA analysis of the 12-minute walking distance test showed a significant training effect (p < 0.001) with the largest effect occurring with leg muscle training (873 to 952 metres), a placebo response with postural drainage (886 to 925 metres) and minimal change with inspiratory muscle training (911 to 920 metres). There was a carry over effect at three months with leg muscle training, that was not seen in the other groups.

The use of protriptyline for respiratory failure in patients with chronic airflow limitation

Treatment of nocturnal hypoventilation in patients with restrictive chest wall disease and respiratory failure, results in improved daytime arterial blood gas tensions, increase in functional ability and longer survival. Success has been achieved with the use of protriptyline which reduces the duration of rapid eye movement (REM) sleep during which nocturnal hypoventilation occurs. Eighteen patients with severe chronic airflow limitation (CAL), took part in a randomized, double-blind, crossover trial of protriptyline and placebo. Seventeen patients completed the study. The use of protriptyline was associated with a fall in the median percentage of total sleep time spent in REM from 16 to 8.8% (p less than 0.01). This was associated with a reduction in the median daytime arterial carbon dioxide tension from 6.4 kPa (range 5.2-8.5 kPa) to 5.8 kPa (range 5.0-8.1 kPa) (p less than 0.01); increased respiratory muscle strength (p less than 0.05), and increased six minute walking distance from a median of 258 m (range 58.5-585 m) to 275 m (range 171-598 m) (p less than 0.02). We found pharmacological treatment of REM-related nocturnal hypoventilation in patients with CAL to be effective, but anticholinergic side-effects, particularly in older male patients, might preclude long-term treatment.

Intrapulmonary distribution of 99mtechnetium labelled ultrafine carbon aerosol (Technegas) in severe airflow obstruction

Technegas (TG), an ultrafine dispersion of carbon aggregates labelled with 99mTechnetium (99mTc), has been recently introduced for clinical imaging of lung ventilation. In 12 selected subjects with severe chronic airflow limitation (FEV1 = 0.89 +/- 0.22; mean +/- SD, l) we have studied the regional intrapulmonary distribution of TG and compared it quantitatively with that of 133Xenon (133Xe). A 133Xe equilibration image was acquired for 10-15 s during a breathhold at total lung capacity (TLC). Six subjects (Group 1) inspired 100 ml boli of TG or 133Xe from functional residual capacity (FRC) and another 6 subjects (Group 2) inspired 1.0 l of labelled gas from FRC followed by air to TLC at a constant flow rate less than 0.5 l.s-1. Lung images were then acquired with the chest position rigorously controlled. From the equilibration image, upper, middle, lower, central and peripheral regions were defined. Relative regional fractional concentrations (RFC) were then calculated using the equilibration image to correct for ventilated lung volume. In addition, in four of the Group 2 subjects, each lung image was divided into multiple regions (12-17 per lung). The RFC were then calculated as above (RFCM). The highest and lowest RFC were not significantly different between 133Xe and TG in either Group 1 or Group 2 subjects. Similarly the RFCM analysis showed no systematic difference between 133Xe and TG. The ratio of peripheral to central RFC constitutes a penetration index which for TG was 0.99 +/- 0.23 that of 133Xe. Our results indicate that even in the presence of severe airflow limitation the radiolabelled tracer TG mimics the regional distribution of a real gas.

Effect of chronic airflow limitation on resting oxygen consumption.

The work of breathing in patients with severe chronic airflow limitation is increased even at rest but little is known about the magnitude of this increase. Resting oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory quotient (RQ) were measured in 13 patients with severe chronic airflow limitation (mean FEV1 0.78 1, vital capacity 2.1 1) and compared with those of 13 age, weight, and height matched control subjects. Whereas mean RQ was the same in the two groups (0.82), mean VO2 and VCO2 were higher in the patients (+ 18 ml min-1 and + 15 ml min-1 respectively). When VO2 was standardised for body surface area it was 10.9% higher in the patients (p less than 0.05). If the increased resting VO2 in these patients were solely due to increased activity of the respiratory muscles, it would represent a fourfold increase in the oxygen cost of breathing.

Effects of Oral Terbutaline in Chronic Airflow Limitation

A randomized, double-blind, crossover study was conducted to assess the efficacy of five weeks' treatment with terbutaline, 15 mg daily, compared with placebo in 17 evaluable patients with moderate to severe chronic airflow limitation (CAL) with a minor reversible component. A significant improvement after terbutaline treatment compared with placebo was observed in subjective assessments of breathlessness after two of the activities of daily living, and in daily peak flow measurements recorded in patient diaries. At the clinical assessment after five weeks' terbutaline therapy, 12 of 17 patients had improved pulmonary symptom scores compared with placebo, and a slight increase in FEV1 was observed relative to placebo (0.09 L, p less than 0.05). Thus, five weeks' treatment with oral terbutaline in patients with CAL resulted in significant improvements in several subjective assessments, despite a lack of effect on the majority of the objective variables.

Negative Pressure Ventilation: Effects on Ventilation during Sleep in Normal Subjects

Negative pressure ventilation (NPV) is used for ventilatory support of patients with respiratory failure due to neuromuscular disorders and thoracic deformities, and to provide ventilatory muscle rest for patients with severe chronic airflow limitation. To determine whether NPV would result in episodes of upper airway obstruction during sleep, we studied five normal subjects on two consecutive nights with the first night serving as a control and NPV being administered on the second night. Ventilators were adjusted so as to reduce the peak phasic diaphragm electromyogram signal by at least 50 percent. All subjects demonstrated an increase in the total number of apneas + hypopneas per hour on NPV control nights. Although differences were not significant, there was a tendency to develop decreased sleep efficiency, sleep fragmentation and altered sleep architecture with NPV. We conclude that nocturnal NPV can induce sleep apneas and impair sleep quality in normal subjects.

High-dose Inhaled Albuterol in Severe Chronic Airflow Limitation

Higher doses of inhaled albuterol have been shown to cause slightly more bronchodilatation than standard doses from a metered-dose inhaler in patients with severe chronic airflow limitation. Higher doses, however, carry an increased risk of side effects, and the optimum dose balancing benefit and adverse effects have yet to be established. We have therefore looked at objective and subjective evidence of beneficial and adverse effects after 4 doses of albuterol in 30 patients with chronic bronchitis, severe airflow limitation, and less than 200 ml increase in FEV1 after 200 micrograms inhaled albuterol. Subjects were given placebo, 400 micrograms, 1 mg, 2 mg, and 4 mg albuterol by dry powder inhaler in random order on separate days in a double-blind study, and FEV1, relaxed VC, PEFR, 12-min walk distance, finger tremor, oxygen saturation, heart rate, and arrhythmias were measured at intervals over 6 h. With increasing doses of albuterol, there was a significant dose-related increase in FEV1, VC, and PEFR, the maximal mean changes being 196 ml, 480 ml, and 50 L/min, respectively. The duration of effect was longer with the higher doses. There was a dose-related increase in heart rate, tremor amplitude, and supraventricular ectopic beats and a dose-related fall in oxygen saturation. There was no drug-related effect on the frequency of ventricular ectopic beats either at rest or during the walk tests. The largest increases in walk distance occurred after the 1 and 2 mg doses and the least after the 4 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Nifedipine dilates the pulmonary vasculature without producing symptomatic systemic hypotension in upright resting and exercising patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease.

Vasodilator therapy may lower pulmonary vascular resistance in patients with chronic air-flow limitation. However, the effects of these agents on left ventricular afterload, cardiac output, and bronchial smooth muscle could lower the calculated pulmonary vascular resistance without specifically affecting pulmonary vascular tone. In addition, systemic hypotension in the upright position and worsening ventilation/perfusion heterogeneity could limit their use. We determined the pulmonary driving pressure (pulmonary arterial-pulmonary arterial wedge pressure) to flow relationship, as well as the transmural pulmonary arterial pressure in 9 patients with severe chronic air-flow limitation with pulmonary hypertension while in a clinically stable condition. Measurements were made at rest and during 3 stages of progressively increasing upright exercise on a bicycle before and after a single 20-mg dose of nifedipine. Nifedipine displaced both the driving pressure to flow and the pulmonary arterial transmural pressure to flow relationships towards higher flows in every subject, suggesting an active vasodilation. In the upright position, PaO2 did not change, and the systemic arterial pressure was only mildly reduced. In patients with pulmonary hypertension from chronic air-flow limitation, acute administration of nifedipine to upright patients causes pulmonary, as well as systemic vasodilation without causing symptomatic hypotension or reducing arterial oxygenation.

Ventilatory muscle function during exercise in air and oxygen in patients with chronic air-flow limitation.

Ventilatory muscle function was examined at rest and during exercise on a cycle ergometer in 8 patients with moderate to severe chronic air-flow limitation (FEV1, 32 +/- 4% predicted) in air and in oxygen. The diaphragmatic electromyogram (EMG) was measured using an esophageal electrode. In addition, measurements of esophageal (Pes), gastric (Pga), and transdiaphragmatic (Pdi) pressures and abdominal wall movements were made. Patients exercised to exhaustion at a constant submaximal workload (80% of maximal power output) inspiring air or 40% O2 in random order on separate days. At end-exercise in air, tidal inspiratory Pes swings were 36 +/- 4% of static maximal inspiratory Pes, and inspiratory Pdi swings were 45 +/- 7% of the static maximal Pdi. Arterial oxygen saturation decreased from 91 +/- 2% at rest to 80 +/- 5% at end-exercise in air. During exercise in air, 5 patients demonstrated a persistent and greater than 20% fall in the ratio of high frequency (150 to 350 Hz) to low frequency (20 to 46 Hz) power (H/L) of the diaphragmatic EMG, indicating impending diaphragmatic fatigue, and 2 patients had paradoxical motion of the abdominal wall. Exercise time at the same constant work load increased from 3.0 +/- 0.6 min in air to 6.4 +/- 1.2 min in O2 (p less than 0.005). At the comparable time during exercise in O2 to end-exercise in air, minute ventilation was less by 13% (p less than 0.005), which was entirely attributable to a lower frequency of breathing. Mean inspiratory and expiratory flows and heart rate were all significantly lower.(ABSTRACT TRUNCATED AT 250 WORDS)