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Biomedical subjects

A S Rebuck

Publications and source records attributed to A S Rebuck.

At least 19 recordsLinked to original sources
PubMed1994

Is the short-term response to inhaled beta-adrenergic agonist sensitive or specific for distinguishing between asthma and COPD?

In view of the ubiquitous practice of using bronchodilator responsiveness to determine suitable patients for clinical trials, we wanted to know whether changes in FEV1 or forced vital capacity (FVC) really were useful in differentiating COPD from asthma. Pulmonary function test results from 450 patients were documented by two technicians who had been asked to select consecutive studies in which flow-volume loops showed an obstructive pattern. The respirologist responsible for the care of each patient was asked to record the clinical diagnosis from the existing outpatient chart using clinical judgment based on American Thoracic Society criteria. In 395 cases, a single, unambiguous diagnosis of asthma or COPD was recorded; this diagnosis then formed the database for subsequent analysis. While the mean change in FEV1 in patients judged to have asthma was different from that found in COPD patients (16.4 vs 10.6 percent, p < 0.01), the change in FVC was similar (9.8 vs 10.3 percent, p > 0.06). However the sensitivities and specificities of postbronchodilator changes in FEV1 (dFEV1) for the diagnosis of asthma were not generally sufficient to diagnose or exclude asthma reliably. The FEV1 correlated better with residual volume (RV) in COPD (r = -0.55 vs r = -0.31), but with total lung capacity (TLC) in asthma (r = 0.51 vs r = -0.09). However, FEV1 correlated better with the RV-TLC ratio than RV or TLC alone in both groups, the correlation in each being similar (asthma, r = -0.72; COPD, r = -0.78). We conclude that acute responses of FEV1 and FVC following a standard dose of inhaled bronchodilator are neither sufficiently sensitive nor sufficiently specific to differentiate asthma from COPD purely on spirometric grounds. Furthermore, neither RV nor TLC reflected degrees of airflow limitation as well as did the RV-TLC ratio.

Administration, Inhalation↗
PubMed1993

Trends in asthma and chronic obstructive pulmonary disease therapy in Canada, 1985 to 1990.

BACKGROUND: In the mid and late 1980s, numerous changes were recommended in the management of obstructive lung diseases. We analyzed drug sales to determine whether these recommendations have resulted in recent changes in prescription drugs used in airway management. METHODS: Data on prescription sales in Canada from 1985 to 1990 were obtained from an international pharmaceutical market research organization. Data from a random sampling of physicians that reported patients seen along with the diagnosis and prescriptions given were also reviewed. RESULTS: From 1985 to 1990, there was a 38% increase in prescriptions of all airway drugs. Prescriptions increased significantly for inhaled drugs as follows: inhaled beta 2-agonists, 70%; inhaled steroids, 139%; cromoglycate, 88%; and ipratropium bromide, 204%. Theophylline prescriptions, by contrast, fell significantly, by 19%. Although theophylline was the most commonly prescribed airway medication in 1985, inhaled beta 2-agonists were the most commonly prescribed drug in 1990, and these changes in proportional use were significant. Increases in ipratropium bromide usage was accounted for by increases in prescriptions for chronic obstructive pulmonary disease. Increases in nonsteroidal antiinflammatory drugs were accounted for by asthma prescriptions. CONCLUSIONS: The increase in airway medication prescriptions dispensed in Canada is consistent with an increase in the number of patients treated, an increase in the severity of disease treated, or both.

Anti-Inflammatory Agents↗
PubMed1993

Tracheobronchial dilation during isocapnic hypoxia in conscious humans.

To assess the effects of isocapnic hypoxia on the pharynx, glottis, extrathoracic trachea (ET), intrathoracic trachea (IT), and main bronchi (MB), we measured the cross-sectional areas of these airways by acoustic reflection technique in 15 healthy volunteers. Measurements were made during tidal volume breathing while subjects were normoxic [arterial O2 saturation (SaO2) > 95%] or were made hypoxic by a rebreathing procedure. Under hypoxemic conditions, airway cross-sectional areas increased significantly at ET, IT, and MB levels (P < 0.001). The magnitude of this dilation was similar for both levels of hypoxemia studied (SaO2 80-85% and 70-75%); at the milder of the two hypoxemic conditions, ET cross-sectional area increased by 12.4 +/- 4.2% (SE), IT by 10.2 +/- 5.9%, and MB by 19.1 +/- 3.2%. No significant changes were found in the pharyngeal or glottic areas. Dilation was not produced by normoxic isocapnic hyperventilation, and the use of hypoxic airway gas mixtures did not artifactually alter acoustic reflection measurements in a mechanical model. Vagal airway tone, as reflected by airway constriction during pauses in tidal breathing, was unaffected by isocapnic hypoxia. We conclude that isocapnic hypoxia produces dilation of the trachea and major bronchi, an effect unaccounted for by an alteration in the ventilatory pattern.

Adult↗
PubMed1993

Assessment of airway tone in asthma. Comparison between double lung transplant patients and healthy subjects.

We investigated the hypothesis that asthmatic patients have an increased cholinergic tone by measuring tracheobronchial cross-sectional areas during transient voluntary apnea. This allowed us to assess bronchomotor tone without the influence of changes in lung recoil or lung volume. Three groups of subjects with potentially different levels of tracheobronchial tone were studied: 14 healthy volunteers (N), 18 stable asthmatic patients (A), and 10 double lung transplant recipients (T). Using the acoustic reflection technique, we measured changes in tracheobronchial cross-sectional areas during short periods (5 to 10 s) of voluntary apnea. In a subset of subjects, studies were repeated before and after the inhalation of the muscarinic antagonist ipratropium. During breath-holding, glottis and extrathoracic trachea remained unchanged but intrathoracic tracheal area decreased by 30 +/- 8% (mean +/- standard error of the mean) in N, by 27 +/- 3% in A, and by 9 +/- 4% in the T group. Bronchial areas decreased by 24 +/- 8% in N, by 45 +/- 3% in A, and by 10 +/- 4% in T. These differences among groups were statistically significant at the tracheal and bronchial levels (p < 0.05), and ipratropium significantly inhibited this airway constriction (p < 0.05) only in the asthmatic group. Assuming that changes in cross-sectional airway areas voluntary apnea reflect airway tone, these results support the view that in humans this tone is mainly vagally controlled and that it is significantly increased in asthmatic compared with nonasthmatic subjects.

Administration, Inhalation↗
PubMed1992

The use of beta-agonists and the risk of death and near death from asthma.

BACKGROUND: Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of beta 2-agonist bronchodilators. METHODS: Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case-control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987. We matched 129 case patients who had fatal or near-fatal asthma with 655 controls (who had received medications for asthma but had not had fatal or near-fatal events) with respect to region of residence, age, receipt of social assistance, and previous hospitalization for asthma. RESULTS: The use of beta-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma (odds ratio, 2.6 per canister per month; 95 percent confidence interval, 1.7 to 3.9) and of death or near death from asthma, considered together (odds ratio, 1.9; 95 percent confidence interval, 1.6 to 2.4). For death from asthma, use of the beta-agonist fenoterol was associated with an odds ratio of 5.4 per canister, as compared with 2.4 for the beta-agonist albuterol. On a microgram-equivalent basis, the odds ratio for this outcome with fenoterol was 2.3, as compared with 2.4 with albuterol. CONCLUSIONS: An increased risk of death or near death from asthma was associated with the regular use of inhaled beta 2-agonist bronchodilators, especially fenoterol. Regardless of whether beta-agonists are directly responsible for these adverse effects or are simply a marker for more severe asthma, heavy use of these agents should alert clinicians that it is necessary to reevaluate the patient's condition.

Administration, Inhalation↗
PubMed1992

Physiologic and nonphysiologic determinants of aerobic fitness in mild to moderate asthma.

We studied 27 patients (seven male, 20 female) with stable mild-to-moderate asthma to measure their level of physical fitness and to determine if a relationship existed between aerobic fitness and the degree of airway reactivity, expiratory flow rates, or the amount of habitual leisure-time physical activity. Nonspecific bronchial hyperreactivity (NSBHR) was quantified by methacholine inhalation challenge. On a separate day, exercise capacity was evaluated with incremental exercise testing to exhaustion after bronchodilator pretreatment. The level of physical activity was assessed with a validated written questionnaire. FEV, was 78 +/- 13% predicted prebronchodilator and 92 +/- 14% predicted postbronchodilator. The mean provoking concentration of methacholine that caused a 20% decrease in FEV1 (PC20) was 1.14 +/- 1.38 mg/ml and ranged from 0.019 to 5.71 mg/ml. There was no correlation between PC20 and prebronchodilator FEV1 r = 0.37, p greater than 0.05). Mean maximal oxygen uptake (VO2max) was not significantly different from predicted normal values (36.9 +/- 10.8 versus 38.5 +/- 5.3, p = 0.32). Mean maximal O2pulse (maximal heart rate/VO2max), anaerobic threshold, and dyspnea index were within normal limits. There was no relationship between VO2max and FEV1 when expressed as percentages of predicted values (r = 0.08, p = 0.71) or between VO2max and PC20 (r = 0.23, p = 0.25). There was, however, a significant relationship between VO2max and the level of habitual leisure-time activity (F = 3.64, p less than 0.05). Results from the exercise questionnaire suggested that asthmatics perceive their disease as a limiting factor to improved aerobic fitness and that they lack adequate knowledge about asthma and exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Changes in cross-sectional airway areas induced by methacholine, histamine, and LTC4 in asthmatic subjects.

To examine whether leukotrienes, histamine, and methacholine have different sites of bronchoconstrictor action, we studied 8 stable asthmatic subjects (mean age +/- SD, 26 +/- 5 yr) on 3 different days. On each day, a randomized challenge with LTC4, methacholine, or histamine was performed until the dose that provoked a fall of 20% in FEV1 (PC20) was obtained. Complete and partial flow-volume curves as well as area-distance profiles generated by the acoustic reflection technique (ART) at a fixed lung volume were obtained in all subjects before and after each inhalation challenge. No significant differences were found in pulmonary function or baseline cross-sectional airway areas for the different study days. The three agonists provoked significant (p less than 0.05) bronchoconstriction at the level of the main bronchi when identical falls of FEV1 were achieved. Similarly, equal reductions of V30p were elicited by the three agonists. However, LTC4 and methacholine induced additional tracheal constriction but histamine inhalation did not. These differences in the degree of tracheal constriction were statistically significant (p less than 0.05; ANOVA). These results may be explained by distinct pharmacologic properties of the agents used and may have relevance in the understanding of the pathophysiology of asthma.

Analysis of Variance↗
PubMed1992

The fatality-prone asthmatic patient. Follow-up study after near-fatal attacks.

We studied 12 fatality-prone patients for 18 months after they had been discharged from the hospital following life-threatening exacerbations of asthma (mean PaCO2 on admission, 97 mm Hg). Our objectives were (1) to evaluate the natural history of their disease during ambulatory care and (2) to investigate whether close follow-up might help to avert further near-fatal events. Only seven of the 12 patients consented to be enrolled in the study, which included monthly scheduled visits to the hospital and monthly telephone calls to record emergency room visits and changes in therapy. By the conclusion of the 18-month follow-up period, two of the noncompliant patients had died during asthmatic attacks. By contrast, all of the seven who had agreed to participate survived; one required intubation and mechanical ventilation, and the other six required occasional unscheduled emergency room visits because of acute exacerbations. Specific precipitants could not be determined, and the most common cause of the acute episodes was likely inadequate steroid therapy. The results suggest that compliance with adequate antiasthmatic therapy and close follow-up may be important in the prevention of near-fatal events.

Adolescent↗
PubMed1992

Erythropoietin response to acute hypoxemia in patients with chronic pulmonary disease.

Chronic hypoxemia is associated with development of secondary polycythemia. To evaluate effects of transient hypoxemia on serum EPO activity in patients with chronic lung disease, we studied six oxygen-dependent patients who underwent either a 4-h oxygen withdrawal or their routine therapy, in a randomized, blinded fashion, on two separate days. Serum EPO did not differ at baseline between study days. Erythropoietin levels did not change significantly over time during normoxic conditions. Under hypoxic conditions, serum EPO levels rose over 4 h with the change from baseline first becoming significant at 2 h. The log of serum EPO response showed an inverse correlation with the level of arterial oxygen saturation. We conclude that patients with chronic lung disease are able to produce EPO in response to acute hypoxemic stress. Transient episodes of hypoxemia, such as occur during sleep or exercise, may result in increased red blood cell production stimulated by this EPO response.

Acute Disease↗
PubMed1991

Effect of a short course of prednisone in the prevention of early relapse after the emergency room treatment of acute asthma.

BACKGROUND: Relapse after the treatment of acute asthma in the emergency room is common (occurring in 25 to 30 percent of cases) and is not accurately predicted by any available measurements. We studied the usefulness of prednisone in reducing this high rate of relapse. METHODS: One hundred twenty-two patients treated in the emergency room for acute exacerbations of asthma were assigned in a randomized, double-blind fashion to receive at discharge either prednisone for eight days (the dose being tapered from 40 to 0 mg per day) or matching placebo. Ninety-three were subsequently discharged from the emergency room and participated in the trial. On days 1, 7, and 14 after discharge, the patients were assessed during home visits with spirometry and diary-card review; they were contacted by telephone on day 21. Relapse was defined as an unscheduled medical visit occasioned by the patient's perceived need for further asthma treatment. RESULTS: The overall risk of relapse was significantly lower in the prednisone group (P less than 0.05), with a significantly reduced rate of relapse during the first 10 days of follow-up (3 of 48, as compared with 11 of 45 in the placebo group; P less than 0.05). Thereafter (days 11 through 21), there was no further significant difference in relapse rates between treatment groups (five in the prednisone group and six in the placebo group). During the first week after discharge, patients receiving prednisone reported significantly lower mean (+/- SD) daily symptom scores for shortness of breath (1.4 +/- 0.4 vs. 2.5 +/- 0.4, P less than 0.01) and less frequent use of an inhaled bronchodilator (5.2 +/- 0.5 vs. 6.9 +/- 0.2 puffs per day, P less than 0.05) than patients receiving placebo. Subsequently, symptom scores and bronchodilator use were similar in the two groups. CONCLUSIONS: A short course of prednisone reduced early relapse rates after the treatment of acute asthma in the emergency room, an effect limited to the period of steroid administration.

Acute Disease↗
PubMed1991

Phrenic neural output during hypoxia in dogs: constant-flow ventilation vs. spontaneous breathing.

We studied the effects of removing cyclic pulmonary afferent neural information on respiratory pattern generation in anesthetized dogs. Phrenic neural output during spontaneous breathing (SB) was compared with that occurring during constant-flow ventilation (CFV) at several levels of eucapnic hypoxemia. Hypoxia caused an increase in both the frequency and the amplitude of the moving time average (MTA) phrenic neurogram during both SB and CFV. The change in frequency as arterial saturation was reduced from 90 to 60% during SB was significantly higher than that during CFV [SB, 32.3 +/- 10.9 (SD) breaths/min; CFV, 10.3 +/- 5.8 breaths/min; P = 0.001]. By contrast, the increase in the amplitude of the MTA phrenic neurogram was smaller (SB, 0.62 +/- 0.68 units; CFV, 1.35 +/- 0.81 units; P = 0.01). The changes in frequency with hypoxia during both modes of ventilation resulted primarily from a shortening of expiratory time. Both inspiratory time and expiratory time were greater during CFV than during SB, but their change in response to hypoxia was not significantly different. We conclude that the amplitude response of the MTA phrenic neurogram to hypoxia is similar to that seen during hypercapnia; in the presence of phasic afferent feedback the MTA amplitude response is decreased and the frequency response is increased relative to the response observed in the absence of phasic afferents.

Afferent Pathways↗
PubMed1991

Clinical complexity and epidemiologic uncertainty in case-control research. Fenoterol and asthma management.

Two recent epidemiologic case-control studies suggested that fenoterol, a selective beta-adrenergic agonist, was associated with an increase in the risk of asthma death. The results of these studies were criticized because of methodologic problems in the choice and selection of control subjects; the different methods used to gather exposure data in cases and control subjects; and because of inadequate classification and adjustment for asthma severity. In response to this controversy, a new study is underway, the Saskatchewan Asthma Epidemiology Project. The SAEP includes two complementary studies, an historic cohort and a case-control analysis, that employ the computerized databases of the Saskatchewan Health Department. A unique aspect of the SAEP is the attempt to incorporate knowledge of asthma physiology and management into the design of the studies. Specifically, the study design recognized the role of antiinflammatory drugs in asthma treatment; the distinction between asthma death and near-fatal asthma; the severity of asthma; patterns of drug use; and the distinction between inadequate clinical care and disease severity. The strategies we employed in the SAEP may prove helpful to investigators whenever clinical and biologic processes create sources of potential bias requiring special procedures for the design and analysis of epidemiologic studies.

Adolescent↗
PubMed1991

Impaired exercise capacity in adults with moderate scoliosis.

We measured lung function and exercise tolerance in 15 adults with moderate kyphoscoliosis (thoracic curvatures between 25 degrees and 70 degrees, mean +/- SD = 46.93 degrees +/- 14.02 degrees). Forced vital capacity showed a slight reduction from values predicted from age and sex matched control subjects (3.39 +/- 1.06 vs 4.06 +/- 0.82 L, p less than 0.05). However, exercise tolerance was significantly lower than previously reported in healthy adults (VO2max = 31.60 +/- 9.12 vs 37.07 +/- 4.91 ml/kg/min, p less than 0.05). Despite the reduced exercise tolerance, the ratio of maximum tidal volume to vital capacity (VTmax/VC) was similar to that observed in healthy adults. The mean dyspnea index (VEmax/MVV) was also normal at 69.4 +/- 19.0. Hypoxic and hypercapnic ventilatory responses were within predicted normal limits at 0.67 +/- 0.37 L/min-1 fall in SaO2-1 and 1.67 +/- 0.92 L/min-1 mm Hg PCO2(-1). We conclude that the impairment of exercise performance found in adults with moderate scoliosis cannot be attributed to any important ventilatory limitation, abnormality in lung volume, or impaired chemoreceptor sensitivity. We suggest that the reduced VO2max likely arises from deconditioning and lack of regular aerobic exercise.

Adult↗
PubMed1991

Dysphagia as a manifestation of occult hypoxemia. The role of oximetry during meal times.

A 25-year-old woman with severe kyphoscoliosis reported a six-month history of increasing dysphagia to both liquids and solids. A barium swallow and esophageal motility studies showed no significant gastrointestinal abnormalities. Trials of antispasmodic agents were unsuccessful in relieving her symptoms. Pulmonary function tests showed a severe restrictive ventilatory defect (vital capacity = 0.67 L) with adequate oxygenation and alveolar ventilation as reflected by arterial blood gas testing during quiet wakefulness. However, continuous noninvasive oximetry demonstrated desaturation to 85 percent while eating. These transient episodes of desaturation were abolished by the administration of supplemental oxygen delivered by nasal prongs. Following the prescription of supplemental oxygen, dysphagia resolved immediately, with weight gain following over several weeks. We conclude that dysphagia may be a presenting feature of hypoxemia. This case report draws attention to the usefulness of continuous noninvasive monitoring of oxygenation and the clinical importance of at least some transient hypoxemic events.

Adult↗
PubMed1991

Response characteristics of a dual transcutaneous oxygen/carbon dioxide monitoring system.

We tested the response characteristics of a dual transcutaneous (tc) PO2/PCO2 monitoring system in healthy subjects who breathed various gas mixtures, and we compared steady-state tc readings to simultaneous arterial blood gas analysis in 20 stable respiratory outpatients. The electrodes were simple to apply, required very little skin preparation, and had trivial signal drift. In healthy subjects, tcPCO2 lag time during CO2 rebreathing was 16.8 seconds, with a 90 percent response time of 77.9 seconds after CO2 breathing was discontinued. The 90 percent response times of the O2 electrode when subjects breathed a hypoxic mixture was 257 seconds after a lag of 31 seconds. When inhaled gas mixtures were changed from hypoxia to room air, the lag time was shorter (12.5 seconds), but 90 percent response time exceeded 5 minutes. In stable patients with respiratory disease, tcPCO2 and tcPO2 were linearly related to PaCO2 (range, 19 to 53 mm Hg) and PaO2 (range, 45 to 99 mm Hg), respectively (tcPCO2 = 1.4 PaCO2-9.44, with r = 0.90 and SEE = 5.35 mm Hg; tcPO2 = 0.56 PaO2 + 20.4, with r = 0.53 and SEE = 11.7 mm Hg). We conclude that the response of the dual transcutaneous monitoring system is more rapid for the CO2 than the O2 electrode and may be rapid enough to be useful in some clinical settings; however, the O2 system fails to offer the response characteristics and accuracy that would allow it to be substituted for arterial gas tensions in unstable clinical situations.

Blood Gas Monitoring, Transcutaneous↗
PubMed1991

Asthma in New Zealand: implications for North America.

In the early 1980s, reports of a significant rise in asthma mortality emanated from New Zealand. Difficulties in accessing medical care, noncompliance with medication, inadequate medical management, lack of patient education, and inadequate recognition of asthma severity have been suggested as factors that may have contributed to the excess of asthma mortality. Asthma mortality has now declined significantly in New Zealand. We traveled to New Zealand to examine why the incidence of asthma deaths declined in that country at the time where it may have continued to rise in North America. We hypothesize that increased patient and physician education, targeting of high-risk socioeconomic groups, and increased public awareness have played a large role in these improved statistics. The measures taken in New Zealand which have involved a cooperative approach between lay organizations, the pharmaceutical industry, government agencies, and medical personnel may be adapted to North America with, it is hoped, similar results.

Ambulatory Care↗