Biomedical subjects

K R Chapman

Publications and source records attributed to K R Chapman.

At least 55 records · Page 3Linked to original sources

PubMed1997

Defining the asthma phenotype for the purpose of genetic analysis.

In 1991, we began a project to search for the genetic basis of asthma using linkage analysis. We encountered discord between a history of asthma and physiological measures of variable airflow obstruction and sought to examine the frequency of such occurrences and the issues surrounding phenotyping of patients with asthma. We reviewed our experience in ascertaining the asthma phenotype in 50 nuclear families comprised of 219 subjects (110 male, 109 female). Three respiratory physicians reviewed data including a questionnaire, skin testing, objective measures of variable airflow obstruction [increase in FEV1 > or = 15% following salbutamol 400 micrograms of PC20 (methacholine) < or = 4 mg/ml], and serum for IgE. Thirty-eight percent of subjects had both objective and questionnaire data consistent with asthma (++) whereas 39% had negative objective and negative questionnaire findings (--) (i.e., no asthma). A positive history but negative objective findings occurred in 7% of subjects, 2% had a negative history and positive objective findings. Retesting was requested in 13% of subjects; review of historical data was requested in 1% (i.e., childhood asthma but no present asthma). Retesting was requested for either (a) positive history, negative objective if symptoms were seasonal or the subject was using medications known to affect the challenge study, (b) viral infection within 6 weeks of a positive methacholine study, or (c) technically inadequate study. Overall, after the initial assessment, all members of only 22 families could be catagorized as either ++ or --. The diagnostic group requested at least 1 retest in 19 families and a review of historical records in 2 families. We conclude that discordance between self-reported questionnaire data and laboratory measures of variable airflow limitation is common and will increase the numbers of asthmatic subjects in studies that seek to determine the genetic basis of asthma.

Adolescent↗

PubMed1996

An international perspective on anticholinergic therapy.

Since the introduction of inhaled quaternary anticholinergic bronchodilators, their clinical usefulness has been explored in a variety of settings. They have emerged as the inhaled bronchodilators of first choice in the management of chronic obstructive pulmonary disease (COPD). In other countries, they have also found an adjunctive role in the management of asthma. This may be best seen in the treatment of acute asthma where the combination of anticholinergic and adrenergic bronchodilators appear more effective than single-agent inhalation therapy. This finding appears consistently in large studies, whether in adult or pediatric populations. Such combination nebulizer therapy would appear to be cost effective, but further study is required.

Bronchodilator Agents↗

PubMed1996

Therapeutic approaches to chronic obstructive pulmonary disease: an emerging consensus.

In response to reports of rising asthma morbidity and mortality, several consensus statements have been drafted to guide the treatment of asthma. More recently, attempts have been made to develop similar guidelines for the management of chronic obstructive pulmonary disease (COPD). Just as the two diseases differ in their pathophysiology, their treatment algorithms have differed. For both disease groups, avoidance of further airway injury is the initial step in treatment. For asthmatics, this is often allergen avoidance, but for patients with COPD the usual inciting factor is cigarette smoking, thereby making smoking cessation the necessary first step. Whereas beta 2-agonist bronchodilators are used as needed in asthma management, regular bronchodilator therapy with anticholinergic drugs is the first-line approach in COPD. The role of anti-inflammatory drugs differs markedly between the two disease groups. Asthmatic patients benefit dramatically from inhaled anti-inflammatory drugs; little or no benefit can be demonstrated for the majority of patients with COPD. In COPD, the role of exercise rehabilitation programs can improve exercise tolerance. For selected patients with COPD with persistent hypoxemia, the use of supplemental oxygen can reduce mortality. For both patient groups, educational interventions can play a valuable role in making patients patients effective partners in their own care.

Adrenal Cortex Hormones↗

PubMed1996

Analysis of the T cell receptor Vgamma region gene repertoire in bronchoalveolar lavage (BAL) and peripheral blood of atopic asthmatics and healthy subjects.

We analyzed the T cell receptor (TCR) Vgamma repertoire in BAL and peripheral blood (PBL) of three mild stable atopic asthmatics and two non-asthmatic controls. We used the polymerase chain reaction (PCR) to establish the expression of the four Vgamma families, and to detect oligo or monoclonal expansion of gammadelta+ T cells, we resolved the PCR projects on denaturing and non-denaturing gels to find the extent of junctional diversity arising from differences in the lengths of the V(D)J junctions. We also subcloned and sequenced the PCR products to characterize fully the sequence diversity. BAL T lymphocytes from two asthmatic patients (treated with inhaled steroids) expressed only VgammaII and, in one of them, VgammaIIJgamma usage was restricted to JgammaP and JgammaP1 gene segments, contrasting with the VgammaJgamma repertoire found in his respective PBL. Analyses in denaturing and non-denaturing gels showed that the BAL VgammaIIJgammaP and VgammaIIJgammaP1 PCR products resolved into few bands, suggesting deletions at the juctions due to oligoclonal expansion. BAL T lymphocytes from the third asthmatic (not receiving inhaled steroids) expressed VgammaI, II and III, and the sequences of the in-frame TCR transcripts from this asthmatic and one healthy volunteer who expressed a similar BAL VgammaTCR repertoire showed clonal expansion of T cells expressing all three Vgamma families. Our analyses showed that much of the GammaDeltaT cell population found in BAL fluid of humans derives from clonally expanded T cells.

Adult↗

PubMed1996

Diagnosis of chronic obstructive pulmonary disease and differentiation from asthma.

In the primary care setting, asthma and chronic obstructive pulmonary disease are common clinical challenges, which together affect approximately 25,000,000 Americans. As our therapeutic strategies for these two diseases diverge, it becomes important to distinguish between them. Although this may be relatively easy at the extremes of age using a combination of history and physical examination, this review focuses on additional information that may allow diagnostic distinctions to be made in the troublesome middle ground.

Adult↗

PubMed1996

The accuracy of a handheld portable spirometer.

BACKGROUND: Objective measurement of lung function is considered essential in the management of patients with asthma and COPD. Many primary care practitioners lack the means necessary to obtain these measurements conveniently. To meet this need, electronic spirometers, offering portability, ease of operation, and timesaving readout options have been introduced. We compared the accuracy of a typical pneumotachograph-based device with a conventional volume displacement spirometer. METHODS: We compared indexes of pulmonary function (FVC, FEV1, mean forced expiratory flow during the middle half of FVC, [FEF25-75%], and peak expiratory flow rate [PEFR]) measured by the handheld device with those measured by a conventional spirometer in 75 white subjects (33 men, 42 women) with a median age of 43 years (22 to 77 years) who were either healthy or were referred to the pulmonary function laboratory of a large tertiary care teaching hospital. The order of the instrument tested first was randomized and the patients were blinded to which instrument was being studied. RESULTS: There was a linear relationship between instruments for all indexes measured (r = 0.97, 0.98, 0.94, 0.94 for FVC, FEV1, FEF25-75%, and PEFR, respectively, for all p < 0.001). The random error (precision) was within 5% only for FEV1. The mean of the differences between the values obtained using both instruments (the bias) +/- limits of agreement (+/- 2 SD) were 0.06 +/- 0.56 L for FVC (p = NS), 0.2 +/- 0.44 L for FEV1 (p < 0.05), 0.61 +/- 1.26 L/s for FEF25-75% (p < 0.05), and 0.44 +/- 1.9 L/s for PEFR (p < 0.05). CONCLUSION: Our data suggest that measurements obtained using the pneumotachograph device are closely related to those obtained by volume displacement spirometry and that the handheld device may be useful in clinical practice. However, because the limits of agreement are wide and the difference between the two instrument measurements are significant for FEV1, FEF25-75%, and PEFR, the bias between them is not consistent nor is it insignificant. Therefore, the measurements made with the two types of machine cannot be used interchangeably.

Adult↗

PubMed1996

Prior diagnosis and treatment of patients with normal results of methacholine challenge and unexplained respiratory symptoms.

OBJECTIVE: Previous research indicates that asthma has been underdiagnosed. However, we suspect that recent widespread attention to the underdiagnosis of asthma has led to an overdiagnosis of asthma in some settings. We therefore sought to examine prior diagnosis and treatment of patients referred to our facility and subsequently found to have no objective evidence of variable airflow limitation. DESIGN: Retrospective chart review. SETTING: Hospital-based asthma center. PATIENTS: A referred sample of 263 patients in whom a methacholine challenge (MCC) was conducted after evaluation by our pulmonologists; complete medical histories were available. MAIN OUTCOME MEASURES: Prior respiratory diagnoses, duration of treatment with asthma medications, and diagnosis following assessment by our pulmonologists in 175 patients with a provocative concentration of the substance causing a 20% fall in FEV1 (PC20) greater than 8.0 mg/mL and 88 with a PC20 of 8.0 mg/mL or less. RESULTS: Of those with a PC20 greater than 8 mg/mL, a diagnosis of asthma or possible asthma prior to the challenge study was recorded by their primary care physician in 129 patients (74%). One hundred sixty of 172 patients (88%) with a PC20 greater than 8 mg/mL were diagnosed as not having asthma by our pulmonologists; 109 of 172 patients (62%) had been previously treated with asthma medication(s). The mean duration of asthma treatment was 25.9+/- 56.3 months, and there was no significant difference in the duration of treatment between this group and those who had a PC20 of 8 mg/mL or less. Most of those treated received inhaled beta2-agonists and inhaled corticosteroids. Approximately 61% received two or more classes of medications. CONCLUSIONS: The misdiagnosis of asthma occurs commonly in the referral practice of a tertiary care asthma center. The more frequent use of objective pulmonary function testing in primary practice might reduce the problem of delayed diagnosis and inappropriate therapy for respiratory symptoms.

Asthma↗

PubMed1996

Cardiovascular safety of high doses of inhaled fenoterol and albuterol in acute severe asthma.

BACKGROUND: It has been suggested that overuse of fenoterol metered-dose inhalers (MDIs) may increase the risk of death from asthma due to cardiac arrhythmias. Our primary objective was to compare the cardiovascular safety of fenoterol and albuterol MDIs when administered in maximal bronchodilating or maximal tolerated doses to an absolute maximum of 16 puffs, for the emergency department (ED) treatment of acute severe asthma. METHODS: Asthmatic patients presenting to the ED with acute severe asthma (FEV1 less than 50% of predicted) were enrolled in a multicenter, randomized, double-blind, parallel-group study. Following baseline measurements, (medical history, physical examination, determination of serum potassium and serum theophylline levels, oximetry, 12-lead ECG, and spirometry), each patient received 4 puffs of either fenoterol, 200 micrograms per puff, or albuterol, 100 micrograms per puff, 1 puff every 30 s via an MDI attached to a holding chamber. Additional doses of inhaled beta 2-agonist were administered by dose titration, 2 puffs every 10 min to a maximal cumulative dose of 16 puffs of albuterol or fenoterol, side effects were intolerable to the patient, or an FEV1 plateau (i.e., < 10% improvement for 2 consecutive doses) occurred. ECG was recorded continuously via Holter monitor, and respiratory rate, BP, dyspnea (Borg scale), and FEV1 were assessed after each dose. RESULTS: 128 patients were randomized to receive fenoterol and 129 to receive albuterol. Overall, fenoterol increased FEV1 160 mL more than albuterol. The mean (SEM) FEV1 increase from baseline was 0.75 +/- 0.06 L in the fenoterol group and 0.59 +/- 0.06 L in the albuterol group (p < 0.03). Both beta 2-agonists caused a decrease in serum potassium level that was significantly greater in the fenoterol (0.23 +/- 0.04 mmol/L) than in the salbutamol (0.06 +/- 0.03 mmol/L) group (p = 0.0002). There was also a greater increase in the Q-Tc interval in the fenoterol group, 0.011 +/- 0.003 s compared with 0.003 +/- 0.003 s in the albuterol group (p < 0.05). Differences in hypokalemia and Q-Tc prolongation associated with fenoterol and albuterol were significantly different only after 8 puffs of fenoterol had been given. 32 patients exhibited ventricular premature beats, 14 in the fenoterol group and 18 in the albuterol group. There were 34 patients with episodes of supraventricular premature beats, 17 in each group. No episodes of sustained ventricular tachycardia were detected in either group. CONCLUSIONS: In adequately oxygenated patients, using dose titration of fenoterol, in a formulation of 200 micrograms per puff by MDI valved holding chamber and mask, to a total dose of 3,200 micrograms and salbutamol (100 micrograms per puff) to a total dose of 1,600 micrograms over 90 min, showed cardiovascular safety in acute severe asthma. This was evidenced by absence of cardiovascular mortality or clinically significant arrhythmias in either group. The 100% greater dose of fenoterol improved FEV1 significantly more than salbutamol and was associated with a relatively small but significantly greater prolongation of the Q-Tc interval and decrease in serum potassium level. This study does not exclude the possibility that adverse cardiac events could occur with severe hypoxemia.

Acute Disease↗

PubMed1996

The effect of structured versus conventional inhaler education in medical housestaff.

Despite the importance of adequate inhaler technique in the care of asthma and chronic obstructive pulmonary disease, physicians have often been shown to have poor knowledge of correct inhaler use. At present, postgraduate teaching programs appear to leave physicians to acquire inhaler handling skills informally in the context of day-to-day patient care. We undertook the present study to determine if one brief structured educational intervention would be adequate to teach postgraduate physicians inhaler skills that would be retained over long periods of time. We also compared the efficacy of this intervention to traditional education methods. We recruited 52 postgraduate trainees in internal medicine at a large university hospital; 26 were in the educational intervention group and 26 were in the control group. Physicians in the intervention group were asked to respond to a questionnaire on inhaler use and to demonstrate the correct use of a metered-dose inhaler (MDI), an MDI with a pacing chamber and a multidose dry-powder inhaler. These intervention subjects were then instructed on proper inhaler usage by a qualified nurse educator. Eight months later, testing was repeated in the intervention group and was undertaken in the control group. Questionnaire scores were significantly higher in the intervention group at the 8-month follow-up than at baseline (59% vs. 42%; p < 0.05). Similarly, the scores of the intervention group at follow-up were significantly higher than those of the control group (59% vs. 39%; p < 0.05). There was no significant difference between the baseline scores of the intervention group and those of the control group. The mean demonstration score was significantly higher in the intervention group at follow-up than at baseline (68% vs. 39%; p < 0.001) and was also higher than that of the control group (68% vs. 44%; p < 0.001). There was no significant difference between the scores for all devices between the intervention group before education and the control group. Our data show that one brief teaching session is sufficient to produce a sustained improvement in knowledge and handling of inhalers by postgraduate physicians. The knowledge and skills of the physicians educated in our study were not only better than before they had received instruction, but were better than the knowledge and skills of postgraduate trainees from the same institution who had received no formal training. This latter observation suggests a failure of traditional unstructured postgraduate training programs to teach this practical patient care skill.

Asthma↗

PubMed1995

Adverse effects of inhaled corticosteroids.

Inhaled corticosteroids are considered by many to be the anti-inflammatory therapy of choice in adult asthma, given their remarkable efficacy and apparent safety. They are presently being prescribed to more patients, at larger doses, and for longer periods of time than ever before. Oropharyngeal candidiasis and dysphonia are the most commonly recognized adverse effects of therapy, but these topical phenomena cause no significant morbidity and are easily managed. By contrast, there is now increasing concern about the potential systemic effects of inhaled corticosteroids. These putative effects may include adrenal suppression, bone loss, skin thinning, increased cataract formation, decreased linear growth in children, metabolic changes, and behavioral abnormalities. Changes in adrenal function have been noted in patients using medications such as beclomethasone dipropionate and budesonide in doses exceeding 1,500 micrograms/day. The clinical relevance of these changes has yet to be clarified. Several short-term and cross-sectional studies have also revealed changes in biochemical markers of bone turnover and retrospective studies have found reduced bone density in asthmatics treated regularly with inhaled steroids. Long-term prospective studies assessing bone density changes remain to be done. Although much controversy exists, there is no unequivocal evidence that conventional doses of inhaled steroids significantly retard bone growth in children. Reports on skin changes, increased cataract formation, and behavioral changes are difficult to interpret because of several confounding factors. Although inhaled steroids should, at the present time, continue to be a recommended therapeutic option to all patients with symptomatic asthma, they should always be used in the lowest dosage compatible with disease control.

Administration, Inhalation↗

PubMed1995

Dose-related decrease in bone density among asthmatic patients treated with inhaled corticosteroids.

BACKGROUND: Inhaled corticosteroids are being prescribed more commonly and in higher doses than previously in the management of asthma. Although these topically active compounds have less potential for systemic impact than oral steroids, biochemical markers suggest that they are not devoid of systemic side effects. We conducted this study to investigate the effect of commonly prescribed doses of inhaled steroids on bone density. METHODS: We studied 36 patients with asthma. Those in group A (n = 18) had been taking inhaled beclomethasone dipropionate or budesonide in a dosage of 800 micrograms or more per day for at least 1 year. Those in group B (n = 18) had used only bronchodilator therapy. Adrenal function was assessed by morning serum cortisol level and by short adrenocorticotropic hormone stimulation test. Bone turnover was assessed by measurement of serum osteocalcin, alkaline phosphatase, and urinary pyridinium cross-links. Bone mineral density was measured by dual-energy x-ray absorptiometry with a Hologic QDR-1000 densitometer (Hologic Inc., Waltham, Mass.). RESULTS: Group A, mean age (SD) = 36.6 (8.4) years, had used inhaled corticosteroids at a mean dose of 1323 micrograms/day (range, 800 to 2000 micrograms/day) for a median duration of 24 months. Group B, mean age (SD) = 33.4 (8.1) years, had not been taking any form of steroid. Four patients from group A had suppressed morning serum cortisol; three of these had abnormal adrenocorticotropic hormone stimulation test results. All patients in group B had normal baseline adrenal function and an appropriate response to adrenocorticotropic hormone. Mean serum osteocalcin level in group A was significantly lower than that in group B (8.8 vs 14.2 ng/ml, p = 0.0003). Bone density measurements showed parallel changes: in group A the mean Z score (SD) of the femoral neck was -0.78 (1.02), significantly below predicted normal values (p = 0.0025). Mean Z scores of the lumbar spine and of femoral Ward's triangle were not significantly reduced. In group B the mean Z scores of the lumbar spine, femoral neck, and femoral Ward's triangle were all within normal limits. In group A the dose duration of inhaled corticosteroid therapy corrected for body mass index correlated negatively with bone density and adrenal function measurements. CONCLUSION: We conclude that the regular use of conventional doses of inhaled corticosteroids by patients with asthma can suppress adrenal function and decrease bone density in a dose-related fashion.

Administration, Inhalation↗

PubMed1995

The choice of inhalers in adults and children over six.

Available delivery systems for ambulatory use include the conventional suspension pressurized metered dose inhaler (MDI), the conventional MDI with add-on devices such as spacing chambers and several powder delivery systems. Gas-driven or ultrasonic nebulizers are also available but are generally reserved for in-hospital use or for the treatment of the most severely obstructed patients. It is difficult to select one best system for use in older children, adolescents and adults; all available systems have their deficiencies and these are outlined here. The most widely prescribed device, the MDI, is misused by some patients with claims of up to one-third of clinic patients showing inadequate inhaler technique. In the 1990s, the MDI has also been criticized for liberating chlorofluorocarbons (CFCs). On occasion, the adjuvants are said to precipitate cough. In some countries, the production of generic or second entry inhalers has been accompanied by vexing concerns over the bioequivalence of therapeutic aerosols. The problem of patient coordination with the inhaler is meant to be dealt with by a variety of add-on devices. Spacing chambers and reservoir systems improve drug delivery and treatment efficacy for some patients. Unfortunately, there are relatively few data on patient spacer technique or optimal teaching methods. There is considerable potential for patient misuse of these superficially simple devices. One common problem is that the devices become dirty and worn but are seldom replaced by patients. A more subtle problem is electrostatic drug adherence to the spacing chamber thereby reducing drug delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1995

Gas trapping as a predictor of positive methacholine challenge in patients with normal spirometry results.

Methacholine challenge studies are often conducted to diagnose asthma in patients with mild or intermittent respiratory symptoms when screening spirometry results are normal. We hypothesized that in patients with increased nonspecific bronchial hyperreactivity (NSB-HR), gas trapping might be present and that this information could be a factor in clinical decision making. To assess the relationship between gas trapping and NSBHR, we conducted a retrospective chart review of 500 patients who had undergone pulmonary function testing, including lung volume measurement and methacholine challenge. Measurements of airflow, lung volumes, and methacholine PC20 values were compiled and analyzed. FRC was determined by body plethysmography (FRCB) and by helium dilution (FRC-He). FRCB-FRC-He, RV (percent of predicted) RV/TLC, and RV/TLC (percent of predicted) were used as measures of gas trapping. RV% and RV/TLC% were the best predictors of a PC20 < or = 8 mg/mL. In the subset of 169 patients who had FEV1/FVC > or = 90% of pred, an RV/TLC% value of 125% of predicted or greater had a positive predictive value of 62.5% and a negative predictive value of 62.0%. RV/TLC% was the only measure of gas trapping that was associated with a PC20 < or = 8 mg/mL (p < 0.05). Linear regression revealed no correlation between any measure of gas trapping and quantified PC20 value (< or = 16 mg/mL). These results suggest that patients with a normal FEV1/FVC who show gas trapping have an increased likelihood of a positive methacholine challenge study. Furthermore, in these patients, RV/TLC (percent of predicted) is the best predictor of a positive methacholine challenge and this parameter may be useful in raising the clinical suspicion of asthma in the large population of patients presenting with respiratory symptoms and normal flow rates.

Adolescent↗

PubMed1994

Regular vs as-needed inhaled salbutamol in asthma control.

Recent studies have suggested that regular use of inhaled beta 2 agonists cause loss of asthma control as measured by worsening peak-flow rates, increased asthma symptoms, and more frequent need for supplementary bronchodilators. However, the magnitude of this effect and the reliability of investigator-originated definitions of control is unknown. We studied 341 people with asthma in a four-week, randomised, crossover trial of regular salbutamol (2 puffs--200 micrograms--four times daily) for two weeks and as needed for two weeks. There were no significant differences in morning and evening peak-flow rates between treatments but asthma symptoms and supplementary bronchodilator use were significantly less frequent when salbutamol was given regularly. Asthma episodes occurred 1.39 (1.52) times per day during regular treatment and 2.44 (1.75) times per day during as-needed treatment (p < 0.0001) and 0.50 (0.56) vs 0.65 (0.66) times per night (p < 0.0001). Daytime use of supplementary salbutamol was 1.14 (1.40) vs 2.35 (1.71) puffs per day, (p < 0.0001); night-time use was 0.45 (0.55) vs 0.64 (0.66) puffs per night (p < 0.0001). When control endpoints were compared between treatment periods for each individual by two blinded investigators and control judged by six different sets of criteria, in 70 asthmatics there was no difference in symptom control between periods but in the remainder, control was achieved more often by regular than by as-needed salbutamol (166 vs 69, p < 0.0001). In asthma of moderate severity, regularly administered salbutamol does not produce lower peak flow rates than as-needed salbutamol and is associated with less frequent asthma symptoms.

Administration, Inhalation↗

PubMed1994

A rapid monoclonal antibody blood theophylline assay; lack of cross-reactivity with enprofylline.

We evaluated a rapid monoclonal antibody theophylline assay for two reasons: (a) to determine its specificity with respect to the possible confounding influence of a structurally related xanthine, enprofylline, and (b) to assess its accuracy relative to high-performance liquid chromatography (HPLC). Blood samples were taken from 233 patients who had been randomized in double-blind fashion to receive either oral theophylline (n = 117) or enprofylline (n = 116) for the treatment of chronic reversible obstructive airways disease. Monoclonal antibody assays (MAAs) were performed in 10 clinical sites by 10 trained paramedical technicians. Three patients, who actually received enprofylline but not theophylline, had MAA theophylline values of > or = 3.2 micrograms/ml, giving a specificity of 97%. HPLC determination of simultaneous blood samples confirmed that theophylline levels were in fact < 3.2 micrograms/ml and that theophylline was not being taken surreptitiously. Good correlation was observed between MAA and HPLC in patients taking theophylline (y = 1.07 x + 0.36; r = 0.93; standard error of the estimate (SEE) = 1.93). However, there was wide variability from technician to technician such that r values for individual sites ranged from 0.67 to 0.99. Based on the overall correlation, the prediction of an individual HPLC value from an individual MAA value had broad 95% confidence limits: when the MAA value was 10 micrograms/ml, the predicted HPLC value was 9.19 +/- 3.32; when MAA = 15 micrograms/ml; HPLC = 13.19 +/- 3.33; and when MAA = 20 micrograms/ml; HPLC = 17.19 +/- 3.36.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Excitability of human motor cortex during hyperventilation and hypercapnia.

We tested the hypothesis that the excitability of corticospinal neurons was altered by changes in PCO2. Magnetic stimulation was used to excite the neurons in the human motor cortex that give rise to the fast-conducting corticospinal pathway. The characteristics of the composite excitatory postsynaptic potentials (EPSPs) produced in individual spinal motoneurons by cortical stimulation were derived from changes in the firing probability of voluntarily activated motor units. The amplitudes of these composite EPSPs in response to a constant cortical stimulus were assumed to reflect the excitability of cortical neurons. In 10 healthy subjects, we found no statistically significant changes in the excitability of the cortical neurons during normocapnic conditions (mean end-tidal PCO2 5.1 kPa), during hyperventilation-induced hypocapnia (mean end-tidal PCO2 2.9 kPa), and during hyperoxic hypercapnia induced by a rebreathing technique (mean end-tidal PCO2 6.9 kPa). We conclude that the excitability of corticospinal neurons activated by magnetic stimulation is not significantly affected by changes in PCO2.

Adult↗

PubMed1994

Changes in pulmonary function and cross-sectional area of trachea and bronchi in asthmatics following inhalation of procaterol hydrochloride and ipratropium bromide.

To determine the sites of action of inhaled adrenergic and anticholinergic bronchodilators, we used the acoustic reflection technique to measure airway area before and after administration of beta 2-selective adrenoreceptor agonist (procaterol hydrochloride) and quaternary anticholinergic agent (ipratropium bromide). Eight stable individuals with asthma (five men and three women; mean age, 34 +/- 12.7 yr) were studied on 2 days in single-blind randomized crossover fashion when they self-administered (using metered-dose inhaler) two puffs of either procaterol hydrochloride hemihydrate (10 micrograms/puff) or ipratropium bromide (20 micrograms/puff). Maximal expiratory flow-volume curve, specific airway resistance, and cross-sectional areas of three airway segments (extrathoracic tracheal, intrathoracic tracheal, and bronchial) were recorded at baseline and 15, 30, 60, and 120 min after drug administration. Both agents produced significant improvements in FEV1, FVC and forced expiratory flow at 50% of vital capacity (V50), and specific airway resistance (SRaw) as early as 15 min after drug administration. These effects were sustained for the 120 min monitoring period. However, all improvements were significantly greater for procaterol than for ipratropium. By contrast, there was no significant difference between drugs in the increased production in the cross-sectional areas of the three airway segments although there was a nonsignificant trend toward greater increases in tracheal area produced by the anticholinergic agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustics↗

PubMed1994

Medical personnel's knowledge of and ability to use inhaling devices. Metered-dose inhalers, spacing chambers, and breath-actuated dry powder inhalers.

BACKGROUND: Current treatment strategies for asthma and chronic obstructive pulmonary disease (COPD) emphasize the inhalation route, yet patients often misuse metered-dose inhalers (MDI). To address this problem, patient education by medical personnel has been recommended and a variety of alternate inhaler devices have been developed. METHODS: We surveyed medical personnel to assess their knowledge of and ability to use three widely used inhaler devices; MDI, MDI with a spacing chamber (Aerochamber, Trudell Medical, Canada), and a breath-actuated multidose dry powder inhaler (Turbuhaler, Astra Pharmacy, Inc., Conada). Thirty respiratory therapists (RT), 30 registered nurses (RN), and 30 medical house staff physicians (MD) were asked to demonstrate the use of each device using placebo inhalers and to answer 11 clinically relevant questions related to the use and maintenance of the tested devices. RESULTS: The RT's percent mean knowledge score (67 +/- 5 percent) was significantly higher than those achieved by either the RNs (39 +/- 7 percent) or the MDs (48 +/- 7 percent) (for all p < 0.0001). Similarly, percent mean demonstration scores for each device were significantly higher for RTs than either RN or MD groups; for MDI, 97 +/- 3 percent versus 82 +/- 13 percent and 69 +/- 24 percent, respectively (p < 0.0001); for the Aerochamber, 98 +/- 2 percent versus 78 +/- 20 percent and 57 +/- 31 percent (p < 0.0001); and for the Turbuhaler, 60 +/- 30 percent versus 12 +/- 23 percent and 21 +/- 30 percent (p < 0.0001). Knowledge of and practical skills with the devices were roughly proportional to the length of time the device had been in clinical use, Turbuhaler demonstration scores being lower than either MDI or Aerochamber scores (p = 0.05 and p = 0.09, respectively). More RTs (77 percent) had received formal instruction on the use of devices at school than either RNs (30 percent) or MDS (43 percent) (p < 0.05). CONCLUSION: We conclude that (1) many medical personnel responsible for monitoring and instructing patients in optimal inhaler use lack rudimentary skills with these devices, (2) nurses and physicians seldom receive formal training in the use of inhaling devices, and (3) newer inhaling devices designed to obviate problems of technique are at present less likely to be used well by medical personnel soon after their introduction.

Clinical Competence↗