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Biomedical subjects

K R Chapman

Publications and source records attributed to K R Chapman.

At least 19 recordsLinked to original sources
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

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↗
PubMed1994

Patient handling of a multidose dry powder inhalation device for albuterol.

BACKGROUND: Studies have suggested that novel inhaling devices may be misused by patients and medical personnel in the clinical setting soon after their introduction. to assess the adequacy of patient handling of a newer multidose dry powder albuterol inhaler, we conducted a comprehensive survey of use in primary and respiratory practices. METHODS: Patients 6 years of age and older and requiring inhaled beta 2-agonist for the treatment of stable obstructive airways disease were recruited from the practices of primary care and specialist physicians. After instruction from their physician or clinic staff in the use of a multidose dry powder albuterol inhalation device (Diskhaler), patients used the device in unblinded fashion for 2 weeks instead of their usual beta 2-agonist. After 2 weeks, patient use of the device was assessed at a return clinic visit. RESULTS: A total of 4,529 patients with reversible airways obstruction participated in a 2-week assessment of the device and compared it with their previous beta 2-agonist delivery system. Significantly more patients preferred the dry powder device (54 percent) over their previous device (29 percent) (p < 0.001), with 17 percent expressing no preference. After instruction, 98.5 percent of patients could demonstrate adequate use at the initial visit. Performance difficulties at the initial visit resulting in exclusion from the trial were infrequent but more common in the elderly (3 percent vs 0.2 percent for all other age groups combined, p < 0.001). Despite adequate use at the initial visit, at the conclusion of the trial, incorrect use of the device was noted in 10.2 percent of the elderly vs 3.2 percent of all other age groups combined (p < 0.001). Albuterol delivered by Diskhaler was well tolerated in all patient groups. CONCLUSIONS: A majority of patients are able to use a multidose dry powder albuterol inhaler device in the clinical setting, and prefer the device to previously used beta 2-agonist inhalation devices. However, follow-up shows that problems with device handling may become apparent in as little as 2 weeks after initial instruction, thereby mandating the need for periodic follow-up and reinstruction.

Administration, Inhalation↗
PubMed1994

Long-term xanthine therapy of asthma. Enprofylline and theophylline compared. International Enprofylline Study Group.

BACKGROUND: Enprofylline is a new xanthine derivative that shares theophylline's bronchodilator properties but is free of theophylline's adenosine receptor antagonist activity. We compared the long-term efficacy and tolerability of enprofylline and theophylline given over a 1-year period to adults with asthma. METHODS: Patients were recruited from 18 centers and 4 countries to participate in a 1-month double-blind comparison of enprofylline or theophylline in the treatment of asthma and were subsequently maintained on a regimen with the assigned medication for a further 11 months. The dosage of each xanthine was incremented from 150 mg twice daily at initiation to 300 and later 450 mg twice daily depending on the patient's tolerance and, in the case of theophylline, the rapidly assayed serum theophylline level. Patients kept a diary in which they recorded peak expiratory flow rate (PEFR) measured morning and evening, asthma symptom score, and the number of beta 2-agonists taken. Spirometry was checked at clinic visits at 3, 6, 9, and 12 months following randomization. RESULTS: Three-hundred forty-eight patients (174 enprofylline, 174 theophylline) participated in the trial. For both drugs there were significant improvements in PEFR and FEV1 during the first month of treatment with no significant difference between drugs (0.25 L for enprofylline vs 0.30 L for theophylline). Similarly, there were no differences in clinical outcome such as asthma exacerbations or beta 2-agonist usage between the two groups over follow-up. However, inhaled steroid dosage was more likely to have been incremented in theophylline-treated than enprofylline-treated patients (18% vs 8%, p = 0.025). Both drugs produced a modest increase in heart rate throughout the trial (approximately 5 beats/min). In 31 patients (26 enprofylline, 5 theophylline), asymptomatic elevations in aspartate aminotransferase and/or alanine aminotransferase occurred at least once during the study. In five patients (four enprofylline, one theophylline), the increase exceeded three times the upper limit of the normal range. In some subjects receiving enprofylline, serum enprofylline levels rose progressively despite constant oral dosage of the drug. CONCLUSIONS: Long-term xanthine therapy is well-tolerated by most adult asthmatics. However, long-term enprofylline administration may be associated with elevation in liver enzyme levels and unpredictable blood levels, thereby limiting its clinical usefulness.

Adolescent↗
PubMed1994

Assessment of an ambulatory care asthma program.

In response to rising asthma morbidity and mortality, numerous comprehensive asthma programs have been developed. However, few studies have examined critically the effectiveness of such programs or the means by which treatment or outcome is altered. To assess the role of a specialized ambulatory asthma care program, we reviewed the interventions recommended to 344 patients referred for the assessment of asthma. A subset of 127 made return visits 6-12 months following their initial assessment, thereby allowing assessment of behavioral and physiological outcomes. At the initial consultation, the recommended medication changes were: inhaled beta-agonists +6% (p < 0.01), inhaled steroids +58% (p < 0.001), intranasal steroids +8% (p < 0.001), dry powdered formulations +13% (p < 0.01), theophylline -7% (p < 0.001). The percentage of patients using spacer devices increased 8% (p < 0.001). Comparing preassessment values to those at a visit at 6-12 months following assessment, a further 25% of patients taking inhaled steroids at the initial assessment had a change to either the dose, device, or frequency of administration. Mean FEV1 improved from 2.41 +/- 0.08 liters at the initial assessment to 2.64 +/- 0.09 liters at the 6-12-month visit (p < 0.001). There was an increase in the number of patients considered mild and not obstructed, with a corresponding decrease in the number considered moderately and severely obstructed (p < 0.05). The number of emergency room visits was reduced by more than 60% (p < 0.001) in patients followed for at least 6 months. We conclude that an ambulatory asthma program marked by increased use of inhaled anti-inflammatory medications and decreased use of theophylline can produce significant decreases in asthma exacerbations requiring hospital care, emergency room care, or systemic steroids while reducing the prevalence and severity of airflow limitation.

Administration, Inhalation↗
PubMed1994

Trends in pharmacotherapy for chronic airflow limitation in Argentina: 1983-1990.

Reported increases in worldwide asthma mortality have prompted the publications of guidelines and consensus statements on the management of airway disease. Overreliance in bronchodilator therapy and lack of anti-inflammatory treatment have been the major findings and the guidelines are aimed at correcting these problems. The Argentinean population appears to have increased prevalence and severity of conditions characterized by chronic airflow limitation and there is no data, to our knowledge, that has analyzed how the treatment of such conditions has been conducted in the past years. Drug sales data in Argentina were surveyed retrospectively to estimate prescriptions dispensed for the treatment of airway disease for the years 1983 to 1990 inclusive. The number of prescriptions of all airway drugs increased significantly (p < 0.01) in the 8-year period except for oral beta 2-agonists and disodium cromoglycate (DSCG). Prescriptions for these agents were 42.7% and 69% less frequent respectively. Thus, oral beta 2-agonists declined from being the single most frequently prescribed class of drugs (40% of prescriptions) in 1983 to the third most frequently prescribed (22%) in 1990. Concurrently, prescriptions of inhaled beta 2-agonists in all forms rose significantly comprising 27% in 1983 and 46% in 1990 becoming the most commonly prescribed airway therapy. Despite this apparent trend away from oral bronchodilator therapy, theophylline prescriptions comprised a significantly higher percentage of prescriptions in 1990 as compared to 1983 (30% vs 20%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗