Neville M. Lefcoe

A graded dose assessment of the efficacy of beclomethasone dipropionate aerosol for severe chronic asthma

In a 26-wk double-blind controlled study of 34 patients whose asthma had been poorly controlled despite oral steroids, valuable clinical and pulmonary function improvement was derived by adding beclomethasone aerosol to the prednisone regimen. The amount of improvement correlated linearly with beclomethasone dosage over the range 200 to 1,600 microng/day. These patients required relatively high dosage. Success in achieving asymptomatic status was only 26% with the conventional 400 microng/day and 60% at 1,600 microng/day. Oropharyngeal candidiasis was also dose-related but did not prohibit the use of high-dosage beclomethasone. Respiratory infections, physical signs, blood glucose, and electrolytes were unaffected by the drug. A dose-related suppression of cortisol secretion was demonstrated, but about 1/4 of the group had normal plasma cortisol even at 1,600 microng/day plus the oral prednisone. An individualized risk-benefit assessment seems a better basis for choosing an optimal beclomethasone regimen for each patient than adherence to a conventionalized fixed dosage of 400 microng/day. This requires definition of: (1) a specific goal of treatment in the individual patient and the beclomethasone dosage required to achieve it; (2) the adrenocortical functional response of that particular patient to the desired dose of beclomethasone; and (3) the presence and degree of any dose-limiting constraints such as preexisting complications of steroid use.

Bioequivalent doses of budesonide and prednisone in moderate and severe asthma

We determined the relative antiasthmatic and systemic glucocorticoid potencies of inhaled budesonide (BUD) versus morning-dose oral prednisone (PRED) in 34 adult patients with asthma over a dose range extending from conventional to high and potentially toxic levels, 3.2 mg of BUD or 40 mg of PRED per day. Changes in symptom frequency and severity, FEV1, and peak expiratory flow rate were measured during a double-blind, double-dummy controlled, crossover protocol. The drugs proved equally effective, provided a sufficient dosage was administered. The dose required to eliminate recurrently disabling asthma relapses in these patients was about 2.0 mg of BUD per day or greater than 40 mg of PRED per day. On the average, BUD doses greater than or equal to 1.84 mg/day/70 kg adult (26.3 micrograms/kg/day) exhibited systemic effects on the 8 AM serum cortisol level and blood eosinophil count equivalent to greater than or equal to 15 mg of PRED per day. The latter doses are known to be associated with steroid-induced complications, such as osteoporosis. However, the level of systemic glucocorticoid activity produced by any particular dose of BUD in these patients was consistently much lower than that produced by the dose of PRED needed to achieve an equivalent level of antiasthmatic response. Thus, the use of high-dose inhaled BUD appears clinically reasonable and ethically acceptable in patients with severe asthma in whom the alternative is their continuing dependency on PRED.

Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol steroid, budesonide

The influence of various dosing regimens on the response of asthmatic patients to aerosol steroid was investigated. Budesonide, a topically active corticosteroid like beclomethasone dipropionate, was given q.i.d. or b.i.d., in the morning or A.M./P.M., at doses of 400, 800, and 1600 micrograms/day. Each patient (n = 34) took every treatment combination for 2 wk. The antiasthmatic and systemic effects, measured by changes in peak expiratory flow rate (PEFR), blood eosinophils, and serum cortisol levels increased approximately linearly on log dose budesonide (p less than 0.0005). Systemic effects of the drug were nonsignificant at low dosage. At high dosage, morning dosing conserved hypothalamic-pituitary-adrenal function, but at the cost of a marginal reduction in efficacy (delta PEFR, p = 0.12). Having the dose frequency reduced the antiasthmatic potency of the drug, i.e., PEFR fell by an amount equivalent to approximately eightfold reduction in daily dosage (p = 0.002). This effect was not evident when asthma was in remission but became so with asthma in relapse. Overall, the q.i.d. A.M./P.M. regimen showed the best risk-benefit relationships. The data indicate (1) that reductions in dose frequency made with the hope of improving patient compliance and thus conserving the drugs long-term efficacy are likely to lead to the reverse effect, (2) that the clinician can conserve a better balance of risk vs benefit by titrating dosage in terms of puffs per dose rather than doses per day, and (3) that patients can increase the antiasthmatic efficacy of this aerosol steroid without any increase in drug costs (or apparent risk) by simply increasing dosing frequency. These therapeutic considerations probably apply to some or all of the other topically active steroids currently used to treat asthma.

The Effects of Counseling on Smoking Cessation Among Patients Hospitalized with Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial

Seventy-four cigarette-smoking patients admitted with COPD to the Chest Unit of a 600-bed teaching hospital served as subjects for a randomized trial of smoking cessation counseling. All patients were advised to quit smoking and smoking in the unit was not allowed. One-half of the patients were, in addition, provided with a self-help manual and three to eight 15- to 20-min counseling sessions on alternate days while in hospital. Self-reports of smoking status were obtained at 3 and 6 months, a sample of which were validated with serum COHb. The results were disappointing. Differences between the counseled group and the controls both in rates of cessation at 6 months (33.3% vs 21.4%) and, for patients still smoking, reductions in amount smoked would have lacked practical significance even if statistical significance had been obtained. Some alternative treatment approaches are suggested for this group of patients.

Minimum dose requirements of steroid-dependent asthmatic patients for aerosol beclomethasone and oral prednisone☆

In 34 steroid-dependent asthma patients who improved markedly during 2 mo of treatment when progressively larger doses of beclomethasone aerosol were added to their oral prednisone regimen, we subsequently reduced both steroids to ascertain the minimum dose of each needed to prevent recurrence of significant asthmatic disability. After 80 wk of follow-up, 15 patients had successfully terminated oral prednisone; 19 were better controlled with a combination of aerosol plus oral steroid than with either drug alone; all patients previously unable to convert to alternate-day prednisone did so successfully during the combined therapy. The minimum effective maintenance dosage varied greatly among these patients-the median values being 2.5 mg prednisone and 1,200 microgram beclomethasone per day. The latter ranged from 200 to 1,8000 microgram. Only 4 patients were satisfactorily controlled without prednisone on 400 microgram beclomethasone per day or less. Seven needed extra intranasal beclomethasone to help control the nasal polyps which worsened after prednisone withdrawal. Suppression of plasma cortisol levels, apparently attributable to the beclomethasone, persisted in most patients, but on the average this was no worse than before commencing this treatment and valuable clinical improvement accrued. There were no other important complications of the regimen. In most of these patients with severe chronic asthma, optimum control of the disease required combined aerosol-oral therapy and maintenance doses of beclomethasone higher than those usually recommended. In some patients, effective control of chronic asthma by beclomethasone treatment may require acceptance of some persisting suppression of adrenal function as a considered risk.

A clinical trial of combined cromolyn/beclomethasone treatment for chronic asthma.

Some patients with chronic asthma treated with beclomethasone aerosol (BA) derive significant symptom benefit, yet have persisting adrenal suppression due in part to their BA therapy. The daily dose of BA required is higher in patients with atopy. We therefore assessed the usefulness of ancillary treatment with cromolyn sodium (CS), a drug known to inhibit atopic asthma, to try to improve the balance of risk vs benefit in such patients. Thirty asthmatics, well controlled on high-dose BA (mean, 1,040 micrograms +/- 97 SE) but with morning cortisol levels averaging approximately 10 micrograms/dl, were allocated randomly to placebo or CS inhalant, used in addition to their regular BA and other asthma medications. After 4 wk, their BA dose was halved. Both groups were monitored for greater than 6 mo by daily symptom diaries and peak flows, and by spirograms and morning serum cortisol tests every 4 wk. Mean cortisol levels rose 27% after BA dose reduction (p less than 0.05) but asthma worsened. Risk-benefit assessments 20 wk after reducing the BA showed a general tendency for higher cortisol values to be coupled with worsening of the asthma symptoms and FEF25%-75%. The distributions of good, fair, and poor risk-benefit responses were the same in both CS and placebo-treated groups (p = 0.20). In other asthmatics who may have less associated bronchitis or small airways obstruction than these patients, CS might prove useful, but in these adult chronic asthmatics with this particular therapeutic problem, there was no discernible BA-sparing effect or other clinical advantage from adding CS to their established BA regimen.

Short- and long-term prediction of self-reported cigarette smoking in a cohort of late adolescents: report of an 8-year follow-up of public school students.

The purpose of this study was to assess accuracy in predicting adolescent smoking status using attitude, knowledge, behavioral, and sociodemographic variables. A cohort of 4,641 schoolchildren was tested in 1975 (grades 4-6), in 1978 (grades 6-8), and, finally, in 1983 (grades 10-12). From 1978 to 1983, eight variables were used to account for 25% of the variance in smoking status. Over the 8-year period, six variables accounted for 13% of the variance. In both models, prior experience with cigarettes, peer and parental smoking, sex, and student intention were used. Tests of the Ajzen-Fishbein model and social learning theory indicate that social factors were more important than attitudinal ones in predicting future smoking, but these relationships were relatively weak. However, for both long- and short-term prediction, previous behavior proved to be the best predictor. Implications for the design of prevention programs are discussed.

A psychological and behavioural comparison of ex-smokers and smokers☆

Abstract The purposes of this investigation were to compare ex-smokers to participants in a smoking withdrawal programme on a number of personality characteristics and to detect consistent phenomena associated with successful quitting. No statistically significant differences were found between the two groups on the personality characteristics which were measured. Successful ex-smokers usually have tried at least once and failed, quit for current health reasons, experienced cravings and discomfort, and used substitutes.

Multivariate Prediction of Cigarette Smoking among Children in Grades Six, Seven and Eight

Cigarette smoking among the young has not declined in a manner similar to that in adults and is a cause for concern. While several studies have been carried out that demonstrate short-term effects of educational programs on the prevalence of youthful cigarette smoking, no longitudinal studies have been conducted with the goal of identifying characteristics associated with high-risk for smoking. The purpose of this study was to relate variables measured in 1975 to smoking status in 1978 using multivariate statistical procedures. Sociodemographic characteristics, smoking environment, school performance, attitude toward smoking and knowledge about the effects of smoking were included. Results were available for 1,082 children who were tested in 1975 in grades four through six and again in 1978 when they were in grades six through eight. Cross-sectional analysis of variables measured in 1978 revealed that six variables accounted for 37 per cent of the variance in smoking status using a multiple regression model. Five variables that were measured in 1975 in the longitudinal analysis accounted for 32 per cent of the variance in 1978 smoking status. The utility of these results for prediction and for development of educational programs is discussed.

Cross-Sectional Analysis of Variables Related to Cigarette Smoking in Late Adolescence.

Prevalence of smoking increases with increasing age during adolescence and, even though some studies report lower levels of smoking in this age group than in the past, it remains a significant problem. The purpose of this study was to compare correlates of smoking in a cohort of 4,641 young people ages sixteen to twenty-one with correlates of smoking in the same group when they were in grades 4 to 6. Questions were included measuring sociodemographic characteristics, smoking status of parents, teachers and peers, fitness and athletic participation, attitudes and knowledge. Stepwise multivariate statistical models were developed that accounted for half of the variance in smoking status. In contrast to the earlier follow-ups, attitude toward smoking has become a more important determinant than it was before, particularly among females. This finding suggests that smoking cessation and prevention programs for this age group should more closely resemble those for adults than those effective at younger ages, where modeling and dealing with peer pressure are stressed.