Flexible work schedules, older workers, and retirement.

Older workers in the United States indicate that they would prefer flexible work arrangements rather than abrupt retirement, yet management has done very little to make this possible. A review of two bodies of literature from the late 1980s is presented: social science writings including sociological, gerontological, and economic literature, and business and management literature. There is a clash between the way jobs are traditionally scheduled and the needs of growing numbers of older workers. Workers continue to be subject to obstacles to phased retirement due to the structuring of health care and pension benefits, downsizing, organizational inflexibility, and "corporate culture." Thus, general views among social scientists regarding the desirability of flexible schedules toward retirement will not produce real changes unless management becomes committed to such changes and they are securely embedded in company policies.

Osteoporosis in the corticosteroid-treated patient with asthma.

Osteoporosis affects 40% of white women older than 45 years of age and 15% of white men older than 50 years of age, resulting in approximately 1.5 million annual fractures in the United States. Systemic corticosteroid therapy increases the probability of osteoporosis, even with alternate-day dosing and with dosages sufficiently low so as not to affect the hypothalamic-pituitary-adrenal axis. Inhaled corticosteroid therapy may affect bone density if high-dose therapy is given to select individuals. The potential of increasing osteoporosis with inhaled corticosteroid asthma therapy is a concern because of the availability of more potent inhaled corticosteroid agents and recommendations that inhaled corticosteroid therapy be initiated earlier in the course of asthma. This article provides suggestions, on the basis of the medical literature and consensus of the authors when specific information was not available, for assessing and treating osteoporosis in subjects with asthma. Suggested risk categories are "low risk" (inhaled corticosteroid dosage of < or =800 microg of heclomethasone dipropionate [BDP]/day in adults or < or =400 microg BDP or equivalent in children), "moderate risk" (inhaled BDP >800 microg/day in adults or >400 microg/day in children), and "high risk" (systemic corticosteroid therapy 4 times a year or daily or alternate-day systemic corticosteroid therapy). Dosage of nasal corticosteroid probably should be added to the orally inhaled corticosteroid for total burden of inhaled corticosteroid. Potential treatment strategies based on risk factors and bone density if indicated are offered to assist physicians treating patients with asthma.

Efficacy and safety of low-dose troleandomycin therapy in children with severe, steroid-requiring asthma.

BACKGROUND: Troleandomycin (TAO), a macrolide antibiotic, was studied as an alternative treatment in 18 children with severe, steroid-requiring asthma. METHODS: In this investigation three treatment arms were used in randomized, double-blind, parallel fashion: combination TAO and methylprednisolone (MPn), combination TAO and prednisone, and MPn alone. RESULTS: All groups tolerated a considerable reduction in glucocorticoid dose over the 12 weeks of the study: 80% +/- 6% for TAO-MPn, 55% +/- 8% for TAO-prednisone, and 44% +/- 14% for MPn alone. These reductions are all statistically significant (p < 0.05) within groups, and the differences between groups were statistically significant between the TAO-MPn and MPn alone groups. The concentration of methacholine required to induce a 20% decrease in forced expiratory volume in 1 second and pulmonary function were not significantly improved in any treatment group. Safety parameters including blood chemistry and hematology, adrenal function assessment; bone densitometry, and muscle strength testing, were not altered significantly. Two patients who received TAO had elevated liver enzyme levels; one required discontinuation of TAO and one experienced spontaneous resolution without intervention. Lack of statistically significant changes in the efficacy parameters were likely a result of small sample size and effects of the glucocorticoid dose taper. CONCLUSIONS: TAO is safe and may be a reasonable treatment alternative in a limited trial for patients who are unable to tolerate tapering of their glucocorticoid dosage. Therapy should be guided by the goal of treatment, that is, glucocorticoid dose reduction or improvement of pulmonary function with appropriate monitoring of pulmonary function and adverse effects.

Effect of low-dose troleandomycin on theophylline clearance: implications for therapeutic drug monitoring.

Troleandomycin (TAO) is an alternative agent used in the treatment of severe, steroid-requiring asthma. Its mechanism of action, once thought to be inhibition of theophylline clearance, remains unclear. Twenty-four-hour theophylline profiles were obtained in 11 children with severe asthma prior to and after 2 and 12 weeks of low-dose TAO therapy. Theophylline dosages were adjusted by blinded investigators to maintain serum theophylline concentrations (STCs) between 10 and 20 micrograms/ml. Dosages were decreased from 877 +/- 60 mg/day (mean +/- SEM) before TAO to 811 +/- 56 mg/day (NS) after 2 weeks and 764 +/- 56 mg/day (p less than 0.05) after 12 weeks. Because of the dosage adjustments, STCs did not increase significantly. Theophylline clearance was reduced from 65.7 +/- 9.8 ml/kg/hour at baseline to 50.2 +/- 4.1 ml/kg/hour (p less than 0.05) after 2 weeks and 50.1 +/- 6.2 ml/kg/hour (p less than 0.05) after 12 weeks of TAO therapy. We conclude that TAO can significantly reduce theophylline clearance, resulting in increased STCs if dosages are not titrated. We recommend an empiric 25% reduction of daily theophylline dose with the initiation of TAO. We also recommend monitoring STCs 4 hours after the morning dose (with twice-daily dosing of sustained-release products) after 3, 7, 14, and 30 days of TAO therapy, then periodically as indicated.

Alternative treatments for asthma: assessing the need.

Alternative treatments such as troleandomycin methotrexate, gold, and intravenous gamma globulin are sometimes considered for severe asthmatics to minimize the need for systemic corticosteroids and reduce adverse effects. These alternative therapies may also be associated with significant toxicity and expense. The ability to reduce corticosteroid use and the need for alternative treatment interventions in 125 pediatric patients at our institution were reviewed. Because corticosteroid requirements were reduced significantly, only 23 of 125 children evaluated were considered for treatment alternatives with only 10 receiving such therapy. This study emphasizes the importance of a thorough and comprehensive review of corticosteroid requirements and usage prior to initiating alternative approaches to treatment in moderate to severe asthmatics as well as in patients thought to be "steroid-dependent."

Monitoring glucocorticoid therapy: a pharmacokinetic approach.

Although glucocorticoid therapy is essential for the treatment of severe inflammatory disorders, there is no systematic approach to patient variables that may affect availability of a steroid dose. After the development of a data base of pharmacokinetic parameters, we examined glucocorticoid pharmacokinetics in 54 patients between 2 and 70 years of age using 70 pharmacokinetic studies after administration of intravenous methylprednisolone (n = 25), oral methylprednisolone (n = 15), intravenous prednisolone (n = 18), and oral prednisone (n = 12). Eleven patients had unusually rapid methylprednisolone elimination (clearance, 565 to 837 ml/min/1.73 m2; population mean, [+/- SD] 380 +/- 100 ml/min/1.73 m2) without an identifiable cause. Incomplete absorption of methylprednisolone and prednisone was observed in three patients and one patient, respectively. Evaluation of glucocorticoid pharmacokinetics in children aged 1 year 8 months to 18 years demonstrated a significant inverse correlation (r = 0.88; p less than 0.001) between prednisolone clearance and age. It is therefore important to consider age in the interpretation of pharmacokinetic data. To simplify measurement of prednisolone clearance, a single-dose single-point method was developed. This was based on a highly significant relationship between the 6-hour postdose prednisolone concentration and prednisolone clearance (log prednisolone clearance = 2.66 + [6-hour postdose concentration] [-0.00167]; r2 = 0.96; p less than 0.0001). Evaluation of glucocorticoid pharmacokinetics in the clinical setting can be used to identify abnormalities in absorption, elimination, and patient compliance. This technique can be used to individualize glucocorticoid dosing regimens.

Prednisolone and methylprednisolone kinetics in children receiving anticonvulsant therapy.

Prednisolone and methylprednisolone pharmacokinetic parameters were evaluated in asthmatic children receiving concomitant anticonvulsant therapy. On separate study days, 15 children receiving either phenobarbital, carbamazepine, phenytoin, or combination anticonvulsant therapy were administered an intravenous dose of prednisolone or methylprednisolone and compared with a pediatric population not receiving anticonvulsant therapy. Plasma clearance of prednisolone in subjects receiving phenobarbital, carbamazepine, and phenytoin and in control subjects was 302.7 +/- 74.6, 383.2 +/- 53.8, 378.9 +/- 50.7, and 214.0 +/- 28.8 ml/min/1.73 m2 (mean +/- 1 SD), whereas plasma clearance of methylprednisolone was 1179.1 +/- 519.4, 1687.0 +/- 109.9, 2209.5 +/- 473.8, and 381.7 +/- 98.4 ml/min/1.73 m2, respectively. Bioavailability of prednisolone after the oral administration of prednisone and methylprednisolone ranged from 86% to 104% during anticonvulsant therapy. Three individuals reevaluated 13 to 20 days after discontinuing anticonvulsant therapy demonstrated pharmacokinetic parameters similar to those of the control group. Limited studies performed in patients receiving combination anticonvulsant therapy did not demonstrate an additive effect on prednisolone elimination. Differences in the degree of enhancement of prednisolone and methylprednisolone disposition in all three anticonvulsant study groups suggest that different metabolic pathways may be involved.

Atropine and exercise-induced bronchoconstriction.

Six asthmatic children were studied to determine whether supplemental, parenteral atropine would increase the effects of bronchodilation and protection against exercise-induced bronchoconstriction after maximal effects had been achieved by inhalation. First, we determined the amount of inhaled atropine sulfate that would give maximal bronchodilation for each patient at rest. This quantity of atropine was designated as "A." Then all subjects exercised for five sessions with the following pre-exercise treatments in a random order: (a) inhaled distilled water plus intramuscular (IM) saline solution; (b) inhaled A dose of atropine plus IM saline solution; (c) inhaled distilled water plus 0.35 mg IM atropine; (d) inhaled A dose of atropine plus 0.35 mg IM atropine; and (e) inhaled double the A dose plus IM saline solution. The results showed that the combination of inhaled and IM atropine had the greatest bronchodilation effect and the greatest protection against exercise-induced bronchoconstriction. Atropine inhalation alone (A dose) or IM injection (0.35 mg) was not as effective in bronchodilation or in alleviation of exercise-induced bronchoconstriction. Doubling the dose of inhalation (2A) did not increase the effects of the A dose. These results support the hypothesis that inhaled atropine does not reach all the airways where cholinergic receptors are present.

Effectiveness of a portable face mask in attenuating exercise-induced asthma.

Recent investigations have demonstrated that exercise-induced asthma (EIA) can be prevented by inspiration of warm, fully humidified air during exercise. We evaluated the success of a surgical face mask, used to retain warm, humidified, expired air, in preventing EIA in ten asthmatic children. subjects underwent six minutes of exercise on a treadmill during two sessions, in one session breathing room air and in another wearing a mask covering the nose and mouth. On the control day, average group forced expiratory volume in 1 s (FEV1) and maximal midexpiratory flow rate (MMEF) decreased from the preexercise baseline value to 66% and 47% of baseline, respectively, at six minutes; on the mask day, FEV1 and MMEF were 91% and 82% of the baseline values (increased in all subjects). A simple face mask may be an inexpensive, nonpharmacologic alternative for alleviation of EIA.

Corticosteroids in the treatment of acute exacerbations of asthma.

In a 72-hour double-blind study 16 moderately to severely asthmatic subjects received either oral prednisone 2 mg/kg/day or placebo in addition to their regular medication as treatment for an acute exacerbation of asthma. The group receiving prednisone demonstrated significant increases in the PEFR and decreased need for beta-2 agonist nebulization or injections the first 12 hours of the study period and these improvements were maintained over the 72 hours. The placebo-treated group showed minimal reduction in nebulization and injection requirements and minimal increase in PEFR. Oral prednisone was found to be effective in controlling acute exacerbations of asthmatic symptoms.