Pharmacotherapy of asthma in children, with special reference to leukotriene receptor antagonists.

Asthma in adults is generally recognized as a chronic inflammatory airway disease, although this association is less well established in childhood asthma. Thus, recent asthma guidelines have emphasized that asthma treatment should be directed toward the underlying inflammatory aspects of the disease. The prevalence of asthma and resultant hospitalizations and deaths have increased or remained stable over the past 10 years in the United States. In part, this appears to be caused by shortcomings of available antiasthma therapeutic agents. Because these trends are particularly troublesome in children and young adults, there is a need for effective anti-inflammatory therapies that are safe and tolerable. The leukotrienes are a family of lipid mediators that appear to play an important role in the symptomology and pathogenesis of asthma. The results of clinical trials in adults with asthma demonstrated that antileukotriene drugs such as zafirlukast, montelukast, and zileuton improve pulmonary function, decrease asthma symptoms, and decrease the concomitant use of other antiasthma drugs. Most antileukotriene agents are orally bioavailable and well tolerated, offering the potential for improved patient compliance. Montelukast and zafirlukast have received approval for use in pediatric asthma patients, and approval of zafirlukast in this patient population is pending.

Fluticasone propionate powder and lack of clinically significant effects on hypothalamic-pituitary-adrenal axis and bone mineral density over 2 years in adults with mild asthma.

BACKGROUND: Although inhaled corticosteroids are widely used for the treatment of inflammation in asthma, prospective, long-term, placebo-controlled trials characterizing their systemic safety with chronic use are lacking. OBJECTIVE: This study was designed to prospectively evaluate the long-term safety of inhaled fluticasone propionate therapy. METHODS: Fluticasone propionate powder, 500 microgram, or placebo was administered twice daily by means of the Diskhaler for 104 weeks to 64 adults with mild persistent asthma in a randomized, double-blind, parallel-group study. Primary safety variables were measured at baseline and every 6 months thereafter. Although evaluation of efficacy was not an objective of this study, pulmonary function testing was performed at monthly intervals. RESULTS: Two years of treatment with fluticasone propionate had no significant effects on the skeletal system. No clinically significant changes were observed in ophthalmic parameters (glaucoma and posterior subcapsular cataracts). Mean change from baseline in lumbar spine (L1 to L4 ) bone density at week 104 was not significantly different between fluticasone propionate (-0.006 +/- 0.008 g/cm2) and placebo (-0.007 +/- 0.010 g/cm2). Markers of bone formation (serum osteocalcin) and resorption (urinary N-telopeptide) did not differ significantly between treatment groups. The effects of fluticasone propionate treatment on the hypothalamic-pituitary-adrenal axis were minimal, with no alterations in morning plasma cortisol concentrations and minor but statistically significant decreases in poststimulation mean peak plasma cortisol concentrations (P =.021) and 8-hour plasma cortisol area under the curve values (P =.020) at week 104. Drug-related adverse events were primarily topical effects of inhaled corticosteroids. Pulmonary function improved significantly during 2 years of fluticasone propionate treatment. CONCLUSION: Fluticasone propionate powder, 500 microgram twice daily for up to 2 years, was efficacious and well tolerated, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis, bone density, or ophthalmic parameters in adults with mild asthma.

Fluticasone propionate reduces oral prednisone use while it improves asthma control and quality of life.

This study examined the ability of fluticasone propionate aerosol to reduce oral prednisone requirements in patients with severe asthma. Ninety-six patients dependent on oral prednisone were treated for 16 wk with placebo or fluticasone propionate aerosol (750 or 1,000 micrograms twice daily). Their dosage of oral prednisone was adjusted weekly according to predetermined criteria. A total of 69% and 88% of patients treated with fluticasone propionate 750 and 1,000 micrograms twice daily, respectively, compared with 3% of placebo-treated patients used no prednisone by the end of the study. In the fluticasone propionate groups, FEV1 and peak expiratory flow rates at the last evaluable visit/date improved and the number of night awakenings and symptomatic albuterol use declined relative to placebo values (p < 0.05). Patient-rated asthma symptoms improved in the groups receiving fluticasone propionate but not in the placebo group (p < 0.005). Fluticasone propionate aerosol was well-tolerated, and it improved some dimensions of health-related quality of life measured using a standard patient survey. Fluticasone propionate aerosol (750 or 1,000 micrograms twice daily) effectively and safely allowed most asthmatics dependent on oral corticosteroids to reduce or eliminate oral prednisone use while improving pulmonary function and quality of life.

A novel breath actuated device (Autohaler) consistently actuates during the early phase of inspiration.

OBJECTIVE: To establish and quantify the point during inspiration that the Autohaler (AH) inhalation system releases a metered dose of aerosol (placebo). The second objective was to determine if the Autohaler system actuates consistently, regardless of the canister life. DESIGN: Double-blind, randomized, two-period crossover, one-day trial. SETTING: Community based allergy and asthma clinic. PARTICIPANTS: Twelve patients with mild to moderate asthma. RESULTS: Mean verbal training time for the AH which included the patient demonstrating their ability to correctly use the AH was approximately 6 minutes. The mean time for actuation for the AH early in its canister life ("new canister") was 195 msec compared to 205 msec for the AH late in its canister life ("old canister") (p = 0.589). This represented the early part of inspiration as patients had a mean inspiratory duration of 2231 msec for the "new" AH and 2343 msec for the "old" AH. The mean percentage of inspiration time required to actuate the "new" AH was 8.92% compared to 8.82% for the "old" AH. Patients rated the system as easier to much easier to use compared with their current standard press and breathe inhaler. CONCLUSIONS: The AH consistently actuates early during inspiration, which is considered the optimal time for drug delivery, regardless of the canister life.

Administration errors with a conventional metered dose inhaler versus a novel breath actuated device.

Metered dose inhalers are difficult for patients to use. A device that eliminates coordination and timing of actuation may simplify the use of metered dose inhalers. This trial compared (1) number of errors made and (2) specific errors made between the conventional press and breathe metered dose inhaler (MDI) and the novel breath actuated Autohaler inhalation device in 24 subjects. We studied the use of each device in 12 patients trained and experienced in using an MDI and in 12 volunteers who had never been exposed to any inhalation device. We observed that even experienced patients continue to have difficulty with the coordination and timing of metered dose inhalers. The volunteer group had equal difficulty with both devices but it appeared that it was easier for them to learn how to use the breath actuated device than the MDI.

Sensitivity of FEV1 response following one and two inhalations of albuterol: a pilot study.

Eleven patients entered a pilot study designed to evaluate the proportion of eligible responders following a single inhalation of albuterol aerosol, the degree of response, and the sensitivity to distinguish between one and two inhalations based on FEV1 response. Each patient received a single inhalation at 0 and 60 minutes. FEV1 was measured 30 and 60 minutes after each inhalation. Most patients (82%) responded to a single inhalation and the majority (73%) were capable of further response after two inhalations. This study design was able to distinguish FEV1 responses to one and two inhalations of albuterol and provide upward and downward sensitivity sufficient to detect major differences in products.

New drugs in treatment of asthma.

Therapy for bronchial asthma should be preventive when possible. Around-the-clock treatment with theophylline is a new way of using an old drug. Beta2-adrenergic receptor stimulators, cromolyn sodium, and steroids in aerosol form are new drugs that are useful in treatment of asthma. The good news with respect to drug treatment of asthma is that in addition to the old reliable medications which have provided good relief-including epinephrine, ephedrine, isoproterenol, aminophylline, and steroids given orally and parenterally-new drugs are available which have been extremely helpful in controlling symptoms in many patients. The bad news is that none of the new agents is a panacea and that many of them have significant undesirable side effects. It is the physician's responsibility to be wary of the new drugs for asthma and to use them appropriately.