Inhaled corticosteroids as rescue medication in acute severe asthma

Systemic corticosteroids (CS) should be considered as first-line treatment for acute asthma exacerbations, especially severe exacerbations. They may sometimes require a few hours or more to achieve their maximum effect. This time delay observed between administration of CS and improvement in lung function or hospital admissions is consistent with the belief that these effects of CS, involving the modification of gene expression, occur with a time lag of hours or days (genomic effect). On the other hand, CS also have effects initiated by specific interactions with membrane-bound or cytoplasmic receptors for CS, or nonspecific interactions with the cell membrane, with a much more rapid response (seconds or minutes; nongenomic effect). This review analyzes the clinical evidence regarding the use of inhaled CS in acute asthma patients, according to the characteristics of the nongenomic effect, and presents a proposal for the use of inhaled CS as a rescue medication in the emergency-department setting.     

Outcome of short-term hospitalization for children with severe asthma.

This study presents results of a family-centered, short-term residential program in which medical, behavioral, and treatment assessments were provided to the child with severe asthma and the family. After a median stay of 15 days, forty-four consecutively admitted children with severe asthma achieved a 93% reduction in hospital days (median, 7 hospital days for the year before treatment versus median 0 hospital days per patient per year at 20 1/2-month follow-up; p less than 0.001) and an 81% reduction in emergency care (median, 4 visits for the year previously versus median, 0.4 visits per patient per year at follow-up; p less than 0.01). There was also a significant reduction in corticosteroid bursts and improvement in FEV1. Unique to this program was mandatory family participation focusing on the child's and family's adaptation to severe asthma and development of family-specific interventions to promote compliance with the treatment regimen. Child and family functioning was assessed at admission and follow-up. Hospital use at follow-up was greater for children from dysfunctional families. Families demonstrating difficulties in disciplining the child with asthma required more hospital days both before admission and at follow-up. Short-term hospitalization for children with severe asthma is associated with significant improvement in pulmonary morbidity when the family of the child is included in assessment and treatment.     

Development of allergic bronchopulmonary aspergillosis during treatment of severe asthma with systemic corticosteroids

Rapid clinical improvement of allergic bronchopulmonary aspergillosis (ABPA) is usually noted with corticosteroid therapy. We report a case of ABPA that developed in a patient who was being treated with prednisone on a maintenance basis for severe asthma. Recovery from the short-term episode of ABPA was protracted and required higher doses of corticosteroids for control of the syndrome than usually necessary. It is suggested that corticosteroids do not prevent the development of ABPA, and that patients who develop the syndrome while on corticosteroids may have a protracted course with poor response to the usually effective doses of corticosteroids.     

Outcome of long-term hospitalization for asthma in children

Children whose asthma continues to be poorly controlled with outpatient management are often referred to a long-term hospital program for care. Although these programs have been in existence since the 1950s, there has been no systematic study of their effectiveness. The purpose of the present study was to determine outcome in 103 children discharged consecutively after a long-term hospitalization. These children had both severe asthma and significant psychologic problems. Eighty-three of the 103 children had required continuous or frequent intermittent steroids for asthma control. In the year before admission, they had been hospitalized for asthma a mean of 2.6 times for 11.8 days and had had 4.6 visits to emergency rooms and 6.6 visits to physician offices for acute wheezing. Use of medical resources for asthma decreased significantly in the year after long-term hospitalization compared to the year before hospitalization (hospitalization: -34%, p less than 0.0001; hospital days: -39%, p less than 0.0002; emergency room visits: -46%, p less than 0.00001; physician office visits for acute asthma, -42%; p less than 0.00001; and a composite score giving increasing weight to more intensive and costly care: -30%, p less than 0.0001). Long-term hospitalization for children with asthma not responsive to outpatient management is associated with improvement in their use of medical resources.     

Outcome measures for asthma disease management

PURPOSE OF REVIEW: Many interventions have been undertaken in managing asthma in a population-based framework. The identification of successful interventions would guide policy implementation to improve outcomes in patient morbidity and mortality and healthcare costs. RECENT FINDINGS: Several studies have focussed on emergency room interventions in asthma management. Many support the existence of the "teachable moment" to lead to interventions that are effective. Other popular interventions are community-based educational programmes, targeting clinician and patient behavior modification. In some cases, it is unclear how these interventions impact patient-specific outcomes such as quality of life, symptom-free days, or missed days of school or work as these were not measured. Most studies separate patients on the basis of age (adults versus children), adding yet another level of complexity to the development of useful interventions. SUMMARY: Several of the interventions failed to show a significant improvement of patient-centered asthma outcomes when they were measured. This was despite an improvement in surrogate measures, such as attendance of follow-up appointments. Many studies did not (or were not designed to) show a durable response. Further research is needed to understand this chronic disease and devise effective interventions with appropriate outcomes for measuring their effectiveness.     

The mechanism of corticosteroids in treating asthma

It would be difficult for physicians or allergists to imagine doing without corticosteroids in managing difficult cases of bronchial asthma. It is beyond any doubt that CS act on many sites to help reverse the pathologic process of bronchial asthma. Corticosteroids enhance the beta-adrenergic response to relieve the muscle spasm. They also act by reversing the mucosal edema, decreasing vascular permeability by vasoconstriction, and inhibiting the release of LTC4 and LTD4. Corticosteroids reduce the mucus secretion by inhibiting the release of secretagogue from macrophages. Corticosteroids inhibit the late phase reaction by inhibiting the inflammatory response and interfering with chemotaxis. This action may be due to the inhibition of LTB4 release. The eosinopenic effect of corticosteroids may help to prevent the cytotoxic effect of the major basic protein and other inflammatory mediators released from eosinophils. Corticosteroids have no effect on the immediate hypersensitivity reaction and have no direct role in bronchial reactivity. By blocking the late reaction, they prevent the increased airway reactivity observed with late bronchial reactions. The limitation of using corticosteroids are their side effects. They vary from tolerable to life threatening side effects. Each tissue in the body is a target for corticosteroids. The mechanism of adverse effects have been studied in extensive detail but many questions are yet to be answered. Alternate-day therapy and inhalation therapy are meant to minimize these side effects. The expansion of using inhaled steroid therapy and finding some inhaled preparations that have even less systemic side effects seems a reasonable approach to deal with severe asthma.     

Significant variability in response to inhaled corticosteroids for persistent asthma

BACKGROUND: A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy. OBJECTIVE: The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs. METHODS: A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day. RESULTS: Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years). CONCLUSIONS: Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.     

Outcome of occupational asthma

PURPOSE OF REVIEW: Occupational asthma is often associated with serious work and financial consequences. Correct management of occupational asthma must be based on a good knowledge of the natural history of the disease and of its prognostic factors. RECENT FINDINGS: Longitudinal studies have demonstrated that improvement of symptoms and airway hyperresponsiveness may be prolonged after cessation of exposure. Severity of asthma at diagnosis is the best predictor of clinical symptoms and functional impairment at follow-up. The molecular weight of the causal agent does not seem to be a prognostic factor. Airway inflammation is associated with persistence of symptoms and airway hyperresponsiveness after cessation of exposure. Reduction of exposure has proved to be effective in improvement of latex-induced asthma. SUMMARY: Further studies are needed to investigate the prognostic value of sputum eosinophils and neutrophils, and to determine whether some specific agents are associated with a better prognosis than others.     

Outcome of women admitted to hospital for depressive illness: factors in the prognosis of severe depression

BACKGROUND: A previous study of women 9 months after discharge from in-patient treatment for depression found that low self-esteem as measured by a self-report questionnaire at admission was associated with a worse prognosis. This study investigates the womens' outcome more than 4 years after discharge and the continued prognostic relevance of self-esteem and other variables. METHOD: Fifty-six women who had been admitted to hospital with major depression and studied in detail during their admission and 9 months following discharge were traced 4-5 years later. Possible prognostic factors were investigated in relation to time to recovery and recurrence, and to a global outcome measure. RESULTS: In keeping with other published work only 16 out of 52 (31%) women had recovered and remained well. Fifteen out of 52 (29%) subjects had experienced depressive symptoms for more than 70% of the follow-up time or died from unnatural causes. Low self-esteem scores recorded at the initial admission correlated with slow recovery but not subsequent recurrence of depression. The occurrence of one or more life events in the year preceding admission was associated with a better prognosis. CONCLUSIONS: The poor long-term prognosis of many women with severe depression was confirmed. Social factors, such as social support and marital relationships were less important for prognosis than in previous studies of less severely ill subjects. The prognostic value of self-esteem warrants further investigation and appears to have therapeutic implications.     

Therapeutic options for severe asthma

As the overall prevalence of asthma has escalated in the past decades, so has the population of patients with severe asthma. This condition is often difficult to manage due to the relative limitation of effective therapeutic options for the physician and the social and economic burden of the disease on the patient. Management should include an evaluation and elimination of modifiable risk factors such as smoking, allergen exposure, obesity and non-adherence, as well as therapy for co-morbidities like gastro-esophageal reflux disease and obstructive sleep apnea. Current treatment options include conventional agents such as inhalational corticosteroids, long acting β₂ agonists, leukotriene antagonists, and oral corticosteroids. Less conventional treatment options include immunotherapy with methotrexate, cyclosporine and tacrolimus, biological drugs like monoclonal antibodies, tumor necrosis factor-α blockers and oligonucleotides, phosphodiesterase inhibitors, antimicrobials and bronchial thermoplasty.     

Outcome of pregnancy in a randomized controlled study of patients with asthma exposed to budesonide.

BACKGROUND: Budesonide is the only inhaled corticosteroid to be given a category B pregnancy rating by the US Food and Drug Administration, based on observational data from the Swedish Medical Birth Registry. However, data from large randomized controlled trials are lacking. OBJECTIVE: To compare pregnancy outcomes among patients with recent-onset mild-to-moderate persistent asthma receiving low-dose budesonide vs placebo. METHODS: In a randomized, double-blind, placebo-controlled trial, 7241 patients aged 5 to 66 years with mild-to-moderate persistent asthma for less than 2 years and no previous regular corticosteroid therapy received once-daily budesonide or placebo via dry powder inhaler in addition to their usual asthma medication for 3 years. This trial was followed by a 2-year open-label treatment period. The daily dose of budesonide was 400 microg for adults. The study included 2473 females aged 15 to 50 years at randomization. Pregnancy was not an exclusion criterion (except for U.S. patients). RESULTS: Of 319 pregnancies reported, 313 were analyzed. Healthy children were delivered in 81% and 77% of all pregnancies in the budesonide and placebo groups, respectively. Of the 196 pregnancies reported by participants taking budesonide, 38 (19%) had adverse outcomes: 23 (12%) had miscarriages, 3 (2%) had congenital malformations, and 12 (6%) had other outcomes. Of the 117 pregnancies reported in the placebo group, 27 (23%) had adverse outcomes: 11 (9%) had miscarriages, 4 (3%) had congenital malformations, and 12 (10%) had other outcomes. CONCLUSIONS: Treatment with low-dose inhaled budesonide in females with mild-to-moderate persistent asthma does not seem to affect the outcome of pregnancy.