Addition of Leukotriene Receptor Antagonists to Inhaled Corticosteroids Improved QOL of Patients with Bronchial Asthma Surveyed in Suburban Tokyo,Japan

BackgroundBronchial asthma is a chronic inflammatory disease that has a severe impact on health worldwide.MethodsA survey of 10,771 patients with bronchial asthma in the Tama region, Tokyo was conducted for 5 years to examine treatment and quality of life (QOL). Subjects were patients aged ≥ 16 years and their physicians who replied to a questionnaire sent in November from 2002 to 2006. Symptoms of bronchial asthma, visits to an emergency room, use of drugs, and severity of asthma were investigated.ResultsAsthmatic symptoms improved over the 5 years, with a reduction in the number of emergency room visits. Since inhaled corticosteroids (ICS) were used by > 80% of patients in 2002, we suspected that increased use of concomitant leukotriene receptor antagonists (LTRA) and long-acting β₂ agonists (LABA) might have contributed to these findings. The effects of these drugs were compared between ICS + LTRA (n = 45) and ICS + LABA (n = 54) groups of patients. There was no significant difference in the ICS dose between these groups. In the ICS + LABA group, 18.5% and 22.2% of patients visited an emergency room before and after initiation of combination therapy, respectively, with no statistically significant difference. In contrast, the rate of emergency room visits in the ICS + LTRA group decreased from 24.4% to 6.6% after addition of LTRA.ConclusionsThese results suggest that the frequency of visits to an emergency room was decreased by complementing the anti-inflammatory effect of ICS with further treatment of inflammation, particularly with LTRA.     

Inhaled Corticosteroids for Asthma: Common Clinical Quandaries

This narrative review provides evidence-based explanations to some of the common clinical concerns regarding inhaled corticosteroids. Inhaled corticosteroids are the treatment of choice for a newly diagnosed asthmatic patient. Better results are obtained when treatment is initiated as soon as the diagnosis is made. Asthma control can be achieved and maintained in most patients with a low or moderate dose of inhaled corticosteroid administered in two daily doses. Longer duration of treatment provides more sustained benefits than treatment that is intermittent and for short periods of time. The clinical benefits can be observed within 24 hours of commencing treatment and may be more pronounced in patients with an eosinophilic bronchitis. Inhaled corticosteroids provide additional benefit when used in conjunction with prednisone in acute severe asthma. Low doses do not have clinically deleterious side effects on the bones, growth, eye, or hypothalamo-pituitary-adrenal-axis. However, they do not normalize lung function and prevent structural changes in the airway wall in all asthmatic patients.     

Tolerability Profiles of Leukotriene Receptor Antagonists and Long-Acting β2-Adrenoceptor Agonists in Combination with Inhaled Corticosteroids for Treatment of Asthma: A Review

Inhaled corticosteroids, long-acting β₂-adrenoceptor agonists, and leukotriene receptor antagonists are widely used for treatment of asthma. Inhaled corticosteroids are recommended as first-line therapy, whereas long-acting β₂-adrenoceptor agonists and leukotriene receptor antagonists are indicated as add-on therapy in patients not adequately controlled with corticosteroids alone. A number of studies have investigated the efficacy of combinations of these drugs in asthma, but several issues concerning the safety of these treatments are highly debated. This review provides a critical appraisal of the tolerability profiles of long-acting β₂-agonists and leukotriene receptor antagonists used in combination with inhaled corticosteroids for the treatment of asthma.     

Montelukast as an Add-On Therapy to Inhaled Corticosteroids in the Treatment of Severe Asthma in Elderly Patients

Background. Severe asthma remains a worldwide medical problem. However, this disease has not been adequately explored in the elderly. This study was performed to determine how the addition of montelukast to antiasthmatic therapy improves the control of severe asthma in elderly patients. Methods. Elderly patients (>60 years old) with diagnoses of severe asthma were observed over 24 months of therapy: the first 12 months using inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) and the second 12 months with oral montelukast added in two-thirds of the patients, with the remaining third representing the control group. The primary efficacy endpoint of the study was the percentage of days without asthma symptoms in the first 12 months of treatment compared with the percentage after adding montelukast therapy. Results. A total of 512 elderly, asthmatic patients were included in the study: seventy-one (13.9%) patients had well-controlled asthma, 211 (41.2%) had partly controlled asthma, and 230 (44.9%) had uncontrolled asthma. During the first year of treatment using ICS and LABA, an increase in the median percentage of days without asthma was observed from 50.1% to 62.1%, as well as a decrease in the percentage of days with short beta-receptor agonist use, from 52.2% to 46.8%. These differences were significantly greater after 12 months, when montelukast was added to the therapy (78.4% and 39.5%, respectively). This improvement was not observed in the control group. After 2 years of observation, the median number of asthma exacerbation incidents per patient decreased from 1.6 per year to 1.2 per year when montelukast was added. Conclusion. Severe asthma in elderly patients is very poorly treated, with this population exhibiting very low compliance with antiasthmatic therapy. Adding montelukast provides benefits and improved control; however, it does not resolve severe asthma control problems.     

Hydrofluoroalkane Formulations of Inhaled Corticosteroids for the Treatment of Asthma

Current international guidelines for the treatment of asthma advocate inhaled corticosteroids as first-line therapy for persistent symptoms. As chlorofluorocarbon (CFC)-based products are being phased out because of environmental concerns, new inhaler propellants, such as hydrofluoroalkane (HFA)-134a, have been developed. The reformulation of existing corticosteroid compounds into HFA propellants has resulted in two distinct classes of corticosteroid aerosols consisting of HFA suspensions and HFA solutions. The new HFA formulations of flunisolide and beclomethasone dipropionate exist as solutions, whereas HFA preparations of fluticasone propionate, triamcinolone acetonide, and mometasone furoate are formulated as suspensions. HFA suspensions retain the same particle size, deposition, and efficacy profiles as their CFC counterparts. HFA solutions, however, exist as extra-fine aerosols which have been shown to penetrate more effectively into the peripheral regions of the lung. Comparisons of HFA solutions with their CFC counterparts have demonstrated equivalent efficacy when given in smaller doses. The safety profiles of both HFA suspensions and solutions, given at equivalent doses, are comparable to CFC formulations. Increasing evidence suggests that inflammation of the small airways plays an important role in the pathogenesis of asthma. Currently, the clinical implications of long-term treatment of the peripheral lung using an extra-fine inhaled corticosteroid aerosol remain uncertain. Future studies, involving histopathologic and clinical endpoints, will be necessary to determine whether treatment with HFA solutions offers significant advantages over currently available therapies.     

护理干预对哮喘患者吸入糖皮质激素治疗依从性的影响

目的护理干预对哮喘患者糖皮质激素吸入治疗的效果与治疗依从性分析。方法选取2010年1月—2011年12月在我科应用糖皮质激素治疗依从性差的84例中重度哮喘患者,随机分为两组,每组42例,调查分析患者治疗依从性,对比两组服药依从性。结果干预组42例患者,治疗依从率为88.10%,哮喘症状评分为(24.1±0.9)分;对照组42例患者,治疗依从率为19.05%,哮喘症状评分为(13.9±0.7)分。护理干预组的治疗依从性明显较好(P<0.05),疗效显著提高(P<0.05)。结论针对性护理干预能够有效提高患者糖皮质激素治疗依从性,提高疗效。     

Inhaled Corticosteroids and Bone Density of Children with Asthma

In this cross-sectional study we aimed to compare anteroposterior (AP) spine and total body bone mineral density (BMD) measurements of children with asthma treated with long-term inhaled budesonide (n = 52, mean age 6.4 ± 2.2 yr, M/F = 22/30) (Group I) with those of asthmatic children who had never received treatment with inhaled corticosteroids (Group II) (n = 22, mean age 6.8 ± 2.2, M/F = 10/12). Boys and girls were comparable for age, weight, height, cumulative corticosteroid (CS) dosage, duration of disease and inhaled corticosteroid (ICS) treatment within each group. The mean total accumulated dosage of budesonide for children in Group I was 154.0 ± 135.3 mg (mean daily dosage = 419 ± 154 µg) and the mean treatment duration was 13.0 ± 9.8 months. The two groups were comparable with respect to age, gender, weight, height, Tanner's stage and duration of disease. There was no significant difference between subjects in the two groups for total (p = 0.214) and (AP) spine BMD results (p = 0.661), respectively. Our results provide additional support for the safety of ICS therapy on bone density of asthmatic children.     

Strategies Used by Older Adults with Asthma for Adherence to Inhaled Corticosteroids

BACKGROUND

Older adults with asthma have low levels of adherence to their prescribed inhaled corticosteroids (ICS). While prior research has identified demographic and cognitive factors associated with ICS adherence among elderly asthmatics, little is known about the strategies that older adults use to achieve daily use of their medications. Identifying such strategies could provide clinicians with useful advice for patients when counseling their patients about ICS adherence.

OBJECTIVE

To identify medication use strategies associated with good ICS adherence in older adults.

PARTICIPANTS

English-speaking and Spanish-speaking adults ages 60 years and older with moderate or severe asthma were recruited from primary care and pulmonary practices in New York City, NY, and Chicago, IL. Patients with chronic obstructive pulmonary disease, other chronic lung diseases or a smoking history of greater than 10 pack-years were excluded.

MAIN MEASURES

Medication adherence was assessed with the Medication Adherence Rating Scale (MARS). Medication use strategies were assessed via open-ended questioning. “Good adherence” was defined as a mean MARS score of 4.5 or greater.

KEY RESULTS

The rate of good adherence to ICS was 37 %. We identified six general categories of medication adherence strategies: keeping the medication in a usual location (44.2 %), integrating medication use with a daily routine (32.6 %), taking the medication at a specific time (21.7 %), taking the medication with other medications (13.4 %), using the medication only when needed (13.4 %), and using other reminders (11.9 %). The good adherence rate was greater among individuals who kept their ICS medication in the bathroom (adjusted odds ration [AOR] 3.05, 95 % CI 1.03–9.02, p?=?0.04) or integrated its use into a daily routine (AOR 3.77, 95 % CI: 1.62–8.77, p?=?0.002).

CONCLUSIONS

Keeping ICS medications in the bathroom and integrating them into daily routines are strategies associated with good ICS adherence. Clinicians concerned with adherence should consider recommending these strategies to their older asthmatic patients, although additional research is needed to determine whether such advice would improve adherence behaviors.     

Long-acting Beta-Agonists with and without Inhaled Corticosteroids and Catastrophic Asthma Events

Background

It is unclear whether long-acting β-agonists with concomitant inhaled corticosteroids increase asthma-related intubations and deaths. We pooled data on long-acting β-agonists with variable and concomitant inhaled corticosteroids to evaluate the risk for catastrophic asthma events.

Methods

We conducted searches of electronic databases, the US Food and Drug Administration website, clinical-trials registries, and selected references through December 2008. We analyzed randomized controlled trials in patients with asthma, which lasted at least 3 months, evaluated long-acting β-agonists compared with placebo or long-acting β-agonists with inhaled corticosteroids compared with corticosteroids alone, and included at least 1 catastrophic event, defined as asthma-related intubation or death.

Results

In pooled trial data that included 36,588 participants, long-acting β-agonists increased catastrophic events 2-fold (Peto odds ratio [OR] 2.10; 95% confidence interval [CI], 1.37-3.22). Statistically significant increases were seen for long-acting β-agonists with variable corticosteroids compared with placebo (OR 1.83; 95% CI, 1.14-2.95) and for concomitant treatment with corticosteroids compared with corticosteroids alone (OR 3.65; 95% CI, 1.39-9.55). Similar increases in risk were seen for variable and concomitant corticosteroid use, salmeterol and formoterol, and children and adults. When the analysis was restricted to trials with controlled corticosteroid use, given as part of the study intervention, concomitant treatment still increased catastrophic events compared with corticosteroids alone (OR 8.19; 95% CI, 1.10-61.18).

Conclusion

Long-acting β-agonists increase the risk for asthma-related intubations and deaths, even when used in a controlled fashion with concomitant inhaled corticosteroids.     

Use of Inhaled Corticosteroids and Healthcare Costs in Mild Persistent Asthma

Healthcare costs were determined for mild persistent asthma patients (n = 796) who used inhaled corticosteroids infrequently (0 to 2 claims) or consistently (3 or more claims). Study patients, selected from a privately insured claims database (1999-2003), had at least one asthma diagnosis, no diagnosis of chronic obstructive pulmonary disease (COPD), and mild persistent asthma as defined by the 2005 Health Plan Employer Data and Information Set (HEDIS), Leidy's reliever and oral steroid methods, and the 2004 Global Initiative for Asthma (GINA) guidelines. Healthcare and asthma-specific costs were significantly higher for the infrequent inhaled corticosteroid users than the consistent users. The infrequent inhaled corticosteroid users had significantly more hospitalizations and emergency department visits compared with consistent users.     

Use of Inhaled Corticosteroids and Healthcare Costs in Mild Persistent Asthma

Healthcare costs were determined for mild persistent asthma patients (n = 796) who used inhaled corticosteroids infrequently (0 to 2 claims) or consistently (3 or more claims). Study patients, selected from a privately insured claims database (1999–2003), had at least one asthma diagnosis, no diagnosis of chronic obstructive pulmonary disease (COPD), and mild persistent asthma as defined by the 2005 Health Plan Employer Data and Information Set (HEDIS), Leidy's reliever and oral steroid methods, and the 2004 Global Initiative for Asthma (GINA) guidelines. Healthcare and asthma-specific costs were significantly higher for the infrequent inhaled corticosteroid users than the consistent users. The infrequent inhaled corticosteroid users had significantly more hospitalizations and emergency department visits compared with consistent users.     

Association of Exhaled Nitric Oxide to Asthma Burden in Asthmatics on Inhaled Corticosteroids

Background. Fractional exhaled nitric oxide (FENO) is a marker of airway inflammation. Its role in assessing asthma burden in clinical practice needs more study. Objective. To determine whether higher FENO levels are associated with greater asthma burden. Methods. This was a multicenter cross-sectional retrospective study of atopic 12- to 56-year-old persistent asthmatics on inhaled corticosteroids (ICS). Questionnaire and 1-year retrospective administrative data were used to analyze by unadjusted and adjusted robust Poisson regression (relative risks) and negative binomial regression [incidence rate ratios (IRRs)] the associations of masked FENO levels (NIOX MINO®) to short-acting beta-agonist (SABA) dispensings and oral corticosteroid (OCS) use in the past year independent of spirometry and an asthma control tool [Asthma Control Test (ACT)]. Results. FENO levels ranged from 7–215ppb (median 28ppb) in 325 patients. Higher FENO levels significantly correlated with more SABA dispensings and OCS courses in the past year, lower FEV₁% predicted levels, but not ACT score. FENO highest (≥48ppb) versus lowest (≤19ppb) quartile values were associated independently in the past year with ≥7 SABA canisters dispensed (relative risk=2.40, 95% CI=1.25–4.62) and total number of SABA canisters dispensed (IRR=1.46, 95% CI=1.12–1.99) and with ≥1 OCS course (relative risk=1.48, 95% CI=1.06-2.07) and total number of OCS courses (IRR=1.71, 95% CI=1.09–2.66). The significant independent relationship of higher FENO levels to increasing SABA dispensings and OCS courses was confirmed by linear trend analyses. Conclusions. Independent and clinically meaningful associations between higher FENO levels and greater asthma burden during a prior year in persistent asthmatics on ICS suggest that FENO measurement may be a complementary tool to help clinicians assess asthma burden.     

Personality Influences the Reporting of Side Effects of Inhaled Corticosteroids in Asthma Patients

Rationale. Negative affectivity is a measure of anxiety associated with increased reporting of symptoms. Few studies have explored this association with respect to drug-induced symptoms in patients taking medication for a chronic disease in real life. Objectives. In this cross-sectional study we examined the relationship between negative affectivity and self-reported side effects of inhaled corticosteroids in patients with asthma. We also investigated differential associations due to side effect type (subjective versus observable side effects) and treatment impact (i.e., hierarchical dosing). Methods. A total of 228 asthma patients, taking inhaled corticosteroids, completed scales measuring inhaled corticosteroid-induced side effects (Inhaled Corticosteroid Questionnaire scored: 0 = none; 100 = worst) and negative affectivity (Positive and Negative Affect Schedule scored: 10–50). Patients were grouped into low, average, and high negative affectivity groups based on published norms. Results. Patients high in negative affectivity reported significantly greater (p < 0.001) side effects (median score 20.5 (IQR: 11.4–33.0) than the groups of patients scoring lower on this measure (low negative affectivity: 7.1 (3.1–15.6); average: 13.3 (4.9–23.3)). The relationship between negative affectivity and side effects was stronger among patients taking low (r = 0.40–0.45) rather than mid to high inhaled corticosteroid doses (r = 0.16–0.28). Conclusions. Asthma patients with higher negative affectivity using inhaled corticosteroids report increased medication-induced symptoms. Clinicians should be aware that aside from inhaled corticosteroid dosage, the personality of the patient is an important factor in the reporting of drug-related side effects.     

Leukotriene Receptor Antagonists: A Good Choice in the Treatment of Premenstrual Asthma?

The aim of this study was to investigate the effects of leukotriene receptor antagonists (LTRAs) on the premenstrual exacerbation of asthma (PMA). Twenty-four female patients with mild asthma were enrolled in the study. Patients were followed for three menstrual cycles and separated into two groups based on whether they exibit premenstrual worsening of asthma symptoms (n = 11) or not (n = 13). During the first month all were treated with only inhaled steroids (IS) (run-in period); during the second month they received IS plus placebo; and during the third month they were given IS plus montelukast. Furthermore, they were advised to use beta ₂ -agonists as needed. Peak expiratory flow rate (PEFR) and symptom scores were recorded during the 3 months. Pulmonary function tests (PFT) and the levels of oestrogen, progesterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured a week before the begining of the menstrual period. At the end of the 3-month period, it was observed that following therapy with montelukast, the patients with PMA showed significant improvement in PEFR variability and symptom scores when compared with the placebo group. Baseline FSH levels were higher, but FSH and other hormone levels and PFTs did not change in these groups. However, in the group without PMA there was no difference between the montelukast or placebo groups in PEFR variability, symptom scores, PFTs, and hormone levels. Based on the data in hand, it could be stated that LTRAs have ensured the control of symptoms and improved PEFR variability in patients with PMA by supressing inflammation. We are of the view that LTRAs would be a right choice in the treatment of patients with PMA.     

Add-on Effects of Suplatast Tosilate in Bronchial Asthma Patients Treated With Inhaled Corticosteroids

Th2 cytokines play an important role in the pathogenesis of asthma. In the present study, we investigated the effect of suplatast tosilate, a selective Th2 cytokine inhibitor, on asthma control, in terms of subjective symptoms and pulmonary function in patients treated with inhaled corticosteroids. Thirty-eight patients with bronchial asthma being treated with inhaled corticosteroids were given suplatast tosilate (100 mg three times daily) for 12 weeks, in a multicenter setting. During the study period, other medications were continued. Morning and evening peak expiratory flow, asthma symptoms, blood eosinophil count and serum IgE levels were monitored. Suplatast tosilate treatment was associated with a significant improvement in mean morning peak expiratory flow (from 295 L/min to 348 L/min, P < 0.01) and evening peak expiratory flow (from 313 L/min to 357 L/min, P < 0.01). The mean daily variation in peak expiratory flow was significantly reduced (from 11.6% to 7.3%, P < 0.01) by suplatast tosilate treatment. The greatest improvement in peak expiratory flow was observed in patients whose blood eosinophil counts were decreased by suplatast tosilate treatment. Treatment with suplatast tosilate improved pulmonary function in patients with bronchial asthma. Our results suggest the therapeutic effects observed may occur through suppression of eosinophilic inflammation.     

High-Dose Inhaled Budesonide May Substitute for Oral Therapy After an Acute Asthma Attack

Patients attending the emergency room with acute asthma, participating in a study comparing salbutamol (albuterol in the United States) via a dry powder inhaler (Turbuhaler®) with pressurized metered-dose inhaler (pMDI), were included in this 1-week follow-up study with the aim of assessing whether inhaled budesonide via Turbuhaler may be an alternative to prednisolone tablets after an acute asthma attack. Eighty-one patients with a mean age of 38 years and forced expiratory volume in 1 sec (FEV₁) of 64% predicted normal value after treatment with salbutamol were randomized in this double-blind, double-dummy, parallel-group study. The doses given were budesonide 1600 μg b.i.d. or prednisolone in daily doses from 40 mg (day 1) decreased to 5 mg (day 7). FEV₁ was recorded before and after the 7-day treatments and peak expiratory flow (PEF) morning and evening, clinical symptoms (visual analogue scale 0–100), and doses of rescue medication (terbutalineTurbuhaler 0.25 mg/dose) were recorded daily. The mean increase in FEV, from baseline to day 7 was 1 7.3% in the budesonide Turbuhaler group and 1 7.6% in the prednisolone group. Mean values of morning PEF increased from day 1 to day 7 by 67 L/min in the budesonide Turbuhaler group and by 57 L/min in the prednisolone group (not significant). There were no statistically significant differences between the groups in clinical symptoms and in the number of doses of rescue medication. Because of disease deterioration, five patients in the Turbuhaler group and three in the prednisolone group needed additional symptomatic as well as corticosteroid treatment. Inhaled budesonide in high doses may be a substitute for oral therapy as follow-up treatment after an acute asthma attack.