Budesonide/formoterol used for both maintenance and reliever therapy has been shown to benefit patients with persistent asthma. We evaluated patient satisfaction and asthma control among Malaysian patients prescribed budesonide/formoterol as single maintenance and reliever therapy in a real-life clinical practice.
Adult patients diagnosed with partially controlled or uncontrolled asthma were recruited in a 6-month, prospective, open-label study involving ten hospital-based chest clinics in Malaysia. Patients were prescribed one or two inhalations of budesonide/formoterol Turbuhaler (160/4.5 μg per inhalation) twice daily as maintenance therapy and additional inhalation as reliever therapy. Maintenance doses were decided by physicians based on Global Initiative for Asthma-defined treatment objectives. The primary outcome measure was the change in mean Satisfaction with Asthma Treatment Questionnaire (SATQ) scores from baseline to an average of 3 months and 6 months. Secondary outcome was the change in mean Asthma Control Questionnaire 5-item version (ACQ-5) scores from baseline to an average of 3 months and 6 months and the proportion of patients achieving the minimum clinically important difference.
Of 201 eligible patients recruited, 195 completed the study. Overall, SATQ mean (standard deviation) score was significantly improved from 5.1 (0.76) at baseline to 5.5 (0.58) (P < 0.001). The increase was observed in all domains of SATQ and had occurred at 3 months for most patients. ACQ-5 mean (standard deviation) score was significantly reduced from 2.2 (1.13) at baseline to 1.2 (0.95) (P < 0.001). A total of 132 (67.7.1%) patients had achieved the minimal clinically important difference (≥0.5) of ACQ-5 scores at study end.
In a nationwide study, budesonide/formoterol maintenance and reliever therapy achieved greater patient satisfaction and better asthma control compared with previous conventional asthma regimes among Malaysian patients treated in a real-life practice setting. Such an approach may represent an important treatment alternative for our local patients with persistent asthma.
asthma; asthma control; Malaysia; maintenance and reliever therapy; satisfaction; Symbicort; budesonide/formoterol
A 45-year-old man presented with a six-month history of progressive dyspnea with productive cough and wheezing. The patient was a heavy smoker and had a history of tongue cancer, hypertension, and asthma. Chest X-ray and computed tomography showed a mass lesion in the left hilar region and total collapse of the upper left lobe of the lung. Bronchoscopy revealed a whitish solid tumor obstructing the left upper lobe bronchus. Positron emission tomography showed increased tracer uptake in the lesion. A thoracoscopic lobectomy of the left upper lobe of the lung was performed. The final pathologic diagnosis was inflammatory myofibroblastic tumor.
We studied 8 adult patients with variable symptoms of cough, dyspnea, stridor, wheezing, or hemoptysis. Fiberoptic bronchoscopy in all showed complete or nearly complete endobronchial obstruction of a main-stem bronchus by neoplasm with a mean bronchial diameter of 1.9 mm +/- 1.6 mm (mean +/- standard deviation). In 4 patients, a lobar bronchus was also completely obstructed. No mass was visible on chest radiographs of any patient; however, computed tomography in each showed main-stem endobronchial obstruction, lobar obstruction (4 instances in 3 patients), and in 6 patients hypoperfusion of the involved lung. Computed tomographic scan showed additional abnormalities that were unsuspected on viewing chest radiographs or at bronchoscopy, including mediastinal adenopathy in 3 patients and an extraluminal tumor component in 4. After therapy with Nd-YAG laser, main-stem airway diameter increased to a mean of 9.6 mm +/- 1.0 mm (P less than .05) and pulmonary functions improved. Results suggest the complementary role of computed tomography and fiberoptic bronchoscopy in the detection and laser-treatment planning of chest radiographically occult severe neoplastic obstruction of the main-stem bronchus.
Schwannoma is a neurogenic tumor originating from the nerve sheath Schwann cells. Intrathoracic location is rare, and the endobronchial location is exceptional. Schwannoma is a rare tumor; the majority of lesions are benign and usually asymptomatic. The authors present a case report of a 83-year-old woman, nonsmoker, observed in the emergency department for wheezing and cough lasting for 2 months. Chest tomography showed a right hilar pulmonary mass, ill defined, with thick and irregular walls, centered on the upper lobe bronchus, which was obliterated. Fiberoptic bronchoscopy showed a necrotic mass obstructing the right upper lobe bronchus whose biopsy allowed the diagnosis of benign schwannoma. Subsequently, the patient carried tumor ablation by laser bronchoscopy, with the resolution of the respiratory symptoms. This case stands out for its rarity but also because it is an excellent example of the importance of endoscopic techniques for therapeutic purposes. Schwannoma is a benign tumor in which surgical or endoscopic intervention generally prevents local recurrence and associated clinical manifestations.
Current national and international asthma guidelines recommend treatment of children with asthma towards achieving and maintaining asthma control. These guidelines provide more stringent recommendations to increase therapy for patients with uncontrolled asthma in order to reduce asthma-related morbidity and mortality. Newer combination agents such as budesonide and formoterol have been shown to be safe and effective in treatment of asthma in children. Use of long-term controller agents like this in combination with improved compliance and treatment of co-morbid conditions have been successful in this endeavor. This review discusses control of pediatric asthma with focus on the use of budesonide in combination with formoterol.
asthma; control; children; budesonide; formoterol; long-term
To evaluate the effectiveness of montelukast as add-on therapy for asthmatic patients who remain uncontrolled with low, moderate or high doses of inhaled corticosteroid monotherapy.
An eight-week, multicentre, open-label, observational study.
Of 320 patients enrolled, 288 (90.0%) completed the study. Of patients who had uncontrolled asthma symptoms (Canadian Asthma Consensus Guidelines Update, 2003) but were controlled according to the Asthma Control Questionnaire (ACQ score of less than 1.5), 93.9% maintained asthma control at week 8. Of patients with uncontrolled asthma at baseline for both definitions, 63.5% achieved asthma control by week 8. The mean ± SD ACQ score decreased from 1.13±0.28 to 0.57±0.50 (P<0.001) for controlled patients at baseline and from 2.38±0.73 to 1.03±0.80 (P<0.001) for patients who were uncontrolled at baseline, each representing a clinically significant improvement.
Montelukast add-on therapy is an effective alternative to inhaled corticosteroid monotherapy.
Asthma; Inhaled corticosteroids; Montelukast add-on
Tracheobronchial amyloidosis is an uncommon localized form of amyloidosis that can simulate a tracheal tumor. Clinical signs are not specific and the diagnosis is rarely given before performing a bronchoscopy with multiples biopsies.
We report the case of a 60-year-old Moroccan woman, complaining of dyspnea and wheezing for three years, who was treated at our institution for management of severe asthma. A bronchoscopy revealed a tumor formation of her trachea; multiples biopsies were performed and a diagnosis made of amyloid light-chain amyloidosis. She successfully received an endoscopic resection.
This case highlights the importance of routinely carrying out an endoscopy in any patient complaining of atypical bronchial symptoms or with uncontrolled asthma. Tracheal amyloidosis is a rare disease, confirmed by histological examination of bronchial biopsies, and the treatment of choice is based on the bronchoscopic resection.
This randomised, double-blind, 6-month study compared budesonide/formoterol for maintenance and relief with salmeterol/fluticasone and a fixed maintenance dose of budesonide/formoterol, both with terbutaline for relief. Following a 2-week run-in, 3335 symptomatic adults and adolescents (mean FEV1 73% predicted, mean inhaled corticosteroid dose 745 μg/day) received budesonide/formoterol 160/4.5 μg one inhalation bid plus additional inhalations as needed, salmeterol/fluticasone 25/125 μg two inhalations bid plus as-needed terbutaline or budesonide/formoterol 320/9 μg one inhalation bid plus as-needed terbutaline. Budesonide/formoterol for maintenance and relief prolonged the time to first severe exacerbation requiring hospitalisation, emergency room treatment or oral steroids (primary variable) vs. fixed-dose salmeterol/fluticasone and budesonide/formoterol (p = 0.0034 and p = 0.023 respectively; log-rank test). Exacerbation rates were 19, 16 and 12 events/100 patients/6 months for salmeterol/fluticasone, fixed-dose budesonide/formoterol and budesonide/formoterol for maintenance and relief, respectively, [rate reduction vs. fixed-dose salmeterol/fluticasone (0.61; 95% CI 0.49–0.76, p < 0.001) and vs. fixed-dose budesonide/formoterol (0.72; 95% CI 0.57–0.90, p = 0.0048)]. Budesonide/formoterol maintenance and relief patients used less inhaled corticosteroid vs. salmeterol/fluticasone and fixed-dose budesonide/formoterol patients. All treatments provided similar marked improvements in lung function, asthma control days and asthma-related quality of life. Budesonide/formoterol for maintenance and relief reduces asthma exacerbations and maintains similar daily asthma control at a lower overall drug load compared with fixed-dose salmeterol/fluticasone and budesonide/formoterol.
To compare the efficacy and safety of budesonide/formoterol (Symbicort®) with formoterol (Oxis®) in the treatment of patients with acute asthma who showed evidence of refractoriness to short-acting β2-agonist therapy.
In a 3 hour, randomized, double-blind study, a total of 115 patients with acute asthma (mean FEV1 40% of predicted normal) and a refractory response to salbutamol (mean reversibility 2% of predicted normal after inhalation of 400 μg), were randomized to receive either budesonide/formoterol (320/9 μg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 1280/36 μg]) or formoterol (9 μg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 36 μg]). The primary efficacy variable was the average FEV1 from the first intake of study medication to the measurement at 90 minutes. Secondary endpoints included changes in FEV1 at other timepoints and change in respiratory rate at 180 minutes. Treatment success, treatment failure and patient assessment of the effectiveness of the study medication were also measured.
FEV1 increased after administration of the study medication in both treatment groups. No statistically significant difference between the treatment groups was apparent for the primary outcome variable, or for any of the other efficacy endpoints. There were no statistically significant between-group differences for treatment success, treatment failure or patient assessment of medication effectiveness. Both treatments were well tolerated.
Budesonide/formoterol and formoterol provided similarly rapid relief of acute bronchoconstriction in patients with asthma who showed evidence of refractoriness to a short-acting β2-agonist.
Oral corticosteroids and inhaled bronchodilators with or without antibiotics represent standard treatment of COPD exacerbations of moderate severity. Frequent courses of oral steroids may be a safety issue. We wanted to evaluate in an out-patient setting whether a 2-week course of inhaled budesonide/formoterol would be equally effective for treatment of acute COPD exacerbations as standard therapy in patients judged by the investigator not to require hospitalisation.
This was a double-blind, randomised, non-inferiority, parallel-group, multicentre study comparing two treatment strategies; two weeks' treatment with inhaled budesonide/formoterol (320/9 μg, qid) was compared with prednisolone (30 mg once daily) plus inhaled formoterol (9 μg bid) in patients with acute exacerbations of COPD attending a primary health care centre. Inclusion criteria were progressive dyspnoea for less than one week, FEV1 30–60% of predicted normal after acute treatment with a single dose of oral corticosteroid plus nebulised salbutamol/ipratropium bromide and no requirement for subsequent immediate hospitalisation, i.e the clinical status after the acute treatment allowed for sending the patient home.
A total of 109 patients (mean age 67 years, 33 pack-years, mean FEV1 45% of predicted) were randomized to two weeks' double-blind treatment with budesonide/formoterol or prednisolone plus formoterol and subsequent open-label budesonide/formoterol (320/9 μg bid) for another 12 weeks. Change in FEV1 was the primary efficacy variable. Non-inferiority was predefined.
Non-inferiority of budesonide/formoterol was proven because the lower limit of FEV1-change (97.5% CI) was above 90% of the efficacy of the alternative treatment. Symptoms, quality of life, treatment failures, need for reliever medication (and exacerbations during follow-up) did not differ between the groups. No safety concerns were identified.
High dose budesonide/formoterol was as effective as prednisolone plus formoterol for the ambulatory treatment of acute exacerbations in non-hospitalized COPD patients. An early increase in budesonide/formoterol dose may therefore be tried before oral corticosteroids are used.
Clinical trial registration
This study was performed to assess the control asthma and quality of care of asthmatic patient in primary health care facilities in Saint-Petersburg, the second largest city in Russia.
We conducted telephone interviews with 205 asthma outpatients (aged 24 to 90 years). Asthma control was assessed by using the Asthma Control Test (ACT).
During the past 12 month spirometry were performed in 26.8%. Only 2% of outpatients were consulted by allergist and 26.8% - by respiratory physicians. Inhaled corticosteroids were prescribed to persistent asthma patients in 79.1%, oral steroids for maintenance therapy were used in 7.3% of outpatients. Fixed combination of budesonide/formoterol and fluticasone/salmeterol were used in 45.4%. Asthma was uncontrolled for 72.2% of patients.
Quality of diagnostics and treatment of asthma in primary health care is not sufficient and should be improved.
Divergent strategies have emerged for the management of severe asthma. One strategy utilises high and fixed doses of maintenance treatment, usually inhaled corticosteroid/long-acting β2-agonist (ICS/LABA), supplemented by a short-acting β2-agonist (SABA) as needed. Alternatively, budesonide/formoterol is used as both maintenance and reliever therapy. The latter is superior to fixed-dose treatment in reducing severe exacerbations while achieving similar or better asthma control in other regards. Exacerbations may be reduced by the use of budesonide/formoterol as reliever medication during periods of unstable asthma. We examined the risk of a severe exacerbation in the period after a single day with high reliever use.
Episodes of high reliever use were quantified and exacerbations occurring post-index day with these episodes were examined post hoc in two double-blind studies comparing the efficacy and safety of budesonide/formoterol maintenance and reliever therapy (Symbicort SMART™, Turbuhaler®) 160/4.5 μg twice daily plus as needed with similar or higher maintenance doses of ICS/LABA plus SABA or formoterol.
Budesonide/formoterol maintenance and reliever therapy significantly reduced the risk of episodes of high reliever use (>6 inhalations/day) vs. all alternative ICS/LABA regimens. With conventional fixed-dose treatment the need for exacerbation treatment within 21 days ranged from 6.0–10.1% of days post-index for all regimens compared with 2.5–3.4% of days with budesonide/formoterol maintenance and reliever therapy.
Budesonide/formoterol maintenance and reliever therapy reduces the incidence of high reliever episodes and the exacerbation burden immediately following these episodes vs. alternative ICS/LABA plus SABA regimens at up to double the maintenance dose of ICS.
These studies do not have registration numbers as they were conducted before clinical trial registration was required
Asthma; Asthma in primary care
Background. The control of severe bronchial asthma, such as corticosteroid-resistant asthma, is difficult. It is also possible that immunosuppressive agents would be effective for bronchial asthma.
Case Summary. A 55-year-old Japanese female presented with severe bronchial asthma controlled with tacrolimus. She had been diagnosed with bronchial asthma during childhood. Her asthma worsened, and a chest radiograph showed atelectasis of the left lung. Bronchoscopy revealed the left main bronchus to be obstructed with viscous sputum consisting of 82% neutrophils and no eosinophils. The atelectasis did not improve with corticosteroid treatment, but was ameliorated by administration of tacrolimus. Discussion. This patient had severe asthma due to neutrophilic inflammation of the airways. Tacrolimus is effective for treating severe asthma, for example, in corticosteroid-resistant cases.
Adjusting medication for uncontrolled asthma involves selecting one of several options from the same or a higher treatment step outlined in asthma guidelines. We examined the relative benefit of introducing budesonide/formoterol (BUD/FORM) maintenance and reliever therapy (Symbicort SMART® Turbuhaler®) in patients previously prescribed treatments from Global Initiative for Asthma (GINA) Steps 2, 3 or 4.
This is a post hoc analysis of the results of five large clinical trials (>12000 patients) comparing BUD/FORM maintenance and reliever therapy with other treatments categorised by treatment step at study entry. Both current clinical asthma control during the last week of treatment and exacerbations during the study were examined.
At each GINA treatment step, the proportion of patients achieving target levels of current clinical control were similar or higher with BUD/FORM maintenance and reliever therapy compared with the same or a higher fixed maintenance dose of inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) (plus short-acting β2-agonist [SABA] as reliever), and rates of exacerbations were lower at all treatment steps in BUD/FORM maintenance and reliever therapy versus same maintenance dose ICS/LABA (P < 0.01) and at treatment Step 4 versus higher maintenance dose ICS/LABA (P < 0.001). BUD/FORM maintenance and reliever therapy also achieved significantly higher rates of current clinical control and significantly lower exacerbation rates at most treatment steps compared with a higher maintenance dose ICS + SABA (Steps 2-4 for control and Steps 3 and 4 for exacerbations). With all treatments, the proportion of patients achieving current clinical control was lower with increasing treatment steps.
BUD/FORM maintenance and reliever therapy may be a preferable option for patients on Steps 2 to 4 of asthma guidelines requiring a more effective treatment and, compared with other fixed dose alternatives, is most effective in the higher treatment steps.
A reduced response to inhaled corticosteroids (ICS) has been reported in smoking asthmatic patients but the effects of other medications remain to be evaluated in this population.
Subjects and Methods:
We evaluated the effects of a combined therapy of budesonide 200 µg twice daily and formoterol 6 µg twice daily compared with budesonide 200 µg twice daily alone on asthma control questionnaire (ACQ), asthma quality of life questionnaire (AQLQ- Juniper), pulmonary function and airway inflammation, in a cross-over randomized double-blind study with treatment periods of two months separated by a one-month wash-out period. Seventeen smoking and 22 non-smoking patients not using inhaled corticosteroids with slightly uncontrolled mild asthma completed the study.
ACQ and AQLQ scores were similar in both groups at baseline and improved similarly after treatments. β2-agonist use was higher in smokers, regardless of the treatment received (p=0.03), as it was on baseline (p=0.003). Smokers treated with budesonide/formoterol showed an increase in the number of asthma episodes (intercurrent asthma symptoms, p=0.016) while non-smoking subjects had a significant decrease in these episodes (p=0.009). No difference was found between smokers and non-smokers in regard to post-treatment airway inflammatory parameters.
No significant differences were found between smoking and non-smoking subjects with mild asthma in regard to clinical changes in asthma control, pulmonary function and airway inflammation following a 2-month treatment period with budesonide or the association of budesonide and formoterol for a period of 2 months. This should be further explored in larger groups of subjects.
Asthma; formoterol; budesonide; smoking.
Symptom control in patients with moderate to severe persistent asthma is essential to reduce the significant morbidity associated with the disease. Poor adherence to controller medications has been identified as a major contributing factor to the high level of uncontrolled asthma. This review examines patient perspectives on, and preferences for, controller medications (inhaled corticosteroid and long-acting β2-agonist combinations [ICS/LABA]), and how this may affect adherence to therapy. Fluticasone/salmeterol and budesonide/formoterol, the currently available ICS/LABA combination products, have similar efficacy and tolerability based on a recent meta-analysis of asthma trials. Adherence is higher with the combination ICS/LABAs than when the components are administered separately. Investigations into patient preferences for desirable attributes of asthma medications indicate that an effective reliever with a fast onset and long duration of action is preferred and may lead to improved adherence. This rapid onset of effect was perceived and highly valued in patient surveys, and was associated with greater patient satisfaction. Thus, future research should be directed at therapy that offers both anti-inflammatory activity and a rapid onset of bronchodilator effect. To further improve patient adherence and treatment outcome, the effect of these characteristics as well as other factors on adherence should also be investigated.
budesonide/formoterol; fluticasone/salmeterol; adherence; onset of effect; patient satisfaction
We report a case of a 70-year-old woman who presented with mild exertional dyspnea and cough. Fiberoptic bronchoscopic findings revealed an endobronchial polypoid lesion with stenotic bronchus. The lesion was very similar to endobronchial tuberculosis. Histologic examination of the biopsy specimen demonstrated Actinomyces infection. There was a clinical response to intravenous penicillin therapy. Primary endobronchial actinomycosis must be considered in the differential diagnosis of an endobronchial lesion, especially endobronchial tuberculosis in Korea.
A case study of 39-year old man with persistent wheezing, episodes of haemoptysis and dry cough unsuccessfully treated with inhaled beta2-agonists and steroids for about 10 months. Chest radiograph revealed a disproportion in dimensions between both lungs, with the left one being smaller than the right one. Spirometry demonstrated a restrictive pattern. During bronchoscopy, a polypoid endobronchial tumor, localized in the left main bronchus, completely occluding its lumen, was found. The tumor was diagnosed as carcinoid. In this case, due to the lack of characteristic symptoms, diagnosis of carcinoid was delayed. Patients unsuccessfully treated for bronchial asthma or chronic obstructive pulmonary disease should undergo bronchoscopic examination.
Clinical trials in children with moderate to severe persistent asthma are limited.
To determine if azithromycin or montelukast are inhaled corticosteroid-sparing.
The budesonide dose [with salmeterol (50 mcg) twice daily] necessary to achieve control was determined in children 6–17 years of age with moderate to severe persistent asthma. After a budesonide-stable period of 6 weeks, children were randomized in a double-masked, parallel, multi-center study to receive once nightly azithromycin, montelukast, or matching placebos, plus the established controlling dose of budesonide (minimum 400 mcg BID) and salmeterol twice daily. Primary outcome was time from randomization to inadequate asthma control following sequential budesonide dose reduction.
Of 292 children screened, only 55 were randomized. Inadequate adherence to study medication (n=80) and improved asthma control under close medical supervision (n=49) were the major reasons for randomization failure. A futility analysis was requested by the Data Safety Monitoring Board. In data available for analyses, no differences were noted for either treatment compared to placebo in time to inadequate control status (median, weeks (95% CL) azithromycin: 8.4 (4.3, 17.3), montelukast 13.9 (4.7, 20.6), placebo 19.1 (11.7, infinity)), with no difference between the groups (logrank test, p = 0.49). The futility analysis indicated that even if the planned sample size was reached, results of this negative study were unlikely to be different and the trial was prematurely terminated.
Based upon these results, neither azithromycin nor montelukast is likely to be an effective ICS-sparing alternative in children with moderate to severe persistent asthma.
Asthma; Moderate to severe; Children; Macrolide; Leukotriene receptor antagonist; Clinical trial
Little is known about vitamin D status and its effect on asthma pathophysiology in children with severe, therapy-resistant asthma (STRA).
Relationships between serum vitamin D, lung function, and pathology were investigated in pediatric STRA.
Serum 25-hydroxyvitamin D [25(OH)D3] was measured in 86 children (mean age, 11.7 yr): 36 with STRA, 26 with moderate asthma (MA), and 24 without asthma (control subjects). Relationships between 25(OH)D3, the asthma control test (ACT), spirometry, corticosteroid use, and exacerbations were assessed. Twenty-two of 36 children with STRA underwent fiberoptic bronchoscopy, bronchoalveolar lavage, and endobronchial biopsy with assessment of airway inflammation and remodeling.
Measurements and Main Results
25(OH)D3 levels (median [IQR]) were significantly lower in STRA (28 [22–38] nmol/L) than in MA (42.5 [29–63] nmol/L) and control subjects (56.5 [45–67] nmol/L) (P < 0.001). There was a positive relationship between 25(OH)D3 levels and percent predicted FEV1 (r = 0.4, P < 0.001) and FVC (r = 0.3, P = 0.002) in all subjects. 25(OH)D3 levels were positively associated with ACT (r = 0.6, P < 0.001), and inversely associated with exacerbations (r=−0.6, P < 0.001) and inhaled steroid dose (r=−0.39, P = 0.001) in MA and and STRA. Airway smooth muscle (ASM) mass, but not epithelial shedding or reticular basement membrane thickness, was inversely related to 25(OH)D3 levels (r=−0.6, P = 0.008). There was a positive correlation between ASM mass and bronchodilator reversibility (r = 0.6, P = 0.009) and an inverse correlation between ASM mass and ACT (r = −0.7, P < 0.001).
Lower vitamin D levels in children with STRA were associated with increased ASM mass and worse asthma control and lung function. The link between vitamin D, airway structure, and function suggests vitamin D supplementation may be useful in pediatric STRA.
vitamin D; asthma; remodeling; airway smooth muscle; pediatrics
Asthma’s cost-effectiveness is a major consideration in the evaluation of its treatment options. Our objective was to perform a systematic review of the cost-effectiveness of asthma medications.
We performed a systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, OHE-HEED, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Health Technology Assessments Database, NHS Economic Evaluation Database, and Web of Science and reviewed references from key articles between 1990 and Jan 2008.
A total of 49 RCTs met the inclusion criteria. Maintenance therapy with inhaled corticosteroids was found to be very cost-effective and in uncontrolled asthmatics patients currently being treated with ICS, the combination of an ICS/LABA represents a safe, cost-effective treatment. The simplified strategy using budesonide and formoterol for maintenance and reliever therapy was also found to be as cost-effective as salmeterol/fluticasone plus salbutamol. Omalizumab was found to be cost-effective. An important caveat with regard to the published literature is the relatively high proportion of economic evaluations which are funded by the manufacturers of specific drug treatments.
Future studies should be completed independent of industry support and ensure that the comparator arms within studies should include dosages of drugs that are equivalent.
asthma; medication; cost-effectiveness; cost of illness; economic costs
Asthma is the most common chronic disease in young children. About 40% of all preschool children regularly wheeze during common cold infections. The heterogeneity of wheezing phenotypes early in life and various anatomical and emotional factors unique to young children present significant challenges in the clinical management of this problem. Anti-inflammatory therapy, mainly consisting of inhaled corticosteroids (ICS), is the cornerstone of asthma management. Since Leukotrienes (LTs) are chemical mediators of airway inflammation in asthma, the leukotriene receptor antagonists (LTRAs) are traditionally used as potent anti-inflammatory drugs in the long-term treatment of asthma in adults, adolescents, and school-age children. In particular, montelukast decreases airway inflammation, and has also a bronchoprotective effect. The main guidelines on asthma management have confirmed the clinical utility of LTRAs in children older than five years. In the present review we describe the most recent advances on the use of LTRAs in the treatment of preschool wheezing disorders. LTRAs are effective in young children with virus-induced wheeze and with multiple-trigger disease. Conflicting data do not allow to reach definitive conclusions on LTRAs efficacy in bronchiolitis or post-bronchiolitis wheeze, and in acute asthma. The excellent safety profile of montelukast and the possibility of oral administration, that entails better compliance from young children, represent the main strengths of its use in preschool children. Montelukast is a valid alternative to ICS especially in poorly compliant preschool children, or in subjects who show adverse effects related to long-term steroid therapy.
Leukotriene receptor antagonists; Asthma; Preschool children; Wheezing; Bronchiolitis
Background: Inhaled corticosteroids (ICS) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes. This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients. This double blind, randomised, parallel group, non-inferiority, multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma.
Methods: After a 1 month single blind run in period, patients inadequately controlled on inhaled budesonide (800 µg/day) were randomised to receive montelukast 10 mg + inhaled budesonide 800 µg/day (n=448) or budesonide 1600 µg/day (n=441) for 12 weeks.
Results: Both groups showed progressive improvement in several measures of asthma control compared with baseline. Mean morning peak expiratory flow (AM PEF) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group (33.5 v 30.1 l/min). During days 1–3 after start of treatment, the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group (20.1 v 9.6 l/min, p<0.001), indicating faster onset of action in the montelukast group. Both groups showed similar improvements with respect to "as needed" ß agonist use, mean daytime symptom score, nocturnal awakenings, exacerbations, asthma free days, peripheral eosinophil counts, and asthma specific quality of life. Both montelukast + budesonide and double dose budesonide were generally well tolerated.
Conclusion: The addition of montelukast to inhaled budesonide is an effective and well tolerated alternative to doubling the dose of inhaled budesonide in adult asthma patients experiencing symptoms and inadequate control on budesonide alone.
The use of a combination inhaler containing budesonide and formoterol as both maintenance and quick relief therapy (SMART) has been recommended as an improved method of using inhaled corticosteroid/long-acting β agonist (ICS/LABA) therapy. Published double-blind trials show that budesonide/formoterol therapy delivered in SMART fashion achieves better asthma outcomes than budesonide monotherapy or lower doses of budesonide/formoterol therapy delivered in constant dosage. Attempts to compare budesonide/formoterol SMART therapy with regular combination ICS/LABA dosing using other compounds have been confounded by a lack of blinding and unspecified dose adjustment strategies. The asthma control outcomes in SMART-treated patients are poor; it has been reported that only 17.1% of SMART-treated patients are controlled. In seven trials of 6–12 months duration, patients using SMART have used quick reliever daily (weighted average 0.92 inhalations/day), have awakened with asthma symptoms once every 7–10 days (weighted average 11.5% of nights), have suffered asthma symptoms more than half of days (weighted average 54.0% of days) and have had a severe exacerbation rate of one in five patients per year (weighted average 0.22 severe exacerbations/patient/year). These poor outcomes may reflect the recruitment of a skewed patient population. Although improvement from baseline has been attributed to these patients receiving additional ICS therapy at pivotal times, electronic monitoring has not been used to test this hypothesis nor the equally plausible hypothesis that patients who are non-compliant with maintenance medication have used budesonide/formoterol as needed for self-treatment of exacerbations. Although the long-term consequences of SMART therapy have not been studied, its use over 1 year has been associated with significant increases in sputum and biopsy eosinophilia. At present, there is no evidence that better asthma treatment outcomes can be obtained by moment-to-moment symptom-driven use of ICS/LABA therapy than conventional physician-monitored and adjusted ICS/LABA therapy.
Budesonide; formoterol; compliance; asthma control; exacerbation; study design; asthma; asthma guidelines; asthma pharmacology; perception of asthma/breathlessness
Multiple strengths of mometasone furoate/formoterol (MF/F) metered-dose inhaler combination therapy have been investigated as new treatments for asthma. We report efficacy/safety findings from an MF/F study in subjects with severe asthma previously uncontrolled on high-dose inhaled corticosteroids (ICS) with or without a long-acting ß2-agonist (LABA).
This was a 3-month, randomized, double-blind, parallel-group, multicenter study with a 2- to 3-week open-label run-in period during which subjects received mometasone furoate (MF) 400 μg twice daily (BID). Subjects (≥12 years) were randomized to MF/F 200/10 μg BID, MF/F 400/10 μg BID, or MF 400 μg BID. The primary endpoint was the area under the curve (AUC) of the change in serial (0−12 hours) forced expiratory volume in 1 second (FEV1) for MF/F 400/10 μg vs MF 400 μg from baseline to week 12. Adverse events (AEs) and other clinical safety measures were recorded.
728 subjects were randomized (mean: age, 47.9 years; asthma duration, 14.0 years; FEV1 % predicted, 66.3; reversibility, 22.9%; Asthma Control Questionnaire score, 1.93). Improvements in mean changes from baseline in FEV1 AUC0−12h at week 12 were: MF/F 200/10 μg = 3.59 L × h; MF/F 400/10 μg = 4.19 L × h; MF 400 μg = 2.04 L × h, with both MF/F doses significantly better than MF (P < 0.001). These FEV1 AUC0–12h values with MF/F 200/10 μg, MF/F 400/10 μg, and MF 400 μg correspond to average hourly increases of 0.30, 0.35, and 0.17 L, respectively. MF/F was associated with a rapid (<5 minutes) and sustained improvement in lung function. The percentages of subjects experiencing an asthma deterioration (ie, severe asthma exacerbation) were 12.4% (MF/F 200/10 μg), 12.2% (MF/F 400/10 μg), and 18.3% (MF 400 μg). There were no notable differences in AEs between the groups.
Both the 200/10 μg BID and 400/10 μg BID doses of MF/F combination therapy led to significantly greater improvements in lung function compared with 400 μg BID MF monotherapy in subjects with severe asthma previously treated with an ICS alone or in combination with LABA.