Pycnogenol® as an Adjunct in the Management of Childhood Asthma

A randomized, placebo‐controlled, double‐blind study involving 60 subjects, aged 6–18 years old, was conducted over a period of 3 months to determine the effect of Pycnogenol® (a proprietary mixture of water‐soluble bioflavonoids extracted from French maritime pine) on mild‐to‐moderate asthma. After baseline evaluation, subjects were randomized into two groups to receive either Pycnogenol® or placebo. Subjects were instructed to record their peak expiratory flow with an Assess® Peak Flow Meter each evening. At the same time, symptoms, daily use of rescue inhalers (albuterol), and any changes in oral medications were also recorded. Urine samples were obtained from the subjects at the end of the run‐in period, and at 1‐, 2‐, and 3‐month visits. Urinary leukotriene C₄/D₄/E₄ was measured by an enzyme immunoassay. Compared with subjects taking placebo, the group who took Pycnogenol® had significantly more improvement in pulmonary functions and asthma symptoms. The Pycnogenol® group was able to reduce or discontinue their use of rescue inhalers more often than the placebo group. There was also a significant reduction of urinary leukotrienes in the Pycnogenol® group. The results of this study demonstrate the efficacy of Pycnogenol® as an adjunct in the management of mild‐to‐moderate childhood asthma.     

Comparison of Mometasone Furoate Dry Powder Inhaler and Fluticasone Propionate Dry Powder Inhaler in Patients with Moderate to Severe Persistent Asthma Requiring High-Dose Inhaled Corticosteroid Therapy: Findings from a Noninferiority Trial

Background. Inhaled corticosteroids (ICSs) are one of the suggested first-line therapies for patients with persistent asthma of moderate severity. Methods: The efficacy and safety of mometasone furoate (MF) 400 μg twice daily (BID) and fluticasone propionate (FP) 500 μ g BID administered for 12 weeks via dry powder inhaler (DPI) were compared in a noninferiority trial, in adults with moderate-to-severe persistent asthma. The primary variable was the change from baseline in am peak expiratory flow rate (PEFR). pm PEFR, forced expiratory volume in 1 second (FEV₁), asthma symptoms, rescue medication use, response to therapy, exacerbation rates, and adverse events were also assessed. Results. The lower bound of 95% CIs for treatment differences in the primary variable ranged from 2.6% to 5.6% throughout the 12-week study and were within the prespecified noninferiority range. No significant between-group differences were observed in lung function, rescue medication use, response to therapy, exacerbation rates, or adverse events. At most of the weeks assessed, there were no between-group differences in asthma symptoms. Most adverse events were mild-to-moderate. Conclusion. MF-DPI 400 μ g BID was therapeutically equivalent to FP-DPI 500 μ g BID in patients with moderate-to-severe persistent asthma.     

Efficacy Response of Inhaled HFA-Albuterol Delivered via the Breath-Actuated Autohaler™ Inhalation Device Is Comparable to Dose in Patients with Asthma

Handling difficulties, such as poor coordination of actuation and inhalation, are common in patients using press and breathe (P&Bs) metered-dose inhalers to administer asthma medication. Although spacers can help overcome some difficulties, the cumbersome nature of these devices often detracts from their use for the administration of rescue medications, where portability is important. This randomized, placebo-controlled, multicenter, crossover study investigated the efficacy, dose-response and safety of HFA-albuterol delivered via a breath-actuated Autohaler inhalation device in comparison with the same medication delivered using a conventional P&B device. In total, 39 patients received six study treatments in a random sequence at clinic visits separated by 2-7 days: 2 puffs from a HFA-placebo Autohaler; 1, 2, or 4 puffs from a HFA-albuterol Autohaler; 1 or 2 puffs from a HFA-albuterol P&B. Both active inhalers delivered 90 µg albuterol base equivalent/actuation from the actuator. The change from baseline in forced expiratory volume in 1 s (FEV₁) and the area under the FEV₁ curve (FEV₁ AUC) were significantly greater than placebo for all active treatment groups (p ≤ 0.01) and were suggestive of a dose response for each inhaler. Examination of the pooled slope of the dose responses for the Autohaler and P&B using Finney's Parallel Line Bioassay Methodology found a highly statistically significant relationship indicating the equivalence of the two inhalers on both parameters (p ≤ 0.002). The relative potency of the two inhalers was 0.8 (95% CI: 0.47, 1.46) for the mean change from baseline in FEV₁ and 0.9 (95% CI, 0.56, 1.48) for the change from baseline in FEV₁ AUC. There was also a trend toward an increase in the mean percentage change from baseline in FEV₁ as the number of puffs increased for both inhalers. Furthermore, there were no significant differences between the treatment groups with regard to time to onset of bronchodilator effect and the duration of effect was significantly greater than placebo (p ≤ 0.01) in each of the active groups. Adverse events were generally mild to moderate in nature and were of similar incidence (≤18% of patients) in each group. This study demonstrates a dose-response for HFA-albuterol on bronchodilation using both the Autohaler and P&B devices and illustrates that, in patients with good coordination of inhalation with actuation, the efficacy and safety of the two inhalers is similar at equivalent doses.     

Formoterol Delivered via the Dry Powder Aerolizer® Inhaler Versus Albuterol MDI and Placebo in Mild-to-Moderate Asthma: A Randomized, Double-Blind, Double-Dummy Trial

The objectives of this study were to compare the efficacy and tolerability of twice-daily formoterol dry powder 12 µg and 24 µg (Foradil) delivered via Aerolizer inhaler with four times daily albuterol (salbutamol) 180 µg delivered via metered dose inhaler (MDI) and placebo. A total of 554 adolescents and adults (ages 12-75 years) with mild-to-moderate asthma were randomized to this 12-week, multicenter, double-blind, double-dummy, placebo-controlled, parallel-group study. Twelve-hour spirometry measurements were taken at weeks 0, 4, 8, and 12. A total of 484 patients completed the study (122, 116, 127, and 119 given formoterol 12 µg, formoterol 24 µg, albuterol, and placebo, respectively). For the primary efficacy variable, the forced expiratory volume in 1 second (FEV₁), both formoterol 12 µg and 24 µg were statistically superior to placebo at all time points on all test days (p ≤ 0.017) and to albuterol at most time points on all test days (p ≤ 0.001). The onset of improvement in FEV₁ was rapid, with 15% increase within 5 min in 57%, 71%, and 65% of formoterol 12 µg, formoterol 24 µg, and albuterol patients, respectively. Formoterol was also superior to placebo and albuterol in terms of secondary efficacy variables: FEV₁ area under the curve, percentage of predicted FEV₁, forced vital capacity and forced expiratory flow, asthma symptom scores, and peak expiratory flows. In conclusion, both formoterol doses were superior to placebo in all lung function measurements. Overall, compared with albuterol, both formoterol doses produced superior bronchodilation. Formoterol and albuterol were safe and well-tolerated.     

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.     

Comparison of Oral Bambuterol and Terbutaline in Elderly Patients with Chronic Reversible Airflow Obstruction

Bambuterol, a carbamate prodrug of terbutaline, is the first once-daily oral β₂-agonist. The effect/side effect ratio of bambuterol oral solution was compared with terbutaline mixture in elderly patients with chronic reversible obstructive airways disease. The study was of a double-blind, crossover, randomized design and consisted of a 4-7-day run-in period followed by four consecutive treatment periods each of 2 weeks. The treatments were bambuterol solution 20 mg nocte (B20), 10 mg nocte (B10), terbutaline mixture 3 mg t.i.d., (T), and placebo solution (P). Patients measured daily peak expiratory flow rate (PEFR), asthma symptoms, use of inhaled β₂-agonist, and tremor. Of 84 patients, 66 completed all periods. Mean age was 67 years (60-90), basal FEV₁1.49 L, and reversibility of FEV¹ 30%. Ninety-four percent of the patients used inhaled/oral steroids in constant dosage. All treatments were significantly more effective than placebo. B20 resulted in higher morning PEFR than T (306 × 2.9 L/min vs. 297 × 2.9 L/min), while B10 gave equivalent results to T. No differences were seen in the use of inhaled β-agonist. Less shortness of breath was experienced during the night with B20 and during the day with B10 compared with placebo. Both B20 and T produced more tremor than B10 and P. In elderly patients with chronic reversible airways obstruction once-daily bambuterol (10-20 mg) has a better effect/side effect ratio than 3 mg terbutaline thrice daily.     

A One-Week Dose-Ranging Study of Inhaled Salmeterol in Children with Asthma

This was a 1-week study evaluating the safety and efficacy of two dosage regimens of salmeterol in children with asthma. A total of 243 children, aged 4-11 years, with mild-to-moderate asthma were enrolled in a randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating salmeterol xinafoate 21 μg and 42 μg administered via metered-dose inhaler (MDI) twice daily for 1 week. Patients were allowed to use albuterol MDI as needed for relief of acute symptoms. Inhaled corticosteroids and/or cromolyn at fixed dosages could be continued during the study, but theophylline and oral β-agonists were not allowed. Twelve-hour serial spirometry (for patients aged 6-11 years) and serial peak expiratory flow rate (PEFR) (all patients) were performed on days 1 and 8 of treatment; morning and evening PEFR were recorded each day prior to inhalation of the study drug. Safety was assessed by monitoring adverse events, clinical laboratory values, vita signs, electrocardiogram (ECC), and 24-hr ECG (Holter) monitoring. Both the 21 -μg and 42-μg doses of salmeterol produced significantly greater bronchodilation, as measured by 12-hr serial forced expiratory volume in 1 sec (FEV₁) (p ≤ 0.02) and PEFR (p ≤ 0.001), than did placebo on days 1 and 8. A small dose-response was observed, with the 42-μg dosage producing consistently higher serial FEV₁and PEFR than did the 21 -μg dosage, although the differences were not statistically significant. Morning and evening PEFR increased significantly (p ≤ 0.008) with both dosages of salmeterol compared with placebo. Twelve patients (5%) experienced potentially drug-related adverse events, with headache (4% in each salmeterol group) being the most common. There were no clinically significant changes in heart rate as measured by Holter monitoring, ECCs, vital signs, or clinical laboratory values following treatment with either dose of salmeterol. Salmeterol 21 μg or 42 μg twice daily was effective in producing bronchodilation in children aged 4-11 years, and both dosages had good safety profiles. Patients treated with salmeterol 42 μg twice daily showed a trend toward greater improvement in asthma control compared with those who received salmeterol 21 μg.     

Efficacy and Tolerability of Budesonide Clickhaler® and Turbuhaler® in Adult Asthma

New dry powder inhalers should be clinically comparable with established devices to ensure the continuity of effective therapy for asthma patients. This randomized, open, parallel group study compared the clinical efficacy and tolerability of budesonide delivered via Clickhaler® or Turbuhaler® dry powder inhalers in adults with mild to moderate stable asthma. Following a 4-week stabilizing period using budesonide Turbuhaler adults aged 18 years or older, who had been treated with inhaled corticosteroids for at least the previous 12 weeks, were randomized to receive budesonide twice daily (≤ 1600 µg/day) via either Clickhaler (n = 110) or Turbuhaler (n = 112) for 12 weeks. Morning peak expiratory flow (PEF), evening PEF, asthma symptoms, and use of inhaled short-acting β₂-agonist were recorded daily by the patients on diary cards. Lung function and tolerability data were recorded at clinic visits following 4, 8, and 12 weeks' treatment. Efficacy was measured primarily by mean change from the run-in baseline in weekly morning PEF. Of the 222 patients randomized to treatment, 167 completed the study according to the protocol. Repeated-measures analysis of covariance indicated that the devices were clinically equivalent; a treatment difference of - 2.3 L/min separated the group mean changes in weekly morning PEF (95% confidence interval - 7.9 to 3.3). Secondary analyses also supported clinical comparability. This study demonstrates the comparable clinical efficacy and tolerability of budesonide Clickhaler and Turbuhaler devices in adult patients with stable asthma.     

Clinical effects of pranlukast, an oral leukotriene receptor antagonist, in mild-to-moderate asthma: a 4 week randomized multicentre controlled trial

OBJECTIVE: Leukotriene antagonists are increasingly used in asthma management. Pranlukast is a new, orally active, selective inhibitor of CysLt1 leukotriene receptor. The present clinical trial was performed to study the effect and safety of pranlukast in mild-to-moderate asthma. METHODOLOGY: A randomized, double-blind, placebo-controlled, parallel group study was performed in eight medical centres in Korea. Mild-to-moderate asthma patients who had been treated with beta2-agonists and/or inhaled corticosteroids were studied. The patients' symptoms were evaluated by asthma diary and twice-daily peak flow monitoring. RESULTS: Of the 206 patients enrolled, 197 were eligible for analysis. The pranlukast group (n = 98) showed statistically significant improvement in asthma symptoms, including asthma attack rate, daily living score, and morning and evening asthma scores. Pranlukast significantly reduced the consumption of beta2-agonist. Compared with the placebo group, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were not significantly higher in the pranlukast group. Morning and evening peak expiratory flow (PEF) were significantly increased after pranlukast treatment at weeks 2 and 4 (380.8 +/- 10.1 L/min at baseline, 394.5 +/- 10.1 at week 2, 396.3 +/- 10.4 at week 4). There were no serious adverse reactions. CONCLUSION: Pranlukast, an oral leukotriene antagonist, was well tolerated and was effective for the management of mild-to-moderate asthma.     

Short-Term Regular β2-Adrenergic Agonists Treatment Is Safe in Mild Asthmatics Taking Low Doses of Inhaled Steroids

Regular treatment with β₂ adrenergic agonists is controversial in bronchial asthma. To investigate whether β₂-adrenergic agonists can be used safely if associated with low doses of inhaled steroids, for a short period, without a deterioration of asthma control, we have examined 24 mild asthmatics. In a parallel, double-blind, placebo-controlled study, 1 week of run-in and run-out period framed 3 weeks of treatment. All patients received inhaled beclometha-sone dipropionate (BDP 250 μg t.i.d.); after 1 week, 12 patients inhaled 400 μg of broxaterol and 12 patients received placebo t.i.d. FVC, FEV₁, PD₂₀-FEV₁ methacholine, morning and evening PEF, and PEF amplitude % mean were measured before, during, and after treatment. No significant changes were noted in patients receiving inhaled broxaterol. There were no differences in symptoms and the use of rescue medication (salbutamol spray). We conclude that short-term regular treatment with (β₂-adrenergic agonists is not associated with a deterioration in asthma control in mild asthmatics inhaling low doses of steroids.     

Airway Effects of Monosodium Glutamate in Subjects with Chronic Stable Asthma

We studied the effect of oral monosodium glutamate (MSG) on airways function in 12 subjects with a history of chronic stable asthma in a double-blind, randomized, crossover protocol. Subjects ingested either 25 mg/kg of MSG or sodium chloride (equimolar to MSG) following a 6-hour fast. Spirometry [forced expiratory volume in 1 second (FEV₁) and forced vital capacity] was performed before administration of the test substances and for a minimum of 4 hours thereafter. At no time during the observation period was the mean change in FEV₁ more negative following MSG than following placebo. MSG is unlikely to be a contributing factor in bouts of broncho-spasm in subjects with asthma, and routine avoidance of MSG by individuals with asthma need not be advised.     

Bronchial Reactivity to Inhaled Methacholine in Infants with Asthma and Age-Matched Controls

To evaluate bronchial hyperresponsiveness (BHR) in infants with asthma and the influence of aging on BHR during the infantile period, bronchial reactivity to inhaled methacholine (BRm) in infants was monitored using the transcutaneous oxygen pressure (tcPO₂) method. One hundred thirty-seven infants with asthma (from 1 to 5 years, mean 3.4 years) and 97 age-matched children without chronic respiratory diseases (from 6 months to 5 years, mean 2.1 years) were enrolled in this study. Consecutive doses of methacholine were doubled until a 10% decrease in tcPO₂ from the baseline was reached. The cumulative dose of methacholine at the inflection point of tcPO₂ (D_min-PO₂) was considered to represent the reactivity of tcPO₂ to inhaled methacholine. D_min-PO₂ values in the asthma groups were lower than those in the control groups in each year-group from 1 to 5. There was no statistical difference in D_min-PO₂ among the 1-4-year-old asthma groups, but D_min-PO₂ in the 5-year-old asthma group was significantly lower than D_min-PO₂ in the 1 -4-year-old asthma groups. The same age-related change in D_min-Po₂ was also seen in the control groups. There was no difference in age-related D_min-PO₂ change between the female group and the male group. We concluded that BRm in asthmatic children increases during the infantile period, and that the age-related changes in BRm, observed in both asthmatic and control infants, may have an effect on the clinical symptoms of asthma during childhood.     

A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge

OBJECTIVES: To compare the effects of addition of montelukast or salmeterol to inhaled corticosteroids (ICS) on the response to rescue beta2-agonist use after exercise-induced bronchoconstriction. METHODS: A double-blind, placebo-controlled study was performed at 16 centers in the United States. Patients with asthma (n = 122, ages 15-58) whose symptoms were uncontrolled on Low-dose inhaled fluticasone and who had a history of exercise-induced worsening of asthma were randomized to receive either montelukast (10 mg once daily), salmeterol (50microg twice daily), or placebo for 4 weeks. Standardized spirometry after exercise challenge and beta2-agonist rescue was performed at baseline, week 1 and 4. RESULTS: Maximum achievable forced expiratory volume in 1 s (FEV1) percent predicted after rescue beta2-agonist improved in the montelukast (+1.5%) and placebo (+1.2%) groups at 4 weeks, but diminished in the salmeterol (-3.9%) group (P < 0.001). Although pre-exercise FEV1 was greatest with salmeterol (P = 0.10), patients taking montelukast had significantly greater protection from an exercise-induced decrease in FEV1 than those taking salmeterol (P < 0.001). Both the magnitude and rate of rescue bronchodilation were greater with montelukast compared with salmeterol (P < 0.001). Five minutes after rescue beta2-agonist, 92% of patients taking montelukast and 68% of those taking placebo had recovered to pre-exercise levels, whereas only 50% of those taking salmeterol had recovered to pre-exercise levels. CONCLUSION: In patients whose asthma symptoms remain uncontrolled using ICS, addition of montelukast permits a greater and more rapid rescue bronchodilation with a short-acting beta2-agonist than addition of salmeterol and provides consistent and clinically meaningful protection against exercise-induced bronchoconstriction.     

A Clinical Trial of the Buteyko Breathing Technique in Asthma as Taught by a Video

The Buteyko Breathing Technique (BBT) is promoted as a drug-free asthma therapy. It is based on the premise that raising blood Pa_CO2 through hypoventilation can treat asthma. Our study was designed to examine whether the Buteyko Breathing Technique, as taught by a video, is an efficacious asthma therapy. Thirty-six adult subjects with mild to moderate asthma were randomized to receive either a BBT or placebo video to watch at home twice per day for 4 weeks. Asthma-related quality of life, peak expiratory flow (PEF), symptoms, and asthma medication intake were assessed both before and after intervention. Our results demonstrated a significant improvement in quality of life among those assigned to the BBT compared with placebo (p = 0.043), as well as a significant reduction in inhaled bronchodilator intake (p = 0.008). We conclude that the BBT may be effective in improving the quality of life and reducing the intake of inhaled reliever medication in patients with asthma. These results warrant further investigation     

Improving Asthma Care for the Elderly: A Randomized Controlled Trial Using a Simple Telephone Intervention

Background. Several studies suggest that asthma is undertreated in the elderly population. Objective. To determine if the use of a simple telephone intervention can improve asthma care in the elderly. Methods. Fifty-two elderly subjects with asthma who required their rescue inhalers more than twice a week and had at least one emergency department or urgent care visit in the previous year were randomized to an intervention or control group. All subjects received two telephone calls over a 12-month period. The intervention group received an asthma-specific questionnaire and the control group received a general health questionnaire. Medication use and health care utilization were evaluated at the beginning and end of a 12-month period. Results. The study was completed by 23 control and 25 intervention subjects. Baseline data were similar in both groups. After 12 months, 72% (n = 18) of the intervention group were on an inhaled corticosteroid compared with 40% (n = 10) of the control group (p = 0.08). The intervention group had fewer emergency department visits when compared with the control group (p = 0.21). Sixty-four percent (n = 16) of the intervention group had an asthma action plan compared with 26% (n = 6) in the control group (p = 0.01). Conclusion. This study suggests that asthma care in the elderly can be improved using a simple telephone intervention. Clinical implications. Clinicians need to recognize that under treatment of asthma in the elderly still exists and to use alternative methods such as a simple telephone questionnaire to improve care in this population.     

Efficacy and Tolerability of Budesonide Clickhaler® and Turbuhaler® in Adult Asthma

New dry powder inhalers should be clinically comparable with established devices to ensure the continuity of effective therapy for asthma patients. This randomized, open, parallel group study compared the clinical efficacy and tolerability of budesonide delivered via Clickhaler® or Turbuhaler® dry powder inhalers in adults with mild to moderate stable asthma. Following a 4-week stabilizing period using budesonide Turbuhaler adults aged 18 years or older, who had been treated with inhaled corticosteroids for at least the previous 12 weeks, were randomized to receive budesonide twice daily (≤ 1600 µg/day) via either Clickhaler (n = 110) or Turbuhaler (n = 112) for 12 weeks. Morning peak expiratory flow (PEF), evening PEF, asthma symptoms, and use of inhaled short-acting β₂-agonist were recorded daily by the patients on diary cards. Lung function and tolerability data were recorded at clinic visits following 4, 8, and 12 weeks' treatment. Efficacy was measured primarily by mean change from the run-in baseline in weekly morning PEF. Of the 222 patients randomized to treatment, 167 completed the study according to the protocol. Repeated-measures analysis of covariance indicated that the devices were clinically equivalent; a treatment difference of ? 2.3 L/min separated the group mean changes in weekly morning PEF (95% confidence interval ? 7.9 to 3.3). Secondary analyses also supported clinical comparability. This study demonstrates the comparable clinical efficacy and tolerability of budesonide Clickhaler and Turbuhaler devices in adult patients with stable asthma.     

The C523A β2 Adrenergic Receptor Polymorphism Associates with Markers of Asthma Severity in African Americans

Our goal was to explore associations between β₂ adrenergic receptor polymorphisms and markers of asthma severity in African American and Caucasian patients with asthma. Polymorphisms at loci -1023, -654, -47, 46, 79, 491, and 523 were genotyped and haplotypes were imputed in 143 African Americans and 336 Caucasians. C523A genotype associated with percentage of African Americans (but not of Caucasians) having an asthma exacerbation: AA, AC, and CC genotypes were 17, 29, and 40%, respectively (p = 0.018). Symptom scores, pulmonary function, and rescue inhaler use paralleled exacerbation prevalence. We conclude the 523 A allele modifies asthma severity in African Americans.     

Expression of Transforming Growth Factor β1 in Bronchial Biopsies in Asthma and COPD

The role of transforming growth factor β₁ (TGF β₁) in airway remodeling in asthma and chronic obstructive pulmonary disease (COPD) has not been fully described. To evaluate the possible pathogenetic role of TGF β₁ in asthma and COPD, immunohistochemical expression of TGF β₁ was described in bronchial biopsies from patients with asthma and COPD compared with healthy individuals. Twelve subjects with asthma, 13 subjects with COPD, and 10 healthy individuals enrolled in the study. Bronchial biopsies were stained with hematoxylin and eosin and anti-TGF β₁ antibody. As a result, immunoreactive TGF β₁ was mainly localized in association with connective tissue in all groups. The staining intensity was not statistically different among the groups in bronchial epithelium, whereas it was significantly higher in the group of asthma in the submucosa. Because there is evidence showing a significant increase of staining intensity in the submucosa from asthmatics but not from subjects with COPD, we may conclude that TGF β₁ may play a significant role in pathogenesis of asthma but not in COPD.     

Formoterol induces tolerance to the bronchodilating effect of Salbutamol following methacholine-provocation test in asthmatic children

OBJECTIVES: To study whether Formoterol treatment affect the bronchodilator response to salbutamol after methacholine-provocation test (MPT) in asthmatic children. STUDY DESIGN: A prospective, double-blind, randomized, placebo-controlled study. Children aged 7-16 years with mild-persistent to moderate asthma treated with inhaled corticosteroids, were enrolled. After 2-weeks of run-in period, subjects were randomized to inhaled Formoterol 9 microg bid (n=19) or placebo (n=19) for 2 weeks. MPT with salbutamol-recovery curve was performed at the beginning and at the end of the trial period. Measurements of peak expiratory flow rate (PEFR), symptoms score, rescue bronchodilator usage and side effects were recorded daily. The primary end-points were the change in FEV1 0-10 min after salbutamol inhalation and the recovery time from 80 to 100% of pretest FEV1. Statistical analyses were performed by ANOVA with repeated measures. RESULTS: There was a decrease in the bronchodilator response to salbutamol and an improved PEFR in the Formoterol group. There was no difference in all other parameters. CONCLUSION: Formoterol decreases the bronchodilator response to salbutamol following MPT. Whether this phenomenon has clinical implication during acute asthma needs further studies.     

Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial.

Leukotriene antagonists block the proinflammatory actions of leukotrienes (LT) and have been introduced as new treatments for asthma. Conventional therapy with glucocorticosteroids does not inhibit the biosynthesis of leukotrienes. We therefore tested whether addition of the leukotriene receptor antagonist montelukast was of therapeutic benefit in a group of aspirin-intolerant patients with asthma of whom 90% already were treated with moderate to high doses of glucocorticosteroids. Under double-blind conditions, 80 aspirin-intolerant patients with asthma were randomized to receive 4 wk oral treatment of either 10 mg of montelukast or placebo once daily at bedtime. Pulmonary function was measured as forced expiratory volume in 1 s (FEV(1)) once a week in the clinic and daily as morning and evening peak expiratory flow rate (PEFR). Asthma symptoms and use of rescue bronchodilator were also recorded daily. Asthma specific quality of life (QoL) was assessed before and after the treatments. The group receiving montelukast showed a remarkable improvement of their asthma, whereas the group given placebo showed no change. Thus, from equal baseline values, the mean difference between the groups over the 4-wk treatment period was 10.2% for FEV(1) and 28.0 L for morning PEFR (p for both < 0.001). The improved pulmonary function in the group receiving montelukast occurred at the same time as 27% less bronchodilator was used (p < 0.05), and it was associated with fewer asthma symptoms than in the group given placebo, including 1.3 nights more of sleep per week and 54% fewer asthma exacerbations (p < 0.05). There was also an improvement in asthma-specific QoL (p < 0.05). The therapeutic response to montelukast was consistent across patients with different baseline characteristics and did not correlate with baseline urinary LTE(4). Addition of a leukotriene receptor antagonist such as montelukast improves asthma in aspirin-intolerant patients over and above what can be achieved by glucocorticosteroids.