FEV1 Reversibility Research Articles

Which patients with chronic obstructive pulmonary disease benefit from the addition of an inhaled corticosteroid to their bronchodilator? A cluster analysis

ObjectiveTo identify subsets of chronic obstructive pulmonary disease (COPD) patients who are more protected from exacerbations with the use of an inhaled corticosteroid/long-acting β2 agonist (ICS/LABA) combination, compared with the...

Drugs potentially affecting the extent of airways reversibility on pulmonary function testing are frequently consumed despite guidelines

BackgroundThe increase in forced expiratory volume in one second (FEV1) effected by a bronchodilator is routinely assessed when patients undertake pulmonary function testing (PFT). Several drug classes can theoretically affect the magnitude of the increase in FEV1. Withholding periods are advised for many but not all such drugs. Anecdotally, many subjects presenting for PFT are found to have taken drugs that might affect the test. We did an audit of patients presenting for PFT to assess the frequency with which FEV1 reversibility might be affected by drugs.MethodsOne hundred subjects presenting to the laboratory for PFT were questioned about recent drug consumption by an independent pharmacy intern. Reversibility of FEV1 was assumed to have been affected if drugs of interest were consumed within defined withholding periods or two half-lives for drugs without such data.ResultsSixty-three subjects were prescribed drugs likely to affect FEV1 reversibility. Thirty-six subjects consumed at least one such drug within the withholding period. Half (18) of these patients consumed β-blockers with or without β-agonists. Sixty-five subjects did not recall receiving any advice about withholding drugs prior to the test and only 10 recalled receiving advice from their clinician or pulmonary function technician.ConclusionSubjects presenting for PFT are infrequently advised to withhold drugs that may affect FEV1 reversibility, and consequently, often take such drugs close to the time of the test. Therefore, it is likely that the increase in FEV1 is frequently affected by interference from drugs and this might impact on diagnosis and/or treatment options.

Efficacy and safety of AZD3199 vs formoterol in COPD: a randomized, double-blind study.

BackgroundWe investigated the efficacy and safety of AZD3199, a novel inhaled ultra-LABA, with the main aim of establishing a dose that would maintain 24-hour bronchodilation in patients with COPD.MethodsPatients (n = 329) were randomized to AZD3199 (200, 400 or 800 μg o.d.), formoterol (9 μg b.i.d.) or placebo via Turbuhaler® in a parallel group study. The primary objective of the study was to compare the clinical efficacy of three doses of AZD3199 inhaled once daily with 9 μg formoterol twice daily and placebo, over a 4-week treatment period in adults with moderate-to-severe COPD. After 4 weeks, peak (0–4 h) and trough (24–26 h) forced expiratory volume in 1 second (FEV1) were assessed as the primary efficacy outcome variables.ResultsAll AZD3199 doses significantly increased mean peak and trough FEV1 versus placebo (106–171 ml and 97–110 ml increases, respectively), but with no clear dose–response; the level of bronchodilation was comparable to or greater than that achieved with formoterol. Forced vital capacity (FVC) at peak bronchodilation also significantly increased with AZD3199 versus placebo (153–204 ml). COPD symptom scores and reliever use were reduced with AZD3199, while FEV1 reversibility was unaltered. Adverse events were mild-to-moderate, with no safety concerns identified. Drug exposure was dose-proportional, but lower than predicted from healthy volunteers.ConclusionsAll three doses of AZD3199 produced 24-hour bronchodilation, but with no clear dose–response, suggesting that doses of 200 μg or less may be sufficient to maintain bronchodilation over 24 hours in patients with COPD. No safety concerns were identified. Further studies are required to determine the once-daily AZD3199 dose for COPD.Trial registrationClinicaltrials.gov, NCT00929708

The Changes of Pulmonary Function in COPD During Four-Year Period

Conflict of interest: none declared.IntroductionCOPD (chronic obstructive pulmonary disease) is characterized by airflow limitation that is not fully reversible. OBJECTIVE: to show the changes of pulmonary function in COPD during the 4 -year evolution of illness.Material and MethodsThe research was done on patients suffering from COPD treated at the Clinic “Podhrastovi” during 2006 and 2007. The tested parameters were examined from the date of receiving patient with COPD to hospital treatment in 2006 and 2007 and then followed prospectively until 2010 or 2011 (the follow-up period was 4 years). There were total 199 treated patients who were chosen at random and regularly attended the control examinations. The study was conducted on adult patients of both sexes, different age group. In each patient the duration of illness was recorded so is sex, age, data of smoking habits, information about the regularity of taking bronchodilator therapy during remissions of disease, about the treatment of disease exacerbations, results of pulmonary functional tests as follows: FVC (forced vital capacity), FEV1 (forced expiratory volume in one second) and bronchodilator reversibility testing. All these parameters were measured at the beginning and at the end of each hospital treatment on the apparatuses of Clinic “Podhrastovi”. We took in elaboration those data obtained in the beginning of the first hospitalization and at the end of the last hospitalization or at the last control in outpatient department when patient was in stable state. Patients were divided into three groups according to the number of exacerbations per year.Resultsairflow limitation in COPD is progressive; both FVC and FEV1 shows the statistically significant decrease during follow-up period of 4 years (p values / for both parameters/ =0.05) . But in patients regularly treated in phases of remission and exacerbations of illness the course of illness is slower. The fall of FVC and FEV1 is statistically significantly smaller in those received regular treatment in phases of remissions and exacerbations of illness (p values / for both parameters/ =0.01). The number of patients responding properly to bronchodilators decreased statistically significantly in patients with COPD during follow-up period (p=0.05).ConclusionCOPD is characterized with airflow limitation which is progressive in the course of illness, but that course may be made slower using appropriate treatment during remission and exacerbations of diseases.

Abdominal adiposity and obstructive airway disease: testing insulin resistance and sleep disordered breathing mechanisms

BackgroundThis study examined associations of abdominal adiposity with lung function, asthma symptoms and current doctor-diagnosed asthma and mediation by insulin resistance (IR) and sleep disordered breathing (SDB).MethodsA random sample of 2500 households was drawn from the community of Whyalla, South Australia (The Whyalla Intergenerational Study of Health, WISH February 2008 - July 2009). Seven-hundred twenty-two randomly selected adults (≥18 years) completed clinical protocols (32.2% response rate). Lung function was measured by spirometry. Post-bronchodilator FEV1/FVC was used to measure airway obstruction and reversibility of FEV1 was calculated. Current asthma was defined by self-reported doctor-diagnosis and evidence of currently active asthma. Symptom scores for asthma (CASS) and SDB were calculated. Intra-abdominal fat (IAF) was estimated using dual-energy x-ray absorptiometry (DXA). IR was calculated from fasting glucose and insulin concentrations.ResultsThe prevalence of current doctor-diagnosed asthma was 19.9% (95% CI 16.7 – 23.5%). The ratio of observed to expected cases given the age and sex distribution of the population was 2.4 (95%CI 2.1, 2.9). IAF was not associated with current doctor-diagnosed asthma, FEV1/FVC or FEV1 reversibility in men or women but was positively associated with CASS independent of IR and SDB in women. A 1% increase in IAF was associated with decreases of 12 mL and 20 mL in FEV1 and FVC respectively in men, and 4 mL and 7 mL respectively in women. SDB mediated 12% and 26% of these associations respectively in men but had minimal effects in women.ConclusionsIn this population with an excess of doctor-diagnosed asthma, IAF was not a major factor in airway obstruction or doctor-diagnosed asthma, although women with higher IAF perceived more severe asthma symptoms which did not correlate with lower FEV1. Higher IAF was significantly associated with lower FEV1 and FVC and in men SDB mechanisms may contribute up to one quarter of this association.

<I>HELICOBACTER PYLORI</I> INFECTION IN NEVER-SMOKING MALE PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ITS RELATION TO LUNG FUNCTION

There is a recent epidemiologic and serologic evidence for relationship between Helicobacter pylori (H. pylori) infection and Chronic Obstructive Pulmonary Disease (COPD). In order to assess the relationship between H. pylori infection and COPD and its impact on lung function we performed a cross-sectional study including 84 never-smoking male patients with COPD and an equal number of never-smoking males without chronic respiratory disease matched to the COPD patients by age. Evaluation of the study subjects included evaluation of H. pylori serological status, baseline and post-bronchodilator spirometry. We found significantly higher H. pylori seropositivity in COPD patients than in controls (76.2 Vs 34.5%, p = 0.041). The prevalence of H. pylori seropositivity did not differ significantly between patients with mild, moderate and severe COPD. Borderline significance was registered for the difference of the forced expiratory volume in one second (FEV1) mean value between seropositive and seronegative COPD patients (56.4 vs. 59.2, p = 0.063). The mean degree of FEV1 reversibility did not differ significantly between seropositive and seronegative COPD patients. Our findings indicate that in cross-sectional analysis there is higher prevalence of H. pylori seropositivity in COPD than in non-COPD patients, as well as that H. pylori infection has not significant impact on lung function in COPD patients.

Asthma Control Test (ACT): Comparison with Clinical, Functional, and Biological Markers of Asthma Control

Background. Asthma Control Test (ACT) is a simple tool for assessing the level of asthma control in clinical practice, and it has been validated in comparison with a general clinical assessment of asthma control, including forced expiratory volume in the first second (FEV1). Objective. To evaluate the relationship between ACT score and clinical and functional findings of asthma control and biomarkers of airway inflammation. Methods. A total of 68 asthmatic patients observed in our asthma clinic (33 regularly treated with inhaled corticosteroids (ICS) and 35 ICS-naïve) filled ACT questionnaire and underwent the following measurements: (a) FEV1 before and after salbutamol; (b) exhaled nitric oxide; (c) bronchial hyperresponsiveness to methacholine; (d) sputum eosinophil count; and (e) daytime and nighttime symptoms, rescue salbutamol, and twice-daily peak expiratory flow (PEF) recording on a 4-week diary card. Results. ACT score significantly correlated with symptom score, rescue medication use, and PEF variability, but not with FEV1, FEV1 reversibility, and markers of airway inflammation, which could not distinguish controlled from uncontrolled patients according to ACT, regardless of ICS treatment. Conclusion. ACT score is a valid tool to simply assess the current level of asthma control in terms of symptoms, rescue medication use, and PEF variability. Pulmonary function and biomarkers of airway inflammation are not related to the clinical asthma control as assessed by ACT and may represent additional measurements potentially useful in asthma management.

Extracellular matrix in airway smooth muscle is associated with dynamics of airway function in asthma

Altered deposition of extracellular matrix (ECM) in the airway smooth muscle (ASM) layer as observed in asthma may influence ASM mechanical properties. We hypothesized that ECM in ASM is associated with airway function in asthma. First, we investigated the difference in ECM expression in ASM between asthma and controls. Second, we examined whether ECM expression is associated with bronchoconstriction and bronchodilation in vivo. Our cross-sectional study comprised 19 atopic mild asthma patients, 15 atopic and 12 nonatopic healthy subjects. Spirometry, methacholine responsiveness, deep-breath-induced bronchodilation (ΔR(rs) ) and bronchoscopy with endobronchial biopsies were performed. Positive staining of elastin, collagen I, III and IV, decorin, versican, fibronectin, laminin and tenascin in ASM was quantified as fractional area and mean density. Data were analysed using Pearson's or Spearman's correlation coefficient. Extracellular matrix expression in ASM was not different between asthma and controls. In asthmatics, fractional area and mean density of collagen I and III were correlated with methacholine dose-response slope and ΔR(rs) , respectively (r=0.71, P<0.01; r=0.60, P=0.02). Furthermore, ASM collagen III and laminin in asthma were correlated with FEV(1) reversibility (r=-0.65, P=0.01; r=-0.54, P=0.04). In asthma, ECM in ASM is related to the dynamics of airway function in the absence of differences in ECM expression between asthma and controls. This indicates that the ASM layer in its full composition is a major structural component in determining variable airways obstruction in asthma.

Efficacy in asthma of once-daily treatment with fluticasone furoate: a randomized, placebo-controlled trial

BackgroundFluticasone furoate (FF) is a novel long-acting inhaled corticosteroid (ICS). This double-blind, placebo-controlled randomized study evaluated the efficacy and safety of FF 200 mcg or 400 mcg once daily, either in the morning or in the evening, and FF 200 mcg twice daily (morning and evening), for 8 weeks in patients with persistent asthma.MethodsAsthma patients maintained on ICS for ≥ 3 months with baseline morning forced expiratory volume in one second (FEV1) 50-80% of predicted normal value and FEV1 reversibility of ≥ 12% and ≥ 200 ml were eligible. The primary endpoint was mean change from baseline FEV1 at week 8 in pre-dose (morning or evening [depending on regimen], pre-rescue bronchodilator) FEV1.ResultsA total of 545 patients received one of five FF treatment groups and 101 patients received placebo (intent-to-treat population). Each of the five FF treatment groups produced a statistically significant improvement in pre-dose FEV1 compared with placebo (p < 0.05). FF 400 mcg once daily in the evening and FF 200 mcg twice daily produced similar placebo-adjusted improvements in evening pre-dose FEV1 at week 8 (240 ml vs. 235 ml). FF 400 mcg once daily in the morning, although effective, resulted in a smaller improvement in morning pre-dose FEV1 than FF 200 mcg twice daily at week 8 (315 ml vs. 202 ml). The incidence of oral candidiasis was low (0-4%) and UC excretion was comparable with placebo for all FF groups.ConclusionsFF at total daily doses of 200 mcg or 400 mcg was significantly more effective than placebo. FF 400 mcg once daily in the evening had similar efficacy to FF 200 mcg twice daily and all FF regimens had a safety tolerability profile generally similar to placebo. This indicates that inhaled FF is an effective and well tolerated once-daily treatment for mild-to-moderate asthma.Trial registrationNCT00398645

Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma

BackgroundInhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD) evening and twice-daily (BD) regimens of the novel inhaled corticosteroid fluticasone furoate (FF) in asthma patients.MethodsPatients with moderate asthma (age ≥ 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV1) 40-85% predicted; FEV1 reversibility of ≥ 12% and ≥ 200 ml) were randomized to FF or fluticasone propionate (FP) regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for ≥ 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 μg OD, FF or FP 100 μg BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough) FEV1; non-inferiority of FF 200 μg OD and FF 100 μg BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs) and 24-hour urinary cortisol excretion were assessed.ResultsThe intent-to-treat population comprised 147 (FF) and 43 (FP) patients. On Day 28, pre-dose FEV1 showed FF 200 μg OD to be non-inferior (pre-defined limit -110 ml) to FF 100 μg BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml); all FF and FP regimens were significantly superior to placebo (p ≤ 0.02). AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 μg OD, 0.75; 100 μg BD, 0.84; p ≤ 0.02).ConclusionsFF 200 μg OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose.Trial registrationClinicaltrials.gov; NCT00766090.

Reduced apoptosis of CD8+ T-Lymphocytes in the airways of smokers with mild/moderate COPD

Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation in airways and lung parenchyma. CD8+ T-lymphocytes, crucial effector and regulatory cells in inflammation, are increased in the central and peripheral airways in COPD. The aim of this study was to assess the role of apoptosis in the accumulation of CD8+ T-lymphocytes within the airway wall in COPD. We examined the submucosa of transverse sections of central and peripheral airways from post-operative tissues from non-smokers (n=16), smokers with normal lung function (n=16), smokers with mild/moderate COPD (n=16), and smokers with severe/very severe COPD (n=9). TUNEL and immunohistochemistry techniques were used to identify apoptosis and cell phenotype, respectively. The percentage of apoptotic CD8+ T-lymphocytes was significantly lower (p<0.0001) in smokers with mild/moderate COPD than in non-smokers, smokers with normal lung function, and smokers with severe/very severe COPD, and was positively related to values of FEV(1) and FEV(1)/FVC ratio, both in central and in peripheral airways. These data suggest that reduced apoptosis of CD8+ T-lymphocytes may be an important mechanism that contributes to the accumulation of these cells in the airway submucosa in smokers with mild/moderate COPD.

Bronchial reversibility with a short-acting β2-agonist predicts the FEV1 response to administration of a long-acting β2-agonist with inhaled corticosteroids in patients with bronchial asthma

A long-acting β2-agonist (LABA) combined with an inhaled corticosteroid (ICS) is frequently prescribed as initial therapy in steroid-naïve asthma patients because of its effective control of symptoms and improvement of pulmonary function. However, it is unclear which patients will be responsive to LABAs and whether bronchial responsiveness to LABAs is similar to that to short-acting β2-agonists (SABAs) in a clinical setting. Therefore, the goal of the present study was to compare the changes in spirometric parameters after SABA (salbutamol) inhalation to those after 1-month LABA/ICS (salmeterol/fluticasone propionate) therapy. Spirometric changes were evaluated as absolute values, as the percentage of predicted normal values and as the percentage of baseline values after salbutamol inhalation or 1-month LABA/ICS therapy in 45 patients with asthma. Compared to SABA inhalation, LABA/ICS therapy produced significant improvements in forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF), forced expiratory flow at 50% of vital capacity expired (FEF50%) from baseline (expressed as the percentage predicted) in all patients. FEV1 and the FEV1/forced vital capacity (FVC) ratio after SABA or LABA/ICS therapy were inversely related to the corresponding baseline values. Analysis of spirometric changes after SABA inhalation showed that FEV1 was the best among spirometric parameters, such as PEF, correlated with responsiveness to LABA/ICS therapy. Reversibility of FEV1 with SABA inhalation predicts the spirometric response to LABA/ICS as initial therapy in patients with bronchial asthma. LABA/ICS therapy had a greater effect on bronchial reversibility in asthmatic patients, compared to SABA inhalation. This suggested that evaluation of bronchial reversibility after LABA/ICS therapy would be superior to that after SABA inhalation.

Exhaled nitric oxide in the diagnosis and management of bronchial asthma: From bench to bedside?

The identification of nitric oxide in exhaled breath and its role as a surrogate marker of eosinophilic inflammation of the airways led to rapid development in the area of its measurement. Standardized measurement techniques have been developed as well as simple, cheap, and reliable equipments. Although a number of factors have been identified as affecting its assay, fractional exhaled nitric oxide (FENO) can reliably be used to distinguish eosinophilic from non-eosinophilic airway inflammation. Unlike the other indirect measures of airway inflammation such as FEV1 reversibility and bronchoprovocative tests, FENO is noninvasive and gives a direct measure of inflammation. There are sufficient data supporting its role in the diagnosis of asthma, monitoring of disease, prediction of relapse, and level of compliance. Measurement of FENO has therefore made the transition from the bench to the bedside. Of recent, there are attempts at devising interpretative strategies for its use in day to day clinical practice.

Omalizumab in the management of oral corticosteroid-dependent IGE-mediated asthma patients

Background:Several studies have demonstrated the beneficial effects of omalizumab in asthma patients. Here we describe the drug’s tolerance and oral corticosteroid sparing capacity in a long-term observational study.Methods:Thirty-two patients aged ≥18 years with obstructive airway disease and FEV1 reversibility ≥12% and 200 mL, with an oral steroid requirement ≥7.5 mg per day of prednisolone during a period of ≥1 year, a positive prick test or in vitro reactivity (RAST) to at least one perennial aeroallergen and a baseline immunoglobulin E level ranking between 30–700 IU/mL were prospectively followed for 17.2 ± 8.5 months. Patients were visited once or twice a month, depending on their schedule for omalizumab administration. Intervention: blood analysis every six months; spirometry and nitric oxide measurement at every visit.Results:One patient who dropped out early was excluded. Follow-up period: the treatment benefited 83.9% (26/31) of the cohort; oral corticosteroids were reduced from 7.19 ± 11.1 to 3.29 ± 11.03 mg (p < 0.002) and withdrawn in 74.2% of patients. FEV1 (percent predicted) was 64.4 ± 22.7 at the beginning and 62.9 ± 24.3 at the end. IgE at entry was 322.2 ± 334.2 IU/mL and increased 2.34-fold. Respiratory function and NO did not present statistically significant changes. We identified three groups of patients: the first (n = 17) receiving oral steroid at entry in whom the accumulated dose of oral steroids progressively decreased; another (n = 10) including patients who had quit oral steroids before starting omalizumab although they had not been instructed to do so and whose oral steroid dose at the end of follow-up was zero; and a third group (n = 4) that did not benefit from omalizumab treatment. The only relevant side effect was a flu-like syndrome which required discontinuation of treatment in one patient.Conclusion:In our series, a substantial, safe decrease in oral corticosteroid requirements was observed due, at least to some extent, to omalizumab therapy. Oral corticosteroids were withdrawn in three-quarters of the patients. We were unable to identify a factor able to predict which patients would benefit most from omalizumab treatment.

Arginase 1 and arginase 2 variations associate with asthma, asthma severity and β2 agonist and steroid response

Arginase probably plays an important role in asthma development, severity and progression. Polymorphisms in arginase 1 and arginase 2 genes have been associated with childhood asthma and FEV1 reversibility to beta2 agonists. We investigated the association between arginase 1 and arginase 2 polymorphisms and adult asthma, asthma severity and treatment response in a longitudinal cohort of 200 asthma patients. Patients were studied during 1962-1975 and reexamined during 1990-1999, together with their families. Longitudinal data on lung function and treatment were extracted from medical records. Associations between haplotype-tagging polymorphisms in arginase 1 (n=3) and arginase 2 (n=8) and asthma, asthma severity, acute response to bronchodilators and chronic response to inhaled corticosteroids were analyzed. Two polymorphisms in arginase 2 (rs17249437 and rs3742879) were associated with asthma and with more severe airway obstruction. Increased airway hyperresponsiveness and lower beta2 agonist reversibility, but not anticholinergic reversibility, were associated with both arginase 1 and arginase 2. Inhaled corticosteroids slowed down the annual FEV1 decline, which was significantly less effective in homozygote carriers of the C-allele of the arginase 1 polymorphism, rs2781667. We show that previously reported associations between arginase polymorphisms and childhood asthma are also present in adult asthma and the previously found associations with lower reversibility are specific for beta2 agonists. Furthermore, we identified associations of arginase 1 and arginase 2 genes with asthma severity, as reflected by a lower lung function, more severe airway hyperresponsiveness, and less long-term response to inhaled corticosteroids. Studies on the functionality of the polymorphisms are warranted to further unravel the complex mechanisms underlying these observations.

Comparison of lung volume response with airflow response to bronchodilator in patients with chronic obstructive pulmonary disease

the reversibility of chronic obstructive pulmonary disease (COPD) is evaluated mainly by FEV(1) after bronchodilators. However, lung volumes also change significantly in COPD, but few studies addressed the characteristics of the changes in post bronchodilator airflow and lung volume in patients with COPD. This study was carried out to evaluate the difference of FEV(1) response and forced vital capacity (FVC) response to bronchodilators in patients with COPD as well as the impact of severity of COPD on the flow and volume reversibility. 465 patients with COPD (male 426, female 39), aged 67.1 +/- 8.3 (42 approximately 86) yrs were enrolled from Jan. 2006 to Aug. 2008. The severity of COPD was graded according to the GOLD criteria. The change and rate of change of FVC and FEV(1) 20 minutes after inhalation of salbutamol 400 microg via spacer were measured and compared. Positive response to the bronchodilator was determined as FEV(1) or FVC increased 12% as well as 200 ml or above. The impacts of severity on flow and volume response were also studied. post-bronchodilator FEV(1) increased 117 ml with a 13.2% improvement on average compared with baseline. Post-bronchodilator FVC increased 258 ml and improved by 14.0% on average. The rate of positive reversibility in FEV(1) and FVC was 18.7% (87/465) and 44.1% (205/465), respectively. The improvement of FEV(1) decreased as a function of the severity of COPD. In contrast, the improvement of FVC was increased in those with more severe disease. the improvement of lung volume is more significant and maybe more important than airflow response in patients with COPD, especially in those with severe disease. In addition to FEV(1), the reversibility of COPD should also be evaluated by FVC.

Predicting short term response to anti-inflammatory therapy in young children with asthma

Background:Currently available anti-inflammatory treatment for young children with asthma includes inhaled corticosteroids (ICS) and the leukotriene receptor antagonist (LTRA) montelukast.Objective:To evaluate potential biomarkers of predicting short-term (6-week) response to ICS and LTRAs in children with asthma.Methods:A total of 102 children aged 4 to 7 years with episodic asthma were enrolled in an open labelled single-centre study. Biomarkers and asthma characteristics were evaluated as predictors of treatment. Of 102 patients 45 became symptomatic during observation and were randomised to treatment either to montelukast or fluticasone for 6 weeks.Clinical trial registration:NCT00543686.Results:Forced Expiratory Volume in one second (FEV1) increased with both treatments: FEV1 at randomisation was 90.2% and after therapy 106.8% with fluticasone vs. 90.8% and 103.7% for montelukast, respectively, showing that montelukast and fluticasone were equally effective in this age group (p = 0.44). Strong correlations to a favourable treatment response were pre-bronchodilatory FEV1 (p < 0.001) and airway reversibility (p = 0.04) at time of randomisation. None of the other biomarkers (methacholine testing, exhaled nitric oxide [eNO], presence of allergy, total Immunoglobulin E [IgE], cumulative specific IgE, eosinophils and parental smoking) were predictive.Conclusion:Despite the small sample size and the open-label design, the study suggests that the use of pre-bronchodilatory FEV1 and airway reversibility appears to be a good indicator of short-term anti-inflammatory therapy in young children with asthma.

A Randomized Study Comparing the Effect of Loratadine Added to Montelukast with Montelukast, Loratadine, and Beclomethasone Monotherapies in Patients with Chronic Asthma

Background. Loratadine added to montelukast has been suggested to improve endpoints of asthma. Objective. This study investigated the additive effects of concomitant montelukast and loratadine when compared with montelukast, loratadine, and inhaled beclomethasone monotherapies in asthma. Methods. Patients (N = 406) were 15 to 65 years of age with a forced expiratory volume in 1 second (FEV1)-predicted of 50% to 85%, FEV1 reversibility ≥ 15%, and a minimal level of daytime symptoms and β -agonist use. This three-part 2X2 crossover-study consisted of two double-blind 6-week treatment periods where patients were administered once daily oral montelukast 10 mg, loratadine 10 mg, montelukast 10 mg + loratadine 10 mg, or twice daily inhaled beclomethasone 200 μ g. A subsequent 48-week extension study compared montelukast+loratadine with beclomethasone. The primary endpoint was the percentage change from baseline in FEV1. Results. Over 6 weeks of double-blind treatment, significant improvements (p < 0.05) in the primary endpoint of FEV1 were seen for montelukast+loratadine versus loratadine (least-square mean percentage-point difference of 5.8%), beclomethasone versus montelukast+loratadine (2.35%), montelukast versus loratadine (5.94%), and beclomethasone versus montelukast (4.65%); a numerical improvement (p = 0.054) was seen for montelukast+loratadine versus montelukast (1.60%). Significant improvements for montelukast+loratadine versus montelukast were seen in some secondary endpoints (evening peak expiratory flow, nocturnal asthma symptom score, nocturnal awakenings, and asthma-specific quality of life) but not others. Significant improvements in most endpoints except daytime asthma symptoms score were seen for montelukast+loratadine versus loratadine. In the extension study, both montelukast+loratadine and beclomethasone improved several endpoints. All treatments were generally comparable in the percentage of patients with clinical and laboratory adverse experiences. Conclusion. In this study, the addition of loratadine to montelukast produced a small numerical, but not statistically significant, improvement in FEV1 and, in general, no consistent improvement in other asthma endpoints. No improvement of montelukast+loratadine versus beclomethasone was seen in any endpoint.

S.140. FEV1 Reversibility in Mild Persistent and Intermittent Asthma in Iranian Children

S.140. FEV1 Reversibility in Mild Persistent and Intermittent Asthma in Iranian Children

Comparison of the clinical efficacy and safety of salmeterol/fluticasone propionate versus current care in the management of persistent asthma in Korea

ABSTRACTObjectives: In the Asia-Pacific region there is a general preference for prescribing oral over inhaled medications for the treatment of asthma. This study compared inhaled salmeterol/fluticasone propionate therapy (SFC) with physician-determined current care (CC) in the management of persistent asthma in Korea.Methods: Adult patients with a documented history of reversibility in FEV1 (≥ 12%) or PEF (≥ 15%), were randomised in a 2:1 ratio to unblinded treatment with SFC (50/250 μg bd or 50/500 μg bd) via Diskus (N = 284) or CC (N = 140) for 52 weeks. Morning peak expiratory flow (PEF) (primary endpoint), exacerbations, asthma symptoms and patient-reported outcome measures were recorded.Trial registration: GSK study number:100614.Results: At baseline, mean morning PEF in the SFC and CC group was 374 and 401 L/min respectively. The adjusted mean morning PEF at 52 weeks was 423 ± 3 and 396 ± 4 L/min for SFC and CC respectively (treatment difference of 27 ± 5 in favour of SFC; 95% CI 17, 37; p < 0.0001). The mean rate of exacerbations over 52 weeks was significantly lower in the SFC group (SFC/CC odds ratio 0.57; 95% CI 0.44, 0.74; p < 0.0001). Treatment with SFC also resulted in a significantly greater improvement in asthma symptoms, in the number of patients assessed to have well controlled asthma (Asthma Control Test score ≥ 20), and in a clinically significant improvement in overall Quality of Life. The incidence of adverse events was low and similar between the two groups and events were of the type expected in this population.Conclusions: The results of this open-label, randomised study showed that SFC provided greater asthma control than CC in the management of persistent asthma.