Comparison between the effects of generic and original salmeterol/fluticasone combination (SFC) treatment on airway inflammation in stable asthmatic patients.

BACKGROUND: Little is known about the effect of inhaled corticosteroids (ICS)/long-acting beta2 agonists (LABA) in combination on inflammatory markers in asthma. In addition, therapeutic equivalence of generic salmeterol/fluticasone combination (SFC) and original SFC is as yet unknown. OBJECTIVE: To determine the effects of SFC and the effects of generic and original SFC on airway inflammation in patients with mild-to moderate stable asthma. MATERIAL AND METHOD: A randomized double-blinded, crossover non-inferiority study was conducted to compare the antiinflammatory effects of generic SFC and original SFC on sputum eosinophils as a primary outcome and fractional exhaled nitric oxide (FENO) as a secondary outcome. PATIENTS: The authors studied 51 mild-to-moderate asthmatic patients who ranged from 18 to 80 years of age and were treated with ICS or ICS/LABA of any dose, and whose asthma was stable without an exacerbation episode for at least 3 months prior to study entry. RESULTS: Both sputum eosinophils percentage and absolute eosinophil counts well correlated with FENO levels at baseline prior to the initiation of study medications. Significant reduction in sputum eosinophil percentage was observed following generic SFC and original SFC treatment. The degree of sputum eosinophil suppression by generic SFC was not inferior to original SFC, and this was not affected by treatments with the sequence of generic SFC first vs. original SFC second or original SFC first vs. generic SFC. In addition, there was no significant difference between treatments in terms of normalized gain in asthma control scores, including the number of patients found to have improved asthma control, irrespective of sequence, as change from baseline. However, this was not the case for the magnitude of FENO reduction that occurred after generic SFC treatment to a significantly larger extent than original SFC treatment. CONCLUSION: This short-term study demonstrated that there was no significant difference between generic SFC and original SFC in terms of anti-inflammatory activity and the control of asthma symptoms. However, it is completely unknown whether generic SFC could effectively prevent the development of asthma exacerbations on a long-term basis. Therefore, longer-term studies are indicated to evaluate generic SFC's relative efficacy on asthma exacerbations.

Bronchodilator effect of Ipraterol on methacholine-induced bronchoconstriction in asthmatic patients.

BACKGROUND: The addition of ipratropium, a synthetic cholinergic antagonist, to beta2-agonist therapy provides an additive improvement in adult with acute severe asthma and COPD because of increased vagal tone in the airways. We asked whether ipratropium in combination with fenoterol (Ipraterol) improved pulmonary function in comparison with original Berodual. MATERIAL AND METHOD: In order to determine the effects of nebulized a single dose of Ipraterol, the study was conducted in a double-blind, randomized and crossover manner by comparing the effect of nebulized a single dose of Berodual on methacholine-induced bronchoconstriction. The study consisted of an 1-week run-in phase and two study visits separated by a washout period of 7 days. PATIENTS: We studied 20 patients who ranged from 18 to 80 years of age and had mild to moderate persistent asthma. RESULTS: Nebulized Ipraterol provided a rapid onset of bronchodilation effect similar to nebulized Berodual within 5 minutes by significantly increasing FEV, from 1.19 L to 1.73 L (p < 0.001) and from 1.19 to 1.69 L (p = 0.0001), respectively. This effect of Ipraterol lasted as long (up to 6 hours) and was similar to that of Berodual. The absolute FEV1 values at 360 min after Ipraterol treatment was still higher than the baseline values. We also found that there were no significant differences in the degree of improvement in FEV1 and hypokalemia following treatment with Ipraterol and Berodual. CONCLUSION: Our data suggest that nebulized Ipraterol offers a statistically significant improvement in pulmonary function without significant systemic absorption causing hypokalemia, with the improvement being comparable to that achieved with nebulized Berodual.

IgE production in allergic asthmatic patients with different asthma control status.

BACKGROUND: Although much is known about the fact that IgE-mediated allergic inflammatory response contributes to airway inflammation, bronchial hyperresponsiveness, and asthma severity, little is known about the degree of IgE response in allergic asthmatics during treatment. OBJECTIVE: To determine the amount of total serum IgE among allergic asthmatic patients with various asthma controls. MATERIAL AND METHOD: A total of 190 non-smoking patients with allergic asthma were divided into three groups by using the asthma control definition according to the GINA 2006 criteria. There were 64 well-controlled, 88 partly-controlled, and 38 uncontrolled. After study entry, patients underwent lung function test, methacholine challenge and skin prick test to establish allergic status. Peripheral venous blood specimens were collected to measure total IgE and absolute eosinophil numbers. The data are expressed as mean +/- SD. RESULTS: The logarithm of total serum IgE was significantly higher in subjects with uncontrolled allergic asthma than in those with well-controlled disease (p < .0001). IgE response in uncontrolled asthmatics was still high despite having been treated with ICS at a dose which was significantly high when compared with well-controlled subjects (1075.4 +/- 420 vs. 703.5 +/- 355, p < .0001). The logarithm of total serum IgE was associated with increased blood eosinophil counts (r = 0.25, p .0007) among three asthmatic groups and with decreased prebronchodilator FEV1 (r = -0.42, p = .0075) and PC20 (r = -0.36, p = .04) only in uncontrolled group. CONCLUSION: In allergic asthmatic patients with various disease control stages, there are differences in IgE immune response. Both high and non-suppressible total serum IgE response may be involved in the development of uncontrolled asthma.

Occurrence and protective level of influenza infections using serology in patients with COPD in vaccination study.

OBJECTIVE: To investigate the prevalence, occurrence and protective level of influenza infections using serology in patients with chronic obstructive pulmonary disease (COPD) during a one-year influenza vaccination study. MATERIAL AND METHOD: A total of 123 patients with COPD were enrolled during the period of 1997 to 1998. There were 61 patients in the vaccine group and 62 patients in the placebo group with a mean age +/- SD of 67.6 +/- 8.0 and 69.1 +/- 7.5, respectively. The vaccine was composed of influenza A/Texas/36/91 (H1N1), A/Nanchang/933/95 (H3N2) and B/Harbin/07/94 strains. Antibodies to influenza viruses were detected by hemagglutination inhibition (HI) test using antigens of vaccine strains. RESULTS: The incidence of influenza proven by serological examination was 22/123 (17.9%) cases. Among 17/62 (27.4%) influenza cases in the placebo group representing natural infections, 3 (17.6%) were diagnosed as A (H1N1), 8 (47.1%) as A (H3N2), 3 (17.6%) as type A, 1 (5.9%) as type B and 2 (11.8%) as untypeable viruses. The 8.2% of influenza cases found in the vaccine group was significantly lower than 27.4% of that in the placebo group (Chi-square test, p = 0.01). The protection rate of influenza vaccination was 71%. Among 23 acute blood samples from 22 influenza cases, the titers ranged from < 10 to 20 corresponding to its type/subtype. In the vaccine group, 5 influenza cases occurred at 7, 7, 10, 11 and 11 months after vaccination. The HI antibodies to influenza A (H1N1), A (H3N2) and B viruses at titers of > or = 10 vs > or = 40 were 50.4% vs 21.9%, 54.5% vs 28.5% and 17.9% vs 4.1%, respectively. CONCLUSION: The findings indicated that from 1997 to 1998, the occurrence of influenza as natural infection was 27.4%. Influenza A (H3N2) was more frequently prevalent than A (H1N1) and B viruses. The influenza vaccination in COPD patients was effective. The protective HI antibody titers were > or = 40. The patients without protective HI antibody to A (H1N1), A (H3N2) and B viruses were 78.1%, 71.5% and 95.9%, respectively. Such patients were considered to be at high-risk for influenza and recommended to have vaccination.

The cost-effectiveness of a questionnaire as a screening test for chronic obstructive pulmonary disease among the Bangkok elderly.

This study aimed to explore the cost-effectiveness of using a questionnaire as a screening test for Chronic Obstructive Pulmonary Disease (COPD) among the Bangkok elderly residing around Siriraj Hospital. The gold standard used for diagnosing COPD followed the guidelines of the Thoracic Society of Thailand. The questionnaire consisted of 10 questions on smoking status, respiratory symptoms and previous history of pulmonary tuberculosis. There were 3,094 elderly who participated, completed the questionnaire, and underwent spirometry as well as chest radiography in the community. The results showed that elderly individuals who are smokers (> 0.5 pack-year) or have ever experienced sudden cough with chest oppression or dyspnea when the weather changes or who have expectorated more than two tablespoons of sputum would be suspected of having COPD with a sensitiviy of 81.4 per cent (95% CI 79.4-83.4), specificity of 62.2 per cent (95% CI 60.4-64.0) false negative rate 1.2 per cent (95% CI 0.7-1.7) and false positive rate 38 per cent (95% CI 35.3-40.7) and subsequently required spirometry and chest X-ray for definitive diagnosis. The test needed to screen 17 elderly individuals to detect one COPD case at a cost of 1,538 baht. This questionnaire is also a self-assessment tool for COPD screening among the elderly in order to encourage them to seek for early medical attention and it is recommended that this should be publicized via the mass media.

The cost-effectiveness of chest radiography as a screening test for chronic obstructive pulmonary disease among the Bangkok elderly.

Regular screening with chest radiography (CXR) in an annual physical check up of the elderly is most frequently practiced. This study aimed to identify the CXR indices and the cost-effectiveness of CXR as a screening test for Chronic Obstructive Pulmonary Disease (COPD) among the elderly in 124 urban communities of Bangkok around Siriraj Hospital. The gold standard for diagnosing COPD followed the guidelines of the Thoracic Society of Thailand. There were 3,094 subjects who participated, completed spirometry and a CXR. The selected nine indices from PA and lateral CXR for diagnosing COPD were based on the presence of hyperinflation. The positive criteria of each index were reported. The cut-off point of best average accuracy ie, Z score of the CXR was 0.07 with a sensitivity of 75.9 per cent (95% CI 70.2-81.6%), specificity of 72.4 per cent (95% CI 70.8-74.0%) and the best average accuracy of 74.1 per cent (95% CI 72.5-75.7%) whereas the cost-effective cut-off point of a Z score of CXR as a screening test for COPD was 0.04 at the lowest grand total cost. The cost to detect one case of COPD was 2,008 baht and needed to screen 17 elderly. It is suggested that CXR is probably not a suitable screening test for COPD in the elderly due to the complicated derivation of the CXR indices. However, its efficacy may be of some value in in-office diagnosis of COPD.

The most cost-effective screening method for chronic obstructive pulmonary disease among the Bangkok elderly.

Our previous studies demonstrated the high prevalence and incidence of Chronic Obstructive Pulmonary Disease (COPD) among the Bangkok elderly, as well as the cost-effectiveness of a questionnaire, chest radiography, and mini peak expiratory flow rate (miniPEF) as screening tools. This final study aimed to identify the most cost-effective screening method among individual, serial and parallel combinations of the above tools, based on the guidelines for diagnosing COPD of the Thoracic Society of Thailand. There were 3,094 elderly aged 60 years and over in 124 urban communities around Siriraj Hospital who participated and completed all the tests. The results showed that the most cost-effective screening method was the miniPEF at cut-off percentage of 62 per cent of predicted value. This needed to screen 19 elderly people at a cost of 923 baht to detect one case of COPD, with a false negative rate of 1.9 per cent (95%CI 1.3-2.5), a false positive rate of 17.5 per cent (95%CI 15.4-19.6). The questionnaire is the alternative choice of screening tool.

The cost-effectiveness of mini peak expiratory flow as a screening test for chronic obstructive pulmonary disease among the Bangkok elderly.

This study aims to explore the cost-effectiveness of Mini Peak Expiratory Flow (miniPEF) as a screening test for Chronic Obstructive Pulmonary Disease (COPD) among the elderly in 124 urban communities around Siriraj Hospital, using the gold standard of diagnosis based on the guidelines of the Thoracic Society of Thailand. There were 3,094 subjects who participated and completed all the tests. The results showed that the cut-off miniPEF percentage of predicted value of highest average accuracy was 62 per cent. The sensitivity was 72.7 per cent (95% CI 67.0-78.6) and the specificity was 81.1 per cent (95% CI 79.7-82.5) The cost of screening 19 elderly to detect one case of COPD is 923 baht, with a false negative rate of 1.9 per cent (95% CI 1.3-2.5%) and a false positive rate of 17.5 per cent (95% CI 15.4-19.6%). It is suggested that measuring a miniPEF is regarded as one of the cost-effective screening tests for COPD in the elderly.

The prevalence and incidence of COPD among urban older persons of Bangkok Metropolis.

COPD substantially affects the national healthcare resource and healthcare cost especially among the older persons. Identifying the accurate prevalence and incidence reflects the scale of problem posed by COPD. This epidemiological study using the criteria for diagnosing COPD based on ratio of FEV1.0/FVC less than 70 per cent and the reversibility of less than 15 per cent increase of post bronchodilator FEV1.0 in the absence of parenchymal lesions and cardiomegaly in CXR (PA and lateral view) revealed the prevalence (1998) of COPD among the 3094 older persons aged 60 years and over in the communities of Bangkok Metropolis 10 km around Siriraj Hospital was 7.11 per cent (95% CI: 6.21-8.01), whereas the incidence (1999) of COPD was 3.63 per cent (95% CI: 2.83-4.43). Both the prevalence and the incidence were increased with increasing age. The disease occurred predominantly among male smokers. The distribution of mild : moderate : severe COPD in the prevalence study was 5.6:2.2:1. The current findings also suggest that tobacco smoking is the prime important cause of COPD and the indoor pollution especially cooking smoke is not significant. In particular, the unexpectedly high incidence compared with prevalence in this population probably represents the warning message to the national policy maker for prompt and effective health promotion and disease prevention to prevent further social and economic loss.