We investigated the effects of indacaterol on cough and phlegm in patients with stable chronic obstructive pulmonary disease (COPD). We performed a meta-analysis with five randomized controlled trials (RCTs) of indacaterol in stable COPD patients. The symptom severity was defined using the St. George's Respiratory Questionnaire (SGRQ). We analyzed patients treated with 150 microg (n = 945) and 300 microg (n = 832) out of 3,325 patients who completed the SGRQ from five RCTs. After a 12-week treatment of 150 microg indacaterol, cough improvement was reported in 36.5% (316/866) of patients treated with indacaterol vs. 32.2% (259/804) patients treated with placebo (Relative Ratio [RR], 1.13; 95% confidence interval [CI], 0.99-1.29). Phlegm improvement was reported in 31.0% (247/798) of patients treated with indacaterol vs. 30.6% (225/736) of patients treated with placebo (RR, 1.01; 95% CI, 0.87-1.18). Dyspnea improvement was reported in 39.5% (324/820) of patients treated with indacaterol vs. 31.5% (237/753) patients treated with placebo (RR, 1.33; 95% CI, 1.03-1.71; P = 0.001, I2 = 55.1%). Only dyspnea improvement was significant compared to placebo even at the 300 microg indacaterol dose. Compared to placebo, a 12-week treatment of the long-acting beta-agonist, indacaterol might not have a significant effect on cough or phlegm in stable COPD.
Administration, Inhalation ; Anti-Bacterial Agents/therapeutic use ; Bronchodilator Agents/*therapeutic use ; Cough/*drug therapy ; Dyspnea/*drug therapy ; Forced Expiratory Volume/drug effects ; Humans ; Indans/*therapeutic use ; Placebos/administration & dosage ; Pulmonary Disease, Chronic Obstructive/*drug therapy ; Quinolones/*therapeutic use ; Sputum/*drug effects ; Surveys and Questionnaires ; Treatment Outcome

The aim of this study was to investigate relationships between acute exacerbation and Forced Expiratory Volume 1 second (FEV1) improvement after treatment with combined long-acting beta-agonist (LABA) and inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD). A total of 137 COPD patients were classified as responders or nonresponders according to FEV1 improvement after 3 months of LABA/ICS treatment in fourteen referral hospitals in Korea. Exacerbation occurrence in these two subgroups was compared over a period of 1 yr. Eighty of the 137 COPD patients (58.4%) were classified as responders and 57 (41.6%) as nonresponders. Acute exacerbations occurred in 25 patients (31.3%) in the responder group and in 26 patients (45.6%) in the nonresponder group (P=0.086). FEV1 improvement after LABA/ICS treatment was a significant prognostic factor for fewer acute exacerbations in a multivariate Cox proportional hazard model adjusted for age, sex, FEV1, smoking history, 6 min walk distance, body mass index, exacerbation history in the previous year, and dyspnea scale.Three-month treatment response to LABA/ICS might be a prognostic factor for the occurrence of acute exacerbation in COPD patients.
Adrenal Cortex Hormones/*therapeutic use ; Adrenergic beta-2 Receptor Agonists/*therapeutic use ; Bronchodilator Agents/*therapeutic use ; Budesonide/therapeutic use ; Drug Therapy, Combination ; Female ; Fluticasone/therapeutic use ; Forced Expiratory Volume/drug effects/*physiology ; Formoterol Fumarate/therapeutic use ; Humans ; Male ; Pulmonary Disease, Chronic Obstructive/*drug therapy/physiopathology ; Recurrence ; Republic of Korea ; Salmeterol Xinafoate/therapeutic use ; Smoking ; Spirometry ; Treatment Outcome

BACKGROUND/AIMS: Amiodarone is one of the most widely used antiarrhythmic agents; however, amiodarone-induced pulmonary toxicity (APT) can be irreversible and sometimes fatal. The aim of this study was to evaluate the feasibility of chest computed tomography (CT) as a diagnostic tool for APT and to assess the utility of the CT APT score as an index for predicting the severity of APT. METHODS: Patients underwent amiodarone treatment for various reasons, most often atrial fibrillation, for more than 2 years, and those that received a cumulative dose > 100 g were enrolled. A total of 34 patients who underwent chest CT between December 2011 and June 2012 were enrolled, whether or not they had clinical symptoms. The APT CT score was defined as the number of involved regions in the lung, which was divided into 18 regions (right and left, upper, middle, and lower, and central, middle, and peripheral). The CT findings were evaluated according to the total dose and duration of amiodarone treatment and the results of a pulmonary function test. Clinical symptoms and outcomes were also evaluated according to APT CT scores. RESULTS: Seven patients had positive APT CT scores (interstitial fibrosis in five, organizing pneumonia in one, and mixed interstitial fibrosis and organizing pneumonia in one), and these patients exhibited significantly lower diffusion capacity for carbon monoxide in the lungs compared with patients without an increased APT CT score (70.2% +/- 6.9% vs. 89.7% +/- 19.4%; p = 0.011). Three of the seven patients experienced overt APT that required hospital admission. CONCLUSIONS: Chest CT is a useful diagnostic tool for APT, and the APT CT score might be a useful index for assessing the severity of APT.
Aged ; Amiodarone/*adverse effects ; Anti-Arrhythmia Agents/*adverse effects ; Atrial Fibrillation/diagnosis/*drug therapy ; Cross-Sectional Studies ; Cryptogenic Organizing Pneumonia/chemically induced/physiopathology/*radiography/therapy ; Feasibility Studies ; Female ; Forced Expiratory Volume ; Hospitalization ; Humans ; Lung/drug effects/physiopathology/*radiography ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Pulmonary Diffusing Capacity ; Pulmonary Fibrosis/chemically induced/physiopathology/*radiography/therapy ; Respiratory Function Tests ; Risk Factors ; Time Factors ; *Tomography, X-Ray Computed ; Vital Capacity

BACKGROUNDA pharmacokinetic study in an Asian population showed that tiotropium 5 µg via Respimat leads to the same plasma levels compared to 18 µg via HandiHaler. The objective of the trial was to compare the efficacy and safety of longterm treatment (1 year) with tiotropium bromide (5 µg) via Respimat® with placebo in patients with chronic obstructive pulmonary disease (COPD).

METHODSA total of 3991 patients were randomized in this double-blind, placebo controlled, parallel group study, while in China 338 patients (309 males, 29 females) received either tiotropium bromide (n = 167) or placebo (n = 171). Tiotropium bromide solution or matching placebo was delivered via Respimat® at a dosage of 5 µg (2×2.5 µg/puff) once daily for 48 weeks. Co-primary endpoints were trough forced expiratory volume in one second (FEV1) and the time to first exacerbation.

RESULTSStatistically significant improvements in trough FEV1 and trough forced vital capacity (FVC) in the tiotropium group were achieved at weeks 4, 24, and 48 compared with those in the placebo group. A statistically significant difference (P = 0.0027) in favour of tiotropium was also observed for the time to first exacerbation. The total numbers of exacerbations during treatment were 90 and 128 in the tiotropium and placebo groups, respectively, with a rate ratio of 0.69 (P = 0.0164). The difference between the treatment groups in the adjusted mean changes from baseline of St. George Respiratory Questionnaire (SGRQ) total score was -3.9 (95% CI: -7.5, -0.2) and was of statistical significance (P = 0.0367). The incidences of serious adverse events (SAEs) in the tiotropium and placebo groups were 16.2% and 17.0%, respectively. Seven deaths occurred whilst patients were on treatment, four in the tiotropium group and three in the placebo group, all of which were assessed as non-related study drugs by the investigators.

CONCLUSIONSTiotropium significantly improved lung function and quality of life, delayed the time to first exacerbation, reduced the number of exacerbations. Overall, tiotropium was well tolerated.

Administration, Inhalation ; Aged ; Bronchodilator Agents ; adverse effects ; therapeutic use ; Cholinergic Antagonists ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Forced Expiratory Volume ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; physiopathology ; Scopolamine Derivatives ; adverse effects ; therapeutic use ; Tiotropium Bromide

OBJECTIVETo observe changes in the lung function of asthmatic children with different symptoms during treatment, and to investigate the clinical significance of bronchial reversibility test in the treatment of asthma in children.

METHODSA total of 417 asthmatic children were treated by salmeterol/fluticasone inhalation for more than 3 months. These patients were divided into asymptomatic, single cough, paroxysmal cough and wheeze (cough+wheeze or wheeze alone) groups based on the symptoms when they revisited the clinic. Thirty-four healthy children were used as a control group. All children underwent bronchial reversibility test using nebulized salbutamol. Lung function testing was performed before and after the test.

RESULTSAfter nebulization of salbutamol, each asthma group showed significantly decreased rate of abnormal lung function and significantly increased forced expiratory volume in one second percent (FEV1%) predicted (P<0.05). Before salbutamol nebulization, the single cough, paroxysmal cough and wheeze groups had significantly higher rates of abnormal lung function and significantly lower FEV1% predicted than the control group (P<0.05). There were significant differences in the rate of abnormal lung function and FEV1% predicted among the asthma groups (P<0.05). After salbutamol nebulization, the paroxysmal cough and wheeze groups had significantly higher rates of abnormal lung function than the control group (P<0.05), but there were no significant differences between other asthma and control groups; the wheeze group had significantly lower FEV1% predicted than the control group, but no significant differences were found between other asthma and the control groups. The positive rate of bronchial reversibility test in each asthma group was significantly higher than in the control group (P<0.05). There were significant differences in the positive rate of the test between the asthma groups except between the asymptomatic and single cough groups (P<0.05).

CONCLUSIONSAsthmatic children with different symptoms demonstrate different lung functions during treatment. Bronchial reversibility test combined with lung function test is useful in assessing asthma control and guiding treatment.

Administration, Inhalation ; Adolescent ; Albuterol ; administration & dosage ; adverse effects ; analogs & derivatives ; Androstadienes ; administration & dosage ; adverse effects ; Asthma ; drug therapy ; physiopathology ; Bronchi ; physiopathology ; Child ; Drug Combinations ; Female ; Fluticasone-Salmeterol Drug Combination ; Forced Expiratory Volume ; Humans ; Lung ; physiopathology ; Male

BACKGROUNDEvidence has demonstrated that the distal lung, which includes airways of < 2 mm in diameter and lung parenchyma, constitutes an important component of asthma pathology. Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and bronchoconstrictors involved in the asthmatic process. Guidelines recommend the leukotriene-modifying agents for asthma treatment. We hypothesized that a leukotriene receptor antagonist with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) combination would improve small airways function in moderate-to- severe asthmatics evaluated by physiological tests and high-resolution computed tomography (HRCT) analysis. This study was performed at a tertiary university hospital in Beijing.

METHODSThis was a randomized, double-blind, parallel study performed in 38 patients with moderate-to-severe asthma treated with salmeterol/futicasone (SFC) plus montelukast (SFC+M) or SFC plus placebo over 24 weeks. Small airway function was assessed by physiological studies and HRCT image analysis.

RESULTSMontelukast significantly improved air trapping as expressed by the residual volume (RV)/total lung capacity (TLC). Over 24 weeks of treatment, RV/TLC was improved by (15.41 ± 6.67)% in patients receiving SFC+M while RV/TLC was decreased by (8.57 ± 10.26)% in patients receiving SFC alone, the difference between the two groups was significant (P = 0.02). There was a trend towards a significant difference in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) in the SFC+M group compared to that in the SFC group ((17.87 ± 8.17)% vs. (12.28 ± 9.20)%, P = 0.056). There was no significant change in percentage wall area (WA%) after 24 weeks of add-on treatment with montelukast. Patients receiving SFC+M showed significant improvement in the ratio of CT-determined values at full expiration to those at full inspiration (E/I ratio) (0.894 ± 0.005 vs. 0.871 ± 0.003, P = 0.002).

CONCLUSIONWe have shown, using lung function tests and HRCT image technique, that add-on therapy with montelukast improves distal lung function reflected by air trapping, but not airway wall thickness in moderate-to-severe asthma.

Acetates ; therapeutic use ; Adult ; Airway Remodeling ; drug effects ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; drug therapy ; physiopathology ; Double-Blind Method ; Female ; Forced Expiratory Volume ; drug effects ; Humans ; Leukotriene Antagonists ; therapeutic use ; Male ; Middle Aged ; Pilot Projects ; Quinolines ; therapeutic use ; Total Lung Capacity ; drug effects

OBJECTIVETo investigate the effect of long-term exposure to toluene diisocyanate (TDI) on the lung function of TDI-exposed workers.

METHODSA factory was selected for this occupational epidemiological investigation. The workers who were exposed to TDI and had complete physical examination records in recent 3 years were the exposed group (n = 45), while the company's administrative staff, logistics staff, and other non-TDI-exposed workers who had complete physical examination records in recent 3 years were the control group (n = 47). The two groups were compared in terms of lung function indices.

RESULTSCompared with the control group, the 2009 exposure group had significantly lower forced expiratory volume in one second (FEV1.0), FEV1.0/forced vital capacity (FVC), and maximal expiratory flow at 25% of FVC (MEF25) (P < 0.05), the 2010 exposure group had significantly lower FEV1.0, FEV1.0/FVC,maximum voluntary ventilation (MVV), and maximal expiratory flow at 50% of FVC (MEF50) (P < 0.05), and the 2011 exposure group had significantly lower FEV1.0, FEV1.0/FVC, peak expiratory flow (PEF), MEF25, and MEF50 (P < 0.05).

CONCLUSIONLong-term exposure to TDI can lead to certain impairment of lung function in workers, which may be reflected by decreased lung function indices such as vital capacity, FVC, FEV1.0, FEV1.0/FVC, PEF, and MVV.

Case-Control Studies ; Forced Expiratory Volume ; Humans ; Lung ; drug effects ; physiopathology ; Male ; Occupational Exposure ; Toluene 2,4-Diisocyanate ; adverse effects ; Vital Capacity ; drug effects

BACKGROUND/AIMS: Recent investigations suggest that histone deacetylase 1 (HDAC1) and HDAC2 may be target molecules to predict therapeutic responses to corticosteroids. We evaluated the effects of variation in HDAC1 and HDAC2 on the response to corticosteroids in asthmatics. METHODS: Two single nucleotide polymorphisms (SNPs) were selected after resequencing HDAC1 and HDAC2. For the first analysis, we evaluated the association between those SNPs and asthma severity in 477 asthmatics. For the second analysis, we evaluated the effects of these SNPs on lung function improvements in response to corticosteroid treatment in 35 independent adult asthmatics and 70 childhood asthmatics. RESULTS: We found that one SNP in HDAC1 (rs1741981) was significantly related to asthma severity in a recessive model (corrected p = 0.036). Adult asthmatics who were homozygous for the minor allele of rs1741981 showed significantly lower % forced expiratory volume in 1 second (%FEV1) increases in response to systemic corticosteroids treatment compared with the heterozygotes or those homozygous for the major allele (12.7% +/- 7.2% vs. 37.4% +/- 33.7%, p = 0.018). Similarly, childhood asthmatics who were homozygous for the minor allele of rs1741981 showed significantly lower %FEV1 increases in response to inhaled corticosteroid treatment compared with the heterozygotes or those homozygous for the major allele (14.1% +/- 5.9% vs. 19.4% +/- 8.9%, p = 0.035). CONCLUSIONS: The present study demonstrated that rs1741981 in HDAC1 was significantly associated with the response to corticosteroid treatment in asthmatics.
Administration, Inhalation ; Adrenal Cortex Hormones/administration & dosage/*therapeutic use ; Adult ; Aged ; Anti-Asthmatic Agents/administration & dosage/*therapeutic use ; Asthma/diagnosis/*drug therapy/enzymology/genetics/physiopathology ; Child ; Female ; Forced Expiratory Volume ; Gene Frequency ; Heterozygote ; Histone Deacetylase 1/*genetics ; Histone Deacetylase 2/genetics ; Homozygote ; Humans ; Lung/*drug effects/physiopathology ; Male ; Middle Aged ; Pharmacogenetics ; Phenotype ; *Polymorphism, Single Nucleotide ; Recovery of Function ; Severity of Illness Index ; Treatment Outcome

BACKGROUND/AIMS: There is a need for new anti-asthmatic medications with fewer side effects. NDC-052, an extract of the medicinal herb Magnoliae flos, which has a long history of clinical use, was recently found to have anti-inflammatory effects. Herein, we evaluated the effects of NDC-052 as an add-on therapy in patients with mild to moderate asthma using inhaled corticosteroids (ICS). METHODS: In a non-comparative, multi-center trial, 148 patients taking ICS received NDC-052 for eight weeks. We evaluated their forced expiratory volume in one second (FEV1), morning and evening peak expiratory flow rate (AM and PM PEFR), AM/PM asthma symptom scores, visual analogue symptom (VAS) scores, night-time wakening, frequency of short-acting beta2-agonist usage, and adverse events. RESULTS: After eight weeks, both AM and PM PEFRs were significantly improved. Asthma symptom scores, VAS scores, the frequency of nights without awakening, and the frequency of beta2-agonist use were also reduced. Most of the adverse drug reactions were mild and resolved spontaneously. CONCLUSIONS: The addition of NDC-052 to ICS had a beneficial effect on asthma control in patients with mild to moderate asthma, with good tolerability and fewer side effects. Further studies are necessary to evaluate the effects of NDC-052 in patients with severe and/or refractory asthma.
Administration, Inhalation ; Adrenal Cortex Hormones/*administration & dosage ; Adrenergic beta-2 Receptor Agonists/therapeutic use ; Adult ; Anti-Asthmatic Agents/administration & dosage/*therapeutic use ; Asthma/diagnosis/*drug therapy/physiopathology ; Drug Therapy, Combination ; Drugs, Chinese Herbal/*therapeutic use ; Female ; Forced Expiratory Volume ; Humans ; Lung/drug effects/physiopathology ; *Magnolia ; Male ; Middle Aged ; Peak Expiratory Flow Rate ; Prospective Studies ; Republic of Korea ; Severity of Illness Index ; Time Factors ; Treatment Outcome

BACKGROUNDMany studies have shown the superior efficacy of budesonide (BUD)/formoterol (FORM) maintenance and reliever therapy, but still lack evidence of its efficacy in Chinese asthma patients in a relative large patient-group. We finished this research to compare BUD/FORM maintenance and reliever therapy and high-dose salmeterol (SALM)/fluticasone (FP) maintenance plus an as-needed short-acting β(2)-agonist in Chinese patients with persistent uncontrolled asthma. This was a post hoc analysis based on a 6-month, multicenter, randomized, double-blind study (NCT00242775).

METHODSA total of 222 eligible asthma patients from nine centers in China were randomized to either BUD/FORM+as-needed BUD/FORM (160/4.5 µg/inhalation) (640/18 µg/d; n = 111), or SALM/FP+as-needed terbutaline (0.4 mg/inhalation) (100/1000 µg/d; n = 111). The primary endpoint was time to first severe exacerbation while secondary endpoints included various measures of pulmonary function, symptom control and quality-of-life.

RESULTSTime to first severe exacerbation over six months was lower with the BUD/FORM than with the SALM/FP treatment (risk ratio = 0.52, 95%CI 0.22 - 1.22), but the difference did not achieve statistical significance (P = 0.13). The cumulative number of severe exacerbations in the BUD/FORM group was lower than in the SALM/FP group (7.2% vs. 13.5%; risk ratio = 0.45, P = 0.028). BUD/FORM produced significantly better improvements in reliever use, cumulative mild exacerbations, symptom-free days (%), and morning/evening peak expiratory flow (PEF) than SALM/FP (P < 0.05 in all cases). The two groups achieved similar improvements in their time to first mild exacerbation, forced expiratory volume in one second (FEV(1)), asthma control questionnaire and asthma symptom scores, and percentage of nights with awakening(s). Both treatments were well tolerated.

CONCLUSIONSIn Chinese patients with persistent asthma, BUD/FORM decreased severe and mild exacerbations, decreased reliever use, increased symptom-free days, and improved morning/evening PEF compared with SALM/FP. There were no significant differences in time to first severe exacerbation or other assessments regarding daily asthma control between BUD/FORM and SALM/FP. BUD/FORM was more effective in this Chinese sub-group than in the total cohort involved in the original study.

Adolescent ; Adult ; Aged ; Asthma ; complications ; drug therapy ; physiopathology ; Budesonide ; administration & dosage ; adverse effects ; Double-Blind Method ; Ethanolamines ; administration & dosage ; adverse effects ; Female ; Forced Expiratory Volume ; Formoterol Fumarate ; Humans ; Male ; Middle Aged