Appropriate pharmacologic therapy can reduce symptoms and risk and severity of exacerbations, as well as improve the health status and exercise tolerance of patients with chronic obstructive pulmonary disease. The most important medications for treating chronic obstructive pulmonary disease are inhaled bronchodilators including beta2-agonist and anticholinergics. Inhaled corticosteroids as anti-inflammatory drug should be considered in certain patients with caution considering risk and benefit. The choice within each class depends on the availability of medication and the patient's responses and preferences. Each treatment regimen needs to be individualized as the relationship between severity of symptoms, airflow limitation and severity of exacerbation can differ between patients.
Adrenal Cortex Hormones ; Bronchodilator Agents ; Cholinergic Antagonists ; Drug Therapy ; Exercise Tolerance ; Humans ; Pulmonary Disease, Chronic Obstructive ; Respiratory Therapy

Bronchodilators provide improvements in lung function and reductions in symptoms and exacerbations, and are the mainstay of pharmacological management of chronic obstructive pulmonary disease (COPD). The Global Initiative for Chronic Obstructive Lung Disease strategy recommends the use of a combination of long-acting β₂-agonist/long-acting muscarinic antagonists (LABA/LAMA) as the first-line treatment option in the majority of symptomatic patients with COPD. This review provides an indirect comparison of available LABA/LAMA fixed-dose combinations (FDCs) through discussion of important efficacy and safety data from the key literature, with the objective of providing physicians with a framework for informed decision-making. LABA/LAMA FDCs provided greater benefits compared with placebo and similar or greater benefits compared with tiotropium and salmeterol/fluticasone in improving lung function, dyspnea, health-related quality of life, reducing rescue medication use and preventing exacerbations, although with some variability in efficacy between individual FDCs; further, tolerability profiles were comparable among LABA/LAMA FDCs. However, there is a disparity in the amount of evidence generated for different LABA/LAMA FDCs. Thus, this review shows that all LABA/LAMA FDCs may not be the same and that care should be taken when extrapolating individual treatment outcomes to the entire drug class. It is important that physicians consider the efficacy gradient that exists among LABA/LAMA FDCs, and factors such as inhaler devices and potential biomarkers, when choosing the optimal bronchodilator treatment for long-term management of patients with COPD.
Asian Continental Ancestry Group ; Biomarkers ; Bronchodilator Agents ; Disease Management ; Dyspnea ; Humans ; Korea ; Lung ; Muscarinic Antagonists* ; Nebulizers and Vaporizers ; Pulmonary Disease, Chronic Obstructive* ; Quality of Life ; Tiotropium Bromide

The goals of management of stable chronic obstructive pulmonary disease (COPD) are to reduce both current symptoms and future risks with minimal side effects from treatment. Identification and reduction of exposure to risk factors are important in the treatment and prevention of COPD. Appropriate pharmacologic therapy can reduce symptoms and exacerbations, and improve health status and exercise tolerance. To date, none of the existing medications for COPD has been shown to modify disease progression or reduce mortality. The classes of medication are bronchodilators including beta2-agonist, anticholinergics and anti-inflammatory drug including inhaled corticosteroid and phosphodiesterase-4 inhibitor such as roflumilast. Each treatment regimen needs to be individualized as the relationship between severity of symptoms, airflow limitation and severity of exacerbation can differ between patients.
Bronchodilator Agents ; Cholinergic Antagonists ; Cyclic Nucleotide Phosphodiesterases, Type 4 ; Disease Progression ; Drug Therapy ; Exercise Tolerance ; Humans ; Mortality ; Phosphodiesterase 4 Inhibitors ; Pulmonary Disease, Chronic Obstructive ; Risk Factors

Despite a range of efficacious therapies for asthma, including inhaled corticosteroids (ICS) and long-acting β₂-agonists (LABA), a significant proportion of patients have poor asthma control and retain a risk of future worsening of their symptoms. Long-acting muscarinic antagonist (LAMA) bronchodilators offer a well-tolerated, efficacious, and cost-effective add-on to a patient's treatment. Of the LAMAs currently under investigation or available for the treatment of asthma, evidence from a comprehensive clinical trial program in adults and children shows that once-daily treatment with tiotropium provides benefits for patients with uncontrolled asthma despite the use of ICS and LABAs. Tiotropium is included in the Global Initiative for Asthma (GINA) strategy document as an add-on therapy option for patients at Step 4 or 5 with a history of asthma exacerbations. Tiotropium Respimat® has demonstrated safety and efficacy in patients with a range of disease severities, ages, and phenotypes. This review describes the evidence for the use of LAMA as add-on therapy for patients with asthma who remain uncontrolled despite the use of ICS and LABA treatments.
Adrenal Cortex Hormones ; Adult ; Asthma* ; Bronchodilator Agents ; Child ; Humans ; Muscarinic Antagonists* ; Phenotype ; Tiotropium Bromide

Bronchodilators are the cornerstone of symptomatic chronic obstructive pulmonary disease (COPD) treatment. They are routinely recommended for symptom reduction, with a preference of long-acting over short-acting drugs. Bronchodilators are classified into two classes based on distinct modes of action, i.e., long-acting antimuscarinics (LAMA, once-daily and twice-daily), and long-acting β2-agonists (LABA, once-daily and twice-daily). In contrast to asthma management, evidence supports the efficacy of both classes of long-acting bronchodilators as monotherapy in preventing COPD exacerbations, with greater efficacy of LAMA drugs versus LABAs. Several novel LAMA/LABA fixed dose combination inhalers are currently approved for COPD maintenance treatment. These agents show superior symptom control to monotherapies, and some of these combinations have also demonstrated superior efficacy in exacerbation prevention versus monotherapies, or combinations of inhaled corticosteroids plus LABA. This review summarizes the current data on clinical effectiveness of bronchodilators alone or in combination to prevent exacerbations of COPD.
Adrenal Cortex Hormones ; Asthma ; Bronchodilator Agents* ; Muscarinic Antagonists ; Nebulizers and Vaporizers ; Pulmonary Disease, Chronic Obstructive* ; Treatment Outcome

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

Adrenergic beta-2 Receptor Agonists ; administration & dosage ; pharmacokinetics ; therapeutic use ; Asthma ; drug therapy ; Bronchitis ; drug therapy ; Bronchodilator Agents ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Delayed-Action Preparations ; Drug Synergism ; Drug Therapy, Combination ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Infant ; Leukotriene Antagonists ; administration & dosage ; therapeutic use ; Respiratory Sounds ; drug effects ; Terbutaline ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; therapeutic use ; Transdermal Patch

Asthma is a chronic respiratory disease characterized by reversible airway obstruction that is secondary to an allergic inflammation and excessive smooth muscle contraction. Cholinergic signals were known to contribute significantly to the pathophysiology of asthma. However, the use of anti-cholinergic agents in asthma has been justified only in acute asthma exacerbations, until tiotropium bromide, a long-acting anti-cholinergic agent was introduced. Recent reports showing a promising role of tiotropium in the treatment of asthma have aroused interest of the use of anti-cholinergic agent for the management of asthma. This report describes pharmacological characteristics, potential effects on inflammatory cells, and the current status of tiotropium in the treatment of asthma.
Airway Obstruction ; Asthma ; Bronchodilator Agents ; Cholinergic Antagonists ; Inflammation ; Muscle, Smooth ; Tiotropium Bromide

This study examined whether propofol and aminophylline affect the mobilization of intracellular calcium in human umbilical vein endothelial cells. Intracellular calcium was measured using laser scanning confocal microscopy. Cultured and serum-starved cells on round coverslips were incubated with propofol or aminophylline for 30 min, and then stimulated with lysophosphatidic acid, propofol and aminophylline. The results were expressed as relative fluorescence intensity and fold stimulation. Propofol decreased the concentration of intracellular calcium, whereas aminophylline caused increased mobilization of intracellular calcium in a concentration-dependent manner. Propofol suppressed the lysophosphatidic acid-induced mobilization of intracellular calcium in a concentration-dependent manner. Propofol further prevented the aminophylline-induced increase of intracellular calcium at clinically relevant concentrations. However, aminophylline reversed the inhibitory effect of propofol on the elevation of intracellular calcium by lysophosphatidic acid. Our results suggest that propofol and aminophylline antagonize each other on the mobilization of intracellular calcium in human umbilical vein endothelial cells at clinically relevant concentrations. Serious consideration should be given to how this interaction affects mobilization of intracellular calcium when these two drugs are used together.
Aminophylline/*antagonists & inhibitors/pharmacology ; Anesthetics, Intravenous/*antagonists & inhibitors/pharmacology ; Bronchodilator Agents/*antagonists & inhibitors/pharmacology ; Calcium/*metabolism ; Cells, Cultured ; Endothelial Cells/*drug effects/metabolism ; Endothelium, Vascular/cytology ; Humans ; Lysophospholipids/pharmacology ; Microscopy, Confocal ; Propofol/*antagonists & inhibitors/pharmacology ; Umbilical Veins/cytology

The general approach to manage stable COPD is characterized by a stepwise increase in treatment, depending on the severity of the disease. None of the existing medications for COPD have been shown to modify the long-term decline in lung function that is the hallmark of the disease. Therefore, pharmacotherapy in COPD is used to decrease symptoms and /or complications. Bronchodilator medications are central to the symptomatic management of COPD. They are given on an as-needed basis or on a regular basis to prevent or reduce symptoms. The principal bronchodilator treatments are beta2-agonists, anticholinergics, theophylline, and a combination of these drugs. Regular treatment with long-acting bronchodilators is more effective and convenient than treatment with short-acting bronchodilators, but more expensive. The addition of regular treatment with inhaled steroids to bronchodilator treatment is appropriate for symptomatic COPD patients with an FEV1<50% predicted (Stage III: Severe COPD and Stage IV: Very Severe COPD) or repeated exacerbations (for example, more than 3 times during the last 3 years). Chronic treatment with systemic steroids should be avoided, if possible.
Bronchodilator Agents ; Cholinergic Antagonists ; Drug Therapy* ; Humans ; Lung ; Pulmonary Disease, Chronic Obstructive* ; Steroids ; Theophylline