The studies on gene polymorphisms in biological pathways of the drugs for the treatment of asthma refer to the studies in which pharmacogenetic methods, such as genome-wide association studies, candidate gene studies, genome sequencing, admixture mapping analysis, and linkage disequilibrium, are used to identify, determine, and repeatedly validate the effect of one or more single nucleotide polymorphisms on the efficacy of drugs. This can provide therapeutic strategies with optimal benefits, least side effects, and lowest costs to patients with asthma, and thus realize individualized medicine. The common drugs for asthma are β2 receptor agonists, glucocorticoids, and leukotriene modifiers. This article reviews the research achievements in polymorphisms in biological pathways of the common drugs for asthma, hoping to provide guidance for pharmacogenetic studies on asthma in future and realize individualized medicine for patients with asthma soon.
Adrenergic beta-2 Receptor Agonists ; therapeutic use ; Asthma ; drug therapy ; genetics ; Glucocorticoids ; therapeutic use ; Leukotrienes ; genetics ; therapeutic use ; Metabolic Networks and Pathways ; Pharmacogenetics ; Polymorphism, Single Nucleotide ; Precision Medicine

OBJECTIVETo observe the effects of combined beta(1) adrenergic receptor (AR) antagonist with beta(2)AR agonist therapy on cardiac function and cardiomyocyte apoptosis in heart failure rats.

METHODSHeart failure was induced by isoproterenol and rats were randomly divided into metoprolol group (50 mg/kg twice daily/gavage, n = 11), combined treatment group (fenoterol 125 microg/kg and metoprolol 50 mg/kg twice daily/gavage, n = 11) and placebo group (saline, n = 10), another normal 9 male Wistar rats served as control group. After 8 weeks' treatment, cardiac function, apoptosis index (AI), Caspase-3 activity, expression levels of bcl-2 and bax protein, organ weight/body weight and collagen volume fraction (CVF) were evaluated.

RESULTS(1) Left ventricular end diastolic dimension, left ventricular end systolic dimension and E/A ratio were significantly increased and fractional shortening, ejection fraction significantly reduced post isoproterenol (all P < 0.05 vs. control) and these changes were significantly attenuated by metoprolol alone (all P < 0.05 vs. placebo) and further attenuated by the metoprolol and fenoterol combination therapy (all P < 0.05 vs. placebo and metoprolol). (2) Left ventricular weight to body weight ratio, lung weight to body weight ratio and CVF were also significantly reduced in metoprolol and combined treatment group than those in placebo group (all P < 0.01). (3) Compared with placebo group, AI and Caspase-3 activity were significantly lower in metoprolol group (all P < 0.01 vs. placebo) and further reduced in combined treatment group (all P < 0.01 vs. metoprolol). (4) The expression level of bax protein was significantly lower in metoprolol group while bcl-2/bax significantly higher than those in placebo group. These changes were more significant in combined treatment group (all P < 0.01 vs. metoprolol).

CONCLUSIONSbeta(1)AR antagonist in combination with beta(2)AR agonist further improved the cardiac function and prevented cardiac remodeling compared with using beta(1)AR antagonist alone in heart failure rats. Downregulated bax and upregulated bcl-2/bax expressions might contribute to the observed beneficial therapy effects by reducing cardiomyocyte apoptosis in these animals.

Adrenergic beta-1 Receptor Antagonists ; Adrenergic beta-2 Receptor Agonists ; Adrenergic beta-Agonists ; pharmacology ; therapeutic use ; Adrenergic beta-Antagonists ; pharmacology ; therapeutic use ; Animals ; Apoptosis ; drug effects ; Drug Therapy, Combination ; Heart Failure ; drug therapy ; Male ; Myocytes, Cardiac ; cytology ; Rats ; Rats, Wistar ; Ventricular Remodeling

OBJECTIVETo compare tulobuterol patch and oral salbutamol sulfate in terms of efficacy and safety in children with mild or moderate acute attack of bronchial asthma.

METHODSA total of 92 children with mild and moderate acute asthmatic attack were randomly divided into salbutamol group (n=46) and tulobuterol group (n=46). Both groups received routine treatment with antihistamine, selective leukotriene receptor antagonist and glucocorticoid. In addition, the salbutamol group was given slow-release capsules of salbutamol sulfate, and the tulobuterol group was treated with tulobuterol patch. The two groups were compared with respect to symptom scores of cough, wheeze, respiratory rate, wheezing sound, three depression sign and peak expiratory flow, as well as adverse events.

RESULTSAs the treatment proceeded, symptom scores decreased in both groups; on the third day of treatment, all symptom scores except cough score showed a significant decrease in both groups (P<0.05), but the tulobuterol group had significantly lower symptom scores than the salbutamol group (P<0.05). On the fourteenth day of treatment, both groups had a significant decrease in cough score (P<0.05), but the tulobuterol group had a significantly lower cough score than the salbutamol group (P<0.05). One child developed hand trembling in the salbutamol group, while no adverse event occurred in the tulobuterol group.

CONCLUSIONSCompared with oral salbutamol sulfate, tulobuterol patch has a better therapeutic efficacy and a higher safety in children with mild or moderate acute asthmatic attack.

Acute Disease ; Administration, Oral ; Adrenergic beta-2 Receptor Agonists ; therapeutic use ; Albuterol ; administration & dosage ; adverse effects ; therapeutic use ; Asthma ; drug therapy ; Female ; Humans ; Terbutaline ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use

OBJECTIVETo observe and evaluate the performances of intermittent positive pressure ventilation, beta-2 adrenergic receptor agonist, and pressure lavage in promoting residual fluid absorption and improving blood oxygen saturation during massive whole lung lavage (WLL).

METHODSA total of 155 patients were randomly divided into pressure ventilation (PV) group (n = 28), adrenaline (Ad) group (n = 31), PV plus Ad group (n = 29), pressure infusion bag (PIB) group (n = 30), and control group (n = 32). The patients underwent staged MWLL of bilateral lungs. The blood oxygen saturation (SpO2) of arterial blood of finger, chest X-ray findings, clinical symptoms, and lung functions were observed before and after MWLL.

RESULTSThere were no significant differences in change in clinical symptoms among the five groups after MWLL (P > 0.05). The Ad group showed 6.3% increase in forced vital capacity (FVC) and 10.9% increase in forced expiratory flow at 25% of vital capacity (FEF(25%)) after MWLL (P < 0.05). The control group showed 5.7% decrease in FVC, 10.9% increase in forced expiratory volume in one second (FEV(1.0)), and 12.0% increase in FEF(25%) after MWLL (P < 0.05). No significant difference was found in other groups (P > 0.05). During and after MWLL, the incidence rates of hypoxemia in PV group, PV plus Ad group, and control group were 0, 0, and 12.5% (8/64), respectively (P < 0.01). There were no significant differences in total amount of lavage fluid and amount of residual fluid in the lung among all groups (P > 0.05). The smallest difference between the optical densities of the two lung fields on chest x-ray at 3 h after WLL was 0.152 ± 0.053 in the PV plus Ad group, compared to 0.194 ± 0.074 in the PV group, 0.197 ± 0.054 in the PIB group, 0.214 ± 0.054 in the Ad group, and 0.241 ± 0.109 in the control group, with significant differences between the saline group and other groups except Ad group (P < 0.05).

CONCLUSIONPressure ventilation, adrenaline, and pressure lavage can promote the transportation and absorption of residual fluid in the lung and decrease the incidence of hypoxemia during WLL.

Adrenergic beta-2 Receptor Agonists ; therapeutic use ; Adult ; Blood Gas Analysis ; Bronchoalveolar Lavage ; methods ; Epinephrine ; therapeutic use ; Female ; Forced Expiratory Volume ; Humans ; Hypoxia ; prevention & control ; Male ; Middle Aged ; Oxygen Consumption ; Pneumoconiosis ; therapy ; Positive-Pressure Respiration ; methods

Adrenergic beta-2 Receptor Agonists ; administration & dosage ; therapeutic use ; Asthma ; diagnosis ; etiology ; therapy ; Child ; Child, Preschool ; Chronic Disease ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Infant ; Pediatrics ; Seasons ; Time Factors

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

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

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