Asthma ; diagnosis ; drug therapy ; physiopathology ; Child, Preschool ; Diagnosis, Differential ; Glucocorticoids ; therapeutic use ; Humans ; Infant ; Recurrence ; Respiratory Sounds ; diagnosis ; drug effects ; etiology ; Treatment Outcome

Anti-Asthmatic Agents ; therapeutic use ; Asthma, Exercise-Induced ; diagnosis ; epidemiology ; physiopathology ; therapy ; Child ; Constriction, Pathologic ; drug therapy ; etiology ; physiopathology ; Diagnosis, Differential ; Glucocorticoids ; therapeutic use ; Humans ; Risk Factors ; Treatment Outcome

Many patients with asthma or chronic obstructive pulmonary disease (COPD) have overlapping characteristics of both diseases. By spirometric definition, patients with both fixed airflow obstruction (AO) and bronchodilator reversibility or fixed AO and bronchial hyperresponsiveness can be considered to have asthma-COPD overlap syndrome (ACOS). However, patients regarded to have ACOS by spirometric criteria alone are heterogeneous and can be classified by phenotype. Eosinophilic inflammation, a history of allergic disease, and smoke exposure are important components in the classification of ACOS. Each phenotype has a different underlying pathophysiology, set of characteristics, and prognosis. Medical treatment for ACOS should be tailored according to phenotype. A narrower definition of ACOS that includes both spirometric and clinical criteria is needed.
Anti-Asthmatic Agents/therapeutic use ; Asthma/*complications/diagnosis/drug therapy/physiopathology ; Bronchodilator Agents/therapeutic use ; Humans ; Lung/drug effects/*physiopathology ; Phenotype ; Predictive Value of Tests ; Pulmonary Disease, Chronic Obstructive/*complications/diagnosis/drug therapy/physiopathology ; Risk Factors ; Spirometry ; Syndrome ; Terminology as Topic ; 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

Inhaled glucocorticosteroids are currently the most effective anti-inflammatory controller medications for treating persistent asthma. The efficacies of glucocorticoids include reducing asthma symptoms, reducing exacerbation frequency, improving quality of life, improving lung function, decreasing airway hyperresponsiveness, controlling airway inflammation, and reducing mortality. However, the treatment response to glucocorticosteroids in asthmatics varies, and certain subtypes of asthma, such as refractory asthma, respond poorly to high-dose inhaled glucocorticoid and systemic steroids. The medical costs of treating refractory asthmatics represent about 50% of the total healthcare cost for asthma. A thorough understanding of the mechanisms of glucocorticoid action, patient responses to glucocorticoids, and steroid resistance observed in refractory asthmatics is necessary for the targeted development of therapeutic drugs. This review discusses the characteristics of severe refractory asthmatics and the mechanisms of steroid response and resistance in asthma treatment.
Administration, Inhalation ; Anti-Asthmatic Agents/administration & dosage/adverse effects/*therapeutic use ; Anti-Inflammatory Agents/administration & dosage/adverse effects/*therapeutic use ; Asthma/diagnosis/*drug therapy/physiopathology ; Drug Resistance ; Glucocorticoids/administration & dosage/adverse effects/*therapeutic use ; Humans ; Lung/*drug effects/physiopathology ; Severity of Illness Index ; Treatment Outcome

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

OBJECTIVETo investigate the Churg-Strauss syndrome (CSS) associated lung involvement, concentrating on clinical characteristics, pathological findings of lung involvements, response to treatment, and prognosis.

METHODSWe retrospectively analyzed the characters of the clinical manifestations, thin-section CT and pathological findings of CSS. The study involved 16 patients. Clinical data were obtained by chart review. All patients underwent transbronchial lung biopsy (TBLB). Six of them underwent surgical lung biopsy as well.

RESULTSThe patients included 7 men and 9 women, aged from 14 to 61 years (median, 47.5 years). Extrathoracic organs involved included nervous system (7/16) and skin (5/16). Respiratory symptoms included cough (12/16), exertional dyspnea (11/16), hemoptysis (4/16), and chest pain (3/16). CT findings included bilateral ground-glass opacities (12/16), bilateral patchy opacities (12/16), and centrilobular nodules (6/16). The pathological findings of TBLB demonstrated increased eosinophils (3/16), vasculitis (3/16), and interstitial pneumonia (16/16). The pathological findings of surgical lung biopsy of 6 cases showed necrotizing vasculitis in 4 cases, capillaries in 5, eosinophilic pneumonia in 3, granulomas in 2, and airway abnormalities in 3. All patients improved in symptoms after therapy during the study period (range, 3 to 51 months; median, 15 months).

CONCLUSIONSAsthma may be present in CSS patient when there is bronchial involvement. Ground-glass opacities and consolidation seen on high-resolution CT reflect the presence of eosinophilic pneumonia, vasculitis, and pulmonary alveolar hemorrhage. TBLB has significant limitations for the diagnosis of CSS. Early diagnosis and therapy can result in satisfactory prognosis.

Adolescent ; Adult ; Asthma ; physiopathology ; Biopsy ; Churg-Strauss Syndrome ; diagnosis ; diagnostic imaging ; drug therapy ; pathology ; Cyclophosphamide ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Lung ; diagnostic imaging ; pathology ; physiopathology ; surgery ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Tomography, X-Ray Computed ; methods ; Treatment Outcome ; Young Adult