ABSTRACT
BACKGROUND AND OBJECTIVE: COPD patients with community-acquired pneumonia (CAP) have worse clinical outcomes, as compared to those without COPD. Cardiovascular disease (CVD) is a common comorbidity for COPD patients. Whether COPD with comorbid CVD will increase the risk of CAP is not well investigated. The incidence and factors associated with CAP in COPD patients with and without CVD were analyzed. METHODS: The medical records of patients with newly diagnosed COPD between 2007 and 2010 were reviewed. The patients' characteristics, medical history of CVD, occurrence of CAP, and type of medication were recorded. Kaplan-Meier curves were used to assess the differences in cumulative incidence of CAP. Cox's proportional hazards regression model was used to determine the adjusted hazard ratios with 95% confidence intervals in relation to factors associated with CAP in COPD patients with and without CVD. RESULTS: Among 2,440 patients, 475 patients (19.5%) developed CAP during the follow-up period. COPD patients who developed CAP were significantly older, had lower forced expiratory volume in 1 second, frequent severe exacerbation and comorbid CVD, as well as received inhaled corticosteroid (ICS)-containing therapy than those without CAP. The cumulative incidence of CAP was higher in COPD patients with CVD compared to those without CVD. Patients who received ICS-containing therapy had significantly increased risk of developing CAP compared to those who did not. CONCLUSION: For patients with COPD, comorbid CVD is an independent risk factor for developing CAP. ICS-containing therapy may increase the risk of CAP among COPD patients.
Subject(s)
Cardiovascular Diseases/epidemiology , Community-Acquired Infections/epidemiology , Pneumonia/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Administration, Inhalation , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Aged , Aged, 80 and over , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Cardiovascular Diseases/diagnosis , Chi-Square Distribution , Community-Acquired Infections/diagnosis , Comorbidity , Female , Humans , Incidence , Kaplan-Meier Estimate , Male , Medical Records , Middle Aged , Multivariate Analysis , Pneumonia/diagnosis , Proportional Hazards Models , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Retrospective Studies , Risk Assessment , Risk Factors , Taiwan/epidemiologyABSTRACT
CONTEXT: Tianhua (TH-R) is extracted from Trichosanthes kirilowii Maxim (Cucurbitaceae) containing trichosanthin, a traditional Chinese medicine, which has been locally reported to have good anticancer effects in vivo in both animal and human models. However, there have been several reports that trichosanthin has an anticancer effect involving apoptosis. OBJECTIVE: To investigate other anticancer effects of TH-R, various tumorigenesis parameters were verified. MATERIALS AND METHODS: Telomerase activity, anti-apoptosis, anti-migration and immunomodulatory activity were estimated by telomeric repeat amplification protocol assay (TRAP), flow cytometry, Boyden chamber assay and ELISA assay, respectively. RESULTS: In our studies, we are the first to find that TH-R had a cytotoxic effect on lung cancer cells in MTS assays; it could change the cell cycle distribution of human lung cancer cells (A549 cell line) and induce apoptosis. Further anti-telomerase effects in human lung adenocarcinoma A549 cells using the TRAP assay were noted. TH-R also had an aggregation effect on peripheral blood lymphocytes, but no effect on stimulating peripheral lymphocytes to produce human interferon-γ(IFN-γ). TH-R could inhibit the migration, or metastatic ability, of A549 cells by Boyden chamber assay. In the oral feeding therapy of an in vivo mouse model, there was an initial inhibition of A549 cancer cell growth, but no statistical difference after one month of therapy. DISCUSSION AND CONCLUSION: It has been proven that medicinal herbs such as Tianhua have positive effects against cancer through preventing or inhibiting the process of lung tumorigenesis.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Immunologic Factors/pharmacology , Plant Extracts/pharmacology , Trichosanthin/pharmacology , Adenocarcinoma/drug therapy , Adenocarcinoma/immunology , Adenocarcinoma/pathology , Administration, Oral , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Migration Inhibition/drug effects , Cell Survival/drug effects , Humans , Immunomodulation/drug effects , Interferon-gamma/biosynthesis , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Telomerase/metabolism , Transplantation, HeterologousABSTRACT
Purified recombinant fungal immunomodulatory protein from Ganoderma tsugae (reFIP-gts) has anti-telomerase effects in human lung adenocarcinoma A549 cells. However, how reFIP-gts affects cancer cell fates remains unclear. Here, we demonstrated that reFIP-gts-treated lung cancer cells are arrested at G1 phase by flow cytometry and possess morphological phenotype consistent with cellular senescence. The senescent nature of these cells was supported by positive staining for senescence-associated beta-galactosidase activity and increased lysosomal content in A549 and CaLu-1 lung cancer cells. Arrest of cells at G1 appears to be the key means through which reFIP-gts induces premature cellular senescence in A549 cells. Finally, reFIP-gts- treated A549 cells grew more slowly and formed significantly fewer cell colonies in soft agar than untreated A549 cells. In an in vivo mouse model, A549 cells treated with reFIP-gts grew significantly slower than cells treated with PBS alone, confirming that lung tumor can be inhibited by reFIP-gts. The use of reFIP-gts may be a powerful new strategy for chemoprevention and antineoplastic therapy.