ABSTRACT
Objective To study the airway inflammation,epithefium apoptosis,p38 MAPK expression level in asthmatic guinea pigs and the effect of dexmethasone therapy.Methods Forty-eight guinea pigs were randomly divided into 4 groups:control group,asthma group,dexmethasone-treated group and MAPK pathway inhibitor SB203580 treated group,12 guinea pigs in each group.Hematoxylin and eosin staining,Massong Trichrome stain,Periodic Acid Schifgtaining were performed.Histological changes were detected under the optical or the electron microscope.Immunohistochemistry assays were used to determine the status of IL-5 and phosphorylated p38 MAPK in airway epitheliam.Inflammatory factor level was detected by enzyme linked immunosorbent assay (ELISA).Immunohistochemistry assays of cleaved caspase 3 was used to detect the level of epithefium apoptosis.Results Compared with the control group,guinea pigs in the asthmatic group showed significantly higher airway epithelium apoptosis (detected as the cleaved caspase-3 imumunoreactive cells),lung tissue phosphorylated p38 MAPK expression level,IL-5 level in BALF (P ＜0.01).Lung tissue phosphorylated p38 MAPK expression level was significantly related to IL-5 level in BALF.Compared with the asthmatic group,guinea pigs in the SB203580 group showed significantly lower airway epithelium apoptosis,lung tissue phosphorylated p38 MAPK expression level (P ＜ 0.01),but not IL-5 level in bronchoalveolar lavage fluid(BALF) (P ＞0.05).Compared with SB203580 group,guinea pigs in the DEX group showed significantly lower airway epithelium apoptosis,lung tissue phosphorylated p38 MAPK expression level,and IL-5 level in BALF (P ＜0.01).Conclusions Airway inflammation is involved in epithefium apoptosis in the asthmatic guinea pigs.The interfering effect of apoptosis by DEX may be partly related to inhibition of lung tissue phosphorylated p38 MAPK expression level,and p38 MAPK may participate in the asthmatic inflammation and induce airway epithelium apoptosis.
ABSTRACT
<p><b>BACKGROUND</b>Chronic kidney disease (CKD) is a growing public health problem with well-established risk factors. Other contributing factors, however, remain to be identified. Systemic inflammation in asthma plays a significant role in the development of other diseases. We therefore initiated a study to assess whether the growing prevalence of asthma is associated with an increase in the risk of CKD.</p><p><b>METHODS</b>We conducted a retrospective cohort study using data from 3015 patients with asthma aged 14 years and older who were registered and followed up in Asthma Control Study at the Department of Respiratory Medicine of three medical centers from 2005 to 2011. History, asthma control test (ACT), and asthma stage were used to assess the traits of asthma. CKD was defined as proteinuria and/or reduced estimated glomerular filtration rate (eGFR) (<60 ml×min(-1)×1.73 m(-2)) in two consecutive follow-up surveys. We used logistic regression models, adjusting for age, sex, and other confounding factor to determine associations between the traits of asthma and CKD. Kaplan-Meier curves were used to analyze patient outcomes.</p><p><b>RESULTS</b>A total of 2354 subjects with complete data were recruited for this study with mean age (45.4±10.4) years. After 6 years of follow-up, 9.6% (n = 227) of the analytic cohort developed proteinuria and 3.1% (n = 72) progressed to eGFR <60 ml×min(-1)×1.73 m(-2). The patients with >20 years asthma history, not well-controlled or persistent asthma patients had higher incidence of proteinuria and reduced eGFR compared with patients with ≤20 years asthma history, at least well-controlled or remission asthma, respectively. The multivariable adjusted OR for proteinuria and reduced eGFR in participants with persistent asthma was 1.49; (95% confidence interval (CI) 1.17-1.91) and 2.07 (95% CI 1.34-4.42). Compared to patients with no asthma traits, there was a significant risk (OR, 3.39; 95% CI 1.36-8.73) for those who met all three traits, including asthma history >20 years, not well-controlled and persistent stage, after adjusting for potential confounding factors.</p><p><b>CONCLUSIONS</b>In this retrospective cohort study, we found that persistent asthma was associated with an increased risk of CKD, which was independent of obesity, diabetes, hypertension, and other well-established risk factors. Future studies should be directed to elucidate the mechanisms underlying the association between asthma and CKD.</p>