The Association Of Daily Mean Temperature, NF-κB And Inflammatory Cytokines Regulated By NF-κB With Acute Exacerbations Of COPD

Objective:To explore the correlation between the daily mean temperature and theadmissions of the patients with acute exacerbations of COPD，and to clarify the effectof daily mean temperature on acute exacerbations of COPD. Our study also comparedthe different expression level of NF-κB in peripheral venous blood and theinflammatory cytokines regulated by it between patients with acute exacerbation ofCOPD and the healthy control population，and to explore the mechanisms ofinflammation in vivo of the patients with acute exacerbation of COPD.Methods：In our study，the clinical data of2564acute exacerbations of COPD patients andmeteorological variables in the same period were collected. A case-crossover studydesign was used to investigate the association between different daily meantemperature and acute exacerbations of COPD in different seasons，in order todetermine the association between daily mean temperature and acute exacerbations ofCOPD. And in our study，case-control study was used. A total of186patients withacute exacerbations of COPD were recruited from a hospital of Jilin Universitybetween August2013and December2014.180control subjects were randomlyselected from the persons who were through the routine checkup as part of annualbody examination during August2014to December2014. And we usedquestionnaire，physical examination and other methods to collect useful data of caseand control groups，and analyzed the relationship between acute exacerbation ofCOPD and risk factors. All the subjects were given an informed consent，and weretold of the study protocol. We collected5mL of peripheral venous blood from casesand controls， and used enzyme-linked immunosorbent assay to compare the expression of inflammatory factors in peripheral venous blood between cases andcontrols. The peripheral venous blood was also used to extract total mRNA，NF-κB1、NF-κB2、REL are selected as candidate genes，and real time fluorescence quantitativePCR was used to test the mRNA levels. SPSS16.0software was used to analyze thedata.Results:1. During2009to2012，daily mean temperature changed significantly in everyseasons in Changchun. The highest daily mean relative humidity appeared insummer，autumn and winter took second place，and the lowest appeared in spring.Daily mean atmospheric pressure was significantly different between differentseasons，The highest daily mean atmospheric pressure appeared in autumn andwinter，spring took second place，and the lowest appeared in summer. The highestdaily mean wind speed appeared in spring，autumn and winter took second place，andthe lowest appeared in summer. The change of climate had different features in everyseasons，it was dry and windy in spring，hot and humid in summer，crisp andinvigorating in autumn，cold and humid in winter.2. During2009to2012，the highest admissions of the patients with acuteexacerbations of COPD appeared in spring and winter, autumn took second place，andthe lowest appeared in summer. These findings suggested that the occurrence of acuteexacerbation of COPD was different in every season.3. The correlation among meteorological factors was significant within the studyperiod (P <0.05). Suggesting that the interaction between the various meteorologicalfactors may affect the development of acute exacerbations of COPD4. The daily mean temperature in Changchun City had hysteresis effect onadmissions of the patients with acute exacerbations of COPD in different seasons.During spring and autumn，the daily mean temperature hysteresis effect on admissionsof the patients with acute exacerbations of COPD were statistically significant at0～3day lag in the study period (P <0.05)，while the impact of daily mean temperature inwinter was statistically significant at3day lag in the study period (P <0.05). Duringspring, summer and autumn，the largest hysteresis effect of daily mean temperaturehappened at the lag3day，while the largest hysteresis effect in winter happened at the lag1day.5. After adjusting the influence of daily mean relative humidity，daily mean windspeed and daily mean pressure，we found that a1℃increase in daily meantemperature was associated with a18.9%（OR=1.189，95%CI=1.152～1.228）and14.2%（OR=1.142，95%CI=1.074～1.214）increase in hospital admissions foracute exacerbations of COPD in spring and summer. contrarily，those decreased by9.7%（OR=0.903，95%CI=0.874～0.933）in autumn. But there is no significantassociation was be found in winter (P>0.05).6. The difference of smoking betweeen case group and control group wasstatistically significant（χ2=9.967，P=0.002），and the proportion of the population incase group who had a history of smoking（39.2%）was significantly higher than theproportion of the population in control group（23.9%）, these findings suggested thatsmoking may be associated with the acute exacerbations of COPD.7. In our study，the history of diabetes was significant different betweeen casegroup and control group（χ2=8.580，P=0.003），and the proportion of the populationin case group who had a history of diabetes（6.5%）was significantly lower than theproportion of the population in control group（16.1%）.In addition, there was nosignificant difference was found in the history of hypertension or coronary heartdisease between the case group and control group (P>0.05).8. Compared with control group，the NF-κB1，NF-κB2and REL mRNAexpression level were significant higher in case group（P＜0.05）.9. The cases’ expression level of seven kinds of inflammatory cytokines inperipheral venous blood included COX2，CRP，IL-1β，IL-6，IL-8，IL-12and TNF-αwere significantly higher than controls’. The case group’s IL-2expression wassignificantly lower than the control group’s.10. There were negative correlations between daily mean temperature andNF-κB1、NF-κB2(P＜0.05), and there were positive correlations between daily meantemperature and IL-6, TNF-α, CRP (P＜0.05). In addition, negative correlations werefound between NF-κB2and IL-6, TNF-α, CRP (P＜0.05), and a positive correlationwere also found between NF-κB2and IL-1β (P＜0.05). Conclusions:1. The increasing of daily mean temperature may be a risk factor of the patientswith acute exacerbations of COPD in spring and summer；however，it may be apreventive factor in autumn and winter.2. The increasing of daily mean temperature may be a risk factor of the patientswith acute exacerbations of COPD in spring and summer; however, it may be apreventive factor in autumn and winter.3. The daily mean temperature in different seasons had an hysteresis effect onadmissions of the patients with acute exacerbations of COPD.4. Somking may be a risk factor of the patients with COPD.5. In peripheral venous blood，the higher mRNA level of NF-κB1，NF-κB2andREL may be related to the patients with acute exacerbations of COPD. And the higherexpression level of inflammatory cytokines included COX2，CRP，IL-1β，IL-6，IL-8，IL-12and TNF-α may be also related to the patients with acute exacerbations ofCOPD.6. In peripheral venous blood of patients with acute exacerbation of COPD, therewere negative correlations between the expression of NF-κB and the levels IL-6,TNF-α, CRP, and there was a positive correlation between the expression of NF-κBand the level of IL-1β.7. The daily mean temperature reduced could lead to increase expression levelsof NF-κB1、NF-κB2in peripheral venous blood of patients with acute exacerbation ofCOPD.