A Clinical Study Of The Impact Of COPD On The Pathogenesis And Prognosis Of Lung Cancer

BackgroundChronic obstructive pulmonary disease(COPD)and lung cancer are common chronic pulmonary diseases,of whith COPD is the most common one,and the mortality of lung cancer is the highest.For many years,the reason of COPD patients at high risk for lung cancer was due to their common pathogenic factor--smoking.However,a number of research data shown,in addition to the common exposure,there may be other important link between COPD and lung cancer.What is the specific relationship between these two heterogeneous diseases?What are the implications and implications of these association rules for the occurrence,development,treatment and prognosis of the two major categories of COPD and lung cancer?So far,the research and discussion on these problems are far from satisfying the needs of theory and clinical practice.Our research attempts to answer these questions.This study was divided into two parts.Part One:The link of COPD and the risk of lung cancer:a case-control studyObjectiveThe aim of this study was to validate the relationship between COPD and lung cancer risk in larger samples,and to explore the relationships between COPD phenotypes and the risk for different histologic subtype of lung cancer.MethodsThe case-control study included the cases with newly pathological-diagnosed lung cancer and non-lung cancer controls.All participants underwent pulmonary function tests.The diagnosis of COPD was based on the Chronic Obstructive Lung Disease(GOLD)criteria.Subtypes of the two diseases were categorized according to 2015 World Health Organization(WHO)classification of lung cancer and computer quantification of the airway collapse on maximum expiratory flow volume(MEFV)curve,respectively.The odds radios was estimated using logistic regression analysis.Results1.A total of 4606 participants were collected:2283 lung cancer cases and 2323 non-lung cancer controls.There was no significant difference in age,sex and smoking status between lung cancers and controls.The histological subtypes found were the following;adenocarcinoma(1120[49.1%]),squamous carcinoma(792[34.7%]),neuroendocrine carcinoma(192[8.4%];SCLC 152[9.6%],LCNC 20[0.9%]and carcinoid tumors 20[0.9%]),large cell carcinoma(58[2.5%]),adenosquamous careinoma(46[2.0%]),other histological types(14[0.6%])and unclassified lung cancer(61[2.7%]).Among them,92.8%(2018 cases)were at early stage(stage IA-IIB).2.The FEV1,FVC and FEV1/FVC of lung cancer patients were significantly lower than those of controls(P<0.001).Significantly higher prevalence of COPD was observed in lung cancer patients(32.8%)compared to controls(16.0%;p<0.001).There was no significant difference in AC between lung cancers and controls(148.8��10.2�VS 148.3��8.8�,P= 0.507).3.COPD and lung cancer risk After adjustment for age,sex,BMI and smoking status,the presence of COPD was an independent risk factor for lung cancer(OR=2.88,95%CI 2.48-3.34).The risk of lung cancer In patients with COPD was significantly increased(ORs=2.30-3.00)in each subgroups(including smoking group,non-smoking group,male group and female group).In the same multivariable logistic regression model,female gender was also a risk factor for lung cancer.4.COPD and the risk for different histologic subtypes of lung cancer After adjustment for age,sex,BMI and smoking status,compared with non-COPD,the presence of COPD indicated an increased risk by 2-to 5-fold for each histological subtype of lung cancer.Among the most common subtypes,the odds for increased risk of SCLC was extremely high(OR=5.14,95%CI 3.58-7.39),followed by LCNC(OR=4.35,95%CI 1.68-11.3),squamous carcinoma(OR=3.51,95%CI 2.90-4.23),large cell carcinoma(OR=3.41,95%CI 1.94-5.98)and adenocarcinoma(OR=2.11,95%CI 1.74-2.55);Additionally,the presence of COPD increased the risk for neuroendocrine lung carcinoma by 4.28-fold(OR=4.28,95%CI 3.20-5.73).5.COPD phenotypes and the risk for different histologic subtypes of lung cancer Logistic regression analysis reve.aled that,compared to patients with non-emphysema-predominant phenotype,patients with emphysema-predominant phenotype of COPD had significantly higher risks for lung cancer(adjusted OR 1.61,95%CI 1.02-2.54),especially squamous carcinoma and SCLC(adjusted OR 1.72,95%CI 1.03-2.89;adjusted OR 3.74,95%CI 1.64-8.53).For the increased risks of other lung cancer subtypes,no significant difference was observed between the two phenotypes.Conclusion1.COPD can independently increase the risk of lung cancer.2.The presence of COPD indicated an increased risk for almost all histological subtypes of lung cancer.3.Both emphysema-predominant and non-emphysema-predominant phenotypes of COPD significantly increased the risk of lung cancer.Relative to non-emphysema-predominant phenotype of COPD,emphysema-predominant phenotype had a higher risk for squamous carcinoma and SCLC.Part Two:The impact of COPD on the prognosis of lung cancerObjectiveThe aim of this part was to observe the impact of COPD on lung cancer prognosis,and to explore the relationship between COPD phenotype and the prognosis of different histologic subtypes of lung cancer.MethodsIn this retrospective-prospective study,participants came from the Qilu Hospital,Shandong University,China(2004-2015),those with a newly pathologically confirmed diagnosis of lung cancer were enrolled from patients preparing for lung cancer surgery.All participants had underwent pulmonary function test(PFT).The diagnosis of COPD was based on GOLD criteria.Lung cancer subtypes and COPD phenotypes were categorized by WHO classification of lung tumors and computer quantitative analysis of PFT.The hazard ratios were estimated by Cox regression analysis.Results1.A total of 2222 patients with newly diagnosed lung cancer were enrolled in this study.The age of lung cancer patients was 60.2�9.5 years.Of the total number of patients,75.2%were male and 53.4%were current smokers or ex-smokers.The histological subtypes identified were as follows:adenocarcinoma(1120[50.4%]),squamous carcinoma(792[35.6%]),SCLC(152[6.8%]),LCLC(58[2.6%]),LCNC(20[0.9%]),adenosquamous carcinoma(46[2.1%]),carcinoid tumors(20[0.9%])and other histologic types(14[0.6%]).Moreover,1821(80.1%)lung cancers had eventually undergone surgery2.The prevalence of COPD in lung cancer patients was 32.6%.Seventy-five emphysema-predominant phenotype(AC=128.6�7.0�)and 581 non-emphysema-predominant phenotype(AC=151.1�7.2�)in COPD patients were identified.There was no significant difference in age,sex,BMI and smoking status between the two phenotypes.3.The median follow-up period was 49.9 months,with a follow-up rate exceeding 95%(2112 of 2222 lung cancers).The 3-/5-year overall survival(OS)rates of all lung cancers were 79.4%/73.5%.The OS rates of LCLC and LCNC were the worst,followed by squamous carcinoma,SCLC and adenosquamous carcinoma,and the OS rates of adenocarcinoma,carcinoid tumors and other types of lung cancer were the best.The 3-/5-year overall survival(OS)rates of lung cancers were 75.2%/68.6%in COPD patients and were-81.5%/76.0%in non-COPD patients.And COPD were significantly associated with worse OS of lung cancers(P<0.001).4.The impact of COPD,COPD severity and COPD phenotypes on the prognosis of lung cancer Multivariate Cox regression analysis showed that,after adjustment for age,sex,BMI,smoking status and therapy method,COPD(especially emphysema-predominant phenotype)was significantly associated with decreased OS of lung cancer(HR 1.28,95%CI,1.05-1.57;HR 1.84,95%CI,1.21-2.80).With the increased severity of COPD,the prognosis of lung cancer was gradually worsened(HR 1.23,95%CI 1.08-1.39).Conversely,the presence of non-emphysema-predominant phenotype of COPD showed no impact on the prognosis of lung cancer(HR 1.14,95%CI 0.91-1.43).5.Comparison of the impact of COPD severity and COPD phenotype on the prognosis of lung cancer After adjustment for age,sex,BMI,smoking status and therapy method,emphysema-predominant phenotype of moderate and severe COPD were significantly associated with decreased OS of lung cancer(HR 1.96,95%CI,1.12-3.46;HR 2.37,95%CI,1.04-5.40).However,the presence of non-emphysema-predominant phenotype of any grades of COPD showed no impact on the prognosis of lung cancer.6.The impact of COPD phenotype on the prognosis of different histologic subtypes of lung cancer Multivariate Cox regression analysis stratified by histology demonstrated that,after adjustment for age,sex,BMI,smoking status and therapy method,emphysema-predominant phenotype of COPD was significantly associated with decreased OS of squamous carcinoma(HR 2.53,95%CI 1.49-4.30),while there was no other significant relationship between COPD phenotypes and the prognosis of adenocarcinoma,SCLC,LCNC,LCLC and other histologic subtypes.Besides,surgical treatment,after adjustment,was still significantly associated with the increased OS of squamous carcinoma and adenocarcinoma(HR 0.43,95%CI 0.32-0.59;HR 0.42,95%CI 0.30-0.60).Conclusion1.COPD can significantly decrease the overall survival of lung cancer.2.The impact of COPD phenotype on the prognosis of lung cancer is more significant than that of COPD severity.3.Emphysema-predominant phenotype,was an independent prognostic risk factor for squamous carcinoma.However,COPD and its phenotypes,were not significantly associated with the prognosis of adenocarcinoma,SCLC,LCNC,LCLC,carcinoid tumors and other histologic subtypes.