Chronic Obstructive Pulmonary Disease Lung Cancer Research Articles

Prevalence of lung cancer in chronic obstructive pulmonary disease: A systematic review and meta-analysis

BackgroundThere is growing evidence that chronic obstructive pulmonary disease (COPD) can increase the risk of lung cancer, which poses a serious threat to treatment and management. Therefore, we performed a meta-analysis of lung cancer prevalence in patients with COPD with the aim of providing better prevention and management strategies.MethodsWe systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library databases from their inception to 20 March 2022 to collect studies on the prevalence of lung cancer in patients with COPD. We evaluated the methodological quality of the included studies using the tool for assessing the risk of bias in prevalence studies. Meta-analysis was used to determine the prevalence and risk factors for lung cancer in COPD. Subgroup and sensitivity analyses were conducted to explore the data heterogeneity. Funnel plots combined with Egger’s test were used to detect the publication biases.ResultsThirty-one studies, covering 829,490 individuals, were included to investigate the prevalence of lung cancer in patients with COPD. Pooled analysis demonstrated that the prevalence of lung cancer in patients with COPD was 5.08% (95% confidence interval [CI]: 4.17–6.00%). Subgroup analysis showed that the prevalence was 5.09% (95% CI: 3.48–6.70%) in male and 2.52% (95% CI: 1.57–4.05%) in female. The prevalence of lung cancer in patients with COPD who were current and former smokers was as high as 8.98% (95% CI: 4.61–13.35%) and 3.42% (95% CI: 1.51–5.32%); the incidence rates in patients with moderate and severe COPD were 6.67% (95% CI: 3.20–10.14%) and 5.57% (95% CI: 1.89–16.39%), respectively, which were higher than the 3.89% (95% CI: 2.14–7.06%) estimated in patients with mild COPD. Among the types of lung cancer, adenocarcinoma and squamous cell carcinoma were the most common, with incidence rates of 1.59% (95% CI: 0.23–2.94%) and 1.35% (95% CI: 0.57–3.23%), respectively. There were also differences in regional distribution, with the highest prevalence in the Western Pacific region at 7.78% (95% CI: 5.06–10.5%), followed by the Americas at 3.25% (95% CI: 0.88–5.61%) and Europe at 3.21% (95% CI: 2.36–4.06%).ConclusionsThis meta-analysis shows that patients with COPD have a higher risk of developing lung cancer than those without COPD. More attention should be given to this result in order to reduce the risk of lung cancer in these patients with appropriate management and prevention.Systematic review registrationInternational prospective register of systematic reviews, identifier CRD42022331872.

SERPINA1 Methylation Levels are Associated with Lung Cancer Development in Male Patients with Chronic Obstructive Pulmonary Disease.

PurposeThe mechanism of lung cancer (LC) in male patients with chronic obstructive pulmonary disease (COPD) has not been well understood, and the early diagnosis is currently challenging. The study aimed to explore the association of DNA methylation levels with LC development in male COPD patients.Patients and MethodsA total of 147 male participants were divided into four groups, ie, COPD+LC group, COPD group, LC group, and control (CON) group. The methylation levels of human serine protease inhibitor A1 (SERPINA1) and the serum levels of inflammatory biomarkers were compared among groups. Multivariate logistic regression was performed to explore the correlation of inflammatory biomarkers and gene methylation with lung cancer combining COPD.ResultsSERPINA1 methylation levels were significantly higher in the COPD+LC group than that in the COPD group and LC group, respectively (all p < 0.05). The serum levels of interleukin (IL)-1β, IL-17, and transforming growth factor (TGF)-β1 were significantly higher in the COPD+LC group than in the LC group (all p < 0.05). The SERPINA1 methylation levels were positively correlated with the IL-1β levels (r = 0.5188, p = 0.0012). The AUC (area under curve) of SERPINA1 methylation for the diagnosis of LC in COPD was 0.677 (sensitivity of 52.2% and specificity of 78.2%).ConclusionThe methylation of SERPINA1 is linked to LC in patients with COPD. The SERPINA1 methylation levels were positively correlated with the IL-1β levels. These findings may be of diagnostic value.

The Incidence and Risk Analysis of Lung Cancer Development in Patients with Chronic Obstructive Pulmonary Disease: Possible Effectiveness of Annual CT-Screening.

PurposeLung cancer is a serious complication in patients with chronic obstructive pulmonary disease (COPD) and accounts for approximately 15% of deaths in patients with COPD. However, with the exception of emphysema, few reports to date have been published on the factors that predict lung cancer development in COPD patients. It has been reported that patients with COPD develop lung cancer at a rate of 0.8% - 1.7%/year, but the incidence may be higher in the Japanese population. Therefore, we investigated the incidence of lung cancer and the lung cancer mortality rate in Japanese COPD patients, as well as factors that are associated with the development of lung cancer in COPD patients.Patients and MethodsWe followed up 224 patients with stable COPD and performed CT examinations at least once per year. The incidence of lung cancer was recorded and data at enrollment were compared with data of the group that did not develop lung cancer.ResultsOver a median follow-up period of 4.58 years, lung cancer was newly diagnosed in 19 patients; the incidence of lung cancer in this population was 1.85%/year. Patients who developed lung cancer had more severe emphysema assessed by CT and GOLD classification and were more likely to be current smokers than those who did not develop lung cancer. No other significant differences were observed between these two groups. Mortality was significantly increased in patients who developed lung cancer compared with those who did not.ConclusionIn COPD patients, the incidence of lung cancer is higher and the development of lung cancer worsens the prognosis; however, lung cancer development is unpredictable and attention should be paid to all patients. Annual CT screening is important for early detection of lung cancer.

Efforts to control air pollution in the Asia-Pacific region.

Efforts to control air pollution in the Asia-Pacific region.

Inhaled corticosteroid use and the incidence of lung cancer in COPD.

Inhaled corticosteroids (ICS) are suggested for potential chemoprevention of lung cancer. Several observational studies in patients with chronic obstructive pulmonary disease (COPD) reported inconsistent results, either significant reductions in lung cancer incidence with ICS use or no effect. We assessed this association, using an approach that avoided biases affecting some of the studies. A cohort of patients with COPD, new users of long-acting bronchodilators over 2000-2014, was formed using the Quebec healthcare databases, and followed until 2015 for a first diagnosis of lung cancer. A 1-year delay after cohort entry was used to avoid protopathic bias and a 1-year latency period was included after the initiation of ICS use. A time-dependent Cox regression model was used to estimate the hazard ratio (HR) of lung cancer associated with ICS exposure, adjusted for covariates. The cohort involved 63 276 subjects, including 63% receiving ICS, with 3743 lung cancers occurring during a mean follow-up of 5 years. The adjusted HR of lung cancer associated with any ICS exposure was 1.01 (95% CI 0.94-1.08), relative to no ICS use. The HR with longer time (>4 years) since ICS initiation was 0.92 (95% CI 0.83-1.03), while with higher mean daily ICS dose (>1000 μg fluticasone equivalents) was 1.36 (95% CI 1.03-1.81). Inhaled corticosteroid use is not associated with a reduction in lung cancer incidence in patients with COPD. Observational studies reporting such reduction may have been affected by time-related biases and the inclusion of patients with asthma. The proposition of a randomised trial warrants some caution.

Effect of annual influenza vaccination on reducing lung cancer in patients with chronic obstructive pulmonary disease from a population-based cohort study.

Chronic obstructive pulmonary disease (COPD) patients are at a higher risk of development of lung cancer. Frequent exacerbations of COPD trigger the disease course to chronic inflammation which likely plays a role in the pathogenesis of lung cancer. Previous studies showed influenza virus infection is one of important causes for exacerbations of COPD. Therefore, the aim of this study was to know whether influenza vaccination could reduce the incidence of lung cancer in patients with COPD.This cohort study enrolled patients (≥55 years old) with a recorded diagnosis of COPD between January 1, 2000 and December 31, 2012 by using the Taiwan Health Insurance Database. A propensity score was calculated to reduce vaccine therapy selection bias. Cox proportional hazard regressions were used to investigate the association between the influenza vaccination and lung cancer incidence after adjusting for known confounding factors. Besides, we categorized the patients into 4 groups according to vaccination status (unvaccinated, total number of vaccinations: 1, 2–3, ≥4) to evaluate the dose-dependent effect on reducing lung cancer occurrence of lung cancer in COPD patients.Our study comprised of 28,752 eligible individuals from the COPD cohort database. Among them, 51% (14,630) received influenza vaccination; the rest (49%) of the COPD patients did not receive influenza vaccination. We observed that COPD patients receiving influenza vaccination had a lower risk of lung cancer (adjusted HR = 0.40, 95% CI (0.35–0.45), P < .001). We also founded comparable protective effect in both sexes and all age groups (55–64, 65–74, ≥75) regardless of influenza seasonality. Furthermore, dose-dependent protective effect could be seen after stratifying patients according to the total number vaccinations, the adjusted HRs for lung cancer risk were 0.48 (0.40–0.54) and 0.24 (0.20–0.29) for patients who received 2 to 3 and ≥4 vaccinations during the follow-up period.This population-based cohort study demonstrated that annual influenza vaccination administration could reduce incidence of lung cancer in COPD patients.

Found in Translation: Multi-omics Assessment of the Chronic Obstructive Pulmonary Disease-Lung Cancer Interaction.

Found in Translation: Multi-omics Assessment of the Chronic Obstructive Pulmonary Disease-Lung Cancer Interaction.

Inhaled corticosteroids and the risk of lung cancer in COPD: a population-based cohort study

Inhaled corticosteroids (ICSs) are often prescribed in patients with chronic obstructive pulmonary disease (COPD). Their impact on the risk of lung cancer, a leading cause of mortality in COPD patients, remains uncertain.Population-based linked administrative data between the years 1997 and 2007 from the province of British Columbia, Canada, were used to evaluate the association between lung cancer risk and ICS use in COPD patients. COPD was defined on the basis of receipt of three COPD-related prescriptions in subjects ≥50 years of age. Exposure to ICS was incorporated into multivariable Cox regression models using several time-dependent methods ("ever" exposure, cumulative duration of use, cumulative dose, weighted cumulative duration of use and weighted cumulative dose).There were 39 676 patients who met the inclusion criteria. The mean±sd age of the cohort was 70.7±11.1 years and 53% were female. There were 994 (2.5%) cases of lung cancer during follow-up. In the reference case analysis (time-dependent "ever" exposure), ICS exposure was associated with a 30% reduced risk of lung cancer (HR 0.70 (95% CI 0.61-0.80)). ICS exposure was associated with a decrease in the risk of lung cancer diagnosis over all five methods of quantifying exposure.This population-based study suggests that ICS use reduces the risk of lung cancer in COPD patients.

DNA repair as an emerging target for COPD-lung cancer overlap.

Cigarette smoking is the leading cause of lung cancer and chronic obstructive pulmonary disease (COPD). Many of the detrimental effects of cigarette smoke have been attributed to the development of DNA damage, either directly from chemicals contained in cigarette smoke or as a product of cigarette smoke-induced inflammation and oxidative stress. In this review, we discuss the environmental, epidemiological, and physiological links between COPD and lung cancer and the likely role of DNA damage and repair in COPD and lung cancer development. We explore alterations in DNA damage repair by DNA repair proteins and pathways. We discuss emerging data supporting a key role for the DNA repair protein, xeroderma pigmentosum group C (XPC), in cigarette smoke-induced COPD and early lung cancer development. Understanding the interplay between cigarette smoke, DNA damage repair, COPD, and lung cancer may lead to prognostic tools and new, potentially targetable, pathways for lung cancer prevention and treatment.

Multi-omic molecular profiling of lung cancer in COPD.

Chronic obstructive pulmonary disease (COPD) is a known risk factor for developing lung cancer but the underlying mechanisms remain unknown. We hypothesise that the COPD stroma contains molecular mechanisms supporting tumourigenesis.We conducted an unbiased multi-omic analysis to identify gene expression patterns that distinguish COPD stroma in patients with or without lung cancer. We obtained lung tissue from patients with COPD and lung cancer (tumour and adjacent non-malignant tissue) and those with COPD without lung cancer for profiling of proteomic and mRNA (both cytoplasmic and polyribosomal). We used the Joint and Individual Variation Explained (JIVE) method to integrate and analyse across the three datasets.JIVE identified eight latent patterns that robustly distinguished and separated the three groups of tissue samples (tumour, adjacent and control). Predictive variables that associated with the tumour, compared to adjacent stroma, were mainly represented in the transcriptomic data, whereas predictive variables associated with adjacent tissue, compared to controls, were represented at the translatomic level. Pathway analysis revealed extracellular matrix and phosphatidylinositol-4,5-bisphosphate 3-kinase-protein kinase B signalling pathways as important signals in the tumour adjacent stroma.The multi-omic approach distinguishes tumour adjacent stroma in lung cancer and reveals two stromal expression patterns associated with cancer.

Year in review 2017: Chronic obstructive pulmonary disease and asthma.

Year in review 2017: Chronic obstructive pulmonary disease and asthma.

The Relationship Between COPD Phenotypes and Severity and Lung Cancer Development: Where We Have to Focused?

SESSION TITLE: COPD 1 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Cross-sectional studies show that the prevalence of chronic obstructive pulmonary disease(COPD) is around 50% of those diagnosed with lung cancer(LC),although the prevalence might change depending on the patient′s age sex,and smoking exposure.The aim of our study was to analyze the clinical and histological characteristics of LC in COPD patients. METHODS: From February 2011 to March 2016 we have evaluated 416 patients with COPD and in all patients with COPD the diagnosis was confirmed by recommendations of GOLD guidelines.All patients with COPD were treated by GOLD guidelines and heve received bronchdilators.The patients were older than 35 years(range:35-85 years) and the diagnosis of LC among COPD patients was confirmed by histological or cytological specimens in all cases.All patients were smokers(ex-or current). RESULTS: Among 416 COPD patients in 89(21%) we have found LC,and 70(79%) were not treated with surgery because of the disseminated disease(stages 3B and IV).In COPD patients poor lung function and chronic cough with sputum significantly impact to the development of LC.In 61(69%) patients the LC was associated with advanced stages of the COPD(GOLD groups C and D) and only in 28(31%) patients the LC was associated with early stages of the disease(GOLD groups A and B; P<0.001). In LC-COPD patients chronic cough with sputum and airway disease predominant phenotype of COPD was common finding compared with emphysema predominant phenotype of the disease(P<0.001).Our this finding might be explain with airway tickening and peribronchial fibrosis in such patients which leads to airway obstruction and remodeling in COPD with excess metalloproteinase and growth factors that may potentially cause a premalignant transformation ,epithelial mesenchymal transition.Advanced stages of the COPD most common were associated with squamous cell lung cancer compared with early stages of the disease (58[65%] vs 9[10%];P<0.001)which most common were associated with adenocarcinoma .Small cell lung cancer was more common finding in COPD patients with groups Cand D(P<0.05). CONCLUSIONS: Our study shown that poor lung function and severity of the COPD were strongly risk factors for development of lung cancer.Airway disease predominant phenotype of the COPD and chronic cough with sputum although increased the risk of the lung cancer in COPD patients.The predominance of airway tickening and peribronchial fibrosis in COPD patients increased risk of lung cancer development.Poor lung function and more severe disease most common was associated with squamous cell lung cancer. CLINICAL IMPLICATIONS: Our findings might be useful for respiratory therapist, thoracic oncologists,pulmonary medicine specialists,nurse specialists. DISCLOSURE: The following authors have nothing to disclose: Alizamin Sadigov I ready discuss any information about our investigation

SC13.02 Increased Risk for Lung Cancer in COPD

SC13.02 Increased Risk for Lung Cancer in COPD

Lung cancer screening in patients with chronic obstructive pulmonary disease.

Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment.

Relationship Between Emphysema Severity and the Location of Lung Cancer in Patients With Chronic Obstructive Lung Disease.

New phenotypes of chronic obstructive pulmonary disease (COPD) based on emphysema severity have been recognized recently. The purpose of this study was to determine the relationship between emphysema severity (phenotype) and lung cancer location in patients with COPD. Four hundred patients with 405 primary lung cancers confirmed pathologically between January 2010 and March 2014 were included in the study. Of these, 193 patients received a diagnosis of COPD according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. We scored emphysema severity (0-4) on thin-section CT and assigned the anatomic tumor location of lung cancer as peripheral or central. Patients with COPD had a higher proportion of centrally located lung cancer compared with those without COPD (36.4% vs 17.4%; p < 0.001). In patients with COPD, lower emphysema grades (odds ratio [OR], 0.69; 95% CI, 0.51-0.93; p = 0.016) and reduced ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) (OR, 0.94; 95% CI, 0.89-0.99; p = 0.024) were associated with central location. After adjusting for age, smoking, and spirometry results, the proportion of central location was approximately four times higher in patients with lower emphysema grades (0-2, < 25%) than in those with severe grades (grade 4, > 51%). Lower emphysema grades and reduced FEV1/FVC seemed to be independent predictors of central location of lung cancer in COPD. Therefore, in patients with COPD with lower grade emphysema and airway-predominant disease, additional screening tools may have to be considered for central lung cancer detection along with thin-section CT.

A randomized controlled trial of inhaled corticosteroids (ICS) on markers of epithelial&amp;ndash;mesenchymal transition (EMT) in large airway samples in COPD: an exploratory proof of concept study

BackgroundWe recently reported that epithelial–mesenchymal transition (EMT) is active in the airways in chronic obstructive pulmonary disease (COPD), suggesting presence of an active profibrotic and promalignant stroma. With no data available on potential treatment effects, we undertook a blinded analysis of inhaled corticosteroids (ICS) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients, as a “proof of concept” study.MethodsAssessment of the effects of inhaled fluticasone propionate (FP; 500 μg twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone propionate and eleven on placebo). The end points were epidermal growth factor receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT: reticular basement membrane (Rbm) fragmentation (“hallmark” structural marker), matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in basal epithelial and Rbm cells (mesenchymal transition markers).ResultsEpithelial activation, “clefts/fragmentation” in the Rbm, and changes in the other biomarkers all regressed on ICS, at or close to conventional levels of statistical significance. From these data, we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study.ConclusionAlthough only a pilot “proof of concept” study, this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways. A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important. Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD.

Systemic Inflammation and Comorbidities in Chronic Obstructive Pulmonary Disease

The relationship between systemic inflammation and comorbidities in patients with chronic obstructive pulmonary disease (COPD) is unclear. This article discusses (1) the prevalence and clinical impact of comorbidities in COPD; (2) the current knowledge on definition, prevalence, consequences, and treatment of systemic inflammation in COPD; and (3) the relationship of systemic inflammation and lung cancer in COPD.