Strange Bedfellows: The Interaction between COPD and Lung Cancer in the Context of Lung Cancer Screening.
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ABSTRACT:
SUBMITTER: Silvestri GA
PROVIDER: S-EPMC7328173 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
Publications
Strange Bedfellows: The Interaction between COPD and Lung Cancer in the Context of Lung Cancer Screening.
Silvestri Gerard A GA Young Robert P RP
Annals of the American Thoracic Society 20200701 7
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Project description:Comorbidities significantly contribute to morbidity, mortality, and health-care costs in individuals with COPD. Comorbidity prevalence does not always correlate with lung disease severity, and the elevated risk of certain comorbidities is often independent of shared risk factors such as tobacco burden. Although COPD management guidelines recognize the importance of identifying and treating comorbidities as part of the comprehensive management of COPD patients, little guidance is provided regarding best screening practices. Whereas universal comorbidity screening in COPD patients is likely not cost-effective, targeted early screening and treatment in those at highest risk may have a significant impact on COPD outcomes. Recent studies suggest that certain radiographic features on thoracic imaging may serve as surrogate markers of comorbidity in patients with COPD. This review evaluates these studies in the context of the growing availability of chest CT scans in the lung cancer screening era and discusses how chest CT imaging can be leveraged to identify those COPD patients at highest risk for comorbid disease.
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Project description:Recent genome-wide association studies have reported a FAM13A variant on chromosome 4q22.1 is associated with lung function and COPD. We examined this variant in a case-control study of current or former smokers with chronic obstructive pulmonary disease (COPD, n = 458), lung cancer (n = 454), or normal lung function (n = 488). Sex, age, and smoking history were comparable between groups. We confirmed the FAM13A variant (rs7671167) confers a protective effect on smoking-related COPD alone (C allele odds ratio [OR] = 0.79, P = 0.013, and CC genotype OR = 0.71, P = 0.024) and those with COPD, both with and without lung cancer (C allele OR = 0.80, P = 0.008, and CC genotype OR = 0.70, P = 0.007). The FAM13A variant also confers a protective effect on lung cancer overall (C allele OR = 0.75, P = 0.002, and CC genotype OR = 0.64, P = 0.003) even after excluding those with co-existing COPD (C allele OR = 0.67, P = 0.0007, and CC genotype OR = 0.58, P = 0.006). This was independent of age, sex, height, lung function, and smoking history. This protective effect was confined to those with nonsmall cell lung cancer (C allele OR = 0.72, P = 0.0009, and CC genotype OR = 0.61, P = 0.003). This study suggests that genetic predisposition to COPD is shared with lung cancer through shared pathogenetic factors such as the 4q22.1 locus implicating the Rho-kinase pathway.
| S-EPMC3681173 | biostudies-literature
Project description:ImportanceAlthough there is a growing recognition that older adults and those with extensive comorbid conditions undergo cancer screening too frequently, there is little information about patients' perceptions regarding cessation of cancer screening. Information on older adults' views of screening cessation would be helpful both for clinicians and for those designing interventions to reduce overscreening.ObjectiveTo obtain a deeper understanding of older adults' perspectives on screening cessation and their experiences communicating with clinicians about this topic.DesignSemistructured interview study.SettingSenior health center affiliated with an urban hospital.ParticipantsWe interviewed 33 older adults presenting to a senior health center. Their median age was 76 years (range, 63-91 years). Of the 33 participants, 27 were women; 15 were African American, 16 were white, 1 was Asian, and 1 was American Indian.Main outcome measuresWe transcribed audio recordings of interviews and analyzed them using methods of grounded theory to identify themes and illustrative quotes.ResultsUndergoing screening tests was perceived by participants as morally obligatory. Although many saw continued screening as a habit or custom not involving any decision, cessation of screening would require a major decision. Many asserted that they had never discussed screening cessation with their physicians or considered stopping on their own; some reported being upset when their physician recommended stopping. Although some would accept a physician's strong recommendation to stop, others thought that such a physician's recommendation would threaten trust or lead them to get another opinion. Participants were skeptical about the role of statistics and the recommendations of government panels in screening decisions but were more favorable toward stopping because of the balance of risks and benefits, complications, or test burdens.Conclusions and relevanceFor many older adults, stopping screening is a major decision, but continuing screening is not. A physician's recommendation to stop may threaten patient trust. Effective strategies to reduce nonbeneficial screening may include discussion of the balance of risks and benefits, complications, or burdens.
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Project description:BackgroundTumor-associated autoantibodies are considered promising markers for early lung cancer detection; so far, however, their capacity to detect cancer has been tested mostly in a clinical context, but not in population screening settings. This study evaluates the early detection accuracy, in terms of sensitivity and specificity, of EarlyCDT®-Lung-a test panel of seven tumor-associated autoantibodies optimized for lung cancer detection-using blood samples originally collected as part of the German Lung Cancer Screening Intervention Trial.MethodsThe EarlyCDT®-Lung test was performed for all participants with lung cancer detected via low-dose computed tomography and with available blood samples taken at detection, and for 180 retrospectively selected cancer-free participants at the end of follow-up: 90 randomly selected from among all cancer-free participants (baseline controls) and 90 randomly selected from among cancer-free participants with suspicious imaging findings (suspicious nodules controls). Sensitivity and specificity of lung cancer detection were estimated in the case group and the two control groups, respectively.ResultsIn the case group, the test panel showed a sensitivity of only 13.0% (95% CI: 4.9-26.3%). Specificity was estimated at 88.9% (95% CI: 80.5-94.5%) in the baseline control group, and 91.1% (95% CI: 83.2-96.1%) among controls presenting CT-detected nodules.ConclusionsThe test panel showed insufficient sensitivity for detecting lung cancer at an equally early stage as with low-dose computed tomography screening.
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Project description:BackgroundCOPD is a major comorbidity in lung cancer screening (LCS) cohorts, with a high prevalence of undiagnosed COPD. Combining symptom assessment with spirometry in this setting may enable earlier diagnosis of clinically significant COPD and facilitate increased understanding of lung cancer risk in COPD. In this study, we wished to understand the prevalence, severity, clinical phenotype and lung cancer risk of individuals with symptomatic undiagnosed COPD in a LCS cohort.Methods16 010 current or former smokers aged 55-77 years attended a lung health check as part of the SUMMIT Study. A respiratory consultation and spirometry were performed alongside LCS eligibility assessment. Those with symptoms, no previous COPD diagnosis and airflow obstruction were labelled as undiagnosed COPD. Baseline low-dose computed tomography (LDCT) was performed in those at high risk of lung cancer (PLCOm2012 score ≥1.3% and/or meeting USPSTF 2013 criteria).ResultsNearly one in five (19.7%) met criteria for undiagnosed COPD. Compared with those previously diagnosed, those undiagnosed were more likely to be male (59.1% versus 53.2%; p<0.001), currently smoking (54.9% versus 47.6%; p<0.001) and from an ethnic minority group (p<0.001). Undiagnosed COPD was associated with less forced expiratory volume in 1 s impairment (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1 and 2: 85.3% versus 68.4%; p<0.001) and lower symptom/exacerbation burden (GOLD A and B groups: 95.6% versus 77.9%; p<0.001) than those with known COPD. Multivariate analysis demonstrated that airflow obstruction was an independent risk factor for lung cancer risk on baseline LDCT (adjusted OR 2.74, 95% CI 1.73-4.34; p<0.001), with a high risk seen in those with undiagnosed COPD (adjusted OR 2.79, 95% CI 1.67-4.64; p<0.001).ConclusionsTargeted case-finding within LCS detects high rates of undiagnosed symptomatic COPD in those most at risk. Individuals with undiagnosed COPD are at high risk for lung cancer.
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Project description:Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of lung cancer; however, the association between COPD and stage of lung cancer diagnosis is unclear. We conducted a population-based cross-sectional analysis of lung cancer patients (2008-2020) in Ontario, Canada. Using estimated propensity scores and inverse probability weighting, logistic regression models were developed to assess the association between COPD and lung cancer stage at diagnosis (early: I/II, advanced: III/IV), accounting for prior chest imaging. We further examined associations in subgroups with previously diagnosed and undiagnosed COPD. Over half (55%) of all lung cancer patients in Ontario had coexisting COPD (previously diagnosed: 45%, undiagnosed at time of cancer diagnosis: 10%). Compared to people without COPD, people with COPD had 30% lower odds of being diagnosed with lung cancer in the advanced stages (OR = 0.70, 95% CI: 0.68 to 0.72). Prior chest imaging only slightly attenuated this association (OR = 0.77, 95% CI: 0.75 to 0.80). The association with lower odds of advanced-stage diagnosis remained, regardless of whether COPD was previously diagnosed (OR = 0.68, 95% CI: 0.66 to 0.70) or undiagnosed (OR = 0.77, 95% CI: 0.73 to 0.82). Although most lung cancers are detected in the advanced stages, underlying COPD was associated with early-stage detection. Lung cancer diagnostics may benefit from enhanced partnership with COPD healthcare providers.
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Project description:BackgroundIn the United States, 9 to 10 million Americans are estimated to be eligible for computed tomographic lung cancer screening (CTLS). Those meeting criteria for CTLS are at high-risk for numerous cardio-pulmonary co-morbidities. The objective of this study was to determine the association between qualitative emphysema identified on screening CTs and risk for hospital admission.Study design and methodsWe conducted a retrospective multicenter study from two CTLS cohorts: Lahey Hospital and Medical Center (LHMC) CTLS program, Burlington, MA and Mount Auburn Hospital (MAH) CTLS program, Cambridge, MA. CTLS exams were qualitatively scored by radiologists at time of screening for presence of emphysema. Multivariable Cox regression models were used to evaluate the association between CT qualitative emphysema and all-cause, COPD-related, and pneumonia-related hospital admission.ResultsWe included 4673 participants from the LHMC cohort and 915 from the MAH cohort. 57% and 51.9% of the LHMC and MAH cohorts had presence of CT emphysema, respectively. In the LHMC cohort, the presence of emphysema was associated with all-cause hospital admission (HR 1.15, CI 1.07-1.23; p < 0.001) and COPD-related admission (HR 1.64; 95% CI 1.14-2.36; p = 0.007), but not with pneumonia-related admission (HR 1.52; 95% CI 1.27-1.83; p < 0.001). In the MAH cohort, the presence of emphysema was only associated with COPD-related admission (HR 2.05; 95% CI 1.07-3.95; p = 0.031).ConclusionQualitative CT assessment of emphysema is associated with COPD-related hospital admission in a CTLS population. Identification of emphysema on CLTS exams may provide an opportunity for prevention and early intervention to reduce admission risk.
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Project description:ImportanceIn 2021, the US Preventive Services Task Force (USPSTF) broadened its age and smoking pack-year requirement for lung cancer screening.ObjectivesTo compare the 2021 USPSTF lung cancer screening criteria with other lung cancer screening criteria and evaluate whether the sensitivity and specificity of these criteria differ by race.Design, setting, and participantsThis study included 912 patients with lung cancer and 1457 controls without lung cancer enrolled in an epidemiology study (INHALE [Inflammation, Health, Ancestry, and Lung Epidemiology]) in the Detroit metropolitan area between May 15, 2012, and March 31, 2018. Patients with lung cancer and controls were 21 to 89 years of age; patients with lung cancer who were never smokers and controls who were never smokers were not included in these analyses. Statistical analysis was performed from August 31, 2020, to April 13, 2021.Main outcomes and measuresThe study assessed whether patients with lung cancer and controls would have qualified for lung cancer screening using the 2013 USPSTF, 2021 USPSTF, and 2012 modification of the model from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCOm2012) screening criteria. Sensitivity was defined as the percentage of patients with lung cancer who qualified for screening, while specificity was defined as the percentage of controls who did not qualify for lung cancer screening.ResultsParticipants included 912 patients with a lung cancer diagnosis (493 women [54%]; mean [SD] age, 63.7 [9.5] years) and 1457 control participants without lung cancer at enrollment (795 women [55%]; mean [SD] age, 60.4 [9.6] years). With the use of 2021 USPSTF criteria, 590 patients with lung cancer (65%) were eligible for screening compared with 619 patients (68%) per the PLCOm2012 criteria and 445 patients (49%) per the 2013 USPSTF criteria. With the use of 2013 USPSTF criteria, significantly more White patients than African American patients with lung cancer (324 of 625 [52%] vs 121 of 287 [42%]) would have been eligible for screening. This racial disparity was absent when using 2021 USPSTF criteria (408 of 625 [65%] White patients vs 182 of 287 [63%] African American patients) and PLCOm2012 criteria (427 of 625 [68%] White patients vs 192 of 287 [67%] African American patients). The 2013 USPSTF criteria excluded 950 control participants (65%), while the PLCOm2012 criteria excluded 843 control participants (58%), and the 2021 USPSTF criteria excluded 709 control participants (49%). The 2013 USPSTF criteria excluded fewer White control participants than African American control participants (514 of 838 [61%] vs 436 of 619 [70%]). This racial disparity is again absent when using 2021 USPSTF criteria (401 of 838 [48%] White patients vs 308 of 619 [50%] African American patients) and PLCOm2012 guidelines (475 of 838 [57%] White patients vs 368 of 619 [60%] African American patients).Conclusions and relevanceThis study suggests that the USPSTF 2021 guideline changes improve on earlier, fixed screening criteria for lung cancer, broadening eligibility and reducing the racial disparity in access to screening.
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Project description:BackgroundLung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier integrity and increases susceptibility to infections. Herein, we hypothesize that somatic mutations together with cigarette smoke generate a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from 33 controls and 143 cancer cases, we conduct 16S ribosomal RNA (rRNA) bacterial gene sequencing, with RNA-sequencing data from lung cancer cases in The Cancer Genome Atlas serving as the validation cohort.ResultsOverall, we demonstrate a lower alpha diversity in normal lung as compared to non-tumor adjacent or tumor tissue. In squamous cell carcinoma specifically, a separate group of taxa are identified, in which Acidovorax is enriched in smokers. Acidovorax temporans is identified within tumor sections by fluorescent in situ hybridization and confirmed by two separate 16S rRNA strategies. Further, these taxa, including Acidovorax, exhibit higher abundance among the subset of squamous cell carcinoma cases with TP53 mutations, an association not seen in adenocarcinomas.ConclusionsThe results of this comprehensive study show both microbiome-gene and microbiome-exposure interactions in squamous cell carcinoma lung cancer tissue. Specifically, tumors harboring TP53 mutations, which can impair epithelial function, have a unique bacterial consortium that is higher in relative abundance in smoking-associated tumors of this type. Given the significant need for clinical diagnostic tools in lung cancer, this study may provide novel biomarkers for early detection.
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Project description: Not available
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