The Pittsburgh Lung Screening Study (PLuSS)

Wilson, David O.; Weissfeld, Joel L.; Fuhrman, Carl R.; Fisher, Stephen N.; Balogh, P; Landreneau, Rodney J.; Luketich, James D.; Siegfried, Jill M.

doi:10.1164/rccm.200802-336oc

Cited by 201 publications

(98 citation statements)

References 24 publications

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“…COPD has been repeatedly demonstrated to be associated with an increased risk of lung cancer, even after adjustment for smoking (31). More recently, the presence of emphysema on CT scan has been more strongly associated with lung cancer risk than is airflow obstruction on spirometry (4, 32) The mechanisms by which COPD confers an increased lung cancer risk are not clear, although a common genetic susceptibility, increased inflammation and oxidant radical exposure all may play a role. We hypothesized that alveolar hypoxia might be critical in the increased risk of lung cancer seen in COPD.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple epidemiological studies have shown an increased risk for lung cancer in individuals with airflow obstruction or chronic bronchitis, even after correction for smoking intensity(3). Recent studies have demonstrated an even stronger relationship between lung cancer and emphysema than airflow obstruction (4) The mechanisms by which chronic obstructive pulmonary disease (COPD) contributes to lung cancer risk are still unknown. In addition to an as yet poorly understood shared genetic susceptibility and smoking, other factors that may contribute are inflammation and oxidant damage (5).…”

Section: Introductionmentioning

confidence: 99%

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Alveolar Hypoxia Promotes Murine Lung Tumor Growth through a VEGFR-2/EGFR-Dependent Mechanism

Karoor

Merrick

et al. 2012

Cancer Prevention Research

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Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for the development of lung cancer, the mechanisms for which are incompletely understood. We hypothesized that the hypoxic pulmonary microenvironment present in COPD would augment lung carcinogenesis. Mice were subjected to chemical carcinogenesis protocols and placed in either hypoxia or normoxia. Mice exposed to chronic hypoxia developed tumors with increased volume compared to normoxic controls. Both lungs and tumors from hypoxic mice showed a preferential stabilization of HIF-2α and increased expression of VEGF-A, FGF2 and their receptors as well as other survival, proliferation and angiogenic signaling pathways regulated by HIF-2α. We demonstrated that tumors arising in hypoxic animals have increased sensitivity to VEGFR-2/EGFR inhibition, as chemoprevention with vandetanib showed markedly increased activity in hypoxic mice. These studies demonstrate that lung tumors arising in an hypoxic microenvironment express increased growth, angiogenic and survival signaling that could contribute to the increased lung cancer risk in COPD. Furthermore, the differential sensitivity of tumors arising in hypoxia to VEGFR-2/EGFR inhibition suggests that the altered signaling present in tumors arising in hypoxic lung might be therapeutically exploited in patients with underlying COPD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alveolar Hypoxia Promotes Murine Lung Tumor Growth through a VEGFR-2/EGFR-Dependent Mechanism

Karoor

Merrick

et al. 2012

Cancer Prevention Research

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“…Kishi and colleagues [15] studied 1,520 patients over the age of 50 with a >20 pack-year smoking history and demonstrated that the likelihood of developing lung carcinoma increased if the forced expiratory volume in 1 s was <40% of predicted. This has been further illustrated by Wilson et al [16] who carried out a study of 3,638 patients, evaluated by visually graded emphysema on CT and airflow obstruction on spirometry.…”

Section: Association Between Copd and Lung Cancermentioning

confidence: 93%

The Epithelial Cell and Lung Cancer: The Link between Chronic Obstructive Pulmonary Disease and Lung Cancer

Rooney

Sethi

2011

Respiration

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Chronic obstructive pulmonary disease (COPD) and lung cancer currently form the basis for an enormous disease burden in the developed world. As a result of changing smoking trends and tobacco use, regrettably, a similar picture is arising rapidly within the developing world. COPD is a recognised risk factor for lung cancer, and a significant proportion of patients diagnosed with lung cancer have COPD. An association between both conditions has long been suspected but has proven difficult to demonstrate thus far. However, the common factors between both conditions are now becoming apparent thanks to recent clinical and molecular advances. Abnormal regulation of the immune system and the establishment of chronic inflammation appear to be key events in this process. In addition, the complex interplay between genes and environment and the possibility of a genetic basis to lung cancer susceptibility in the context of COPD are becoming clearer concepts. As we begin to unravel the common pathways and molecules in the pathogenesis of both conditions, we may be able to not only identify novel strategies to prevent and treat COPD and lung cancer, but also recognise molecular markers to identify patients at high risk of developing lung cancer.

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“…There are convincing observations from numerous studies that some NCNs observed on LDCT represent active lung cancer (4–6). However, data from the National Lung Screening Trial (NLST) show that only about 4% of subjects with (4+mm) NCNs were diagnosed with lung cancer within one year (4).…”

Section: Introductionmentioning

confidence: 95%

Short- and Long-term Lung Cancer Risk Associated with Noncalcified Nodules Observed on Low-Dose CT

Pinsky

Nath

Gierada

et al. 2014

Cancer Prevention Research

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Chemoprevention is an important potential tool in reducing lung cancer incidence. Non-calcified nodules (NCNs) observed on low-dose computed tomography (LDCT) have been proposed as intermediate endpoints in chemoprevention trials, but whether NCNs represent cancer precursors is unclear. We analyzed data from subjects in the LDCT arm of the National Lung Screening Trial (NLST) to examine short and long-term lung cancer risks associated with NCNs and to elucidate whether some NCNS may be cancer precursors. NLST subjects received a baseline and two additional LDCT screens and were followed for a median of 6.5 years. We examined lung cancer incidence over three distinct periods from baseline – 0–23 months (short-term), 24–59 months (medium-term) and 60–84 months (long-term) – in relation to baseline NCN characteristics. Spatially, lung cancer incidence was analyzed at the person, lung and lobe levels relative to NCN location. 26,272 subjects received the baseline LDCT screen, with 468, 413, and 190 lung cancers observed in the three periods. The presence of an NCN gave significantly elevated long-term lung cancer risk ratios (RRs) of 1.8, 2.4 and 3.5 at the person, lung and lobe levels; corresponding short-term RRs were 10.3, 16.8 and 38.0. Ground glass attenuation was positively associated with long term-lung cancer risk but inversely associated with short-term risk; NCN size was positively associated with short-term risk but not significantly associated with long-term risk. That NCNs convey significantly elevated excess long-term of lung cancer lends evidence to the hypothesis that some NCNs may be cancer precursors.

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The Pittsburgh Lung Screening Study (PLuSS)

Cited by 201 publications

References 24 publications

Alveolar Hypoxia Promotes Murine Lung Tumor Growth through a VEGFR-2/EGFR-Dependent Mechanism

Alveolar Hypoxia Promotes Murine Lung Tumor Growth through a VEGFR-2/EGFR-Dependent Mechanism

The Epithelial Cell and Lung Cancer: The Link between Chronic Obstructive Pulmonary Disease and Lung Cancer

Short- and Long-term Lung Cancer Risk Associated with Noncalcified Nodules Observed on Low-Dose CT

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