COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma

Papi, Alberto

doi:10.1136/thx.2003.018291

Cited by 190 publications

(155 citation statements)

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“…Our previous study showed that for every 1-L decrease in FEV 1 , the odds of high-grade preinvasive lesion increased by approximately 50% (odds ratio, 1.49) (24). Papi and colleagues showed that the odds of squamous cell carcinoma increased by over fourfold when patients developed COPD (25). The mechanisms linking reduced FEV 1 with airway dysplasia and squamous cell carcinoma are uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…Several of these genes are homologous to the human asthma loci (7). Intriguingly, it has been known for decades that obstructive and fibrosing lung conditions associated with chronic inflammation, such as pulmonary fibrosis, sarcoidosis, and chronic obstructive pulmonary disease, also increase the risk of lung cancer (8)(9)(10). More recently, it has been shown that these conditions also present with systemic inflammation (11)(12)(13).…”

mentioning

confidence: 99%

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Progression of Airway Dysplasia and C-Reactive Protein in Smokers at High Risk of Lung Cancer

Sin

Man

McWilliams

et al. 2006

Am J Respir Crit Care Med

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Rationale: Chronic inflammation has been implicated in the development of airway dysplasia and lung cancer. It is unclear whether circulating biomarkers of inflammation could be used to predict progression of airway dysplasia. Objective: We determined whether circulating levels of C-reactive protein (CRP) or other inflammatory biomarkers could predict progression of bronchial dysplasia in smokers over 6 mo. Methods: The plasma levels of CRP, interleukins 6 and 8, and monocyte chemoattractant protein 1 were measured at baseline in 65 ex-and current smokers who had at least one site of bronchial dysplasia Ͼ 1.2 mm in size. Additional bronchial biopsies were taken after 6 mo from the same sites where dysplastic lesions were discovered at baseline. Progressive dysplastic lesions were defined as worsening of the dysplastic lesion by at least two grades or development of new dysplastic lesions. Results: Half of the participants developed progressive dysplastic lesions after 6 mo. The baseline CRP levels in these participants were 64% higher than those without progressive disease (p ϭ 0.027). Only one of eight (13%) participants with CRP р 0.5 mg/L developed progressive disease, whereas 31 of 57 (54%) participants with CRP Ͼ 0.5 mg/L developed progressive disease (p ϭ 0.011). The odds of developing progressive disease were 9.6-fold higher in the latter than in the former group. Conclusion: Plasma CRP, in concert with lung function and packyears of smoking, appears to have excellent predictive powers in identifying participants with bronchial dyplastic lesions whose lesions progress to more advanced stages of dysplasia. Keywords: airway dysplasia; C-reactive protein; lung inflammationLung cancer is a worldwide epidemic. More than 1 million people die of this disease annually (1). In the United States alone, 170,000 new cases of lung cancer are reported each year (2). Most of these are non-small cell lung cancer (NSCLC) and the overall prognosis once diagnosed is dismal (2). The only reasonable chance of cure for NSCLC is surgical resection for early-stage tumors (3). However, most patients with early lung cancer are often asymptomatic (4). Symptoms usually develop when the tumors become invasive or disseminated and curative resection is infeasible. In response, there has been a growing effort to discover novel (non-or semiinvasive) methods to identify individuals harboring precancerous lesions and to use a In animal models, chronic inflammation has been demonstrated to be an important risk factor for tumor genesis (6), and several susceptibility loci in mice for lung neoplasia also contain susceptibility genes for lung injury and inflammation. Several of these genes are homologous to the human asthma loci (7). Intriguingly, it has been known for decades that obstructive and fibrosing lung conditions associated with chronic inflammation, such as pulmonary fibrosis, sarcoidosis, and chronic obstructive pulmonary disease, also increase the risk of lung cancer (8-10). More recently, it has been shown that these conditions a...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Progression of Airway Dysplasia and C-Reactive Protein in Smokers at High Risk of Lung Cancer

Sin

Man

McWilliams

et al. 2006

Am J Respir Crit Care Med

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“…In a study on patients undergoing lung resection for non-small cell lung cancer (NSCLC), impaired FEV1% was associated with significant increase in risk for SCC subtype [17]. In another study, Malhotra et al also reported that impaired FEV1 was associated with greater chance of SCC [30].…”

Section: Discussionmentioning

confidence: 87%

“…Several previous studies have reported that ILF and COPD are consistently associated with an increased risk of incident LC [14][15][16][17][18][19]. ILF has also been shown to be related to LC mortality [14,22,23].…”

Section: Discussionmentioning

confidence: 96%

“…Spirometry is a widely available and inexpensive test for evaluating the airflow limitation and lung function (LF). It has been shown that patients with moderate to severe COPD are at more than 4 fold increased risk of LC, with a significant linear increase in risk with a greater degree of airway obstruction [14][15][16][17][18][19]. However, the relationship between impaired LF (ILF) and the risk of development and progression of EPLs is less clear.…”

Section: Introductionmentioning

confidence: 98%

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Effect of Impaired Lung Function on the Development and Progression of Endobronchial Premalignant Lesions

Jayaprakash¹,

Loewen²,

Mahoney³

et al. 2012

JCT

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Background: Chronic obstructive pulmonary disease (COPD) and the presence of endobronchial premalignant lesions (EPL) are individual risk factors for lung cancer (LC). However, effect of impaired lung function (ILF) on the natural history of EPL has not been explored. Patients and Methods: This study included 217 high-risk participants from a hospital-based LC surveillance cohort who underwent pulmonary function testing followed by bronchoscopy with endobronchial biopsies. Baseline histopathology diagnoses included 91 cases (41.9%) with squamous metaplasia (SM), 25 (11.5%) with squamous dysplasia (SD), 1 (0.5%) with in-situ carcinoma and 5 (2.3%) with invasive LC. Follow-up biopsies were obtained for 69 patients, and 16 (23.2%) patients demonstrated progression to a higher grade lesion. Regression models were used to evaluate the relationship between ILF and EPL. All the models were adjusted for age, gender and tobacco smoking. Results: Patients with FEV 1 % of <50% had 4.5 times greater risk of being diagnosed with an EPL [95% confidence interval: 1.93 -10.80] and 8-fold greater risk of SD, compared to patients with FEV1% ≥ 80. COPD was associated with 2.7 and 4.8 times greater risk of SM and SD, respectively. The mean time to progression to a higher-grade lesion was shorter in COPD patients compared to patients without COPD (27 versus 50 months, p = 0.02). Conclusion: Our results indicate that ILF may be a predictor of prevalence and progression of EPLs among patients at high risk of LC. Therefore, spirometry can be a complementary pre-screening tool for identifying patients with EPL who need more intense LC surveillance.

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Personalizing annual lung cancer screening for patients with chronic obstructive pulmonary disease: A decision analysis

Lowry

Gazelle

Gilmore

et al. 2015

Cancer

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Background Lung cancer screening with annual chest CT is recommended for current and former smokers with ≥30+ pack-year smoking history. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lung cancer and may benefit from screening at lower pack-year thresholds. Methods We used a previously validated simulation model to compare the health benefits of lung cancer screening in current and former smokers ages 55-80 with ≥30 pack-years to hypothetical programs using lower pack-year thresholds for individuals with COPD (≥20, ≥10, and ≥1 pack-years). Calibration targets for COPD prevalence and associated lung cancer risk were derived using the Framingham Offspring Study Limited Dataset. We performed sensitivity analyses to evaluate the stability of results across different rates of adherence to screening, increased competing mortality risk due to COPD, and increased surgical ineligibility in individuals with COPD. The primary outcome was projected life expectancy. Results Programs using lower pack-year thresholds for individuals with COPD yielded the highest life expectancy gains for a given number of screens. Highest life expectancy was achieved when lowering the pack-year threshold to ≥1 pack-year for individuals with COPD, which dominated all other screening strategies. These results were stable across different adherence rates to screening and increases in competing mortality risk for COPD and surgical ineligibility. Conclusion Current and former smokers with COPD may disproportionately benefit from lung cancer screening. A lower pack-year threshold for screening eligibility may benefit this high-risk patient population.

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COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma

Cited by 190 publications

References 9 publications

Progression of Airway Dysplasia and C-Reactive Protein in Smokers at High Risk of Lung Cancer

Progression of Airway Dysplasia and C-Reactive Protein in Smokers at High Risk of Lung Cancer

Effect of Impaired Lung Function on the Development and Progression of Endobronchial Premalignant Lesions

Personalizing annual lung cancer screening for patients with chronic obstructive pulmonary disease: A decision analysis

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