Interstitial Lung Abnormalities and Lung Cancer Risk in the National Lung Screening Trial.

BACKGROUND Some interstitial lung diseases are associated with lung cancer. However, it is unclear whether asymptomatic interstitial lung abnormalities convey an independent risk. OBJECTIVES To assess whether interstitial lung abnormalities are associated with an increased risk of lung cancer. METHODS We analyzed data from all participants in the National Lung Cancer Trial (NSLT) except for subjects with pre-existing interstitial lung disease or prevalent lung cancers. The primary analysis included those who underwent low-dose computed tomography; those undergoing chest radiography were included in a confirmatory analysis. Participants with evidence of reticular/reticulonodular opacities, honeycombing, fibrosis, or scarring were classified as having interstitial lung abnormalities. Lung cancer incidence and mortality in participants with and without interstitial lung abnormalities were compared using Poisson and Cox regression, respectively. RESULTS Of the 25,041 participants undergoing LDCT included in the primary analysis, 20.2% had interstitial lung abnormalities. Participants with interstitial lung abnormalities had higher incidence of lung cancer (IRR 1.61, 95% CI: 1.30-1.99). Interstitial lung abnormalities were associated with higher lung cancer incidence on adjusted analyses (IRR: 1.33, 95% CI: 1.07-1.65). Lung cancer-specific mortality was also greater in participants with interstitial lung abnormalities. Similar findings were obtained in the analysis of participants undergoing chest radiography. CONCLUSIONS Asymptomatic interstitial lung abnormalities are an independent risk factor for lung cancer which can be incorporated into risk score models.

[1]  Wei Gao,et al.  Paraseptal emphysema: Prevalence and distribution on CT and association with interstitial lung abnormalities. , 2015, European journal of radiology.

[2]  Jae Ho Lee,et al.  Lung cancer in patients with idiopathic pulmonary fibrosis: clinical characteristics and impact on survival. , 2013, Respiratory medicine.

[3]  Katherine P Andriole,et al.  Lung volumes and emphysema in smokers with interstitial lung abnormalities. , 2011, The New England journal of medicine.

[4]  Raúl San José Estépar,et al.  Identification of early interstitial lung disease in smokers from the COPDGene Study. , 2010, Academic radiology.

[5]  A. Dirksen,et al.  Interstitial lung abnormalities are associated with increased mortality in smokers. , 2018, Respiratory medicine.

[6]  G. Omenn,et al.  Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. , 1996, The New England journal of medicine.

[7]  Gorka Bastarrika,et al.  Assessing the relationship between lung cancer risk and emphysema detected on low-dose CT of the chest. , 2007, Chest.

[8]  R. Hubbard,et al.  Lung cancer and cryptogenic fibrosing alveolitis. A population-based cohort study. , 2000, American journal of respiratory and critical care medicine.

[9]  H. Hatabu,et al.  Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival. , 2015, European journal of radiology.

[10]  V. Poletti,et al.  The impact of lung cancer on survival of idiopathic pulmonary fibrosis. , 2015, Chest.

[11]  D. Shin,et al.  MUC5AC and MUC5B enhance the characterization of mucinous adenocarcinomas of the lung and predict poor prognosis , 2015, Histopathology.

[12]  K. Straif,et al.  Is previous respiratory disease a risk factor for lung cancer? , 2014, American journal of respiratory and critical care medicine.

[13]  I. Noth,et al.  A variant in the promoter of MUC5B and idiopathic pulmonary fibrosis. , 2011, The New England journal of medicine.

[14]  C. Gatsonis,et al.  Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening , 2012 .

[15]  H. Boeing,et al.  Selecting High-Risk Individuals for Lung Cancer Screening: A Prospective Evaluation of Existing Risk Models and Eligibility Criteria in the German EPIC Cohort , 2015, Cancer Prevention Research.

[16]  Edwin J R van Beek,et al.  Cigarette smoking is associated with subclinical parenchymal lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA)-lung study. , 2009, American journal of respiratory and critical care medicine.

[17]  Harry J de Koning,et al.  Risk prediction models for selection of lung cancer screening candidates: A retrospective validation study , 2017, PLoS medicine.

[18]  Fecundability in relation to body mass and menstrual cycle patterns. , 1999 .

[19]  W. Weiss Asbestosis: a marker for the increased risk of lung cancer among workers exposed to asbestos. , 1999, Chest.

[20]  Raúl San José Estépar,et al.  Development and Progression of Interstitial Lung Abnormalities in the Framingham Heart Study. , 2016, American journal of respiratory and critical care medicine.

[21]  G. Washko,et al.  Histopathology of Interstitial Lung Abnormalities in the Context of Lung Nodule Resections , 2017, American journal of respiratory and critical care medicine.

[22]  Jack Gauldie,et al.  Regulation of transforming growth factor-β1-driven lung fibrosis by galectin-3. , 2012, American journal of respiratory and critical care medicine.

[23]  Yung‐Chie Lee,et al.  Overexpression of MUC5 genes is associated with early post‐operative metastasis in non‐small‐cell lung cancer , 1996, International journal of cancer.

[24]  P. Piesiak,et al.  Galectin-3 and cyclin D1 expression in non-small cell lung cancer , 2011, Journal of experimental & clinical cancer research : CR.

[25]  C. Muir,et al.  International Classification of Diseases for Oncology , 1990 .

[26]  I. D. Johnston,et al.  Cryptogenic fibrosing alveolitis and lung cancer: the BTS study , 2009, Thorax.

[27]  A. Raz,et al.  Galectin-3 binding and metastasis. , 2012, Methods in molecular biology.

[28]  T. Shim,et al.  Lung cancer in patients with idiopathic pulmonary fibrosis. , 2001, The European respiratory journal.

[29]  G. Caldito,et al.  Risk of development of lung cancer is increased in patients with rheumatoid arthritis: a large case control study in US veterans. , 2008, The Journal of rheumatology.

[30]  Benjamin M. Smith,et al.  Emphysema detected on computed tomography and risk of lung cancer: a systematic review and meta-analysis. , 2012, Lung cancer.

[31]  Interstitial lung abnormalities and reduced exercise capacity. , 2012, American journal of respiratory and critical care medicine.

[32]  Raúl San José Estépar,et al.  MUC5B promoter polymorphism and interstitial lung abnormalities. , 2013, The New England journal of medicine.

[33]  R. Hubbard,et al.  The incidence of cancer in patients with idiopathic pulmonary fibrosis and sarcoidosis in the UK. , 2007, Respiratory medicine.

[34]  C. Compton,et al.  AJCC Cancer Staging Manual , 2002, Springer New York.

[35]  Ling-Yen Chung,et al.  Galectin-3 augments tumor initiating property and tumorigenicity of lung cancer through interaction with β-catenin , 2014, Oncotarget.

[36]  Raúl San José Estépar,et al.  The MUC5B promoter polymorphism is associated with specific interstitial lung abnormality subtypes , 2017, European Respiratory Journal.

[37]  W. Travis WHO classification of tumours of the lung, pleura, thymus and heart , 2015 .

[38]  H. Sørensen,et al.  Systemic sclerosis and the risk of cancer: a nationwide population‐based cohort study , 2010, The British journal of dermatology.

[39]  S. Markowitz,et al.  Asbestos, asbestosis, smoking, and lung cancer. New findings from the North American insulator cohort. , 2013, American journal of respiratory and critical care medicine.

[40]  N. Inui,et al.  Lung cancer development in patients with connective tissue disease–related interstitial lung disease , 2016, Medicine.

[41]  R. Kalluri The biology and function of fibroblasts in cancer , 2016, Nature Reviews Cancer.

[42]  Ning Wu,et al.  CT screening for lung cancer: Importance of emphysema for never smokers and smokers. , 2015, Lung cancer.

[43]  Hans-Joachim Gabius,et al.  Prognostic Significance of Endogenous Adhesion/Growth-Regulatory Lectins in Lung Cancer , 2005, Oncology.

[44]  D. Levy,et al.  Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities. , 2016, American journal of respiratory and critical care medicine.

[45]  K. Chida,et al.  Cumulative incidence of and predictive factors for lung cancer in IPF , 2009, Respirology.

[46]  C. Begg,et al.  Variations in lung cancer risk among smokers. , 2003, Journal of the National Cancer Institute.

[47]  Fu-Tong Liu,et al.  Role of galectin-3 in human pulmonary fibrosis. , 2007, Allergology international : official journal of the Japanese Society of Allergology.

[48]  Ivana V. Yang,et al.  A common MUC5B promoter polymorphism and pulmonary fibrosis. , 2011, The New England journal of medicine.

[49]  Asger Dirksen,et al.  Visual assessment of early emphysema and interstitial abnormalities on CT is useful in lung cancer risk analysis , 2016, European Radiology.

[50]  G. Raghu,et al.  Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review , 2015, European Respiratory Journal.

[51]  Y. Murakumo,et al.  Diagnostic and Prognostic Significances of MUC5B and TTF-1 Expressions in Resected Non-Small Cell Lung Cancer , 2015, Scientific Reports.

[52]  D. Lynch,et al.  Interstitial lung abnormalities in a CT lung cancer screening population: prevalence and progression rate. , 2013, Radiology.

[53]  Raúl San José Estépar,et al.  Association Between Interstitial Lung Abnormalities and All-Cause Mortality. , 2016, JAMA.

[54]  Maria Padilla,et al.  JOURNAL CLUB: Evidence of Interstitial Lung Disease on Low-Dose Chest CT Images: Prevalence, Patterns, and Progression. , 2016, AJR. American journal of roentgenology.