Emphysema detected on computed tomography and risk of lung cancer: A systematic review and meta-analysis
Introduction
Lung cancer is the leading cause of cancer death globally [1], [2]. Despite recent advances in targeted therapies over the past decade, lung cancer outcomes remain poor with an overall 5-year survival of 15.7% [3]. Identification of individuals at highest risk for lung cancer will help to focus preventive interventions (e.g. smoking cessation) and lung cancer screening strategies [4], [5].
Pulmonary emphysema is defined morphologically as the enlargement of airspaces distal to the terminal bronchiole from dilatation or destruction of alveolar walls [6], [7]. The advent of chest computed tomography (CT) has greatly advanced our understanding of emphysema by affording accurate pre-mortem detection and prospective study [8], [9], [10]. Several studies have validated qualitative and quantitative methods of detecting presence and severity of emphysema on CT with pathologic specimens (reviewed by Thurlbeck et al. [10]) [8], [9]. More recently, studies have explored the association between emphysema detected on chest CT and lung cancer [11], [12], [13], [14], [15].
The two largest prospective studies were derived from screening trials; after adjustment for smoking history and airflow obstruction, they reported a significant risk of lung cancer when emphysema was detected visually on chest CT [11], [12]. In contrast, two case–control studies found no association with lung cancer when emphysema was assessed quantitatively using a continuous densitometry measure [13], [14]. A subsequent case–control study observed an even stronger effect measure than previous reports when scans were assessed visually by thoracic radiologist [15]. Finally, a study comparing quantitative and qualitative emphysema detection methods by Wilson et al. only found an association with lung cancer when the latter technique was used [16].
A recent systematic review of lung disease and lung cancer risk reported a significant association with emphysema [17]. However, the review included several case–control studies in which the diagnosis of emphysema was based on interview. This may have inflated the observed associations. For example, subjects diagnosed with lung cancer may be more concerned about the health consequences of previous smoking, so they may tend to report emphysema more often than controls. In addition, the accuracy of self-reported diagnosis of emphysema is limited [15]. Furthermore, several of the included studies did not account for airflow obstruction, which is a potential confounder.
Motivated by the mixed conclusions of recent studies with respect to CT-detected emphysema and lung cancer risk, we conducted a systematic review of the literature in an effort to synthesize the available evidence. Particular attention was paid to the method used to detect emphysema on CT and consideration of airflow obstruction. Our objective was to provide an objective synthesis of the evidence, as well as increase precision beyond any single study by pooling data, where appropriate, to provide the most accurate estimate of association between emphysema on CT and lung cancer.
Section snippets
Methods
A systematic review of the literature was performed to summarize the evidence of association between emphysema detected on CT and lung cancer risk. This manuscript was prepared using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines [18]. A copy of the review protocol is available upon request from the corresponding author.
Study selection and characteristics
Our search strategy identified 187 citations. Fig. 1 summarizes the screening process and reasons for exclusion. One publication was excluded from the systematic review because data were reported in another included study with longer follow-up period [23]. A second candidate study reporting previously published data was included in the qualitative synthesis because it made direct comparison between visual and automated emphysema techniques with respect to lung cancer risk [16]. This study was
Discussion
Our systematic review of the literature identified seven studies exploring the association of emphysema detected on CT and lung cancer [11], [12], [13], [14], [15], [16], [26]. Meta-analysis of studies reporting non-duplicate data on lung cancer diagnosis demonstrated significantly increased odds of lung cancer with presence of emphysema on CT [11], [12], [13], [14], [15]. When stratified by emphysema detection method, this association remained significant among studies using qualitative
Conflict of interest statement
None declared.
Funding
This work was funding by the Quebec Health Research Fund. This public funding agency had no role in the conduct of the research. No writing assistance outside of the authors listed was used in preparing this manuscript.
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