Although a pulmonary apical cap has been recognized as a non-specific fibrotic change at the apex of the lung for half a century [6], only a few studies with small sample sizes have investigated the prevalence of an apical cap in the general population and the associations with clinical features [2,3,4]. Our study of 28,727 individuals confirmed that pleural thickening was the most common finding on routine chest X-rays (Additional file 1: Table S1). We found that more than 90% of the cases involved apical pleural thickening, or an apical cap (Fig. 2). The prevalence of pleural thickening increased with age: the percentages of cases in individuals in their 20s, 30s, 40s, and 50s were 2.4, 2.9, 4.1, and 6.7%, respectively (Fig. 3). It is worth noting that pleural thickening (an apical cap, in most cases) was found in 1.8% of subjects under the age of 20 years, suggesting that pleural thickening is not simply an aging phenomenon. Healthcare providers should consider these findings when reviewing routine chest X-rays.
A limitation of our study is that the sample was drawn from a single academic institution, the University of Tokyo, and consisted primarily of Japanese students and university employees (> 90%). Additional studies are needed to examine ethnic and socioeconomic differences in the prevalence of pleural thickening and an apical cap. Of the 16,043 males in our study, 6.2% (n = 1001) were current smokers and 6.7% (n = 1072) were ex-smokers, whereas 2.2% (n = 204) of the 9248 females were current smokers and 3.7% (n = 339) were ex-smokers. These figures are considerably lower than the nationwide smoking rates in Japan in 2017 (29.4% in males and 7.2% in females) or those reported in the United States in 2016 (17.5% in males and 13.5% in females) [7, 8]. Given our finding that the frequency of an apical cap was higher in individuals with a smoking history compared with never smokers (Additional file 1: Table S5), pleural thickening may be more prevalent in the general population with higher smoking rates than in our study population.
Another limitation of our study population is the lack of detailed information about past medical history and medication. Further studies are necessary to evaluate the possible association of pleural thickening with comorbid diseases.
To date, few studies have investigated the pathological features of an apical cap [2,3,4,5]. It is generally accepted that an apical cap is a distinct fibroelastic plaque in the lung that contains mature collagen and elastin fibers [6]. In 1970, Butler et al. [2] examined 48 autopsy lung specimens and noted mural thickening in the small muscular arteries subjacent to the apical cap and chronic bronchitis in more than half of the cases. Based on these observations, the authors concluded that an apical cap is a localized parenchymal lesion, which is presumably the result of persistent or repeated inflammation. They further postulated that the relatively decreased perfusion at the apex of the lung may impede the resolution of inflammation. More recently, Yousem [5] reviewed 13 surgically resected lung specimens with an apical cap and reported consistent pathological findings suggesting chronic ischemia as a major cause of an apical cap [5].
Due to the effects of gravity, ventilation and perfusion rates are lowest at the apex and highest at the base of the lung in the upright position [9]. Furthermore, the ventilation/perfusion ratio is highest at the apex because ventilation is relatively greater than perfusion compared with other lung areas [9]. As such, it seems reasonable that the apex is more susceptible to chronic ischemia, which may explain why pleural thickening is found predominantly at the apex and in the upper portion of the lung (Fig. 2). Moreover, lower ventilation and perfusion at the apex may increase the risk of sustained exposure to pathogens or environmental irritants that can trigger the inflammation associated with pleural thickening. Furthermore, intrapleural pressure is more negative, and transpulmonary pressure is greater at the apex than in the lower portion of the lung [9]. Therefore, mechanical forces generated by repeated cycles of respiration may be greater at the apex, which may in turn promote the fibrotic response [10]. However, these pathogenic mechanisms remain a matter of speculation.
Importantly, we found that pleural thickening (primarily an apical cap) was associated with greater height and lower body weight and BMI (Fig. 4). We suggest two possible explanations for this finding. Given that the lungs are proportional to body mass, the anatomical and pathophysiological differences between the apex and lower portion of the lung may be greater among taller, thinner individuals leading to an increased risk of inflammation and/or ischemia at the apex. Alternatively, individuals with a genetic predisposition for greater height or lower BMI may be more prone to developing pleural thickening [11]. Future genome-wide association studies of pleural thickening or apical cap may clarify this issue.
We found that pleural thickening occurred predominantly in the right lung. Anatomical differences may account for this finding. The left lung has two lobes and thus a lower volume than the right lung, which has three lobes, and the heart is located on the left side. Conceivably, there may be a greater ventilation/perfusion mismatch and stronger mechanical forces acting at the apex of the right lung than at the left lung.
Pleuroparenchymal fibroelastosis is a rare form of idiopathic interstitial pneumonia that affects the visceral pleura and subpleural parenchyma with upper lobe predominance. Although no case of pleuroparenchymal fibroelastosis was identified in our study, it is conceivable that an early lesion of pleuroparenchymal fibroelastosis mimics an apical cap on chest X-rays. Intriguingly, a previous study found that the BMI in patients with pleuroparenchymal fibroelastosis was significantly lower than that of patients with idiopathic pulmonary fibrosis, a common form of idiopathic interstitial pneumonia with lower lobe predominance (mean BMI 18.6 vs. 25.1, respectively) [12]. Moreover, another study found that the histological findings for pleuroparenchymal fibroelastosis were “strikingly similar” to those for pulmonary apical cap [6]. Thus, it is tempting to speculate that a similar causative mechanism related to tall, thin body shapes may be involved in both apical cap and pleuroparenchymal fibroelastosis.