**Abstract**

The progression of asbestosis is supposed to begin with the first order of respiratory bronchiole and extend outward. Recently, grade 4 asbestosis was reported to begin with the subpleural peripheral lobular area or the subpleural lobule. Grade 4 asbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive numbers of asbestos fibers. Pathologically, the presence of more than two asbestos bodies/cm2 on a glass slide is required. There are many cases of diffuse interstitial pneumonia, mainly usual interstitial pneumonia, that does not fulfill the above criteria among asbestos workers or high-grade environmentally exposed persons. I call these cases "usual interstitial pneumonia seen in asbestos workers" and not idiopathic pulmonary fibrosis. In this chapter, I discuss the above subjects, including the dose-response relationship for asbestos exposure, the heterogeneous response to asbestos exposure, and the relationship between asbestosis and idiopathic pulmonary fibrosis.

**Keywords:** pathological examination, usual interstitial pneumonia, atelectatic induration, asbestos body, idiopathic pulmonary fibrosis

### **1. Introduction**

It is well known that moderate- to high-grade exposures to asbestos cause serious diffuse pulmonary fibrosis called diffuse asbestosis. Asbestosis is believed to start in the region of the first order of respiratory bronchiole (grade 1, **Figure 1**) and gradually extends outward to involve more and more of the lung acinus until separate foci of fibrosis link or attach to the pleura and the interlobular septum (grade 3), finally resulting in a diffuse pattern of the fibrosis (grade 4) [1, 2]. However, this description has not yet been proved. Asbestosis is defined as diffuse interstitial fibrosis of the lung as a consequence of exposure to asbestos dust. A histological diagnosis of asbestosis requires the presence of two or more asbestos bodies (ABs) in the tissue with a section area of 1 cm2 [3]. Meanwhile, diffuse interstitial pneumonia, mainly usual interstitial pneumonia (UIP), that does not fulfill the above histological criteria is called idiopathic pulmonary fibrosis (IPF) even if the patient is a worker exposed to asbestos [4].

In this review, I discuss the process of asbestosis progression, the pathological definition and the features of asbestosis, the lower limit of asbestos fiber exposure

#### **Figure 1.**

*Grade 0 to grade 2 lesions. (A) Grade 0 lesion without respiratory bronchiolar fibrosis but with three asbestos bodies (arrows). Hematoxylin and eosin staining (HE), ×100. Inset: enlarged asbestos bodies. (B) Grade 1 lesion with fibrosis of the respiratory bronchiole and surrounding lung. HE, ×60. Inset: enlarged asbestos bodies. (C) Grade 2 lesion with fibrosis of the respiratory bronchiole and surrounding lung. Elastica van Gieson staining (EvG), ×60. Inset: many enlarged asbestos bodies. (D) Grade 2 lesion with fibrosis of the respiratory bronchiole, alveolar duct, and surrounding lung including luminal organization. EvG, ×60. Inset: enlarged asbestos bodies.*

causing asbestosis and the dose-response relationship of asbestos exposure, various causes of UIP, and how to think about diffuse interstitial pneumonia or UIP that does not fulfill the histological criteria of asbestosis. The term "asbestosis" is used differently in the literature. I term diffuse interstitial fibrosis due to asbestos exposure as pathological grade 4 asbestosis and clinical diffuse asbestosis. The term asbestosis alone can indicate various extents of severity from grade 1 to grade 4 pathologically and early to diffuse asbestosis clinically.
