**6. UIP seen in various diseases**

Various diseases cause UIP including various pneumoconioses, chronic hypersensitivity pneumonitis, and collagen vascular diseases. Histological features of pneumoconiosis are characterized by bronchiolocentric fibrous nodule formation predominantly in the upper lobes. Arakawa et al. reported a prevalence of chronic interstitial pneumonia in 243 pneumoconiosis cases of approximately 12% on CT, and three fourths of these cases showed a typical IPF pattern. Pathological data obtained by autopsy or lobectomy in 11 cases indicated UIP [79]. The prevalence of chronic interstitial pneumonia among pneumoconiosis cases is 10–20% [80–82]. Arakawa et al. reported that the earliest CT abnormalities (faint ground-glass opacity or coarse reticular opacity) of 14 cases appeared at the lung bases and then fibrosis progressed to honeycombing over a median period of 12.1 years in the silica-exposed patients, with autopsy in 8 cases confirming a diagnosis of typical UIP [83]. Generally, latent periods from occupational exposure to disease onset are quite long [79–83]. Occasionally, hard metal lung disease appears as UIP when the degree of exposure has been mild [84]. Histological features of acute and subacute hypersensitivity pneumonitis are characterized by bronchiolo-alveolitis with loose granulomas diffusely spread throughout both lungs. In contrast, most chronic hypersensitivity pneumonitis shows UIP pathologically, with points of differentiation from that of IPF being the presence of bronchiolitis, peribronchiolar fibrosis

#### **Figure 6.**

*Histology of chronic hypersensitivity pneumonia. A 66-year-old woman who had been breeding birds developed progressive dyspnea. Specific antigen for pigeon was markedly elevated. Surgical lung biopsy was performed from the left lingula and S8 (case from the Department of Respiratory Medicine, Kobe City Medical Center West Hospital). A panoramic view of the lingula showed mainly subpleural dense fibrosis. Elastica van Gieson staining (EvG). Patchy dense fibrosis was noted mainly in the subpleural area and peripheral lobular areas (next to an interlobular septum by EvG) of the lung. Box in A: hematoxylin and eosin (HE), ×40. A clear fibroblastic focus was noted at the edge of the dense fibrosis (red arrow), and one loose granuloma was seen in the fibrosis (black arrow). Box in B: HE, ×200. Panoramic view of the S8 showing subpleural dense fibrosis and honeycombing (black arrow). EvG.*

*Asbestos Exposure Results in Asbestosis and Usual Interstitial Pneumonia Similar to Other… DOI: http://dx.doi.org/10.5772/intechopen.89247*

or centrilobular fibrosis, bridging fibrosis, epithelioid cell granuloma, and giant cells [85–87]. Still, it is impossible to think of UIP as an extension of respiratory bronchiolar lesions as UIP begins within the subpleural peripheral lung. Typical histological features of chronic hypersensitivity pneumonitis are shown in **Figure 6**. Recently, telomere-related gene variants were reported in chronic hypersensitivity pneumonitis [88]. UIP is the one of the major pulmonary complications in cases of collagen vascular diseases, especially in rheumatoid arthritis (RA). As with IPF, the prevalence is higher in smokers and males [89]. UIP in RA shares a number of radiological and histopathological features with IPF [90–92]. An additional histological feature of UIP in RA is frequent germinal center formation [93]. RA-related UIP also begins within basal, subpleural peripheral areas as does IPF. Recently, the *MUC5B* promoter variant was reported in RA-related UIP [94].

#### **7. Conclusion**

Moderate to severe exposure to asbestos causes asbestosis. However, there are a number of cases of UIP in asbestos workers or high-grade environmentally exposed people that do not fulfill the Helsinki criteria. The susceptibility to asbestos exposure varies. UIP-type grade 4 asbestosis begins within the basal, subpleural peripheral areas as do cases of IPF, other pneumoconioses, chronic hypersensitivity pneumonitis, and RA. The suspected relationship between asbestos exposure, numbers of exposed persons, and the development of diffuse pulmonary fibrosis is shown in **Figure 7**. Cases of diffuse UIP with less than 200–1000 ABs/g dry lung

#### **Figure 7.**

*Schematic of suspected cases of diffuse pulmonary fibrosis related to asbestos exposure. The black line is the suspected dose-response curve related to the degree of asbestos exposure and disease frequency. The lower line indicates the degree of asbestos exposure, with 200–100/g dry lung indicating higher than the environmental or low occupational exposure level, 25 f/mL-y indicating the beginning of the asbestosis level, and 2 asbestos bodies/cm2 or 4000–20,000/g dry lung indicating the beginning of the grade 4 asbestosis exposure level. The blue line indicates the numbers of people exposed. The red line indicates the numbers of diffuse pulmonary fibrosis. Disease in patients with less than the low occupational level can be called idiopathic pulmonary fibrosis, whereas that in patients between the low occupational exposure level and grade 4 asbestosis exposure level can be called diffuse usual interstitial pneumonia seen in asbestos workers (or a high-grade environmentally exposed person).*

#### *Asbestos-Related Diseases*

can be called IPF when there is no other etiology. Diffuse interstitial fibrosis with more than 2 ABs/cm<sup>2</sup> can be called grade 4 asbestosis. There might be significant numbers of cases of diffuse interstitial fibrosis that lie between IPF and grade 4 asbestosis, and these cases can be called diffuse interstitial pneumonia seen in asbestos workers or high-grade environmentally exposed persons.

I hope future more genetic research can reveal the phenotypes that can acquire diffuse pulmonary fibrosis through mild occupational and environmental exposure to dust.
