Smoking-related interstitial fibrosis: radiographic morphological comparisons

Smoking-related lung diseases are diverse, but the most difficult to diagnose remain diseases that involve interstitial changes, in some pathologies combined with emphysema. The aim of the research is to compare the X-ray and morphological features of smoking-related interstitial fibrosis (SRIF). Methods. A histological analysis of surgical samples from 119 patients (smokers and ex-smokers) who underwent lobectomy for lung cancer or other focal lesions in the lungs was performed. Results. Twenty seven patients (18 men, 9 women, 4 ex-smokers) with histological signs of SRIF were identified based on the pathology results; the mean age was 69.1 ± 8.9 years, the smoking index (SI) was 42.06 ± 11.8 pack-years. Results. The prevalence of fibrosis, assessed semi-quantitatively by histological examination, was significantly associated with the SI (r = 0.44; p < 0.05). Fibrosis of the interalveolar septa was observed in areas of emphysema; in addition, signs of chronic bronchiolitis were detected in a third of patients, and constrictive bronchiolitis in 2/3 of patients. The presence of emphysema was correlated with the presence of constrictive bronchiolitis (r = 0.67; p < 0.05). In 11 of 27 patients, fibroblastic foci were found in the walls of the respiratory bronchioles, and their presence also correlated with emphysematous changes (r = 0.40; p < 0.05). CT scans revealed signs of emphysema in 80% patients. In addition; polysegmental areas with ground glass opacities were detected in 12/20 patients, reticular and/or cord-like attenuations were detected in 14 patients, and interlobular interstitial thickening was detected in 8 patients. These signs were assessed as “fibrous” when localized in the emphysema zone. When conducting a correlation analysis, a relationship was found between radiologically detected emphysema and fibrotic changes detected by histological examination (r = 0.50), and the prevalence of CT signs of fibrosis correlated with the presence of fibroblastic foci in the bronchiolar wall (r = 0.51). Conclusion. SRIF is more common in individuals with a smoking history of more than 20 pack-years. CT examination does not always identify the signs of SRIF. In our study, signs of emphysema were detected in 80% patients, and signs possibly associated with fibrosis – in less than half of the cases. Histological results suggest that SRIF is the end stage of the respiratory bronchiolitis of smokers.

1. Katzenstein A.L., Mukhopadhyay S., Zanardi C., Dexter E. Clinically occult interstitial fibrosis in smokers: classification and significance of a surprisingly common finding in lobectomy specimens. Hum. Pathol. 2010; 41 (3): 316–325. DOI: 10.1016/j.humpath.2009.09.003.

2. Kawabata Y., Hoshi E., Murai K. et al. Smoking-related changes in the background lung of specimens resected for lung cancer: a semiquantitative study with correlation to postoperative course. Histopathology. 2008; 53 (6): 707–714. DOI: 10.1111/j.1365-2559.2008.03183.

3. Attili A.K., Kazerooni E.A., Gross B.H. et al. Smoking-related interstitial lung disease: radiologic-clinical pathologic correlation. Radiographics. 2008; 28 (5): 1383–1398. DOI: 10.1148/rg.285075223.

4. Otani H., Tanaka T., Murata K. et al. Smoking-related interstitial fibrosis combined with pulmonary emphysema: computed tomography-pathologic correlative study using lobectomy specimens. Int. J. COPD. 2016; 11: 1521–1532. DOI: 10.2147/COPD.S107938.

5. Yousem S.A. Respiratory bronchiolitis-associated interstitial lung

6. disease with fibrosis is a lesion distinct from fibrotic nonspecific interstitial pneumonia: a proposal. Mod. Pathol. 2006; 19 (11): 1474–1479. DOI: 10.1038/modpathol.3800671.

7. Cottin V., Selman S., Inoue Y. et al. Syndrome of combined pulmonary fibrosis and emphysema: An official ATS/ERS/JRS/ALAT Research Statement. Am. J. Respir. Crit. Care Med. 2022; 206 (4): e7–41. DOI: 10.1164/rccm.202206-1041ST.

8. Katzenstein A.L.A. Smoking-related interstitial fibrosis (SRIF): pathologic findings and distinction from other chronic fibrosing lung diseases. J. Clin. Pathol. 2013; 66 (10): 882–887. DOI: 10.1136/jclinpath-2012-201338.

9. El-Kersh K., Perez R.L., Smith J.S., Fraig M. Smoking-related in-terstitial fibrosis (SRIF) and pulmonary hypertension. BMJ Case Rep. 2013; 2013: bcr2013008970. DOI: 10.1136/bcr-2013-008970.

10. Reddy T.L., Mayo J., Churg A. Respiratory bronchiolitis with fibrosis. High-resolution computed tomography findings and correlation with pathology. Ann. Am. Thorac. Soc. 2013; 10 (6): 590–601. DOI: 10.1513/AnnalsATS.201304-088OC.

11. Сhae K.J., Jin G.Y., Jung H.N. et al. Differentiating smoking-related interstitial fibrosis (SRIF) from usual interstitial pneumonia (UIP) with emphysema using CT features based on pathologically proven cases. PLoS One. 2016; 11 (9): e0162231. DOI: 10.1371/journal.pone.0162231.

12. Iwasawa T., Takemura T., Ogura T. Smoking-related lung abnormalities on computed tomography images: comparison with pathological findings. Jpn. J. Radiol. 2018; 36 (3): 165–180. DOI: 10.1007/s11604-017-0713-0.

13. Katzenstein A.LA. Smoking-related interstitial fibrosis (SRIF): pathologic findings and distinction from other chronic fibrosing lung diseases. J. Clin. Pathol. 2013; 66 (10): 882–887. DOI: 10.1136/jclinpath-2012-201338.

14. Flaherty K.R., Fell C., Aubry M.C. et al. Smoking-related idiopathic interstitial pneumonia. Eur. Respir. J. 2014; 44 (3): 594–602. DOI: 10.1183/09031936.00166813.

15. Wick M.R. Pathologic features of smoking-related lung diseases, with emphasis on smoking-related interstitial fibrosis and a consideration of differential diagnoses. Semin. Diagn. Pathol. 2018; 35 (5): 315–323. DOI: 10.1053/j.semdp.2018.08.002.

16. Popper H. Pathology of lung disease. Morphology – pathogenesis – etiology. 2nd Ed. Zurich (Switzerland): Springer; 2021. DOI: 10.1007/978-3-030-55743-0.

17. Fabro A.T., Minatel I.O., Rangel M.P. et al. Usual interstitial pneumonia and smoking-related interstitial fibrosis display epithelial to mesenchymal transition in fibroblastic foci. Respir Med. 2014; 108 (9): 1377–1386. DOI: 10.1016/j.rmed.2014.06.008.

18. Barata M., Caetano Mota P., Melo N. et al. Transbronchial lung cryobiopsy in smoking-related interstitial lung diseases. Sarcoidosis Vasc. Diffuse Lung Dis. 2020; 37 (4): e2020013. DOI: 10.36141/svdld.v37i4.9934.