Dual pathology, dual burden: Functional impact of emphysema and fibrosis in Hypersensitivity Pneumonitis
Keywords:
Hypersensitivity Pneumonitis; fibrosis; emphysema; lung function; dual pathology; radiological phenotypeAbstract
Background and aim: Hypersensitivity pneumonitis (HP) is a complex interstitial lung disease with heterogeneous presentations. In some patients, radiological coexistence of emphysema and fibrosis creates a distinct functional phenotype that complicates disease progression and management. To evaluate the functional impact of combined emphysema and fibrosis in HP patients and to identify clinical predictors associated with this dual pathology.
Methods: We retrospectively analyzed 215 patients diagnosed with HP between 2010 and 2023. Demographic data, exposure history, radiological findings (HRCT), and pulmonary function parameters (FVC, DLCO, FEV₁) were collected. Patients were classified into three groups: fibrotic HP, non-fibrotic HP, and combined emphysema with fibrosis (CE-HP). Statistical analyses were performed using SPSS v22.0.
Results: Of the 215 patients, 68 (31.6%) had fibrotic HP and 42 (19.5%) presented with CE-HP. Patients with CE-HP were significantly older (mean 66.2 ± 9.1 years) and more often male and smokers (p < 0.05). FVC and DLCO values were lower in CE-HP compared with non-fibrotic and fibrotic groups. A moderate negative correlation was found between extent of emphysema and DLCO (r = −0.56, p < 0.001). In multivariate analysis, age > 65 years, male gender, and smoking history were independent predictors of CE-HP development.
Conclusions: The coexistence of emphysema and fibrosis in HP represents a distinct clinical phenotype with significant functional impairment. Recognition of this dual pathology is crucial for accurate prognostication and individualized management strategies.
References
1. Salisbury ML, Myers JL, Belloli EA, Kazerooni EA, Martinez FJ, Flaherty KR. Diagnosis and treatment of fibrotic hypersensitivity pneumonitis: Where we stand and where we need to go. Am J Respir Crit Care Med. 2017;196(6):690–699. doi:10.1164/rccm.201611-2201PP.
2. Vasakova M, Morell F, Walsh S, et al. Hypersensitivity pneumonitis: perspectives in diagnosis and management. Am J Respir Crit Care Med. 2017;196(6):680–689. doi:10.1164/rccm.201611-2201PP.
3. Raghu G, Remy-Jardin M, Ryerson CJ, et al. Diagnosis of hypersensitivity pneumonitis in adults: an official ATS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2020;202(3):e36–e69. doi:10.1164/rccm.202005-2032ST.
4. Fernández Pérez ER, Travis WD, Lynch DA, et al. Hypersensitivity pneumonitis: current concepts of pathogenesis and potential targets for treatment. Am J Respir Crit Care Med. 2018;197(6):688–697. doi:10.1164/rccm.201708-1675PP.
5. Hanak V, Golbin JM, Ryu JH. Causes and presenting features in 85 consecutive patients with hypersensitivity pneumonitis. Mayo Clin Proc. 2007;82(7):812–816. doi:10.4065/82.7.812.
6. Morisset J, Johannson KA, Jones KD, et al. Identification of diagnostic criteria for chronic hypersensitivity pneumonitis: an international modified Delphi survey. Am J Respir Crit Care Med. 2018;197(8):1036–1044. doi:10.1164/rccm.201710-1986OC.
7. Morell F, Villar A, Montero MA, et al. Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case–cohort study. Lancet Respir Med. 2013;1(9):685–694. doi:10.1016/S2213-2600(13)70191-7.
8. Okazaki Y, Kurashima K, Nakano Y, Taniguchi H, Kondoh Y, Ogura T, et al. Changes in computed tomography findings in chronic hypersensitivity pneumonitis: relationship with pulmonary function and prognosis. Respir Investig. 2016;54(5):350–357. doi:10.1016/j.resinv.2016.03.002.
9. Ohtani Y, Saiki S, Sumi Y, Inase N, Miyake S, Costabel U, Yoshizawa Y. Clinical features of recurrent and insidious chronic bird fancier's lung. Ann Allergy Asthma Immunol. 2003 Jun;90(6):604-10. doi: 10.1016/S1081-1206(10)61863-7. PMID: 12839317.
10. Koyuncu A, Sarı G, Şimşek C. Evaluation of cases with hypersensitivity pneumonia: 10 year analysis. Clin Respir J. 2023 Apr;17(4):329-338. doi: 10.1111/crj.13598. Epub 2023 Feb 13. PMID: 36780898; PMCID: PMC10113273.
11. Adegunsoye A, Oldham JM, Chung JH, Montner SM, Lee C, Witt LJ,et al. Phenotypic Clusters Predict Outcomes in a Longitudinal Interstitial Lung Disease Cohort. Chest. 2018 Feb;153(2):349-360. doi: 10.1016/j.chest.2017.09.026. Epub 2017 Sep 28. PMID: 28964798; PMCID: PMC5815877.
12. Spagnolo P, Rossi G, Cavazza A, Bonifazi M, Paladini I, Bonella F, et al. Hypersensitivity Pneumonitis: A Comprehensive Review. J Investig Allergol Clin Immunol. 2015;25(4):237-50; quiz follow 250. PMID: 26310038.
13. De Sadeleer LJ, Hermans F, De Dycker E, Yserbyt J, Verschakelen JA, Verbeken EK, et al. Effects of Corticosteroid Treatment and Antigen Avoidance in a Large Hypersensitivity Pneumonitis Cohort: A Single-Centre Cohort Study. J Clin Med. 2018 Dec 21;8(1):14. doi: 10.3390/jcm8010014. PMID: 30577667; PMCID: PMC6352061.
14. Fernández Pérez ER, Swigris JJ, Forssén AV, Tourin O, Solomon JJ, Huie TJ, et al. Identifying an inciting antigen is associated with improved survival in patients with chronic hypersensitivity pneumonitis. Chest. 2013 Nov;144(5):1644-1651. doi: 10.1378/chest.12-2685. PMID: 23828161; PMCID: PMC4694094.
15. Cottin V, Hirani NA, Hotchkin DL, Nambiar AM, Ogura T, Otaola M, et al. Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev. 2018 Dec 21;27(150):180076. doi: 10.1183/16000617.0076-2018. PMID: 30578335; PMCID: PMC9489068.
16. Jacob J, Bartholmai BJ, Rajagopalan S, Kokosi M, Nair A, Karwoski R et al. Mortality prediction in idiopathic pulmonary fibrosis: evaluation of computer-based CT analysis with conventional severity measures. Eur Respir J. 2017 Jan 25;49(1):1601011. doi: 10.1183/13993003.01011-2016. PMID: 27811068.
17. Tokura S, Okamoto T, Tsuchiya T, et al. Outcome of chronic hypersensitivity pneumonitis: importance of bronchiolocentric fibrosis on histology. Respirology. 2017;22(5):965–972. [Epub ahead of print, not indexed in PubMed].
18. Falfán-Valencia R, Camarena Á, Juárez A, et al. Genetic susceptibility to hypersensitivity pneumonitis: TNF and IL-6 promoter polymorphisms. Eur Respir J. 2004;23(5):821–825. doi:10.1183/09031936.04.00078304.
19. Ley B, Newton CA, Arnould I, Elicker BM, Henry TS, Vittinghoff E, et al. The MUC5B promoter polymorphism and telomere length in patients with chronic hypersensitivity pneumonitis: an observational cohort-control study. Lancet Respir Med. 2017 Aug;5(8):639-647. doi: 10.1016/S2213-2600(17)30216-3. Epub 2017 Jun 22. PMID: 28648751; PMCID: PMC5555581.
20. Fernández Pérez ER, Kong AM, Raimundo K, Koelsch TL, Kulkarni R, Cole AL. Epidemiology of Hypersensitivity Pneumonitis among an Insured Population in the United States: A Claims-based Cohort Analysis. Ann Am Thorac Soc. 2018 Apr;15(4):460-469. doi: 10.1513/AnnalsATS.201704-288OC. PMID: 29236517.
21. Jacobs RL, Andrews CP, Coalson JJ. Hypersensitivity pneumonitis: beyond classic occupational disease-changing concepts of diagnosis and management. Ann Allergy Asthma Immunol. 2005 Aug;95(2):115-28. doi: 10.1016/S1081-1206(10)61200-8. PMID: 16136760.
22. Takemura T, Akashi T, Kamiya H, Ikushima S, Ando T, Oritsu M, et al. Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia. Histopathology. 2012 Dec;61(6):1026-35. doi: 10.1111/j.1365-2559.2012.04322.x. Epub 2012 Aug 8. PMID: 22882269.
23. Jacob J, Bartholmai BJ, Rajagopalan S, Kokosi M, Nair A, Karwoski R, et al. Mortality prediction in idiopathic pulmonary fibrosis: evaluation of computer-based CT analysis with conventional severity measures. Eur Respir J. 2017 Jan 25;49(1):1601011. doi: 10.1183/13993003.01011-2016. PMID: 27811068.
24. Cerri S, Monari M, Guerrieri A, Donatelli P, Bassi I, Garuti M, et al. Real-life comparison of pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis: A 24-month assessment. Respir Med. 2019 Nov;159:105803. doi: 10.1016/j.rmed.2019.105803. Epub 2019 Oct 18. PMID: 31670147.
25. Mooney JJ, Elicker BM, Urbania TH, Agarwal MR, Ryerson CJ, Nguyen MLT, et al. Radiographic fibrosis score predicts survival in hypersensitivity pneumonitis. Chest. 2013 Aug;144(2):586-592. doi: 10.1378/chest.12-2623. PMID: 23392130.
26. Ojanguren I, Morell F, Ramón MA, Villar A, Romero C, Cruz MJ, et al. Long-term outcomes in chronic hypersensitivity pneumonitis. Allergy. 2019 May;74(5):944-952. doi: 10.1111/all.13692. Epub 2019 Jan 13. PMID: 30515826.
How to Cite
Issue
Section
License
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.



