Critical care management of Interstitial Lung Disease with a focus on Idiopathic Pulmonary Fibrosis: Optimizing diagnosis and treatment

Yusuke Hirao, Shunsuke Kondo,  Joshua Hu, Brent Matsuda

Abstract

Introduction

Exacerbations of interstitial lung disease (ILD), diffuse parenchymal lung diseases, or idiopathic pulmonary fibrosis can often lead to acute hypoxia, resulting in intensive care unit (ICU) admission. For those patients who require invasive mechanical ventilation, mortality rates can exceed 80%.

Methods

This review discusses the fundamental aspects of ILD exacerbations in the ICU setting, comprising diagnostic modalities, criteria, and management options. These include high-resolution computerized tomography, sputum analysis, treatment with immunomodulating agents, and both non-invasive and invasive ventilatory support strategies.

Conclusion 

Exacerbations of ILD requiring mechanical ventilation are associated with poor prognostic outcomes. Understanding diagnostic criteria and treatment options is crucial to studying the high morbidity & mortality rates, leading to future directions focused on delivery of optimal care for this vulnerable patient population.

Keywords: Interstitial lung disease, idiopathic pulmonary fibrosis, ILD exacerbation, critical care medicine, invasive mechanical ventilation.

References

1. Maher TM. Interstitial Lung Disease: A Review. JAMA 2024; 331:1655-1665. https://doi.org/10.1001/jama.2024.3669 PMid:38648021

2. Oldham JM, Lee CT, Wu Z, et al. Lung function trajectory in progressive fibrosing interstitial lung disease. Eur Respir J 2022; 59(6):2101396. https://doi.org/10.1183/13993003.01396-2021 PMid:34737223 PMCid:PMC10039317

3. Charokopos A, Moua T, Ryu JH, Smischney NJ. Acute exacerbation of interstitial lung disease in the intensive care unit. World J Crit Care Med 2022; 11(1):22-32. https://doi.org/10.5492/wjccm.v11.i1.22 PMid:35433309 PMCid:PMC8788209

4. Nishimoto K, Fujisawa T, Yoshimura K, et al. The prognostic significance of pneumothorax in patients with idiopathic pulmonary fibrosis. Respirology 2018;23(5):519-525. https://doi.org/10.1111/resp.13219 PMid:29130562

5. Nishimoto K, Fujisawa T, Yoshimura K, et al. Pneumothorax in connective tissue disease-associated interstitial lung disease. PLoS One 2020;15(7):e0235624. https://doi.org/10.1371/journal.pone.0235624 PMid:32634173 PMCid:PMC7340294

6. Tsubouchi K, Hamada N, Tokunaga S, et al. Survival and acute exacerbation for patients with idiopathic pulmonary fibrosis (IPF) or non-IPF idiopathic interstitial pneumonias: 5-year follow-up analysis of a prospective multi-institutional patient registry. BMJ Open Respir Res 2023;10(1):e001864. https://doi.org/10.1136/bmjresp-2023-001864 PMid:37963676 PMCid:PMC10649622

7. Collard HR, Ryerson CJ, Corte TJ, et al. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report. Am J Respir Crit Care Med 2016; 194(3):265-275. https://doi.org/10.1164/rccm.201604-0801CI PMid:27299520

8. Smith RA, Sathananthan M, Kaur P, Jeganathan N. The characteristics and outcomes of patients with idiopathic pulmonary fibrosis admitted to the ICU with acute respiratory failure. Heart Lung 2021;50(1):192-196. https://doi.org/10.1016/j.hrtlng.2020.05.006 PMid:32522418

9. Peredo RA, Mehta V, Beegle S. Interstitial Lung Disease Associated with Connective Tissue Diseases. Adv Exp Med Biol 2021; 1304:73-94. https://doi.org/10.1007/978-3-030-68748-9_5 PMid:34019264

10. Fernandez-Perez ER, Yilmaz M, Jenad H, et al. Ventilator settings and outcome of respiratory failure in chronic interstitial lung disease. Chest 2008;133(5):1113-1119. https://doi.org/10.1378/chest.07-1481 PMid:17989156 PMCid:PMC4003484

11. Baydur A. Mechanical ventilation in interstitial lung disease: which patients are likely to benefit? Chest 2008; 133(5):1062-1063. https://doi.org/10.1378/chest.07-2615 PMid:18460510

12. Leuschner G, Behr J. Acute Exacerbation in Interstitial Lung Disease. Front Med (Lausanne) 2017; 4:176. https://doi.org/10.3389/fmed.2017.00176 PMid:29109947 PMCid:PMC5660065

13. Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2022; 205(9):e18-e47. https://doi.org/10.1164/rccm.202202-0399ST PMid:35486072 PMCid:PMC9851481

14. Molyneaux PL, Smith JJ, Saunders P et al. BAL Is Safe and Well Tolerated in Individuals with Idiopathic Pulmonary Fibrosis: An Analysis of the PROFILE Study. Am J Respir Crit Care Med 2021; 203(1):136-139. https://doi.org/10.1164/rccm.202004-1138LE PMid:32857629 PMCid:PMC7781115

15. Patolia S, Tamae Kakazu M, Chami HA et al. Bronchoalveolar Lavage Lymphocytes in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung Disease. Ann Am Thorac Soc 2020; 17(11):1455-1467. https://doi.org/10.1513/AnnalsATS.202005-420OC PMid:32757946

16. Gharsalli H, Mlika M, Sahnoun Iet al. The utility of bronchoalveolar lavage in the evaluation of interstitial lung diseases: A clinicopathological perspective. Semin Diagn Pathol 2018; 35(5):280-287. https://doi.org/10.1053/j.semdp.2018.08.003 PMid:30173880

17. Wong AK, Walkey AJ. Open lung biopsy among critically ill, mechanically ventilated patients. A Metaanalysis. Ann Am Thorac Soc 2015; 12(8):1226-1230. https://doi.org/10.1513/AnnalsATS.201502-077BC PMid:26065712 PMCid:PMC4566408

18. Hutchinson JP, Fogarty AW, McKeever TM, et al. In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States. 2000 to 2011. Am J Respir Crit Care Med 2016; 193(10):1161-1167. https://doi.org/10.1164/rccm.201508-1632OC PMid:26646481

19. Miadlikowska E, Milkowska-Dymanowska J, Bialas AJ et al. Serum KL-6 and SP-D: Markers of Lung Function in Autoimmune-Related Interstitial Lung Diseases. Int J Mol Sci 2025 27; 26(3):1091. https://doi.org/10.3390/ijms26031091 PMid:39940859 PMCid:PMC11817276

20. Ohnishi H, Yokoyama A, Kondo K et al. Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med 2002; 165(3):378-381. https://doi.org/10.1164/ajrccm.165.3.2107134 PMid:11818324

21. Wang T, Yao Y, Wang Y, et al. Evaluating the diagnostic and therapeutic significance of KL-6 in patients with interstitial lung diseases. Heliyon 2024; 10(7):e27561. https://doi.org/10.1016/j.heliyon.2024.e27561 PMid:38560233 PMCid:PMC10979234

22. Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2018; 198(5):e44-e68. https://doi.org/10.1164/rccm.201807-1255ST PMid:30168753

23. Travis WD, Costabel U, Hansell DM, et al. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013; 188(6):733-748. https://doi.org/10.1164/rccm.201308-1483ST PMid:24032382 PMCid:PMC5803655

24. Pagliaro R, Aronne L, Fomez R, et al. High-flow nasal cannula system in respiratory failure associated with interstitial lung diseases: A systematic review and narrative synthesis. J Clin Med 2024; 13(10):2956. https://doi.org/10.3390/jcm13102956 PMid:38792497 PMCid:PMC11122032

25. Koyauchi T, Hasegawa H, Kanata K, et al. Efficacy and tolerability of high-flow nasal cannula oxygen therapy for hypoxemic respiratory failure in patients with interstitial lung disease with do-not-intubate orders: A retrospective single-center study. Respiration 2018; 96(4):323-329. https://doi.org/10.1159/000489890 PMid:29954000

26. Tomii K, Tachikawa R, Chin K, et al. Role of non-invasive ventilation in managing life-threatening acute exacerbation of interstitial pneumonia. Intern Med 2010; 49(14):1341-1347. https://doi.org/10.2169/internalmedicine.49.3491 PMid:20647646

27. Martin MJ, Moua T. Mechanical ventilation and predictors of in-hospital mortality in fibrotic interstitial lung disease with acute respiratory failure: A cohort analysis through the paradigm of acute respiratory distress syndrome. Crit Care Med 2020; 48(7):993-1000. https://doi.org/10.1097/CCM.0000000000004366 PMid:32355133

28. Nolan TJ, Dwyer I, Geoghegan P. The use of mechanical ventilation in interstitial lung disease. Breathe (Sheff) 2025; 21(2):240172. https://doi.org/10.1183/20734735.0172-2024 PMid:40255290 PMCid:PMC12004253

29. Stern JB, Mal H, Groussard O, et al. Prognosis of patients with advanced idiopathic pulmonary fibrosis requiring mechanical ventilation for acute respiratory failure. Chest 2001; 120(1):213-219. https://doi.org/10.1378/chest.120.1.213 PMid:11451841

30. Mollica C, Paone G, Conti V, et al. Mechanical ventilation in patients with end-stage idiopathic pulmonary fibrosis. Respiration 2010; 79(3):209-215. https://doi.org/10.1159/000225932 PMid:19546508

31. Kim SH, Lee DH, Yang B, et al. Which factors are helpful for the early determination of treatment level in patients with interstitial lung disease in the intensive care unit to minimize the suffering in their end of life?: A retrospective study. Medicine (Baltimore) 2022; 101(37):e30524. https://doi.org/10.1097/MD.0000000000030524 PMid:36123841 PMCid:PMC9478284

32. Hyung K, Lee JH, Kim JY, et al. Pulse versus non-pulse corticosteroid therapy in patients with acute exacerbation of idiopathic pulmonary fibrosis. Respirology 2024; 29(3):235-242. https://doi.org/10.1111/resp.14643 PMid:38087838

33. Jang HJ, Yong SH, Leem AY et al. Corticosteroid responsiveness in patients with acute exacerbation of interstitial lung disease admitted to the emergency department. Sci Rep 2021; 11(1):5762. https://doi.org/10.1038/s41598-021-85539-1 PMid:33707643 PMCid:PMC7952556

34. Tashkin DP, Elashoff R, Clements PJ et al.: Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006; 354(25):2655-2666 https://doi.org/10.1056/NEJMoa055120 PMid:16790698

35. Mankikian J, Caille A, Reynaud-Gaubert M, et al. Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomized, placebo-controlled trial. Eur Respir J 2023; 61(6):2202071. https://doi.org/10.1183/13993003.02071-2022 PMid:37230499

36. Ebata S, Yoshizaki A, Oba K, et al. Safety and efficacy of rituximab in systemic sclerosis (DESIRES): a double-blind, investigator-initiated, randomised, placebo-controlled trial. Lancet Rheumatol 2021; 3(7):e489-e497. https://doi.org/10.1016/S2665-9913(21)00107-7 PMid:38279402

37. Valapour M, Lehr CJ, Schladt DP, et al. OPTN/SRTR 2023 Annual Data Report: Lung. Am J Transplant 2025; 25(2S1):S422-S489. https://doi.org/10.1016/j.ajt.2025.01.025 PMid:39947808 PMCid:PMC12334194

38. Ronan NJ, Helly F, Murray MA. Lung transplantation for interstitial lung disease. Breathe (Sheff). 2025; 21(2):240169. https://doi.org/10.1183/20734735.0169-2024 PMid:40365094 PMCid:PMC12070198

39. Kapnadak SG, Raghu G. Lung transplantation for interstitial lung disease. Eur Respir Rev 2021; 30(161):210017. https://doi.org/10.1183/16000617.0017-2021 PMid:34348979 PMCid:PMC9488499

40. Leard LE, Holm AM, Valapour M, et al. Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2021; 40(11):1349-1379. https://doi.org/10.1016/j.healun.2021.07.005 PMid:34419372 PMCid:PMC8979471