Idiopathic Pulmonary Fibrosis (IPF) Exacerbations: How to identify them and how to treat them - Presented by Dr. Onofre Moran-Mendoza
By Maria Korovina, MSc Candidate, TMED801 Student
On October 27th, the students of TMED 801 had the pleasure of attending the Medical Grand Round at which Dr. Onofre Moran-Mendoza, MSc, PhD, MD, spoke on the current gaps in research surrounding the treatment and early identification of idiopathic pulmonary fibrosis exacerbations.
Idiopathic pulmonary fibrosis (IPF) is a form of interstitial lung disease characterized by chronic and progressive fibrosing pneumonia of unknown cause.1 IPF is progressive, unpredictable, and fatal with a reported median survival of 2-3 years after diagnosis without any treatment.2 Acute exacerbation (AE) IPF is defined as clinically significant respiratory deteriorations characterized by the worsening or development of dyspnea over one month, the appearance of new bilateral ground-glass opacities, and deterioration that are not fully explained by cardiac failure or fluid overload.3Dr. Moran-Mendoza highlighted the frequency of AE being greater in IPF patients compared to other fibrotic interstitial lung diseases (ILD), with a 1-year incidence of 7.6% in IPF and 3% in ILD.4,5 Furthermore, the increase in mortality from IPF following an AE was emphasized since the median survival of IPF-AE drops to 2.6 months.6
Considering the severity of IPF-AE, a minimal number of treatment options are currently available that are supported by evidence-based research. Two antifibrotic drugs, Pirfenidone & Nintedanib, are currently used to reduce the risk of exacerbations but are only used as preventative treatment due to their delayed effects.7,8 Furthermore, Dr. Moran-Mendoza discussed the frequent use of corticosteroids that have yet to be researched for their efficiency in managing IPF-AE but have shown some improvement in patient’s oxygen requirements.
Moreover, a number of trials that have been conducted in the past need further validation using newer data. A study conducted in Japan from 2001-2004 looked at the effects in treating IPF patients using prednisolone alone or with anticoagulation.9 The patient were prescribed oral warfarin after their first exacerbation, and IV Dalteparin was started if the patients were re-admitted due to respiratory failure. In the end, the study found that mortality in the Dalteparin group decreased from 71% to 18%.9 Nevertheless, duplications of this study have not been done to validate these findings, but further investigation needs to be conducted as this drug therapy may save many lives.
Considering the progression rate of IPF-AE, Dr. Moran-Mendoza provided an example of how he uses the recognition of early symptoms within his ILD clinic. If patients observe a drop in their oxygen level or a worsening in their breathing, they are instructed to notify the clinic. These observations are key for identifying flares early on, which have shown to help with prognosis. Nonetheless, there is no research-based evidence supporting early detection of oxygen level drops and its relationship with disease prognosis.
Following the MGR, Dr. Moran-Mendoza met with TMED students to further discuss how his research benefits patients, its representation in the lay press, as well as to share his career path. He discussed a recent study where patients within his ILD clinic were evaluated for fine crackles as a potential early sign of IPF. The study found that 93% of IPF patients had fine crackles during their first visit, which presented more often than other symptoms, illustrating the potential advantages fine crackles may have on early IPF diagnosis.10 Dr. Moran-Mendoza also highlighted the importance of circulating accurate information regarding IPF-AE to the lay audience before ending off on his final note regarding his career. He spoke on his career path which has allowed him to not only practice medicine but to investigate his own research interest. Thanks to these ambitions, Dr. Moran-Mendoza has created an ILD database with longitudinal clinical, radiologic, physiologic, and bronchoscopic data on over 700 ILD patients.
All in all, IPF-AE is an aggressive disease with gaps in therapeutic research that need to be addressed. Throughout his presentation, Dr. Moran-Mendoza highlighted the current treatment options that are widely used in the hospital along with the lack of evidence-based research to support these drugs. As a fellow TMED student, I want to thank Dr. Moran-Mendoza for shedding light on some of these challenges and providing examples of his work in contributing to a better understanding of IPF-AE.
1. Barratt SL, Creamer A, Hayton C, Chaudhuri N. Idiopathic Pulmonary Fibrosis (IPF): An Overview. J Clin Med. Aug 6 2018;7(8)doi:10.3390/jcm7080201
2. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. Mar 15 2011;183(6):788-824. doi:10.1164/rccm.2009-040GL
3. 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. Aug 1 2016;194(3):265-75. doi:10.1164/rccm.201604-0801CI
4. Yoo J-W, Kim J, Song JW. Impact of the revised definition on incidence and outcomes of acute exacerbation of idiopathic pulmonary fibrosis. Scientific Reports. 2022/05/25 2022;12(1):8817. doi:10.1038/s41598-022-12693-5
5. Biondini D, Balestro E, Sverzellati N, et al. Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF): an overview of current and future therapeutic strategies. Expert Rev Respir Med. Apr 2020;14(4):405-414. doi:10.1080/17476348.2020.1724096
6. Salonen J, Purokivi M, Bloigu R, Kaarteenaho R. Prognosis and causes of death of patients with acute exacerbation of fibrosing interstitial lung diseases. BMJ Open Respir Res. Apr 2020;7(1)doi:10.1136/bmjresp-2020-000563
7. Richeldi L, Cottin V, du Bois RM, et al. Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS(®) trials. Respir Med. Apr 2016;113:74-9. doi:10.1016/j.rmed.2016.02.001
8. Ley B, Swigris J, Day BM, et al. Pirfenidone Reduces Respiratory-related Hospitalizations in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. Sep 15 2017;196(6):756-761. doi:10.1164/rccm.201701-0091OC
9. Kubo H, Nakayama K, Yanai M, et al. Anticoagulant therapy for idiopathic pulmonary fibrosis. Chest. Sep 2005;128(3):1475-82. doi:10.1378/chest.128.3.1475
10. Moran-Mendoza O, Ritchie T, Aldhaheri S. Fine crackles on chest auscultation in the early diagnosis of idiopathic pulmonary fibrosis: a prospective cohort study. BMJ Open Respir Res. Jul 2021;8(1)doi:10.1136/bmjresp-2020-000815