PF-ILD
Course of disease
Interstitial lung diseases (ILDs) are a group of rare respiratory, nonmalignant disorders, characterized by varying degrees of damage to the lung parenchyma via inflammation and fibrosis.1 While idiopathic pulmonary fibrosis (IPF) may be regarded as the prototype PF- ILD, a proportion of patients with other ILDs develop a similar progressive-fibrosing phenotype.1 The pathophysiology in patients with PF-ILD is characterized by self-sustaining fibrosis and a deterioration in lung function over time, with worsening respiratory symptoms1, worsening health-related quality of life (HRQoL)2, resistance to immunomodulatory therapies and ultimately early mortality.1
Development of progressive fibrosing phenotype3
An online survey estimated that 18-32% of patients diagnosed with non-IPF ILDs will develop a progressive fibrosing phenotype, defined as evidence of fibrosis (reticular abnormality with traction bronchiectasis with or without honeycombing) detected by HRCT, accompanied by worsening of lung function (FVC and/or DLCO) and/or respiratory symptoms and/or chest images (Figure 1).3 The non-IPF ILDs that physicians believed most likely to have a progressive fibrosing phenotype were iNSIP, SSc-ILD, unclassifiable IIP and RA-ILD, with 32%, 31%, 29% and 26% of patients with these types of ILD, respectively, estimated to develop a progressive fibrosing phenotype.3
Figure 1. Percentage of patients with non-IPF ILDs who develop a progressive fibrosing phenotype.3
Patient journey in non-IPF progressive fibrosing ILDs3
According to the online survey, physicians estimated that the time from diagnosis of ILD to development of progressive fibrosing ILD is 11-15 months, and that it takes 9-12 months for physicians to detect this progressive fibrosing phenotype. Estimated time between detection of progressive fibrosis and death was 30-45 months, meaning that the estimated time from onset of symptoms to death in patients with progressive fibrosing ILDs was 61-80 months (Figure 2).3
Figure 2. Patient journey in non-IPF progressive fibrosing ILDs.3
Survival in patients with PF‑ILD4
Based on the data provided by Nasser et al.(2021), 6,096 (42.3%) patients were still alive at the end of follow-up; 1,537 (10.7%) were lost to follow-up or censored, and 6,780 (47.0%) had died. Median overall survival from the beginning of progression was 3.7 years (95% CI 3.6-3.8) (Figure 3A). Median overall survival was longer in females compared with males (4.6 vs 3.0 years) (Figure 3B), and older age groups showed a marked decline in overall survival (Figure 3C).4 When split by underlying disease, patients with sarcoidosis-ILD had the longest median overall survival (7.9 years) and patients with exposure-related ILD other than HP had the shortest (2.4 years) (Figure 3D).4 The crude multivariable Cox model found male gender, age categories ≥ 50 years and underlying disease to be significantly associated with mortality (all p < 0.0001). A check of the proportional hazards assumption for the factors selected for the multivariable analysis found a significant interaction for time with age and underlying disease (both p < 0.0001).4
Figure 3. Overall survival for PF-ILD.*
Footnotes:
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* (A) Overall survival among all patients, and by (B) sex, (C) age, and (D) diagnosis subgroup. Overall survival was defined as the time in years from the date of progression to the date of death due to any cause.CTD, Connective tissue disease; HP, Hypersensitivity pneumonitis; HRQoL, health-related quality of life; IIP, Idiopathic interstitial pneumonias; ILD, Interstitial lung disease; iNSIP, Idiopathic non-specific interstitial pneumonia; IPF, Idiopathic pulmonary fibrosis; RA, Rheumatoid arthritis; SSc, Systemic sclerosis.
References:
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Richeldi L et al. Eur Respir Rev. 2018. 27(150).
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Flaherty K. R et al. BMJ Open Respir Res. 2017. 4(1): e000212.
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Wijsenbeek M et al. Curr Med Res Opin. 2019. 35(11): 2015-2024.
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Nasser M et al. Respir Res. 2021. 22(1): 162.