Content sponsored by Boehringer Ingelheim
By Victoria Tan
Fibrotic interstitial lung diseases (ILDs) represent a large and varied group of parenchymal disease. Idiopathic pulmonary fibrosis (IPF) is the most extensively studied fibrotic ILD and is progressive by definition1. A subset of patients with fibrotic ILD (with etiologies other than IPF) also display evidence of progressive pulmonary fibrosis (PPF). They resemble IPF in both clinical behavior and underlying pathologic mechanisms1. Fibrotic ILDs that can display PPF are varied, and include idiopathic interstitial pneumonias (i.e. nonspecific interstitial pneumonia [NSIP]), auto-immune ILDs (i.e. those related to rheumatoid arthritis [RA-ILD], scleroderma [Ssc-ILD], and other connective tissue disease-related ILDs), exposure related (i.e. fibrotic hypersensitivity pneumonitis [fHP]), fibrotic ILD related to chronic sarcoidosis, and unclassifiable ILD. Although the prevalence of PPF in fibrotic ILD is unknown; a recent study from the Canadian Registry for Pulmonary Fibrosis found that progression is common among patients with fibrotic ILD and has similar prevalence in fHP and IPF2.
Detection of fibrotic ILD and assessment of progression by the radiologist are important to patient management as antifibrotic therapies, pirfenidone and nintedanib, have been approved by Health Canada, for the treatment of IPF. Antifibrotics have been shown to reduce the rate of decline in lung function and to reduce mortality in patients with IPF3. This has led to investigation of antifibrotics in other fibrotic ILDs. A recent paradigm shift toward antifibrotic treatment for non-IPF fibrotic ILDs has occurred, after a clinical trial found a beneficial effect4,5.
The natural history of IPF is disease progression, with a variable course of decline. Similarly, in other fibrotic ILDs with PPF, the course of progression can be heterogeneous and difficult to predict. Mortality is high in fibrotic ILDs with PPF. In IPF, median survival is only 3-4 years after diagnosis in patients not treated with antifibrotics1,6. The mortality for non-IPF fibrotic ILDs is variable. Prognosis is poor in fHP and RA-ILD (with a UIP pattern)1. SSc-ILD is a leading cause of death in patients with scleroderma1. However, the prognosis appears to be better in idiopathic NSIP where 5-year survival has been reported at 75%1.
Progression of pulmonary fibrosis is defined by a 2022 ATS/ERS/JRS/ALAT Clinical Practice Guideline on IPF and PPF as two of the following three findings, being attributable to pulmonary fibrosis: 1) worsening of respiratory symptoms, 2.) physiologic disease progression (decline in FVC or DLCO), and 3.) radiologic disease progression4. Specific radiologic features include new ground glass opacity with traction bronchiectasis, and new or worsening traction bronchiectasis/bronchiolectasis, reticulation, honeycombing, or volume loss.
Radiologic findings as predictors of progressive disease have garnered increasing interest. In IPF, progression of traction bronchiectasis has been reported as a strong independent predictor of mortality4. In fibrotic ILDs, honeycombing and traction bronchiectasis are associated with a worse prognosis1,4. Greater extent of fibrosis is predictive of mortality in IPF and in many non-IPF fibrotic ILDs4.
Radiologic progression is assessed visually by radiologists. However, this method is limited by subjectivity and interobserver variability. A 2016 study of 112 radiologists found only moderate inter-observer agreement between thoracic radiologists for ATS/ERS/JRS/ALAT CT criteria for UIP7. Computer based quantitative CT (QCT) offers the potential of an objective and reproducible method of assessment. A 2021 study of patients in Korea using quantitative CT analysis found extent and interval change of ILD severity to be moderately associated with pulmonary function tests, serum biomarkers, and visual assessment in patients with RA-ILD8. A recent retrospective analysis of a national IPF registry in Australia using data-driven texture analysis (DTA) found that the extent of fibrosis quantified on baseline CT, was associated with outcomes, independent of pulmonary function9.
In summary, radiologists play a key role in diagnosis of fibrotic ILDs and detection of progression. This aids in management decisions, including initiation of antifibrotic therapy. Given the important role of imaging, further study and validation of QCT would be beneficial for implementation in research and clinical settings.