Reply to Ni et al.: Comprehensive Strategies for the Follow-Up of Interstitial Lung Abnormality

From the Authors:

We appreciate Ni and colleagues for their great interest regarding our paper on interstitial lung abnormality (ILA) (1). We largely agree with the points raised by Ni and colleagues but want to highlight several aspects. First, we acknowledge the importance of standardized imaging evaluation processes in detecting ILA. Despite being a retrospective study with its inherent limitations, evaluation of ILA in our study adhered to the definition outlined in the Fleischner Society’s position paper, differentiating centrilobular nodularity (indicating smoking-related respiratory bronchiolitis) and dependent abnormalities resulting from insufficient inspiration or atelectasis from true ILAs (2). Second, we agree that there is uncertainty surrounding the diagnosis of interstitial lung disease (ILD) when ILAs are identified on computed tomographic scans in clinical settings, because clear criteria are lacking, and these categories may represent a spectrum of ILD development and progression. Although ILA is a radiological entity, defining ILD necessitates a multifactorial approach that incorporates not only radiologic findings but also symptoms and pulmonary function measures. ILAs have been incidentally found in patients with mild symptoms and/or marginal pulmonary functional impairment, which were previously overlooked. When such clinically significant findings are present, ILAs are likely to represent mild ILD rather than merely ILAs. However, a recent study by Bando and colleagues demonstrated that incidentally detected preclinical interstitial pulmonary fibrosis (IPF) cases with preserved pulmonary function and no symptoms exhibited a similar decline in pulmonary functional measures over time compared with those with clinical IPF (3). This suggests that radiologic evidence of early-stage IPF on computed tomography may hold greater significance than symptomatic or functional impairment status. As demonstrated in our study, employing radiologic risk assessment along with quantitative analysis can assist in the objective evaluation of ILAs and in the risk stratification of patients who are rapidly progressing to clinically significant disease. Furthermore, we agree that evaluating the relationship between smoking cessation and the natural remission of ILA could be valuable; however, our retrospective study was limited in collecting accurate timelines of smoking cessation. Future investigations would be valuable in prospectively analyzing other potential risk factors that Ni and colleagues pointed out, such as environmental exposures and medication use, as well as smoking history, to assess their utility for patient stratification.

Last, we would like to clarify that we do not strictly advocate a 3-year follow-up for all patients, particularly those with high risk factors for lung cancer. Certainly, follow-up intervals should be individualized, considering other risk factors besides ILAs, if present. Given the current follow-up strategies in clinical practice at our center, individuals with ILAs who are also at high risk for lung cancer (e.g., heavy smoking, such as a 30 pack-year smoking history, or a family history of lung cancer) may require an annual follow-up specifically for lung cancer screening. However, for those initially detected with ILAs who are not at high risk of lung cancer, a 3-year follow-up may generally be sufficient to monitor ILA progression. If the patient is at high risk of adverse outcomes, such as having extensive fibrotic ILAs or the presence of honeycombing, shortening the interval for follow-up scans may also be beneficial, as suggested by our study.