Reply: Subclinical Interstitial Lung Disease: No Place for Crackles?

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From the Authors: We thank Professors Cottin and Cordier for their thoughtful response to our perspective of subclinical interstitial lung disease (ILD) (1). We agree with the authors that the physical exam is an important skill to be taught and refined and not to be supplanted by more complex physiologic testing but rather supplemented by it. However, the only data addressing the significance of crackles in subclinical ILD that we are aware of is what we have previously shown in individuals with subclinical rheumatoid arthritis–associated ILD (RA-ILD) (2). In this study, we found a statistically significant difference in the percentage of subjects having audible crackles on physical exam when comparing those with subclinical RA-ILD (24%) to those with only RA (4.7%, P = 0.02) or to those with clinically significant RA-ILD (100%, P < 0.001). We did not include physical exam in our diagnostic algorithm as it is unclear if these findings can be extrapolated to other groups affected with subclinical ILD. Despite the above, we agree with Cottin and Cordier that the presence of crackles could improve the assessment of populations at risk of developing subclinical ILD. We agree with Cottin and Cordier that the identification of subjects with subclinical ILD may come with increased psychological and financial burdens and with a risk of additional radiation exposure. As outlined in our perspective, we believe that future research into subclinical ILD can be structured to minimize these risks while maximizing the benefit of early identification. Longitudinal studies will be crucial in determining which subset of patients with subclinical ILD will go on to develop clinically significant ILD and which individuals may have reversible causes, such as hypersensitivity pneumonitis; it is in this population that a work-up for subclinical ILD would be most justified. More sensitive noninvasive metrics to assess subclinical ILD, such as clinical predictive modeling and biomarker and genetic assays, can also work to reduce the indiscriminate use of imaging. Additionally, an improved understanding of subclinical ILD will hopefully lead to a better understanding of the pathophysiology of ILD and the development of more effective treatments targeted at earlier stages of disease. Our hope is that efforts targeted at early identification will ultimately have a positive impact on the morbidity and mortality of ILD.