**5. Conclusions**

The role of the lung in RA is dual: a site of autoimmunity generation and of disease-related injury. The identification of subclinical lung abnormalities can be relevant in the management of the disease, but a reliable biomarker that can easily identify lung involvement in RA patients is still lacking in clinical practice. HRCT is the gold standard for the evaluation of lung parenchyma but entails a significant exposure to ionizing radiations. Stratifying the risk for lung abnormalities in the individual patients may help to identify who needs to be referred early to a HRCT scan.

This study shows that PFR and CPET may help to identify RA patients who have an increased likelihood of HRCT abnormalities, and provide information about the kind of lung involvement that may have an impact on the clinical management and the therapeutic decision. SPD shows a good accuracy in identifying HRCT abnormalities in ACPA-positive subjects, confirming its role as a biomarker of lung involvement. The combination of serum biomarkers and PFT may provide a safe and harmless tool to identify subjects who require further investigations. SPD and functional parameters, especially DLCO, also have a potential application among individuals in the preclinical phase of the disease, contributing to identifying ACPA-positive subjects who likely have subclinical lung abnormalities, for research and clinical purposes. However, larger studies are needed to validate the potential role of PFR, CPET and SPD in ACPA-positive subjects.

**Author Contributions:** Conceptualization, B.L. and M.D.F.; Data curation, B.L., M.D.P., C.G. and C.M.; Formal analysis, B.L., M.D.P. and C.M.; Investigation, B.L., M.D.P. and C.G.; Methodology, B.L., M.D.P., C.G., M.V., D.D. (Diacinti Davide) and D.D. (Diacinti Daniele); Project administration M.D.F.; Supervision, C.A., P.P. and M.D.F.; Validation, B.L., M.D.P., P.P. and M.D.F.; Writing—original draft, B.L.; Writing—review & editing, B.L., M.D.P. and M.D.F. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


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