Rationale Sustained activation of lung fibroblasts and the resulting oversynthesis of the extracellular matrix are detrimental events for patients with interstitial lung diseases (ILDs). Lung biopsy is a primary evaluation technique for the fibrotic status of ILDs, and is also a major risk factor for triggering acute deterioration. Fibroblast activation protein (FAP) is a long-known surface biomarker of activated fibroblasts, but its expression pattern and diagnostic implications in ILDs are poorly defined. Objectives The present study aims to comprehensively investigate whether the expression intensity of FAP could be used as a potential readout to estimate or measure the amounts of activated fibroblasts in ILD lungs quantitatively. Methods FAP expression in human primary lung fibroblasts as well as in clinical lung specimens was first tested using multiple experimental methods, including real-time quantitative PCR (qPCR), Western blot, immunofluorescence staining, deep learning measurement of whole slide immunohistochemistry, as well as single-cell sequencing. In addition, FAP-targeted positron emission tomography/computed tomography imaging PET/CT was applied to various types of patients with ILD, and the correlation between the uptake of FAP tracer and pulmonary function parameters was analyzed. Measurements and Main Results Here, it was revealed, for the first time, FAP expression was upregulated significantly in the early phase of lung fibroblast activation event in response to a low dose of profibrotic cytokine. Single-cell sequencing data further indicate that nearly all FAP-positive cells in ILD lungs were collagen-producing fibroblasts. Immunohistochemical analysis validated that FAP expression level was closely correlated with the abundance of fibroblastic foci on human lung biopsy sections from patients with ILDs. We found that the total standard uptake value (SUV) of FAP inhibitor (FAPI) PET (SUVtotal) was significantly related to lung function decline in patients with ILD. Conclusions Our results strongly support that in vitro and in vivo detection of FAP can assess the profibrotic activity of ILDs, which may aid in early diagnosis and the selection of an appropriate therapeutic window.

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0.81-2.33; P = .243), and operation time (MD = À1.37; 95% CI, À4.11 to 1.38; P = .33), RSL have comparable outcomes vs WGL.Ahmed 5 combined six RCTs involving ROLL versus WGL together with one RSL versus WGL for meta-analysis. RSL had favorable outcomes in operative time; however, it was inferior to WGL in volume of excised breast tissue. Lovrics 6 analyzed five RCTs and seven nonrandomized studies involving ROLL and RSL together versus WGL. RSL was found to be superior to WGL in surgical margins and re-operation rates. Chan BKY 7 combined six RCTs involving ROLL versus WGL together with two RSL versus WGL for meta-analysis. RSL demonstrated superior results in positive tumor margins, and re-operation rates over WGL, but neither had statistical significance. Besides,they also found that WGL had fewer postoperative complications to RSL, although this was also not statistically significant. Ahmed 8 combined one RCT and four nonrandomized studies involving RSL vs WGL for meta-analysis. RSL was found to be superior to WGL in terms of involved surgical margin status, re-operation rates, and operative time. However, there was no significant difference in volume of specimen excised.