Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal disease with a heterogeneous clinical course. This study aimed to evaluate the usefulness of circulating biomarkers in routine IPF clinical practice. We conducted an exploratory study in a cohort of 28 IPF subjects qualified for anti-fibrotic therapy with up to 24 months serial measurements of seven IPF biomarkers, including those that are well-established, Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), matrix metalloproteinase 7 (MMP-7), and more recently introduced ones, cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA-125), chemokine (C-C motif) ligand 18 (CCL18), and periostin. Among studied biomarkers, SP-D had the highest diagnostic accuracy to differentiate IPF subjects from controls, followed by MMP-7 and KL-6. At each study timepoint, KL-6 levels correlated inversely with forced vital capacity % predicted (FVC% pred.), and transfer factor of the lung for carbon monoxide % predicted (T_L,CO% pred.), while SP-D levels correlated inversely with FVC% pred. and T_L,CO% pred. at 24 months of anti-fibrotic therapy. Baseline KL-6 and CA19-9 concentrations were significantly elevated in patients with progressive disease in comparison to patients with stable disease. In addition, in the progressors subgroup CA19-9 concentrations significantly increased over the second year of study follow-up. In patients with progressive disease, we observed a significant inverse correlation between a change in SP-D levels and a change in FVC% pred. in the first year of treatment, whereas in the second year a significant inverse correlation between a change in KL-6 levels and a change in FVC% pred. was noted. Our study findings support the view that both well-established IPF biomarkers, including KL-6, SP-D, and MMP-7, and more recently introduced ones, like CA19-9, have the potential to support clinical practice in IPF.

Studies have shown that eosinophilic COPD (eCOPD) is a distinct phenotype of the disease. It is well established that innate lymphoid cells are involved in the development of eosinophilic inflammation. Interleukin(IL)-25, thymic stromal lymphopoietin (TSLP) and IL-33 are a group of cytokines produced by epithelium in response to danger signals, e.g., cigarette smoke, and potent activators of ILC2s. In the present study, we examined circulating and sputum ILC2 numbers and expression of intracellular IL-5 as well as receptors for TSLP, IL-33 and IL-25 by ILC2s in non-atopic COPD patients with and without (neCOPD) airway eosinophilic inflammation and healthy smokers. In addition, we examined the association between ILC2s and clinical indicators of COPD burden (i.e., symptom intensity and risk of exacerbations). ILC2s were enumerated in peripheral blood and induced sputum by means of flow cytometry. We noted significantly greater numbers of airway IL-5⁺ILC2s and TSLPR⁺ILC2s in eCOPD compared with neCOPD (p < 0.05 and p < 0.01, respectively) and HSs (p < 0.001 for both). In addition, we showed that IL-5⁺ILC2s, IL-17RB⁺ILC2s and ST2⁺ILC2s are significantly increased in the sputum of eCOPD patients compared with HSs. In all COPD patients, sputum ILC2s positively correlated with sputum eosinophil percentage (r = 0.48, p = 0.002). We did not find any significant correlations between sputum ILC2s and dyspnea intensity as measured by the modified Medical Research Council scale (mMRC) and symptom intensity measured by the COPD Assessment Test (CAT). These results suggest the involvement of epithelial alarmin-activated ILC2s in the pathobiology of eosinophilic COPD.