BIOMARKERS WITH CLINICAL SIGNIFICANCE IN PATIENTS WITH INTERSTITIAL LUNG DISEASES

Idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) are the most frequent entities among the rare idiopathic interstitial pneumonias. Bronchoalveolar lavage (BAL) is able to give relevant information about the cellular composition at alveolar level and is commonly part of the diagnostic algorithm of ILD. Several biomarkers in peripheral blood or BAL fluid have been studied in patients with ILD, however at the moment there are no biomarkers universally recognized in clinical practice. The objectives of the present study were to analyse the cellular composition of BAL and to establish the levels of KL-6, Calgranulin B and Pepsin in BAL of patients with IPF and i-NSIP and a group of healthy controls. In the present study were included 60 patients suffering from IPF (n = 30; males n = 24; age = 68.73 ± 8.63 years) and idiopathic-NSIP (fibrotic NSIP pattern) (n = 30; males n = 17; age = 68.33 ± 7.45 years). Patients with IPF and i-NSIP showed a percentage of macrophages in BAL significantly lower than healthy controls (p <0.05). In IPF patients, we identified significant correlations of BAL neutrophils % with FiO2 and SpO2% at rest, final BORG dyspnea at 6MWT and DLCO worsening after 12 months. In i-NSIP patients, BAL neutrophils correlated with FVC %, RV%, TLC% and FiO2 at rest and DLCO worsening after 6 months. Moreover, in i-NSIP patients eosinophils% in BAL > 13% was significantly associated with shorter survival. KL-6 and Calgranulin B in BAL were found significantly higher in the whole patients’ population (IPF and i-NSIP) than in healthy controls (p <0.05). Pepsin was not different among the three groups. In IPF patients, KL-6 was increased in patients with chronic respiratory failure and correlated directly with FiO2 at rest and with the amount of oxygen required at the 6MWT. In patients suffering from i-NSIP, it correlated directly with the eosinophils% in BAL and indirectly with FVC%, TLC%, DLCO% and with the walked distance at the 6MWT. Calgranulin B was found increased in advanced IPF and i-NSIP patients with chronic respiratory failure and an indirect correlation with DLCO worsening at 18 months was shown in i-NSIP patients. Calgranulin B also showed a significant correlation with survival. In conclusion, BAL data on cellularity confirmed to play a relevant role in the diagnosis of ILD and in prognosis assessment. KL-6 and Calgranulin B in BAL demonstrated to be reliable non-invasive biomarkers of IPF and i-NSIP. They showed to be able to discriminate more severe patients and to correlate with other clinical and functional variables recognizing a significant prognostic role.