Subject(s)
COVID-19/blood , Lymphocyte Subsets/cytology , Aged , Analysis of Variance , COVID-19/immunology , Female , Flow Cytometry , Humans , Italy , Male , Middle Aged , ROC Curve , Statistics, NonparametricABSTRACT
The original version of this article unfortunately contained a mistake. First and last names of the authors were interchanged.
ABSTRACT
Bronchoalveolar lavage (BAL) is a useful procedure for differential diagnosis of interstitial lung diseases (ILDs) and for identification of granulomatous lung diseases. We investigated a panel of biomarkers from BAL fluid of ILD patients to evaluate their utility in differentiating ILDs. Bronchoscopy with BAL was performed in 100 consecutive patients with suspected ILD (41 sarcoidosis, 11 cHP and 24 other ILDs); the 24 patients negative for ILD diagnosis were included as control group. BAL phenotypes and cell profiles (CD4+/CD8+ ratio, NK and CD103+ cell counts, chitotriosidase and KL-6 levels in BAL) were determined by flow cytometry. A decision-tree statistical algorithm was applied. Sarcoidosis was discriminated by a higher BAL CD4+/CD8+ ratio (p = 5.8E-05), a lower BAL CD103+CD4+ count (p = 5.0E-02) and lower BAL NK percentages (p = 8.8E-03) than the other groups. BAL KL-6 concentrations were higher in sarcoidosis than in other ILDs (p = 1.5E-02) and were directly correlated with CD4+/CD8+ ratio. We used decision-tree statistical analysis to combine our biomarkers into two diagnostic algorithms for differential diagnosis of ILDs. A panel of BAL biomarkers for diagnosis of ILDs is proposed; CD4+/CD8+ ratio, KL-6 concentrations, and NK and CD103+CD4+ cell percentages in BAL could improve the identification and differential diagnosis of sarcoidosis.
Subject(s)
Biomarkers/analysis , Bronchoalveolar Lavage Fluid , Lung Diseases, Interstitial/diagnosis , Aged , Antigens, CD/analysis , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Diagnosis, Differential , Female , Humans , Immunophenotyping , Integrin alpha Chains/analysis , Lung Diseases, Interstitial/pathology , Male , Middle Aged , Mucin-1/analysis , Neutrophils/pathology , Sarcoidosis/diagnosisABSTRACT
Diffuse lung diseases (DLD) are a heterogeneous group of diseases with different etiopathogenesis, clinical course, and prognosis. It has been demonstrated that oxidative stress can contribute to the pathogenesis of these diseases. In the present study we measured carbonylated protein concentrations in the BAL of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis, idiopathic pulmonary fibrosis, and for the first time in patients with chronic eosinophilic pneumonia and extrinsic allergic alveolitis. Our aim was to further investigate oxidation products in diffuse lung diseases. Oxidatively modified protein concentrations were increased in the BAL of patients than in that of controls (0.22 nmol/mg protein vs 0.05 nmol/mg protein; p < 0.001) and in each group of disease versus controls, suggesting that proteins that have become dysfunctional by oxidation could play a role in the pathogenesis of diffuse lung diseases. Further studies in a greater number of patients are needed to understand the contribution of oxidatively modified proteins to the pathogenesis of DLD and, in particular, to the development of extrinsic allergic alveolitis where the highest levels of carbonylated proteins were found.
Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , Lung Diseases, Interstitial/pathology , Proteins/analysis , Pulmonary Eosinophilia/pathology , Adult , Aged , Bronchoalveolar Lavage Fluid/cytology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Oxidative Stress , Protein Carbonylation , Proteins/adverse effects , Respiratory Function Tests , Scleroderma, Systemic/pathology , Statistics, NonparametricABSTRACT
Oxygen-derived free radicals produced by phagocytes have been postulated to contribute to lung tissue damage occurring during diffuse lung diseases (DLD). The two-dimensional electrophoretic (2-DE) analysis of bronchoalveolar lavage (BAL) protein composition revealed different protein profiles in sarcoidosis (S), idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) with a significant increase of low molecular weight proteins in IPF. Some of these proteins are involved in antioxidant processes. The aims of this report were to analyse the oxidative stress occurring in patients with DLD through determination of BAL protein carbonyl content and to identify target proteins of oxidation by a proteomic approach (2-DE combined with immunoblotting with specific antibodies for carbonyl groups). Carbonylated proteins detected by enzyme-linked immunosorbent assay (ELISA) were increased in BAL of patients with S, IPF and SSc compared to healthy controls with a significant difference for S and IPF. The proteomic approach to the analysis of BAL revealed that protein carbonylation was a process involving specific carbonylation-sensitive proteins and that in IPF a greater number of proteins target of oxidation were present. In conclusion, to our knowledge, this is the first report providing a database of proteins target of oxidation in BAL of patients with sarcoidosis, idiopathic pulmonary fibrosis and systemic sclerosis.
