Most cited article - PubMed ID 19281539
Bronchoalveolar lavage fluid cellular characteristics, functional parameters and cytokine and chemokine levels in interstitial lung diseases
Idiopathic interstitial pneumonia (IIP) entails a variable group of lung diseases of unknown etiology. Idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, interstitial lung diseases related to connective tissue disease (CTD-ILD), and hypersensitivity pneumonitis (HP) can manifest with similar clinical, radiological, and histopathological features. In a differential diagnosis, biomarkers can play a significant role. We assume that levels of specific cyto- or chemokines or their receptors can signal pathogenetic processes in the lungs. Eighty patients with different types of idiopathic interstitial pneumonia were enrolled in this study. Cell counts and concentrations of tumor necrosis factor (TNF)-α, interleukin-4 receptor α, proteinase-activated receptor (PAR)-2, matrix metalloproteinase (MMP)-7, and B cell-activating factor were measured in bronchoalveolar lavage fluid using commercial ELISA kits. High resolution computer tomography results were evaluated using alveolar and interstitial (IS) score scales. Levels of TNF-α were significantly higher in HP compared to fibrosing IIP (p < 0.0001) and CTD-ILD (p = 0.0381). Concentrations of IL-4Rα, PAR-2, and MMP-7 were positively correlated with IS (p = 0.0009; p = 0.0256; p = 0.0015, respectively). Since TNF-α plays a major role in inflammation, our results suggest that HP is predominantly an inflammatory disease. From the positive correlation with IS we believe that IL-4Rα, PAR-2, and MMP-7 could serve as fibroproliferative biomarkers in differential diagnosis of IIP.
BACKGROUND: Bronchoalveolar lavage (BAL) as complementary method is still used as ancillary tool in diagnosis of interstitial lung diseases. Tobacco smoking has been described to affect the BAL lavage cellular profile. To our knowledge, only few reports have so far investigated CD3+CD4+ and CD3+CD8+ lymphocyte subsets in non-smoking sarcoidosis patients additionally stratified according to CXR stage, and compared them to other non-smoking patients with interstitial lung diseases (ILDs). METHODS: We compared lymphocytes immune phenotypes, subsets, with CD3+, CD3+CD4+ and CD3+CD8+ cell markers, in the non-smoking subjects (n=297) including the patients with pulmonary sarcoidosis (S), idiopathic pulmonary fibrosis (IPF) (n=22), hypersensitivity pneumonitis (HP) (n=15), other interstitial idiopathic pneumonias (OIIPs) (n=39). According to prognosis, the patients with S were divided into four groups: 18 patients with Löfgren's syndrome (LS) in chest X-ray (CXR) ≤1 stage, 64 patients without LS in CXR ≤1 stage, 113 patients in CXR 2 stage and 26 patients with advanced CXR ≥3 stage. RESULTS: After the use of false discovery rate (FDR) correction, relative numbers (%) of CD3+, CD3+CD4+, CD3+CD8+ and CD3+CD4/CD3+CD8 ratio showed the most significant differences between the non-smokers with S (both with/without LS) and the non-smokers with other ILDs (IPF, OIIPs, HP). These lymphocytes subsets were further altered in the non-smokers with CXR stage 2 compared to the non-smokers with other ILDs (IPF, OIIPs, HP). We did not observe any differences in these lymphocyte subsets and CD3+CD4+/CD3+CD8+ ratio between the non-smokers with advanced sarcoidosis stage (CXR ≥3) and the non-smokers with IPF. CONCLUSIONS: Our data on the non-smokers confirmed the presence of the typical BAL cellular profile in sarcoidosis. The BAL cellular profile was helpful namely for differentiation of less advanced sarcoidosis. Its definite diagnostic utility should be the subject of further clinical studies with large numbers of the well characterized patients taking into consideration other clinical factors influencing BAL cellular profile, such as smoking or treatment.
- Keywords
- Sarcoidosis, bronchoalveolar lavage (BAL), lymphocytes, non-smokers,
- Publication type
- Journal Article MeSH
AIMS: The main feature of fibrosing idiopathic interstitial pneumonias (fIIPs) is the fibroproliferative potential of underlying pathogenetic process. We hypothesize that the concentration of potential markers of fibroproliferative healing, PAR-2, TGF-β1, TNF-α and IL-4Rα in bronchoalveolar lavage fluid (BALF) differ in patients with fIIPs compared to controls (C). PATIENTS AND METHODS: 10 patients with fIIPs and 9 controls (C) were included to the study. Concentrations of CD124 (IL4Rα), PAR-2, TGF-β1 and TNF-α in BALF were determined using the ELISA method. RESULTS: We observed higher concentrations of IL4Rα (fIIPS 1499.4 pg/ml vs C 255.5 pg/ml; p < 0.05), PAR-2 (fIIPS 1807.9 pg/ml vs C 421.0 pg/ml; p < 0.05) and TGF-β1(fIIPS 283.0 pg/ml vs C 197.1 pg/ml; p < 0.01) in BALF in fIIPs versus C. The values of TNF-a in BALF did not differ significantly in fIIPs compared to controls. The ratios also showed differences in fIIPS and C: IL4Rα/TGF-β1 (fIIPS 6.19 vs C 0.68; p = 0.0143); TNF-α/IL4Rα (fIIPS 0.84 vs C 7.93; p = 0.043); TGF-β1/TNF-α (fIIPS 0.21 vs C 0.16; p = 0.0179) and protein/PAR-2 (fIIPS 0.06 vs C 0.28; p = 0.0033). CONCLUSIONS: We found that PAR-2, TGF-β1 and IL-4Rα are significantly up-regulated in the BALF of fIIPs compared to controls, therefore we suppose they could become biomarkers of fibroproliferative healing.
- Keywords
- IL4R., Idiopathic interstitial pneumonias, PAR-2, TGF-beta, biomarkers, bronchoalveolar lavage fluid, fibroproliferative healing,
- Publication type
- Journal Article MeSH
