Bacterial load and related innate immune response in the bronchi of rapid decliners with chronic obstructive pulmonary disease.

BACKGROUND: Characterization of COPD patients with rapid lung functional decline is of interest for prognostic and therapeutic reasons. We recently reported an impaired humoral immune response in rapid decliners. OBJECTIVE: To determine the microbiota associated to markers of innate immune host response in COPD patients with rapid lung functional decline. METHODS: In COPD patients monitored for at least 3 years (mean ± SD: 5.8 ± 3 years) for lung functional decline, the microbiota and related markers of immune response was measured in bronchial biopsies of patients with different lung functional decline (rate of FEV1% lung functional decline: no decline FEV1%, ≤20 ml/year n = 21, slow decline FEV1%, >20 ≤ 70 ml/year, n = 14 and rapid decline FEV1%, >70 ml/year, n = 15) using qPCR for microbiota and immunohistochemistry for cell-receptors and inflammatory markers. MAIN RESULTS: Pseudomonas aeruginosa and Streptococcus pneumoniae were increased in rapid decliners vs slow decliners, S. pneumoniae was also increased compared to non decliners. In all patients, S. pneumoniae (copies/ml) positively correlated with pack-years consumption, lung function decline, TLR4, NOD1, NOD2 scored in bronchial epithelium and NOD1/mm2 in lamina propria. CONCLUSION: These data show an imbalance of microbiota components in rapid decliners which is associated to the expression of the related cell-receptors in all COPD patients. These findings may help in the prognostic stratification and treatment of patients.

Decreased humoral immune response in the bronchi of rapid decliners with chronic obstructive pulmonary disease.

BACKGROUND: Identification of COPD patients with a rapid decline in FEV1 is of particular interest for prognostic and therapeutic reasons. OBJECTIVE: To determine the expression of markers of inflammation in COPD patients with rapid functional decline in comparison to slow or no decliners. METHODS: In COPD patients monitored for at least 3 years (mean ± SD: 5.8 ± 3 years) for lung functional decline, the expression and localization of inflammatory markers was measured in bronchial biopsies of patients with no lung functional decline (FEV1% + 30 ± 43 ml/year, n = 21), slow (FEV1% ml/year, - 40 ± 19, n = 14) and rapid decline (FEV1% ml/year, - 112 ± 53, n = 15) using immunohistochemistry. ELISA test was used for polymeric immunoglobulin receptor (pIgR) quantitation "in vitro". RESULTS: The expression of secretory IgA was significantly reduced in bronchial epithelium (p = 0.011) and plasma cell numbers was significantly reduced in the bronchial lamina propria (p = 0.017) of rapid decliners compared to no decliners. Bronchial inflammatory cell infiltration, CD4, CD8, CD68, CD20, NK, neutrophils, eosinophils, mast cells, pIgR, was not changed in epithelium and lamina propria of rapid decliners compared to other groups. Plasma cells/mm2 correlated positively with scored total IgA in lamina propria of all patients. "In vitro" stimulation of 16HBE cells with LPS (10 µg/ml) and IL-8 (10 ng/ml) induced a significant increase while H2O2 (100 µM) significantly decreased pIgR epithelial expression. CONCLUSION: These data show an impaired humoral immune response in rapid decliners with COPD, marked by reduced epithelial secretory IgA and plasma cell numbers in the bronchial lamina propria. These findings may help in the prognostic stratification and treatment of COPD.

Pathogenesis of COPD at the cellular and molecular level.

Chronic inflammatory responses in the lung of patients with stable mild-to-severe forms of chronic obstructive pulmonary disease (COPD) play a central role in the definition, comprehension and monitoring of the disease state. A better understanding of the COPD pathogenesis cannot avoid a detailed knowledge of these inflammatory changes, altering the functional health of the lung during the disease progression. We summarize and discuss the role and principal functions of the inflammatory cells populating the large, small airways and lung parenchyma of patients with COPD of increasing severity in comparison with healthy control subjects: T and B lymphocytes, NK and innate lymphoid cells, macrophages, and neutrophils. The differential inflammatory distribution in large and small airways of patients is also discussed. Furthermore, relevant cellular mechanisms controlling the homeostasis and the "normal" balance of these inflammatory cells and of structural cells in the lung, such as autophagy, apoptosis, necroptosis and pyroptosis are as well presented and discussed in the context of the COPD severity.