Features of immune response in different phenotypes of chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is considered a heterogeneous disorder exhibiting different phenotypes. Chronic systemic inflammation is an important link in the COPD pathogenesis. The studies of immune response in the context of clinical and functional phenotypes seems relevant. Objective of our work was to study the features of immune response in clinical and functional phenotypes of COPD.Eighty-three COPD patients of different severity grade and 22 apparently healthy volunteers were examined. After determining the COPD phenotype by clinical and functional signs, the patients were divided in two groups, i.e., 38 subjects with bronchitis, and 45 patients with emphysematous phenotype. Clinical, functional and laboratory research was carried out in standard mode. Static lung volumes and respiratory capacities were investigated, i.e., functional residual capacity, residual lung volume, total lung capacity, bronchial resistance on inspiration and expiration to assess phenotype of the disease. Subpopulations of Th1 and Th17 lymphocytes were determined by the level of blood serum cytokines, tumor necrosis factor (TNFá), interleukins (IL) IL-4, IL-10, IL-17A, IFNã).Different features of immune response were revealed in bronchitic and emphysematous phenotypes of the COPD patients. Activation of inflammatory process with differentiation of naive T lymphocytes along the Th1-dependent pathway was found in 68% of cases with bronchitis and 16% of patients with emphysematous phenotypes. As compared with control group, the patients showed a statistically significant increase in the level of TNFá, IFNã, along with decrease in IL-4. Development of immune response by the Th17 type was found in 32% of cases with bronchitis, and 84% of cases with emphysematous phenotypes. Its emergence was associated with increased IL-17A and IL-10 levels, and a decrease in IFNã/IL-17A compared to the control. Differentiation of T helper cells towards Th1 pathway of immune response has been shown to predominate in bronchitic phenotype and at early stages of the disease. The Th17 type of immune response prevailed with increasing severity of the disorder. In emphysematous phenotype of COPD, the Th17-pathway of immune response develops at early stages of the disease. Some relationships are revealed between the systemic inflammation indexes and functional parameters of external respiration. An inverse relationship between TNFá and the OOL/OEL ratio in Th1 type of immune response has been shown. A direct correlation was found between the level of IL-17A and the parameters of external respiration function (FEV1, FEV1/FVC), as well as between IFNã/IL-17A and functional residual capacity in Th17 type of immune response.The type of immune response is associated with severity of the disease, as well with clinical and functional phenotype of COPD. Progression of the disease, broncho-obstructive disorders and hyperinflation are associated with increased levels of cytokines that provide cell polarization along the Th17 pathway. Determination of COPD phenotype and the type of immune response already at an early stage of the disease will enable prediction of its course and justify the choice of phenotype-oriented therapy.

Keywords

• chronic obstructive pulmonary disease
• clinical phenotypes
• th-dependent type immune response