Background: IL-6 is strongly implicated in the development of chronic obstructive pulmonary disease (COPD). IL-13 is the well-documented central mediator in allergic asthma. IL-6 is attributed to the proinflammatory activities in COPD as well as asthma. In COPD patients exacerbation is increased by serum IL-6. The association of IL-13 as well as IL-6 with the impaired respiratory function of asthma patients remains controversial. Objectives: The aim of this study was to compare the concentration of IL-6 and IL-13 in the induced sputum of asthma and COPD patients, and to assess the possible association of these cytokines with the impairment of lung function. Methods: Twenty-six subjects with COPD and 18 subjects with asthma were enrolled in this study. IL-6 and IL-13 levels were measured in induced sputum by ELISA and correlated with the results of respiratory tests. Results: The induced sputum of COPD patients had a significantly higher IL-6 level than the sputum of asthma subjects while no significant differences were found in the levels of IL-13. There was a statistically significant negative correlation between IL-6 level and FEV1 or FEV1/FVC in asthma patients (r = –0.59 and –0.54, respectively) and a negative correlation that did not reach statistical significance between IL-6 level and FEV1, FEV1% or FVC in COPD subjects (r = –0.30, –0.30 and –0.38, respectively). There was no relationship between concentrations of IL-13 and impaired respiratory function. Conclusions: Our results confirmed that IL-6, but not of IL-13, is associated with respiratory disorders in both asthma and COPD patients.

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with different inflammatory phenotypes. Various inflammatory mediators play a role in these diseases. The aim of this study was to analyze the neutrophilic and eosinophilic airway and systemic inflammation as the phenotypic characterization of patients with asthma and COPD. Twenty-four patients with asthma and 33 patients with COPD were enrolled in the study. All the patients were in mild-to-moderate stage of disease, and none of them were treated with inhaled corticosteroids. Concentrations of IL-6, neutrophil elastase (NE), matrix metalloproteinase 9 (MMP-9), eosinophil cationic protein (ECP), and IL-33 and IL-17 in serum and induced sputum (IS) were measured by enzyme-linked immunosorbent assay (ELISA). The cellular composition of blood and IS was evaluated. Hierarchical clustering of patients was performed for the combination of selected clinical features and mediators. Asthma and COPD can be differentiated based on eosinophilic/neutrophilic systemic or airway inflammation with unsatisfactory efficiency. Hierarchical clustering of patients based on blood eosinophil percentage and clinical data revealed two asthma clusters differing in the number of positive skin prick tests and one COPD cluster with two subclusters characterized by low and high blood eosinophil concentrations. Clustering of patients according to IS measurements and clinical data showed two main clusters: pure asthma characterized by high eosinophil/atopy status and mixed asthma and COPD cluster with low eosinophil/atopy status. The neutrophilic phenotype of COPD was associated with more severe airway obstruction and hyperinflation.

Microplastic particles from the air are inhaled and accumulate in the lungs, potentially causing immunological reactions and airway tissue injury. This study aimed to evaluate the biological effects of polyamide fibres on nasal epithelium co-cultivated with macrophages in control, asthma, and COPD groups. Nasal epithelial cells alone or in co-culture with monocyte-derived macrophages were exposed to polyamide fibres for 48 h. We identified 8 differentially expressed genes (DEGs) in controls, 309 DEGs in asthma (including ANKRD36C, BCL2L15, FCGBP, and IL-19), and 22 DEGs in COPD (e.g., BCL2L15, IL-19, CAPN14, PGBD5, PTPRH), particularly in epithelial/moMφ co-cultures. Microplastic exposure induced inflammatory cytokine secretion only for IL-8 production in controls (epithelial/ moMφs co-culture) and asthmatic (monoculture) epithelial cells in contrast to PM_2.5, which was a strong inflammatory inducer. Gene Ontology analysis revealed that microplastic exposure affected sterol and cholesterol biosynthesis, secondary alcohol metabolism, and acetyl-CoA metabolism in asthma, and cell motility, chemokine signaling, leukocyte migration, and chemotaxis in COPD. Microplastic stimulation altered the response of airway epithelial cells in obstructive lung diseases differently than in controls, linking to Th2 inflammation, stress response modulation, and carcinogenesis. Asthmatic and COPD epithelial cells are more susceptible to damage from microplastic fibre exposure.

Idiopathic pulmonary fibrosis (IPF) is a progressive and eventually fatal lung disease with a complex etiology. Approved drugs, nintedanib and pirfenidone, modify disease progression, but IPF remains incurable and there is an urgent need for new therapies. We identified chitotriosidase (CHIT1) as new driver of fibrosis in IPF and a novel therapeutic target. We demonstrate that CHIT1 activity and expression are significantly increased in serum (3-fold) and induced sputum (4-fold) from IPF patients. In the lungs CHIT1 is expressed in a distinct subpopulation of profibrotic, disease-specific macrophages, which are only present in patients with ILDs and CHIT1 is one of the defining markers of this fibrosis-associated gene cluster. To define CHIT1 role in fibrosis, we used the therapeutic protocol of the bleomycin-induced pulmonary fibrosis mouse model. We demonstrate that in the context of chitinase induction and the macrophage-specific expression of CHIT1, this model recapitulates lung fibrosis in ILDs. Genetic inactivation of Chit1 attenuated bleomycin-induced fibrosis (decreasing the Ashcroft scoring by 28%) and decreased expression of profibrotic factors in lung tissues. Pharmacological inhibition of chitinases by OATD-01 reduced fibrosis and soluble collagen concentration. OATD-01 exhibited anti-fibrotic activity comparable to pirfenidone resulting in the reduction of the Ashcroft score by 32% and 31%, respectively. These studies provide a preclinical proof-of-concept for the antifibrotic effects of OATD-01 and establish CHIT1 as a potential new therapeutic target for IPF.

Urban particulate matter (UPM) is an important trigger of airway inflammation. The cross-talk between the external and internal matrix in the respiratory tract occurs due to the transepithelial network of macrophages/dendritic cells. This study characterized the immune processes induced by the epithelium after UPM exposure in special regard to interactions with monocyte-derived dendritic cells (moDCs) and monocyte-derived macrophages (moMφs) in obstructive lung diseases. A triple-cell co-culture model (8 controls, 10 asthma, and 8 patients with COPD) utilized nasal epithelial cells, along with moMφs, and moDCs was exposed to UPM for 24 h. The inflammatory response of nasal epithelial cells to UPM stimulation is affected differently by cell–cell interactions in healthy people, asthma or COPD patients of which the interactions with DCs had the strongest impact on the inflammatory reaction of epithelial cells after UPM exposure. The epithelial remodeling and DCs dysfunction might accelerate the inflammation after air pollution exposure in asthma and COPD.