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Background: Previous studies have shown that IL-25 levels are increased in patients with asthma with fixed airflow limitation (FAL). However, the mechanism by which IL-25 contributes to airway remodeling and FAL remains unclear. Here, we hypothesized that IL-25 facilitates pro-fibrotic phenotypic changes in bronchial epithelial cells (BECs) and circulating fibrocytes (CFs), orchestrates pathological crosstalk from BECs to CFs, and thereby contributes to airway remodeling and FAL., Methods: Fibrocytes from asthmatic patients with FAL and chronic asthma murine models were detected using flow cytometry, multiplex staining and multispectral imaging analysis. The effect of IL-25 on BECs and CFs and on the crosstalk between BECs and CFs was determined using cell culture and co-culture systems., Results: We found that asthmatic patients with FAL had higher numbers of IL-25 receptor (i.e., IL-17RB) + -CFs, which were negatively correlated with forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC). The number of airway IL-17RB + -fibrocytes was significantly increased in ovalbumin (OVA)- and IL-25-induced asthmatic mice versus the control subjects. BECs stimulated with IL-25 exhibited an epithelial-mesenchymal transition (EMT)-like phenotypic changes. CFs stimulated with IL-25 produced high levels of extracellular matrix (ECM) proteins and connective tissue growth factors (CTGF). These profibrotic effects of IL-25 were partially blocked by the PI3K-AKT inhibitor LY294002. In the cell co-culture system, OVA-challenged BECs facilitated the migration and expression of ECM proteins and CTGF in CFs, which were markedly blocked using an anti-IL-17RB antibody., Conclusion: These results suggest that IL-25 may serve as a potential therapeutic target for asthmatic patients with FAL., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Interleukin (IL)-25 is a T helper (Th) type-2 cytokine implicated in the pathogenesis of asthma. Fibrocytes are progenitor cells that can migrate into circulation and inflamed bronchial epithelium., Objectives: We aim to test the hypothesis that circulating fibrocytes may be the novel cellular targets of IL-25 and the recruitment of IL-25R + circulating fibrocytes may correlate with asthmatic airway obstruction., Methods: By using flow cytometry analysis, IL-25R + fibrocytes (i.e., IL-17RB + fibrocytes) in the freshly isolated peripheral blood mononuclear cells (PBMCs) from 15 control subjects and 35 patients with asthma were enumerated and compared. Enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of IL-25., Results: We found the percentage of total and IL-25R + (IL-17RB + ) fibrocytes in PBMCs was significantly increased in patients with asthma when compared with control subjects. Subgroup analysis further showed that the percentage of circulating total and IL-25R + fibrocytes in PBMCs was markedly increased in asthma patients with severe-to-very severe fixed airflow limitation. Furthermore, IL-25R + circulating fibrocytes in asthma patients were shown to significantly correlate with forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC), FEV 1 % predicted, blood eosinophils, serum IgE and plasma IL-25 levels., Conclusion: We concluded that circulating fibrocytes are the novel potential cellular targets of IL-25. IL-25R + fibrocytes are increased in asthma patients. Increased proportions of IL-25R + fibrocytes predict a distinct asthma phenotype with fixed airflow limitation. Biological therapy-targeting IL-25-fibrocytes axis may offer great promise for the control of asthma patients with severe airway remodelling and obstruction., (© 2021 John Wiley & Sons Ltd.)

Background: As a typical "united airway" disease, asthma-chronic rhinosinusitis (CRS) overlap has recently drawn more attention. Bronchiectasis is a heterogeneous disease related to a variety of diseases. Whether bronchiectasis exists and correlates with asthma-CRS patients has not been fully elucidated. The purpose of the study was to explore the presence and characteristics of bronchiectasis in patients with overlapping asthma and CRS., Methods: This report describes a prospective study with consecutive asthma-CRS patients. The diagnosis and severity of bronchiectasis were obtained by thorax high-resolution computed tomography (HRCT), the Smith radiology scale and the Bhalla scoring system. CRS severity was evaluated by paranasal sinus CT and the Lund-Mackay (LM) scoring system. The correlations between bronchiectasis and clinical data, fraction of exhaled nitric oxide, peripheral blood eosinophil counts and lung function were analyzed., Results: Seventy-two (40.91%) of 176 asthma-CRS patients were diagnosed with bronchiectasis. Asthma-CRS patients with overlapping bronchiectasis had a higher incidence rate of nasal polyps (NPs) (P = 0.004), higher LM scores (P = 0.044), higher proportion of ≥ 1 severe exacerbation of asthma in the last 12 months (P = 0.003), lower postbronchodilator forced expiratory volume in one second (FEV 1 ) % predicted (P = 0.006), and elevated peripheral blood eosinophil counts (P = 0.022). Smith and Bhalla scores were shown to correlate positively with NPs and negatively with FEV 1 % predicted and body mass index. Cutoff values of FEV 1 % predicted ≤ 71.40%, peripheral blood eosinophil counts > 0.60 × 10 9 /L, presence of NPs, and ≥ 1 severe exacerbation of asthma in the last 12 months were shown to differentiate bronchiectasis in asthma-CRS patients., Conclusions: Bronchiectasis commonly overlaps in asthma-CRS patients. The coexistence of bronchiectasis predicts a more severe disease subset in terms of asthma and CRS. We suggest that asthma-CRS patients with NPs, severe airflow obstruction, eosinophilic inflammation, and poor asthma control should receive HRCT for the early diagnosis of bronchiectasis.

Background: Interleukin-27 (IL-27) modulates CD4+ T-cell differentiation and function. The aim of this study is to investigate the effect and molecular mechanisms of IL-27 on the development of asthma., Methods: IL-27 was intranasally administered in an ovalbumin-induced asthma model, and lung mononuclear cells and different Th cell classes were detected by fluorescence-activated cell sorting. The effect and mechanisms of IL-27 on human bronchial epithelial (HBE) cells were investigated by measuring changes in chemotactic factors, cytokines, transcription factors, and signaling pathways., Results: We found that intranasal administration of IL-27 could attenuate airway inflammation and hyperresponsiveness, upregulate the type 1 T helper (Th1)-T memory (Tm) cells and regulatory T (Treg) cells subgroups of lung tissue lymphocytes, and diminish the levels of type 2 T helper (Th2) cytokines. IL-27 upregulated the expression of C-C motif chemokine ligand 2 (CCL2), CCL3, and CCL4 in HBE cells and promoted the production of chemotactic factors to attract monocyte recruitment. Recruited monocytes secondarily secreted IL-27 to influence HBE cells in a positive feedback cycle. After IL-27 intervention, signal transducer and activator of transcription 1 (STAT1) phosphorylation increased, while STAT4 and STAT6 phosphorylation declined., Conclusions: Preventative intranasal administration of IL-27 can recruit more IL-27-secreted monocytes to the airway and change the different T-cell classes in lung. The improved Th1 environment helps to alleviate Th2-mediated allergic asthma by repairing the STAT1 pathway but not the STAT4 pathway., (© 2018 Wiley Periodicals, Inc.)

Telocytes (TCs) newly discovered as the mesenchyme-derived interstitial cells were found to have supportive effects on mesenchymal stem cells (MSCs). The present study aimed at investigating effects of TCs or TCs gathered with MSCs on experimental airway inflammation and hyper-responsiveness. The TCs were isolated from the lung tissue of the female BALB/c mice. The ovalbumin (OVA)-induced asthma model was established. TCs (1 × 10 6 /2 × 10 6 ) and/or MSCs (1 × 10 6 ) were injected through mice tail vein for consecutive three days before OVA excited the mice. This study at first demonstrated that the transplantation of TCs could improve allergen-induced asthma by obviously inhibiting airway inflammation and airway hyper-responsiveness preclinically, with the down-regulation of Th2-related cytokine IL-4, transcription factor GATA-3 and Th2 cell differentiation, while up-regulation of Th1-related cytokine IFN-γ, transcription factor T-bet and Th1 cells proliferation in asthma, just like MSCs. Co-transplantation of TCs with MSCs showed better therapeutic effects on experimental asthma, even though the therapeutic effects of TCs alone were similar to those of MSCs alone. TCs and the combination of TCs with MSCs could improve the airway inflammation and airway hyper-responsiveness and can be a new alternative for asthma therapy., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: Recent data have demonstrated that long-lived memory T cells are present in the human lung and can play significant roles in the pathogenesis of specific allergic and autoimmune diseases. However, most evidence has been obtained from mouse studies, and the potential roles of memory T cells in human allergic diseases, such as asthma, remain largely unknown., Methods: Thirty-three asthmatics, 26 chronic obstructive pulmonary disease (COPD) patients, and 22 healthy volunteers were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood, and cell surface staining (CD4, CD45RO, CRTH2, CD62L, and CCR7) was performed for the detection of memory CD4 + T cells in blood. After stimulation with interleukin-27 (IL-27) or IL-4 for 15 min, the STAT1/STAT6 phosphorylation of memory CD4 + T cells was measured separately by flow cytometric techniques. The cytokine-releasing profiles after 6 days of culture under neutralization, T H 2, T H 2 + lipopolysaccharide (LPS), and T H 2 + house dust mite (HDM) conditions were detected by intracellular protein (IL-5, IL-17, and interferon (IFN)-γ) staining. Correlation analyses between the profile of memory CD4 + T cells and clinical characteristics of asthma were performed., Results: The number of circulating memory CD4 + T (CD4 + Tm) cells in asthmatics was increased compared with that in the healthy subjects (48 ± 5.7 % vs. 32 ± 4.1 %, p < 0.05). Compared with COPD and healthy subjects, the phosphorylation of signal transducer and activator of transcription 1 (STAT1-py) was impaired in asthmatics, whereas the phosphorylation of signal transducer and activator of transcription 6 (STAT6-py) was slightly enhanced. This imbalance of STAT1-py/STAT6-py was attributed to T H 2 memory cells but not non-T H 2 memory cells in blood. The cytokine-releasing profiles of asthmatics was unique, specifically IL-5 high , IL-17 high , and IFN-r low , compared with those of COPD patients and healthy subjects. The IL-17 production levels in CD4 + Tm cells are associated with disease severity and positively correlated with medication consumption in asthma., Conclusions: The long-lived, antigen-specific memory CD4 + T cells, rather than PBMCs or peripheral lymphocytes, might be the ideal T cell subset candidates for analyzing the endotype of asthma. Memory CD4 + T cells exhibiting a shift in STAT phosphorylation and specific cytokine-releasing profiles have the potential to facilitate the understanding of disease heterogeneity and severity, allowing the more personalized treatment of patients.

Type 2 innate lymphoid cells (ILC2s) have been shown to produce large amounts of type 2 cytokines in a non-antigen-specific manner. These cytokines act upstream and downstream of ILC2 and are increasingly common in asthma drug development, thus warranting a closer investigation of the mechanism-related clinical manifestations of ILC2 in the selection of patients with asthma. We hypothesized that IL-13 + ILC2s in the circulation might correlate with asthma control status as a result of persistent T-helper cell type 2 (Th2) inflammation in the lung. Furthermore, we aimed to explore ILC2s' responsiveness to glucocorticoid. The percentages of ILC2s and IL-13 + ILC2s in different asthma subgroups were checked, and correlation analyses between ILC2s and asthma-related clinical parameters were performed. Dexamethasone treatments in ILC2s and Th2 cells were performed to clarify their response properties. ILC2s were identified as a Lin - CD45 hi IL-7Rα + CRTH2 + cell population distinct from human peripheral blood mononuclear cells. Frequencies of ILC2s were increased dramatically in those with asthma (0.04 ± 0.02%) compared with healthy donors (0.025 ± 0.011%). The percentages of IL-13 + ILC2s were significantly higher in patients in the uncontrolled group (49.7 ± 16.9%) and partly controlled groups (30.8 ± 13.1%) than in those in the well-controlled group (16.7 ± 5.9%) and healthy control subjects (18.7 ± 8.7%). Effective treatment of uncontrolled IL-13 + ILC2-positive patients with asthma resulted in dynamic modulation of IL-13 + ILC2 levels back to baseline. ILC2s were more resistant to glucocorticoid than Th2 cells in vitro. ILC2s are strong responders to IL-25/IL-33 stimulation. IL-13 + ILC2s show a positive correlation with patient asthma control status and are more resistant to glucocorticoid than Th2 cells in humans.

Objectives/hypothesis: To investigate the role of airway patency and factors associated with airway patency in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma., Study Design: Retrospective study., Methods: The upper and lower airway patency of 140 patients with CRSwNP and asthma (asthma group) and 42 patients with CRSwNP without asthma (nonasthma control group) was measured using acoustic rhinometry, rhinomanometry, and spirometry. Total serum immunoglobulin E and eosinophil counts were also compared. The severity of nasal diseases in these patients was assessed via the Lund-Mackay score (LMS) and Lund-Kennedy score (LKS)., Results: There was no difference between the asthma and nonasthma groups in terms of total nasal resistance at 75 Pa (R(75T)), bilateral minimum cross-sectional area (MCA(R+L)), or bilateral nasal cavity volume between 0 and 7.0 cm(3) (V7(R+L)). Forced expiratory volume in 1 second (FEV(1)) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF(25-75)) of the asthma group were significantly lower than those of the nonasthma group. FEV(1) and FEF(25-75) were not correlated with R(75T), MCA(R+L), V7(R+L), or severity of nasal disease. For the patients with asthma, LMS and serum eosinophil counts were independent predictors of MCA(R+L)., Conclusions: The presence of asthma may not influence upper airway patency in CRSwNP patients. In CRSwNP patients with asthma, impairment of upper airway patency was associated with changes in LMS and eosinophilia, and in these patients lower airway patency was significantly lower than that of the control group (without asthma). In CRSwNP patients with asthma, there was little or no association between upper and lower airway patency., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Ovalbumin (OVA)-induced asthma in mouse lungs causes changes in the mRNA and protein levels of aquaporins (AQPs). AQP expression was examined in the presence of various anti-asthmatic agents, including dexamethasone, ambroxol, and terbutaline. The influence of these agents on OVA-induced airway inflammation was also evaluated. The mRNA expression levels of AQP1, 4, and 5 were significantly reduced and that of AQP3 was significantly increased 24h after the last OVA exposure. The protein levels of AQP1, 3, and 5 mirrored the mRNA expression profiles, but AQP4 did not exhibit any changes. Only the mRNA and protein expression levels of AQP1 and AQP5 were significantly increased by these three anti-asthmatic agents. Dexamethasone and ambroxol improved the eosinophil infiltration, mucus secretion, and pulmonary edema caused by OVA, but terbutaline only alleviated pulmonary edema. These results indicate that AQP1 and AQP5 are closely related to pulmonary edema but not to eosinophil infiltration or mucus secretion during asthma. Anti-asthmatic agents could alleviate pulmonary edema through upregulating the expression of AQP1 and AQP5 in mouse lungs that have OVA-induced asthma., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Airway inflammation and mucus hyperproduction play the central role in the development of asthma, although the mechanisms remain unclear. The aquaporin (AQP)-5 may be involved in the process due to its contribution to the volume of liquid secreted from the airways. The present study firstly found the overexpression of AQP5 in the airway epithelium and submucosal glands of asthmatics. Furthermore, we aimed at evaluating the role of AQP5 in airway inflammation and mucous hyperproductions during chronic allergic responses to house dust mite (HDM). Bronchoalveolar lavage levels of interleukin (IL)-2, IL-4, IL-10, interferon-γ and Mucin 5AC (MUC5AC), and number of peribronchial and perivascular cells were measured in AQP5 wild-type and AQP5 knockout (KO) mice. We found that HDM induced airway inflammation, lung Th2 cell accumulation and mucin hypersecretion in C57BL/6 mice rather than AQP5 KO mice. Expression of MUC5AC and MUC5B proteins and genes in the lung tissue was significantly lower in AQP5 KO mice. Thus, our results implicate involvement of AQP5 in the development of airway inflammation and mucous hyperproduction during chronic asthma., (© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.)

Asthma and allergic rhinitis frequently coexist in the same patient. There is a similarity and variation as well as potential relationship between asthma and allergic rhinitis. There is an increasing evidence to suggest a major involvement of airway epithelial cells in the pathogenesis of asthma and allergic rhinitis. The present review describes the importance of the airway epithelial cell in the development of allergic airway diseases, its role as the primary airway defense against exposure of the airway and lung to inflammatory stimuli and antigens and as an important player through activation of epithelial Toll-like receptors (TLRs) to provide an important link between innate immunity and allergic disease. Additionally, airway epithelial cells can act as inflammatory promoters capable of directing dendritic cells (DCs) towards a T helper 2 (Th2) response, and as active producers of several inflammatory/anti-inflammatory mediators. It is hypothesized that airway epithelial cells may play as both inflammatory initiator and immuno-pathological feedback regulation between allergic rhinitis and asthma via release of systemic inflammatory mediators. Thus, airway epithelial cells may be valuable therapeutic targets for discovery and development of new drugs and/or new therapeutic strategies to treat asthma and allergic rhinitis.

Introduction: Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysine residues of histones and other proteins, generally leading to a closed chromosomal configuration and transcriptional repression. Different HDACs have distinct substrate specificities and functions in different biological processes. Accumulating evidence indicates that HDACs play a key role in the pathogenesis of multiple respiratory diseases. Areas covered: After an extensive search of the PubMed database, Web of Science and ClinicalTrials.gov, covering the period from 1992 to 2024, this review summarizes recent advances in understanding the role of HDACs in inflammatory respiratory diseases, including allergic rhinitis (AR), chronic rhinosinusitis (CRS), asthma and chronic obstructive pulmonary disease (COPD). We also examine recent progress on the efficacy and potential use of histone deacetylase inhibitors (HDACi) for the treatment of these diseases. Expert opinion: Available data indicate that HDACs play an important role in the development of common inflammatory respiratory diseases, and HDACi have shown promise as treatments for these diseases. However, the exact roles and underlying mechanisms of specific HDACs in disease pathogenesis require further study. Additional work is necessary to develop novel potent HDACi with high isoform selectivity. [ABSTRACT FROM AUTHOR]

Introduction: Interleukin (IL)‐25 is a T helper (Th) type‐2 cytokine implicated in the pathogenesis of asthma. Fibrocytes are progenitor cells that can migrate into circulation and inflamed bronchial epithelium. Objectives: We aim to test the hypothesis that circulating fibrocytes may be the novel cellular targets of IL‐25 and the recruitment of IL‐25R+ circulating fibrocytes may correlate with asthmatic airway obstruction. Methods: By using flow cytometry analysis, IL‐25R+ fibrocytes (i.e., IL‐17RB+ fibrocytes) in the freshly isolated peripheral blood mononuclear cells (PBMCs) from 15 control subjects and 35 patients with asthma were enumerated and compared. Enzyme‐linked immunosorbent assay (ELISA) was used to detect the plasma levels of IL‐25. Results: We found the percentage of total and IL‐25R+ (IL‐17RB+) fibrocytes in PBMCs was significantly increased in patients with asthma when compared with control subjects. Subgroup analysis further showed that the percentage of circulating total and IL‐25R+ fibrocytes in PBMCs was markedly increased in asthma patients with severe‐to‐very severe fixed airflow limitation. Furthermore, IL‐25R+ circulating fibrocytes in asthma patients were shown to significantly correlate with forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), FEV1% predicted, blood eosinophils, serum IgE and plasma IL‐25 levels. Conclusion: We concluded that circulating fibrocytes are the novel potential cellular targets of IL‐25. IL‐25R+ fibrocytes are increased in asthma patients. Increased proportions of IL‐25R+ fibrocytes predict a distinct asthma phenotype with fixed airflow limitation. Biological therapy‐targeting IL‐25‐fibrocytes axis may offer great promise for the control of asthma patients with severe airway remodelling and obstruction. [ABSTRACT FROM AUTHOR]

Background: The preoperative prediction of the recurrence of chronic rhinosinusitis with nasal polyps (CRSwNP) remains difficult in clinical practice. Objective: We aimed to develop a nomogram that combined peripheral risk factors to clinically predict the recurrence of CRSwNP. Methods: Data from 158 CRSwNP patients who underwent endoscopic sinus surgery (ESS) from January 2012 to December 2016 were collected, and the patients were followed up for 3 years. Of these, 96 patients who underwent ESS in an earlier period formed the training cohort for nomogram development, and 62 patients who underwent ESS thereafter formed the validation cohort to confirm the model's performance. Risk factors for recurrence identified by univariate and multivariate logistic regression were used to create a nomogram. Results: The recurrence rate was 29.2% (28/96) for the training cohort and 35.5% (22/62) for the validation cohort. Univariate analysis identified blood eosinophils (Eos), serum IgE level, asthma comorbidity, and the number of previous ESSs as risk factors for recurrence. Among those four parameters, serum IgE level and a previous ESS surgery were identified as two independent risk factors. A nomogram consisting of blood Eos, total serum IgE level, asthma comorbidity, and the number of previous ESSs was constructed, demonstrating a C index of 0.81 (95% CI, 0.79-0.83) and 0.80 (95% CI, 0.77-0.83) for predicting recurrence in the training and validation cohorts, respectively. The nomogram had well-fitted calibration curves. Conclusion: The nomogram might be able to preoperatively predict the recurrence of CRSwNP by using currently available and objective parameters. Further studies are required to validate its reliability and effectiveness. [ABSTRACT FROM AUTHOR]

Background: There is clinical evidence for impaired lung function in chronic rhinosinusitis with nasal polyps (CRSwNP) patients, which may be due to a high incidence of asthma comorbidity. The lung function characteristics of non‐asthmatic CRSwNP patients are not known. Small airway dysfunction (SAD) is involved in the pathogenesis of asthma. However, whether SAD is detected in non‐asthmatic patients with CRSwNPs remains unclear. Objective: This study analysed the lung function of non‐asthmatic patients with CRSwNPs and evaluated its clinical relevance in CRSwNPs. Methods: The clinical data for 191 consecutive CRSwNP patients (73 asthmatic and 118 non‐asthmatic) and 30 control subjects were prospectively collected. The patients were followed up for at least 3 years (mean [standard deviation], 42.47 ± 8.38 months). Serum and tissue total IgE levels were measured in 95 and 93 patients, respectively. Tissue eosinophil counts were documented in 63 patients. Results: Non‐asthmatic CRSwNP patients had decreased forced expiratory flow at 75% of the FVC (FEF75) and FEF50 compared to the control subjects, and this difference was related to the severity of CRSwNP. The risk factors for impaired lung function in asthmatic and non‐asthmatic patients were duration of asthma and smoking. A multivariate logistic analysis showed that decreased FEF50 was associated with the recurrence of non‐asthmatic CRSwNPs. The lung function of CRSwNP patients negatively correlated with the degree of type‐2 inflammation, which was defined by the levels of Eos and IgE in polyp tissues and blood. The SAD of non‐asthmatic CRSwNP patients was related to serum IgE levels. Conclusions and clinical relevance: This study provides evidence that non‐asthmatic CRSwNP patients may have SAD, which correlated with the severity and recurrence of CRSwNP. The decreased lung function of patients with CRSwNP was related to the degree of type‐2 inflammation. [ABSTRACT FROM AUTHOR]

Background: Recent data have demonstrated that long-lived memory T cells are present in the human lung and can play significant roles in the pathogenesis of specific allergic and autoimmune diseases. However, most evidence has been obtained from mouse studies, and the potential roles of memory T cells in human allergic diseases, such as asthma, remain largely unknown. Methods: Thirty-three asthmatics, 26 chronic obstructive pulmonary disease (COPD) patients, and 22 healthy volunteers were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood, and cell surface staining (CD4, CD45RO, CRTH2, CD62L, and CCR7) was performed for the detection of memory CD4 T cells in blood. After stimulation with interleukin-27 (IL-27) or IL-4 for 15 min, the STAT1/STAT6 phosphorylation of memory CD4 T cells was measured separately by flow cytometric techniques. The cytokine-releasing profiles after 6 days of culture under neutralization, T2, T2 + lipopolysaccharide (LPS), and T2 + house dust mite (HDM) conditions were detected by intracellular protein (IL-5, IL-17, and interferon (IFN)-γ) staining. Correlation analyses between the profile of memory CD4 T cells and clinical characteristics of asthma were performed. Results: The number of circulating memory CD4 T (CD4 Tm) cells in asthmatics was increased compared with that in the healthy subjects (48 ± 5.7 % vs. 32 ± 4.1 %, p < 0.05). Compared with COPD and healthy subjects, the phosphorylation of signal transducer and activator of transcription 1 (STAT1-py) was impaired in asthmatics, whereas the phosphorylation of signal transducer and activator of transcription 6 (STAT6-py) was slightly enhanced. This imbalance of STAT1-py/STAT6-py was attributed to T2 memory cells but not non-T2 memory cells in blood. The cytokine-releasing profiles of asthmatics was unique, specifically IL-5, IL-17, and IFN-r, compared with those of COPD patients and healthy subjects. The IL-17 production levels in CD4 Tm cells are associated with disease severity and positively correlated with medication consumption in asthma. Conclusions: The long-lived, antigen-specific memory CD4 T cells, rather than PBMCs or peripheral lymphocytes, might be the ideal T cell subset candidates for analyzing the endotype of asthma. Memory CD4 T cells exhibiting a shift in STAT phosphorylation and specific cytokine-releasing profiles have the potential to facilitate the understanding of disease heterogeneity and severity, allowing the more personalized treatment of patients. [ABSTRACT FROM AUTHOR]

Lung hyperinflation is a critical characteristic of pathophysiological changes in chronic obstructive pulmonary disease (COPD), and is associated with the severity and prognosis of the disease. In an attempt to understand the importance of lung hyperinflation in the pathogenesis of chronic lung disease, we will discuss in this review the understanding of the disease, measurements of lung hyperinflation in COPD, clinical findings of lung hyperinflation in emphysema, potential mechanisms of lung hyperinflation, its potential reversibility and comparison of lung hyperinflation between asthma and COPD. Multiple factors may contribute to the development of lung hyperinflation, including compromised alveolar walls, increased intra-airway pressure, inflammation, goblet cell hyperplasia and metaplasia and tissue remodeling. The development of new technology to measure lung hyperinflation will be helpful in the diagnosis and monitoring of the disease. Improvement in lung hyperinflation should become one of the most important criteria to evaluate the therapeutic effects of drugs. [ABSTRACT FROM AUTHOR]

Background Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS. Objective We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes. Methods In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1β, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-β1, IgE, Staphylococcus aureus enterotoxin–specific IgE, and albumin. We used partition-based clustering. Results Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5–negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a T H 17 profile and had mixed CRSsNP/CRSwNP. The IL-5–positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin–specific IgE. Conclusion Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only. [ABSTRACT FROM AUTHOR]