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Serum CXCL9 and CCL17 as biomarkers of declining pulmonary function in chronic bird-related hypersensitivity pneumonitis.

ABSTRACT: The clinical course of chronic hypersensitivity pneumonitis (HP) with fibrosis is similar to that of idiopathic pulmonary fibrosis (IPF). Current research is expected to identify biomarkers effective in predicting the deterioration of lung function in a clinical setting. Our group analyzed the relationships between the following parameters in chronic bird-related HP: patient characteristics, serum markers, lung function, HRCT findings, BALF profiles, and the worsening of lung function. We also analyzed serum levels of CXCL9, CCL17, and Krebs von den Lungen 6 (KL-6) as serum markers. Patients showing declines in vital capacity (VC) of over 5% at 6 months after first admission were categorized as the "decline group"; the others were categorized as the "stable group." The serum level of CCL17 and the percentage of BALF macrophages were significantly higher in the decline group compared to the stable group. Serum levels of CXCL9 and CCL17 were significant variables in a multivariate logistic regression analysis of factors associated with VC decline. Patients with a chemokine profile combining lower serum CXCL9 and higher serum CCL17 exhibited significantly larger VC decline in a cluster analysis. Higher serum CCL17 and lower serum CXCL9 were important predictors of worsening lung function in patients with chronic bird-related HP.

SUBMITTER: Nukui Y

PROVIDER: S-EPMC6675044 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Higher serum CCL17 may be a promising predictor of acute exacerbations in chronic hypersensitivity pneumonitis.

Project description:BackgroundRecent research has suggested that the Th1 and Th2 chemokine/cytokine axis contributes to the development of chronic hypersensitivity pneumonitis (HP). Acute exacerbations (AE) are significant factors in the prognosis of chronic HP. Little is known, however, about these biomarkers in association with AE in chronic HP patients.MethodsFifty-six patients with chronic HP were evaluated, including 14 patients during episodes of AE. Th1 mediators (C-X-C chemokine ligand [CXCL]10 and interferon [IFN]-?), Th2 mediators (C-C chemokine ligand [CCL]17, interleukin-4, and interleukin-13), and pro-fibrotic mediator (transforming growth factor [TGF]-?) were measured to evaluate the mediators as predictors of AE. C-C chemokine receptor (CCR)4 (receptor for CCL17)-positive lymphocytes were quantified in lung specimens.ResultsSerum CCL17 levels at baseline independently predicted the first episode of AE (HR, 72.0; 95% CI, 5.03-1030.23; p?=?0.002). AE was significantly more frequent in the higher-CCL17 group (?285 pg/ml) than in the lower-CCL17 group (<285 pg/ml) (log-rank test, p?=?0.0006; 1-year incidence: higher CCL17 vs. lower CCL17, 14.3% vs. 0.0%). Serum CCL17 levels and CCR4-positive cells during episodes of AE were increased from the baseline (p?=?0.01 and 0.031).ConclusionsHigher serum concentrations of CCL17 at baseline may be predictive of AE in patients with chronic HP, and CCL17 may contribute to the pathology of AE by inducing the accumulation of CCR4-positive lymphocytes in the lungs.

| S-EPMC3665443 | biostudies-literature

Protein antigen of bird-related hypersensitivity pneumonitis in pigeon serum and dropping.

Project description:BackgroundAvian antigen is a common cause of hypersensitivity pneumonitis (HP). Inhalation challenge with pigeon serum and pigeon dropping extract (PDE) elicits a hypersensitivity reaction in patients with bird-related hypersensitivity pneumonitis (BRHP), but the antigenic components in these materials have yet to be fully elucidated.MethodPigeon serum, pigeon intestine homogenates, and PDE were immunoblotted with serum samples from 8 patients with BRHP, 2 patients with summer-type HP, 2 patients with humidifier lung, and 3 healthy volunteers. Among the protein spots found in both pigeon serum and PDE, those that reacted with sera from BRHP patients were identified by mass spectrometry. Immunoassays using recombinant protein were performed to confirm the antigenicity of the identified protein. Cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant protein was also assessed.ResultsImmunoglobulin lambda-like polypeptide-1 (IGLL-1) was identified from all spots on 2-DE immunoblots of both pigeon serum and PDE. The BRHP patients exhibited higher levels of serum IgG antibody against the recombinant IGLL-1 (rIGLL-1) compared to the control subjects, as well as a stronger PBMCs proliferative response to rIGLL-1. Cytokine production by PBMCs from BRHP patients after rIGLL-1 exposure indicated that the protein could induce Th1 prone immune responses: an increase in TNF-α and an absence of elevated IL-10 production.ConclusionsPigeon IGLL-1 was identified as the BRHP antigen present in both pigeon serum and PDE.

| S-EPMC5397797 | biostudies-literature

Telomeropathy in Chronic Hypersensitivity Pneumonitis.

Project description: Not available

| S-EPMC6888653 | biostudies-literature

RNA-Sequencing of Chronic hypersensitivity pneumonitis compared with Idiopathic Pulmonary Fibrosis and Control Lung

Project description:Chronic hypersensitivity pneumonitis (CHP) is caused by an immune response to antigen inhalation and is characterized by variable histopathological and clinical features. A subset of CHP subjects have usual interstitial pneumonia and appear to be clinically similar to subjects with idiopathic pulmonary fibrosis (IPF). However, the molecular relationship between CHP and IPF is not well understood. We report an RNA-seq based transcriptomic analysis for whole lung tissues from CHP, IPF and control subjects.

2020-07-01 | GSE150910 | GEO

The Respiratory Microbiome in Chronic Hypersensitivity Pneumonitis Is Distinct from That of Idiopathic Pulmonary Fibrosis.

Project description:Rationale: Chronic hypersensitivity pneumonitis (CHP) is a condition that arises after repeated exposure and sensitization to inhaled antigens. The lung microbiome is increasingly implicated in respiratory disease, but, to date, no study has investigated the composition of microbial communities in the lower airways in CHP.Objectives: To characterize and compare the airway microbiome in subjects with CHP, subjects with idiopathic pulmonary fibrosis (IPF), and control subjects.Methods: We prospectively recruited individuals with a CHP diagnosis (n = 110), individuals with an IPF diagnosis (n = 45), and control subjects (n = 28). Subjects underwent BAL and bacterial DNA was isolated, quantified by quantitative PCR and the 16S ribosomal RNA gene was sequenced to characterize the bacterial communities in the lower airways.Measurements and Main Results: Distinct differences in the microbial profiles were evident in the lower airways of subjects with CHP and IPF. At the phylum level, the prevailing microbiota of both subjects with IPF and subjects with CHP included Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. However, in IPF, Firmicutes dominated, whereas the percentage of reads assigned to Proteobacteria in the same group was significantly lower than the percentage found in subjects with CHP. At the genus level, the Staphylococcus burden was increased in CHP, and Actinomyces and Veillonella burdens were increased in IPF. The lower airway bacterial burden in subjects with CHP was higher than that in control subjects but lower than that of those with IPF. In contrast to IPF, there was no association between bacterial burden and survival in CHP.Conclusions: The microbial profile of the lower airways in subjects with CHP is distinct from that of IPF, and, notably, the bacterial burden in individuals with CHP fails to predict survival.

| S-EPMC7874329 | biostudies-literature

Relevance of RNA N6-Methyladenosine Regulators for Pulmonary Fibrosis: Implications for Chronic Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis.

Project description:N6-methyladenosine (m6A) modification plays a pivotal role in post-transcriptionally regulating gene expression and biological functions. Nonetheless, the roles of m6A modification in the regulation of chronic hypersensitivity pneumonitis (CHP) and idiopathic pulmonary fibrosis (IPF) remain unclear. Twenty-two significant m6A regulators were selected from differential gene analysis between the control and treatment groups from the GSE150910 dataset. Five candidate m6A regulators (insulin-like growth factor binding protein 2, insulin-like growth factor binding protein 3, YTH domain-containing protein 1, zinc finger CCCH domain-containing protein 13, and methyltransferase-like 3) were screened by the application of a random forest model and nomogram model to predict risks of pulmonary fibrosis. The consensus clustering method was applied to divide the treatment samples into two groups with different m6A patterns (clusters A and B) based on the 22 m6A regulators. Our study performed principal component analysis to obtain the m6A-related score of the 288 samples to quantify the two m6A patterns. The study reveals that cluster A was linked to T helper cell (Th) 2-type cytokines, while the immune infiltration of Th1 cytokines was higher in cluster B. Our results suggest that m6A cluster A is likely related to pulmonary fibrosis, indicating m6A regulators play notable roles in the occurrence of pulmonary fibrosis. The m6A patterns could be considered as biomarkers to identify CHP and IPF, which will be helpful to develop immunotherapy strategies for pulmonary fibrosis in the future.

| S-EPMC9329921 | biostudies-literature

Predictors of pulmonary hypertension in patients with hypersensitivity pneumonitis.

Project description:BackgroundHypersensitivity pneumonitis (HP) is an immunologically induced inflammation of the lung parenchyma that occurs in susceptible individuals in response to a variety of antigens. Repeated exposures to the causative antigens lead to chronic HP. The condition could be complicated with pulmonary hypertension (PH).Methodology60 patients with established diagnosis of HP were included, clinical examination, high resolution computed tomography (HRCT) of chest, arterial blood gases, six minute walking test (6MWT), desaturation index, spirometry, echocardiography were performed to all patients and right heart catheter was done for patients with high echo probability of PH.ResultsThe mean age of patients was 41.67 ± 13.4 years with female predominance 83.3% of patients had history of raising birds. 71.7% of cases suffered from resting hypoxia with oxygen saturation 89 ± 11% with desaturation index 9% ± 8%, Echo probability of PH ranged from low to high 71.67, 21.67 and 6.67% respectively, mean pulmonary artery systolic pressure was 63.65 (18.48) mmHg. PH was diagnosed in 17 (28.33%) patients. HP with PH patients were significantly more symptomatic with predominant fibrotic pattern in HRCT chest P < 0.001, 82% of them had hypoxia P < 0.001 with significant desaturation after 6MWT P = 0.001. Predictors of PH in study group were fibrotic pattern in HRCT chest and hypoxia OR = 62.22, P < 0.001; 49.2, P < 0.001 respectively.ConclusionPH was prevalent in 28.33% of patients with HP, predictors of development of PH were fibrotic pattern in HRCT chest and hypoxia.Trial registrationRetrospectively registered, registration number is NCT05458635, date of registration 07/12/2022.

| S-EPMC9909854 | biostudies-literature

Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis.

Project description:In chronic hypersensitivity pneumonitis (CHP), lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival. Patients with CHP were identified. Demographic features, pulmonary function tests, incidence of treatment-emergent adverse events (TEAEs) and transplant-free survival were characterised, compared and analysed between patients stratified by immunosuppressive therapy. A multicentre comparison was performed across four independent tertiary medical centres. Among 131 CHP patients at the University of Chicago medical centre (Chicago, IL, USA), 93 (71%) received immunosuppressive therapy, and had worse baseline forced vital capacity (FVC) and diffusing capacity, and increased mortality compared with those who did not. Compared to patients treated with prednisone alone, TEAEs were 54% less frequent with azathioprine therapy (p=0.04) and 66% less frequent with mycophenolate mofetil (p=0.002). FVC decline and survival were similar between treatment groups. Analyses of datasets from four external tertiary medical centres confirmed these findings. CHP patients who did not receive immunosuppressive therapy had better survival than those who did. Use of mycophenolate mofetil or azathioprine was associated with a decreased incidence of TEAEs, and no difference in lung function decline or survival when compared with prednisone alone. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP, but more studies are needed.

| S-EPMC5570511 | biostudies-literature

Pharmacokinetic evaluation of two pirfenidone formulations in patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

Project description:Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by an abnormal activation of lung epithelium and fibroblasts, as well as an excessive accumulation of extracellular matrix. Pirfenidone was introduced as a therapeutic option for IPF and chronic hypersensitive pneumonitis (cHP), a related disease. However, high plasma concentrations, which can be achieved even at recommended doses, are frequently associated with adverse events. Hence, an extended release formulation (XP), yielding lower peak plasma concentrations, has been developed. The aim of this study was to compare the pharmacokinetic properties of XP with those of the immediate (IR) formulation in patients with IPF or cHP. Data were analyzed using two pharmacokinetic approaches, conventional non compartmental analysis and a population analysis using the nonlinear mixed effects model technique. Results observed with both approaches were consistent. Drug exposure was similar with both formulations. However, XP exhibited less concentration fluctuations and a longer mean resident time. These results suggest that XP could be a feasible option to reduce adverse events associated to pirfenidone elevated concentrations. Nevertheless, efficacy studies are required to fully document the therapeutic potential of XP.

| S-EPMC7610245 | biostudies-literature

A comparison of health-related quality of life in idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

Project description:BackgroundPatients with interstitial lung disease (ILD) have poor health-related quality of life (HRQL). However, whether HRQL differs among different subtypes of ILD is unclear. The aim of this study was to determine whether HRQL was different among patients with idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP).MethodsWe identified patients from an ongoing longitudinal cohort of patients with ILD. HRQL was assessed using the Short Form (SF)-36 medical outcomes form (version 2.0). Regression analysis was used to determine the association between clinical covariates and HRQL, primarily the physical component summary (PCS) and mental component summary (MCS) score. A multivariate regression model was created to identify potential covariates that could help explain the association between the ILD subtype and HRQL.ResultsPatients with IPF (n = 102) were older, more likely to be men, and more likely to have smoked. Pulmonary function was similar between the groups. The patients with CHP (n = 69) had worse HRQL across all eight domains of the SF-36, as well as the PCS and MCS, compared with patients with IPF (P < .01-.09). This pattern remained after controlling for age and pulmonary function (P < .01-.02). Covariates explaining part of the relationship between disease subtype and PCS score included severity of dyspnea (P < .01) and fatigue (P < .01). Covariates explaining part of the relationship between disease subtype and MCS score included severity of dyspnea (P < .01), female sex (P = .02), and fatigue (P = .02).ConclusionsHRQL is worse in CHP compared with IPF. HRQL differences between ILD subtypes are explained in part by differences in sex, dyspnea, and fatigue.

| S-EPMC4042514 | biostudies-literature

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