Relevance between clinical status and exhaled molecules related to neutrophilic inflammation in pediatric cystic fibrosis.
- 作者列表："Kanik ET","Yilmaz O","Ozdogru E","Alper H","Ulman C","Kanık A","Simsek Y","Yuksel H
INTRODUCTION:Cystic fibrosis (CF) is characterized with chronic inflammation with neutrophil and related cytokines in airway secretions. We aimed to measure the levels of neutrophil related inflammatory markers as nitric oxide, IL-8, IL-17, leukotriene B4 and neutrophil elastase as well as e-cadherin in exhaled breath condensate (EBC) and to determine their relation with clinical findings. METHODS:We consecutively enrolled cystic fibrosis patients in our clinics aged above five years who could cooperate for exhaled breath condensate to this case-control study (n=30). The age and sex matched control group (n=26) was enrolled. Spirometry was performed during the stable period and EBC samples were obtained for measurement of the markers. RESULTS:Mean age of the subjects enrolled was 12.1(4.2) years and 40% were positive for pseudomonas aeruginosa in sputum. Subjects who had pseudomonas aeruginosa in sputum cultures had significantly lower FEV1, FVC and FEF 25/75 values compared to the ones without pseudomonas aeruginosa (p=0.002, p=0.002 and p=0.005 respectively). EBC neutrophil elastase levels were significantly higher in the CF patients compared to non-CF controls (3.11 ±4.71 vs 0.90 ±2.68, p=0.04). Nitric oxide, IL-17, IL-8, e-cadherin, neutrophil elastase or leukotriene B4 levels in EBC of CF patients were not related to pseudomonas infection, FEV1 levels or hospital admission in the last year. CONCLUSION:In our study, neutrophil elastase levels in EBC are higher in CF patients compared to non-CF controls. This is independent of acute infection and is evidence to persistence of neutrophilic lung injury. However, EBC NO, IL-8, IL-17, e-cadherin, neutrophil elastase and leukotriene B4 levels as inflammatory markers, are not correlated with disease progression or clinical findings.
导读: 囊性纤维化 (CF) 以气道分泌物中中性粒细胞及相关细胞因子的慢性炎症为特征。我们旨在测量呼出气冷凝液 (EBC) 中中性粒细胞相关炎症标志物的水平，如一氧化氮、 IL-8 、 IL-17 、白三烯 B4 和中性粒细胞弹性蛋白酶以及 e-钙黏素并确定其与临床表现的关系。 方法: 我们连续招募了我们诊所中年龄在 5 岁以上的囊性纤维化患者，他们可以配合呼出气冷凝液参加本病例对照研究 (n = 30)。纳入年龄和性别匹配的对照组 (n = 26)。在稳定期进行肺活量测定，获得 EBC 样本用于标记物的测量。 结果: 受试者的平均年龄为 12.1 (4.2) 岁，40% 的患者痰中铜绿假单胞菌阳性。痰培养中铜绿假单胞菌的受试者 FEV1 、 FVC 和 FEF 25/75 值显著低于无铜绿假单胞菌的受试者 (分别为 p = 0.002 、 p = 0.002 和 p = 0.005)。CF 患者的 EBC 中性粒细胞弹性蛋白酶水平显著高于非 CF 对照组 (3.11 ± 4.71 vs 0.90 ± 2.68，p = 0.04)。CF 患者 EBC 中的一氧化氮、 IL-17 、 IL-8 、 e-cadherin 、中性粒细胞弹性蛋白酶或白三烯 B4 水平与过去一年的假单胞菌感染、 FEV1 水平或入院无关。 结论: 在我们的研究中，与非 CF 对照组相比，CF 患者 EBC 中的中性粒细胞弹性蛋白酶水平较高。这与急性感染无关，是中性粒细胞肺损伤持续存在的证据。然而，EBC NO，IL-8，IL-17，e-钙黏素，中性粒细胞弹性蛋白酶和白三烯 B4 水平作为炎症标志物，与疾病进展或临床发现无关。
METHODS:OBJECTIVES:To asses the clinical course in RA-related interstitial lung disease (RA-ILD) patients with and without rituximab (RTX). The influence of other variables was also evaluated. METHODS:A longitudinal multicentre study was conducted in RA diagnosed with ILD from 2007 until 2018 in Madrid. Patients were included in a registry [pNEumology RhEumatology Autoinmune diseases (NEREA)] from the time of ILD diagnosis. The main endpoint was functional respiratory impairment (FI), when there was a decline ≥5% in the predicted forced vital capacity compared with the previous one. Pulmonary function was measured at baseline and in follow-up visits every 6-12 months. The independent variable was therapy with RTX. Covariables included sociodemographic, clinical, radiological and other therapies. Survival techniques were used to estimate the incidence rate (IR) and 95% CI of functional impairment, expressed per 100 patient-semesters. Cox multivariate regression models were run to examine the influence of RTX and other covariates on FI. Results were expressed as the hazard ratio (HR) and CI. RESULTS:A total of 68 patients were included. FI occurred in 42 patients [IR 23.5 (95% CI 19, 29.1)] and 50% of them had FI within 1.75 years of an ILD diagnosis. A multivariate analysis showed that RTX exposure resulted in a lower risk of FI compared with non-exposure [HR 0.51 (95% CI 0.31, 0.85)]. Interstitial pneumonia, glucocorticoids, disease activity and duration also influenced FI. CONCLUSION:RA-ILD patients deteriorate over time, with the median time free of impairment being <2 years. Patients exposed to RTX had a higher probability of remaining free of FI compared with other therapies. Other factors have also been identified. Key words: rheumatoid arthritis, interstitial lung disease, observational study, rituximab and prognosis
METHODS:The safety of anti-programmed cell death 1 (PD-1) antibody for patients with preexisting interstitial lung disease (ILD) remains unknown. The aim of this study was to evaluate the dependence of preexisting ILD on anti-PD-1 antibody-induced pneumonitis in non-small cell lung cancer (NSCLC) patients. We retrospectively reviewed the association of preexisting ILD with the incidence, radiographic pattern, and outcome of pneumonitis in NSCLC patients receiving anti-PD-1 antibody. A total of 331 patients were included in this study. Of these patients, 17 had preexisting ILD. The incidence of pneumonitis was higher among the patients with preexisting ILD than among those without preexisting ILD (29% vs. 10%, P = 0.027). The distributions of the CT appearances at the onset of anti-PD-1 antibody-induced pneumonitis were as follows: for the patients with preexisting ILD, two patients (40%) had diffuse alveolar damage (DAD), one patient each with organizing pneumonia-like (OP), hypersensitivity pneumonitis (HP), and other patterns (20% each); for the patients without preexisting ILD, 19 patients (61%) had OP, 8 (26%) had HP, 3 (10%) had DAD, and 1 (3.2%) had other patterns. The median onset time from the initiation of anti-PD-1 antibody treatment until the development of pneumonitis was 1.3 months (range 0.3–2.1 months) for the patients with preexisting ILD and 2.3 months (range 0.2–14.6 months) for the patients without preexisting ILD. Careful attention to the development of pneumonitis is needed, especially within the first 3 months after the start of anti-PD-1 antibody treatment, when using anti-PD-1 antibody to treat patients with preexisting ILD.
METHODS::Bacteria of the Burkholderia cepacia complex (Bcc) are ubiquitous multidrug resistant organisms and opportunistic pathogens capable of causing life threatening lung infections among cystic fibrosis (CF) patients. No effective therapies are currently available to eradicate Bcc bacteria from CF patients, as these organisms are inherently resistant to the majority of clinically available antimicrobials. An immunoproteomics approach was used to identify Bcc proteins that stimulate the humoral immune response of the CF host, using bacterial cells grown under conditions mimicking the CF lung environment and serum samples from CF patients with a clinical record of Bcc infection. 24 proteins of the Bcc strain B. cenocepacia J2315 were identified as immunoreactive, 19 here reported as immunogenic for the first time. Ten proteins were predicted as extracytoplasmic, 9 of them being conserved in Bcc genomes. The immunogenic Bcc extracytoplasmic proteins are potential targets for development of novel therapeutic strategies and diagnostic tools to protect patients against the onset of chronic Bcc lung infections.