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Bacterial burden in the lower airways predicts disease progression in idiopathic pulmonary fibrosis and is independent of radiological disease extent
European Respiratory Journal ( IF 16.6 ) Pub Date : 2020-01-24 , DOI: 10.1183/13993003.01519-2019
Rachele Invernizzi , Joseph Barnett , Bhavin Rawal , Arjun Nair , Poonam Ghai , Shaun Kingston , Felix Chua , Zhe Wu , Athol U. Wells , Elizabeth R. Renzoni , Andrew G. Nicholson , Alexandra Rice , Clare M. Lloyd , Adam J. Byrne , Toby M. Maher , Anand Devaraj , Philip L. Molyneaux

Increasing bacterial burden in the lower airways of patients with idiopathic pulmonary fibrosis confers an increased risk of disease progression and mortality. However, it remains unclear whether this increased bacterial burden directly influences progression of fibrosis or simply reflects the magnitude of the underlying disease extent or severity. We prospectively recruited 193 patients who underwent bronchoscopy and received a multidisciplinary diagnosis of idiopathic pulmonary fibrosis. Quantification of the total bacterial burden in bronchoalveolar lavage fluid was performed by 16S rRNA gene qPCR. Imaging was independently evaluated by two readers assigning quantitative scores for extent, severity and topography of radiographic changes and relationship of these features with bacterial burden was assessed. Increased bacterial burden significantly associated with disease progression (HR 2.1; 95% CI 1.287–3.474; p=0.0028). Multivariate stepwise regression demonstrated no relationship between bacterial burden and radiological features or extent of disease. When specifically considering patients with definite or probable usual interstitial pneumonia there was no difference in bacterial burden between these two groups. Despite a postulated association between pleuroparenchymal fibroelastosis and clinical infection, there was no relationship between either the presence or extent of pleuroparenchymal fibroelastosis and bacterial burden. We demonstrate that bacterial burden in the lower airways is not simply secondary to the extent of the underlying architectural destruction of the lung parenchyma seen in idiopathic pulmonary fibrosis. The independent nature of this association supports a relationship with the underlying pathogenic mechanisms and highlights the urgent need for functional studies. Elevated bacterial burden predicts mortality in IPF and is independent of both radiological features and extent of disease http://bit.ly/2RaDbdv

中文翻译:

下呼吸道的细菌负荷可预测特发性肺纤维化的疾病进展,并且与放射学疾病程度无关

特发性肺纤维化患者下呼吸道细菌负荷增加会增加疾病进展和死亡的风险。然而,尚不清楚这种增加的细菌负担是否直接影响纤维化的进展,还是仅仅反映了潜在疾病程度或严重程度的大小。我们前瞻性地招募了 193 名接受支气管镜检查并接受多学科诊断的特发性肺纤维化患者。通过 16S rRNA 基因 qPCR 对支气管肺泡灌洗液中的总细菌负荷进行量化。影像学由两名阅读者独立评估,对放射学变化的范围、严重程度和地形进行定量评分,并评估这些特征与细菌负荷的关系。细菌负荷增加与疾病进展显着相关(HR 2.1;95% CI 1.287–3.474;p=0.0028)。多变量逐步回归表明细菌负荷与放射学特征或疾病程度之间没有关系。当特别考虑患有明确或可能的普通间质性肺炎的患者时,这两组之间的细菌负荷没有差异。尽管假设胸膜弹性纤维变性与临床感染之间存在关联,但胸膜弹性纤维变性的存在或程度与细菌负荷之间没有关系。我们证明下气道中的细菌负荷不仅仅是继发于特发性肺纤维化中肺实质潜在结构破坏的程度。这种关联的独立性支持与潜在致病机制的关系,并突出了对功能研究的迫切需要。细菌负荷升高可预测 IPF 的死亡率,并且与放射学特征和疾病程度无关 http://bit.ly/2RaDbdv
更新日期:2020-01-24
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