scholarly journals Lung Tissue Microbiome Is Associated With Clinical Outcomes of Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Hee-Young Yoon ◽  
Su-Jin Moon ◽  
Jin Woo Song

Background: Several studies using bronchoalveolar lavage fluid (BALF) reported that lung microbial communities were associated with the development and clinical outcome of idiopathic pulmonary fibrosis (IPF). However, the microbial communities in IPF lung tissues are not well known. This study is aimed to investigate bacterial microbial communities in lung tissues and determine their impact on the clinical outcomes of patients with IPF.Methods: Genomic DNA extracted from lung tissues of patients with IPF (n = 20; 10 non-survivors) and age- and sex-matched controls (n = 20) was amplified using fusion primers targeting the V3 and V4 regions of the 16S RNA genes with indexing barcodes.Results: Mean age of IPF subjects was 63.3 yr, and 65% were male. Alpha diversity indices did not significantly differ between IPF patients and controls, or between IPF non-survivors and survivors. The relative abundance of Lactobacillus, Paracoccus, and Akkermansia was increased, whereas that of Caulobacter, Azonexus, and Undibacterium decreased in patients with IPF compared with that in the controls. A decreased relative abundance of Pelomonas (odds ratio [OR], 0.352, p = 0.027) and Azonexus (OR, 0.013, p = 0.046) was associated with a diagnosis of IPF in the multivariable logistic analysis adjusted by age and gender. Multivariable Cox analysis adjusted for age and forced vital capacity (FVC) revealed that higher relative abundance of Streptococcus (hazard ratio [HR], 1.993, p = 0.044), Sphingomonas (HR, 57.590, p = 0.024), and Clostridium (HR, 37.189, p = 0.038) was independently associated with IPF mortality. The relative abundance of Curvibacter (r = 0.590) and Thioprofundum (r = 0.373) was correlated positively, whereas that of Anoxybacillus (r = −0.509) and Enterococcus (r = −0.593) was correlated inversely with FVC. In addition, the relative abundance of the Aquabacterium (r = 0.616) and Peptoniphilus (r = 0.606) genera was positively correlated, whereas that of the Fusobacterium (r = −0.464) and Phycicoccus (r = −0.495) genera was inversely correlated with distance during the 6-min walking test.Conclusions: The composition of the microbiome in lung tissues differed between patients with IPF and controls and was associated with the diagnosis, mortality, and disease severity of IPF.

2021 ◽  
Vol 10 (7) ◽  
pp. 1427
Author(s):  
Steven D. Nathan ◽  
Jayesh Mehta ◽  
John Stauffer ◽  
Elizabeth Morgenthien ◽  
Ming Yang ◽  
...  

Identification of prognostic and predictive biomarkers in idiopathic pulmonary fibrosis (IPF) could aid assessment of disease severity and prediction of progression and response to treatment. This analysis examined reference ranges for neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) in IPF, and the relationship between NLR or PLR changes and clinical outcomes over 12 months. This post hoc analysis included patients with IPF from the Phase III, double-blind trials of pirfenidone, ASCEND (NCT01366209) and CAPACITY (NCT00287716 and NCT00287729). The relationship between change from baseline to Month 12 in NLR or PLR (divided into quartiles (Q1–Q4)) and outcomes (mortality, respiratory hospitalization, declines in lung function, exercise capacity and quality of life) was assessed. Estimated reference ranges at baseline for all patients analyzed (n = 1334) were 1.1–6.4 for NLR and 56.8–250.5 for PLR. Significant trends were observed across NLR and PLR quartiles for all outcomes in placebo-treated patients, with patients manifesting the greatest NLR or PLR changes experiencing the worst outcomes. These results suggest that the greatest NLR or PLR changes over 12 months were associated with worse clinical outcomes. Further research is needed to determine the utility of NLR and PLR as prognostic biomarkers in IPF.


2021 ◽  
Vol 9 (11) ◽  
pp. 2339
Author(s):  
Aleksei O. Zverev ◽  
Arina A. Kichko ◽  
Aleksandr G. Pinaev ◽  
Nikolay A. Provorov ◽  
Evgeny E. Andronov

The rhizosphere community represents an “ecological interface” between plant and soil, providing the plant with a number of advantages. Despite close connection and mutual influence in this system, the knowledge about the connection of plant and rhizosphere diversity is still controversial. One of the most valuable factors of this uncertainty is a rough estimation of plant diversity. NGS sequencing can make the estimations of the plant community more precise than classical geobotanical methods. We investigate fallow and crop sites, which are similar in terms of environmental conditions and soil legacy, yet at the same time are significantly different in terms of plant diversity. We explored amplicons of both the plant root mass (ITS1 DNA) and the microbial communities (16S rDNA); determined alpha- and beta-diversity indices and their correlation, and performed differential abundance analysis. In the analysis, there is no correlation between the alpha-diversity indices of plants and the rhizosphere microbial communities. The beta-diversity between rhizosphere microbial communities and plant communities is highly correlated (R = 0.866, p = 0.01). ITS1 sequencing is effective for the description of plant root communities. There is a connection between rhizosphere communities and the composition of plants, but on the alpha-diversity level we found no correlation. In the future, the connection of alpha-diversities should be explored using ITS1 sequencing, even in more similar plant communities—for example, in different synusia.


2020 ◽  
Vol 52 (9) ◽  
pp. 1564-1573
Author(s):  
Da Hyeon Choi ◽  
Jiwon Park ◽  
Ju Kwang Choi ◽  
Kyeong Eun Lee ◽  
Won Hee Lee ◽  
...  

Abstract Oral microbes have the capacity to spread throughout the gastrointestinal system and are strongly associated with multiple diseases. Given that tonsils are located between the oral cavity and the laryngopharynx at the gateway of the alimentary and respiratory tracts, tonsillar tissue may also be affected by microbiota from both the oral cavity (saliva) and the alimentary tract. Here, we analyzed the distribution and association of the microbial communities in the saliva and tonsils of Korean children subjected to tonsillectomy because of tonsil hyperplasia (n = 29). The microbiome profiles of saliva and tonsils were established via 16S rRNA gene sequencing. Based on the alpha diversity indices, the microbial communities of the two groups showed high similarities. According to Spearman’s ranking correlation analysis, the distribution of Treponema, the causative bacterium of periodontitis, in saliva and tonsils was found to have a significant positive correlation. Two representative microbes, Prevotella in saliva and Alloprevotella in tonsils, were negatively correlated, while Treponema 2 showed a strong positive correlation between saliva and tonsils. Taken together, strong similarities in the microbial communities of the tonsils and saliva are evident in terms of diversity and composition. The saliva microbiome is expected to significantly affect the tonsil microbiome. Furthermore, we suggest that our study creates an opportunity for tonsillar microbiome research to facilitate the development of novel microbiome-based therapeutic strategies.


2020 ◽  
Vol 56 (5) ◽  
pp. 2001769
Author(s):  
Hee-young Yoon ◽  
Kwanghun Choi ◽  
Miae Kim ◽  
Hak-Su Kim ◽  
Jin Woo Song

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Wim A. Wuyts ◽  
Caroline Dahlqvist ◽  
Hans Slabbynck ◽  
Marc Schlesser ◽  
Natacha Gusbin ◽  
...  

Abstract Background The PROOF registry is an observational study initiated in October 2013 with the aim to monitor disease progression in a real-world population of patients with idiopathic pulmonary fibrosis (IPF). Here, we present longitudinal clinical outcomes from the PROOF registry. Methods Patients with IPF were enrolled across eight centers in Belgium and Luxembourg. For all patients, clinical outcomes data were collected, including mortality, lung transplant, acute exacerbations, and pulmonary hypertension. For patients treated with pirfenidone at any time during follow-up (2013–2017), for any duration of treatment (the pirfenidone-treated population): pirfenidone treatment patterns were collected; changes in pulmonary function (forced vital capacity [FVC] and carbon monoxide diffusing capacity [DLco]) were reviewed up to 24 months post-inclusion; and time-to-event analyses from the time of registry inclusion were performed. Results The PROOF registry enrolled a total of 277 patients. During follow-up, 23.1% of patients died, 5.1% received a lung transplant, 5.4% experienced an acute exacerbation, and 6.1% had comorbid pulmonary hypertension. In the pirfenidone-treated population (N = 233, 84.1%), 12.9% of patients had a temporary dose discontinuation and 31.8% had a temporary dose reduction; 4.3% of patients permanently discontinued pirfenidone due to an adverse drug reaction. Mean percent predicted FVC was 81.2% (standard deviation [SD] 19.0) at Month 0 and 78.3% (SD 25.0) at Month 24, and mean percent predicted DLco was 47.0% (SD 13.2) and 45.0% (SD 16.5), respectively. Rates of ≥ 10% absolute decline in percent predicted FVC and ≥ 15% absolute decline in percent predicted DLco over 24 months were 31.0% and 23.2%, respectively. Mean times from registry inclusion to categorical absolute decline in percent predicted FVC and percent predicted DLco were 20.1 (standard error [SE] 0.6) months and 23.4 (SE 0.5) months, respectively; mean time from registry inclusion to death was 31.0 (SE 0.9) months. Conclusions The PROOF registry is a source of European data characterizing longitudinal clinical outcomes of patients with IPF. Over 12 months of follow-up, pulmonary function remained largely stable in patients with IPF who received pirfenidone for any duration of treatment. Pulmonary function remained similar at 24 months of follow-up, although patient numbers were lower. Trial registration PROOF is registered with the relevant authorities in Belgium and Luxembourg, with registration to Comité National d’Éthique et de Recherche (CNER) N201309/03–12 September 2013 and a notification to Comité National de Protection des Données (CNDP) for Luxembourg.


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