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Abstract：
BACKGROUND: The lung microbiome is an inflammatory stimulus whose role in the development of lung malignancies is incompletely understood. We hypothesized that the lung microbiome associates with multiple clinical factors, including the presence of a lung malignancy.
OBJECTIVE: To assess associations between the upper and lower airway microbiome and multiple clinical factors including lung malignancy.
METHODS: We conducted a prospective cohort study of upper and lower airway microbiome samples from 44 subjects undergoing lung lobectomy for suspected or confirmed lung cancer. Subjects provided oral (2), induced sputum, nasopharyngeal, bronchial, and lung tissue (3) samples. Pathologic diagnosis, age, tobacco use, dental care history, lung function, and inhaled corticosteroid use were associated with upper and lower airway microbiome findings.
RESULTS: Older age was associated with greater Simpson diversity in the oral and nasopharyngeal sites (p = 0.022 and p = 0.019, respectively). Current tobacco use was associated with greater lung and bronchus Simpson diversity (p < 0.0001). Self-reported last profession dental cleaning more than 6 months prior (vs. 6 or fewer months prior) was associated with lower lung and bronchus Simpson diversity (p < 0.0001). Diagnosis of a lung adenocarcinoma (vs. other pathologic findings) was associated with lower bronchus and lung Simpson diversity (p = 0.024). Last professional dental cleaning, dichotomized as ≤ 6 months vs. >6 months prior, was associated with clustering among lung samples (p = 0.027, R2 = 0.016). Current tobacco use was associated with greater abundance of pulmonary pathogens Mycoplasmoides and Haemophilus in lower airway samples. Self-reported professional dental cleaning ≤ 6 months prior (vs. >6 months prior) was associated with greater bronchial Actinomyces and lung Streptococcus abundance. Lung adenocarcinoma (vs. no lung adenocarcinoma) was associated with lower Lawsonella abundance in lung samples. Inhaled corticosteroid use was associated with greater abundance of Haemophilus among oral samples and greater Staphylococcus among lung samples.
CONCLUSIONS: Current tobacco use, recent dental cleaning, and a diagnosis of adenocarcinoma are associated with lung and bronchial microbiome α-diversity, composition (β-diversity), and the abundance of several respiratory pathogens. These findings suggest that modifiable habits (tobacco use and dental care) may influence the lower airway microbiome. Larger controlled studies to investigate these potential associations are warranted.
OBJECTIVE: To assess associations between the upper and lower airway microbiome and multiple clinical factors including lung malignancy.
METHODS: We conducted a prospective cohort study of upper and lower airway microbiome samples from 44 subjects undergoing lung lobectomy for suspected or confirmed lung cancer. Subjects provided oral (2), induced sputum, nasopharyngeal, bronchial, and lung tissue (3) samples. Pathologic diagnosis, age, tobacco use, dental care history, lung function, and inhaled corticosteroid use were associated with upper and lower airway microbiome findings.
RESULTS: Older age was associated with greater Simpson diversity in the oral and nasopharyngeal sites (p = 0.022 and p = 0.019, respectively). Current tobacco use was associated with greater lung and bronchus Simpson diversity (p < 0.0001). Self-reported last profession dental cleaning more than 6 months prior (vs. 6 or fewer months prior) was associated with lower lung and bronchus Simpson diversity (p < 0.0001). Diagnosis of a lung adenocarcinoma (vs. other pathologic findings) was associated with lower bronchus and lung Simpson diversity (p = 0.024). Last professional dental cleaning, dichotomized as ≤ 6 months vs. >6 months prior, was associated with clustering among lung samples (p = 0.027, R2 = 0.016). Current tobacco use was associated with greater abundance of pulmonary pathogens Mycoplasmoides and Haemophilus in lower airway samples. Self-reported professional dental cleaning ≤ 6 months prior (vs. >6 months prior) was associated with greater bronchial Actinomyces and lung Streptococcus abundance. Lung adenocarcinoma (vs. no lung adenocarcinoma) was associated with lower Lawsonella abundance in lung samples. Inhaled corticosteroid use was associated with greater abundance of Haemophilus among oral samples and greater Staphylococcus among lung samples.
CONCLUSIONS: Current tobacco use, recent dental cleaning, and a diagnosis of adenocarcinoma are associated with lung and bronchial microbiome α-diversity, composition (β-diversity), and the abundance of several respiratory pathogens. These findings suggest that modifiable habits (tobacco use and dental care) may influence the lower airway microbiome. Larger controlled studies to investigate these potential associations are warranted.
摘要：
背景：肺微生物组是一种炎症刺激，其在肺恶性肿瘤发展中的作用尚未完全了解。我们假设肺微生物组与多种临床因素相关，包括肺部恶性肿瘤的存在。
目的：评估上、下气道微生物组与包括肺部恶性肿瘤在内的多种临床因素之间的关联。
方法：我们对44例疑似或确诊肺癌患者行肺叶切除术的上、下气道微生物组样本进行了前瞻性队列研究。受试者提供口服（2），诱导痰，鼻咽,支气管,和肺组织(3)样品。病理诊断,年龄,烟草使用,牙科护理史,肺功能,吸入性皮质类固醇的使用与上、下气道微生物组的发现相关.
结果：年龄较大与口腔和鼻咽部位的Simpson多样性有关（分别为p=0.022和p=0.019）。目前的烟草使用与肺和支气管Simpson多样性有关（p<0.0001）。自我报告的最后一次职业牙齿清洁超过6个月(与前6个月或更少）与下肺和支气管Simpson多样性有关（p<0.0001）。肺腺癌的诊断（vs.其他病理发现）与较低的支气管和肺Simpson多样性有关（p=0.024）。最后的专业牙齿清洁，二分为≤6个月vs.>6个月前，与肺样本之间的聚类相关（p=0.027，R2=0.016）。当前的烟草使用与下气道样本中肺部病原体支原体和嗜血杆菌的丰度增加有关。自我报告专业牙齿清洁≤6个月前(vs.>6个月前）与更大的支气管放线菌和肺链球菌丰度相关。肺腺癌（vs.无肺腺癌）与肺样本中Lawsonella丰度较低相关。吸入皮质类固醇的使用与口腔样本中嗜血杆菌的丰度增加和肺样本中葡萄球菌的丰度增加相关。
结论：目前的烟草使用，最近的牙齿清洁，腺癌的诊断与肺和支气管微生物组α-多样性有关，组成(β-多样性)，以及多种呼吸道病原体的丰富。这些发现表明，可改变的习惯（烟草使用和牙科护理）可能会影响下气道微生物组。有必要进行更大规模的对照研究来调查这些潜在的关联。
目的：评估上、下气道微生物组与包括肺部恶性肿瘤在内的多种临床因素之间的关联。
方法：我们对44例疑似或确诊肺癌患者行肺叶切除术的上、下气道微生物组样本进行了前瞻性队列研究。受试者提供口服（2），诱导痰，鼻咽,支气管,和肺组织(3)样品。病理诊断,年龄,烟草使用,牙科护理史,肺功能,吸入性皮质类固醇的使用与上、下气道微生物组的发现相关.
结果：年龄较大与口腔和鼻咽部位的Simpson多样性有关（分别为p=0.022和p=0.019）。目前的烟草使用与肺和支气管Simpson多样性有关（p<0.0001）。自我报告的最后一次职业牙齿清洁超过6个月(与前6个月或更少）与下肺和支气管Simpson多样性有关（p<0.0001）。肺腺癌的诊断（vs.其他病理发现）与较低的支气管和肺Simpson多样性有关（p=0.024）。最后的专业牙齿清洁，二分为≤6个月vs.>6个月前，与肺样本之间的聚类相关（p=0.027，R2=0.016）。当前的烟草使用与下气道样本中肺部病原体支原体和嗜血杆菌的丰度增加有关。自我报告专业牙齿清洁≤6个月前(vs.>6个月前）与更大的支气管放线菌和肺链球菌丰度相关。肺腺癌（vs.无肺腺癌）与肺样本中Lawsonella丰度较低相关。吸入皮质类固醇的使用与口腔样本中嗜血杆菌的丰度增加和肺样本中葡萄球菌的丰度增加相关。
结论：目前的烟草使用，最近的牙齿清洁，腺癌的诊断与肺和支气管微生物组α-多样性有关，组成(β-多样性)，以及多种呼吸道病原体的丰富。这些发现表明，可改变的习惯（烟草使用和牙科护理）可能会影响下气道微生物组。有必要进行更大规模的对照研究来调查这些潜在的关联。
