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The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus–predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis. [ABSTRACT FROM AUTHOR]

Patients with mild asthma had already developed airway remodeling (wall thickening without notable airway luminal narrowing) from the 3rd to 9th generation. Keywords: airway remodeling; asthma; bronchodilation; optical coherence tomography EN airway remodeling asthma bronchodilation optical coherence tomography 646 649 4 02/01/22 20220201 NES 220201 ACKNOWLEDGMENTS We thank Prof. Zheng Jing-ping, Prof. Gao Yi, Prof. Xie Yan-qing, Dr. [Extracted from the article]

Background: Although FEV1 remains the gold standard for staging COPD, the association between airway remodeling and airflow limitation remains unclear. Endobronchial optical coherence tomography (EB-OCT) was performed to assess the association between disorders of large and medium to small airways and COPD staging. We also evaluated small airway architecture in heavy smokers with normal FEV1 (SNL) and healthy never-smokers.Methods: We recruited 48 patients with COPD (stage I, n = 14; stage II, n = 15; stage, III-IV, n = 19), 21 SNL, and 17 healthy never-smokers. A smoking history inquiry, as well as spirometry, chest CT, bronchoscopy, and EB-OCT were performed. Mean luminal diameter (Dmean), inner luminal area (Ai), and airway wall area (Aw) of third- to ninth-generation bronchi were measured using EB-OCT.Results: Patients with more advanced COPD demonstrated greater abnormality of airway architecture in both large and medium to small airways, followed by SNL and never-smokers. Abnormality of airway architecture and EB-OCT parameters in SNL were comparable to those in stage I COPD. FEV1% predicted correlated with Dmean and Ai of seventh- to ninth-generation bronchi in COPD; however, neither Dmean nor Ai of third- to sixth-generation bronchi correlated with FEV1% in stage I and stage II COPD and in SNL.Conclusions: FEV1-based COPD staging partially correlates with small airway disorders in stage II-IV COPD. Small airway abnormalities detected by EB-OCT correlate with FEV1-based staging in COPD and identify early pathologic changes in healthy heavy smokers. [ABSTRACT FROM AUTHOR]

Background: Response-dose ratio (RDR) and cumulative provocative dosage (PD) are useful indices reflecting airway responsiveness in asthma. Objectives: To compare the diagnostic value of RDR and PD, by conducting leukotriene D (LTD-BPT) and methacholine bronchial provocation test (MCh-BPT), in different asthma control levels. Methods: Healthy subjects and asthmatic patients underwent LTD-BPT and MCh-BPT, at 2-14-day interval. This entailed assessment of the distribution characteristics, correlation, and diagnostic value of PD inducing 20 % fall in forced expiratory volume in one second (PDFEV) and the RDR, defined as FEV fall (%) at the final step divided by the corresponding provocative dosage. Results: Twenty uncontrolled, 22 partly controlled, 20 controlled asthmatics, and 21 healthy subjects were enrolled. LogRDR was positively correlated with logPDFEV in both BPTs (all P < 0.05). Poorer asthma control was associated with significantly lower PDFEV and higher RDR (both P < 0.05). The differences in PDFEV and RDR between partly controlled and controlled asthma were unremarkable (both P > 0.05). Compared with logPDFEV, the logRDR yielded similar diagnostic values in both BPTs. A lower percentile of RDR (≤25th percentile) was associated with higher baseline FEV ( P < 0.05) and an increased proportion of well-controlled asthmatic patients. The combination of RDR and PDFEV led to an increased diagnostic value compared with either parameter alone. Conclusions: RDR is a surrogate of PDFEV for BPTs in asthma. This finding was not modified by different asthma control levels or the types of bronchoprovocants. [ABSTRACT FROM AUTHOR]