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Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and infective exacerbations, however, in-vitro model systems for the study of host-pathogen interaction at the individual level are lacking. Here, we describe the establishment of nasopharyngeal and bronchial organoids from healthy individuals and COPD that recapitulate disease at the individual level. In contrast to healthy organoids, goblet cell hyperplasia and reduced ciliary beat frequency were observed in COPD organoids, hallmark features of the disease. Single-cell transcriptomics uncovered evidence for altered cellular differentiation trajectories in COPD organoids. SARS-CoV-2 infection of COPD organoids revealed more productive replication in bronchi, the key site of infection in severe COVID-19. Viral and bacterial exposure of organoids induced greater pro-inflammatory responses in COPD organoids. In summary, we present an organoid model that recapitulates the in vivo physiological lung microenvironment at the individual level and is amenable to the study of host-pathogen interaction and emerging infectious disease., (© 2022. The Author(s).)

Introduction: Dyspnoea-12 scale is a validated assessment tool, capturing the perception of dyspnoea and its physical and affective effects in individuals with chronic obstructive pulmonary disease (COPD). A validated version for the Chinese-speaking population has been unavailable., Objective: To develop a Chinese version of D-12 (D-12-C) scale and evaluate its validity and reliability., Methods: D-12 was translated from English to traditional Chinese in collaboration with a physician and a linguist. Back translation was adopted to ensure accuracy of the translation. A total of 155 COPD patients were recruited to test the reliability and validity of the D-12-C scale. Internal reliability and test-retest reliability were measured with Cronbach's alpha coefficient and intra-class correlation coefficient, respectively. Construct validity was assessed through exploratory factor analysis (EFA). Concurrent validity was assessed by the correlation of D-12-C total score and sub-scores and the Chinese version of Saint George's Respiratory Questionnaire (SGRQ), 36-Item Short Form Health Survey (SF-36), COPD Assessment Test (CAT) and Hospital Anxiety and Depression Scale (HADS) total score and sub-scores., Results: The two-factor structure of D-12-C was confirmed by EFA. D-12-C and its sub-scores demonstrated high level of internal reliability (Cronbach's alpha = 0.88) and moderate level of test-retest reliability. D-12-C total score, physical and affective sub-scores were significantly correlated to SGRQ total score (r s  = 0.59, p < 0.001) and activity sub-score (r s  = 0.38, p = 0.006), SF-36 mental health sub-score (r s  = -0.36, p < 0.001), CAT (r s  = 0.56, p < 0.001), HADS anxiety (r s  = 0.51, p < 0.001) and depression sub-scores (r s  = 0.44, p < 0.001)., Conclusion: D-12-C scale was developed, which demonstrated satisfactory reliability and validity in measuring dyspnoea among COPD patients., (© 2021 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Objective: To review the airway microbiome in chronic obstructive pulmonary disease (COPD), bronchiectasis and bronchiectasis-COPD overlap (BCO)., Data Source and Study Selection: Relevant studies were selected from PubMed, Google scholar, EMBASE and Web of Science. All studies involving human microbiomes, published in the English language, and using the search terms "COPD", "Chronic Obstructive Pulmonary Disease", "Bronchiectasis", "BCO" or "Bronchiectasis and COPD overlap", AND "microbiome", "mycobiome" or "metagenomics" were included., Results: Despite variability in sampling methods and specimen types used, microbiome composition remains relatively comparable in COPD and bronchiectasis with prominence of Proteobacteria, Firmicutes and Bacteroidetes. Alterations to airway microbiomes occur in association to disease severity and/or exacerbations in COPD and bronchiectasis. Decreased alpha diversity and Haemophilus-predominant microbiomes are associated with poorer survival in COPD, while, in bronchiectasis, Pseudomonas-predominant microbiomes demonstrate high exacerbation frequency and greater symptom burden while Aspergillus-dominant mycobiome profiles associate with exacerbations. The role of the microbiome in BCO remains understudied., Conclusion: Use of next-generation sequencing has revolutionised our detection and understanding of the airway microbiome in chronic respiratory diseases such as COPD and bronchiectasis. Targeted amplicon sequencing reveals important associations between the respiratory microbiome and disease outcome while metagenomics may elucidate functional pathways. How best to apply this information into patient care, monitoring and treatment, however, remains challenging and necessitates further study., (© 2020 John Wiley & Sons Ltd.)

Background: Prior studies illustrate the presence and clinical importance of detecting Aspergillus species in the airways of patients with chronic respiratory disease. Despite this, a low fungal biomass and the presence of PCR inhibitors limits the usefulness of quantitative PCR (qPCR) for accurate absolute quantification of Aspergillus in specimens from the human airway. Droplet digital PCR (ddPCR) however, presents an alternative methodology allowing higher sensitivity and accuracy of such quantification but remains to be evaluated in head-to-head fashion using specimens from the human airway. Here, we implement a standard duplex TaqMan PCR protocol, and assess if ddPCR is superior in quantifying airway Aspergillus when compared to standard qPCR., Methods: The molecular approaches of qPCR and ddPCR were applied to DNA fungal extracts in n = 20 sputum specimens obtained from non-diseased ( n = 4), chronic obstructive pulmonary disease (COPD; n = 8) and non-cystic fibrosis bronchiectasis ( n = 8) patients where Aspergillus status was known. DNA was extracted and qPCR and ddPCR performed on all specimens with appropriate controls and head-to-head comparisons performed., Results: Standard qPCR and ddPCR were both able to detect, even at low abundance, Aspergillus species ( Aspergillus fumigatus - A. fumigatus and Aspergillus terreus - A. terreus ) from specimens known to contain the respective fungi. Importantly, however, ddPCR was superior for the detection of A. terreus particularly when present at very low abundance and demonstrates greater resistance to PCR inhibition compared to qPCR., Conclusion: ddPCR has greater sensitivity for A. terreus detection from respiratory specimens, and is more resistant to PCR inhibition, important attributes considering the importance of A. terreus species in chronic respiratory disease states such as bronchiectasis.