Antiviral Responses of Tissue-resident CD49a+ Lung Natural Killer Cells Are Dysregulated in Chronic Obstructive Pulmonary Disease.

Rationale: Tissue-resident natural killer (trNK) cells have been identified in numerous organs, but little is known about their functional contribution to respiratory immunity, in particular during chronic lung diseases such as chronic obstructive pulmonary disease (COPD). Objectives: To investigate the phenotype and antiviral responses of trNK cells in murine cigarette smoke-induced experimental COPD and in human lung parenchyma from COPD donors. Methods: Mice were exposed to cigarette smoke for 12 weeks to induce COPD-like lung disease. Lung trNK cell phenotypes and function were analyzed by flow cytometry in both murine and human disease with and without challenge with influenza A virus. Measurements and Main Results: In the mouse lung, CD49a+CD49b+EOMES+ and CD49a+CD49b-EOMESlo NK cell populations had a distinct phenotype compared with CD49a- circulating NK cells. CD49a+ NK cells were more extensively altered earlier in disease onset than circulating NK cells, and increased proportions of CD49a+ NK cells correlated with worsening disease in both murine and human COPD. Furthermore, the presence of lung disease delayed both circulating and trNK cell functional responses to influenza infection. CD49a+ NK cells markedly increased their NKG2D, CD103, and CD69 expression in experimental COPD after influenza infection, and human CD49a+ NK cells were hyperactive to ex vivo influenza infection in COPD donors. Conclusions: Collectively, these results demonstrate that trNK cell function is altered in cigarette smoke-induced disease and suggests that smoke exposure may aberrantly prime trNK cell responsiveness to viral infection. This may contribute to excess inflammation during viral exacerbations of COPD.

Predicting and preventing hospital readmission for exacerbations of COPD.

More than a third of patients hospitalised for acute exacerbation of COPD are readmitted to hospital within 90 days. Healthcare professionals and service providers are expected to collaboratively drive efforts to improve hospital readmission rates, which can be challenging due to the lack of clear consensus and guidelines on how best to predict and prevent readmissions. This review identifies these risk factors, highlighting the contribution of multimorbidity, frailty and poor socioeconomic status. Predictive models of readmission that address the multifactorial nature of readmissions and heterogeneity of the disease are reviewed, recognising that in an era of precision medicine, in-depth understanding of the intricate biological mechanisms that heighten the risk of COPD exacerbation and re-exacerbation is needed to derive modifiable biomarkers that can stratify accurately the highest risk groups for targeted treatment. We evaluate conventional and emerging strategies to reduce these potentially preventable readmissions. Here, early recognition of exacerbation symptoms and the delivery of prompt treatment can reduce risk of hospital admissions, while patient education can improve treatment adherence as a key component of self-management strategies. Care bundles are recommended to ensure high-quality care is provided consistently, but evidence for their benefit is limited to date. The search continues for interventions which are effective, sustainable and applicable to a diverse population of patients with COPD exacerbations. Further research into mechanisms that drive exacerbation and affect recovery is crucial to improve our understanding of this complex, highly prevalent disease and to advance the development of more effective treatments.