Daily Respiratory Research Analysis

Emphysema's significant morbidity and mortality underscore the need for reliable outcome metrics in clinical trials. However, commonly accepted chronic obstructive pulmonary disease outcome measures do not adequately capture emphysema severity or progression. Computed tomography (CT) metrics have been validated as accurate indicators of pathological emphysema and predictors of chronic obstructive pulmonary disease progression, exacerbations, and mortality. This position paper reviews the evidence supporting CT densitometry as a biomarker for emphysema, establishes implementation standards, and highlights areas for future research. A systematic literature review addressed three key questions: whether CT densitometry can be used as a diagnostic biomarker of emphysema, whether CT densitometry can be used as a prognostic biomarker, and whether longitudinal change in densitometry can be used as a disease progression monitoring biomarker. Emphysema metrics, such as the percentage of low attenuation areas below -950 Hounsfield units, are validated, highly reproducible diagnostic and prognostic biomarkers. Volume-adjusted lung density is recommended for disease monitoring. Both metrics demonstrate a scan-rescan intraclass correlation coefficient of 0.99 with proper technique. The paper also discusses relevant CT physics, techniques, and sources of variation, including technical factors, physiological changes, and software analysis. Key recommendations for clinical trials include using standardized CT techniques, proper subject selection, and longitudinal evaluation with volume-adjusted lung density.

Highly pathogenic avian influenza (HPAI) virus (e.g. H5N1) infects the lower airway to cause severe infections, and constitute a prime candidate for the emergence of disease X. The nasal epithelium is the primary portal of entry for respiratory pathogens, serving as the airway's physical and immune barrier. While HPAI virus predominantly infects the lower airway, not much is known about its interactions with the nasal epithelium. Hence, we sought to elucidate and compare the differential responses of the nasal epithelium against HPAI infection that may contribute to its pathology, and to identify critical response markers. We infected human nasal epithelial cells (hNECs) cultured at the air-liquid interface from multiple healthy donors with clinical isolates of major human seasonal influenza viruses (H1N1, H3N2, influenza B) and HPAI H5N1. The infected cells were subjected to virologic, transcriptomic and secretory protein analyses. While less adapted to infecting the nasal epithelium, HPAI H5N1 elicited unique host responses unlike seasonal influenza. Interestingly, H5N1 infection of hNECs induced responses indicative of subdued antiviral activity (e.g. reduced expression of IFNβ, and inflammasome mediators, IL-1α and IL-1β); decreased wound healing; suppressed re-epithelialization; compromised epithelial barrier integrity; diminished responses to oxidative stress; and increased transmembrane solute and ion carrier gene expression. These unique molecular changes in response to H5N1 infection may represent potential targets for enhancing diagnostic and therapeutic strategies for better surveillance and management of HPAI infection in humans.

INTRODUCTION: Current bronchiectasis guidelines advise against the use of inhaled corticosteroids (ICS) except in patients with associated asthma, allergic bronchopulmonary aspergillosis (ABPA) and/or chronic obstructive pulmonary disease (COPD). This study aimed to describe the use of ICS in patients with bronchiectasis across Europe. METHODS: Patients with bronchiectasis were enrolled into the European Bronchiectasis Registry from 2015 to 2022. Patients were grouped into ICS users and non-users at baseline and clinical characteristics associated with ICS use were investigated. Patients were followed up for clinical outcomes of exacerbation, hospitalisation and mortality for up to 5 years. We evaluated if elevated blood eosinophil counts (above the laboratory upper limit of normal) modified the effect of ICS on exacerbations. RESULTS: 19 324 patients were included for analysis and 10 109 (52.3%) were recorded as being prescribed ICS at baseline. After exclusion of patients with a history of asthma, COPD and/or ABPA, 3174/9715 (32.7%) patients with bronchiectasis were prescribed ICS. Frequency of ICS use varied across countries, ranging from 17% to 85% of included patients. ICS users had more severe disease, with significantly worse lung function, higher Bronchiectasis Severity Index scores and more frequent exacerbations at baseline (p<0.0001). Overall, ICS users did not have a reduced risk of exacerbation or hospitalisation during follow-up, but a significant reduction in exacerbation frequency was observed in the subgroup of ICS users with elevated blood eosinophil counts (relative risk 0.70, 95% CI 0.59 to 0.84, p<0.001). CONCLUSION: ICS use is common in bronchiectasis, including in those not currently recommended ICS according to bronchiectasis guidelines. ICS use may be associated with reduced exacerbation frequency in patients with elevated blood eosinophils.