Daily Respiratory Research Analysis

BACKGROUND: A novel airway balloon cryoablation (ABC) system using liquid nitrogen as cryogen was developed for bronchoscopic intervention in malignant central airway obstruction (MCAO). This study aimed to evaluate the efficacy and safety of this system. METHODS: This was a prospective, randomised, controlled, non-inferiority study that enrolled MCAO patients at 15 sites in China. Patients were assigned to the ABC group and the ERBOKRYOCA Cryosurgical (EC) system group in a 1:1 ratio. Airway tumour debulking with multimodality was permitted before cryoablation. The primary outcome was the airway patency rate after 6 weeks of intervention with a non-inferiority margin of -10%. Secondary outcomes included modified Medical Research Council (mMRC) Dyspnoea Scale and Karnofsky Performance Scale (KPS) assessment, and the duration of cryoablation. RESULTS: 198 patients were randomised. After 6 weeks of intervention, the airway patency rate was 78.49% in the ABC group and 60.92% in the EC group, showing that the difference was over the non-inferiority margin of -10% at 17.58% (95% CI 4.35% to 30.80%), p<0.001. The mMRC and KPS scores were significantly improved after 3 and 6 weeks in both groups, with no difference. The duration of cryoablation was shortened remarkably in the ABC group (378.29±399.54 s vs 624.93±443.72 s, p<0.001). The prevalence of bleeding was similar in the two groups, without life-threatening events. CONCLUSIONS: The ABC system provided non-inferior and subsequent superior effect in airway patency rate compared with traditional carbon dioxide-driven cryoprobe in MCAO. This study supports this novel system as an alternative to cryoablation via bronchoscope for MCAO patients. TRIAL REGISTRATION NUMBER: ChiCTR2100042051.

Type I interferons (IFN-Is) are cytokines with potent antiviral and inflammatory capacities. IFN-I signaling drives the expression of thousands of IFN-I-stimulated genes (ISGs), whose aggregate function results in the control of viral infections. A few of these ISGs are tasked with negatively regulating the IFN-I response to prevent overt inflammation. ISG15 is a negative regulator whose absence leads to persistent, low-grade elevation of ISG expression and concurrent, often self-resolving, mild autoinflammation. The limited breadth and low-grade persistence of ISGs expressed in ISG15 deficiency are sufficient to confer broad-spectrum antiviral resistance. Inspired by the antiviral state of humans with ISG15 deficiency, we identified a nominal collection of 10 ISGs that recapitulated the broad antiviral potential of the IFN-I system, which typically induces the expression of thousands of ISGs. The expression of this 10-ISG collection in an IFN-I-nonresponsive cell line increased cellular resistance to Zika virus, vesicular stomatitis virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A lipid nanoparticle-encapsulated messenger RNA (mRNA) formulation of this 10-ISG collection reduced influenza A virus plaque size in samples collected from infected mice when given prophylactically. Moreover, when used collectively and delivered prophylactically, the 10-ISG collection was able to protect hamsters against a lethal SARS-CoV-2 challenge, in contrast with the lack of efficacy when mRNAs were delivered individually. These findings suggest that these 10 ISGs have potential as a broad-spectrum antiviral prophylactic.

BACKGROUND: Tuberculosis (TB) treatment monitoring is hindered by the lack of a rapidly measured biomarker that accurately predicts clinically relevant outcomes. Symptom screening poorly correlates with bacillary burden. Although culture is a direct measure of viable bacillary burden, the long turnaround time makes it clinically irrelevant. METHODS: The TB treatment monitoring potential of stool-based, quantitative polymerase chain reaction (qPCR) was prospectively assessed among 231 participants of all ages from Eswatini, Tanzania, and Mozambique with microbiologically confirmed TB. Stool qPCR results were compared to sputum culture, persistent symptoms, drug resistance, and World Health Organization TB outcomes. RESULTS: Quantitative bacillary burden measured by stool qPCR strongly correlated with sputum culture at baseline (Spearman correlation CONCLUSIONS: Stool-based TB treatment monitoring correlates with sputum culture but provides results faster, leverages a more accessible specimen, and identifies patients with TB who are at risk for drug resistance and persistent 2-month culture positivity. None of the quantitative tests of bacillary burden singularly could predict symptom resolution or death.