Omicron XBB.1.16-Adapted Vaccine for COVID-19: Interim Immunogenicity and Safety Clinical Trial Results.

(1) Background: The global coronavirus disease 2019 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB.1.16-adapted PHH-1V81 protein-based vaccine compared to an XBB.1.5-adapted mRNA vaccine against various acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. (2) Methods: In a Phase IIb/III pivotal trial, adults previously vaccinated with a primary scheme and at least one booster dose of an EU-approved mRNA vaccine randomly received either the PHH-1V81 or BNT162b2 XBB.1.5 vaccine booster as a single dose. The primary efficacy endpoint assessed neutralization titers against the Omicron XBB.1.16 variant at day 14. Secondary endpoints evaluated neutralization titers and cellular immunity against different variants. Safety endpoints comprised solicited reactions up to day 7 post-vaccination and serious adverse events until the cut-off date of the interim analysis. Changes in humoral responses were assessed by pseudovirion-based or virus neutralization assays. (3) Results: At the cut-off date, immunogenicity assessments included 599 participants. Both boosters elicited neutralizing antibodies against XBB.1.16, XBB.1.5, and JN.1, with PHH-1V81 inducing a higher response for all variants. The PHH-1V8 booster triggers a superior neutralizing antibody response against XBB variants compared to the mRNA vaccine. A subgroup analysis consistently revealed higher neutralizing antibody responses with PHH-1V81 across age groups, SARS-CoV-2 infection history, and the number of prior vaccination shots. A safety analysis (n = 607) at the day 14 visit revealed favorable safety profiles without any serious vaccine-related adverse events. (4) Conclusions: PHH-1V81 demonstrates superiority on humoral immunogenicity compared to the mRNA vaccine against XBB variants and non-inferiority against JN.1 with a favorable safety profile and lower reactogenicity, confirming its potential as a vaccine candidate.

Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.

Inhaler Adherence in COPD: A Crucial Step Towards the Correct Treatment.

COPD is a typical example of chronic disease. As such, treatment adherence tends to be as low as between 30% and 50%, with specific issues in COPD due to the use of inhaled therapies. Decreased adherence in COPD is associated with worse outcomes, with increased risk for exacerbations and long-term mortality. Factors that impact adherence are multiple, some related to patient, some related to clinicians and finally some related to healthcare system. Among clinician factors, prescription of simplified treatment regimens delivered by an inhaler adapted to the patient's characteristics is crucial. Although it has been observed a huge improvement in the design and usability of inhaler devices for COPD in the last two centuries, there is still a clear gap in this field. Smart inhalers as well as simplified treatment regimens could improve adherence and therefore improve long-term outcomes in COPD.

Prevalence of anaemia associated with chronic obstructive pulmonary disease. Study of associated variables.

BACKGROUND: Anaemia is one of the extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD). Its real prevalence, physiopathology and clinical repercussion are unknown. The objectives of our study were: to determine the prevalence of anaemia in patients with stable COPD not attributable to other causes and to establish the relationship of anaemia with clinical, prognostic and inflammatory markers with an important role in COPD. METHODS: The study included stable COPD patients with no other known causes of anaemia. The following tests were carried out: respiratory function tests; serum determination of erythropoietin and inflammatory markers: high sensitivity C-reactive protein (hs-CRP), fibrinogen, interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor α (TNF-α). Body mass index (BMI), Charlson and BODE indices, the number of exacerbations in the previous year, dyspnoea and quality of life were also calculated. RESULTS: One hundred and thirty patients were included. Anaemia prevalence was 6.2%. Mean haemoglobin value in anaemic patients was 11.9±0.95g/dL. Patients with anaemia had a lower BMI (P=.03), higher Charlson index (P=.002), more elevated erythropoietin levels (P=.016), a tendency to present a lower FEV1% value (P=.08) and significantly lower IL-6 values when compared to non-anaemic patients (P=.003). CONCLUSIONS: In our series, the anaemia associated with COPD was less prevalent than that published in the literature to date, and was related to certain clinical and inflammatory markers.

Analysis of the molecular expression profile of non small cell lung carcinoma associated to chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is an independent risk factor to develop lung cancer but there are no different functional clusters of biomarkers between patients with non-small cell lung cancer (NSCLC) with or without COPD. To analyse protein expression, in order to find out whether samples of resected NSCLC from patients with COPD present a different molecular expression. Observational, cohort, concurrent study with sampling since treatment of disease in patients with NSCLC in initial stages (pIA-pIIB) treated surgically in our hospital between October 1993 and September 1997. The study consisted of the elaboration of tissue arrays with samples from resected tumor, using immunohistochemistry as a study method. Univariate analysis and logistic regression analysis were performed in order to determine molecular markers that showed a differential expression in NSCLC of the patients with COPD. We studied thirty-two proteins in 146 patients. 30% of the patients had COPD. Univariate analysis in patients with COPD showed one molecular marker to be overexpressed and five molecular markers to be underexpressed. Multivariate analysis in patients with COPD identified membranous beta-Catenin as a differential biomarker, which displayed an underexpression, with an Odds Ratio (95% Confidence Interval) of 0.26 (0.07-1.01). A significant lowest expression of membranous beta-catenin was detected in NSCLC of the patients with COPD.