Are inhaled mRNA vaccines safe and effective? A review of preclinical studies.

INTRODUCTION: Injected mRNA vaccines have been proven effective and safe in the SARS-CoV-2 pandemic. Using the machinery of the cell, mRNA vaccines translate into an antigen, which triggers an adaptive immune response. The effectiveness of intramuscular administered mRNA vaccines wanes in the months post-vaccination, which makes frequent booster administrations necessary. To make booster administration easier and increase efficacy, pulmonary administration could be investigated. The aim of this literature study was therefore to review the published preclinical (animal) studies on the safety and efficacy of pulmonary administered mRNA vaccines. AREAS COVERED: We first provide background information on mRNA vaccines and immunological mechanisms of vaccination. Thereafter, we provide an evaluation of published animal studies, in which mRNA vaccines (or mRNA containing nanoparticles) were delivered into the lungs. We covered the following areas: biodistribution, cellular uptake, immune response, protection, and safety. All relevant papers were found using PubMed/MEDLINE database. EXPERT OPINION: In our opinion, head-to-head comparison studies examining the safety and efficacy of intramuscular injected and pulmonary administered liquid mRNA vaccines should be performed first. When pulmonary delivered mRNA vaccines are shown to be effective and safe, inhalable dry powder formulations should be engineered. Finally, the tolerability of patients with respiratory diseases should be considered.

Global burden of medication non-adherence in chronic obstructive pulmonary disease (COPD) and asthma: a narrative review of the clinical and economic case for smart inhalers.

Medication non-adherence to asthma and chronic obstructive pulmonary disease therapy poses a significant burden for patients and societies. Non-adherence encompasses poor initiation, implementation (including poor inhalation technique) and non-persistence. Globally, non-adherence is associated with poor clinical outcomes, reduced quality of life and high healthcare and societal costs. Costs are mainly caused by excess hospitalizations and impaired work productivity. Multiple intervention programs to increase adherence in patients with asthma and chronic obstructive pulmonary disease have been conducted. However, these intervention programs are generally not as effective as intended. Additionally, adherence outcomes are mostly examined with non-objective or non-granular measures (e.g., self-report, dose count, pharmacy records). Recently developed smart inhalers could be the key to objectively diagnose and manage non-adherence effectively in patients with asthma and chronic obstructive pulmonary disease. Smart inhalers register usage of the inhaler, record time and date, send reminders, give feedback about adherence and some are able to assess inhaler technique and predict exacerbations. Still, some limitations need to be overcome before smart inhalers can be incorporated in usual care. For example, their cost-effectiveness and budget impact need to be examined. It is likely that smart inhalers are particularly cost-effective in specific asthma and chronic obstructive pulmonary disease subgroups, including patients with asthma eligible for additional GINA-5 therapy (oral corticosteroids or biologics), patients with severe asthma in GINA-5, patients with asthma with short-acting beta2 agonists overuse, patients with asthma and chronic obstructive pulmonary disease with frequent exacerbations and patients with asthma and chronic obstructive pulmonary disease of working-age. While there is high potential and evidence is accumulating, a final push seems needed to cost-effectively integrate smart inhalers in the daily management of patients with asthma and chronic obstructive pulmonary disease.