Participants in a clinical study breathed into a specially designed instrument to generate tiny

Measuring Lower Airway Antibodies Through Exhaled Breath

Participants in a clinical study breathed into a specially designed instrument to generate tiny exhaled particles from the respiratory tract lining fluid of their small airways, capturing samples that allow researchers to measure virus-specific antibodies directly from the lungs without invasive procedures. This non-invasive method, known as PExA (Particles in Exhaled Air), was detailed in a study published in eBioMedicine.

PExA Method Samples Small Airways Without Invasive Bronchoscopy

While antibodies in the nasal mucosa offer frontline defense against respiratory infections, immune responses located further down in the lungs are crucial for preventing severe complications such as pneumonia. Previously, obtaining samples from these small airways required invasive procedures like bronchoscopy, which limited routine clinical evaluation. The PExA method collects particles originating directly from the respiratory tract lining fluid, providing a paired view alongside blood and nasal secretion samples. In analyzing these samples, researchers successfully detected IgA and IgG antibodies directed against SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV).

The distribution of these antibodies revealed distinct patterns between the systemic circulation and local mucosal sites. Virus-specific IgG levels in the lower airway samples largely mirrored those observed in blood, whereas IgA displayed a different pattern consistent with a greater contribution from local mucosal antibody responses.

Observational Study Includes Twenty-Eight Participants from Danderyd Hospital

The observational proof-of-concept study included 28 participants from the COMMUNITY cohort at Danderyd Hospital, 18 of whom had recently experienced a respiratory tract infection. Financial support for the investigation was provided by the European Research Council (ERC), the Knut and Alice Wallenberg Foundation, and the Swedish Society for Medical Research (SSMF), alongside a cooperative effort uniting Karolinska Institutet, Danderyd Hospital, Uppsala University, and SciLifeLab.

“Antibodies in the nasal mucosa are important for protection against respiratory infections, but immune responses further down the lungs are also crucial, particularly for preventing severe disease such as pneumonia. This method opens up new possibilities for understanding how immunity differs between the upper and lower airways,” said Charlotte Thålin, Adjunct Professor at the Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, and co-last author of the study.

Technique Monitors Immune Responses Following Respiratory Infections

The study was described by the authors as a preliminary methodological trial featuring a small cohort, noting that additional confirmation through larger investigations will be necessary. Looking ahead, the technique could help investigators monitor how immune responses in the lower airways evolve following respiratory infections or vaccinations, as well as assist in evaluating the effectiveness of preventive treatments.