New method detects lung antibodies through non-invasive exhaled breath

For the first time, researchers have succesfully measured antibodies against specific respiratory viruses in exhaled air. This is shown in a new study involving, amongst others, the Karolinska Institutet, published in eBioMedicine. The method may make it easier to study the immune system in the small airways of the lungs.

Antibodies in the mucosal lining of the respiratory tract play an important role in protecting against respiratory viruses such as influenza virus, SARS-CoV-2 and respiratory syncytial virus (RSV). While antibodies in the upper airways are relatively easy to measure, sampling from the lower airways has previously required invasive procedures such as bronchoscopy.

In the new study, researchers used a non-invasive method called PExA (Particles in Exhaled Air). By breathing into a specially designed instrument, participants generated tiny exhaled particles originating from the respiratory tract lining fluid of the small airways. These particles were collected and analysed for virus-specific antibodies.

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." 

Charlotte Thålin, Adjunct Professor, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, and co-last author of the study

The study included 28 participants in the COMMUNITY cohort at Danderyd Hospital, 18 of whom had recently experienced a respiratory tract infection. The researchers analysed paired samples from blood, nasal secretions and exhaled breath.

In the exhaled breath samples, the researchers successfully detected IgA and IgG antibodies directed against SARS-CoV-2, influenza virus and RSV. Virus-specific IgG levels in the lower airway samples largely mirrored those observed in blood, whereas IgA showed a different pattern, consistent with a greater contribution from local mucosal antibody responses.

In the future, the method could help researchers investigate how immune responses in the lower airways change following respiratory infections or vaccinations, and and support the evaluation of preventive treatments. The researchers emphasize that this was an initial methodological study involving a limited number of participants and that further validation in larger studies is needed.

The study was conducted in collaboration between Karolinska Institutet, Danderyd Hospital, Uppsala University, and SciLifeLab. Funding was provided by the European Research Council (ERC), the Knut and Alice Wallenberg Foundation and the Swedish Society for Medical Research (SSMF).