Humming, nitric oxide and paranasal sinus ventilation

The paranasal sinuses are air-filled bony cavities surrounding the nose. They communicate with the nose via the sinus ostia through which fluid and gases pass in both directions. A proper ventilation is crucial for sinus integrity and blockage of the ostia is a major risk factor for development of sinusitis.

In this thesis we have explored an entirely new approach to monitor sinus ventilation - the nasal humming test. We show in human studies in vivo and in a sinus/nasal model that the oscillating sound waves generated during humming produce a dramatic increase in sinus ventilation. Interestingly, this increased gas exchange can be readily monitored on-line by simultaneously measuring the levels of the gas nitric oxide (NO) in nasally exhaled air.

The sinuses constitute a major natural reservoir of NO and when gas-exchange increases during humming NO escapes rapidly into the nasal cavity thereby creating a highly reproducible peak in exhaled NO.When exploring the different factors that determine the humming peak in NO we found that sinus ostium size was the most important but the humming frequency also influenced the sinus NO release. In patients with severe nasal polyposis and completely blocked sinus ostia the humming peak in NO was abolished. Moreover, in patients with allergic rhinitis absence of a NO peak was associated with endoscopic signs suggestive of ostial obstruction. In the last study we went on to study if oscillating sound waves could be used not only to wash a gas out from the sinuses but also to enhance passage of substances into the sinuses. Indeed, we found evidence of an increased intra-sinus drug deposition by adding a sounding airflow to an aerosol.

In conclusion, the ventilation of the paranasal sinuses increases greatly when a person is humming; a finding that could have both diagnostic and therapeutic implications. Measurements of nasal NO during humming may represent a test of sinus ostial function. In addition, aerosol in combination with a sounding airflow could possibly be useful to increase the delivery of drugs into the paranasal sinuses.

List of scientific papers

I. Maniscalco M, Weitzberg E, Sundberg J, Sofia M, Lundberg JO (2003). Assessment of nasal and sinus nitric oxide output using single-breath humming exhalations. Eur Respir J. 22(2): 323-9.
https://doi.org/10.1183/09031936.03.00017903

II. Lundberg JO, Maniscalco M, Sofia M, Lundblad L, Weitzberg E (2003). Humming, nitric oxide, and paranasal sinus obstruction. JAMA. 289(3): 302-3.
https://doi.org/10.1001/jama.289.3.302-b

III. Maniscalco M, Sofia M, Weitzberg E, De Laurentiis G, Stanziola A, Rossillo V, Lundberg JO (2004). Humming-induced release of nasal nitric oxide for assessment of sinus obstruction in allergic rhinitis: pilot study. Eur J Clin Invest. 34(8): 555-60.
https://doi.org/10.1111/j.1365-2362.2004.01384.x

IV. Maniscalco M, Sofia M, Weitzberg E, Carratu L, Lundberg JO (2003). Nasal nitric oxide measurements before and after repeated humming maneuvers. Eur J Clin Invest. 33(12): 1090-4.
https://doi.org/10.1111/j.1365-2362.2003.01277.x

V. Maniscalco M, Sofia M, Weitzberg E, Lundberg JO (2006). A sounding airflow enhances aerosol delivery into the paranasal sinuses. Eur J Clin Invest. [Accepted]
https://doi.org/10.1111/j.1365-2362.2006.01654.x