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Humming, Nitric Oxide, and Paranasal Sinus Obstruction
To the Editor: The paranasal sinuses communicate with the nasal cavity through narrow ostia. It is essential for sinus health that the ostia remain patent so that air and fluid can pass freely. Indeed, blockage of the ostia is a major risk factor for sinusitis.1 Therefore, the main goal in medical as well as surgical treatment of chronic sinusitis is to restore ventilation of the sinuses.
The mucosa of the nose and sinuses release nitric oxide that can be measured easily in nasally exhaled air.2-3 Sinus epithelium produces an especially large amount of nitric oxide and the concentrations in the sinuses can reach levels of greater than 20 ppm.3 We recently reported that levels of exhaled nasal nitric oxide increase dramatically if a person hums while exhaling rather than exhaling silently.4 This is most likely due to a great increase in paranasal sinus ventilation caused by the oscillating sound waves.4 We now hypothesize that patients with obstructed sinus ostia will exhibit less of an increase in exhaled nasal nitric oxide levels.
Methods
Ten healthy nonsmoking control patients (ages 25-52 years; 5 men) without any history of allergy or chronic airway disorder and 10 patients with chronic sinusitis and nasal polyposis (ages 30-56 years; 5 men) participated in the study. None of the control patients had any ongoing respiratory tract infection at the time of the study. All patients were on a waiting list for sinus surgery. All had bilateral polyps and completely opaque sinuses according to a previous computed tomography scan. All were being treated with topical nasal corticosteroids.
Nitric oxide levels were measured in single-breath nasal exhalations using a chemiluminescence system (Aerocrine AB, Stockholm, Sweden) developed to meet the criteria of the American Thoracic Society guidelines5 for exhaled nitric oxide measurements. A tight-fitting mask covering the nose was used and the subjects exhaled nasally with closed mouth at a fixed flow rate (0.10 L/s) for 10 seconds, first silently and then humming. Nitric oxide levels were calculated as the mean output (nanoliters per minute) during the last 80% of the exhalation. Experimenters were not blinded to the patients' conditions. Nonetheless, there was minimal variation (<0.02 L/s) in the exhalation flow rate as determined by the monitoring system's computer.
Results
During quiet exhalation, mean (SD) output of nasal nitric oxide was similar in control patients and patients with sinusitis (189 [27] nL/min vs 162 [22] nL/min, respectively). Mean output of nasal nitric oxide increased 7-fold during humming (to 1285 [189] nL/min) in control patients but remained completely unchanged in the patients with sinusitis (169 [21] nL/min).
Comment
Humming causes the air to oscillate which in turn greatly speeds up the exchange of air between the sinuses and the nasal cavity.4 The high levels of nitric oxide accumulated in the sinuses pass quickly into the nose where they can be measured.4 We found that the physiological increase in nasal nitric oxide levels during humming is completely absent in a small sample of patients with nasal polyposis. The most likely explanation is a lack of an air passage between the sinuses and the nasal cavity. Indeed, computed tomography had revealed obstructed sinuses bilaterally in all patients. Interestingly, one of the patients had surgery during the course of this study, and in this patient nasal nitric oxide levels increased during humming to almost normal levels 2 weeks after the operation (data not shown).
It is possible that it is the actual production of nitric oxide that is reduced in the patients with nasal polyposis. However, this seems less likely since nasal nitric oxide levels during quiet breathing were not significantly reduced in the patients in this study. Also, in an earlier study, levels of nasal nitric oxide were only somewhat lower in patients with nonallergic polyposis and normal in those with allergic polyposis.6 Although the humming test presented here appears promising, it should not be used in the clinical situation until further studies establish its sensitivity and specificity.
Financial Disclosure: Drs Lundberg and Weitzberg own shares in Aerocrine AB, which manufactures a system for measuring exhaled nitric oxide.
Funding/Support: This study was supported by grants from the Swedish Heart-Lung Foundation, the Vårdal Foundation, and the Swedish Research Council. The foundations had no role in the study design or in its writing.
Jon O. Lundberg, MD, PhD
Department of Physiology and Pharmacology
Mauro Maniscalo, MD
Department of Physiology and Pharmacology
Karolinska Institute
Stockholm, Sweden
Matteo Sofia, MD, PhD
Department of Respiratory Medicine
University Frederico II
Naples, Italy
Lars Lundblad, MD, PhD
Department of Surgical Science
Eddie Weitzberg, MD, PhD
Department of Otorhinolaryngology
Karolinska Hospital
Stockholm
1. Hamilos D. Chronic sinusitis. J Allergy Clin Immunol. 2000;106:213-227.
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2. Lundberg JO, Weitzberg E, Nordvall SL, Kuylenstierna R, Lundberg JM, Alving K. Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome. Eur Respir J. 1994;7:1501-1504.
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3. Lundberg JO, Farkas-Szallasi T, Weitzberg E, et al. High nitric oxide production in human paranasal sinuses. Nature Med. 1995;1:370-373.
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4. Weitzberg E, Lundberg JO. Humming greatly increases nasal nitric oxide. Am J Respir Crit Care Med. 2002;166:144-145.
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5. American Thoracic Society. Recommendations for standardized procedures for online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide in adults and children. Am J Respir Crit Care Med. 1999;160:2104-2117.
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6. Arnal J, Flores P, Rami J, et al. Nasal nitric oxide concentrations in paranasal sinus inflammatory diseases. Eur Respir J. 1999;13:307-312.
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Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.
JAMA. 2003;289:302-303.
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
ATS Workshop Proceedings: Exhaled Nitric Oxide and Nitric Oxide Oxidative Metabolism in Exhaled Breath Condensate.
Proc Am Thorac Soc 2006;3:131-145.
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Temporal nitric oxide dynamics in the paranasal sinuses during humming
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