A Review of Nasal Nitric Oxide's Powerful Effects

Key Points

• Nasal nitric oxide (NO) acts as our first line of defense against airborne pathogens by sterilizing incoming air and enhancing cilia movement

• Nasal NO plays a role in warming the air we breathe as it travels into the lungs

• Humming significantly increases nasal NO and could be used as a test for sinus disorders
  

The Breathing Diabetic Summary

I spend a lot of time reading about nitric oxide (NO).  But, the more I learn, the more interested I become. It seems to pop up everywhere I look. Sometimes I wonder what it can’t do.

Nitric oxide’s physiological relevance was discovered in 1987, the same year I was born. Its effects were known several years prior, but it wasn’t until two separate papers (both in prestigious journals, PNAS and Nature) were published that NO’s benefits became “official.”

In the respiratory system, the primary source of NO is the upper airways. The paranasal sinuses, in particular, produce ~90% of the NO measured in exhaled air.  

Previously, we have learned that NO acts as our first line of defense against airborne pathogens by sterilizing incoming air.  The breathing community often touts aspect of NO.  Here, we learn there is more to it: nitric oxide also increases the cilia motility.  

Cilia are tiny hairs lining the back of your nose and respiratory tract. They oscillate back and forth to move mucus out of the upper and lower airways, bringing pathogens and other potentially harmful agents along for the ride.  Cilia are your lung’s first defense against inhaled particles and nitric oxide enhances their activity.  

Nitric oxide also plays a role in warming incoming air. The precise mechanism is unclear, but increased nasal NO release is associated with increased temperature in the nasal airways.

Here is my speculation: NO increases blood flow in your nose, which warms the nasal passages and airways. As air travels through, it extracts this warmth before entering the lungs. Makes sense, but is just a hypothesis and likely oversimplifies what is going on…

Nasal nitric oxide also redistributes blood flow in the lungs when in the upright position, leading to better oxygen uptake. (Nasal NO might even be an adaptation to gravity, allowing us to walk upright.)  

Finally, humming causes a significant increase in nasal NO. However, some sinus disorders inhibit this enhanced NO release. Therefore, the measurement of nasal NO after humming might be a way to test for sinus disorders.

To summarize, nasal nitric oxide is a powerful gas. It acts as our first line of defense against airborne pathogens by sterilizing incoming air and by improving cilia motility. Additionally, NO helps warm the air we breathe as it travels into our lungs. NO also redistributes blood flow in the lungs, resulting in better oxygen uptake. Lastly, humming increases NO significantly and might provide a way to test for sinus disorders.

Abstract

Exhaled nitric oxide (NO) originates from the upper airways, and takes action, to varying extents, in regulation, protection and defense, as well as in noxious processes. Nitric oxide retains important functions in a wide range of physiological and pathophysiological processes of the human body, including vaso-regulation, antimicrobial activity, neurotransmission and respiration. This review article reports the ongoing investigations regarding the source, biology and relevance of NO within upper respiratory tract. In addition, we discuss the role of NO, originating from nasal and paranasal sinuses, in inflammatory disorders such as allergic rhinitis, sinusitis, primary ciliary dyskinesia, and cystic fibrosis.

Journal Reference:

Maniscalco M, Bianco A, Mazzarella G, Motta A.  Recent Advances on Nitric Oxide in the Upper Airways.  Curr Med Chem. 2016;23(24):2736-2745.

Nasal breathing synchronizes brain wave activity and improves cognitive function

Key Points

• Nasal breathing synchronizes brain wave oscillations in the piriform cortex, amygdala, and hippocampus

• Nasal breathing improves cognitive function when compared to mouth breathing

• Breathing affects emotional and mental state, shifting the paradigm for why we breathe

The Breathing Diabetic Summary

It is established that emotions and mental state affect breathing.  When you’re anxious, you breathe faster and shallower.  When you’re relaxed, you breathe quiet and light.  Intuitively, I think we all know that the opposite is true too: Your breathing can affect your emotions and mental state.  However, the brain mechanisms behind this shift have remained elusive.

This study sheds light on the issue.  Intracranial EEG (iEEG) was used to assess how breathing impacts electrical oscillations in different regions of the brain.  Then, emotional recognition and memory tests were used to see how breathing impacts cognitive function.

The results showed that oscillations in the piriform cortex are directly related to nasal breathing. The piriform cortex is associated with the nose through smell, so it makes sense that nasal breathing would cause oscillations in this region (although the participants were breathing odorless air).

Interestingly, two other regions of the brain also showed these oscillations: the amygdala and hippocampus.  When breathing was switched to the mouth, however, this brainwave activity became disorganized.  Thus, nasal breathing is critical to synchronizing electrical brainwave oscillations.

If nasal breathing affects these regions of the brain, it follows that it would potentially impact cognition.  And that’s exactly what they found.

They showed participants faces expressing either fear or surprise and had them quickly decide which one it was.  When breathing through the nose, the response times were faster than when breathing through the mouth.  Additionally, the participants identified fearful faces faster during inhalation than exhalation.  This effect wasn’t present when mouth breathing. 

Next, they had the participants perform a memory task involving picture recognition.  They found that their memory retrieval was more accurate during nasal inhalation, which was not observed for mouth breathing.  However, there was not a statistically significant difference in the overall accuracy between nose and mouth breathing.

Taken together, the iEEG measurements and cognitive tasks suggest that nasal breathing promotes coherent brainwave oscillations in the piriform cortex, amygdala, and hippocampus.  This coherence leads to improved cognitive function, especially during nasal inhalation.

“We also found that the route of breathing was critical to these effects, such that cognitive performance significantly declined during oral breathing.”

We’ve already established that breathing can no longer be thought of as a 2-gas system.  Now, we might have to extend beyond gases altogether.  Breathing acts to synchronize brain activity and enhance cognitive function…but only when performed through the nose.

I think that bears repeating.  Nasal breathing synchronizes brainwave activity and enhances cognitive function.  Pretty remarkable.

Abstract

The need to breathe links the mammalian olfactory system inextricably to the respiratory rhythms that draw air through the nose. In rodents and other small animals, slow oscillations of local field potential activity are driven at the rate of breathing (∼2-12 Hz) in olfactory bulb and cortex, and faster oscillatory bursts are coupled to specific phases of the respiratory cycle. These dynamic rhythms are thought to regulate cortical excitability and coordinate network interactions, helping to shape olfactory coding, memory, and behavior. However, while respiratory oscillations are a ubiquitous hallmark of olfactory system function in animals, direct evidence for such patterns is lacking in humans. In this study, we acquired intracranial EEG data from rare patients (Ps) with medically refractory epilepsy, enabling us to test the hypothesis that cortical oscillatory activity would be entrained to the human respiratory cycle, albeit at the much slower rhythm of ∼0.16-0.33 Hz. Our results reveal that natural breathing synchronizes electrical activity in human piriform (olfactory) cortex, as well as in limbic-related brain areas, including amygdala and hippocampus. Notably, oscillatory power peaked during inspiration and dissipated when breathing was diverted from nose to mouth. Parallel behavioral experiments showed that breathing phase enhances fear discrimination and memory retrieval. Our findings provide a unique framework for understanding the pivotal role of nasal breathing in coordinating neuronal oscillations to support stimulus processing and behavior.

 SIGNIFICANCE STATEMENT:

Animal studies have long shown that olfactory oscillatory activity emerges in line with the natural rhythm of breathing, even in the absence of an odor stimulus. Whether the breathing cycle induces cortical oscillations in the human brain is poorly understood. In this study, we collected intracranial EEG data from rare patients with medically intractable epilepsy, and found evidence for respiratory entrainment of local field potential activity in human piriform cortex, amygdala, and hippocampus. These effects diminished when breathing was diverted to the mouth, highlighting the importance of nasal airflow for generating respiratory oscillations. Finally, behavioral data in healthy subjects suggest that breathing phase systematically influences cognitive tasks related to amygdala and hippocampal functions.

Journal Reference:

Zelano C, Jiang H, Zhou G, Arora N, Schuele S, Rosenow J, Gottfried JA.  Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function.  J Neurosci. 2016;36(49):12448-12467.