Inhalation of nasally derived nitric oxide modulates pulmonary function in humans

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Citation

Lundberg JO, Settergren G, Gelinder S, Lundberg JM, Alving K, Weitzberg E. Inhalation of nasally derived nitric oxide modulates pulmonary function in humans. Acta Physiol Scand. 1996 Dec;158(4):343-7. doi: 10.1046/j.1365-201X.1996.557321000.x. PMID: 8971255.

Additional Note

When you see in books or social media posts that nasal breathing increase oxygenation by 10-18%, this is “the paper” it comes from.

4 FUNDAMENTALS

 

1. Essential Background Material

 

Nitric oxide (NO) has many beneficial properties.  For instance, it’s anti-microbial, anti-viral, and a potent vasodilator (it improves blood flow).

Interestingly, NO is continuously produced in the paranasal sinuses. Because of this, NO is carried through the airways and into the lungs with each nasal inhale we take. However, for this same reason, mouth breathing does not bring as much NO into the airways and lungs.

Thus, since nasal breathing harnesses NO, the authors of this study wondered if nose breathing might improve blood flow in the lungs, thereby leading to better oxygenation than mouth breathing?  And if so, is it purely due to NO, or are other factors playing a role?

 

They did several neat experiments to test these hypotheses.

 

 

2. What Did this Research Do?

 

First Experiment: Nose vs. Mouth in Healthy Subjects

 

They had eight healthy participants perform two different breathing protocols:

  • Nasal Breathing: Inhale through the nose and exhale through the mouth (exhaling through the mouth does not wash out residual NO in the nasal airways, maximizing NO delivery to the lungs on the next inhale).

  • Mouth Breathing: Inhale through the mouth and exhale through the nose (this minimizes NO delivery because it bypasses the nasal airways during inhalation and washes NO out of the airways during exhalation).

 

They repeated 5-min segments of each breathing protocol (5-min mouth breathing, 5-min nose breathing, 5-min mouth breathing, etc.) while transcutaneous oxygen tension was measured. 

 

Sub-Experiment 1: They had two people perform mouth breathing with added NO to see if it could reproduce some of the same nasal-breathing results.

 

Sub-Experiment 2: They also had two participants perform mouth breathing with added moisture to see if humidification might explain the differences.

 

Second Experiment: Intubated Mechanically Ventilated Participants

 

In patients who were on long-term mechanical ventilation (and therefore receiving no nasally-derived air), they did something simple yet profound.  They extracted air from the patients’ noses and added it to the inspiratory air of the ventilator.  Arterial oxygenation was measured in these participants.

 

Sub-Experiment 3: They also added just exogenous NO to the inspiratory air of the ventilator to see if that affected arterial oxygenation similarly to nasal air.

 

There was another experiment with coronary bypass grafting patients, which I am leaving off for simplicity—the results presented next are the most critical.

 

 

3. What Were the Major Findings?

  • In six of the eight healthy participants, nasal breathing increased oxygenation by an average of 10% compared to mouth breathing.

  • Mouth breathing with exogenous NO increased oxygenation by 6% in one participant and 23% in another compared to mouth breathing without NO; mouth breathing with added moisture did not impact oxygenation.

  • Adding nasal air to long-term ventilated patients increased arterial oxygenation by an average of 18%.

  • Adding exogenous NO to long-term ventilated patients increased arterial oxygenation by an average of 20%.




4. Why Do These Results Matter?


Nose vs. Mouth Breathing

The 10% increase in transcutaneous oxygen tension is meaningful because this is a measurement of tissue oxygenation, which is a function of blood oxygen levels, blood flow, and oxygen release. Thus, it shows that nasal breathing increases the amount of oxygen actually getting to the tissues by 10%. That’s crazy.

However, note that there were only eight participants, and nasal breathing did not increase oxygenation in two (the authors were unsure why).  So, we’d like a much bigger sample size, but we have to take what we can get.

 

Lastly, the additional sub-experiments suggest that NO is the primary mechanism through which nasal breathing increases oxygenation, not humidification.

 

Intubated Mechanically-Ventilated Patients

 

These results are perhaps even more crucial. Here’s why.  The structure of the nose and nasal airways does all kinds of amazing things for our breath.  But the intubated mechanically ventilated patients bypass all of this.

Yet, adding nasally-derived air still increased oxygenation by 18%, and adding NO alone increased it by 20%. This suggests that, of all the nose’s features, the production of NO might be the most significant factor for body oxygenation.



 

1 BIG TAKEAWAY

 

Nasal breathing increases tissue oxygenation more than mouth breathing (an average of 10%) due to inhalation of nasally-derived nitric oxide.

 

 

1 PRACTICAL APPLICATION

 

This one is pretty straightforward: Breathe primarily through your nose.

 

Another practical takeaway is that we can use nose-in/mouth-out to maximize NO delivery to the lungs.  Thus, you might start or end each breathing exercise with a few breaths (or a few minutes) like this to optimize oxygenation.

 

Lastly, in my opinion, these results might also support the standard advice to breathe in nasally and out orally during exercise.  This would maximize NO delivery and enhance oxygenation.  But, it could also dehydrate us faster, so we just have to be careful not to overdo it.