Empty Nose Syndrome is primarily a postoperative nasal disorder, but the sensation of breathing involves the respiratory system, autonomic regulation and the brain. This article reviews evidence relevant to hyperventilation, carbon dioxide, nasal airflow resistance, lung volumes and cerebral processing. It also separates findings demonstrated in ENS patients from broader respiratory physiology and from hypotheses that have not yet been directly proven in ENS.
- Direct ENS evidence: paradoxical obstruction, altered cerebral processing of nasal patency, abnormal airflow/cooling in multiple studies, and a high prevalence of hyperventilation syndrome in one small prospective cohort.
- General respiratory physiology: CO₂ influences acid–base balance and oxygen–hemoglobin affinity; upper-airway resistance can influence lung volumes.
- Not yet established: that ENS routinely lowers cardiac output, causes systemic tissue hypoxia, or produces nocturnal hypoventilation solely because the nasal cavity is too open.
Why ENS can feel like a breathing disorder
Patients with ENS may have a physically patent nasal airway yet experience severe obstruction, air hunger or an inability to sense satisfying airflow. This apparent contradiction is one of the defining features of the syndrome. The sensation of nasal breathing depends on more than the diameter of the airway: airflow distribution, mucosal cooling, trigeminal sensory input and central processing all contribute to perceived patency.
That is why simply measuring a large nasal cross-sectional area does not explain the patient’s experience. In a 2011 functional MRI study, ten ENS patients and fifteen controls had similar objective nasal flow, but the ENS group rated their nasal patency substantially worse. The study also found different activation in temporal, cerebellar and limbic regions during the patency-rating task.
What the fMRI study actually demonstrated
Freund and colleagues exposed participants to limonene and menthol while performing functional MRI. Menthol improved the subjective perception of nasal patency in the ENS group and was accompanied by differences in temporal-cortex activation. The comparison between patients and controls also showed ENS-specific activation involving the amygdala and other regions during the rating task.
This is evidence that the sensation of nasal patency is processed differently in ENS and that a cooling stimulus can modify both perception and brain activation. It is not proof that ENS permanently locks the entire autonomic nervous system into a single “fight-or-flight” state, but it gives a biological basis for why a nasal sensory disturbance can produce intense respiratory and emotional distress.
Hyperventilation syndrome has been measured in ENS
One of the strongest direct links between ENS and respiratory physiology comes from a prospective study by Mangin and colleagues. Twenty-nine patients were referred during the study period; 22 were eligible and completed the full work-up. Hyperventilation syndrome was diagnosed in 17 of those 22 patients, or 77.3%, using a hyperventilation provocation test with delayed recovery of end-tidal CO₂ as the defining criterion.
The study also used arterial blood gases and cardiopulmonary testing. Its authors concluded that HVS was frequent in their ENS cohort and that the pathophysiological link deserved further investigation. Because the sample came from a referral center and was small, 77.3% should not be presented as a universal prevalence for every ENS population.
What hyperventilation does to CO₂ and pH
Ventilation in excess of metabolic CO₂ production lowers arterial carbon dioxide tension. When CO₂ falls, blood pH rises, producing respiratory alkalosis. This can cause light-headedness, tingling, chest discomfort, muscle symptoms and a sensation of breathlessness even when pulse oximetry remains normal.
CO₂ also influences hemoglobin’s affinity for oxygen. A rise in pH shifts the oxyhemoglobin dissociation curve to the left, meaning hemoglobin tends to hold oxygen more tightly. This is part of the Bohr-effect physiology. It is reasonable to discuss reduced oxygen unloading as a possible consequence of marked hypocapnia, but a normal SpO₂ plus a low CO₂ value does not by itself prove clinically significant systemic tissue hypoxia.
SpO₂, oxygen delivery and lactate are not interchangeable
Pulse oximetry estimates the percentage of hemoglobin saturated with oxygen; it does not directly measure tissue oxygen extraction. Lactate, meanwhile, can rise for many reasons, including high exercise intensity, adrenergic stimulation, reduced clearance and local metabolic conditions. Elevated lactate is therefore not a specific test for “ENS-related tissue hypoxia.”
The original version of this article suggested that lactate should replace SpO₂ when assessing oxygen delivery in ENS. That conclusion goes beyond the evidence. In a clinical assessment, oxygen saturation, blood gases, hemoglobin concentration, circulation, symptoms and – when indicated – lactate can provide different pieces of information. None should be interpreted in isolation.
Nasal resistance and lung volumes
The nose normally contributes substantial resistance to airflow. A classic 1988 Lancet study examined how changes in oronasal resistance affected lung volumes. The investigators found that total lung capacity, functional residual capacity and residual volume changed when nasal or oral resistance was experimentally altered. They concluded that expiratory resistance provided by the nose can help maintain lung volumes and may indirectly influence arterial oxygenation.
This study is relevant to the concept that the upper airway is mechanically coupled to breathing, but it was not an ENS study. It does not demonstrate that a surgically enlarged nasal cavity necessarily causes major loss of lung expansion in every ENS patient. Translating those findings to ENS requires direct measurements in ENS cohorts.
Intrathoracic pressure, venous return and cardiac output
Normal inspiration lowers intrathoracic pressure and contributes to venous return. Airway resistance, respiratory effort, lung volume and cardiovascular loading conditions all influence this interaction. It is therefore physiologically plausible that large changes in breathing mechanics could affect cardiopulmonary dynamics.
However, the original article made a much stronger claim: that reduced nasal resistance in ENS leads step-by-step to reduced negative intrathoracic pressure, impaired venous return, lower cardiac output and impaired systemic gas exchange. This causal chain has not been established in ENS clinical studies. It should be treated as a hypothesis rather than a demonstrated complication of turbinate surgery.
Nasal nitric oxide: relevant physiology, but avoid overstatement
Nitric oxide is produced in the upper airway, especially the paranasal sinuses, and participates in local vascular and respiratory physiology. Research has examined nasal nitric oxide in ENS and its relationship to symptom and psychological measures. This makes nNO a legitimate area of ENS research.
What cannot be concluded from a reduced nasal NO measurement alone is that the entire body or brain is receiving insufficient blood flow. Systemic vascular regulation is far more complex, and nasal NO measurements are not a direct measure of cerebral perfusion or cardiac output.
Slow breathing and autonomic regulation
A 2018 systematic review of slow breathing in healthy subjects found recurring changes in HRV, respiratory sinus arrhythmia, EEG activity and psychological measures. These findings support the broader principle that respiratory pattern can interact with autonomic and central nervous system function.
For ENS, the most cautious interpretation is that an abnormal breathing pattern may amplify symptoms in some patients and that respiratory rehabilitation could therefore be useful as an adjunct. This does not imply that breathing exercises reverse anatomical tissue loss or normalize damaged mucosal sensory pathways.
The nose–brain sensory pathway
ENS research increasingly emphasizes the role of trigeminal sensation and mucosal cooling. The perception that air is moving through the nose partly depends on thermal and sensory changes at the mucosal surface. When turbinate anatomy and airflow distribution are altered, a patient may have high measured flow but inadequate stimulation in the regions that normally contribute to the sensation of patency.
This provides a more evidence-based framework than attributing ENS to a single type of “vagal C-fiber.” The nasal cavity contains multiple sensory pathways, and the brain integrates these signals with respiratory drive, attention and emotion.
Menthol and the sensation of airflow
Menthol activates cold-sensitive TRPM8 pathways and can increase the sensation of nasal openness without necessarily increasing objective airflow. In the ENS fMRI study, menthol was perceived as beneficial and changed cerebral activation patterns. This reinforces the idea that perceived airflow and measured airflow are related but distinct variables.
For patients, this helps explain why interventions that improve the sensation of cooling may sometimes feel useful even when they do not physically enlarge the nasal airway.
Secondary atrophic changes after extensive surgery
Moore and Kern’s review of 242 cases of atrophic rhinitis documented secondary atrophic rhinitis after several causes, including sinonasal surgery. Their work is relevant to the long-term consequences of excessive tissue loss, particularly when dryness, crusting and mucosal atrophy develop.
The original version of this page stated that most patients will eventually develop a combined ENS/atrophic-rhinitis condition if follow-up is long enough. The review does not support that population-wide conclusion. It documents a serious complication and historical follow-up observations, but it does not provide the denominator needed to calculate the long-term incidence after modern turbinate procedures.
Daytime hyperventilation does not imply nocturnal hypoventilation
The previous article proposed that some ENS patients may hyperventilate during the day but hypoventilate at night simply because the nose is surgically too open. This is an interesting possibility in an individual patient, but it is not an established ENS pattern in published cohort research.
Nocturnal hypoventilation has specific diagnostic criteria and should be demonstrated with appropriate overnight CO₂ monitoring, blood gases or sleep-laboratory testing. It should not be inferred from nasal anatomy alone.
Personal physiological measurements versus general evidence
Individual capnography, blood-gas, spirometry or lactate measurements can be valuable when documenting a particular patient’s physiology. They should not automatically be generalized to all people with ENS. A single person may have reproducible hypocapnia, altered respiratory rate or changes after temporarily increasing nasal resistance, while another patient may show a different pattern.
For a research-oriented information site, the distinction is important: case observations can generate hypotheses, while controlled studies are needed to establish how common a mechanism is and whether it is causally related to ENS.
How to evaluate respiratory symptoms objectively
When an ENS patient has prominent air hunger or suspected overbreathing, useful objective tests can include respiratory rate, capnography, arterial or venous blood gas interpreted in clinical context, and cardiopulmonary exercise testing when appropriate. Nasal testing may include endoscopy, ENS6Q, Cotton testing and measurements of airflow or resistance.
These tests answer different questions. Capnography evaluates exhaled CO₂; blood gas evaluates systemic acid–base and gas status; spirometry evaluates pulmonary volumes and flows; rhinomanometry evaluates nasal pressure–flow relationships. No single test captures the complete ENS syndrome.
A more defensible model of systemic symptoms
A cautious model is that ENS can disturb the perception of nasal breathing and, in some patients, contribute to an abnormal respiratory pattern. Hyperventilation can then produce real systemic symptoms through hypocapnia and respiratory alkalosis. At the same time, sleep loss, chronic distress, pain and autonomic arousal can further amplify respiratory symptoms.
This model is supported more directly than claims that ENS universally causes reduced cardiac output or systemic hypoxia. Future studies measuring CO₂, cardiovascular variables, exercise physiology and sleep in well-characterized ENS cohorts would be needed to establish those broader effects.
Hypocapnia can affect cerebral blood flow
Carbon dioxide is a potent regulator of cerebral vascular tone. When arterial CO₂ falls substantially, cerebral vessels constrict and cerebral blood flow decreases. This is a well-established effect of hypocapnia in general respiratory physiology and helps explain why acute hyperventilation can cause light-headedness, visual disturbance, cognitive slowing or a sense of unreality.
This mechanism is relevant if an ENS patient has objectively documented hypocapnia. It is not necessary to invoke reduced nasal nitric oxide or low cardiac output to explain every neurological symptom during an episode of marked overbreathing. A low PaCO₂ by itself can alter cerebral perfusion.
Again, the conditional wording matters: ENS does not automatically equal hypocapnia. The direct ENS evidence is that hyperventilation syndrome was common in one small referral cohort. Individual blood-gas or capnography measurements are needed to determine whether hypocapnia is actually present in a particular patient.
Respiratory alkalosis and ionized calcium
Acute respiratory alkalosis can also change the fraction of calcium bound to albumin, lowering ionized calcium even when total serum calcium remains normal. This can contribute to tingling around the mouth or hands, muscle tightness, tremor and, in more pronounced cases, carpopedal spasm.
These symptoms are familiar in hyperventilation syndromes and can intensify the feeling that something is seriously wrong with breathing or circulation. They are physiologically real consequences of altered acid–base balance, but they are not specific to ENS.
Hyperventilation can become self-reinforcing
Air hunger can prompt a person to breathe faster or deeper. If the increased ventilation lowers CO₂, hypocapnia can produce dizziness, chest sensations and neurological symptoms, which may then be interpreted as evidence that even more air is needed. This creates a feedback loop in which the compensatory breathing response itself adds symptoms.
In ENS, a disturbed sensory signal from the nose could plausibly be one trigger for this loop. Psychological distress can be another. These mechanisms do not compete with each other: physical nasal dysfunction, autonomic arousal and learned respiratory responses may coexist and reinforce one another.
Lactate during exercise: what an elevated value means
Lactate production rises normally as exercise intensity increases and glycolytic flux exceeds the rate at which pyruvate is oxidized. A very high post-exercise lactate can reflect intense exertion, low conditioning, altered recruitment of muscle fibers, catecholamine effects or impaired clearance. It does not automatically prove systemic hypoxia.
Resting lactate above a laboratory reference range deserves clinical interpretation, especially if reproducible, but its differential diagnosis is broad. If a patient with ENS also has hypocapnia, the two findings may be physiologically related in some circumstances, yet a causal conclusion requires more than simultaneous measurement.
Exercise testing could clarify ENS physiology
Cardiopulmonary exercise testing is potentially valuable because it measures ventilation, oxygen uptake, carbon dioxide production, heart rate and workload together. In a research setting, adding arterial or capillary blood gases and lactate could show whether a subgroup of ENS patients develops excessive ventilation relative to CO₂ production during exercise.
Such studies would be more informative than inferring gas-exchange impairment from symptoms alone. They could also distinguish deconditioning from primary pulmonary, cardiovascular or ventilatory abnormalities.
Abnormal nasal aerodynamics and mucosal cooling
Computational fluid-dynamics studies of ENS have shown that surgery can redistribute airflow within the nasal cavity. A wider airway does not necessarily mean that airflow is delivered to the same mucosal regions as before surgery. Some studies have found reduced airflow interaction and reduced cooling in regions that contribute to the sensation of breathing.
This provides a mechanistic bridge between anatomy and perception. The total volume of air may be high, yet the spatial pattern of the flow may produce inadequate sensory feedback. A patient can therefore experience air hunger without a conventional obstructive lesion.
From a treatment perspective, this is one reason the Cotton test can be informative: adding temporary volume may redirect airflow and increase mucosal interaction. A positive response does not prove every proposed mechanism, but it shows that changing geometry can alter symptoms quickly.
Low resistance is not the same as “no resistance”
All airways have resistance. ENS usually involves a reduction or redistribution of nasal resistance rather than its complete disappearance. The physiological effect of that reduction depends on the rest of the respiratory system, breathing route, posture and respiratory drive.
Describing the ENS nose as having “no resistance” can therefore lead to exaggerated downstream claims. A better formulation is that surgical alteration may produce abnormally low or poorly distributed resistance and airflow in some patients, and that the clinical consequences of this need to be measured rather than assumed.
Nasal nitric oxide findings in ENS
A 2019 prospective study measured nasal nitric oxide in 19 ENS patients and 12 patients with chronic hypertrophic rhinitis. Before surgery, the ENS group had significantly lower nNO. In the ENS group, nNO increased after implantation and the change correlated with improvements in BDI-II and BAI scores.
This is a genuine ENS-specific finding. However, the study did not demonstrate that low nNO caused reduced cerebral blood flow, systemic vascular dysfunction or impaired lung perfusion. The authors proposed nNO as a potentially useful biomarker related to clinical and psychiatric status, not as a direct measure of whole-body oxygen delivery.
Sleep and respiratory regulation
ENS is frequently associated with sleep complaints, and severe sleep loss can itself increase sympathetic activation, alter ventilatory control and worsen pain and emotional regulation. This creates another potential feedback pathway between nasal symptoms and systemic distress.
If nocturnal breathing abnormalities are suspected, the appropriate approach is objective sleep assessment. Depending on the question, this can include polysomnography, oximetry and transcutaneous or end-tidal CO₂ monitoring. Daytime symptoms alone cannot distinguish obstructive events, central instability, hyperventilation, hypoventilation or non-respiratory insomnia.
Autonomic symptoms: distinguish observation from mechanism
Many ENS patients describe palpitations, internal agitation, inability to relax and marked stress responses. Research on symptom burden and brain activation makes autonomic involvement plausible. Chronic air hunger is itself a powerful arousal signal.
But statements such as “the vagus nerve has been disconnected” are not supported by current ENS evidence. Nasal surgery does not anatomically sever the vagus nerve. The relevant issue is altered afferent sensory input and central processing, which may secondarily influence autonomic state.
This distinction makes the biological argument stronger, not weaker. It replaces an anatomically inaccurate claim with a testable model involving trigeminal sensation, respiratory drive, limbic processing and autonomic output.
What future studies should measure
To determine whether ENS produces broader cardiopulmonary effects, future studies should recruit well-characterized patients and controls and measure several systems simultaneously. Useful variables would include nasal airflow distribution, rhinomanometry, ENS6Q, respiratory rate, end-tidal and arterial CO₂, oxygen uptake, lactate, blood pressure, cardiac output and HRV.
Overnight studies could add transcutaneous CO₂, sleep staging and respiratory-event scoring. Exercise studies could determine whether abnormal ventilation appears at rest, only during exertion, or in recovery. Repeating measurements before and after a reversible Cotton test would be especially informative because it could test whether changing nasal geometry produces immediate physiological effects.
These designs would help separate three questions that are often mixed together: whether ENS changes the sensation of breathing, whether it changes the breathing pattern, and whether that altered pattern then changes systemic physiology.
Additional ENS source: Fu CH, Wu CL, Huang CC, et al. Nasal nitric oxide in relation to psychiatric status of patients with empty nose syndrome. Nitric Oxide. 2019;92:55–59. PubMed.
General hypocapnia physiology: Krishnaprasadh D, Sharma S. Hypocarbia. StatPearls. Updated 2026. NCBI Bookshelf.
Interpreting CO₂ values correctly
Reference ranges depend on the type of sample. Arterial PaCO₂ is commonly about 35–45 mmHg in adults, while venous pCO₂ is normally higher because venous blood has collected CO₂ from the tissues. End-tidal CO₂ is related to arterial CO₂ but can differ because of dead space, ventilation–perfusion relationships and sampling technique.
This matters when comparing home capnography with hospital blood gases. A low end-tidal value can support excessive ventilation, but it is not numerically interchangeable with a venous blood-gas result. Trends measured with the same method are often more informative than comparing isolated values obtained with different technologies.
Respiratory rate alone does not define hyperventilation
A person can hyperventilate with a normal respiratory rate if each breath is excessively large, and can breathe quickly without becoming hypocapnic if tidal volumes are small or metabolic demand is high. Minute ventilation and alveolar ventilation depend on both rate and depth.
This is especially relevant in ENS, where patients may describe either rapid shallow breathing or repeated deep ”sigh” breaths. Objective CO₂ measurement is therefore more informative than respiratory rate alone when the clinical question is whether ventilation exceeds metabolic requirements.
Why careful wording strengthens the ENS case
ENS already has direct objective research in airflow, sensory testing, fMRI, validated symptom instruments and respiratory physiology. There is no need to present unproven systemic mechanisms as established facts. Separating demonstrated findings from plausible hypotheses makes it easier for clinicians and researchers to identify what is known and what should be tested next.
For patients, this distinction is equally important. A mechanism can be biologically plausible and worth investigating without being proven in every individual. Documentation of a patient’s own CO₂, blood gas, sleep or exercise abnormalities can then be presented as individual objective evidence rather than automatically generalized to the entire ENS population.
For research and clinical documentation, repeated measurements are particularly valuable. A reproducible physiological abnormality observed on separate days, under comparable conditions, carries more weight than a single isolated value. This is especially true for respiratory rate, end-tidal CO₂, lactate and autonomic measures, all of which can vary with activity, posture, stress, sleep and recent exertion.
Conclusion
ENS is not simply a matter of an airway being “too open,” nor is it adequately explained as a purely psychological response. Research demonstrates altered perception of nasal patency, measurable differences in brain activation and a significant association with hyperventilation syndrome in at least one prospective referral cohort.
The strongest scientific presentation is therefore to distinguish direct ENS findings from general physiology and from hypotheses. Doing so does not minimize the severity of the condition; it makes the case more credible and identifies exactly where further research is needed.
ENS hyperventilation: Mangin D, Bequignon E, Zerah-Lancner F, et al. Investigating hyperventilation syndrome in patients suffering from empty nose syndrome. Laryngoscope. 2017;127:1983–1988. PubMed.
ENS fMRI: Freund W, Wunderlich AP, Stöcker T, Schmitz BL, Scheithauer MO. Empty nose syndrome: limbic system activation observed by functional magnetic resonance imaging. Laryngoscope. 2011;121:2019–2025. PubMed.
Upper-airway resistance and lung volumes: Swift AC, Campbell IT, McKown TM. Oronasal obstruction, lung volumes, and arterial oxygenation. Lancet. 1988;1(8577):73–75. PubMed.
Atrophic rhinitis: Moore EJ, Kern EB. Atrophic Rhinitis: A Review of 242 Cases. Am J Rhinol. 2001;15(6):355–361. PubMed.
Slow breathing physiology: Zaccaro A, Piarulli A, Laurino M, et al. How Breath-Control Can Change Your Life. Front Hum Neurosci. 2018;12:353. PubMed.
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