HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Guest Access | Sign In via User Name/Password

This Article Abstract Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (22) Citing Articles via Google Scholar Google Scholar Articles by Rappai, M. Articles by deShazo, R. Search for Related Content PubMed PubMed Citation Articles by Rappai, M. Articles by deShazo, R.

The Nose and Sleep-Disordered Breathing^*

What We Know and What We Do Not Know

^* From the Divisions of Pulmonary/Critical Care Medicine (Dr. Rappai) and Allergy/Immunology (Drs. Kemp and deShazo), University of Mississippi Medical Center; Jackson, MS; and the Division of Pulmonary/Critical Care Medicine (Dr. Collop), Johns Hopkins University, Baltimore, MD.

Correspondence to: Nancy Collop, MD, FCCP, Division of Pulmonary/Critical Care Medicine, Johns Hopkins University DOM, 600 North Wolfe St, Blalock 910, Baltimore, MD 21287; e-mail: ncollop{at}aol.com

	Abstract

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 
The relationship between sleep-disordered breathing (SDB) and nasal obstruction is unclear. In order to better understand, we performed an extensive computer-assisted review and analysis of the medical literature on this topic. Data were grouped into reports of normal control subjects, patients with isolated nasal obstruction, and those with SDB. We conclude that SDB can both result from and be worsened by nasal obstruction. Nasal breathing increases ventilatory drive and nasal occlusion decreases pharyngeal patency in normal subjects. Nasal congestion from any cause predisposes to SDB. Although increased nasal resistance does not always correlate with symptoms of congestion, nasal congestion typically results in a switch to oronasal breathing that compromises the airway. Moreover, oral breathing in children may lead to the development of facial structural abnormalities associated with SDB. We postulate that the switch to oronasal breathing that occurs with chronic nasal conditions is a final common pathway for SDB.

Key Words: nasal obstruction • nose • obstructive sleep apnea syndrome • rhinitis • sleep-disordered breathing

	Introduction

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 
Sleep-disordered breathing (SDB) is common, afflicting as much as 2 to 4% of the population.¹ The most studied form, obstructive sleep apnea syndrome (OSAS), occurs most often in middle-aged men and obese individuals. Thus, risk factors for OSAS were originally thought to be morbid obesity and male gender. As our understanding of OSAS and other forms of SDB improved, other risk factors surfaced. These include central obesity, family history, smoking, alcohol consumption, menopause, ethnicity, and craniofacial abnormalities.² We have observed a number of patients in our pulmonary, allergy, and sleep medicine practices who have nasal disorders, including allergic rhinitis, in association with SDB. Since both nasal obstruction and SDB are common and occur together, we asked if there is a cause-and-effect relationship. In order to address this question, a brief review of the anatomy and physiology of the nose, nasal airway resistance, syndromes of rhinitis, as well as how they relate to disturbance of sleep seems appropriate.

	Literature Review

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 
Computer-based literature searches were used to identify all reports and reviews concerned with nasal conditions and SDB. These reports were read by the authors, reanalyzed, and grouped into those evaluating nasal-associated effects on SDB in normal control subjects, patients with nasal conditions or SDB, and children.

	Anatomy and Physiology of the Nose

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 
The nose is lined by pseudostratified epithelium resting on a basement membrane, separating it from deeper submucosal layers. The submucosa contains mucous, seromucous, and serous glands.³ The small arteries, arterioles, and arteriovenous anastamoses determine regional blood flow. Capacitance vessels, consisting of veins and cavernous sinusoids, determine nasal patency. Constriction and relaxation of these venous capacitance vessels is regulated by the sympathetic nervous system. The cavernous sinusoids lie beneath the capillaries and venules, are most dense in the inferior and middle turbinates, and contain smooth-muscle cells controlled by the sympathetic nervous system. Loss of sympathetic tone or, to a lesser degree, cholinergic stimulation causes this sinusoidal erectile tissue to become engorged. Cholinergic stimulation causes arterial dilation and promotes the passive diffusion of plasma proteins into glands and the active secretion by mucous glands in cells.

Novel neurotransmitters, including substance P, calcitonin gene-related peptide, and vasointestinal peptide, have been detected in nasal secretions after nasal allergen challenge of patients with allergic rhinitis.⁴ Antidromic stimulation of sensory nerve fibers in the nose can release a variety of neurotransmitters including substance P, a mediator of increased vascular permeability. Because neurotransmitters also produce changes in regional blood flow and glandular secretion, their role in rhinitis may be important.

	Origins of Nasal Resistance

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 
Nasal patency is predominantly controlled by changes in the capacitance vessels. Nasal airway resistance is responsible for approximately two thirds of the total airway resistance.⁵ Primary sites of nasal obstruction to airflow include the nasal vestibule, the nasal valves, and the nasal turbinates (Fig 1 ).

View larger version (33K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Cross-section of nasal cavity. Vest = nasal vestibule; NV = nasal valve; IT = inferior turbinate; MT = middle turbinate; ST = superior turbinate.

NR is greatest during infancy, decreases with age, and is primarily controlled by vascular engorgement in the middle and inferior turbinates.⁹ Exercise increases sympathetic discharge, which vasoconstricts the nasal capacitance vessels thereby decreasing nasal airflow resistance.^{10 11} Similarly, sympathomimetic medications, such as oxymetazoline, decrease nasal congestion via topical vasoconstriction.¹²

The physiologic variation in nasal patency, known as the nasal cycle, is mediated by changes in the engorgement of the submucosal capacitance vessels in the middle and lower turbinates. The magnitude of NR alternates between the two nasal cavities every 2 to 4 h in 60 to 70% of healthy individuals.^{11 13} Posture also influences the degree of vascular congestion. Nasal obstruction increases bilaterally as a subject assumes the supine position, and increases in the dependent nasal passage in the lateral recumbent position.¹⁴ This may have implications in the development of SDB in susceptible individuals.

	Clinical Syndromes Associated With Symptoms of Nasal Obstruction

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 
Symptoms of nasal obstruction include stuffiness, congestion, pressure, or difficulty breathing through one or both nasal passages. The nasal obstruction may result from a variety of anatomic abnormalities and rhinitis (Table 1 ).¹⁵ In rhinitis, symptoms result from dilation of venous capacitance vessels in the nasal submucosa, mucosal edema, and excess secretions.

Nonallergic rhinitis with nasal eosinophilia syndrome (NARES) occurs in as many as 15% of patients with rhinitis. It is characterized by perennial symptoms, an older average age than in patients with allergic rhinitis (39 years vs 25 years), and less nasal itching and sneezing.¹⁹ Formation of IgE to inhalant allergens is unusual. The clear nasal secretions contain > 25% eosinophils. Fifty percent of patients with NARES have sinusitis, 33% have nasal polyps, and 14% have asthma.

Vasomotor rhinitis is a common form of perennial nonallergic rhinitis associated with chronic nasal congestion intensified by rapid changes in temperature and relative humidity, odors, or alcohol consumption. Several lines of evidence suggest that symptoms result from nasal autonomic nervous system dysfunction. Patients have little nasal itching or sneezing and often no family history of allergy, but headaches, anosmia, and sinusitis are common. Positive immediate hypersensitivity skin test responses to inhalant allergens and nasal eosinophilia are unusual.

Atrophic rhinitis is a syndrome of progressive atrophy of the nasal mucosa in elderly patients who experience chronic nasal congestion and perceive a bad odor. Rhinitis medicamentosa develops after chronic use of vasoconstrictor nasal sprays or intranasal cocaine abuse; patients have chronic nasal obstruction and nasal inflammation manifest as beefy red nasal membranes on physical examination. Nasal obstruction may also be a side effect of antihypertensive drugs especially those with vasodilatory capacity. Rhinitis of pregnancy and rhinitis associated with birth control pills or hypothyroidism reflect nasal obstruction that occurs on a hormonal basis. The coexistence of nasal polyps with rhinitis suggests chronic sinusitis, aspirin hypersensitivity, coexistent allergic fungal sinusitis, or cystic fibrosis.

	Correlation of Nasal Obstruction With Symptoms and Measurement

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 
There are several clinical paradoxes concerning nasal obstruction. Symptoms of nasal obstruction often correlate poorly with actual resistance to airflow. For example, patients who have atrophic rhinitis following extensive turbinate resection may perceive nasal obstruction despite objective evidence of excellent nasal patency. Some patients may have significant nasal mucosal edema or nasal polyps but report no symptoms of nasal obstruction.¹⁵ The distribution of ventilation between mouth and nose in patients with allergic rhinitis may not correspond to the degree of nasal obstruction.²⁰ Mouth breathing, particularly in children, does not always signify severe nasal obstruction.²¹ Nasal congestion measured subjectively by symptom score or by direct visualization is imprecise.

The "sniff test" observation of a single forced inhalation through the nose is unreliable as a clinical method of assessing nasal airflow because of nares alar collapse in some patients¹¹ ; however, obstruction of nasal airflow is suggested on physical examination by audible nasal congestion as a patient inhales forcibly through the nose. The patency of each nasal passage may be assessed individually as the patient sniffs while the clinician compresses the contralateral nostril. Structural or dynamic assessment of nasal obstruction often clarifies the clinical impression or symptomatic report of nasal obstruction. A number of tests have been used to provide quantitative and qualitative data on nasal obstruction and nasal airflow. In order to interpret the literature of SDB, a review of these other tests is required.

	Assessment of Nasal Airway Structure

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 
Structural abnormalities of the nose may be evaluated objectively by clinical examination, fiberoptic rhinoscopy, rhinostereoscopy, or radiologic studies (CT and MRI). Details of the radiographic evaluation of the nose will not be reviewed here.

Fiberoptic rhinoscopy, the insertion of a flexible telescope into the nasal cavity, allows the detailed visualization of the posterior two thirds of the nose not visible with a nasal speculum inserted into the anterior nares. The procedure is generally well tolerated, and has particular clinical value when nasal obstruction is persistent or unilateral and whenever direct visualization of the nasal passages and the pharynx might facilitate diagnosis.^{22 23}

Rhinoscopy has limitations since it is unlikely to detect structural or mucosal displacement of the medial or lateral wall of the nasal valve < 1 mm, a distance that nonetheless may exponentially affect nasal resistance or patency. These changes in resistance and airflow are readily detectable by rhinomanometry^{24 25} or acoustic rhinometry (see below). Rhinostereoscopy uses a precise surgical microscope to make direct and noninvasive topographic measurements of the nasal mucosa. This technique is reviewed elsewhere.^{9 26}

	Assessment of Nasal Air Flow and Resistance

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 
Dynamic measurements of nasal congestion include nasal peak flow, rhinomanometry, and acoustic rhinometry. Each procedure has its limitations, but most have diagnostic sensitivities between 80% and 95% for nasal obstruction⁹ (Table 3 ).

Rhinomanometry
Since air flows from an area of high pressure to an area of low pressure, pressure gradients and flow measurements may be used to calculate NR. Rhinomanometry, the measurement of nasal airway resistance, is probably the test most frequently performed because it measures both flow and resistance. It is classically divided into passive or active phases, and into anterior or posterior rhinomanometry. Active rhinomanometry requires the subject to generate airflow through the nose by their own effort. Passive rhinomanometry utilizes external generation of a constant flow of air at a given pressure and requires no respiratory effort. Active rhinomanometry is a quick test to perform, and the International Committee on Standardization of Rhinomanometry recommends it for most studies.^{9 31} Anterior and posterior rhinomanometry primarily differ in the location of the transducer used to measure posterior pharyngeal pressure. Anterior rhinomanometry may be affected by deformation of the anterior nares and/or valves, nasal cycling, and by the instrument inserted to the nares for measurement.¹¹ Posterior rhinomanometry does not have these disadvantages, but is more expensive and requires more patient cooperation, with approximately 15% of subjects being unable to place the probe properly in the oral cavity.³² Despite these drawbacks, it is an excellent tool for determining the degree of airflow obstruction before and after surgical procedures and medical interventions (Table 4 ). It may also help to distinguish functional causes of upper airway obstruction from structural causes. For example, decongestants or exercise will improve airflow due to inflammation and vascular engorgement, whereas fixed abnormalities such as concha bullosa do not change after exercise or decongestants.³³ Rhinomanometric measurements before and after treatment with a potent intranasal decongestant agent are recommended.^{16 31}

Other Dynamic Methods To Measure Nasal Patency
Chilled mirrors or other polished surfaces have been used for more than a century to detect asymmetry in nasal expiratory airflow. The patient exhales through the nose against a polished surface held close to the nostrils, and dimensions of the two resulting areas of condensation are noted and compared. Camera recordings of thermographic surfaces or calibration by concentric markings on the condensing surface enhances this technique.²⁹

Oscillometry measures impedance in order to calculate NR. A loudspeaker is applied first to the nostrils and then to the mouth to generate sinusoidal oscillations that are superimposed on normal breathing. The difference between the two impedance measurements provides data for resistance calculations.³⁹

In summary, symptoms of nasal congestion often correlate poorly with actual resistance to airflow. Structural or dynamic assessment of nasal obstruction often clarifies the clinical impression or reported nasal symptoms. A number of diagnostic options are available. Fiberoptic rhinoscopy permits direct, three-dimensional visualization of the nasal passages, and is generally well tolerated. CT, MRI, and rhinostereoscopy (where available) provide greater structural detail.

Nasal congestion as evaluated by symptom score or by direct visualization is unreliable and highly variable. Measurement of nasal peak flow is inexpensive and has the potential advantage of permitting home assessment of nasal obstruction to airflow. It also may be more sensitive to mucosal changes than rhinomanometry.⁴⁰ An abnormal peak flow should prompt consideration of more detailed studies, such as rhinomanometry or acoustic rhinometry. Unlike nasal peak flow measurements, rhinomanometry is not effort dependent and measures nasal resistance as well as airflow. Rhinomanometry has been used previously to evaluate SDB (see below).

	SDB

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 
SDB is a spectrum of breathing abnormalities related to increased airway resistance that includes snoring, the upper airway resistance syndrome (UARS), and the OSAS. Snoring and OSAS are common. Snoring affects 19 to 37% of the general population and > 50% of middle-aged men.⁴¹ The estimated prevalences of OSAS in men and women are 9% and 4%, respectively.⁴² The prevalence of UARS in the adult general population is unknown, but has been estimated to be as high as 10 to 15% as defined by adults with snoring and excessive daytime sleepiness (EDS).⁴³

Snoring
Snoring is sound generated from the upper airway due to vibration of the uvula and soft palate. It occurs during inspiration, and rarely in expiration.⁴⁴ Snoring is associated with changes in the caliber of the upper airway, which reduces flow and increases airway resistance. These changes may not be significant enough to produce clinical symptoms or create disruption in sleep.⁴⁵ Snoring under these circumstances is termed primary snoring. When it occurs in conjunction with disordered sleep, it may be associated with symptoms that range from daytime sleepiness to severe OSAS with nocturnal hypoxemia and multiple cardiovascular effects.

Snoring and OSAS are thought to represent opposite ends of a continuum of SDB; however, snoring may actually represent a distinct comorbidity. Support for this concept is found in the characterization of sleep-related breathing disorders with clinically significant symptoms that occur in the absence of snoring.⁴⁶ To date, there has been no study that conclusively demonstrates an evolution from snoring to OSAS. Also, studies have shown improvement in snoring but not OSAS following upper airway surgery. These combined factors lend weight to the concept of snoring as a discrete condition, which may have additive or synergistic effects on SDB.

UARS
The UARS is characterized by sleep-related flow limitation and increases in upper airway resistance that precipitates arousals resulting in fragmented sleep and EDS.⁴⁷ By definition, these alterations occur without apneas or desaturations. This term was first applied to patients who had EDS defined by a shortened mean sleep latency on a multiple sleep latency test, without clear cause documented by overnight polysomnography.⁴⁸ These patients were assumed to have idiopathic hypersomnia. Utilizing "invasive polysomnography" with an esophageal pressure (Pes) transducer and full-face pneumotachograph increased upper airway resistance as demonstrated by increasingly negative inspiratory Pes in conjunction with reduced oral/nasal airflow.

UARS events are typically short (one to three breaths), with EEG arousals and immediate reduction in upper airway resistance after arousal. Such events are termed respiratory effort-related arousals. Generation of negative intrathoracic pressure seems to be the physiologic change that causes arousal. The mechanoreceptors associated with arousals may be located in the upper airway, as topical anesthetic applied to this area has been shown to create more negative Pes and to delay arousal times.^{49 50}

OSAS
Like UARS, patients with OSAS also display sleep fragmentation and EDS. The clinical manifestations are typically more severe and include both "hypopneas" in which there is partial collapse of the upper airway with either an arousal or oxygen desaturation for 10 s, or "apneas" resulting in complete collapse of the upper airway for 10 s. Oxygen desaturation in OSAS can be quite severe.

The primary site of airway collapse is the posterior pharynx, an area of minimal bony support, which relies on musculature for patency. Patients with OSAS have been shown to have smaller airways, but no particular minimal airway predictive volume of OSAS has been determined. Increased muscle tone during waking hours prevents obstruction while the subject is awake. Collapse occurs with the onset of sleep and relaxation of this support.⁵¹ The differences between gender, men having a higher prevalence than women particularly prior to female menopause, is thought to be related to less upper airway compliance (more rigidity) in women, perhaps an effect of female sex hormones.⁵² As the apnea continues, desaturation occurs, inducing hypoxemia, vasoconstriction of the pulmonary vascular bed, and increase in pulmonary artery pressures. Upper airway obstruction prevents inhalation but exhalation continues, further reducing lung volumes and worsening desaturation. Attempted inspiration against the obstruction further decreases intrathoracic pressure, which eventually triggers a central arousal⁵³ and stimulates the sympathetic nervous system. Heart rate and BP both rise in response,⁵⁴ and oxygen saturation improves but may not return to baseline before the next apneic episode.

Diagnosis of SDB
The diagnosis of SDB is usually based on overnight polysomnography, where a variety of physiologic parameters are monitored in an attended laboratory setting. These parameters typically include the following: EEG, electromyography (EMG) of chin and legs, electrooculography, nasal and oral airflow or pressure, chest and abdominal effort, ECG (lead II), and oxygen saturation. Some sleep laboratories also monitor snoring with a snore microphone, end-tidal carbon dioxide, EMG of the masseter muscle, and EMG of intercostal muscles. The patient will usually stay overnight in the sleep laboratory for a minimum of 6 to 7 h for data accumulation. The polysomnogram is then examined for sleep stages utilizing the EEG, electrooculography, and chin EMG channels; respiratory events utilizing the airflow or nasal pressure channel, effort channels, and oximetry; arrhythmias; and body movements. Arousals and awakenings from sleep are also quantitated. An arousal is scored when there is a shift in the EEG to an or rhythm for 3 s.⁵⁵ An awakening is scored when these or waves persist for > 15 s.

From these calculations, an assessment can be made as to the degree of sleep disruption that occurred during the study and the severity of SDB. Sleep disruption can be assessed in a number of ways, including the following: the arousal index (the number of arousals per hour of sleep), the number and frequency of sleep stage changes, the percentage of time spent in stage 1 (light sleep) or stage 0 (awake), the sleep efficiency (amount of time asleep divided by amount of time recorded), and the time spent awake after sleep onset. Most sleep laboratories calculate an apnea-hypopnea index (AHI) to assess SDB severity. This index is the number of apneic episodes plus the number of hypopneic events divided by the total sleep time as measured in hours. An AHI > 5 is considered abnormal. Decisions about treatment revolve around the degree of SDB and the amount of sleep disruption.

	Relationships Between the Nose and SDB

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 
Only a few studies have examined the relationship of increased NR and SDB. Anecdotal evidence for a relationship between nasal obstruction, impaired sleep, memory loss, and excessive daytime somnolence were first noted in the 1800s (Table 5 ).^{56 57} These observations triggered other studies evaluating the relationship of the nose and SDB. These studies will be reviewed here by the different patient populations studied: normal control subjects, patients with increased NR, patients with SDB including snorers, and children.

These findings were supported in another study,⁶³ which measured minute ventilation during obligate nasal or mouth breathing in normal subjects during sleep. Ventilation was greater with the nasal breathing, supporting the notion that nasal airflow has a stimulant effect on breathing. Centrally controlled airway tone (phasic activity) of the upper airway is higher with nasal breathing than oral breathing.⁶⁴

Another study⁶⁵ examined the effects of topical vasoconstrictors on sleep. Phenylephrine sprayed into the nasopharynx and oropharynx decreased both NR and pharyngeal resistance in normal subjects. The decrease in pharyngeal resistance was independent of the change in NR and upper airway muscle activity, suggesting that the decrease was a direct effect of phenylephrine on the pharyngeal mucosa; therefore, vasoconstriction of the tissues of the nasopharynx does not have a significant effect on the patency of the pharyngeal airway in normal subjects.

Several studies have investigated the effects of experimental nasal occlusion on sleep in normal subjects (Table 6 ). In four of five such studies,^{66 67 68 70} nasal occlusion was induced immediately prior to sleep. In the other study,⁶⁹ nasal occlusion was induced during the entire day prior to, and during, the sleep study. The participants in all these studies had disturbed sleep as manifested by increased arousals and/or awakenings, frequent sleep stage changes, and less stage III and IV sleep. In those studies that monitored for SDB, participants also had increased SDB with apneas and/or hypopneas associated with EEG arousals.

Patients With Abnormal NR
Several reports evaluated the effects of increased NR secondary to an anatomic obstruction or to nasal inflammation like that seen in allergic rhinitis. Increased NR (using a pediatric feeding tube to measure transmural pressure) in awake, upright subjects was not predictive of SDB in 683 patients referred for evaluation of SDB⁷² ; however, epidemiologic studies⁷³ of middle-aged adults have shown that complaints of nasal congestion, particularly nocturnal nasal congestion, are a strong independent risk factor for habitual snoring. Similarly, patients with complaints of nasal congestion due to allergy have been reported to be 1.8 times (odds ratio) more likely to have moderate-to-severe SDB compared to those without symptomatic nasal congestion.⁷⁴ This group of articles suggests that the presence of nasal congestion may predispose patients to OSAS even though actual measurements of NR are not abnormal.

Two studies^{70 76} evaluated patients with anatomic nasal obstruction before and after surgery for nasal septal deviation. These patients consistently exhibited a worsening of sleep quality, increased SDB, and frequent oxygen desaturation postoperatively compared to preoperatively, in association with the attendant nasal packing. Short-term packing of the nose therefore can clearly result in SDB. It cannot be determined from this short-term trial whether this effect would continue over time if nasal obstruction persisted or if adaptive changes would occur.

The chronic eosinophilic mucosal inflammation associated with allergic rhinitis results in nasal obstruction and increased NR. Although clinicians are aware that allergic rhinitis results in sleep disruption and fatigue, there are few studies investigating its role in SDB (Table 7 ). Two studies^{77 78} showed that exacerbations of allergic rhinitis cause an increase in SDB and sleep disruption. A third, placebo-controlled study⁷⁹ showed treatment of allergic rhinitis with nasal steroids resulted in significant subjective improvement in sleep quality.

Patients With SDB
The studies in this section will deal with SDB in the form of snoring, UARS, and OSAS. Some of the studies chose to specifically differentiate these types of SDB and are noted with such designations herein.

In one study mentioned above,⁷² there was no correlation between upright, awake NR and the degree of SDB in patients referred for SDB.⁷² A second study⁸³ measured NR in 36 patients with OSAS using basal anterior active rhinomanometry in both upright and supine positions, and found 7 of 36 patients with abnormal upright NR, 9 of 36 patients with a normal upright but abnormal supine NR, and 20 of 36 patients with normal NR in both positions. There was no correlation between NR and AHI; however, two other studies^{84 85} compared patients with either snoring or OSAS to normal subjects and found higher levels of NR in the SDB group as measured by rhinomanometry. In one study, the patients with SDB (both snorers and OSAS) switched from nasal to oronasal breathing during sleep more frequently.⁸⁴ The change to oronasal breathing has been postulated to increase the work of breathing and peripheral pulmonary resistance by triggering the "nasal-pulmonary" reflexes, and the end result is alveolar hypoventilation.⁸⁶ A study⁸⁷ of nasal flow volume loops in a group of patients with OSAS showed that the area under the flow volume loop independently contributed to the prediction of AHI as compared to normal subjects. These studies suggest that although the degree of NR is not predictive of SDB, the presence of increased NR may result in a switch to oronasal breathing during sleep, which further compromises the airway and increases work of breathing.

Nasal inflammation has been shown to be present in patients with OSAS compared to control subjects, as measured by nasal lavage before and after sleep. Increased numbers of cells, specifically neutrophils, and increased concentration of bradykinin-like and vasoactive intestinal peptide-like immunoreactivity were found in the absence of symptoms of rhinitis⁸⁸ ; therefore, patients with SDB but without obvious symptoms of rhinitis may have increased concentration of inflammatory mediators in the nose.

Perhaps the best way to examine the role of NR in patients with SDB is to reduce the resistance and examine the effect on sleep and breathing. This has been done in a variety of ways. Mechanical nasal dilators are marketed to relieve snoring, and have been shown to have a similar effect on NR as measured by active posterior rhinometry as a topical decongestant (fenoxazoline hydrochloride).⁸⁹ Their effect on snorers without significant nasal pathology is unclear, as some studies⁹⁰ failed to demonstrate changes in SDB events or arterial oxygen saturation levels, while others⁹¹ showed improvement in sleep quality, ease of breathing, and a decreased intensity of snoring. In patients with OSAS, one study⁹² showed that only 4 of 21 patients with moderate-to-severe OSAS had a significant reduction in SDB events, while another study⁹³ showed no significant change in SDB events in a group of patients with UARS. It appears that the overall effect on SDB with mechanical nasal dilators is likely small and inconsistent.

Dental prostheses have been used to treat all forms of SDB. These devices keep the upper and lower jaws opposed during sleep and advance the mandible forward. This prevents posterior movement of the mandible during sleep and increases nasal breathing. When evaluated in a group of snoring patients without symptoms of OSAS, one type of prosthesis did not alter the frequency or intensity of snoring or sleep quality or oxygen saturation despite decreasing SDB events⁹⁴ ; from this one small study, it does not appear dental prostheses improve SDB by any effect on the nasal airway.

Reducing NR by surgical correction of nasopharyngeal anatomic obstruction has been examined by a number of investigators (Table 8 ). Surgical approaches have included correction of the nasal valve area, septoplasty, and turbinate reduction. Only one small study⁹⁵ (n = 6, no control subjects) examined the effect of correction of nasal valve obstruction, showing both subjective and objective improvement in snoring and daytime somnolence. Two uncontrolled studies^{96 98} in patients with nasal obstruction showed that septoplasty or turbinate reduction had some positive effects on SDB. In one study,⁹⁶ 77% (47 of 113 patients) who snored had improvement or elimination of snoring postoperatively. The second study⁹⁸ involved patients with mild OSAS where cephalometrics (measurements made from a standardized lateral head radiograph) were performed preoperatively; patients with abnormal cephalometrics (increase in mandibular plane to hyoid, decreased posterior airspace, retroposition of mandible, or length of soft palate), implying a skeletal anatomic defect, did not respond to improvement of their nasal airway. In a study⁹⁹ of a diverse group of adults (n = 94) and children (n = 55) with SDB, who had a variety of surgical procedures (including uvulopalatopharyngoplasty, midline laser glossectomy, and nasal surgery), significant improvement (defined as 75% reduction in AHI or a postoperative AHI < 10) occurred in only 48% of adults.

It appears from this group of surgical series that surgical improvement of the nasal airway may be most effective to improve SDB in those patients without skeletal anatomic abnormalities. Surgery also often improves snoring and decreases CPAP levels in patients with an abnormal nasopharynx.

Children
A number of common features of childhood predispose to SDB. Allergic rhinitis is common in children, as is adenoidal and tonsillar hypertrophy. The latter is the leading cause of SDB in children, and corrective surgery is usually curative.¹⁰² Nasal obstruction secondary to adenoidal enlargement may result in changes of the craniofacial structures during growth and development. These latter effects may have long-lasting consequences on craniofacial structures, and we postulate that they may predispose to SDB.

Epidemiologic studies have shown that children with habitual snoring frequently have allergies. Allergic sensitization, as assessed by radioallergosorbent test, has also been associated with increased prevalence of OSAS.¹⁰³ At least one study¹⁰⁴ has shown that treatment of allergic rhinitis in children with nasal steroids decreases SDB events without any change in adenoidal or tonsillar size. The long-term effects of allergic rhinitis on adenoidal and tonsillar size are unknown.

Adenotonsillectomy results in marked improvement of SDB in > 80% of children.¹⁰² One study¹⁰⁵ showed that children with SDB have larger adenoids and tonsils (as measured by cephalometrics) than age-matched control subjects; interestingly, skeletal abnormalities appeared to also play a role, particularly in older children ( 5 years old). These children had more protrusion of the maxilla (as measured by the angle measured from the sella to the nasion to subspinale; Fig 2 ). This suggests that adenoidal hypertrophy is a major factor for SDB in younger children (aged 1 to 4 years), in contrast to older children, where adenoidal hypertrophy and bony changes combine to increase risk. Another controlled study¹⁰⁶ in which cephalometrics were performed on children showed that the angle measured from the sella to the nasion to the supramentale and hyoid position was significantly less in SDB children than control subjects, even at an early age, and did not improve with aging. The authors suggested that genetic factors governing facial bone development may play a role in retrognathia in children with SDB. These skeletal changes often give a child a characteristic facial appearance, sometimes called adenoid faces. These children have a long, narrow face, a short upper lip, prominent upper incisor teeth, a high arched palate, and lips-apart mouth breathing.

View larger version (30K): [in this window] [in a new window] [Download PPT slide]   Figure 2. Cephalogram showing bony angles. S = sella; N = nasion; A = subspinale; B = supramentale.

In children, obstruction of the upper airway by enlarged tonsils and adenoids clearly plays an important role in the pathophysiology of SDB, and may lead to growth characteristics of the bony structures that predispose to upper airway obstruction later in life. The association between SDB and allergic rhinitis appears strongest in children.

	Conclusion

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 
SDB appears to result from several common pathways, including anatomic and neuromuscular abnormalities of the upper airway. Our review provides convincing evidence that there is an association between SDB and nasal obstruction. Available data suggest that nasal obstruction resulting from allergic rhinitis may precipitate SDB, at least in the short term.^{77 78 79} Unfortunately, to date, there are no compelling data to demonstrate specific causality between nasal obstruction and persistent SDB. Most of the studies reviewed herein are either short-term, used odds ratios, or only examined subjective measures to analyze the effect on SDB. Clearly, further studies are needed to prove specific causality.

Future Directions
Several theories have tried to explain the relationship between SDB and nasal obstruction. Of these, the following theories are most credible: (1) the switch from nasal to oronasal breathing (due to nasal obstruction) causes loss of nasal airflow resulting in decreased nasal receptor-derived stimulation of ventilation and changes in phasic activity leading to decreased upper airway patency; and (2) the increased nasal airway resistance (due to nasal obstruction) generates an increased negative inspiratory force/pressure causing turbulence in the relaxed soft tissues and upper airway collapse (retropharyngeal) resulting in upper airway obstruction and SDB.

These hypotheses are based on a few studies that have used varying methods and small numbers of study subjects and therefore require further confirmation. If this is found to be true, technologies and treatments aimed at facilitation of nasal breathing should be explored further in the context of SDB. In the interim, use of topical nasal steroids in patients with SDB and preferential use of nasal CPAP in treatment may be reasonable.

Longitudinal studies in children with nasal obstruction are required to determine the risk factors for SDB, including the relationship of nasal obstruction to structural abnormalities of the face and upper airway. It is possible that certain congenital variations in facial structures are deleterious to nasal breathing and exacerbated by nasal obstruction from other causes. Knowledge of these factors could be useful in preventing the development of SDB.

The effect of CPAP on the nasal airway is relatively unexplored. Anecdotally, it appears that CPAP may increase nasal inflammation and, in some, promote vasomotor rhinitis. It is possible this may lead to decreased adherence to treatment. This is another area in need of further research.

	Acknowledgements

 
The authors thank Rosemary Hoffman, PhD, for editorial assistance.

	Footnotes

 
Abbreviations: AHI = apnea-hypopnea index; CPAP = continuous positive airway pressure; EDS = excessive daytime sleepiness; EMG = electromyography; NARES = nonallergic rhinitis with nasal eosinophilia syndrome; NR = nasal resistance; OSAS = obstructive sleep apnea syndrome; Pes = esophageal pressure; SDB = sleep-disordered breathing; UARS = upper airway resistance syndrome

Received for publication September 11, 2002. Accepted for publication February 28, 2003.

	References

TOP Abstract Introduction Literature Review Anatomy and Physiology of... Origins of Nasal Resistance Clinical Syndromes Associated... Correlation of Nasal Obstruction... Assessment of Nasal Airway... Assessment of Nasal Air... SDB Relationships Between the Nose... Conclusion References

 

1. Young, T, Palta, M, Dempsey, J, et al (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328,1230-1235[Abstract/Free Full Text]
2. Davies, R, Stradling, J The epidemiology of sleep apnea. Thorax 1996;51(suppl 2),S65-S70
3. Ayars, G Nonallergic rhinitis. Immunol Allergy Clin North Am 2000;20,283-302[CrossRef]
4. Christodoulopoulos, P, Cameron, L, Duraham, S, et al Molecular pathology of allergic disease: II. Upper airway disease. J Allergy Clin Immunol 2000;105,211-223[CrossRef][ISI][Medline]
5. Ferris, B, Mead, J, Opie, L Partitioning of respiratory flow resistance in man. J Appl Physiol 1964;19,653-658[Abstract/Free Full Text]
6. Kasperbauer, JL, Kern, EB Nasal valve physiology: implications in nasal surgery. Otolaryngol Clin North Am 1987;20,699-719[ISI][Medline]
7. Cole, P, Haight, J, Cooper, P, et al A computed tomographic study of nasal mucosa: effects of vasoactive substances. J Otolaryngol 1983;12,58-60[ISI][Medline]
8. Cole, P Physiology of the nose and paranasal sinuses. Gershwin, ME Incaudo, GA eds. Diseases of the sinuses 1996,33-51 Humana Press. Totowa, NJ:
9. Dunagan, D, Georgitis, J Intranasal disease and provocation. Kemp, S Lockey, R eds. Diagnostic testing of allergic disease 2000,151-173 Marcel Dekker. New York, NY:
10. Raphael, G, Baraniuk, J, Kaliner, M How and why the nose runs. J Allergy Clin Immunol 1991;87,457-467[CrossRef][ISI][Medline]
11. Schumacher, M Rhinomanometry. J Allergy Clin Immunol 1989;83,711-718[CrossRef][ISI][Medline]
12. Naclerio, R Allergic rhinitis. N Engl J Med 1991;325,860-869[ISI][Medline]
13. Heetderks, D Observations on the reaction of normal nasal mucous membrane. Am J Med Sci 1927;174,231-238
14. Haight, J, Cole, P Unilateral nasal resistance and asymmetrical body pressures. J Otolaryngol 1986;Suppl 16,1-31
15. Hollingsworth, H, Irwin, R Nasal obstruction, rhinorrhea, and postnasal drip. Irwin, R Curley, F Grossman, R eds. Diagnosis and treatment of symptoms of the respiratory tract 1997,523-556 Futura. Armonk, NY:
16. Diagnosis and management of rhinitis: complete guidelines of the Joint Force on Practice Parameters in Allergy, Asthma Immunology. Dykewicz, MS Fineman, S eds. Ann Allergy Asthma Immunol 1998;81,478-518[ISI][Medline]
17. Ray, N, Baraniuk, J, Thames, M, et al Direct expenditures for the treatment of allergic rhinoconjuctivitis in 1996, including the contributions of related airway illness. J Allergy Clin Immunol 1999;103(3 pt 1),401-407[CrossRef][ISI][Medline]
18. Skone, B Allergic rhinitis: definition, epidemiology, pathophysiology, detection and diagnosis. J Allergy Clin Immunol 2001;108,52-58[CrossRef][ISI][Medline]
19. Settipeane, R, Lieberman, P Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 2001;86,494-507[ISI][Medline]
20. Chowanetz, W, Schott, J, Jany, B Nasal admixture during mouth breathing in awake normal subjects. Bull Eur Physiopathol Respir 1987;23,125-130[ISI][Medline]
21. Chadha, T, Birch, S, Sackner, M Oronasal distribution of ventilation during exercise in normal subjects and patients with asthma and rhinitis. Chest 1987;92,1037-1041[Abstract/Free Full Text]
22. Dolen, W, Selner, J Endoscopy of the upper airway. Middleton, E Reed, C Ellis, Eet al eds. Allergy: principles and practice 5th ed. 1998,1017-1023 Mosby-Year Book. St. Louis, MO:
23. Druce, H, Ledford, D Fiberoptic rhinoscopy. Kemp, SF Lockey, RF eds. Diagnostic testing of allergic disease 2000,233-245 Marcel Dekker. New York, NY:
24. Chaban, R, Cole, P, Naito, K Simulated septal deviations (2). Arch Otolaryngol Head Neck Surg 1988;114,413-415[Abstract]
25. Cole, P, Chaban, R, Naito, K, et al The obstructive nasal septum: effect of simulated deviations on nasal air-flow resistance. Arch Otolaryngol Head Neck Surg 1988;114,410-412[Abstract]
26. Juto, J, Lundberg, C An optical method for determining changes in mucosal congestion in the nose in man. Acta Otolaryngol 1982;94,149-156[Medline]
27. Cho, S, Hauser, R, Christiani, D Reproducibility of nasal peak inspiratory flow among healthy adults: assessment of epidemiologic utility. Chest 1997;112,1547-1553[Abstract/Free Full Text]
28. Wilson, A, Dempsey, O, Sims, E, et al Evaluation of treatment response in patients with seasonal allergic rhinitis using domiciliary nasal peak inspiratory flow. Clin Exp Allergy 2000;30,833-838[CrossRef][ISI][Medline]
29. Cole, P, Roithmann, R Rhinomanometry. Gershwin, ME Incaudo, GA eds. Diseases of the sinuses 1996,451-468 Humana Press. Totowa, NJ:
30. Holmstrom, M, Scadding, G, Lund, V, et al Assessment of nasal obstruction: a comparison between