The role of the nose in the pathogenesis of obstructive sleep apnoea and snoring

Obstructive sleep apnoea syndrome (OSAS) is a common disorder affecting 2–4% of males and 1–2% of females in middle age 1, 2. It is caused by periodic reduction or cessation of airflow during sleep resulting from pharyngeal narrowing or collapse. Risk factors for OSAS in adults may include obesity, male sex, craniofacial dysmorphia, hypothyroidism and nasal obstruction 1, 3–5. The prevalence of snoring is high; 25–50% of middle-aged males are estimated to snore regularly 3, 6. Male sex, obesity, alcohol, sedatives, smoking and nasal obstruction are generally believed to be causative factors in the pathogenesis of snoring 3, 7–10.

Data from early physiological studies suggest that upper airway narrowing and consequent snoring and apnoea can be induced by subatmospheric nasal pressure 11, indicating the upper airway may resemble a Starling resistor with a collapsible segment in the oropharynx 12. If the pharynx indeed behaves as a true Starling resistor then it may be destabilised during sleep by the decreased pharyngeal luminal pressure associated with inspiratory nasal obstruction so that vibrations (snoring) and a partial collapse occur. In theory, inspiratory nasal obstruction would not provoke continuing collapse of the pharynx. This is because once there is no flow, upstream resistance becomes irrelevant, intrapharyngeal pressure returns to atmospheric, and the pharynx would re-open, a cycle generating snoring in theory but not apnoeas. However, it is unlikely that the pharynx does behave as a perfect Starling resistor, partly due to hysteresis and partly due to surface tension forces from mucus, which will tend to hold the pharynx closed once collapsed. Various observational and cross-sectional studies have documented a relationship between chronic nasal obstruction, snoring and obstructive sleep apnoea (OSA) 4, 5, 13, 14. Therefore, it seems reasonable to assume that nasal obstruction plays a role in the pathogenesis of snoring and, to some extent, OSA, and improved nasal patency might thus alleviate sleep-disordered breathing (SDB).

Recently, different interventional trials with randomised controlled design have been published on the topic and have added important new data. Therefore, the current authors have reviewed the literature to clarify the role of the nose in the pathogenesis of OSA and snoring. Findings from physiological, observational and cross-sectional studies concerning the relationship between the nose, snoring and OSA will be discussed before systematically reviewing randomised controlled interventional trials. Finally, a suggestion for future research in this field is given and the authors approach to patients with chronic nasal obstruction presenting in a sleep clinic is briefly described.

BASIC CONSIDERATIONS

The nose usually accounts for ∼50–60% of the total airway resistance, and the anterior part of the nose, including the nasal valve, contributes most to total nasal resistance (NR) in a normal nasal airway 15. The lumen of the nasal valve is modulated by the alar, procerus and compressor naris muscles, as well as by erectile mucosa. Other sites of nasal airflow resistance are the nasal vestibule and nasal turbinates. NR is predominantly influenced by mucosal swelling of the turbinates, which fill a large proportion of the nasal cavity. During exercise, sympathetic nasal mucosal vasoconstriction in the capacitance vessels can decrease NR markedly, similar to the effects of sympathomimetic medication, such as xylometazoline 16.

In up to 80% of healthy individuals, mucosal congestion undergoes a cyclical reciprocal change across the two sides of the nose every 0.5–10 h, known as the nasal cycle 17, 18. This cycle can be interrupted by a reflex mediated by pressure on the side of the chest wall 19–21, consequently in the decubitus position, thus the upper nostril becomes clearer and the lower more congested. Recent publications have documented the existence of the nasal cycle during sleep, but the physiological role remains largely unknown 22. NR is highly variable both over time 23 and during sleep 16, but its interaction with sleep architecture and SDB has not been investigated rigorously because convenient and unobtrusive measurement techniques have been lacking until recently 16.

In addition to the mechanism described above, nasal congestion increases on lying down due to a hydrostatic capillary pressure rise. These physiological effects may have important implications in the pathogenesis of OSA and snoring.

CLINICAL CONSIDERATIONS

Nasal obstruction may result from rhinitis and anatomic abnormalities. Primary anatomical abnormalities are septal deviation, nasal polyps and hypertrophied turbinates, among others. The most common rhinitis syndrome causing nasal obstruction is the allergic form, but a variety of nonallergic rhinitis types are recognised in clinical practice (table 1⇓) 24. Vasomotor rhinitis, in which no specific aetiology can be found, represents almost two-thirds of all cases of nonallergic rhinitis 25. Data from large epidemiological studies suggest that the prevalence of allergic rhinitis compared with nonallergic rhinitis is 3:1 26, 27.

Allergic rhinitis affects 9–42% of the population 24, and peak prevalence is found in early adulthood. It is caused by inhalation of airborne allergens resulting in production of immunoglobulin (Ig)E antibodies, which bind to IgE receptors on mast cells in the nasal mucosa and to basophils in the blood. As a consequence, mast cells release chemical mediators and cytokines that lead to inflammation of the nasal mucosa resulting in nasal congestion, sneezing, nasal pruritus and rhinorrhoea 28.

Data from epidemiological and physiological studies suggest that nasal congestion is a risk factor for snoring and OSA. Oral breathing during sleep has been shown to increase pharyngeal resistance and the propensity to OSA 29. Suratt et al. 30 induced obstructive apnoeas in eight normal males by occluding the nose with petrolatum gauze. Lavie et al. 31 investigated the influence of partial and complete obstruction of the nose in 10 normal subjects and found a significant increase in the number of apnoeas during sleep. Zwillich et al. 32 reported a loss of deep sleep stages and a two-fold increase in sleep arousals in 10 male subjects during an upper respiratory infection associated with nasal obstruction.

Based on the theory that nasal receptors are sensitive to airflow, and may have a reflex effect on ventilation and muscle tone in the upper airways, McNicholas et al. 33 found that ventilation was greater during obligate nasal breathing than during mouth breathing in normal subjects. These findings are supported in another study, which showed that resting breathing frequency and minute ventilation were also greater with nose rather than with mouth breathing in awake normal males 34.

Data from an electromyographic study in healthy males by Basner et al. 35 showed that upper airway tone is lower with oral breathing than nasal breathing, suggesting that upper airway dilating muscle activity may be modulated by receptors in the nasal mucosa sensitive to airflow or pressure. However, two other studies found that the breathing route did not influence electromyographic activity of genioglossus muscles in normal subjects, but other pharyngeal dilators were not studied 36, 37.

There is evidence from various observational and cross-sectional studies that objectively measured increases in NR 4, 5, 38 and allergic rhinitis 13, 39–41 are associated with OSA. Lofaso et al. 5 performed posterior rhinomanometry in 528 patients, and found higher NR in patients with OSA than in patients without OSA. In a large population-based study, Young et al. 13 identified chronic nasal congestion as a risk factor for OSA. Participants who reported nasal congestion due to allergic rhinitis were 1.8 times more likely to suffer from moderate-to-severe SDB than those without nasal congestion. However, there was no such association in participants with chronic night-time symptoms of rhinitis without allergy, and nasal airflow measured by rhinometry was not correlated with sleep apnoea.

Recent publications have suggested that daytime sleepiness in patients with allergic rhinitis is caused by disrupted sleep due to nasal congestion 42–45. There is evidence from three randomised controlled trials that intranasal steroids improve subjective daytime sleepiness in patients with chronic allergic rhinitis 42–44. Although these studies did not specifically include patients with OSA, and no data are given on snoring, the subjective improvement in daytime sleepiness provides an indirect suggestion that nasal congestion due to allergic rhinitis may lead to sleep fragmentation from OSA or snoring.

Snoring has been associated with chronic nasal congestion in multiple cross-sectional studies. Data from the Wisconsin sleep cohort study 14 showed that chronic rhinitis is an independent risk factor for snoring. Virkkula et al. 46 found that high NR was related to snoring in male subjects who were referred to an ear, nose and throat (ENT) hospital for evaluation of suspected SDB. NR was found to be a determinant of the frequency of snoring in a cross-sectional study including 361 snorers 47.

The potential effects of surgical treatment of chronic nasal obstruction on snoring and OSA have been investigated in various nonrandomised, uncontrolled trials 48–53. In an early study, Dayal and Phillipson 51 investigated the effect of nasal valve correction on snoring and OSA in six patients, and found significant improvement in snoring and apnoea/hypopnoea index (AHI) post-operatively. Fairbanks 52 found post-operative elimination of snoring in 77% of patients who underwent operative correction of nasal septum and turbinate deformity. Sériès and co-workers 49, 50 found that NR decreased (at 2–3 months) after surgical intervention to the nose (septoplasty, turbinectomy and polypectomy), which was associated with a decrease of AHI to <5 in patients with normal cephalometrics, but not in patients with abnormal cephalometrics. In the study by Friedman et al. 53, which included 50 patients with nasal airway obstruction and OSA, nasal surgery did not improve respiratory disturbance index and only 34% of the patients noticed an improvement in snoring. In the same study, continuous positive airway pressure (CPAP) pressure levels required to correct OSA decreased significantly after nasal surgery. However, in a recently published observational, uncontrolled, prospective study including 40 snoring males, operative treatment of nasal obstruction decreased NR but did not improve snoring, nocturnal breathing or sleep architecture 48.

Adenotonsillar hypertrophy is a frequent cause of OSA in children and may be associated with impaired nasal patency 54–56. Adenotonsillectomy has been shown to improve oxygen dip rate during sleep, sleep disturbance and multiple daytime symptoms compatible with sleep disturbance in a partially controlled trial including 61 snoring children 57. Mitchell and Kelly 58 found that children with severe OSA who undergo adenotonsillectomy show a significant improvement in respiratory disturbance index and quality of life after surgery, but OSA did not fully resolve in the majority of these children. Similarly, a recently published prospective survey of children with OSA submitted to adenotonsillectomy showed that almost 50% of the children still had abnormal polysomnography after surgery 59. It has to be mentioned that there is an absence of randomised controlled trials investigating the efficacy of adenotonsillectomy in the treatment of OSA in children 60.

SEARCH AND REVIEW METHODS FOR IDENTIFICATION OF RANDOMISED CONTROLLED STUDIES

Trials concerned with nasal conditions and SDB were identified by searches of bibliographic databases including EMBASE, PubMed, and hand-searching of respiratory journals. All abstracts found in the databases were assessed by two authors (M. Kohler and J.R. Stradling) to determine potential relevance for full review. Subsequently the full text of studies with randomised controlled (single- or double-blind) design including adults of either sex was reviewed. No restriction was placed upon the kind of intervention to the nose or the duration of the study.

THE AUTHORS’ CLINICAL APPROACH

Since the available evidence on the value of treating chronic nasal congestion in patients with OSA and snoring is limited, the current authors' clinical approach is outlined briefly in the following paragraph. Nasal congestion is a common complaint in patients with OSA and snoring, and can interfere with, or result from, CPAP usage; therefore, the history behind this symptom should be taken systematically. This might include questions concerning symptoms of allergic rhinitis, nonallergic rhinitis and other forms of chronic nasal obstruction, previous injuries or surgery, and nasal discharge, as well as the ability to breathe through the nose in the sitting and supine positions.

Inspection of the shape of the nose, checking the position of the nasal septum, and anterior rhinoscopy are sufficient to assess most anatomical causes of nasal obstruction. Objective measurement of NR by anterior or posterior rhinomanometry 70 on the awake patient, or during sleep with recently developed unobtrusive techniques 16, 71, 72, can be useful in selected patients, e.g. to monitor pharmacological treatment efficacy or to assess the outcome of surgical interventions.

In patients with allergic rhinitis, topical intranasal steroids (e.g. fluticasone and beclomethasone) should be prescribed as first-line therapy in addition to avoidance of allergens, and medication should be continued for ≥2–4 weeks before assessing treatment efficacy 73. An oral antihistamine or oral decongestant can be effective in treating symptoms of allergic rhinitis, but these medications may be associated with significant side-effects. Topical decongestant nasal sprays (e.g. oxymetazoline) can also reduce nasal congestion, but treatment duration is limited, as therapy lasting >5 days can lead to rebound nasal congestion 74.

In the case of nonallergic rhinitis, treatment of the underlying disease and avoidance of irritants is the mainstay of therapy. Patients with nonallergic rhinitis might also benefit from treatment with intranasal steroids or a locally applied antihistamine (e.g. azelastine), and if rhinorrhoea is a prominent symptom, ipratropium nasal spray is appropriate 73–76.

It must also be mentioned that about one-quarter of all patients with rhinitis have a mixed allergic–nonallergic variant 77, and symptoms of nonallergic rhinitis might be indistinguishable from those occurring in allergic rhinitis 24. Therefore, from the current authors’ point of view, a trial of intranasal steroids can be performed in all patients with characteristic symptoms of chronic rhinitis without specific IgE or skin testing. Whether these patients benefit from long-term topical steroid treatment, and whether this approach is cost-effective, remains to be proven.

Patients with chronic nasal obstruction often struggle to tolerate nasal CPAP. Humidification of inhaled air, correcting potential leakage of the nasal mask and a trial of a full-face mask are initial steps to dealing with this problem. Patients who still cannot tolerate CPAP, or have obvious nasal polyps, severe turbinate hypertrophy or a distinctive abnormality of the nasal anatomy should be referred to an ENT specialist for a surgical opinion.

PRIORITIES FOR FUTURE RESEARCH

Although some progress has been made in recent years in exploring the relationship between snoring, OSA and chronic nasal congestion, substantial areas of uncertainty remain. Many of the studies investigating this topic lack an appropriate sample size, carefully defined patient populations, objectively measured snoring variables and suitable techniques for the assessment of objective NR. Therefore, it is not surprising that conflicting findings have been reported in some of the recently published studies. From the current authors’ point of view, objective measurement of snoring, indices of SDB and NR are essential outcome variables in a randomised controlled trial investigating the role of the nose, since there is poor agreement between subjective assessment with questionnaires or visual analogue scales and objectively measured data during a sleep study 22, 78.

Possible strategies for future research could include large-scale randomised, controlled studies in carefully defined patient populations with OSA or snoring, and chronic nasal congestion, allowing identification of patients who benefit from either surgery or pharmacological treatment of the nose in the long term. In addition to the end-points of objectively measured snoring, indices of SDB and daytime sleepiness, such randomised controlled studies should perhaps include measurements of nocturnal NR due to the considerable variability of NR over time.

CONCLUSIONS

Data from epidemiological and physiological studies suggest that nasal congestion contributes to the pathogenesis of snoring and obstructive sleep apnoea. Randomised controlled trials that used nasal dilators, topically applied steroids and nasal decongestants to reduce nasal resistance are not sufficiently robust and showed only minor improvement of obstructive sleep apnoea symptoms and severity. Snoring was positively influenced by nasal dilators. Architecture and quality of sleep could be improved by treating nasal congestion, but clinical relevance remains to be proven. Although nasal surgery may be helpful in patients who are unable to tolerate continuous positive airway pressure because of nasal obstruction, this has never been proven in randomised, controlled trials. As there are no data from adequately designed and sized trials investigating the effect of nasal surgery on obstructive sleep apnoea or snoring, surgical intervention should be used within the context of a randomised controlled trial, or reserved for highly selected cases. Taken together, the current evidence suggests that the nose may not play a significant role in the pathogenesis of obstructive sleep apnoea, but it seems to be of some relevance in the origin of snoring, as might have been predicted based on the Starling resistor model of the pharynx discussed earlier.