Sleep apnea–hypopnea syndrome (SAHS) is characterized by complete or partial obstruction of the upper airway while the patient is asleep, accompanied by oxyhemoglobin desaturation or micro-awakenings. SAHS is associated with a higher risk of cardiovascular disease, arterial hypertension, neurocognitive changes and death.1 Continuous positive airway pressure (CPAP) is the treatment of choice in most patients with moderate-severe SAHS, and helps control the disease, improves quality of life and reduces morbidity and mortality.2

Treatment must be applied continuously to be effective, but adverse reactions mean that mid-term compliance is only achieved in 60% of patients.3 CPAP tolerability and compliance studies have shown varying results.4 Lack of compliance has been associated with mask discomfort, feeling of claustrophobia, noise disturbance, nasal inflammation, pharyngeal dryness, eye symptoms, non-specific ear discomfort, sleepiness or excessive fatigue.5,6 The patient's psychological profile must also be taken into account, and educational and behavioral support play an important role in improving tolerability and compliance.7,8

CPAP-related rhinitis is a significant problem, but it is not always associated with poorer compliance.9 We hypothesized that an in-depth study of changes occurring in the eyes, nose and throat (ENT) of patients receiving CPAP treatment could lead to the detection and early treatment of potential patients with bad adherence, and that personalized medicine in these cases will optimize management.

Our objective was to analyze changes occurring in the nostrils of SAHS patients with no previous nasal pathology after the introduction of CPAP, and the impact on treatment compliance.

A total of 41 consecutive CPAP candidates with a diagnosis of SAHS were included. Five were excluded after the initial evaluation when exclusion criteria were detected. Of the remaining 36 (31 men and 5 women with a mean age of 55.72±9.50 years), only 31 completed the 2-month study (Fig. 1). Twenty of these were partients with good adherence and 11 were patients with bad adherence.Results of variables before and after CPAP are described in Table 2. A significant improvement in daytime sleepiness (P=.000), anxiety (P=.006), and depression (P=.023) was observed. Nasal dryness (P=.000) and elevated neutrophils in nasal cytology (P=.000) were also detected. No significant differences were found among the other variables.

Fig. 1.

Patient disposition.

*Includes full medical history, body mass index, head circumference, otoscopy and flexible fiberoptic nasal endoscopy.

**Includes standardized symptom and quality of life questionnaires, audiometry, impedanciometry, rhinomanometry, saccharin test, nasal curettage, and nasal cavity computed tomography.

AHI: apnea–hypopnea index; CPAP: continuous positive airway pressure; ENT: eyes, nose and throat; h/d: hours/day; m: months.

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Partients with good adherence (Table 3) showed a more significant improvement on the Epworth test (P=.000), and anxiety (P=.052) and depression (P=.054) showed a clear trend toward improvement. Surprisingly, partients with good adherence had a higher rate of nasal dryness (P=.001), higher neutrophil levels in nasal cytology (P=.002), tended to have worsening mucociliary clearance (P=.050), and blood eosinophils were higher (P=.058) but within normal limits (<5%).

Patients with bad adherence only showed worsening body pain (P=.046).

In the univariate study (Table 4), daytime sleepiness was the only predictive factor for non-compliance (P=.014), and a trend toward poorer compliance was also observed in patients with poorer general health status (P=.059) and better CT 90 (P=.064). In the multivariate analysis, a higher Epworth score was the only independent factor for non-compliance (odds ratio: 1.243; confidence interval: 1.000–1.545]; P<.050).

The results of this study are surprising and diverge from the proposed hypothesis by showing that while CPAP improves sleepiness and anxiety-depression, it causes, particularly in partients with good adherence, rhinitis, airway dryness, and slower mucociliary clearance. No significant changes were found in other study variables. The only prognostic factor for intolerance was initial sleepiness; none of the ENT variables were prognostic of this outcome.

Some authors consider that the main cause of CPAP intolerance is treatment-related rhinitis, but the published results vary widely. Others have evaluated if patients with CPAP-associated rhinitis improve if the rhinitis is treated, but results were unsatisfactory.24 We were unable to find any evidence that CPAP administered in patients without previous disease causes clinically significant rhinitis, or if this was a reason for therapeutic non-compliance. Nor did we observe any improvement in nasal symptoms in compliant patients.

Previous studies have evaluated the appearance or increase of neutrophils and/or other inflammatory cells in the nasal cytology of patients and CPAP animal models. Again, results varied.25,26 Other authors described specific mediators of nasal inflammation.27 It seems likely that the flow of dry air would stimulate nerve endings to release inflammatory cell mediators28 that could stimulate the secretion of neuropeptides,29 recruiting the neutrophils, thus explaining increased nasal mucosa in CPAP patients.

In a mouse model study performed in our hospital, we showed neutrophilic inflammation after acute application of CPAP.30 Lacedonia et al.,26 however, did not observe any increase in neutrophils in the nasal mucosa of patients receiving CPAP, although nearly all their subjects had elevated neutrophil levels before starting the intervention, suggesting previous nasal pathology. Moreover, in a study recently published by Gelardi et al., the continuous use of CPAP was found to improve rhinitis in SAHS patients, reducing the number of inflammatory cells in nasal cytology.31

In this study, we have confirmed the presence of nasal inflammation, and found it to be more marked in partients with good adherence. Although our results support the presence of nasal cell inflammation, it seems to be generally subclinical if other variables are taken into account. It would be interesting to evaluate if an adaptive phenomenon occurs over time, with improved inflammatory infiltrate, or if, in contrast, inflammatory infiltrate worsens, leading to exacerbation of symptoms.

Assuming that CPAP causes nasal inflammation, this might be reflected in hypertrophy of the mucosa of the nasal cavity causing a reduction of the nasal air space. In our study, analysis of the nasal cavity air volume by CT did not show any significant differences after CPAP. This finding, previously described by Weerdt et al.,32 would suggest that inflammation is mild-moderate. Nasal patency, measured clinically and by rhinomanometry, was not significantly altered in our study, coinciding with Skoczinski et al.,33 who reported that CPAP does not cause nasal obstruction, nor is nasal obstruction a predictive factor for lack of compliance.

Some series have found that nasal dryness affects more than 60% of CPAP patients. We also found this to be true, but it did not interfere with treatment compliance. Humidifiers are usually used to treat dryness, but while they improve symptoms, they do not always improve tolerance or compliance.34,35

In our series, we observed a trend toward worsening mucociliary clearance in partients with good adherence only. This would suggest that changes in mucociliary clearance are due to a time-dependent phenomenon. Similar studies in the literature show contradictory results,36,37 but these did not evaluate the degree of compliance nor mean CPAP pressure.

CPAP obviously provokes an unusual situation of positive pressure within the rhinopharyngeal and oropharygeal cavities.38 This might increase pressure in the middle ear, causing various kinds of symptoms in the ear; some studies even propose CPAP as a possible treatment for ears with mean negative pressures.39,40 However, our results are in line with those of Aksoy et al.,41 who found no significant differences in middle ear pressure. Our auditory assessments, also in line with previous studies,42 revealed no significant auditory changes after treatment.

In conclusion, CPAP treatment can be generally said to improve a series of clinical parameters, but it causes rhinitis and nasal dryness. The various ENT variables analyzed do not differ greatly between partients with good adherence and patients with bad adherence, and none of them predicts the degree of compliance. Initial sleepiness is the only predictive factor for poor compliance.

The importance of this study is that it is the first to question the generalized impression that adverse ENT effects caused by CPAP impact compliance. There is a need for more larger, randomized, translational studies that also include patients with prior nasal pathology, to clarify the relationship between CPAP and nasal pathology in SAHS patients receiving CPAP.

Grant FISSPI07/0318.

Francina Aguilar and Ariel Cisternass: study design. Patient visits, ENT examinations, nasal cytology and saccharin test. Coordination of additional tests in all patients, pre- and post-CPAP. Data collection and database construction. Statistical analysis and drafting the manuscript.

Antonio Manuel Ávila and Juan Berenguer: study and calculation of nasal cavity volumes pre- and post-CPAP in all patients and critical review of the manuscript.

Isabel Vilaseca: study design. Clinical follow-up, statistical analysis and drafting the manuscript.

Alejandro Iranzo: patient diagnosis and follow-up and critical review of the manuscript.

Josep Maria Montserrat: patient diagnosis and follow-up and critical review of the manuscript

Marta Torres-López: cytology study and critical review of the manuscript.

The authors state that they have no conflict of interests.