Nasal symptoms in patients with obstructive sleep apnea and their impact on therapeutic compliance with continuous positive airway pressure F. Lasters1, C. Mallegho1, A. Boudewyns1,2, O. Vanderveken1,2, T. Cox1,3, K. Ketelslagers3, J. Verbraecken1,4 1

Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium, 2Department of Otorhinolaryngology, Head and Neck Surgery, Antwerp University Hospital, Edegem, Belgium, 3Department of Otorhinolaryngology, Head and Neck Surgery, Jessa Hospital, Hasselt, Belgium, 4Department of Pulmonary Medicine and Multidisciplinary Sleep Disorders Centre, Antwerp University Hospital, Edegem, Belgium Continuous positive airway pressure (CPAP) is the first line treatment for moderate to severe obstructive sleep apnea syndrome. Despite the high effectiveness of this treatment, its use is often limited by suboptimal compliance and/or intolerance. Nasal side effects are considered a major cause of low therapeutic compliance. At present, there are no data to predict which patients will develop CPAP intolerance caused by nasal symptoms and only few studies looked at the effect of treatment of nasal symptoms on CPAP compliance. The first section of this review focuses on the impact of nasal symptoms (pre-existing or as a side effect of CPAP) on CPAP compliance/intolerance. The second section deals with the effect of nasal symptom treatment on CPAP compliance.

Keywords: Continuous positive airway pressure, Obstructive sleep apnea syndrome, Treatment compliance, Nasal symptoms

Introduction Obstructive sleep apnea syndrome (OSAS) is characterized by repetitive episodes of upper airway obstruction accompanied by arousal and/or oxygen desaturation.1 The main features of OSAS include loud snoring, excessive sleepiness and non-restorative sleep. The diagnosis is made by polysomnography and the severity is expressed in the apnea hypopnea index (AHI). An AHI >5/hour or sleep and complaints of hypersomnia during the daytime indicate sleep apnea syndrome.1–4 The prevalence of OSAS is 4% in males and 2% in females.5,6 Obesity plays an important role in OSAS as approximately 70% of OSAS patients are obese.7 General measures, such as weight reduction and smoking cessation, form the basis of a successful treatment. Continuous positive airway pressure (CPAP) is the standard treatment for moderate to severe OSAS.8 Continuous positive pressure acts as a pneumatic splint that prevents the upper airway to collapse. This positive pressure can be applied by a

Correspondence to: J. Verbraecken, Department of Pulmonary Medicine and Multidisciplinary Sleep Disorders Centre, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium. Email: [email protected]

ß Acta Clinica Belgica 2014 MORE OpenChoice articles are open access and distributed under the terms of the Creative Commons Attribution License 3.0 DOI 10.1179/0001551214Z.00000000028

nasal, oral or oronasal mask.9 CPAP is not the only treatment modality for OSAS. Use of a mandibular repositioning device and surgery are also valid treatment modalities in selected patients.10,11

Methodology In order to retrieve relevant information on nasal obstruction and CPAP intolerance, predictive factors for CPAP intolerance and the influence of treatment on CPAP intolerance, the authors conducted a systematic review in the database of PubMed. The authors independently searched PubMed for relevant articles. The limits used in PubMed were: English or Dutch, humans, RCT, meta-analysis and 5 years. Papers were selected based upon one or more of the following key features: diagnosis of OSAS, nasal obstruction, CPAP intolerance and/or nasal resistance (NR) and effect of treatment. Diagnosis of OSAS had to be confirmed by polysomnography with an AHI >10/hour. The first screening of the articles was based on the title. Hereafter, the abstracts of the possible relevant articles were independently evaluated. At last, the articles were fully analyzed. Of the initial 92 articles found, only 35 articles matched our inclusion criteria.

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CPAP Compliance For a regular user, compliance to CPAP therapy is defined as CPAP usage for >4 hours for 70% of the nights.12 Two different methods can be used to determine compliance, namely a subjective and an objective method. It has been demonstrated that subjective measurement of CPAP compliance might lead to an overestimation of approximately 1 hour of actual use of the CPAP device.13 Objective evaluation of compliance is therefore more accurate and can be performed by recording the mask-on time with effective pressure.13,14 Traditional predictors of CPAP compliance are the severity of the disease, symptomatic improvement, side effects and complaints, psychosocial factors, experience, education/ support and finally the use of novel techniques as less noisy CPAP machines and new masks.15 Although CPAP is an extremely efficient therapy for OSAS, its use is limited by a lack of compliance. Overall, studies reported that between 25 and 50% of all patients are non-compliant after one year of treatment. Reasons for non-compliance are extremely divergent, ranging from CPAP intolerance (due to side effects) to gender and age related effects.16 Large loco-regional differences may however exist related to severity level (in terms of symptoms and AHI) used to start and reimburse treatment, and technical and logistic support provided following CPAP titration. No figures on CPAP compliance are available for the Belgian population. However, use of CPAP for at least 3 hours/night as measured by a time counter in the device, is a prerequisite for continued reimbursement. In addition, the criteria for reimbursement (AHI of more than 20 events/hour and a micro arousal index of at least 30/hour) by itself select those patients with more severe disease.

Non-adherence to CPAP (CPAP Intolerance) Classical factors for CPAP intolerance are: (1) poor fitting masks, (2) patient characteristics, (3) severity of the disease and (4) side effects of CPAP treatment.13,14,16 Zozula et al.16 summarized all these

factors in a comprehensive table. The main categories, as a cause of inadequate compliance, are problems regarding tolerance (e.g. side effects and partner intolerance), psychosocial problems (e.g. motivation and claustrophobia) and lack of education, support and follow-up. For the purpose of this review, the relevant features are summarized in Table 1. Nasal side effects such as nasal congestion, rhinorrhea and mucosal dryness, have been observed in 15 to 45% of all patients treated with CPAP.16 These nasopharyngeal side effects are the main cause of non-compliance or intolerance. Baltzan et al.17 revealed that the three most common problems are nasal congestion, mouth leak and unconsciously taking off the mask during sleep. In their study 34% of the patients had at least two of these three symptoms, a finding that was associated with a lower subjective quality of sleep and a reduced objective compliance. Taking off the mask prematurely can be explained by an increased NR. Increased NR results in a subjective nasal congestion with CPAP intolerance and, consequently, patients take off their mask. Moreover, nasal congestion promotes opening of the mouth and vice versa. These factors intensify each other leading to a vicious circle which can only be interrupted by taking off the mask. Possible therapies for nasal side effects are summarized in Table 1, such as making use of a filter with allergic rhinitis. However, due to the specific nature of some of these pathologies, it will not be discussed in this review.

Nasal resistance The nose is responsible for 50–60% of the total airway resistance. Normal NR varies between 2 and 3 cm H2O/L/s. There are three important features which contribute to NR, namely nasal anatomy, the nasal cycle and positional nasal congestion. The anterior part of the nose contributes most to the NR. During sleep, there is a mild but non-significant increase in the NR. There is also a significant sleep related rise of the total upper airway resistance,

Table 1 Frequent nasal problems with CPAP usage and possible therapies Problem

Possible etiology

Therapy

Dry nose and/or throat Nasal congestion Epistaxis Dry mouth

Dry air

Nasal spray with physiologic serum Heated humidification Nasal decongestion* Heated humidification

Rhinorrhea

Dry air

Allergic rhinitis

Allergens in environmental air

Sinusitis

Initial adaptation period

Sleeping with open mouth

Nasal spray with physiologic serum Heated humidification Nasal decongestion* Heated humidification Nasal decongestion* Make use of a filter Reduction of CPAP pressure

Note: *Nasal decongestion with topical steroids and/or external nasal dilator strip.

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resulting from the transpalatal and hypopharyngeal resistances. The nasal cycle is a cyclical change of mucosal congestion between both sides of the nose. This cycle exists during daytime as well as during sleep. One cycle lasts between 0.5 and 10 hours.18 However, a study conducted by Flanagan et al.19 showed that only 21–39% of the population has a true nasal cycle. Positional nasal congestion is due to an augmentation of the central venous pressure by approximately 8 mmHg when lying down. As a result of this rise in central venous pressure, there is an associated rise of the filling pressure in the nasal capacity vessels causing consecutive vascular congestion of the mucosa. This results in a rise of the NR, which can be superimposed on the nasal cycle.18,20 The breathing route during sleep plays an important role in the NR and in the AHI. During normal sleep, the nasal breathing route dominates. Fitzpatrick et al.21 revealed a significant increase in upper airway resistance and the AHI during oral breathing. Oral breathing during sleep is associated with retroposition of the chin and shortening of the genioglossus muscle, resulting in a diminished dilator force of the upper airways.18,22 This diminished dilator force is accompanied by an increased tendency towards upper airway collapse and increase in AHI.18,22,23 Nasal pathologies can be responsible for nasal obstruction with an increase in NR promoting a shift towards oral breathing.24 They can be divided into anatomical abnormalities, inflammatory conditions and nasal valve incompetence, as shown in Table 2.18 In the literature, we found two studies which tried to clarify the relation between nasal obstruction/ resistance and CPAP compliance. Hollandt et al.25 examined the role of nasal obstruction on long-term compliance but could not draw a formal conclusion. On the other hand, Sugiura et al.26 demonstrated a significant rise of NR in the non-compliant CPAP group compared to the compliant CPAP group. They concluded that NR before CPAP initiation is an important determinant for acceptance of CPAP therapy.

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Treatment of Nasal Side Effects to Improve Nasal Breathing and CPAP Compliance The four interventions, discussed in detail below, could have an influence on CPAP tolerance, namely the use of a heated humidifier, nasal decongestion, topical steroids and nasal surgery.

Heated humidification Use of heated humidification has gained major interest. Different authors agree about the positive effect of a heated humidifier on nasal side effects, mainly on a dry nose, mouth and throat and a complaint of nasal congestion. The data about the effect of heated humidification on CPAP compliance are, however, inconsistent.27–31 Mador et al.28 showed that there were significantly more side effects in the control group versus the heated humidification group in the first month of treatment. This effect however disappeared after 3 months of treatment with no difference left between the two groups. They were also unable to demonstrate an improvement in compliance between both groups.28 Koutsourelakis et al.27 also demonstrated a significant reduction in side effects. In this study, patients were randomized to a 3-week nasal CPAP therapy with heated humidification followed by 3-week nasal CPAP therapy with sham-heated humidity or the reverse order of treatment. They demonstrated a positive effect of heated humidification on the inflammatory mediators in the nasal mucosa associated with OSAS. The study of Ryan et al.31 showed a significant reduction in objective nasal obstruction, but without a significant rise in compliance. Similar to these studies, Massie et al. found a significant reduction in nasal side effects. In contrast to the previous studies, they found a significant improvement in CPAP compliance.29 Patients were more likely to be compliant because of a reduction in nasal side effects. Ruhle et al.30 demonstrated a trend towards an improved compliance, but this was not statistically significant.

Nasal decongestion Nasal obstruction can produce a shift from nasal breathing towards oral breathing due to a rise in NR.

Table 2 Etiology of nasal obstruction Anatomical abnormalities

Inflammatory conditions

Nasal valve incompetence

Nasal septum deviation Turbinate hypertrophy Nasal polyps Adenoid hypertrophy Corpora aliena Postoperative or posttraumatic stenosis Tumours

Allergic rhinitis Perennial non-allergic Rhinitis Infectious rhinitis Acute Chronic Atrophic Others Pregnancy Medication-induced Tissue infiltration

Trauma Flaccid nasal cartilage Post-rhinoplasty

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The consequence is a rise in AHI and hence an increase in OSAS severity. McLean et al.32 studied the effect of nasal decongestion on the severity of OSAS, by use of oxymetazoline and an external nasal dilator strip. The AHI declined with an average of 12 episodes per hour. However, compared to the placebo nights, this reduction in AHI was not statistically significant, while the oral fraction of inhaled air decreased significantly. Clarenbach et al.33 also studied the effect of nasal decongestion with xylomethazoline on OSAS severity. Nasal airflow increased by 70%, while a significant improvement in AHI could not be demonstrated.

Topical steroids Strobel et al. examined the effects of nasal steroids (fluticasone) on CPAP compliance and nasal side effects. In the fluticasone group as well as in the placebo group, a significant reduction in nasal side effects was observed after 10 days treatment. After 4 weeks, the effect disappeared and even a rise in nasal side effects was noted as compared to baseline. A tendency towards longer CPAP usage per night (z0.3 h) was shown in the fluticasone group.34 Ryan et al.31 examined not only the role of heated humidification, as discussed above, but also assessed the effect of fluticasone on CPAP compliance. The patients were however not screened for associated rhinitis and were randomly assigned to a group. Nasal side effects, like sneezing and a runny nose, were most frequently reported after one month of treatment with fluticasone. In the control group, nasal congestion was the most frequent side effect. A tendency towards greater compliance was observed in the group treated with fluticasone. Kiely et al.35 studied the efficacy of fluticasone on OSAS severity in patients with associated allergic rhinitis. Those with an AHI .10/hour were assigned into the OSAS group, whereas patients with an AHI,10 were assigned into the snoring group. In both groups, patients were either treated with fluticasone or with a placebo spray. In this RCT study, OSAS patients treated with fluticasone had a significantly lower AHI. Furthermore, in the OSAS group, a significantly lower NR level was observed in patients treated with fluticasone. In the snoring group, only a trend towards lower AHI and NR was observed. This study clearly demonstrated that treatment with intranasal corticosteroids only has a beneficial effect in selected patients with allergic rhinitis.

Nasal surgery Friedman et al.36 found a significant reduction in effective CPAP pressure from 9.3 to 6.7 cmH2O (P, 0.01) in 22 OSA patients following nasal surgery. These authors concluded that nasal surgery alone does not consistently improve OSAS, but may

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contribute to a decrease in CPAP level. Surgical interventions are comprehensively discussed in an ERS Task Force paper by Randerath et al.37 They concluded that nasal surgery is recommended for reducing high CPAP pressure due to nasal obstruction (recommendation grade C).

Discussion Nasal complaints are the most common side effects of CPAP. Approximately 50% of all patients treated with CPAP develop nasal side effects. Nevertheless, little is known about the role of nasal obstruction as causality for CPAP intolerance or about the predictive factors for CPAP intolerance. Of the seven articles we initially found about the role of nasal obstruction in CPAP intolerance, only two examined this relationship.25,26 We hypothesize that a reduction in NR and an improvement of nasal patency (either by medical or surgical treatment) may result in a lower effective CPAP pressure. This in turn may have a beneficial effect on CPAP compliance. However, due to unequivocal results in several publications, further research is needed to support this hypothesis. Different treatment modalities are available to treat nasal obstruction in OSAS patients: heated humidification, nasal decongestion, topical steroids and nasal surgery. Heated humidification is an effective preventive measure for nasal side effects, and has a possible therapeutic role in the treatment of CPAP side effects in selected patients. Further research is required to draw conclusions on the role of a heated humidifier in preventing CPAP intolerance. To our knowledge, there are no publications which examined the role of nasal decongestion in CPAP intolerance. There are only few studies which examined the role of topical steroids in improving CPAP tolerance. Ryan et al.31 indicated a trend towards increased compliance. Nasal surgery may result in lower CPAP pressures required to alleviate upper airway obstruction although the impact of this intervention on CPAP compliance, remains unclear. At present, we could not find evidence about the predictability of CPAP intolerance. Although many factors which may result in CPAP intolerance are defined, it is impossible at the moment to identify patients who will develop CPAP intolerance. Studies in this area are needed in order to take preventive measures to enhance compliance. These preventive measures may be heated humidification, topical steroids, nasal decongestion or nasal surgery.

Conclusions Nasal symptoms are common during CPAP therapy and can interfere with its short- and long-term outcome, although CPAP intolerance cannot be predicted based on these factors. Heated humidification and topical

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steroids are often indicated in the presence of nasal comorbidity and are useful to reduce the burden of chronic rhinitis and improve CPAP compliance. Therefore, a better focus on nasal symptoms is warranted to improve treatment outcome.

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Nasal symptoms in patients with obstructive sleep apnea and their impact on therapeutic compliance with continuous positive airway pressure.

Continuous positive airway pressure (CPAP) is the first line treatment for moderate to severe obstructive sleep apnea syndrome. Despite the high effec...
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