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Acta Otolaryngol 2001; 121: 494 499

Allergic Rhinitis does not Constitute a Risk Factor for Obstructive Sleep Apnea Syndrome
M. F. KRAMER, R. DE LA CHAUX, A. DREHER, E. PFROGNER and G. RASP
From the Department of Oto -Rhino -Laryngology, Head and Neck Surgery, Ludwig -Maximilians -Uniersity, Munich, Germany

Kramer MF, de la Chaux R, Dreher A, Pfrogner E, Rasp G. Allergic rhinitis does not constitute a risk factor for obstructie sleep apnea syndrome. Acta Otolaryngol 2001; 121: 494 499. Obstructive sleep apnea syndrome (OSAS) is a condition characterized by recurrent episodes of obstruction of the upper airway. The aim of this study was to evaluate whether nasal obstruction due to allergic rhinitis constitutes a risk factor for OSAS. Patients (n 119) presenting typical symptoms of sleep apnea were tested for OSAS using polysomnography. Additionally all patients were tested in io and in itro (including nasal eosinophilic cationic protein) for allergic rhinitis. Examination for allergic rhinitis revealed that 88.3% of all patients had no allergic rhinitis, whereas only 11.7% were diagnosed as allergic. No signi cant differences in sleeping parameters were observed between allergic and non-allergic patients. Comparison of parameters indicative of relevant OSAS (apnea hypopnea index [AHI] \ 10) revealed that 60% of non-allergic patients had relevant OSAS, compared to only 50% of allergic patients. Investigation of allergic subgroups revealed similar results: no signi cant differences in sleeping parameters or elevated rates of relevant OSAS parameters were observed, especially in perennial allergic rhinitis due to house dust mites. No elevated rates of allergic rhinitis were observed in the studied cohort of patients suffering from sleep apnea or OSAS. Furthermore, no signi cant differences in sleeping behavior or polysomnography parameters were found on comparing allergic and non-allergic patients. In summary, our data rule out allergic rhinitis as a major risk factor for OSAS. Key words : allergic rhinitis, apnea, apnea hypopne a index, hypopnea , obstructi e sleep apnea, non -allergic rhinitis with eosinophilia syndrome, perennial rhinitis, polysomnography .

INTRODUCTION Obstructive sleep apnea is a condition characterized by repetitive obstruction of the upper airway resulting in oxygen desaturation and arousal from sleep (1). In 1976 Guilleminault et al. (2) introduced the term obstructive sleep apnea syndrome (OSAS), characterized by daytime hypersomnolence and polysomnographically-prove n obstructive apneas. The initial description of OSAS by Guilleminault et al. included a criterion of a minimum duration of 10 s in order for apnea to be scored. The number of episodes of apnea per hour of sleep was standardized as the apnea index. The apnea index cutoff for OSAS was set at ve (2). According to the American Academy of Sleep Medicine (1), OSAS (or obstructive sleep apnea hypopnea syndrome) is characterized by recurrent episodes of partial or complete upper airway obstruction during sleep. This manifests as a reduction in (hypopnea) or a complete cessation of (apnea) air ow despite ongoing inspiratory efforts. The lack of adequate alveolar ventilation results in oxygen desaturation of at least 3%. These events are often associated with arousal. While snoring is reported by 40 60% of adults (3), the prevalence of OSAS has been estimated to be 2% and 4% for women and men, respectively (1, 4) Characteristic symptoms of patients suffering from OSAS include, in addition to excessive daytime sleepiness, choking or gasping during sleep, recurrent awakening from sleep, unrefreshing sleep,
2001 Taylor & Francis. ISSN 0001-648 9

daytime fatigue and impaired concentration. Sleep-related obstructive breathing events (hypopneas and apneas) are characterized by transient ( ] 10 s) reduction in, or complete cessation of, breathing. Cutoff points for hypopnea and apnea indices as a criterion for OSAS were set at ve (1). OSAS is associated with snoring, obesity, systemic or pulmonary hypertension, sleep-related cardiac dysrhythmias, nocturnal angina, gastroesophagea l re ux, impaired quality of life and insomnia. Therefore OSAS constitutes a possibly life-threatening condition. Predisposing factors include: obesity, male gender, craniofacial abnormalities, familial history, increased pharyngeal soft or lymphoid tissue and nasal obstruction (1). Nasal obstruction due to allergic rhinitis represents the main focus of the present study. Three interacting factors play a critical role in obstruction of the upper airway in OSAS: the muscle activity of the dilators of the pharyngeal airway, the negative pressure generated during inspiration, which opposes the activity of the dilators, and the structural anatomy of the airway (5, 6). The biologic basis for nasal obstruction as a cause of sleep-disordered breathing lies in the effect of nasal breathing on resistance and ow velocity, which affects the pressure differential between the atmosphere and the intrathoracic space (7). Partial or complete obstruction can occur when the intrathoracic negative pressure generated by the inspiratory muscles pulls on the compliant soft tissue in the upper airway, sucking the airway closed (6). It is

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worth pointing out that the nose accounts for half of the total respiratory system resistance (8). Although the primary site of obstruction in patients with OSAS is believed to be the oropharyngea l hypopharyngea l region, numerous studies examining the effects of experimentally-induce d nasal obstruction on OSAS have indicated a positive and signi cant association (9 11). Therefore nasal obstruction constitutes a predisposing factor for OSAS (1, 6, 9 12). Allergic rhinitis constitutes a Th2-type in ammation primarily affecting the upper airways. Prevalence rates of allergic rhinitis are increasing by : 3.5% per decade and are estimated to be 15 25% in Europe (13 15). Consecutively, allergic rhinitis constitutes a pathologic condition associated with immense socioeconomic costs. This is re ected in the direct and indirect costs of allergic rhinitis treatment in the US, estimated at US$ 4 billion per year (16). Allergic rhinitis can be roughly divided into seasonal and perennial allergic rhinitis. Seasonal allergic rhinitis, or pollinosis, is caused by pollen and constitutes the largest allergic subgroup: 49% of German patients suffering from allergic rhinitis are sensitized against pollen (17). The main symptoms are watery nasal secretion, sneezing, itching of the nose and, to a lesser extent, nasal obstruction. Perennial allergic rhinitis is caused by allergen exposure throughout the whole year. Typical perennial allergens are allergens of animals, occupational allergens and indoor allergens such as house dust mites (14). House dust mites constitute the largest and most important group of perennial allergens: 19.8% of German patients suffering from allergic rhinitis are sensitized to house dust mites according to recent data (17). Allergic rhinitis due to house dust mites is characterized by nasal congestion as the primary symptom. Sneezing, itching or rhinorrhea are less important. House dust mites are mainly found in bed, and therefore symptoms are prominent during night-time. In general, allergic rhinitis constitutes a pathologic condition characterized by a transient increase in nasal airway resistance due to mucosal swelling (18 20) and therefore theoretically constitutes a risk factor for OSAS. Investigation of allergic rhinitis as a possible risk factor for OSAS drew our attention especially to the perennial allergic rhinitis caused by house dust mites as the primary symptom is nasal congestion and the natural environment for the house dust mite is known to be the bed. The aim of our study was to evaluate whether nasal obstruction due to allergic rhinitis constitutes a risk factor for OSAS. Patients (n 119) presenting typical symptoms of sleep apnea were tested by polysomnography for OSAS. Additionally all patients were tested in io and in itro for allergic rhinitis. Measurement

of eosinophilic cationic protein (ECP) in nasal secretions allowed us to determine nasal eosinophilic in ammation. One would expect to nd increased numbers of patients suffering from allergic rhinitis (especially those sensitized against house dust mites) among the cohort of patients with symptoms of sleep apnea or OSAS if allergic rhinitis constitutes a risk factor for these conditions. Furthermore, allergic patients should reveal more severe pathologic sleeping disturbances. MATERIALS AND METHODS Methods Patients (n 119) in our ENT outpatient department presenting typical symptoms of sleep apnea were tested by polysomnography for OSAS. All patients were examined for allergic rhinitis. As obesity constitutes a risk factor for OSAS we determined the body mass index (BMI) for each patient. Polysomnography . Polysomnograph y was performed as described previously (21). Brie y, patients slept for two nights in our sleep laboratory but only the second night was monitored, in order to avoid the so-called rst night effect (22, 23). Monitoring included electroencephalograph y (C3: A2, C4:A1 of the international electrode placement system), electro-oculogram , chin and leg electromyogram and electrocardiography (modi ed V-2 lead). Respiration was investigated by oronasal air ow (thermal sensors), thoracic and abdominal movements (piezo sensors), snoring sound (microphone) and oxygen saturation (pulse oximetry). Records were scored in accordance with the Rechtschaffen Kales international criteria for sleep:wake determination (24). As the most important parameters for determination of OSAS we choose the apnea index (AI), hypopnea index (HI), apnea hypopnea index (AHI) and minimum O2 saturation during sleep. In accordance with the American Academy of Sleep Medicine, we choose index values B 5 as the cutoff for OSAS. AHI values of 5 10 were regarded as being indicative of borderline OSAS and AHI values \ 10 were regarded as being indicative of relevant OSAS. Differential diagnoses for OSAS, i.e. simple snoring, central sleep apnea syndrome, narcolepsy, restless leg syndrome, etc., were excluded by polysomnography. Allergic rhinitis. Allergic rhinitis was determined by the patients history and by in io (prick, intranasal provocation) and in itro tests (Sx1 screening test, similar to Phadiatop [Pharmacia Cap-FEIA, Freiburg, Germany]; total IgE; and allergen-speci c IgE in serum). ECP levels were studied in nasal secretions by routine ELISA in order to determine nasal

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Table I. Epidemiological data


(AHI B 5) All patients (n 119) No OSAS, (AHI B5) (n 29) OSAS (AHI \ 5) (n 90) AHI 510 (n 20) AHI \ 10 (n 70) (BMI 28.7 kg:m2 , age 56.7 years, 84.8% male) Non-allergic patients 88.3% (BMI 28.7 kg:m2 , age 56.7 years, 84.8% male) 93.1% (BMI 28.0 kg:m2 , age 52.4 years, 77.2% male) 86.7% (BMI 28.9 kg:m2 , age 58.3 years, 85.9% male) 75.0% (BMI 29.1 kg:m2 , age 57.7 years, 92.9% male) 90.0% (BMI 28.9 kg:m2 , age 58.4 years, 81.2% male) (BMI 28.9 kg:m2, age 52.0 years, 100% male) Allergic rhinitis patients 11.7% (BMI 28.9 kg:m2, age 52.0 years, 100% male) 6.9% (BMI 27.0 kg:m2, age 41.5 years, 100% male) 13.3% (BMI 29.2 kg:m2, age 53.7 years, 100% male) 25.0% (BMI 32.3 kg:m2, age 53.6 years, 100% male) 10.0% (BMI 27.0 kg:m2, age 53.8 years, 100% male)

(BMI body mass index [kg:m2 ); AHI Apnea-Hypopnea Index; AHI 5-10 borderline OSAS; AHI \ 10 relevant OSAS)

in ammation characterized by tissue eosinophilia, such as allergic rhinitis, but also by non-allergic forms of rhinitis such as non-allergic rhinitis with eosinophilia syndrome (NARES) as described elsewhere (25, 26). Statistics A standard PC equipped with SPSS 9.0 software was used for the statistical evaluation and graphical presentation of the results. Signi cance was evaluated by the independent samples t -test. P -values B 0.05 were regarded as signi cant. Box plots, presenting median (horizontal line), interquartile area (box) and highest and lowest counts (lines), were chosen for the graphical presentation of the results. RESULTS Epidemiological data for the patients studied were as follows. Non-allergic patients comprised the largest patient group (88.3%). Their mean age was 56.7 9 5.8 years, 84.8% were male and the mean BMI was 28.7 9 2.0 kg:m2 . The group of allergic patients comprised 11.7% of the studied cohort. They were characterized by a mean age of 52.0 9 6.76 years, 100% male sex and a mean BMI of 28.9 9 1.9 kg:m2 . For further characterization see Table I. No signi cant differences in age or BMI were observed between the groups. A small but interesting subgroup of non-allergic patients were diagnosed as suffering from NARES (3.4%). They were characterized by a mean age of 47.5 9 2.3 years, 100% male sex and a mean BMI of 28.8 9 2.5 kg:m2 . Polysomnograph y of all 119 patients revealed that despite typical symptoms as many as 24.4% of all studied patients did not suffer from OSAS. Borderline or mild OSAS was found in 16.8% of patients and de nite OSAS was determined in 58.8% of all patients.

Examination for allergic rhinitis revealed that no signi cantly elevated rates of allergic rhinitis were found in any of the studied OSAS groups (Table I). Furthermore, no signi cant differences in sleeping parameters were observed between allergic and non-allergic patients (Figs. 1 4). Sixty percent of the non-allergic patients had an AHI \ 10, compared with only 50% of allergic patients. Allergic patients were analyzed in order to determine rhinitis subgroups: 21.4% suffered from an isolated perennial allergic rhinitis, the major perennial allergen being house dust mite (Dermatophagoides pteronyssinus and :or farinae ). Furthermore, 42.9% of the allergic patients suffered from an isolated seasonal allergic rhinitis and 35.7% suffered from both forms of allergic rhinitis. No signi cant differences in sleeping parameters were observed between these allergic subgroups. Relevant OSAS was observed in 50% of all patients suffering from perennial rhinitis.

Fig. 1. Comparison of AI for non-allergic patients and patients with allergic rhinitis. No signi cant differences could be observed.

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Fig. 2. Comparison of HI for non-allergic patients and patients with allergic rhinitis. No signi cant differences could be observed.

Fig. 4. Comparison of minimal oxygen saturation (%) during sleep for non-allergic patients and patients with allergic rhinitis. No signi cant differences could be observed.

Interestingly, only the small group of patients suffering from NARES comprising 3.4% of all patients and characterized by symptoms of perennial rhinitis, negative allergy tests and signi cantly elevated ECP levels revealed pathologic results in all measured sleeping parameters and 75.0% of them suffered from relevant OSAS. DISCUSSION Several reports in which nasal congestion due to allergic rhinitis as a risk factor for OSAS was studied produced different results. Lavie et al. (27) reported on 14 patients with allergic rhinitis and 7 controls. The ndings revealed that although allergic rhinitis patients had multiple microarousals from sleep, these

Fig. 3. Comparison of AHI for non-allergic patients and patients with allergic rhinitis. No signi cant differences could be observed.

arousals were generally associated with non-apneic breathing events. Craig et al. (12) studied the effects on sleep disturbance and daytime fatigue of decreasing the nasal resistance of 20 patients with perennial allergic rhinitis using topical corticosteroids. They showed that nasal congestion and subjective sleep quality improved signi cantly with corticosteroids but found no signi cant effects on sleepiness. Duchna et al. (28) found elevated positive allergy skin tests in 75 patients suffering from OSAS but failed to demonstrate signi cant changes in pathologic sleep parameters such as AI, HI or AHI. In contrast McNicholas et al. (18), in seven patients, found that during the asymptomatic phase of seasonal allergic rhinitis caused by ragweed pollen both the number of obstructive apneas and the duration of the apneas signi cantly decreased, and that these changes were associated with a signi cant decrease in mean nasal resistance. In a study of 39 children with habitual snoring, McColley et al. (20) concluded that, in the population studied, the presence of allergy was associated with an increased risk of OSAS. Using the population-base d sample of the Wisconsin Sleep Cohort Study, Young et al. (7) reported that participants with nasal congestion due to allergy were 1.8 times more likely to have moderate-to-sever e sleepdisordered breathing than those without nasal congestion due to allergy. Nevertheless, a linear relationship between nasal obstruction and the severity of sleep-disordered breathing was not found. Our data clearly support the ndings of those authors who could not demonstrate signi cant effects of nasal congestion due to allergic rhinitis on OSAS. Compared to the normal European population (13, 17) no elevated rates of allergic rhinitis

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could be observed in the studied cohort of patients suffering from sleep apnea or OSAS. Furthermore, no signi cant differences in sleeping behavior or polysomnograph y parameters were found comparing allergic versus non-allergic patients suffering from OSAS. Consideration of relevant OSAS revealed the same picture: allergic patients had even lower counts of relevant OSAS than non-allergics. As nasal congestion is the primary symptom of perennial rhinitis and the major antigen (house dust mite) is localized mainly in bed, we were especially interested in this allergic subgroup. No elevated rates of perennial allergic rhinitis could be found in our patients when compared to the normal European population. As above, rates of de nite OSAS were lower in perennial rhinitis patients than in non-allergic patients. To summarize, our data rule out allergic rhinitis as a major risk factor for OSAS. It is worth pointing out that allergic rhinitis may cause daytime fatigue or sleep fragmentation without having effects on breathing. Rhinitis symptoms per se may cause cortical arousal and fragmented sleep. Furthermore, somnolence due to sleep fragmentation may be compounded by daytime use of anti-allergic medication (7). Investigation of NARES revealed surprising ndings. NARES constitutes a very rare non-allergic form of rhinitis characterized by tissue eosinophilia. Prevalence rates of 2% in a population of 363 patients suffering from chronic or recurrent nasal symptoms were reported (29). Patients with NARES suffer from typical symptoms of perennial rhinitis without having elevated counts of total IgE or allergen-speci c IgE. The pathogenesis of this condition is far from being understood. Non-speci c liberation of histamine is considered to be the main pathogenic motor of the disease. The diagnosis is based on elevated ECP in nasal secretion without evidence of allergen-speci c IgE or elevated total IgE (30). Our data identi ed a population of 3.4% of the studied patients with pathologic results in all measured sleeping parameters for OSAS. Of these, 75.0% suffered from relevant OSAS. The limited number of patients in this study meant that the statistical signi cance of the observed pathologic differences in sleeping parameters could not be elucidated. However, this group of patients would appear to be a promising target for further studies. Our data are in accordance with those of other workers who suggested that nasal in ammation (other than eosinophilic forms of rhinitis), even without clinical signs of rhinitis, is a risk factor for OSAS (31, 32).

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Submitted July 25, 2000 ; accepted October 19, 2000 Address for correspondence: Dr. med. Matthias F. Kramer ENT Department, Klinikum Grosshadern Marchioninistrasse 15, DE-81377 Munich Germany Fax: 49 89 7095 6880 E-mail: mkramer@hno.med.uni-muenchen.de