- Email: [email protected]
Nares: a risk factor for obstructive sleep apnea?
NARES: A Risk Factor for Obstructive Sleep Apnea? Matthias F. Kramer, MD, Richard de la Chaux, MD, Rose Fintelmann, MD, and Gerd Rasp, MD Background: Nonallergic rhinitis with eosinophilia syndrome (NARES) constitutes a rare nasal condition characterized by a chronic, eosinophilic inflammation. Patients’ major complaints constitute nasal congestion and rhinorrhea. Obstructive sleep apnea syndrome (OSAS) is a potentially life-threatening condition characterized by recurrent episodes of obstruction of the upper airways resulting in oxygen desaturation. Nasal congestion constitutes one predisposing factor for OSAS. Objective: The purpose was to study whether NARES constitutes a risk factor for OSAS. Methods: The study included 26 patients presenting typical symptoms of sleep apnea. Ten patients were diagnosed to suffer from NARES (mean age 56.8 ⫾ 12.5, body mass index [BMI] 29.3kg/m2 ⫾ 2.8; 9 men:1 woman) and were compared with 16 age- and BMI-matched individuals (mean age 58.8 ⫾ 11.6, BMI 29.7kg/m2 ⫾ 3.8, 16 men) without any nasal inflammation, such as allergic rhinitis, sinusitis, nasal polyposis, or vasomotor rhinitis. All patients were tested by polysomnography for an OSAS. Results: Patients suffering from NARES revealed significantly (P ⬍ .01) impaired polysomnographic parameters (hypopnea index, apnea-hypopnea index, mean and minimal oxygen saturation) compared with patients without any nasal inflammation. Conclusions: Our data point to NARES as a risk factor for the induction or augmentation of OSAS. NARES patients suffered from severe OSAS, whereas nondiseased individuals suffered only from moderate OSAS, according to the criteria of the American Academy of Sleep Medicine. Our data support results of others, suggesting chronic nasal inflammation to cause OSAS. Mechanisms for our observations are not fully understood yet. Nasal obstruction or neuronal reflexes might be involved. (Am J Otolaryngol 2004;25:173-177. © 2004 Elsevier Inc. All rights reserved.)
Nonallergic rhinitis with eosinophilia syndrome (NARES) constitutes a rare nasal condition characterized by a chronic, eosinophilic inflammation.1 Patients complain about typical symptoms of perennial allergic rhinitis, mainly nasal congestion and rhinorrhea, but all in vitro and in vivo allergy tests fail to detect an atopy. A chronic, unspecific liberation of histamine and a self-perpetuating chronic and eosinophilic nasal inflammation are suggested to constitute the main pathogenic factors of the disease.
From the Department of Oto-Rhino-Laryngology/ Head and Neck Surgery, Ludwig-Maximilians-University, Munich, Germany. Address correspondence to: Matthias F. Kramer, MD, Department of Oto-Rhino-Laryngology/Head and Neck Surgery, Ludwig-Maximilians-University Munich, Klinikum Grosshadern, Marchioninistr.15, 81377 Munich, Germany. E-mail: [email protected]. © 2004 Elsevier Inc. All rights reserved. 0196-0709/$ - see front matter doi:10.1016/j.amjoto.2003.12.004
Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent episodes of partial or complete upper airway obstruction during sleep, according to the American Academy of Sleep Medicine.2 This manifests as a decrease of airflow despite ongoing inspiratory efforts. The lack of adequate alveolar ventilation results in oxygen desaturation of at least 3%. Sleep-related obstructive breathing events are characterized by transient (10 seconds or longer) reduction in (hypopnea) or complete cessation of (apnea) respiratory flow. OSAS is associated to snoring, obesity, systemic or pulmonary hypertension, sleeprelated cardiac dysrhythmias, nocturnal angina, gastroesophageal reflux, impaired quality of life, and insomnia. Therefore, OSAS constitutes a potentially life-threatening condition. Nasal congestion constitutes a predisposing factor for OSAS,2,3 although not without controversy. Nasal congestion might be caused by anatomic variation, such as septal deviation
American Journal of Otolaryngology, Vol 25, No 3 (May-June), 2004: pp 173-177
173
174
or mucosal swelling because of nasal inflammation. Allergic rhinitis, especially perennial allergic rhinitis caused by house dust mites, is under controversial discussion as a risk factor for OSAS. In a former study, we supported those who did not find a relevant association between these 2 conditions.4 However, it is generally accepted that chronic nasal inflammation causes an increase in nasal airway resistance because of mucosal swelling.5-7 And there is evidence for nasal inflammation causing OSAS.8 The objection was to study whether NARES might constitute a risk factor for an OSAS. Therefore, we polysomnographically analyzed 26 patients presenting typical symptoms of sleep apnea. Ten patients, diagnosed to suffer from NARES, were compared with 16 age- and body mass index (BMI)-matched individuals without any nasal inflammation to work out differences in their sleeping parameters pointing to NARES as a risk factor for OSAS. MATERIAL AND METHODS Patients The study was performed at the Department of Oto-Rhino-Laryngology/Head and Neck Surgery of Ludwig-Maximilians-University Munich, Klinikum Grosshadern, Germany. We included 26 patients presenting themselves in our outpatient department, reporting typical symptoms of sleep apnea, such as choking or gasping during sleep, recurrent awakening from sleep, unrefreshing sleep, daytime fatigue, impaired concentration, or snoring. Ten patients were diagnosed to suffer from NARES (9 men: 1 woman). They were compared with 16 age- and BMI-matched individuals (16 men) without any nasal inflammation. Ear, nose, and throat status, with special regard to the size of the palatine tonsils, elongation of the uvula, velum, septal deviation, and so on (determined by semiquantitative scores), was similar in all patients.
KRAMER ET AL
wool pieces at 4,000 rpm for 10 minutes, as described earlier.9 Patients’ sera were analyzed for total and specific immunoglobulin E and the routine in vitro allergy screening test SX1 (identical to Phadiatop; Pharmacia Diagnostic, Freiburg, Germany). Nasal secretions were analyzed for eosinophilic cationic protein (ECP) (Pharmacia Diagnostics) as a marker of tissue eosinophilia.10 Nasal inflammatory diseases, such as sinusitis, allergic rhinitis, nasal polyposis, or vasomotor rhinitis, were excluded in all patients. None of the patients were under nasal medication. Patients suffering from NARES showed the typical history of year-long nasal congestion and rhinorrhea.
Rhinomanometry To estimate nasal obstruction, we were able to perform standard rhinomanometry in 4 of the NARES patients and in 5 of the noninflamed patients. Nasal flow as a summary score of both nostrils in milliliters per second at 150 Pa inspiration was used for comparison, as generally accepted.
Polysomnography Polysomnography was performed as described earlier.11 Briefly, patients slept 2 nights in our sleeping laboratory, whereas the second night was measured to avoid the so-called first-night effect.12 The monitoring included electroencephalogram (C3/A2, C4/A1 of the international electrode placement system), electrooculogram, chin and leg electromyogram, and electrocardiogram (modified V-2 lead). Respiration was investigated by oronasal airflow (thermal sensors), thoracic and abdominal movements (piezo sensors), snoring sound (microphone), and oxygen saturation (pulse oximetry). Records were scored following the Rechtschaffen and Kales international criteria for sleep/wake determination.2,13 As the most important parameters for determination of an OSAS, we choose the apnea-hypopnea index (AHI), the apnea index (AI), the hypopnea index (HI), and mean and minimum oxygen-saturation during sleep. Differential diagnoses for OSAS, such as simple snoring, central sleep apnea syndrome, narcolepsy, restless leg syndrome, and so on, were excluded by polysomnography.
Nasal Inflammation
Statistic
All patients were tested for an underlying nasal disease by patient’s history, endoscopic nasal examination, and, if needed, computed tomography scans of paranasal sinuses. Serum and nasal secretions were obtained from every patient. Nasal secretions were gained by placing small cotton wool pieces into the middle meatus of the nose for 10 minutes, followed by centrifugation of the cotton
A standard PC with SPSS 10.0 software was used for the statistical evaluation and graphic presentation of the results. Significance was evaluated by the independent samples t test. Box plots presenting median (horizontal line), interquartile area (box), and highest and lowest counts, respectively (lines), were chosen for the graphic presentation of the results (*P ⬍ .05; **P ⬍ .01; ns, not significant).
NARES
175
correlation was observed in nondiseased individuals. Polysomnography Patients suffering from NARES revealed significantly (P ⬍ .01) impaired polysomnographic parameters (AHI, HI, mean and minimal oxygen saturation) compared with noninflamed individuals (Figs 1-5). NARES patients suffered from severe OSAS (7/10), whereas patients without any nasal inflammation suffered from moderate OSAS or less (13/16), according to the criteria of the American Academy of Sleep Medicine.2 DISCUSSION Fig 1. Apnea-hypopnea index. Significantly elevated AHI in NARES compared with patients without any nasal inflammation. Box plots present median (horizontal line), interquartile area (box), and highest and lowest counts, respectively (lines). *P < .05; **P < .01; n.s., not significant.
RESULTS There was no significant difference in age (NARES mean age 56.8 ⫾ 12.5 v no nasal inflammation: 58.8 ⫾ 11.6 ) or BMI (NARES: 29.3kg/m2 ⫾ 2.8 v no nasal inflammation: 29.7kg/m2 ⫾ 3.8) between both groups studied. ECP (ng/mL) was highly significantly (P ⬍ .001) elevated in patients suffering from NARES (NARES: 660.7 ⫾ 282.0 v no nasal inflammation 31.2 ⫾ 61.3).
We compared polysomnographic parameters of age- and BMI-matched patients presenting typical symptoms of OSAS in regards whether they suffer from NARES or not. Other forms of underlying nasal inflammation were excluded. Patients with NARES were significantly more impaired by OSAS then noninflamed individuals. NARES patients suffered from severe OSAS, whereas the latter suffered from only moderate OSAS, according to the
Rhinomanometry Rhinomanometric data displayed no significant difference between both groups. Nasal flow (mL/s) as summary score of both nostrils at 150 Pa inspiration was NARES: 564.5 ⫾ 116.9 v no nasal inflammation: 367.0 ⫾ 210.8. Looking for correlations (Pearson’s) revealed in patients suffering from NARES a significant (P ⬍ .01) inverse correlation between nasal flow measured by rhinomanometry and AI (r ⫽ ⫺0.99), HI (r ⫽ ⫺0.93), and AHI (r ⫽ ⫺0.97) and a significant (P ⬍ .01) correlation between nasal flow and mean oxygen saturation (r ⫽ 0.97). No such significant
Fig 2. Apnea index. Elevated AI in NARES compared with patients without any nasal inflammation. Box plots present median (horizontal line, interquartile area (box), and highest and lowest counts respectively (lines). *P < .05; **P < .01; n.s., not significant.
176
Fig 3. Hypopnea index. Significantly elevated HI in NARES compared with patients without any nasal inflammation. Box plots present median (horizontal line, interquartile area (box), and highest and lowest counts respectively (lines). *P < .05; **P < .01; n.s., not significant.
criteria of the American Academy of Sleep Medicine.2 Our data support results of others, suggesting chronic nasal inflammation to cause
Fig 4. Mean oxygen saturation. Significantly decreased mean oxygen saturation during sleep in NARES compared with patients without any nasal inflammation. Box plots present median (horizontal line, interquartile area (box), and highest and lowest counts respectively (lines). *P < .05; **P < .01; n.s., not significant.
KRAMER ET AL
Fig 5. Minimal oxygen saturation. Significantly decreased minimal oxygen saturation during sleep in NARES compared with patients without any nasal inflammation. Box plots present median (horizontal line, interquartile area (box), and highest and lowest counts respectively (lines). *P < .05; **P < .01; n.s., not significant.
OSAS.8 Interestingly, our data show that NARES deteriorates hypopneas more than apneas. One might interpret this that way that nasal obstruction because of NARES causes primarily a partial obstruction of the upper airways and consecutively deteriorates hypopneas more than apneas. Both groups revealed no significant differences in nasal flow measured by standard rhinomanometry. This evokes discussion; NARES patients tended to have lower nasal obstruction than noninflamed individuals (although difference not significant), challenging the causative role of nasal congestion caused by mucosal swelling in nasal inflammation as the pivotal factor for the observed differences in polysomnographic parameters. On the other hand, we observed highly significant correlations between nasal flow and impaired polysomnographic parameters in the NARES group, whereas we did not find any of these correlations in noninflamed individuals. Further studies involving more patients are certainly needed to answer this question. Rare prevalences of NARES make this a challenging target. Furthermore, one would ask for an objective measurement of nasal congestion, such as acoustic rhinometry, measuring nasal
NARES
airflow continuously during the whole night and in the supine position, and not while sitting, as we did. However, as far as we know, these methodological problems are unsolved to date. Neuronal reflex branches might help to interpret our data: chronic, eosinophilic nasal inflammation, such as NARES, might activate and/or augment neuronal reflex branches, such as the nasal-pulmonary reflex, described to cause alveolar hypoventilation.3 As a hypothesis, this might result in an increase in hypopnea index, as we observed. Such neuronal nasal (pharyngeal)-pulmonary (bronchial) reflex branches are well described in rhinitis and asthma.14-16 Furthermore, Leone and coworkers17 showed pathologic bronchial responsiveness and elevated sputum ECP in 46% of NARES patients without any respiratory symptoms as a sign of a pulmonary inflammation in these patients. Studies on sudden infant death syndrome detected a positive correlation between respiratory tract infections and apneas.18 Thus, nasal inflammation, transmitted via circulating mediators or neuronal reflexes, might count for the observed impaired polysomnographic parameters in NARES.18 CONCLUSIONS We observed significantly impaired polysomnographic parameters (HI, AHI, mean and minimal oxygen saturation) in patients suffering from NARES compared with patients without any nasal inflammation. Our data point to NARES as a risk factor for the induction or augmentation of OSAS. Our data support results of others, suggesting chronic nasal inflammation to cause OSAS. Mechanisms for our observations are not fully understood yet. Nasal obstruction or neuronal reflexes might be involved.
177
REFERENCES 1. Jacobs RL, Freedmann PM, Boswell RN: Nonallergic rhinitis with eosinophilia (NARES) syndrome. J Allergy Clin Immunol 61:253-262, 1981 2. AASM Task Force: Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 22: 667-689, 1999 3. Papsidero MJ: The role of nasal obstruction in obstructive sleep apnea syndrome. Int Arch Allergy Immunol 72:82-84, 1993 4. Kramer MF, de la Chaux R, Dreher A, et al: Allergic rhinitis does not constitute a risk factor for obstructive sleep apnea syndrome. Acta Otolaryngol 121:494-499, 2001 5. McNicholas WT, Tarlo S, Cole P: Obstructive apneas during sleep in patients with seasonal allergic rhinitis. Am Rev Respir Dis 126:625-628, 1982 6. Olsen KD, Kern EB: Nasal influences on snoring and obstructive sleep apnea. Mayo Clin Proc 65:1095-1105, 1990 7. McColley SA, Carroll JL, Curtis S, et al: High prevalences of allergic sensitization in children with habitual snoring and obstructive sleep apnea. Chest 111:170-173, 1997 8. Rubinstein I: Nasal inflammation in patients with obstructive sleep apnea. Laryngoscope 105:175-177, 1995 9. Klimek L, Rasp G: Norm values for eosinophil cationic protein in nasal secretions: Influence of specimen collection. Clin Exp Allergy 29:367-374, 1999 10. Klimek L, Rasp G: Cell activation markers in rhinitis and rhinosinusitis. 1: Eosinophilic cationic protein (ECP). Laryngorhinootologie 75:665-670, 1996 11. American Thoracic Society: Indications and standards for cardiopulmonary sleep studies. Am Rev Respir Dis 139:569-578, 1989 12. Browman CP, Cartwright RD: The first night effect on sleep and dream. Bol Psychiatry 15:809-812, 1980 13. Rechtschaffen A, Kales A (eds): A manual of standardized technology, techniques and scoring system for sleep stages of human subjects. Los Angeles, CA, Brain Information Service/Brain Research Institute, UCLA, 1968 14. Sluder G: Asthma as a nasal reflex. JAMA 73:589, 1919 15. Slavin RG: Complications of allergic rhinitis: implications for sinusitis and asthma. J Allergy Clin Immunol 101:S357-S360, 1998 16. Hoehne JH, Reed CE: Where is the allergic reaction in ragweed asthma? J Allergy Clin Immunol 48:36-39, 1971 17. Leone C, Teodoro C, Pelucchi A, et al: Bronchial responsiveness and airway inflammation in patients with nonallergic rhinitis with eosinophilia syndrome. J Allergy Clin Immunol 100:775-780, 1997 18. Lindgren C, Gro¨ gaard J: Reflex apnoea response and inflammatory mediators in infants with respiratory tract infection. Acta Paediatr 85:798-803, 1996
Nonallergic rhinitis with eosinophilia syndrome (NARES) constitutes a rare nasal condition characterized by a chronic, eosinophilic inflammation.1 Patients complain about typical symptoms of perennial allergic rhinitis, mainly nasal congestion and rhinorrhea, but all in vitro and in vivo allergy tests fail to detect an atopy. A chronic, unspecific liberation of histamine and a self-perpetuating chronic and eosinophilic nasal inflammation are suggested to constitute the main pathogenic factors of the disease.
From the Department of Oto-Rhino-Laryngology/ Head and Neck Surgery, Ludwig-Maximilians-University, Munich, Germany. Address correspondence to: Matthias F. Kramer, MD, Department of Oto-Rhino-Laryngology/Head and Neck Surgery, Ludwig-Maximilians-University Munich, Klinikum Grosshadern, Marchioninistr.15, 81377 Munich, Germany. E-mail: [email protected]. © 2004 Elsevier Inc. All rights reserved. 0196-0709/$ - see front matter doi:10.1016/j.amjoto.2003.12.004
Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent episodes of partial or complete upper airway obstruction during sleep, according to the American Academy of Sleep Medicine.2 This manifests as a decrease of airflow despite ongoing inspiratory efforts. The lack of adequate alveolar ventilation results in oxygen desaturation of at least 3%. Sleep-related obstructive breathing events are characterized by transient (10 seconds or longer) reduction in (hypopnea) or complete cessation of (apnea) respiratory flow. OSAS is associated to snoring, obesity, systemic or pulmonary hypertension, sleeprelated cardiac dysrhythmias, nocturnal angina, gastroesophageal reflux, impaired quality of life, and insomnia. Therefore, OSAS constitutes a potentially life-threatening condition. Nasal congestion constitutes a predisposing factor for OSAS,2,3 although not without controversy. Nasal congestion might be caused by anatomic variation, such as septal deviation
American Journal of Otolaryngology, Vol 25, No 3 (May-June), 2004: pp 173-177
173
174
or mucosal swelling because of nasal inflammation. Allergic rhinitis, especially perennial allergic rhinitis caused by house dust mites, is under controversial discussion as a risk factor for OSAS. In a former study, we supported those who did not find a relevant association between these 2 conditions.4 However, it is generally accepted that chronic nasal inflammation causes an increase in nasal airway resistance because of mucosal swelling.5-7 And there is evidence for nasal inflammation causing OSAS.8 The objection was to study whether NARES might constitute a risk factor for an OSAS. Therefore, we polysomnographically analyzed 26 patients presenting typical symptoms of sleep apnea. Ten patients, diagnosed to suffer from NARES, were compared with 16 age- and body mass index (BMI)-matched individuals without any nasal inflammation to work out differences in their sleeping parameters pointing to NARES as a risk factor for OSAS. MATERIAL AND METHODS Patients The study was performed at the Department of Oto-Rhino-Laryngology/Head and Neck Surgery of Ludwig-Maximilians-University Munich, Klinikum Grosshadern, Germany. We included 26 patients presenting themselves in our outpatient department, reporting typical symptoms of sleep apnea, such as choking or gasping during sleep, recurrent awakening from sleep, unrefreshing sleep, daytime fatigue, impaired concentration, or snoring. Ten patients were diagnosed to suffer from NARES (9 men: 1 woman). They were compared with 16 age- and BMI-matched individuals (16 men) without any nasal inflammation. Ear, nose, and throat status, with special regard to the size of the palatine tonsils, elongation of the uvula, velum, septal deviation, and so on (determined by semiquantitative scores), was similar in all patients.
KRAMER ET AL
wool pieces at 4,000 rpm for 10 minutes, as described earlier.9 Patients’ sera were analyzed for total and specific immunoglobulin E and the routine in vitro allergy screening test SX1 (identical to Phadiatop; Pharmacia Diagnostic, Freiburg, Germany). Nasal secretions were analyzed for eosinophilic cationic protein (ECP) (Pharmacia Diagnostics) as a marker of tissue eosinophilia.10 Nasal inflammatory diseases, such as sinusitis, allergic rhinitis, nasal polyposis, or vasomotor rhinitis, were excluded in all patients. None of the patients were under nasal medication. Patients suffering from NARES showed the typical history of year-long nasal congestion and rhinorrhea.
Rhinomanometry To estimate nasal obstruction, we were able to perform standard rhinomanometry in 4 of the NARES patients and in 5 of the noninflamed patients. Nasal flow as a summary score of both nostrils in milliliters per second at 150 Pa inspiration was used for comparison, as generally accepted.
Polysomnography Polysomnography was performed as described earlier.11 Briefly, patients slept 2 nights in our sleeping laboratory, whereas the second night was measured to avoid the so-called first-night effect.12 The monitoring included electroencephalogram (C3/A2, C4/A1 of the international electrode placement system), electrooculogram, chin and leg electromyogram, and electrocardiogram (modified V-2 lead). Respiration was investigated by oronasal airflow (thermal sensors), thoracic and abdominal movements (piezo sensors), snoring sound (microphone), and oxygen saturation (pulse oximetry). Records were scored following the Rechtschaffen and Kales international criteria for sleep/wake determination.2,13 As the most important parameters for determination of an OSAS, we choose the apnea-hypopnea index (AHI), the apnea index (AI), the hypopnea index (HI), and mean and minimum oxygen-saturation during sleep. Differential diagnoses for OSAS, such as simple snoring, central sleep apnea syndrome, narcolepsy, restless leg syndrome, and so on, were excluded by polysomnography.
Nasal Inflammation
Statistic
All patients were tested for an underlying nasal disease by patient’s history, endoscopic nasal examination, and, if needed, computed tomography scans of paranasal sinuses. Serum and nasal secretions were obtained from every patient. Nasal secretions were gained by placing small cotton wool pieces into the middle meatus of the nose for 10 minutes, followed by centrifugation of the cotton
A standard PC with SPSS 10.0 software was used for the statistical evaluation and graphic presentation of the results. Significance was evaluated by the independent samples t test. Box plots presenting median (horizontal line), interquartile area (box), and highest and lowest counts, respectively (lines), were chosen for the graphic presentation of the results (*P ⬍ .05; **P ⬍ .01; ns, not significant).
NARES
175
correlation was observed in nondiseased individuals. Polysomnography Patients suffering from NARES revealed significantly (P ⬍ .01) impaired polysomnographic parameters (AHI, HI, mean and minimal oxygen saturation) compared with noninflamed individuals (Figs 1-5). NARES patients suffered from severe OSAS (7/10), whereas patients without any nasal inflammation suffered from moderate OSAS or less (13/16), according to the criteria of the American Academy of Sleep Medicine.2 DISCUSSION Fig 1. Apnea-hypopnea index. Significantly elevated AHI in NARES compared with patients without any nasal inflammation. Box plots present median (horizontal line), interquartile area (box), and highest and lowest counts, respectively (lines). *P < .05; **P < .01; n.s., not significant.
RESULTS There was no significant difference in age (NARES mean age 56.8 ⫾ 12.5 v no nasal inflammation: 58.8 ⫾ 11.6 ) or BMI (NARES: 29.3kg/m2 ⫾ 2.8 v no nasal inflammation: 29.7kg/m2 ⫾ 3.8) between both groups studied. ECP (ng/mL) was highly significantly (P ⬍ .001) elevated in patients suffering from NARES (NARES: 660.7 ⫾ 282.0 v no nasal inflammation 31.2 ⫾ 61.3).
We compared polysomnographic parameters of age- and BMI-matched patients presenting typical symptoms of OSAS in regards whether they suffer from NARES or not. Other forms of underlying nasal inflammation were excluded. Patients with NARES were significantly more impaired by OSAS then noninflamed individuals. NARES patients suffered from severe OSAS, whereas the latter suffered from only moderate OSAS, according to the
Rhinomanometry Rhinomanometric data displayed no significant difference between both groups. Nasal flow (mL/s) as summary score of both nostrils at 150 Pa inspiration was NARES: 564.5 ⫾ 116.9 v no nasal inflammation: 367.0 ⫾ 210.8. Looking for correlations (Pearson’s) revealed in patients suffering from NARES a significant (P ⬍ .01) inverse correlation between nasal flow measured by rhinomanometry and AI (r ⫽ ⫺0.99), HI (r ⫽ ⫺0.93), and AHI (r ⫽ ⫺0.97) and a significant (P ⬍ .01) correlation between nasal flow and mean oxygen saturation (r ⫽ 0.97). No such significant
Fig 2. Apnea index. Elevated AI in NARES compared with patients without any nasal inflammation. Box plots present median (horizontal line, interquartile area (box), and highest and lowest counts respectively (lines). *P < .05; **P < .01; n.s., not significant.
176
Fig 3. Hypopnea index. Significantly elevated HI in NARES compared with patients without any nasal inflammation. Box plots present median (horizontal line, interquartile area (box), and highest and lowest counts respectively (lines). *P < .05; **P < .01; n.s., not significant.
criteria of the American Academy of Sleep Medicine.2 Our data support results of others, suggesting chronic nasal inflammation to cause
Fig 4. Mean oxygen saturation. Significantly decreased mean oxygen saturation during sleep in NARES compared with patients without any nasal inflammation. Box plots present median (horizontal line, interquartile area (box), and highest and lowest counts respectively (lines). *P < .05; **P < .01; n.s., not significant.
KRAMER ET AL
Fig 5. Minimal oxygen saturation. Significantly decreased minimal oxygen saturation during sleep in NARES compared with patients without any nasal inflammation. Box plots present median (horizontal line, interquartile area (box), and highest and lowest counts respectively (lines). *P < .05; **P < .01; n.s., not significant.
OSAS.8 Interestingly, our data show that NARES deteriorates hypopneas more than apneas. One might interpret this that way that nasal obstruction because of NARES causes primarily a partial obstruction of the upper airways and consecutively deteriorates hypopneas more than apneas. Both groups revealed no significant differences in nasal flow measured by standard rhinomanometry. This evokes discussion; NARES patients tended to have lower nasal obstruction than noninflamed individuals (although difference not significant), challenging the causative role of nasal congestion caused by mucosal swelling in nasal inflammation as the pivotal factor for the observed differences in polysomnographic parameters. On the other hand, we observed highly significant correlations between nasal flow and impaired polysomnographic parameters in the NARES group, whereas we did not find any of these correlations in noninflamed individuals. Further studies involving more patients are certainly needed to answer this question. Rare prevalences of NARES make this a challenging target. Furthermore, one would ask for an objective measurement of nasal congestion, such as acoustic rhinometry, measuring nasal
NARES
airflow continuously during the whole night and in the supine position, and not while sitting, as we did. However, as far as we know, these methodological problems are unsolved to date. Neuronal reflex branches might help to interpret our data: chronic, eosinophilic nasal inflammation, such as NARES, might activate and/or augment neuronal reflex branches, such as the nasal-pulmonary reflex, described to cause alveolar hypoventilation.3 As a hypothesis, this might result in an increase in hypopnea index, as we observed. Such neuronal nasal (pharyngeal)-pulmonary (bronchial) reflex branches are well described in rhinitis and asthma.14-16 Furthermore, Leone and coworkers17 showed pathologic bronchial responsiveness and elevated sputum ECP in 46% of NARES patients without any respiratory symptoms as a sign of a pulmonary inflammation in these patients. Studies on sudden infant death syndrome detected a positive correlation between respiratory tract infections and apneas.18 Thus, nasal inflammation, transmitted via circulating mediators or neuronal reflexes, might count for the observed impaired polysomnographic parameters in NARES.18 CONCLUSIONS We observed significantly impaired polysomnographic parameters (HI, AHI, mean and minimal oxygen saturation) in patients suffering from NARES compared with patients without any nasal inflammation. Our data point to NARES as a risk factor for the induction or augmentation of OSAS. Our data support results of others, suggesting chronic nasal inflammation to cause OSAS. Mechanisms for our observations are not fully understood yet. Nasal obstruction or neuronal reflexes might be involved.
177
REFERENCES 1. Jacobs RL, Freedmann PM, Boswell RN: Nonallergic rhinitis with eosinophilia (NARES) syndrome. J Allergy Clin Immunol 61:253-262, 1981 2. AASM Task Force: Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep 22: 667-689, 1999 3. Papsidero MJ: The role of nasal obstruction in obstructive sleep apnea syndrome. Int Arch Allergy Immunol 72:82-84, 1993 4. Kramer MF, de la Chaux R, Dreher A, et al: Allergic rhinitis does not constitute a risk factor for obstructive sleep apnea syndrome. Acta Otolaryngol 121:494-499, 2001 5. McNicholas WT, Tarlo S, Cole P: Obstructive apneas during sleep in patients with seasonal allergic rhinitis. Am Rev Respir Dis 126:625-628, 1982 6. Olsen KD, Kern EB: Nasal influences on snoring and obstructive sleep apnea. Mayo Clin Proc 65:1095-1105, 1990 7. McColley SA, Carroll JL, Curtis S, et al: High prevalences of allergic sensitization in children with habitual snoring and obstructive sleep apnea. Chest 111:170-173, 1997 8. Rubinstein I: Nasal inflammation in patients with obstructive sleep apnea. Laryngoscope 105:175-177, 1995 9. Klimek L, Rasp G: Norm values for eosinophil cationic protein in nasal secretions: Influence of specimen collection. Clin Exp Allergy 29:367-374, 1999 10. Klimek L, Rasp G: Cell activation markers in rhinitis and rhinosinusitis. 1: Eosinophilic cationic protein (ECP). Laryngorhinootologie 75:665-670, 1996 11. American Thoracic Society: Indications and standards for cardiopulmonary sleep studies. Am Rev Respir Dis 139:569-578, 1989 12. Browman CP, Cartwright RD: The first night effect on sleep and dream. Bol Psychiatry 15:809-812, 1980 13. Rechtschaffen A, Kales A (eds): A manual of standardized technology, techniques and scoring system for sleep stages of human subjects. Los Angeles, CA, Brain Information Service/Brain Research Institute, UCLA, 1968 14. Sluder G: Asthma as a nasal reflex. JAMA 73:589, 1919 15. Slavin RG: Complications of allergic rhinitis: implications for sinusitis and asthma. J Allergy Clin Immunol 101:S357-S360, 1998 16. Hoehne JH, Reed CE: Where is the allergic reaction in ragweed asthma? J Allergy Clin Immunol 48:36-39, 1971 17. Leone C, Teodoro C, Pelucchi A, et al: Bronchial responsiveness and airway inflammation in patients with nonallergic rhinitis with eosinophilia syndrome. J Allergy Clin Immunol 100:775-780, 1997 18. Lindgren C, Gro¨ gaard J: Reflex apnoea response and inflammatory mediators in infants with respiratory tract infection. Acta Paediatr 85:798-803, 1996