Clinical control in the dual diagnosis of obstructive sleep apnea syndrome and rhinitis: A prospective analysis Neil G. Parikh, M.D., Imran Junaid, M.D., Lee Sheinkopf, M.D., Inderpal Randhawa, M.D., Silverio M. Santiago, M.D., and William B. Klaustermeyer, M.D.
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ABSTRACT
Background: Obstructive sleep apnea syndrome (OSAS) and allergic rhinitis (AR) are common coexisting disorders. Upper airway, specifically nasal resistance, is thought to increase during exacerbations of AR and nonallergic rhinitis (NAR), as well as in OSAS. The study objective was to determine if a correlation exists between clinical control of rhinitis and OSAS. Methods: This prospective study followed 43 patients with concurrent OSAS and AR or NAR. OSAS was diagnosed by polysomnography, and AR or NAR was diagnosed by history, skin testing, serum-specific IgE, and total IgE levels. Measurements of control of OSAS included the Epworth Sleepiness Scale (ESS) survey and compliance with continuous positive airway pressure (CPAP) device. Measurements of rhinitis control included Assessment of Nasal Symptom Severity and Assessment of Nonnasal Symptom Severity (NSS refers to both) and Global Assessment of Nasal and Nonnasal Symptom Severity surveys (GSS). Higher NSS scores correlate with more rhinitis symptoms, whereas higher GSS scores correlate with less symptoms. Results: All patients completed the study. There was a positive correlation between ESS and NSS scores (p ⬍ 0.001), inverse correlation between ESS and GSS scores (p ⬍ 0.001), inverse correlation between CPAP compliance and NSS scores (p ⬍ 0.001), and positive correlation between CPAP compliance and GSS scores (p ⬍ 0.001). There was no statistically significant difference between the AR, NAR, and AR/NAR groups. Conclusion: Our study showed a statistically significant positive correlation between clinical control of rhinitis symptoms and clinical control of OSAS. This study emphasizes the importance of achieving concurrent optimal control of both OSAS and AR/NAR. (Am J Rhinol Allergy 28, e52–e55, 2014; doi: 10.2500/ajra.2014.28.3977)
T
O
bstructive sleep apnea syndrome (OSAS) is caused by collapse of the upper airway, leading to apneas, oxygen desaturation, and sleep arousals. Potential risk factors include obesity, upper airway anatomic abnormalities (including increased soft or lymphoid tissue), family history, and nasal obstruction. OSA has been recognized as an independent risk factor in the development of hypertension,1 stroke,2 and ischemic heart disease.3,4,5 With an estimated 12 million patients affected in the United States,6 the association of OSA with other diseases is presently being investigated. Allergic rhinitis (AR) and nonallergic rhinitis (NAR) are characterized by nasal congestion, pruritus, sneezing, and difficulty with nasal breathing leading to nasal obstruction and increased nasal airflow resistance. Combined, AR and NAR afflict up to 25% of the population.7 Rhinitis transiently increases nasal resistance8 and therefore has been implicated as a risk factor for OSAS. OSAS and AR are common comorbid disorders. Upper airway resistance is thought to transiently increase during exacerbations of AR and NAR and has been reported to correlate with the presence of sleep apnea.9,10,11 Multiple studies have proposed subjective and objective benefits of treatment with topical nasal steroids in patients with OSAS and rhinitis.12,13 Patients with OSAS who complain of nasopharyngeal symptoms have limited compliance with therapy.8 This study is the first to prospectively follow this subset of patients with these comorbidities and attempt to establish a correlation between symptom and control of OSAS and rhinitis.
O D
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From the Division of Allergy and Immunology, Veterans Affairs Greater Los Angeles Healthcare Systems/The David Geffen School of Medicine at University of California– Los Angeles, Los Angeles, California The authors have no conflicts of interest to declare pertaining to this article Address correspondence to Neil G. Parikh, M.D., University of California–Los Angele– Veterans Affairs Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Allergy/Immunology (111R), Los Angeles, CA 90073 E-mail address: [email protected] Copyright © 2014, OceanSide Publications, Inc., U.S.A.
e52
METHODS
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This study was approved by the Research and Development Committee. Forty-three nonconsecutive patients, mean age 59 years, were enrolled from the Allergy and Immunology clinic at the University of California–Los Angeles West Los Angeles Veterans Affairs hospital. Informed consent was obtained from all subjects. Inclusion criteria included patients with either AR and/or NAR with a concurrent diagnosis of OSAS. AR was determined by patient history, allergen skin-prick testing and intradermal (aeroallergens) or serum-specific serum IgE levels, and total serum IgE levels. Elevated total serum IgE levels were used as a potential marker for atopy and aided in classification of patient’s rhinitis as being allergic. NAR was diagnosed by history, exclusion of the aforementioned, and response to targeted therapy such as anticholinergic therapy. The AR/NAR group was characterized by patient’s who showed evidence of allergy via allergen skin testing or serum-specific serum IgE levels but clinically had typical symptoms and triggers of AR and NAR and also often required targeted treatment such as anticholinergic therapy. OSAS was diagnosed at the West Los Angeles Sleep Center, by history and either ambulatory or overnight laboratory-based polysomnography. The Epworth Sleepiness Scale (ESS) is a subjective measure of daytime sleepiness used to measure clinical control of OSAS where lower scores reflect lesser sleepiness. Nasal continuous positive airway pressure (nCPAP) compliance was monitored monthly and tabulated as a percentage of days per month of usage. Measurements of clinical control of rhinitis included Assessment of Nasal Symptom Severity and Assessment of Nonnasal Symptom Severity (NSS refers to both assessments) and Global Assessment of Nasal and Nonnasal Symptom Severity surveys (GSS). Part of the NSS involves assessment of nasal symptom severity including patient evaluation of nasal symptoms such as sneezing, runny nose, congestion (stuffiness), itchy nose, postnasal drip, and total nasal symptoms using a seven-point visual analog scale. The other part of the NSS involves using a similar visual analog scale but assessing nonnasal symptoms such as eye symptoms, throat symptoms, chronic cough, ear symptoms, headache, and mental function. The visual analog scale ranges from ranking severity of symptoms from 1 (none, to an occasional limited episode) to 7 (unbearably severe, impairment in function). Hence,
January–February 2014, Vol. 28, No. 1
Delivered by Ingenta to: Guest User IP: 5.101.220.230 On: Tue, 05 Jul 2016 12:49:26 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
Table 1 Demographics Race Black White Hispanic Age (yr) Mean Range Gender Male Female Rhinitis type AR AR/NAR NAR
11 (26%) 27 (63%) 5 (11%) 59 33–84
Y P
39 (91%) 4 (9%) 20 (47%) 15 (35%) 8 (19%)
AR ⫽ allergic rhinitis; NAR ⫽ nonallergic rhinitis.
higher NSS scores represent more severe nasal and nonnasal symptoms. The GSS asks the patient to globally assess nasal and nonnasal symptom severity also using a seven-point visual analog scale; however, in this case a score of 7 represents having no symptoms with no functional impairment (opposite of NSS). Hence, higher GSS scores represent minimal to no symptom burden. Surveys were administered monthly by the primary investigators in the Allergy and Immunology clinic or via telephone. Patients were followed for a period of 6 months. For each patient, assessment of control of their rhinitis was based on their NSS and GSS scores. To achieve improved control, patients were treated with different combinations of medications, such as intranasal corticosteroid, antihistamine, anticholinergic sprays, appropriate environmental controls, oral antihistamines, and oral leukotriene modifiers. Treatment plans or regimens were based on their complaints, specific type of rhinitis, and underlying conditions.
RESULTS
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All 43 patients (39 men and 4 women) completed the study. Twenty patients were diagnosed with AR, 8 with NAR and 15 with both AR and NAR (Table 1). No significant correlation was found between age groups, race, sex, or smoking when compared with ESS, NSS, GSS, or nCPAP compliance. There was no difference between the AR, NAR, and AR/NAR groups when considering nCPAP compliance, GSS, ESS, NSS, or ESS scores (p ⬍ 0.01). Use of humidifier, nCPAP setting, lying on side, or use of dental appliance were not statistically significant when compared with ESS, NSS, GSS, or nCPAP compliance. One-way ANOVA in conjunction with standard linear regression was used to compare ESS and NSS scores. A direct relationship was shown between ESS score and NSS scores (p ⬍ 0.001; Fig. 1). Lower ESS and NSS scores were consistent with fewer episodes of sleepiness and fewer nasal symptoms. An inverse relationship was found between ESS and GSS scores (p ⬍ 0.001; Fig. 2). Higher GSS scores represented less patient symptoms. An inverse relationship was shown between CPAP compliance and NSS scores (p ⬍ 0.001). Additionally, there was a direct relationship between improved GSS scores and CPAP compliance (p ⬍ 0.001; Fig. 3).
DISCUSSION Increase in nasal resistance has been implicated in worsening OSA. Experimental models on healthy individuals with induced nasal obstruction produced sleep-disordered breathing.14,15 However, there appears to be no correlation between the degree of nasal obstruction/ resistance and sleep-disordered breathing symptoms.16
AR is secondary to an IgE-mediated nasal response to an allergen resulting in activation of mast cells and the release of inflammatory cytokines. This inflammation leads to increased nasal congestion and nasal resistance.17 This nasal resistance results in microarousal and fragmented sleep throughout the night. It is estimated that patients with AR experience microarousals 10 times more often than normal subjects.11 The sleep disturbances that occur lead to daytime somnolence and fatigue. Increased nasal resistance has also been shown to play a role in hypoxemic apnea in obese patients with OSAS.18 Additionally, some studies have established another link between AR and sleep disturbances and fatigue. Inflammatory mediators, such as lymphokines, interferon ␥, TNF, and IL-1, may be implicated in regulation of sleep. Some of these cytokines may themselves cause symptoms of daytime somnolence and fatigue.19 Although data are limited regarding the association between NAR and sleep disturbances, it is accepted that NAR shares in common with AR an underlying syndrome of nasal mucosal inflammation. This may be a common pathway to the increased nasal resistance and consequent sleep disturbances described. One study found that patients with OSAS who did not have rhinitis did have increased nasal inflammation.20 Additionally, the proinflammatory effect of OSAS on the nasal mucosa may cause increased nasal resistance. High levels of circulating cytokines are found in patients with OSA without AR. These cytokines may disrupt sleep architecture, leading to alteration of rapid eye movement and non-rapid eye movement sleep patterns.19 Additional studies are needed to establish an association between these inflammatory markers, nasal inflammation, and clinical control in these conditions. The effect of reducing nasal resistance via nasal surgery in patients with OSA has been studied. In a study looking at the effect of nasal surgery alone on sleep quality in patients with OSAS and nasal obstruction, surgery was only partially effective in improving sleep quality, architecture, and snoring. It had no effect on the change of the distribution of sleep positions and obstructive apnea.22 A meta-analysis of nasal surgery for obstructive sleep apnea showed efficacy in reducing daytime sleepiness and snoring (determined by ESS scores and individual questionnaires, respectively) but had a limited success rate of 16.7% in treating OSA.23 Hence, multiple mechanisms such as nasal inflammation in chronic rhinitis, in addition to nasal structure, may be involved in nasal resistance/obstruction and OSA. We hypothesize that there may be a link between patients with chronic rhinitis and OSAS, such that, as rhinitis symptoms improve, so do symptoms of OSAS. Our study showed that the specific type of rhinitis did not affect the control of rhinitis symptoms (as measured by NSS and GSS scores) or OSA (ESS scores). From this, we also hypothesize that the amount of nasal inflammation and associated rhinitis symptoms, regardless of the etiology, is the most important determinant. As rhinitis is better controlled, nasal inflammation, nasal resistance, and nasal and circulating cytokines may decrease. The decreased nasal resistance may improve airflow and lessen hypoxia and apneas. In addition, with lower amounts of circulating cytokines, there may be less disturbance of sleep architecture, yielding improved sleep quality and restfulness. A leading cause of patient discontinuation of nCPAP is rhinitis and as shown in this study, there exists a direct relationship with improved nCPAP compliance and improved rhinitis symptoms. Our study shows a statistically significant correlation between clinical control of OSAS and rhinitis through comparisons among ESS, NSS, GSS scores, and CPAP compliance. Based on the direct relationship established between ESS and NSS scores, we interpret this to represent improved control of nonnasal and nasal symptoms correlated (lower NSS scores) to mean concomitant decreased
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American Journal of Rhinology & Allergy
Delivered by Ingenta to: Guest User IP: 5.101.220.230 On: Tue, 05 Jul 2016 12:49:26 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
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Figure 1. One-way ANOVA in conjunction with standard linear regression comparing Epworth Sleepiness Scale (ESS) scores versus nasal symptom severity scores (p ⫽ 0.001) and nonnasal symptom severity scores (p ⬍ 0.001).
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Figure 2. One-way ANOVA in conjunction with standard linear regression comparing Epworth Sleepiness Scale (ESS) scores versus global severity scores (p ⬍ 0.001).
subjective sleepiness (lower ESS scores). Also, an inverse relationship was shown between ESS and GSS scores, representing the similar concept. This study emphasizes the clinical need to approach OSAS with a concurrent clinical approach to AR/NAR. Although larger studies are necessary to confirm these findings, the optimal treatment of AR/ NAR may significantly impact the clinical control of OSAS and its negative sequelae.
REFERENCES 1.
2.
3.
e54
Nieto FJ, Young TB, Lind BK, et al. Association of sleep disordered breathing, sleep apnea, and hypertension in a large community based study: Sleep Heart Health Study. JAMA 283:1829–1836, 2000. Parra O, Arboix A, Bechich S, et al. Time course of sleep-related breathing disorders in first-ever stroke or transient ischemic attack. Am J Respir Crit Care Med 161:375–380, 2000. Shahar E, Whitney CW, Redline S, et al. Sleep-disordered breathing and cardiovascular disease: Cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 163:19–25, 2001.
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Figure 3. One-way ANOVA in conjunction with standard linear regression comparing continuous positive airway pressure (CPAP) compliance versus global severity scores (p ⬍ 0.001).
4.
Wang H, Parker JD, Newton GE, et al. Influence of obstructive sleep apnea on mortality in patients with heart failure. J Am Coll Cardiol 49:1632–1633, 2007. 5. Campos-Rodriguez F, Pen˜a-Grin˜an N, Reyes-Nun˜ez N, et al. Mortality in obstructive sleep apnea-hypopnea patients treated with positive airway pressure. Chest 128:624–633, 2005. 6. Sher AE. An overview of sleep disordered breathing for the otolaryngologist. Ear Nose Throat J 78:694–695, 698–700, 703–706, 1999. 7. Bousquet J, Van Cauwenberge P, and Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 108:147–334, 2001. 8. Hollandt JH, and Mahlerwein M. Nasal breathing and continuous positive airway pressure (CPAP) in patient with obstructive sleep apnea (OSA). Sleep Breath 7:72–94, 2003. 9. Canova CR, Downs SH, Knoblauch A, et al. Increased prevalence of perennial allergic rhinitis in patients with obstructive sleep apnea. Respiration 71:138–143, 2004. 10. Young T, Finn L, and Kim H. Nasal obstruction as a risk factor for sleep- disordered breathing. J Allergy Clin Immunol 99:S757–S762, 1997.
January–February 2014, Vol. 28, No. 1
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11.
12.
13.
14.
15.
16. 17.
McNicholas WT, Tarlo S, Cole P, et al. Obstructive apneas during sleep in patients with seasonal allergic rhinitis. Am Rev Respir Dis 126:625–628, 1982. Hughes K, Glass C, Ripchinski M, et al. Efficacy of the topical nasal steroid budesonide on improving sleep and daytime somnolence in patients with perennial allergic rhinitis. Allergy 58:380–385, 2003. Kiely JL, Nolan P, and McNicholas WT. Intranasal corticosteroid therapy for obstructive sleep apnea in patients with co-existing rhinitis. Thorax 59:50–55, 2004. Zwillich CW, Pickett C, Hanson FN, and Weil JV. Disturbed sleep and prolonged apnea during nasal obstruction in normal men. Am Rev Respir Dis 124:158–160, 1981. Olsen KD, Kern EB, and Westbrook PR. Sleep and breathing disturbance secondary to nasal obstruction. Otolaryngol Head Neck Surg 89:804–810, 1981. Blakeley BW, and Mahowald MW. Nasal resistance and sleep apnea. Laryngoscope 97:752–754, 1987. Sly RM. Changing prevalence of allergic rhinitis and asthma. Ann Allergy Asthma Immunol 82:233–252, 1999.
18.
19.
20. 21.
22.
23.
Tagaya M, Nakata S, Yasuma F, et al. Pathogenetic role of increased nasal resistance in obese patients with obstructive sleep apnea syndrome. Am J Rhinol Allergy 24:51–54, 2010. Vuurman EF, van Veggel LM, Uiterwijk MM, et al. Seasonal allergic rhinitis and antihistamine effects on children’s learning. Ann Allergy 71:121–126, 1993. Rubinstein I. Nasal inflammation in patients with obstructive sleep apnea. Laryngoscope 105:175–177, 1995. Bergeron C, Kimoff J, and Hamid Q. Obstructive sleep apnea syndrome and inflammation. J Allergy Clin Immunol 116:1393–1396, 2005. Choi JH, Kim EJ, Kim YS, et al. Effectiveness of nasal surgery alone on sleep quality, architecture, position, and sleep-disordered breathing in obstructive sleep apnea syndrome with nasal obstruction. Am J Rhinol Allergy 25:338–341, 2011. Li HY, Wang PC, Chen YP, et al. Critical appraisal and meta-analysis of nasal surgery for obstructive sleep apnea. Am J Rhinol Allergy 25:45–49, 2011. e
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American Journal of Rhinology & Allergy
Delivered by Ingenta to: Guest User IP: 5.101.220.230 On: Tue, 05 Jul 2016 12:49:26 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
e55
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ABSTRACT
Background: Obstructive sleep apnea syndrome (OSAS) and allergic rhinitis (AR) are common coexisting disorders. Upper airway, specifically nasal resistance, is thought to increase during exacerbations of AR and nonallergic rhinitis (NAR), as well as in OSAS. The study objective was to determine if a correlation exists between clinical control of rhinitis and OSAS. Methods: This prospective study followed 43 patients with concurrent OSAS and AR or NAR. OSAS was diagnosed by polysomnography, and AR or NAR was diagnosed by history, skin testing, serum-specific IgE, and total IgE levels. Measurements of control of OSAS included the Epworth Sleepiness Scale (ESS) survey and compliance with continuous positive airway pressure (CPAP) device. Measurements of rhinitis control included Assessment of Nasal Symptom Severity and Assessment of Nonnasal Symptom Severity (NSS refers to both) and Global Assessment of Nasal and Nonnasal Symptom Severity surveys (GSS). Higher NSS scores correlate with more rhinitis symptoms, whereas higher GSS scores correlate with less symptoms. Results: All patients completed the study. There was a positive correlation between ESS and NSS scores (p ⬍ 0.001), inverse correlation between ESS and GSS scores (p ⬍ 0.001), inverse correlation between CPAP compliance and NSS scores (p ⬍ 0.001), and positive correlation between CPAP compliance and GSS scores (p ⬍ 0.001). There was no statistically significant difference between the AR, NAR, and AR/NAR groups. Conclusion: Our study showed a statistically significant positive correlation between clinical control of rhinitis symptoms and clinical control of OSAS. This study emphasizes the importance of achieving concurrent optimal control of both OSAS and AR/NAR. (Am J Rhinol Allergy 28, e52–e55, 2014; doi: 10.2500/ajra.2014.28.3977)
T
O
bstructive sleep apnea syndrome (OSAS) is caused by collapse of the upper airway, leading to apneas, oxygen desaturation, and sleep arousals. Potential risk factors include obesity, upper airway anatomic abnormalities (including increased soft or lymphoid tissue), family history, and nasal obstruction. OSA has been recognized as an independent risk factor in the development of hypertension,1 stroke,2 and ischemic heart disease.3,4,5 With an estimated 12 million patients affected in the United States,6 the association of OSA with other diseases is presently being investigated. Allergic rhinitis (AR) and nonallergic rhinitis (NAR) are characterized by nasal congestion, pruritus, sneezing, and difficulty with nasal breathing leading to nasal obstruction and increased nasal airflow resistance. Combined, AR and NAR afflict up to 25% of the population.7 Rhinitis transiently increases nasal resistance8 and therefore has been implicated as a risk factor for OSAS. OSAS and AR are common comorbid disorders. Upper airway resistance is thought to transiently increase during exacerbations of AR and NAR and has been reported to correlate with the presence of sleep apnea.9,10,11 Multiple studies have proposed subjective and objective benefits of treatment with topical nasal steroids in patients with OSAS and rhinitis.12,13 Patients with OSAS who complain of nasopharyngeal symptoms have limited compliance with therapy.8 This study is the first to prospectively follow this subset of patients with these comorbidities and attempt to establish a correlation between symptom and control of OSAS and rhinitis.
O D
O N
From the Division of Allergy and Immunology, Veterans Affairs Greater Los Angeles Healthcare Systems/The David Geffen School of Medicine at University of California– Los Angeles, Los Angeles, California The authors have no conflicts of interest to declare pertaining to this article Address correspondence to Neil G. Parikh, M.D., University of California–Los Angele– Veterans Affairs Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Allergy/Immunology (111R), Los Angeles, CA 90073 E-mail address: [email protected] Copyright © 2014, OceanSide Publications, Inc., U.S.A.
e52
METHODS
O C
This study was approved by the Research and Development Committee. Forty-three nonconsecutive patients, mean age 59 years, were enrolled from the Allergy and Immunology clinic at the University of California–Los Angeles West Los Angeles Veterans Affairs hospital. Informed consent was obtained from all subjects. Inclusion criteria included patients with either AR and/or NAR with a concurrent diagnosis of OSAS. AR was determined by patient history, allergen skin-prick testing and intradermal (aeroallergens) or serum-specific serum IgE levels, and total serum IgE levels. Elevated total serum IgE levels were used as a potential marker for atopy and aided in classification of patient’s rhinitis as being allergic. NAR was diagnosed by history, exclusion of the aforementioned, and response to targeted therapy such as anticholinergic therapy. The AR/NAR group was characterized by patient’s who showed evidence of allergy via allergen skin testing or serum-specific serum IgE levels but clinically had typical symptoms and triggers of AR and NAR and also often required targeted treatment such as anticholinergic therapy. OSAS was diagnosed at the West Los Angeles Sleep Center, by history and either ambulatory or overnight laboratory-based polysomnography. The Epworth Sleepiness Scale (ESS) is a subjective measure of daytime sleepiness used to measure clinical control of OSAS where lower scores reflect lesser sleepiness. Nasal continuous positive airway pressure (nCPAP) compliance was monitored monthly and tabulated as a percentage of days per month of usage. Measurements of clinical control of rhinitis included Assessment of Nasal Symptom Severity and Assessment of Nonnasal Symptom Severity (NSS refers to both assessments) and Global Assessment of Nasal and Nonnasal Symptom Severity surveys (GSS). Part of the NSS involves assessment of nasal symptom severity including patient evaluation of nasal symptoms such as sneezing, runny nose, congestion (stuffiness), itchy nose, postnasal drip, and total nasal symptoms using a seven-point visual analog scale. The other part of the NSS involves using a similar visual analog scale but assessing nonnasal symptoms such as eye symptoms, throat symptoms, chronic cough, ear symptoms, headache, and mental function. The visual analog scale ranges from ranking severity of symptoms from 1 (none, to an occasional limited episode) to 7 (unbearably severe, impairment in function). Hence,
January–February 2014, Vol. 28, No. 1
Delivered by Ingenta to: Guest User IP: 5.101.220.230 On: Tue, 05 Jul 2016 12:49:26 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
Table 1 Demographics Race Black White Hispanic Age (yr) Mean Range Gender Male Female Rhinitis type AR AR/NAR NAR
11 (26%) 27 (63%) 5 (11%) 59 33–84
Y P
39 (91%) 4 (9%) 20 (47%) 15 (35%) 8 (19%)
AR ⫽ allergic rhinitis; NAR ⫽ nonallergic rhinitis.
higher NSS scores represent more severe nasal and nonnasal symptoms. The GSS asks the patient to globally assess nasal and nonnasal symptom severity also using a seven-point visual analog scale; however, in this case a score of 7 represents having no symptoms with no functional impairment (opposite of NSS). Hence, higher GSS scores represent minimal to no symptom burden. Surveys were administered monthly by the primary investigators in the Allergy and Immunology clinic or via telephone. Patients were followed for a period of 6 months. For each patient, assessment of control of their rhinitis was based on their NSS and GSS scores. To achieve improved control, patients were treated with different combinations of medications, such as intranasal corticosteroid, antihistamine, anticholinergic sprays, appropriate environmental controls, oral antihistamines, and oral leukotriene modifiers. Treatment plans or regimens were based on their complaints, specific type of rhinitis, and underlying conditions.
RESULTS
O D
T
O N
All 43 patients (39 men and 4 women) completed the study. Twenty patients were diagnosed with AR, 8 with NAR and 15 with both AR and NAR (Table 1). No significant correlation was found between age groups, race, sex, or smoking when compared with ESS, NSS, GSS, or nCPAP compliance. There was no difference between the AR, NAR, and AR/NAR groups when considering nCPAP compliance, GSS, ESS, NSS, or ESS scores (p ⬍ 0.01). Use of humidifier, nCPAP setting, lying on side, or use of dental appliance were not statistically significant when compared with ESS, NSS, GSS, or nCPAP compliance. One-way ANOVA in conjunction with standard linear regression was used to compare ESS and NSS scores. A direct relationship was shown between ESS score and NSS scores (p ⬍ 0.001; Fig. 1). Lower ESS and NSS scores were consistent with fewer episodes of sleepiness and fewer nasal symptoms. An inverse relationship was found between ESS and GSS scores (p ⬍ 0.001; Fig. 2). Higher GSS scores represented less patient symptoms. An inverse relationship was shown between CPAP compliance and NSS scores (p ⬍ 0.001). Additionally, there was a direct relationship between improved GSS scores and CPAP compliance (p ⬍ 0.001; Fig. 3).
DISCUSSION Increase in nasal resistance has been implicated in worsening OSA. Experimental models on healthy individuals with induced nasal obstruction produced sleep-disordered breathing.14,15 However, there appears to be no correlation between the degree of nasal obstruction/ resistance and sleep-disordered breathing symptoms.16
AR is secondary to an IgE-mediated nasal response to an allergen resulting in activation of mast cells and the release of inflammatory cytokines. This inflammation leads to increased nasal congestion and nasal resistance.17 This nasal resistance results in microarousal and fragmented sleep throughout the night. It is estimated that patients with AR experience microarousals 10 times more often than normal subjects.11 The sleep disturbances that occur lead to daytime somnolence and fatigue. Increased nasal resistance has also been shown to play a role in hypoxemic apnea in obese patients with OSAS.18 Additionally, some studies have established another link between AR and sleep disturbances and fatigue. Inflammatory mediators, such as lymphokines, interferon ␥, TNF, and IL-1, may be implicated in regulation of sleep. Some of these cytokines may themselves cause symptoms of daytime somnolence and fatigue.19 Although data are limited regarding the association between NAR and sleep disturbances, it is accepted that NAR shares in common with AR an underlying syndrome of nasal mucosal inflammation. This may be a common pathway to the increased nasal resistance and consequent sleep disturbances described. One study found that patients with OSAS who did not have rhinitis did have increased nasal inflammation.20 Additionally, the proinflammatory effect of OSAS on the nasal mucosa may cause increased nasal resistance. High levels of circulating cytokines are found in patients with OSA without AR. These cytokines may disrupt sleep architecture, leading to alteration of rapid eye movement and non-rapid eye movement sleep patterns.19 Additional studies are needed to establish an association between these inflammatory markers, nasal inflammation, and clinical control in these conditions. The effect of reducing nasal resistance via nasal surgery in patients with OSA has been studied. In a study looking at the effect of nasal surgery alone on sleep quality in patients with OSAS and nasal obstruction, surgery was only partially effective in improving sleep quality, architecture, and snoring. It had no effect on the change of the distribution of sleep positions and obstructive apnea.22 A meta-analysis of nasal surgery for obstructive sleep apnea showed efficacy in reducing daytime sleepiness and snoring (determined by ESS scores and individual questionnaires, respectively) but had a limited success rate of 16.7% in treating OSA.23 Hence, multiple mechanisms such as nasal inflammation in chronic rhinitis, in addition to nasal structure, may be involved in nasal resistance/obstruction and OSA. We hypothesize that there may be a link between patients with chronic rhinitis and OSAS, such that, as rhinitis symptoms improve, so do symptoms of OSAS. Our study showed that the specific type of rhinitis did not affect the control of rhinitis symptoms (as measured by NSS and GSS scores) or OSA (ESS scores). From this, we also hypothesize that the amount of nasal inflammation and associated rhinitis symptoms, regardless of the etiology, is the most important determinant. As rhinitis is better controlled, nasal inflammation, nasal resistance, and nasal and circulating cytokines may decrease. The decreased nasal resistance may improve airflow and lessen hypoxia and apneas. In addition, with lower amounts of circulating cytokines, there may be less disturbance of sleep architecture, yielding improved sleep quality and restfulness. A leading cause of patient discontinuation of nCPAP is rhinitis and as shown in this study, there exists a direct relationship with improved nCPAP compliance and improved rhinitis symptoms. Our study shows a statistically significant correlation between clinical control of OSAS and rhinitis through comparisons among ESS, NSS, GSS scores, and CPAP compliance. Based on the direct relationship established between ESS and NSS scores, we interpret this to represent improved control of nonnasal and nasal symptoms correlated (lower NSS scores) to mean concomitant decreased
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American Journal of Rhinology & Allergy
Delivered by Ingenta to: Guest User IP: 5.101.220.230 On: Tue, 05 Jul 2016 12:49:26 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
e53
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Figure 1. One-way ANOVA in conjunction with standard linear regression comparing Epworth Sleepiness Scale (ESS) scores versus nasal symptom severity scores (p ⫽ 0.001) and nonnasal symptom severity scores (p ⬍ 0.001).
T
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Figure 2. One-way ANOVA in conjunction with standard linear regression comparing Epworth Sleepiness Scale (ESS) scores versus global severity scores (p ⬍ 0.001).
subjective sleepiness (lower ESS scores). Also, an inverse relationship was shown between ESS and GSS scores, representing the similar concept. This study emphasizes the clinical need to approach OSAS with a concurrent clinical approach to AR/NAR. Although larger studies are necessary to confirm these findings, the optimal treatment of AR/ NAR may significantly impact the clinical control of OSAS and its negative sequelae.
REFERENCES 1.
2.
3.
e54
Nieto FJ, Young TB, Lind BK, et al. Association of sleep disordered breathing, sleep apnea, and hypertension in a large community based study: Sleep Heart Health Study. JAMA 283:1829–1836, 2000. Parra O, Arboix A, Bechich S, et al. Time course of sleep-related breathing disorders in first-ever stroke or transient ischemic attack. Am J Respir Crit Care Med 161:375–380, 2000. Shahar E, Whitney CW, Redline S, et al. Sleep-disordered breathing and cardiovascular disease: Cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 163:19–25, 2001.
O C
Figure 3. One-way ANOVA in conjunction with standard linear regression comparing continuous positive airway pressure (CPAP) compliance versus global severity scores (p ⬍ 0.001).
4.
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