October 23, 2007
Therapeutic Options for Reducing Sleep Impairment in Allergic Rhinitis, Rhinosinusitis, and Nasal Polyposis
By Storms, William Yawn, Barbara; Fromer, Leonard
Key words: Congestion - Nasal obstruction - Nasal polyposis - Rhinitis - Rhinosinusitis - Sleep ABSTRACTBackground: Patients with inflammatory disorders of the upper airways, such as allergic rhinitis, rhinosinusitis, and nasal polyposis, often have significant sleep disturbances. Poor sleep can lead to fatigue, daytime somnolence, impaired daytime functioning as reflected in lower levels of productivity at work or school, and a reduced quality of life. Although the exact mechanisms by which these inflammatory nasal conditions disturb sleep is not fully understood, congestion appears to be a key factor and is generally the most common and bothersome symptom for patients with these conditions. Successful therapy should improve patients' sleep and well-being without introducing any negative effects on sleep.
Scope of literature search: Literature searches of Medline, Embase, and abstracts from medical/ scientific conferences were conducted for the period of 1995 through mid-2006 for primary and review articles and conference presentations about sleep disturbance related to allergic rhinitis, rhinosinusitis, and nasal polyposis. These searches also sought to identify articles examining how treatments for those diseases improved sleep and, consequently, patients' quality of life. Surveys of the impact of congestion on patients' quality of life and their sleep also were consulted. Clinical studies were selected for discussion if they were randomized, double-blind, and placebo-controlled. Limitations of this review include the absence of any direct comparisons of the effectiveness of different drugs on improving sleep and shortcomings in the statistical methods of the patient surveys.
Findings: Intranasal corticosteroids (INSs) are the most effective medication for reducing congestion in patients with inflammatory nasal conditions. There is a growing amount of evidence that a reduction in congestion with INSs is associated with improved sleep, reduced daytime sleepiness, and enhanced patient quality of life.
Conclusion: Relief of sleep impairment associated with inflammatory disorders of the nose and sinuses can be addressed with INS therapy.
Allergic rhinitis (AR), rhinosinusitis, and nasal polyposis are inflammatory disorders of the nose and sinuses that are commonly encountered in clinical practice. Sleep impairment is often a significant problem for patients with these conditions, and should be established and addressed. For example, in a population-based study of 5838 people (data on nasal congestion and sleep problems identified by questionnaire in 4927 participants and by objective laboratory measurement in 911), nearly 75% who either 'always' (> 15 nights per month) or Often' (5-15 nights per month) had nighttime rhinitis symptoms reported chronic nonrestorative sleep1. Similar results were seen in other studies which concluded that nasal congestion is a significant predictor of snoring and that congestion can lead to sleep fragmentation and deprivation, daytime tiredness, and altered behavioral patterns23. Sleep impairment is also reported by patients with rhinosinusitis and nasal polyposis4'5. The sleep disturbances experienced by patients with these conditions include difficulty going to sleep, snoring, interrupted sleep, sleep apnea, and hypopnea. Such disturbances, together with nocturnal symptoms such as congestion, sneezing, rhinorrhea, and pruritus, can reduce patient quality of life and lead to daytime sleepiness, fatigue, irritability, and decreased learning and productivity at school and work.
Congestion (nasal and sinus) is thought to be the main cause of sleep impairment and is a common, and the most bothersome symptom, of all three inflammatory disorders of the upper airways. Other factors that may play a role in causing sleep disturbance include other symptoms of these conditions, inflammatory mediators released as part of the underlying disease processes, and the effects of some of the medications used to treat these disorders.
Intranasal corticosteroids (INSs) improve the symptoms - especially congestion - of AR, rhinosinusitis, and nasal polyposis. In addition, INSs have been shown to improve patients' sleep and quality of life.
This review summarizes the existing literature about the sleep- associated burden of AR, rhinosinusitis, and nasal polyposis, and examines how it can be managed effectively. Several electronic literature searches of Medline and Embase were conducted in November and December 2005 and in June and July 2006 to identify primary research and review articles addressing the impact on sleep of the three inflammatory nasal and sinus conditions, as well as the effectiveness of treatments for those conditions in improving patients' ability to sleep and quality of life. The references cited in relevant papers were reviewed for related articles. This search also sought to identify abstracts presented at the annual meetings of the American Academy of Allergy Asthma and Immunology, the American College of Allergy Asthma and Immunology, and the World Allergy Congress by searching supplements of the Journal of Allergy and Clinical Immunology, the Annals of Asthma, Allergy & Immunology, and Allergy and Clinical Immunology International, the journals which publish abstracts from the three congresses, respectively. The words allergic rhinitis, rhinosinusitis (also sinusitis), and nasal polyposis (also polyps) combined with the words sleep, sleep disturbance(s), and sleep impairment(s) were used as search terms. Other search terms included intranasal corticosteroids (also steroids), antihistamines, and immune response mediators with sleep; congestion and sleep; and quality of life and sleep. Searches also were conducted by the brand and generic names of the intranasal corticosteroids - Nasonex (mometasone furcate), Flonase (fluticasone propionate), Rhinocort (budesonide), Beconase or Vancenase (beclomethasone dipropionate), Nasacort (triamcinolone acetonide), and Nasalide or Nasarel (flunisolide) - coupled with the terms on sleep noted above. Both review and primary research papers were consulted, but primary papers were assigned a priority in selecting the data included in this manuscript.
The current burden of AR, rhinosinusitis, and nasal polyposis
Allergic rhinitis, rhinosinusitis, and nasal polyposis affect 2- 40% of the population in the USA and Europe, as shown in Table I6"14.
Congestion is a common, and the most troublesome, symptom of inflammatory disorders of the upper respiratory tract. Nasal congestion is a major symptom of AR, together with rhinorrhea, sneezing, and pruritus of the eyes, nose, and throat15. A large Internet survey of individuals with AR (adults and children) was conducted by an independent market research company, Roper Public Affairs Group of NOP World, New York, New York, on behalf of Schering-Plough Corporation, Kenilworth, New Jersey. Roper Public Affairs Group prepared the survey questions. Participants were part of the NOP World panel of consumers, recruited voluntarily through telephone surveys and Internet advertisements. Eligible individuals were asked to complete the Internet survey, which questioned respondents about the symptoms and effects of AR and its treatment. The survey found that 85% (margin of error +- 2%) of respondents experienced nasal congestion16. Of these respondents, 40% considered their nasal congestion to be severe, and 50% stated that congestion was the most bothersome of their symptoms. This result is similar to that of other patient surveys of adults and adolescents in which congestion (also referred to as a stuffy nose or a stuffy/blocked nose) was found to be the most frequently occurring symptom of AR and the one with the most impact on quality of life17'18.
Table 1. Prevalence of allergie rhinitis, rhinosinusitis, and nasal polyposis
Allergic rhinitis may also cause sinus congestion and blockage. A recent survey of allergy symptoms in the United States and five European countries (France, Germany, Italy, Spain, and the UK) was conducted by an independent market research company, Forbes Consulting Group, on behalf of Schering-Plough. The survey, which focused on patients' attitudes toward allergy suffering and approaches to allergy treatment, was administered by an online panel of people with allergy (adults and children). Respondents reporting both nasal and sinus congestion had the highest number of 'suffering days' per year across all countries19. The symptoms of AR display a circadian rhythm, increasing during the night and peaking in the early morning hours19"21. Fatigue and irritability, the most common morning complaints in this survey, reported by 31-59% and 26-58% of individuals, respectively, depending on the country19, may be a consequence of subjects' disturbed sleep during the previous night.
The major symptoms of rhinosinusitis and nasal polyposis include congestion/obstruction, nasal discharge or postnasal drip, facial pain/pressure, and, especially in individuals with nasal polyps, reduction or loss of sense of smell10'22. As in AR, congestion/ obstruction, including both nasal and sinus congestion, is typically the most problematic symptom22'23. For individuals with acute rhinosinusitis (ARS), symptoms generally last for up to 4 weeks, although recent information suggests they can persist (continuously or intermittently) for up to 12 weeks22. The most common causes of ARS are viral infection or allergic reaction, both of which induce an inflammatory response, leading to obstruction of the sinus ostia, retention of secretions, and bacterial invasion; these, in turn, produce the signs and symptoms characteristic of ARS and will have an effect on sleep24. Sleep impairment in AR, rhinosinusitis, and nasal polyposis
Allergic rhinitis adversely affects sleep25 in children26, adolescents17, and adults19. Children with AR are three times more likely to have disturbed sleep than unaffected children27. In the survey of allergy sufferers in the United States and five European countries, among the large proportion of patients who reported trouble falling asleep or getting enough sleep, up to 79% reported the problem as disruptive19. Both sleep-disordered breathing (snoring, sleep apnea, and/or hypopnea) and 'microarousals', which are brief awakenings that occur many times during the night, but of which patients are unaware, have been associated with AR; they are reviewed in Table 227'3'. These sleep disturbances may be the cause of daytime fatigue in AR patients. Sleep-disordered breathing in children, particularly snoring, is associated with an increased risk of obstructive sleep apnea syndrome32. In fact, nasal obstruction associated with AR and adenoidal hypertrophy causes children to breathe through their mouth and to snore while sleeping32. In a study involving children with snoring problems, McColley et al. found that 36% were sensitized to allergens, which is about three times higher than expected for the general pediatrie population. The frequency of obstructive sleep apnea in these subjects was about 50% greater than in the nonatopic group of children who snored. The authors reported an increased frequency of obstructive sleep apnea in children with AR and suggested an association between snoring and allergy32.
Patients with rhinosinusitis23'33 and nasal polyposis5 also experience sleep disturbances and fatigue. A recent study conducted in France found that the risk of sleep disturbance was more than doubled in patients with nasal polyposis compared with controls, and snoring was reported by a significantly greater proportion of people with nasal polyposis than by those without the condition34.
Table 2. Sleep disturbances associated with allergic rhinitis, rhinosinusitis, and/or nasal polyposis
The effects of sleep impairment
Sleep disturbances from AR, rhinosinusitis, and nasal polyposis can adversely affect cognitive function, daytime alertness, work or school performance, emotion, mood, and social interactions35'39. Daytime fatigue, difficulty concentrating, and decreased psychomotor performance are all commonly reported by individuals with AR37'39'40. Children with AR suffer from reduced learning ability and poor performance at school, compared with healthy children41'42. Adolescents with AR report difficulties getting a good night's sleep and problems doing their school work17, and children with snoring have poorer school performance than controls43. Sleep-disordered breathing (especially habitual snoring) in children has been associated with hyperactive and inattentive behavior similar to that seen in attention-deficit hyperactivity disorder27'44. The sleep disturbances seen in adult patients with seasonal AR (SAR) and perennial AR (PAR) have also been associated with reduced psychological well-being45.
Causes of sleep impairment
Is congestion the key factor in sleep impairment?
Congestion has been reported to be a significant factor in the sleep impairment and daytime fatigue associated with AR, rhinosinusitis, and nasal polyposis46"48. Nasal congestion (or nasal airway resistance) tends to increase when an individual lays down49. In addition, the normal circadian rhythm increases congestion during the late night and early morning2021. The combination of worsened congestion at night and increased congestion in the recumbent position may be additive, further aggravating sleep problems.
In the large Internet survey of more than 2000 individuals with AR mentioned earlier, approximately half of the respondents reported that nasal congestion woke them up during the night or made it difficult for them to fall asleep16. The adverse effects on sleep were greater among those with severe congestion than in those with mild or moderate congestion. Congestion was the symptom that adults (50%) and caregivers of children (65%) wanted most to prevent, and that was most likely to trigger a visit to a physician (54% and 69%, respectively)16 (Figure 1).
More objective studies have also demonstrated that the congestion associated with rhinitis and other upper respiratory tract disorders may lead to the onset or worsening of sleep disturbances, including obstructive sleep apnea50 and that congestion is a risk factor for habitual snoring1'5'. Indeed, allergic patients with congestion are almost twice as likely to have moderateto-severe sleep-disordered breathing as those without congestion1. Rhinorrhea and, to lesser degrees, pruritus and sneezing, can also interfere with sleep46'48'52.
The suggestion that congestion is largely responsible for the disturbed sleep and daytime sleepiness associated with AR is further supported by data from treatment studies that have shown that relief of congestion reduces these problems5354. Indeed, it has been suggested that physicians should consider evaluation and treatment of this symptom for all patients diagnosed with a sleepdisordered breathing condition55.
Immune response mediators
Inflammatory mediators (specifically, histamine and cytokines) released during allergic reactions may have a role in the sleep impairment associated with AR, rhinosinusitis, and nasal polyposis. Brain histamine is associated with regulation of the sleep-wake cycle56. Increased levels of proinflammatory cytokines have been linked in polysomnography studies to an increased time to onset of rapid eye movement (REM) sleep and a shorter time in REM sleep57. These findings suggest that the mediators may directly effect the central nervous system, where the sleep-wake cycle is regulated, and could contribute to disturbed sleep and feelings of fatigue or sleepiness during the day56" 58. As with the symptoms of congestion, the levels of these inflammatory mediators peak during the early morning hours, which could explain the greater sleep disturbances during this period and the higher level of AR symptoms upon awakening2859. Treatments that reduce the nocturnal release or activity of inflammatory mediators may decrease central nervous system effects on sleep and, in turn, diminish the associated sleep impairment.
Figure 1. Effects of nasal congestion on sleep in allergic rhinitis'6. Results are expressed as a proportion of all survey respondents. Data were collected in response to the question: 'In what ways, if any, has the nasal congestion affected you/ your child during the night?'
Effects of therapy
Medication choices for patients with AR, such as second- generation or nonsedating antihistamines, intranasal ipratropium bromide, and INSs, have all been shown to improve health-related quality of life60, but they are not equally effective in reducing congestion and sleep impairment; indeed, some may even have adverse effects on sleep.
Nonsedating oral antihistamines (e.g. cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine) are widely used to treat AR, and effectively relieve nasal symptoms such as rhinorrhea, sneezing, and pruritus61. They are generally less effective in relieving congestion, although recent studies have shown some efficacy in reduction of congestion62"65. They are sometimes administered in combination with a decongestant for additional congestion relief8. Intranasal or oral decongestants can effectively reduce congestion, but may have adverse effects on sleep as a result of their stimulatory effects, and are also associated with systemic side effects, such as tachycardia and urinary retention61. Intranasal decongestants should not be used for prolonged periods because of the risk of developing rebound congestion (rhinitis medicamentosa)61. Antihistamine nasal sprays, such as azelastine, can reduce congestion in patients with rhinitis66, and recent studies have shown that this reduction is accompanied by improvements in sleep, ability to perform daily activities67, and quality of life68. It has been suggested that the efficacy of antihistamine nasal sprays, including their greater effectiveness in reducing congestion than oral antihistamines, and their rapid onset of effect, are due to their local action at the inflammatory site68'69. Most studies show that antihistamine nasal sprays are not as effective in relieving congestion as corticosteroid nasal sprays; e.g. in one randomized, controlled trial (N = 44), azelastine did not improve symptoms of congestion as well as flunisolide70. However, a recent study noted that the combination of azelastine plus fluticasone nasal spray improved congestion in patients with SAR to a greater extent than the individual therapies71. Antihistamine nasal sprays can also cause daytime drowsiness72.
Intranasal corticosteroids are the primary treatment option for patients with significant nasal congestion6''73'74. They are effective in relieving congestion associated with AR, ARS, and nasal polyposis10'73'75. Mometasone furoate, for example, has demonstrated efficacy in relieving congestion in all three conditions76"82. Mometasone alleviated congestion in patients with SAR81 and PAR80, nasal congestion and obstruction in nasal polyposis82, and was significantly more effective than amoxicillin or placebo in relieving congestion in patients with ARS77. Results from clinical studies have demonstrated that intranasal fluticasone propionate reduces congestion in patients with AR83, chronic rhinosinusitis84, and nasal polyposis8586. Additionally, it has been reported that sinus pain and pressure are reduced in patients with AR during treatment with fluticasone propionate87. Congestion in patients with AR is also reduced by the INS medications budesonide, flunisolide, and triamcinolone acetonide88'91. Intranasal budesonide has been shown to relieve congestion in patients with chronic rhinosinusitis or nasal polyps92'93.
Intranasal corticosteroids also have been used to treat children with enlarged tonsils and adenoids, which cause sleep apnea and disturbed sleep. Demain et al. administered beclomethasone 336 mug a day or placebo for 8 weeks to a small cohort (N = 17) of children with adenoidal hypertrophy and sleep apnea. Investigators found significant reductions in adenoidal hypertrophy and symptoms such as restless sleep and nasal congestion with INS therapy compared with placebo94.
Numerous small studies have indicated that alleviation of congestion with INSs may have beneficial effects on sleep, daytime sleepiness, and quality of life in patients with inflammatory upper respiratory tract disorders (Table 3)27,53,70,82,88,89,95-103 The sleep-related symptoms that elicit the greatest amount of patient complaints are daytime somnolence or sleepiness and fatigue27,52,88,89,95 and, to a slightly lesser extent, difficulty falling and then remaining asleep88'89. Treatment of adults or children with AR with INSs resulted in significant improvements in subjective assessments of sleep, daytime sleepiness, fatigue, and quality of life, compared with placebo or alternative treatments such as azelastine, although not all sleep-related problems were significantly improved in all studies.
Treatment with INSs also improves sleep and quality of life in patients with rhinosinusitis and nasal polyposis. In schoolchildren with symptomatic rhinitis or chronic rhinosinusitis, therapy with intranasal budesonide for at least 3 months reduced symptoms, improved performance at school and concentration, and decreased the number of sleepless nights (p
Table 3. Clinical studies of the effects of intranasal corticostiroids on sleep and/or quality of life in patients with allergic rhinitis, rhinosinusitis, and nasal polyposis
Table 3. Clinical studies of the effects of intranasal corticostiroids on sleep and/or quality of life in patients with allergic rhinitis, rhinosinusitis, and nasal polyposis
Intranasal corticosteroids are not associated with adverse effects on sleep, such as those observed with decongestants. Further, INSs are safe and well tolerated and, when used properly, exert their beneficiai effects without significant systemic effects104. The mild side effect profile of the INSs is related to intranasal administration placing the drug at the site of inflammation, thereby allowing therapeutic concentrations to be achieved in the nose. In addition, most of the INS is swallowed and undergoes first-pass metabolism in the liver without entering the systemic circulation73. When administered at recommended doses, INSs appear to have a negligible effect on the hypothalamic pituitary adrenal (HPA) axis of children or adults75,76,105,106. Clinical studies have assessed the potential effect of the INSs on HPA axis function using measurements such as knemometry107 (a sensitive noninvasive measure for evaluating lower leg growth), blood and urinary cortisol levels108, cosyntropin stimulation testing109, and stadiometry"0. Most studies concluded that INSs did not affect HPA axis function or have any impact on the rate of growth in children. In one of the few exceptions, lower leg growth velocity as measured by knemometry in children (n = 11) treated with budesonide (given at a high dose of 200 [mu]g BID) was significantly slower after 6 weeks than during a pretreatment run-in period (p
Long-term studies in children with AR have shown that mometasone furoate and fluticasone propionate do not adversely affect growth velocity109. Moreover, the INSs have been shown in long-term clinical studies not to cause nasal atrophy, and mometasone and fluticasone have been found to restore nasal mucosa to normal114"118.
Many people with inflammatory disorders of the upper airways do not see a physician, choosing instead to treat themselves with over- the-counter (OTC) products119'120 such as isotonic/hypertonic saline as a nasal douche; sedating antihistamines such as diphenhydramine, brompheniramine, and chlorpheniramine; and decongestants. The most common oral decongestants vary in efficacy; pseudoephedrine and phenylpropanolamine are effective, but phenylephrine undergoes first- pass metabolism, rendering it considerably less effective at currently recommended doses. Because pseudoephedrine is no longer available as an OTC product, people seeking relief may opt for the less appropriate phenylephrine121. It is important to determine whether patients are using those products or herbal preparations to treat their symptoms, because they may adversely affect sleep.
The anticholinergic agent ipratropium bromide improves rhinorrhea, but usually does not relieve congestion61. Nevertheless, there is some evidence that sleep and quality of life improve during treatment with ipratropium bromide in patients with AR97. A few studies in patients with AR or sleep-disordered breathing have shown an improvement in sleep and quality of life following therapy with a leukotriene receptor antagonist122'123 or a combination of an antihistamine and a leukotriene receptor antagonist124. However, leukotriene receptor antagonists alone or in combination with antihistamines are not as effective as INSs in reducing congestion or improving quality of life in AR patients125'126.
Surgical treatment can improve congestion and quality of life in patients with nasal polyposis127'128 or chronic rhinosinusitis10129. However, nasal polyps tend to recur, and surgery is indicated for chronic rhinosinusitis/nasal polyposis only when conservative, medical treatment, such as INS administration, has failed.
Several limitations of this review should be acknowledged. First, randomized, placebo-controlled, blinded clinical trials comparing the effectiveness in reducing sleep disturbances of the drugs for the three upper respiratory diseases have not been conducted. Comparisons across different classes of drugs (e.g. antihistamines versus INSs) in improving congestion have been reported, but the efficacy of the different INSs in reducing sleep disturbances has not been compared.
second, the Roper survey cited above has some inherent limitations. Only people with nasal congestion could participate, people with more troublesome symptoms may have been more motivated to respond, and the survey was limited to people with Internet access. Consequently, people with symptoms (e.g. rhinorrhea, itching) that were more severe than congestion may have been excluded from the survey. Finally, AR was self-reported and not confirmed by a physician's diagnosis, so the survey may have included people with rhinitis that did not derive from an allergic reaction16.
Allergic rhinitis has a significant adverse impact on patients' lives through sleep impairment. Effectively treating congestion, which is associated with sleep disturbances, could be the key to reducing needless patient suffering. Intranasal corticosteroids are the most efficacious treatments for nasal congestion. Moreover, data on sleep-related endpoints from clinical trials with INSs indicate that alleviation of congestion is associated with a trend toward improved sleep, reduced daytime fatigue, and improved quality of life. The effectiveness of INSs in relieving sleep impairment and improving quality of life in AR, rhinosinusitis, and nasal polyposis needs to be confirmed in further studies. The use of INSs could help to ensure optimal management of all aspects of these bothersome conditions.
Declaration of interest: This study was funded by the Schering- Plough Corporation. None of the authors received any payment for this manuscript. Editorial support in the preparation of this manuscript was provided by Gardiner Caldwell-London and Adelphi Eden Health Communications.
1. Young T, Finn L, Kim H. Nasal obstruction as a risk factor for sleep-disordered breathing. J Allergy Clin Immunol 1997;99: S757-62
2. Stradling JR, Crosby JH. Predictors and prevalence of obstructive sleep apnoea and snoring in 1001 middle aged men. Thorax 1991;46:85-90
3. Olsen KD, Kern EB. Nasal influences on snoring and obstructive sleep apnea. Mayo CUn Proc 1990;65:1095-105
4. Kenny TJ, Duncavage J, Bracikowski J, et al. Prospective analysis of sinus symptoms and correlation with paranasal computed tomography scan. Otolaryngol Head Neck Surg 2001;125:40-3
5. Radenne F, Lamblin C, Vandezande LM, et al. Quality of life in nasal polyposis. J Allergy Clin Immunol 1999;104:79-84 6. Bousquet J, van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. Allergy 2002;57:841-55
7. Dykewicz MS, Fineman S, Skoner DP, et al. Diagnosis and management of rhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 1998;81:478-518
8. Bauchau V, Durham SR. Prevalence and rate of diagnosis of allergic rhinitis in Europe. Eur Respir J 2004;24:758-64
9. Anand VK. Epidemiology and economic impact of rhinosinusitis. Ann Otol Rhinol Laryngol Suppl 2004;193:3-5
10. Bachert C, Hermann K, Mosges R, et al. An update on the diagnosis and treatment of sinusitis and nasal polyposis. Allergy 2003;58:176-91
11. Benninger MS, Ferguson BJ, Hadley JA. Adult chronic rhinosinusitis: definitions, diagnosis, epidemiology, and pathophysiology. Otolaryngol Head Neck Surg 2003;129:Sl-32
12. Klossek JM, Neukirch F, Pribil C, et al. Prevalence of nasal polyposis in France: a cross-sectional, case-control study. Allergy 2005;60:233-7
13. Johansson L, Akerlund A, Holmberg K, et al. Prevalence of nasal polyps in adults: the Skovde population-based study. Ann Otol Rhinol Laryngol 2003;! 12:625-9
14. Hedman J, Kaprio J, Poussa T, et al. Prevalence of asthma, aspirin intolerance, nasal polyposis and chronic obstructive pulmonary disease in a population-based study. Int J Epidemiol 1999;28:717-22
15. D'Alonzo GE. Scope and impact of allergic rhinitis. J Am Osteopath Assoc 2002;102(Suppl 2):S2-6
16. Shedden A. Impact of nasal congestion on quality of life and work productivity in allergic rhinitis. Findings from a large online survey. Treat Respir Med 2005;4:438-46
17. Juniper EF, Guyatt GH, Dolovich J. Assessment of quality of life in adolescents with allergic rhinoconjunctivitis: development and testing of a questionnaire for clinical trials. J Allergy Clin Immunol 1994;93:413-23
18. Juniper EF, Guyatt GH. Development and testing of a new measure of health status for clinical trials in rhinoconjunctivitis. Clin Exp Allergy 1991;21:77-83
19. Forbes Consulting Group. Understanding the dynamics surrounding allergy suffering and treatment: US and global results. September 2005
20. Reinberg A, Gervais P, Levi F, et al. Orcadian and circannual rhythms of allergic rhinitis: an epidemiologic study involving chronobiologic methods. J Allergy CUn Immunol 1988;81:51-62
21. Smolensky MH, Reinberg A, Labrecque G. Twenty-four hour pattern in symptom intensity of viral and allergic rhinitis: treatment implications. J Allergy CUn Immunol 1995;95: 1084-96
22. Fokkens W, Lund V, Bachert C, et al. EAACI position paper on rhinosinusitis and nasal polyps executive summary. Allergy 2005;60:583-601
23. Bhattacharyya N. The economic burden and symptom manifestations of chronic rhinosinusitis. Am J Rhinol 2003; 17:27- 32
24. Meltzer EO, Hamilos DL, Hadley JA, et al. Rhinosinusitis: establishing definitions for clinical research and patient care. J Allergy Clin Immunol 2004;114:S155-212
25. Settipane RA. Complications of allergic rhinitis. Allergy Asthma Proc 1999;20:209-13
26. Lack G. Pediatrie allergic rhinitis and comorbid disorders. J Allergy Clin Immunol 2001;108:S9-15
27. Mansfield LE, Diaz G, Posey CR, et al. Sleep disordered breathing and daytime quality of Ufe in children with allergic rhinitis during treatment with intranasal budesonide. Ann Allergy Asthma Immunol 2004;92:240-4
28. Ferguson BJ. Influences of allergic rhinitis on sleep. Otolaryngol Head Neck Surg 2004; 130:617-9
29. Lavie P, Gertner R, Zomer J, et al. Breathing disorders in sleep associated with 'microarousals' in patients with allergic rhinitis. Acta Otolaryngol 1981;92:529-33
30. McNicholas WT, Tarlo S, Cole P, et al. Obstructive apneas during sleep in patients with seasonal allergic rhinitis. Am Rev Respir Dis 1982; 126:625-8
31. Staevska MT, Mandajieva MA, Dimitrov VD. Rhinitis and sleep apnea. Curr Allergy Asthma Rep 2004;4:193-9
32. McColley SA, Carroll JL, Curtis S, et al. High prevalence of allergic sensitization in children with habitual snoring and obstructive sleep apnea. Chest 1997; 111:170-3
33. Chester AC. Symptoms of rhinosinusitis in patients with unexplained chronic fatigue or bodily pain: a pilot study. Arch Intern Med2003;163:1832-6
34. Serrano E, Neukirch F, Pribil C, et al. Nasal polyposis in France: impact on sleep and quality of life. J Laryngol Otol 2005; 119:543-9
35. Flemons WW, Tsai W. Quality of life consequences of sleepdisordered breathing. J Allergy Clin Immunol 1997;99:S750-6
36. Marshall PS, O'Hara C, Steinberg P. Effects of seasonal allergic rhinitis on selected cognitive abilities. Ann Allergy Asthma Immunol 2000;84:403-10
37. Wilken JA, Berkowitz R, Kane R. Decrements in vigilance and cognitive functioning associated with ragweed-induced allergic rhinitis. Ann Allergy Asthma Immunol 2002;89:372-80
38. Kessler RC, Almeida DM, Berglund P, et al. Pollen and mold exposure impairs the work performance of employees with allergic rhinitis. Ann Allergy Asthma Immunol 2001;87:289-95
39. Spaeth J, Klimek L, Mosges R. Sedation in allergic rhinitis is caused by the condition and not by antihistamine treatment. Allergy 1996;51:893-906
40. Meltzer EO. Quality of life in adults and children with allergic rhinitis. J Allergy Clin Immunol 2001;108:S45-53
41. Vuurman EF, van Veggel LM, Uiterwijk MM, et al. Seasonal allergic rhinitis and antihistamine effects on children's learning. Ann Allergy 1993;71:121-6
42. Simons FE. Learning impairment and allergic rhinitis. Allergy Asthma Proc 1996;17:185-9
43. Urschitz MS, Guenther A, Eggebrecht E, et al. Snoring, intermittent hypoxia and academic performance in primary school children. Am J Respir Crit Care Med 2003; 168:464-8
44. Urschitz MS, Eitner S, Guenther A, et al. Habitual snoring, intermittent hypoxia, and impaired behavior in primary school children. Pediatrics 2004;114:1041-8
45. Kremer B, den Hartog HM, Jolies J. Relationship between allergic rhinitis, disturbed cognitive functions and psychological well-being. Clin Exp Allergy 2002;32:1310-5
46. Juniper EF, Rohrbaugh T, Meltzer EO. A questionnaire to measure quality of life in adults with nocturnal rhinoconjunctivitis. J Allergy Clin Immunol 2003;111:484-90
47. Kakumanu S, Glass C, Craig T. Poor sleep and daytime somnolence in allergic rhinitis: significance of nasal congestion. Am J Respir Med 2002; 1:195-200
48. Storms WW. Pharmacologie approaches to daytime and nighttime symptoms of allergic rhinitis. J Allergy Clin Immunol 2004;114:5146- 53
49. Rundcrantz H. Postural variations of nasal patency. Acta Otolaryngol 1969;68:435-43
50. Corey JP, Houser SM, Ng BA. Nasal congestion: a review of its etiology, evaluation, and treatment. Ear Nose Throat J 2000;79:690- 3, 696, 698
51. Young T, Finn L, Palta M. Chronic nasal congestion at night is a risk factor for snoring in a population-based cohort study. Arch Intern Med 2001;161:1514-9
52. Quraishi SA, Davies MJ, Craig TJ. Inflammatory responses in allergic rhinitis: traditional approaches and novel treatment strategies. J Am Osteopath Assoc 2004;104(Suppl 5):S7-15
53. Craig TJ, Teets S, Lehman EB, et al. Nasal congestion secondary to allergic rhinitis as a cause of sleep disturbance and daytime fatigue and the response to topical nasal corticosteroids. J Allergy Clin Immunol 1998;101:633-7
54. Craig TJ, McCann JL, Gurevich F, et al. The correlation between allergic rhinitis and sleep disturbance. J Allergy Clin Immunol 2004; 114:S 139-45
55. Chen W, Kushida CA. Nasal obstruction in sleep-disordered breathing. Otolaryngol Clin North Am 2003;36:437-60
56. Tashiro M, Mochizuki H, Iwabuchi K, et al. Roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine Hl receptors in human brain. Life Sci 2002;72: 409-14
57. Krouse HJ, Davis JE, Krouse JH. Immune mediators in allergic rhinitis and sleep. Otolaryngol Head Neck Surg 2002; 126: 607-13
58. Mullington JM, Hinze-Selch D, Pollmacher T. Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions. Ann N Y Acad Sci 2001;933:201-10
59. Gelfand EW. Inflammatory mediators in allergic rhinitis. J Allergy Clin Immunol 2004;114:5135-8
60. Blaiss M. Quality of life in allergic rhinitis. Ann Allergy Asthma Immunol 1999;83:449-54
61. American Academy of Allergy, Asthma and Immunology 2000. The Allergy Report. Available from http://www.aaaai.org/ar/ default.htm [Last accessed 12 December 2006]
62. Berger WE, Lumry WR, Meltzer EO, et al. Efficacy of desloratadine, 5mg, compared with fexofenadine, 180mg, in patients with symptomatic seasonal allergic rhinitis. Allergy Asthma Proc 2006;27:214-23
63. Meltzer EO, Scheinmann P, Rosado Pinto JE, et al. Safety and efficacy of oral fexofenadine in children with seasonal allergic rhinitis - a pooled analysis of three studies. Pediatr Allergy Immunol 2004; 15:253-60
64. Potter PC, on behalf of the Study Group. Levocetirizine is effective for symptom relief including nasal congestion in adolescent and adult (PAR) sensitized to house dust mites. Allergy 2003;58:893-9
65. Horak F, Stubner P, Zieglmeyer R, et al. Comparison of the effects of desloratadine 5-mg daily and placebo on nasal airflow and seasonal allergic rhinitis symptoms induced by grass pollen exposure. Allergy 2003;58:481-5
66. lieberman P, Kaliner MA, Wheeler WJ. Open-label evaluation of azelastine nasal spray in patients with seasonal allergic rhinitis and nonallergic vasomotor rhinitis. Curr Med Res Opin 2005;21:611-8
67. Corren J, Storms W, Bernstein J, et al; Azelastine Cetirizine Trial No. 1 (ACT 1) Study Group. Effectiveness of azelastine nasal spray compared with oral cetirizine in patients with seasonal allergic rhinitis. Clin Ther 2005;27:543-53
68. lieberman P, Kaliner MA, Wheeler WJ. Open-label evaluation of azelastine nasal spray in patients with seasonal allergic rhinitis and nonallergic vasomotor rhinitis. Curr Med Res Opin 2005;21:611-8 69. Davies RJ, Bagnall AC, McCabe RN, et al. Antihistamines: topical vs oral administration. Clin Exp Allergy 1996;26(Suppl 3):ll-7
70. Berlin JM, Golden SJ, Teets S, et al. Efficacy of a steroid nasal spray compared with an antihistamine nasal spray in the treatment of perennial allergic rhinitis. J Am Osteopath Assoc 2000;100(Suppl7):S8-13
71. Ratner P, Sacks H. Randomized, double-blind trial of azelastine nasal spray plus fluticasone nasal spray compared to either agent alone in patients with allergy to Texas mountain cedar. Presented at: 2006 ACAAI Annual Scientific Meeting; November 9-15, 2006; Philadelphia, Pa
72. Astelin [package insert]. Somerset, NJ: Medpointe Pharmaceuticals; 2003
73. Bousquet J, van Cauwenberge P, Khaltaev N; ARIA Workshop Group, WHO. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108(Suppl):S147-336
74. Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ 1998;317:1624-9
75. van Cauwenberge P, Bachert C, Passalacqua G, et al. Consensus statement on the treatment of allergic rhinitis. Allergy 2000;55:116- 34
76. Nayak AS, Settipane GA, Pedinoff A, et al. Effective dose range of mometasone furoate nasal spray in the treatment of acute rhinosinusitis. Ann Allergy Asthma Immunol 2002;89:271-8
77. Meltzer EO, Bachert C, Staudinger H. Treating acute rhinosinusitis: comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo. J Allergy Clin Immunol 2005; 116:1289-95
78. Bloom M, Staudinger H. Effect of mometasone furoate nasal spray (MFNS) on nasal polyposis. J Allergy Clin Immunol 2004;113(Suppl):S282
79. Gawchik S, Goldstein S, Prenner B, et al. Relief of cough and nasal symptoms associated with allergic rhinitis by mometasone furoate nasal spray. Ann Allergy Asthma Immunol 2003;90:416-21
80. Mandl M, Nolop K, Lutsky BN. Comparison of once daily mometasone furoate (Nasonex) and fluticasone propionate aqueous nasal sprays for the treatment of perennial rhinitis. Ann Allergy Asthma Immunol 1997;79:370-8
81. Berger WE, Nayak AS, Staudinger HW. Mometasone furoate improves congestion in patients with moderate-to-severe seasonal allergic rhinitis. Ann Pharmacother 2005;39:1984-9
82. Stjarne P, Blomgren K, Caye-Thomasen P, et al. The efficacy and safety of once-daily mometasone furoate nasal spray in nasal polyposis: a randomized, double-blind, placebo-controlled study. Acta Otolaryngol 2006;126:606-12
83. Ortolani C, Foresi A, Di Lorenzo G, et al; FLNCO2 Italian Study Group. A double-blind, placebo-controlled comparison of treatment with fluticasone propionate and levocabastine in patients with seasonal allergic rhinitis. Allergy 1999;54:1173-80
84. Parikh A, Scadding GK, Darby Y, et al. Topical corticosteroids in chronic rhinosinusitis: a randomized, double- blind, placebocontrolled trial using fluticasone propionate aqueous nasal spray. Rhinology 2001;39:75-9
85. Holmberg K, Juliusson S, Balder B, et al. Fluticasone propionate aqueous nasal spray in the treatment of nasal polyposis. Ann Allergy Asthma Immunol 1997;78:270-6
86. Penttila M, Poulsen P, Hollingworth K, et al. Dose-related efficacy and tolerability of fluticasone propionate nasal drops 400microg once daily and twice daily in the treatment of bilateral nasal polyposis: a placebo-controlled randomized study in adult patients. Clin Exp Allergy 2000;30:94-102
87. Ratner PH, Howland WC 3rd, Jacobs RL, et al. Relief of sinus pain and pressure with fluticasone propionate aqueous nasal spray: a placebo-controlled trial in patients with allergic rhinitis. Allergy Asthma Proc 2002;23:259-63
88. Gurevich F, Glass C, Davies M, et al. The effect of intranasal steroid budesonide on sleep disturbance and daytime somnolence in patients with perennial allergic rhinitis. Allergy Asthma Proc 2005;26:268-74
89. 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 2003;58:380-5
90. Berger WE, Kaiser H, Gawchik SM, et al. Triamcinolone acetonide aqueous nasal spray and fluticasone propionate are equally effective for relief of nasal symptoms in patients with seasonal allergic rhinitis. Otolaryngol Head Neck Surg 2003; 129:16-23
91. Ozturk F, Turktas I, Asal K, et al. Effect of intranasal triamcinolone acetonide on bronchial hyperresponsiveness in children with seasonal allergic rhinitis and comparison of perceptional nasal obstruction with acoustic rhinometric assessment. Int J Pediatr Otorhinolaryngol 2004;68:1007-15
92. Lund VJ, Black JH, Szabo LZ, et al. Efficacy and tolerability of budesonide aqueous nasal spray in chronic rhinosinusitis patients. Rhinology 2004;42:57-62
93. Tos M, Svendstrup F, Arndal H, et al. Efficacy of aqueous and a powder formulation of nasal budesonide compared in patients with nasal polyps. Am J Rhinol 1998; 12:183-9
94. DeMain JG, Goetz DW. Pediatrie adenoidal hypertrophy with nasal airway obstruction: reduction with nasal beclomethasone. Pediatrics 1995;95:355-64
95. Craig TJ, Mende C, Hughes K, et al. The effect of topical nasal fluticasone on objective sleep testing and the symptoms of rhinitis, sleep and daytime somnolence in perennial allergic rhinitis. Allergy Asthma Proc 2003;24:53-8
96. Bender BG, Milgrom H. Comparison of the effects of fluticasone propionate aqueous nasal spray and loratadine on daytime alertness and performances in children with seasonal allergic rhinitis. Ann Allergy Asthma Immunol 2004;92:344-9
97. Kiely JL, Nolan P, McNicholas WT. Intranasal corticosteroid therapy for obstructive sleep apnoea in patients with co-existing rhinitis. Thorax 2004;59:50-5
98. Milgrom H, Biondi R, Georgitis JW, et al. Comparison of ipratropium bromide 0.03% with beclomethasone dipropionate in the treatment of perennial rhinitis in children. Ann Allergy Asthma Immunol 1999;83:105-11
99. Potter PC, Van Niekerk CH, Schoeman HS. Effects of triamcinolone on quality of life in patients with persistent allergic rhinitis. Ann Allergy Asthma Immunol 2003;91:368-74
100. Mintz M, Garcia J, Diener P, et al. Triamcinolone acetonide aqueous nasal spray improves nocturnal rhinitis-related quality of life in patients in a primary care setting: the Quality of Sleep in Allergic Rhinitis study. Ann Allergy Asthma Immunol 2004;92:255-61
101.Bachert C, Meltzer EO, Staudinger H, et al. Effect of mometasone furcate on the health-related quality of life of patients with acute rhinosinusitis. Presented at: World Allergy Congress 2005; June 26-July 1, 2005; Munich, Germany [Abstract 112]
102. Cutler DL, Banfield C, Melton B, et al. Safety of mometasone furoate nasal spray in children with allergic rhinitis as young as 2 years of age: a randomized controlled trial. Pediatr Asthma Allergy Immunol 2006; 19:46-53
103. Kamenov S, Kamenov B, Moskovljevic J, et al. Intranasal budesonide treatment of rhino-sinusitis improves quality of life in school children. Presented at: World Allergy Congress 2005; June 26- July 1, 2005; Munich, Germany [Abstract 713]
104.Benninger MS, Ahmad N, Marple BF. The safety of intranasal steroids. Otolaryngol Head Neck Surg 2003; 129:739-50
105. Alien DB. Systemic effects of intranasal steroids: an endocrinologist's perspective. J Allergy Clin Immunol 2000;106:S17990
106. Boner AL. Effects of intranasal corticosteroids on the hypothalamic-pituitary-adrenal axis in children. J Allergy Clin Immunol 2001;108(1 Suppl):S32-9
107. Wolthers OD, Pedersen S. Knemometric assessment of systemic activity of once daily intranasal dry-powder budesonide in children. Allergy 1994;49:96-9
108. Cutler DL, Banfield C, Affrime MB. Safety of mometasone furoate nasal spray in children with allergic rhinitis as young as 2 years of age: a randomized controlled trial. Pediatr Asthma Allergy Immunol 2006;19:146-53
109. Schenkel EJ, Skoner DP, Bronsky EA, et al. Absence of growth retardation in children with perennial allergic rhinitis after one year of treatment with mometasone furoate aqueous nasal spray. Pediatrics 2000;105:E22
110. Moller C, Ahlstrom H, Henricson KA, et al. Safety of nasal budesonide in the long-term treatment of children with perennial rhinitis. Clin Exp Allergy 2003;33:816-22
111. Wolthers OD, Pedersen S. Short-term growth in children with allergic rhinitis treated with oral antihistamine, depot and intranasal glucocorticosteroids. Acta Paediatr 1993;82:635-40
112. Skoner DP, Gentile D, Angelini B, et al. The effects of intranasal triamcinolone acetonide and intranasal fluticasone propionate on short-term bone growth and HPA axis in children with allergic rhinitis. Ann Allergy Asthma Immunol 2003;90:56-62
113.Agertoft L, Pedersen S. Short-term lower leg growth rate in children with rhinitis treated with intranasal mometasone furoate and budesonide. J Allergy Clin Immunol 1999;104:948-52
114. Minshall E, Ghaffar O, Cameron L, et al. Assessment by nasal biopsy of long-term use of mometasone furoate aqueous nasal spray (Nasonex) in the treatment of perennial rhinitis. Otolaryngol Head Neck Surg 1998;! 18:648-54
115.Baroody FM, Cheng CC, Moylan B, et al. Absence of nasal mucosal atrophy with fluticasone aqueous nasal spray. Arch Otolaryngol Head Neck Surg 2001;127:193-9
116. Lindqvist N, Balle VH, Karma P, et al. Long-term safety and efficacy of budesonide nasal aerosol in perennial rhinitis. A 12month multicentre study. Allergy 1986;41:179-86
117.Klossek JM, Laliberte F, Laliberte MF, et al. Local safety of intranasal triamcinolone acetonide: clinical and histological aspects of nasal mucosa in the long-term treatment of perennial allergic rhinitis. Rhinology 2001 ;39:17-22
118. Klimek L, Bachert C, Hermann K. Steroid sprays in non- infectious rhinitis and sinusitis. Proper and regular spraying does not damage the nasal mucosa. MMW Fortschr Med 2002;144:41-3 119. Meltzer EO. Intranasal steroids: managing allergic rhinitis and tailoring treatment to patient preference. Allergy Asthma Proc 2005;26:445-51
120. Dupclay L Jr, Doyle J. Assessment of intranasal corticosteroid use in allergic rhinitis: benefits, costs, and patient preferences. Am J Man Care 2002;8(Suppl):S335-40
121.Hendeles L, Hatton RC. Oral phenylephrine: an ineffective replacement for pseudoephedrine? J Allergy CUn Immunol 2006; 118:279- 80
122. Goldbart AD, Goldman JL, Veling MC, et al. Leukotriene modifier therapy for mild sleep-disordered breathing in children. Am J Respir Crit Care Med 2005; 172:364-70
123. Ohta N, Sakurai S, Yoshitake H, et al. Study of the effects of anti-leukotriene receptor antagonists on chronic allergic rhinitis - using QOL as an index. Presented at: World Allergy Congress 2005; June 26-July 1, 2005; Munich, Germany [Abstract 704]
124. Moinuddin R, deTineo M, Maleckar B, et al. Comparison of the combinations of fexofenadine-pseudoephedrine and loratadinemontelukast in the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol 2004;92:73-9
125. Wilson AM, O'Byrne PM, Parameswaran K. Leukotriene receptor antagonists for allergic rhinitis: a systematic review and meta- analysis. Am J Med 2004; 116:338-44
126. Di Lorenzo G, Pacor ML, Pellitteri ME, et al. Randomized placebo-controlled trial comparing fluticasone aqueous nasal spray in monotherapy, fluticasone plus cetirizine, fluticasone plus montelukast and cetirizine plus montelukast for seasonal allergie rhinitis. Clin Exp Allergy 2004;34:259-67
127. Alobid I, Benitez P, Bernal-Sprekelsen M, et al. Nasal polyposis and its impact on quality of life: comparison between the effects of medical and surgical treatments. Allergy 2005;60:452-8
128. Tuncer U, Soylu L, Aydogan B, et al. The effectiveness of steroid treatment in nasal polyposis. Auris Nasus Larynx 2003;30: 263-8
129. Ragab SM, Lund VJ, Scadding G. Evaluation of the medical and surgical treatment of chronic rhinosinusitis: a prospective, randomised, controlled trial. Laryngoscope 2004;! 14: 923-30
CrossRef links are available in the online published version of this paper: http://www.cmrojournal.com
Paper CMRO-3879_4, Accepted for publication: 29 June 2007
Published Online: 30 July 2007
William Storms(a), Barbara Yawn(b) and Leonard Fromer(c)
a The William Storms Allergy Clinic, Colorado Springs, CO, USA
b Department of Primary Care Research, Olmsted Medical Center, Rochester, MN, USA
c David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Address for correspondence: Leonard Fromer, David Geffen School of Medicine at UCLA, 15525 Hamner Drive, Los Angeles, CA 90077, USA. Tel.: +1 310 383 8168; Fax: +1 310 471 5392; [email protected]
Copyright Librapharm Sep 2007
(c) 2007 Current Medical Research and Opinion. Provided by ProQuest Information and Learning. All rights Reserved.