DO NOT COPY. Allergic rhinitis (AR), an inflammatory disease of

Transcription

1 Burden of allergic rhinitis: Allergies in America, Latin America, and Asia-Pacific adult surveys Eli O. Meltzer, M.D., 1 Michael S. Blaiss, M.D., 2 Robert M. Naclerio, M.D., 3 Stuart W. Stoloff, M.D., 4 M. Jennifer Derebery, M.D., 5 Harold S. Nelson, M.D., 6 John M. Boyle, Ph.D., 7 and Mark A. Wingertzahn, Ph.D. 8 ABSTRACT Allergic rhinitis (AR; also nasal allergies or hay fever ) is a chronic upper airway inflammatory disease that affects 60 million adults and children in the United States. The duration and severity of AR symptoms contribute to a substantial burden on patients quality of life (QoL), sleep, work productivity, and activity. This study was designed to examine symptoms, QoL, productivity, comorbidities, disease management, and pharmacologic treatment of AR in United States and ex-u.s. sufferers. Allergies in America was a comprehensive telephone-based survey of 2500 adults with AR. These data are compared and contrasted with findings from the Pediatric Allergies in America, Allergies in Latin America, and Allergies in Asia-Pacific telephone surveys. The prevalence of physician-diagnosed AR was 14% in U.S. adults, 7% in Latin America adults, and 9% in Asia-Pacific adults. Nasal congestion is the most common and bothersome symptom for adults. Approximately two-thirds of adults rely on medication to relieve intolerable AR symptoms. Incomplete relief, slow onset, 24-hour relief, and reduced efficacy with sustained use were commonly reported with AR medications, including intranasal corticosteroids. One in seven U.S. adults reported achieving little to no relief with AR medications. Bothersome adverse effects of AR medications included drowsiness, a drying feeling, medication dripping down the throat, and bad taste. Perception of inadequate efficacy was the leading cause of medication discontinuation or change and contributed to treatment dissatisfaction. These findings support the assertion that AR burden has been substantially underestimated and identify several important challenges to successful management of AR. (Allergy Asthma Proc 33:S113 S141, 12; doi:.2500/aap ) Allergic rhinitis (AR), an inflammatory disease of the upper airways, is the most common allergic disease and constitutes a global health problem that is From the 1 Allergy and Asthma Medical Group and Research Center, San Diego, California, 2 University of Tennessee Health Sciences Center, Memphis, Tennessee, 3 University of Chicago Pritzker School of Medicine, Chicago, Illinois, 4 University of Nevada School of Medicine, Reno, Nevada, 5 House Clinic and Ear Institute, Los Angeles, California, 6 National Jewish Health, Denver, Colorado, 7 Abt SRBI (Schulman, Ronca, and Bucuvalas), Inc., New York, New York, and 8 Pfizer Consumer Healthcare, Madison, New Jersey Funded by Sunovion Pharmaceuticals, Inc. EO Meltzer reports financial support as a consultant for Alcon, Allergan, AstraZeneca, GlaxoSmithKline, Greer, ISTA, Johnson & Johnson, Meda, Merck, Sanofi, Sunovion, and Teva; reports financial support for grant/research from Alcon, Astra- Zeneca, GlaxoSmithKline, Johnson & Johnson, Meda, Merck, Sanofi, Sunovion, and Teva; reports financial support as a speaker for Alcon, AstraZeneca, GlaxoSmithKline, Meda, Merck, Sanofi, Sunovion, and Teva. MS Blaiss reports financial support as a consultant for Alcon, Allergan, AstraZeneca, ISTA, Merck, Nycomed, Pfizer, Sanofi, and Sunovion; reports financial support for grant/research from GlaxoSmithKline; reports financial support as a speaker for Allergan, AstraZeneca, GlaxoSmithKline, ISTA, Merck, Nycomed, Sanofi, and Sunovion. RM Naclerio reports financial support as a consultant for Meda, and Teva; reports financial support for grant/research from GlaxoSmithKline, Merck, and NasoNeb; reports financial support as a speaker for Merck and Sunovion; reports receiving unrestricted financial gifts to the University of Chicago from Lasser and McHugh. SW Stoloff reports financial support as a consultant for AstraZeneca, Genentech, Merck, Sunovion, and Teva; reports financial support as a speaker for Merck, and Teva. MJ Derebery reports financial support as a consultant for Alcon, Sunovion, and Teva; reports financial support as a speaker for Alcon, Merck, and Sunovion. HS Nelson reports financial support as a consultant for Merck, and Sunovion. JM Boyle reports financial support as a consultant for Merck, Nycomed, and Teva. M Wingertzahn reports financial support as an employee of Pfizer Consumer Healthcare. Address correspondence and reprint requests to Eli O. Meltzer, M.D., Allergy and Asthma Medical Group and Research Center, 5776 Ruffin Road, San Diego, CA increasing in prevalence. 1 Despite a reported prevalence ranging from to 30% in adults and up to % in children, AR is frequently underrecognized, misdiagnosed, and ineffectively treated. 2 Therefore, obtaining accurate estimates of the incidence and prevalence of AR has been difficult, and reports vary widely. This may be caused by, in part, different definitions of AR or failure to differentiate AR from a mechanical rhinopathy (e.g., deviated septum) or nonallergic types of rhinitis such as vasomotor, medication-induced, and viral rhinitis. Moreover, a growing body of evidence suggests that more than one-half of patients with AR may suffer from mixed rhinitis, whereby they experience rhinitis symptoms in response to both traditional allergens and other triggers. 3 Frequent symptoms of AR include nasal congestion (often reported by the patient as a stuffy, blocked, or obstructed nose), rhinorrhea (runny nose), sneezing, and nasal itching. In the United States, AR is most commonly categorized as being either seasonal or perennial, depending on allergen sensitivity. Seasonal symptoms occur after exposure to outdoor allergens such as tree, grass, or weed pollens that are present in the environment at specific times of the year. Perennial, or year-round, symptoms occur in response to indoor address: eomeltzer@aol.com Copyright 12, OceanSide Publications, Inc., U.S.A. S113

2 allergens such as dust mites, mold, animal dander, and cockroaches. Approximately % of U.S. adults diagnosed with AR have perennial allergies, % have seasonal allergies, and % have perennial AR (PAR) with seasonal exacerbations. 4 One in five adults experience AR symptoms for 9 months of the year and approximately one-half experience AR symptoms for at least 4 months. 5 The duration and severity of AR symptoms contribute to a significant burden on patients quality of life (QoL), work performance, and day-to-day level of activity. 5 7 In particular, sleep disturbances associated with AR may be part of the cause of the physical, social, mental, and emotional toll of the disease. 5 In addition to the direct costs of treatment for patients and insurance providers, indirect costs through lost wages or decreased productivity have a large economic impact. 8,9 A first step in the treatment of AR is to implement environmental controls to reduce exposure to allergens or other noxious stimuli that may trigger nasal symptoms. This intervention is often insufficient to completely eliminate them. Therefore, treatment with medications, including intranasal corticosteroids (INCSs), over-the-counter (OTC) or prescription antihistamines (oral and intranasal), decongestants (oral and topical), and leukotriene receptor antagonists, is often required to alleviate the discomfort. Prescription INCS sprays are the current gold standard of pharmacotherapy for AR in both adults and children, although systemic effects of INCSs may be of concern in children In general, recommended agents may not provide complete relief of all symptoms or provide long-term symptom relief. In addition, adverse effects such as epistaxis, nasal dryness, and irritation from intranasal medications and drowsiness from antihistamines can limit the usefulness of these medications.,15,16 These limitations could contribute to reduced patient satisfaction and poorer adherence to therapy. Although data on prevalence, burden, and QoL effects of AR are available in the literature, no such survey information on the adverse effects from treatment or on patient preference for nasal allergy treatments is available. It should also be noted that although national health surveys such as the National Health Interview Survey (NHIS) and the National Health and Nutrition Examination Survey (NHANES) collect data on current sufferers of hay fever, they do not collect data on AR or on nasal symptoms. 17 Limited data from the Allergies in America survey of nasal allergy sufferers have been published previously. 5,6,18,19 This updated report reviews the previously published results of the Allergies in America survey of U.S. adults and provides additional analyses and findings from this survey. Moreover, this report compares the results of the adult U.S. survey data with those from several other more recent surveys of adult patients with nasal allergies conducted in Latin America and Asia-Pacific. Additional comparisons with survey findings in pediatric patients in the United States are also highlighted, where noteworthy; however, data from these surveys of pediatric patients with AR outside the United States are not included in this document, but are available elsewhere. 22 Finally, because current practice guidelines for both AR and AR with comorbid asthma place INCSs as first-line pharmacotherapy over other treatments for these disorders, this article and the survey questionnaires focus on INCSs where possible. 23 METHODS Because this was a telephone-based survey, no Institutional Review Board oversight was required. Survey Design Physician experts in the field of AR, in collaboration with Abt Schulman, Ronca and Bucuvalas, Inc. (Abt SRBI), a national public opinion research organization, developed the Allergies in America, Allergies in Latin America, and Allergies in Asia-Pacific surveys, as well as the Pediatric Allergies in America questionnaire. Leading clinicians from the various regions reviewed and approved the survey questionnaires. They were developed through analysis of the relevant literature and identification of questions used to study similar diseases in other accepted health surveys. The AR patient questionnaires focused on general health, AR triggers, AR symptoms, the effects of allergies on QoL and productivity, AR comorbidities, and the effectiveness and side effects of nasal allergy medications. Relevant questions from the surveys are included in the Appendix. United States surveys were conducted solely by random digit dialing and telephone interviews, as noted later in text. Surveys outside of the United States were conducted by either telephone interview, as was done in the United States, or by in-person interviewing, as noted later in text. Each survey was conducted independently with respect to internal controls (e.g., for survey translation and socioeconomic status). The authors acknowledge that comparing data across surveys, as has been done in this supplement, introduces potential bias. However, because this report is focused on AR in the United States and provides supportive evidence from adults with AR in Latin America and Asia-Pacific countries, we believe that any potential bias should not affect survey conclusions. The questionnaire was translated by the survey contractors who conducted the data collection within each country. The translated questionnaires were then sent to the study advisors and/or industry medical staff for review. Any revisions from the advisors were incorporated into the questionnaire before the translation was finalized. S114 September October 12, Vol. 33, No. 5 (Suppl 2)

3 Allergies in America, A Survey of Adult Nasal Allergy Sufferers. Allergies in America is a comprehensive national telephone survey of 30,927 households in the United States that was conducted to identify and interview adult ( 18 years of age) nasal allergy sufferers. 6,18 Among these households, the survey identified 61,655 adults, of whom 8735 had been diagnosed with AR, nasal allergies, or hay fever by a health care provider (HCP). Individual screening of this respondent group subsequently identified 2933 adults (only 1 per household participated even if multiple individuals were eligible) who had experienced symptoms or had taken medication to treat their nasal allergy symptoms during the previous 12 months. From this group of adult patients diagnosed and suffering from recent AR symptoms, 2500 participants completed the full questionnaire. 18 The calculation of overall prevalence of the disease was based on all adults who reported having been diagnosed with nasal allergies of all individuals from households dialed. The telephone surveys were conducted between January 5 and 31, 06, and lasted an average of 35 minutes. 6 Detailed methods, statistical methodology, and sampling error values have been previously published. 5,6,19 Pediatric Allergies in America. The Pediatric Allergies in America survey was conducted between March and April 07. Detailed methods, statistical methodology, and sampling error values have been previously published. 7 Allergies in Latin America. The Allergies in Latin America survey was conducted in Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, and Venezuela. In total, 22,012 households were screened and 88 interviews of adults with AR were conducted. Data collection consisted of both telephone and in-person interviewing between February and April 08. For telephone interviews (Argentina and Brazil), the questionnaire was programmed into a Computer-Assisted Telephone Interviewing (CATI) system that dialed random regional phone numbers and collected data using range checks and automatically implementing skip patterns. Although CATI is computer assisted, a live trained interviewer read all appropriate questions to the respondents and entered the response data manually. For in-person interviews (Chile, Columbia, Ecuador, Mexico, Peru, and Venezuela), when possible, the screeners and interviewers were allocated to cities and/or neighborhoods based on socioeconomic levels in such a way as to match the structure of each individual country. Supervisors monitored screening and interviews for accuracy of data entry and screening and interviewing procedures. Responses were recorded on paper questionnaires and entered into a database at the central office where they were reviewed by experienced supervisors. No call-back or reinterview validation process was used in the Latin America survey. Detailed methods, statistical methodology, and sampling error values have been previously published.,22 Allergies in Asia-Pacific. The Allergies in Asia-Pacific survey was conducted in Australia, China, Hong Kong, South Korea, Malaysia, the Philippines, Singapore, Taiwan, and Vietnam. 24 In total, 33,378 households were screened and 43 interviews of adults with AR were conducted. Data collection consisted of both telephone and in-person interviewing between December 09 and January. 24 For telephone interviews (Australia, China, Hong Kong, Taiwan, and Vietnam), the questionnaire was programmed into a CATI system as noted previously, and the interview was conducted by a live interviewer. Supervisors monitored screening and interviews for accuracy of data entry and screening and interviewing procedures. 21 For in-person interviews (South Korea, Philippines, Malaysia, and Singapore), when possible, the screeners were allocated to cities or neighborhoods based on socioeconomic levels in such a way as to match the structure of each individual country. In South Korea, patients were referred by a physician and in-person household screening was conducted. Most interviews were conducted in urban areas because of low telephone penetration and lack of appropriate infrastructure in rural areas. Responses were recorded by the interviewer on paper questionnaires and entered into a database at the central office. For validation purposes, households were recalled and reasked the screening questions, medications used, and a few additional variables from the questionnaire. Depending on the country, validation was performed on (Australia) to 66% (China) of interviews. In most cases, if the validation interview did not match the first on key questions, the interview was conducted again. 21 Detailed methods, statistical methodology, and sampling error values have been previously reported. 21,24 Statistics For each of the surveys the statistical methodology and maximum expected sampling error values were published previously. 6,22,24 Surveys such as the Allergies in America telephone survey tend to obtain responses and opinions that cannot be clinically verified. Much like the analysis of reported adverse events that occur in a clinical trial, results from surveys are typically reported via descriptive measures. Therefore, except where noted, most survey results have been reported descriptively. Population surveys are not traditionally validated to determine sensitivity and specificity as medical tests are validated. This type of analysis is not done in the S115

4 NHIS, Behavioral Risk Factor Surveillance System, or other national health surveys. The NHANES does include select medical exams and testing so that reported diagnoses can be compared, but the tests are not designed to validate the survey responses. The authors, in conjunction with Abt SRBI, analyzed categorical response data to confirm that patients who responded to the survey were suffering from AR. Briefly, responses were classified by whether patients reported having had a skin or blood test or by having not received a confirmatory test. Participant responses to 9 questions (listed in the Appendix in bold) and 57 possible responses were analyzed by cross-tabulation and chi-square analysis with two-sided asymptotic significance test (Statistical Package for the Social Sciences; IBM Corporation, Armonk, NY). Survey Questions Questions from the adult U.S. patient survey and the survey of HCPs in the United States relevant to this publication are detailed by chapter in the Appendix. PREVALENCE OF AR AR is a common chronic disease that affects as many as 60 million people in the United States. 7,25 This number has risen substantially over the past years and is expected to continue to rise. Unfortunately, obtaining an accurate estimate of the number of individuals suffering from AR symptoms in the United States has been difficult. Large, federally funded national health surveys, such as NHIS and NHANES, do not collect data on AR or on nasal symptoms, but they do collect data on patients with hay fever, and, in the case of NHANES, data from allergen skin tests. 17,26 Moreover, NHANES II ( ) and III ( ) collected data from allergen skin tests to evaluate patient sensitivity to common allergens. These tests were conducted on all patients 6 19 years of age, and a random half of participating patients 59 years of age. 26 In NHANES III, 54.3% of patients were sensitive to at least one allergen, with each sensitive patient having a median of three positive allergen responses. Moreover, among the six common allergens tested between surveys, positive responses were times higher in the latter survey. 26 Despite this high prevalence, many individuals in the health care field or members of the public consider AR to be an unimportant condition rather than a serious disease. 5,25,27 Approximately 80% of all individuals with AR develop symptoms by age years. 4 In 03, the Agency for Healthcare Research and Quality estimated the self-reported prevalence of AR to be between and 30% in adults and nearer to % in children. 2 The Allergies in America survey of adults and the Pediatric Allergies in America survey of children with nasal allergies in the United States independently estimated that one in seven adults and children (14 and 13%, respectively) had an HCP-confirmed diagnosis of AR (Fig. 1 A). 6,7 In adults, this prevalence was calculated based on 8735 adults with nasal allergies among 61,655 adults in households screened. 28 For the pediatric survey, 68 children diagnosed with nasal allergies were identified among 8119 households surveyed with children 4 17 years of age. 7 Slightly lower estimates of HCP-confirmed nasal allergy prevalence (Fig. 1 A) were reported in two additional surveys of adults, conducted by Abt SRBI using the same format: Allergies in Latin America (mean, 6.6%; range, %) and Allergies in Asia-Pacific (mean, 8.7%, range, %). 22,24 Patient demographics for adults in the United States are provided in Table 1 (demographics for children and adolescents are available elsewhere 7 ). It is important to recognize that because these surveys required an HCP diagnosis of AR and current nasal allergy symptoms and/or medication, they likely underestimate the true prevalence of disease. Approximately two-thirds of survey participants were women and most (66%) respondents were between the ages of 35 and 64 years (Table 1). When asked to identify the medical specialty of the diagnosing HCP, U.S. respondents said that general (27%) and family (%) practitioners; allergists (19%); and ear, nose, and throat specialists (ENTs; 12%) provided the bulk (78%) of the diagnoses. Similarly, Latin America respondents said that general practice physicians (37%), otolaryngologists (29%), and allergists (13%) provided the majority of diagnoses. 22 In contrast, nearly one-half (49%) of respondents in Asia-Pacific countries were initially diagnosed by an otolaryngologist or ENT, with an additional one-third (34%) of respondents having been diagnosed by a general practitioner 21 (Fig. 1 B 21,22,24 ). Just over one-half (57%) of U.S. patients reported use of diagnostic tools such as a skin test (49%) or blood test (23%) to confirm AR diagnosis (multiple responses were permitted). Similarly, Latin America respondents reported a 57% rate of receiving blood or skin tests to confirm an AR diagnosis. 22 In contrast to these rates for confirmatory testing in the United States and Latin America, even fewer (41%) Asia-Pacific respondents reported receiving a blood or skin test. 24 Several approaches are used to categorize AR. In Europe and other regions outside of the United States, AR is often categorized by duration (intermittent or persistent) and patient-reported severity (mild, moderate, or severe). In contrast, the most commonly used AR classification criteria in the United States are based on the type of allergic triggers and seasonality of symptoms and, therefore, broadly separate AR into seasonal or perennial allergy categories. Although some pa- S116 September October 12, Vol. 33, No. 5 (Suppl 2)

5 Figure 1. Prevalence of allergic rhinitis (AR). (A) Prevalence of AR 6,7, 22,24,28 ; (B) diagnosing health care provider 21,22 ; (C) percentages of patients with seasonal or perennial allergies 6,22,24 ; (D) common triggers of nasal allergy symptoms in U.S. patients (multiple responses permitted). ENT, ear, nose, and throat specialist; OTO, otolaryngologist. Table 1 U.S. Demographics (n 2500) Parameter Patients (%) Gender Male 35 Female 65 Age Mean, yr Race White 81 Black 8 Mixed 3 Hispanic 3 Asian 1 American Indian/Alaskan 2 Pacific Islander 1 Other 1 Refused 1 Do not know 1 Percentages do not equal 0% as a result of rounding. A Prevalence, % B United States adults Other/not sure Internal medicine Pediatrician ENT/OTO Allergist Family practice General practice * 2 13 United States children Latin America adults Asia-Pacific adults Asia-Pacific Latin America United States C D Not sure Other < 5% Fumes, odors Plants/trees/leaves Tobacco smoke Perfume Damp/mold/mildew Animal dander Weather Grass Dust Pollen United States tients may have discrete triggers, most patients experience allergy symptoms year-round, likely because of the fact that they are allergic to both seasonal and perennial triggers, although symptom severity may be greater during certain times of the year. As such, many patients are considered to have seasonal exacerbations. Because this article focuses on U.S. patient experience but also includes data from patients in Latin America and Asia-Pacific regions, it should be noted that, for consistency, only the usual U.S. classification system was used. 23,25,29 When adult respondents to the Allergies in America survey were asked whether they had seasonal AR (SAR) or PAR, most (56%) reported that their nasal allergies occurred throughout the year, and 43% felt that they occurred seasonally. 6 In fact, a previous report from the Allergies in America survey observed that approximately one-half of patients experience AR symptoms for 4 months of the year, with one in five patients experiencing those symptoms for 9 months of the year. 5 In contrast, respondents to the Allergies in Latin America and Allergies in Asia-Pacific surveys reported that seasonal or intermittent allergies were more common (61 and 63%, respectively) than perennial allergies 22,24 (Fig. 1 C 6,22,24 ). In terms of time of the year, 56% of U.S. patients said that their allergies were worse during spring months, whereas 45% reported that their allergies were worse Latin America Asia-Pacific Don't know Seasonal Perennial 0 60 S117

6 during autumn months (multiple answers were permitted). 6 Asia-Pacific respondents were not asked about a specific season, but were asked during what months of the year they experienced peak allergy symptoms. Asia-Pacific respondents reported an extensive period of allergy severity in September, which peaked in November and December, and continued on through April (multiple answers permitted). It should be noted that telephone interviews and/or fieldwork for the surveys were conducted during the peak period for nasal allergy symptoms in each region. Because of the broad geographic distribution and diverse climatic regions (especially in Latin America and Asia-Pacific), responses to questions aimed at determining seasonality of peak symptoms varied substantially in each survey. Moreover, specific questions relating to worst month/season for AR symptoms were not asked of Latin America respondents in a comparable form. In the U.S. and Asia-Pacific surveys, most patients reported that their nasal allergy symptoms were worse outside (39 and 36%, respectively) rather than inside (9 and 27%, respectively). 24 This question was not asked of Latin America patients in a comparable form. When asked what triggers their nasal allergies, most U.S. patients reported multiple allergens, the most common of which were pollen (41%); dust (34%); grass (22%); animal dander (18%); dampness, mold, and mildew (11%); and plants, trees, or leaves (6%). Among nonallergic triggers, weather (22%) ranked highest in patient estimates (Fig. 1 D). For respondents in Latin America and Asia-Pacific, the questions centered on what contributing factors exacerbated their AR. Climate/humidity (55 and 55%) and dust (71 and 49%) were the two triggers ranked highest by respondents in Latin America and Asia-Pacific, respectively.,21,24 Survey inclusion criteria required that respondents have either symptoms or medication use in the past year for AR symptom control. Among adult U.S. respondents, 67% reported both symptoms and medication use in the past year and 32% experienced symptoms in the past year but did not treat them; few reported medication use only during the past year (Fig. 2). Similar percentages of Latin America and Asia-Pacific respondents (67 and 63%, respectively), reported using medications of any type during the previous 12 months to control their nasal allergies, whereas the remaining one-third of respondents in each survey outside of the United States did not use any medications to treat AR symptoms. 22,24 Conclusions for Prevalence of AR The Allergies in America survey indicated that approximately one in seven adults queried had an HCP diagnosis of AR. This estimate is the same as that reported in the Pediatric Allergies in America survey 64% 2% 32% 1% Symptoms only Medication only Both symptoms and medication Neither symptoms nor medication Figure 2. Symptoms and medication use. Percentage of U.S. patients experiencing symptoms and/or using medication for symptoms during past 12 months. and slightly higher than that obtained in the Latin America and Asia-Pacific surveys. Because participation in each of the allergies surveys required an HCP diagnosis, these results likely underestimate the overall prevalence of the disease in the United States and in the other countries surveyed. Indeed, these estimates are somewhat lower than those cited in other publications of nasal allergy prevalence, possibly as a result of the requirement for a diagnosis of AR. 4,30,31 Adult allergy sufferers in the United States experience perennial allergies more than seasonal allergies, whereas U.S. children appear to have mostly seasonal allergies. 7 In both adults and children in the United States, seasonal exacerbations were more severe during the spring and fall seasons, whereas these exacerbations were most prevalent from September through April in Asia-Pacific countries. Diagnoses of nasal allergies in the United States and in Latin America are generally made by a primary care physician (PCP), whereas AR diagnoses in Asia-Pacific regions are typically made by an ENT or otolaryngologist. Both in the United States and abroad, the surveys found that blood or skin tests were not universally applied during AR diagnosis. These findings suggest that most adults, irrespective of the region in which they live, appear to be diagnosed after observation of symptoms and medical history alone, with limited use of blood or skin tests to confirm the diagnosis. SYMPTOMS OF AR Although AR is an inflammatory condition characterized by nasal congestion, rhinorrhea, repeated sneezing, and nasal itching, it is important to recognize that, in some individuals, ocular symptoms including itching, tearing, redness of the eye, and lid puffiness may also occur after allergen exposure. 32 When both nasal and ocular symptoms are present, the term allergic rhinoconjunctivitis can be used. Because the body s inflammatory response to allergen exposure may vary in intensity and by tissue, the frequency of specific allergy symptoms may vary S118 September October 12, Vol. 33, No. 5 (Suppl 2)

7 A Ear pain/pressure Facial pain/pressure Sleep disturbance Headache Nasal itching Watering eyes Runny nose Postnasal drip Repeated sneezing Nasal congestion among patients. Patients in the United States were asked which of 12 common symptoms of AR they experienced during their worst month for allergy symptoms during the previous year. Respondents overwhelmingly agreed that nasal congestion or stuffy nose (60%) was the most common symptom, occurring either every day or most days (combined categories). Postnasal drip (46%), repeated sneezing (46%), runny nose (45%), and watering eyes (%) were experienced by nearly one-half of patients every day or most days during their worst allergy month. 6 Approximately onethird (35%) of patients reported nasal itching. Less commonly reported symptoms occurring every day or most days during the worst month for allergy symptoms included headache, facial pain, or ear pain (Fig. 3 A). 6 Latin America and Asia-Pacific respondents also reported nasal congestion (54 and 42%, respectively), repeated sneezing (47 and 39%, respectively), runny nose (45 and 37%, respectively), and nasal itching (49 and 31%, respectively) on at least most days of their worst month for nasal allergy symptoms. 21,22 Although experienced less frequently than nasal symptoms, headache (not including migraine) was still reported by one in four U.S. (25%) and Latin America (22%) patients and by one in seven (13%) Asia-Pacific patients every day or most days. 6,21,22 When asked how bothersome the aforementioned symptoms were, three of four (78%) U.S. respondents agreed that nasal congestion was extremely or moderately bothersome (combined categories). 5 More than three in five patients also reported runny nose (62%) and postnasal drip (61%) as being extremely or moderately bothersome (combined categories). Red/itching eyes (53%), headache (51%), repeated sneezing (51%), watering eyes (51%), nasal itching (46%), facial pain (43%), and ear pain (30%) were also extremely or moderately bothersome to U.S. respondents (Fig. 3 B). 5 Similar proportions of adults with nasal allergies from B Ear pain/pressure Facial pain/pressure Nasal itching Watering eyes Headache Repeated sneezing Red/itching eyes Postnasal drip Runny nose Nasal congestion C Ear pain/pressure Nasal itching Watering eyes Facial pain/pressure Repeated sneezing Red/itching eyes Runny nose Headache Postnasal drip Nasal congestion the Latin America (89%) and Asia-Pacific (78%) surveys found nasal congestion to be extremely or moderately bothersome.,21 When patients in the Allergies in America survey were asked which one nasal allergy symptom was most bothersome, nasal congestion (22%) was overwhelmingly named. In order of decreasing rank as the most bothersome AR symptom, postnasal drip and headache (14% each) were the next most common replies from U.S. adults, followed by runny nose and red itching eyes (% each), repeated sneezing (9%), facial pain (7%), watering eyes (5%), and nasal itching or ear pain (4% each; Fig. 3 C). 5 Latin America (25%) and Asia-Pacific (23%) respondents also agreed that nasal congestion was the most bothersome symptom of nasal allergies.,24 It is interesting to note that postnasal drip, identified as the second most bothersome symptom of AR in the United States (14%), was infrequently considered by respondents in the Latin America and Asia-Pacific surveys (2 and 3%, respectively) as being among the most bothersome symptoms of nasal allergies. 5,,24 Aside from possible cultural differences related to the reporting of bothersome AR symptoms between the respondents from different geographic regions, the authors cannot speculate on why this may be so. Conclusions for Symptoms of AR These data support the premise that AR symptoms adversely affect the lives of both adults and children with nasal allergies. In all of the allergies surveys conducted to date, nasal congestion was identified as the most frequent and most bothersome symptom of AR in adult patients worldwide and in children in the United States. Although most symptoms are experienced at similar frequencies among adults worldwide, these common symptoms affect adults from different regions Figure 3. Common bothersome symptoms of allergic rhinitis (AR) in the United States. (A) Most common nasal allergy symptoms during the worst month in the past year (multiple responses permitted) 6 ; (B) severity of nasal allergy symptoms extremely or moderately bothersome (multiple responses permitted) 5 ; (C) report of the most bothersome nasal allergy symptom (multiple responses permitted). 5 S119

8 differently, with some symptoms considered as very bothersome by U.S. adults being considered less problematic by Latin America or Asia-Pacific respondents. The authors can only speculate that cultural differences between patients from different geographic regions may explain some of these discrepancies. An important consideration for the HCP who treats patients with AR is that, although adults and children suffer the same disease, they experience subtly different manifestations in both frequency and severity of AR symptoms. This may be especially true in the case of nasal congestion and runny nose. Adults suffering from nasal congestion may experience less frequent and less severe facial and ear pain as a result of increased pressure than is experienced by children. The authors speculate that because adults have larger airway lumens than children, adults may experience less pressure and pain in the ears and paranasal sinuses. Although adults in the United States may experience less congestion than children, they may experience greater postnasal drip. Both adults and children experience bothersome nasal allergy symptoms that contribute to AR being ranked as among the most common reasons for visits to PCPs in the United States. 32,37 BURDEN OF AR Despite the considerable prevalence and substantial effect on QoL for patients, AR is still considered by some to be of little concern. Although most patients and practitioners recognize the burden of physical symptoms affecting the nose and eyes, other factors, often unrecognized, inflict an equal or greater burden on the patient. These nonphysical effects also decrease QoL, including reducing emotional well-being, disrupting social behavior, and impairing cognitive and interpretive abilities. 5 Sleep Problems It is generally accepted that AR symptoms can overtly reduce QoL among allergy sufferers. However, AR symptoms also have less conspicuous, but sometimes profound, effects on QoL through sleep disruption, which can cause daytime somnolence, fatigue, irritability, and depression, coupled with memory and learning deficits. 17,38,39 Nasal congestion or runny nose caused by AR can disrupt normal breathing patterns, possibly through increasing upper airway resistance. 39 At night, these symptoms can cause rhinitis-disturbed sleep and contribute to sleep-disordered breathing and brief awakenings, or microarousals, which reduce the quality and quantity of sleep In addition, frequent nighttime AR symptoms may cause a state of chronic nonrestorative sleep that contributes substantially to daytime sleepiness and possibly the mood and emotional problems observed with this disorder. Adult patients with AR are times more likely to experience microarousals during nights when their allergy symptoms are at their worst. 17 Sleep-disordered breathing and AR have been independently associated with reduced learning performance, attention deficit disorder, behavioral difficulties, and decreased cognitive functioning Daytime fatigue is a logical result of increased sleep disruption in patients with AR, but there appears to be a direct added effect of AR on daytime drowsiness that is above and beyond impairment of sleep. 45,46 Findings from the surveys support the negative effects of AR symptoms and physiology on sleep quality. Nearly one in four (22%) adult U.S. survey respondents reported that they were awakened or unable to sleep every day or most days (combined categories) because of nasal allergy symptoms. 28 Adult respondents in Latin America and Asia-Pacific regions reported that they too had difficulty sleeping because of nasal allergies. Although no direct comparison with U.S. data can be made because of differences in the wording of individual questions, nearly one-half (44%) of Latin America respondents and 70% of Asia-Pacific adults reported suffering from sleep problems because of nasal allergies. 22,24 Latin America respondents replied on a 7-point scale that they were extremely troubled (the most severe of the 7 replies) over falling asleep (18%), waking during the night (%), or lack of a good night s sleep (23%). Asia-Pacific adult respondents replied on a 4-point scale that they were extremely troubled (the most severe of the 4 replies) over falling asleep (7%), waking during the night (7%), or lack of a good night s sleep (%). 21 Similarly, children with AR in the United States and abroad are more likely to experience difficulty falling asleep, waking during the night, and lack of a good night s sleep compared with children without nasal allergies. 7,22,24 Although questions to address sleep disruption were phrased differently in the Allergies in America and subsequent surveys, it seems reasonable to conclude that a comparable percentage of adults experience sleep disruption, and based on the data from children, 26 45% experience sleep disruption in at least one of the aforementioned categories. 7,22,24 Physical and Emotional Health Nasal allergies have a profound effect on the physical and emotional health of adults worldwide. Nasal allergy sufferers were asked several descriptive questions regarding their mood and feelings. Four of five (80%) U.S. adults with allergies reported feeling tired frequently or sometimes (combined categories) during allergy season. Respondents also reported that they felt miserable (65%), irritable (64%), depressed or blue S1 September October 12, Vol. 33, No. 5 (Suppl 2)

9 A C Productivity, % Tired Miserable Irritable Depressed or blue United States Latin America Asia-Pacific (36%), or embarrassed (23%) at least sometimes (combined categories) during allergy season (Fig. 4 A). 5 Frequent fatigue or depression was also commonly reported by Latin America (35 and 17%, respectively) and Asia-Pacific (27 and 16%, respectively) respondents. 22,24 Social Health When applied to the individual, social health can be viewed as a measure by which the person interacts with the larger society, whether through work, school, or daily relationship activities. Nasal allergies interfere substantially with the daily lives of individuals in the United States and abroad. Nasal allergies may interfere with work and the social life of adult sufferers in many ways. Absenteeism from work is well recognized. Presenteeism, in contrast, reflects the negative effect on work performance or productivity while at work. When asked if their nasal allergies caused respondents to miss work or whether they interfered with work, % of allergy sufferers in the United States reported missing work, 22% reported work interference, and Sometimes Frequently 15 8 Embarassed No symptoms Symptoms at worst 65 B D % said that they experienced both because of nasal allergy symptoms. Respondents outside the United States reported work loss, interference, or both to a somewhat smaller degree compared with their U.S. counterparts. Outside the United States, allergy sufferers said that allergies caused them to miss work (4% for both), interfered with work (17 and 25%, respectively), or both (16 and 21%, respectively) in the Latin America and Asia-Pacific surveys (Fig. 4 B). 22,24,28 Adult allergy sufferers in the United States reported a 23% decrease in work productivity on days when allergies were at their worst compared with days when the respondent experienced no symptoms. 6 This estimate of lost productivity secondary to allergy symptoms was comparable with that reported in the Latin America (33% decrease) and Asia-Pacific (24% decrease) surveys (Fig. 4 C).,21,28 In addition to the effects of nasal allergies on the individual and family, lost worker productivity because of nasal allergy symptoms comes at a substantial economic cost to the employer. It is interesting to note that nearly one in seven (14%) adult survey respondents reported that United States Latin America Asia-Pacific None of these Pink eye/conjunctivitis Fever Skin rashes Migraines Earaches Cold or flu Heartburn or GERD Sinus problems Don't know Neither Both Interfered only Missed work only Latin America United States 0 60 Figure 4. Burden of allergic rhinitis (AR). (A) Effect of AR on the physical and mental health of adults in the United States (multiple responses permitted) 5 ; (B) effects of AR on work absenteeism and presenteeism 22,24,28 ; (C) effect of nasal allergy symptoms on productivity,21,28 ; (D) comorbid disorders associated with AR (multiple responses permitted). 6,22 GERD, gastroesophageal reflux disease. (Panel D adapted in part from Ref. 22.) S121

10 Table 2 Comorbidity of AR and asthma nasal allergies either kept them from working full time or otherwise limited the kind or amount of work that they do. Among respondents who were employed full time and who reported that allergies interfered with work, greater than one-half (58%) said that they were exposed to triggers at work that affect their nasal allergies. In addition to the effect of AR on absenteeism from and presenteeism at work, nasal allergy sufferers are also limited in their daily activities and in their ability to spend time with family. Nearly three of four (71%) U.S. adult AR sufferers agreed strongly or somewhat (combined categories) that nasal allergies usually cause some lifestyle limitations. Greater than one-third (35%) of U.S. adults said that they avoid activities because of their nasal allergies. Importantly, 13% of U.S. adults report that their nasal allergies interfere with activities that they like to do with their children. Allergy sufferers also described the degree to which their nasal allergies limited their daily lives and ability to engage in activities. Similarly, Latin America and Asia-Pacific respondents reported that allergies restricted a lot of their ability to participate in social activities (16% [Latin America only]), or enjoy outdoor (18 and 9%, respectively) or indoor (12 and 7%, respectively) activities.,21 Comorbid Conditions Increasing evidence supports the concept of a oneairway model for chronic inflammatory disease that includes both upper-airway disorders such as AR and lower-airway disorders such as asthma. 47 Crosstalk between neurological and inflammatory pathways in the upper and lower airways lends credence to the oneairway model of inflammatory disease. 48 There appears to be a clear correlation between AR and asthma risk, such that greater than one half of U.S. adults with asthma, and nearly 0% of those with allergic asthma, have nasal allergies. 49 A reciprocal relationship also holds true: 38% of U.S. adults with AR have concomitant asthma. 50 The high coprevalence of AR and asthma is supported by several studies conducted in patients outside of the United States In addition to the link between AR and risk for developing asthma, uncontrolled AR may exacerbate asthma. Patients (%) United States Latin America Asia-Pacific Asthma diagnosis Asthma symptoms in last 12 mo N/A 11 AR allergic rhinitis; N/A data not available. The Allergies in America findings support a link between AR and asthma in both adults and children. Overall, one-third (32%) of adult U.S. respondents have been diagnosed with asthma and nearly twothirds (63%) of these patients have experienced asthma symptoms during the last 12 months. 6 Similar prevalence of asthma diagnoses and symptoms during the last 12 months exists among Latin America (21%, and data not reported, respectively) and Asia-Pacific ( and 11%, respectively) respondents (Table 2).,54,55 Interestingly, the relationship between AR and asthma prevalence in the United States diverges along both age and gender lines. Approximately 45% of male children and 33% of female children with AR reported having a diagnosis of asthma. 7 These findings are supported (albeit to a lesser degree) by those from the Pediatric Allergies in America survey. 30,56 60 This gender discrepancy in asthma diagnoses among individuals with AR disappears by adulthood such that 29% of adult males and 34% of adult females with AR reported having been diagnosed with asthma. 4 These observations on the comorbid incidence of AR and asthma are important; in fact, treatment of AR symptoms in adults has been shown to reduce the incidence and severity of asthma In addition to asthma, ocular and facial symptoms including conjunctivitis, headaches, and ear problems (otitis, especially in children) may occur frequently in individuals with nasal allergies. 66 Sinus problems have also been associated with nasal allergies in the general AR population. Estimates from two studies looking at this association indicated that between 25 and 80% of individuals with AR also had sinus problems. 66,67 The Allergies in America surveys revealed that 50% of adults and 43% of children with nasal allergies reported having chronic sinus problems, supporting the assertion that AR may be a common contributing factor to acute or chronic sinus issues. 6,7 When adult respondents to the Allergies in America survey were asked whether they had experienced any other disorders in addition to sinus problems during the previous week, 17% reported having cold or flu symptoms, 16% had earaches, and 15% had experienced migraines (multiple responses permitted). Moreover, in support of findings previously published in the literature, approxi- S122 September October 12, Vol. 33, No. 5 (Suppl 2)

11 A C mately one in four survey respondents reported heartburn or gastroesophageal reflux disease (23%). 68 Skin rashes (%), fever (9%), and pink eye (2%) were also reported; however, one-third of those queried reported experiencing no other symptoms during the previous week. 6 In contrast to the high incidence of sinus problems reported by U.S. adults, cold or flu (47%) or migraines (41%) were the most commonly reported comorbid disorders experienced by Latin America respondents 22 (Fig. 4 D). 6,22 This question was not asked of Asia-Pacific patients in a comparable form United States Latin America Asia-Pacific 33% 14% 1% 24% 28% Completely Well Somewhat Poorly/not at all Not sure Not sure No impact Little Some Moderate A lot B D % United States Latin America Asia-Pacific 11% 23% 36% No symptoms Mild symptoms Moderate symptoms Severe symptoms Conclusions for Burden of AR Data from the allergies surveys support the assertion that nasal allergy symptoms exert a substantial negative effect not only on the physical health of patients but also on the emotional and social health of adults and children in the United States and abroad. Improved understanding of the burden of AR in individuals is the first step in addressing shortcomings of disease management that limit effectiveness of therapy. Therapies that effectively treat nasal congestion and runny nose may improve QoL in U.S. adults by decreasing disruptions to sleep and reducing daytime fatigue associated with nasal allergies. 69 Many of these problems are infrequently considered when evaluating the burden of AR on individuals. These symptoms may cause chronic nonrestorative sleep, resulting in daytime fatigue that contributes further to the burden of AR. Furthermore, chronic upper-airway inflammation caused by AR clearly increases the risk for development of comorbid disorders including allergic conjunctivitis, sinusitis, and asthma. This observation, together with the potential for AR to decrease patient QoL, indicates that U.S. adult patients need to be categorized by the magnitude of their disease. Individuals with milder AR symptoms may still perceive their general health as being good and, therefore, they either use OTC medications or do not pursue treatment. Others with moderate or severe AR require greater interventions and better management of their disease. NEED FOR TREATMENT OF AR SYMPTOMS Nasal allergies exert a substantial effect on the daily lives of allergy sufferers. Bothersome symptoms and sleep disruption associated with AR greatly undermine the physical, mental, and emotional health of adults and children worldwide. When asked to estimate the effect of nasal allergies on their daily lives, 85% of U.S. adult respondents felt that AR affected their lives to some degree (i.e., at least a little). The percentage of U.S. adults reporting that nasal allergies have at least a moderate effect on their daily lives (%) was similar to that reported by Latin America (50%) and Asia-Pacific (35%) survey respondents (Fig. 5 A,21 ; combined cat Not sure Can ignore Can tolerate Can't tolerate Figure 5. Need for treatment of allergic rhinitis (AR). (A) Patient perceptions of effect of nasal allergy symptoms on daily life,21 ; (B) patient perceptions of ability to tolerate nasal allergy symptoms without relief,21 ; (C) U.S. patient estimates of nasal allergy control in past week; (D) U.S. patient estimates of nasal allergy symptom severity during past week. S123