SEARCH

SEARCH BY CITATION

Keywords:

  • Allergic Rhinitis and its Impact on Asthma;
  • asthma;
  • Global Initiative for Asthma;
  • rhinitis;
  • Visual Analog Scale

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Source of funding
  9. Author contributions
  10. Conflict of interest
  11. References
  12. Supporting Information

To cite this article: Ohta K, Bousquet P-J, Aizawa H, Akiyama K, Adachi M, Ichinose M, Ebisawa M, Tamura G, Nagai A, Nishima S, Fukuda T, Morikawa A, Okamoto Y, Kohno Y, Saito H, Takenaka H, Grouse L, Bousquet J. Prevalence and impact of rhinitis in asthma: SACRA, a cross-sectional nation-wide study in Japan. Allergy 2011; 66: 1287–1295.

Abstract

Background:  Asthma and rhinitis are common co-morbidities everywhere in the world but nation-wide studies assessing rhinitis in asthmatics using questionnaires based on guidelines are not available.

Objective:  To assess the prevalence, classification, and severity of rhinitis using the Allergic Rhinitis and its Impact on Asthma (ARIA) criteria in Japanese patients with diagnosed and treated asthma.

Methods:  The study was performed from March to August 2009. Patients in physicians’ waiting rooms, or physicians themselves, filled out questionnaires on rhinitis and asthma based on ARIA and Global Initiative for Asthma (GINA) diagnostic guides. The patients answered questions on the severity of the diseases and a Visual Analog Scale. Their physicians made the diagnosis of rhinitis.

Results:  In this study, 1910 physicians enrolled 29 518 asthmatics; 15 051 (51.0%) questionnaires were administered by physician, and 26 680 (90.4%) patients were evaluable. Self- and physician-administered questionnaires gave similar results. Rhinitis was diagnosed in 68.5% of patients with self-administered questionnaires and 66.2% with physician-administered questionnaires. In this study, 994 (7.6%) patients with self-administered and 561 (5.2%) patients with physician-administered questionnaires indicated rhinitis symptoms on the questionnaires without a physician’s diagnosis of rhinitis. Most patients with the physician’s diagnosis of rhinitis had moderate/severe rhinitis. Asthma control was significantly impaired in patients with a physician’s diagnosis of rhinitis for all GINA clinical criteria except exacerbations. There were significantly more patients with uncontrolled asthma as defined by GINA in those with a physician’s diagnosis of rhinitis (25.4% and 29.7%) by comparison with those without rhinitis (18.0% and 22.8%).

Conclusion:  Rhinitis is common in asthma and impairs asthma control.

Abbreviations
ARIA

Allergic Rhinitis and its Impact on Asthma

CI

confidence interval

GINA

Global Initiative for Asthma

OR

odds ratio

SACRA

State of the Impact of Allergic Rhinitis on Asthma Control

VAS

Visual Analog Scale

Asthma and rhinitis are common co-morbidities (1–3). Self-reported rhinitis is a significant problem for asthmatics (4). The characterization of rhinitis is difficult as allergic and nonallergic rhinitis may share similar symptoms and may coexist in the same patient (5). However, both allergic and nonallergic rhinitis are associated with asthma. In Japan, it is reported that 44–68% of asthmatics suffer from allergic rhinitis (6, 7). The percentage of co-morbidity varies depending on the area of the country. However, no large national study of this co-morbidity has been performed.

Some studies have suggested an association between asthma and rhinitis severity (8, 9). Asthmatics with documented concomitant allergic rhinitis may experience more asthma-related hospitalizations and physician visits, and incur higher costs than those with asthma alone (10–12). However, the studies are small and/or post hoc analyses. Thus, relationships between asthma and rhinitis severity are still unclear.

In the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, patients are categorized as either having intermittent or persistent rhinitis. The severity of allergic rhinitis has been classified as ‘mild’ or ‘moderate/severe’ depending on symptom severity and effect on quality of life (13). This classification better reflects the patient’s needs (14) and makes it simpler for primary care physicians to diagnose, assess, and manage rhinitis.

The purpose of this cross-sectional study is to assess rhinitis co-morbidity (prevalence and severity) in patients with diagnosed asthma who are receiving medication for their asthma in a large nation-wide survey in Japan and to determine whether rhinitis impairs control.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Source of funding
  9. Author contributions
  10. Conflict of interest
  11. References
  12. Supporting Information

Study design

A cross-sectional multicenter study [State of the Impact of Allergic Rhinitis on Asthma Control (SACRA)] was carried out throughout Japan to assess the prevalence, classification, and severity of rhinitis using the ARIA criteria (1) in patients with diagnosed and treated asthma. The impact of rhinitis on asthma control was also assessed.

The study was performed from March to August 2009. Patients in the waiting room of physicians, or physicians, filled a questionnaire on rhinitis and asthma based on ARIA (1) and the Global Initiative for Asthma (GINA) (15). Questions about the severity of the diseases and Visual Analog Scales (VAS) for both diseases were recorded. Rhinitis diagnosis was made by physicians (Fig. 1) based on ARIA guidelines.

image

Figure 1.  Design of the study.

Download figure to PowerPoint

The primary outcome was the prevalence of physician-diagnosed rhinitis in asthmatics. Secondary parameters included individual symptoms of rhinitis, rhinitis severity assessed according to ARIA, and the control of asthma assessed according to GINA. The VAS data for both asthma and rhinitis were used to assess the patients’ perceptions of the diseases.

Setting

In the study, 1910 physicians in 1805 offices throughout Japan participated (Fig. S1): 1642 primary care physicians, 155 allergists, and 113 chest physicians. Specialists were randomly selected from the list of members of the Japanese Society of Allergology or the Japanese Respiratory Society. The other physicians were primary care physicians who were following a large number of asthmatics in their practices.

Participants

A maximum of 30 consecutive patients over 15 years of age consulting for asthma and receiving a treatment for asthma were included. All patients fulfilled the following inclusion criteria: The diagnosis of asthma was made prior to the consultation using the Asthma Prevention and Management Guidelines of Japan (16) based on the American Thoracic Society recommendations (Table 1). All patients with asthma were enrolled in the study without any consideration of a previous diagnosis of rhinitis. There was no specific training of participating physicians concerning the use of the ARIA and GINA questionnaires.

Table 1.   Diagnosis of asthma
Consideration factors when diagnosing asthma
  1. All subjects had symptoms suggestive of asthma (item 1) excluding other diseases (item 6). Those followed by a specialist had a reversible airflow obstruction (item 2 and eventually 3). Subjects followed in primary care did not always have a pulmonary function test, and items 4–6 were used as minor criteria.

1. Repeated episode of dyspnea, wheezing, cough (especially at nighttime and in early morning)
2. Reversible airflow limitation : An increase in FEV1 of ≥12% and ≥200 ml after administration of a bronchodilator or diurnal variation in PEF of more than 20%
3. Airway hyperresponsiveness: indicated by increase in airway responsiveness to acetylcholine, and histamine
4. Atopic predisposition: indicated by presence of specific IgE antibodies to environmental allergens
5. Presence of airway inflammation: sputum (increases in sputum and peripheral blood eosinophils, elevated ECP, creola bodies, elevated levels of exhaled NO)
6. Exclusion of other underlying disorders: Symptoms are not owing to other pulmonary disorders or cardiovascular disease

Subjects were enrolled after informed consent was obtained. The study conformed to the Ethical Guideline for Epidemiology Research and was approved by the Central Institutional Review Board of Kimura Hospital (Tokyo, Japan).

Variables

Questionnaires

The same questionnaires on asthma and rhinitis were filled in by patients in the physician’s waiting room (self-administered) or by the physician during consultation (physician-administered). The questionnaire for rhinitis was approved by ARIA (1), and the questionnaire for asthma by GINA (15) (Tables S1 and S2). The Japanese translation of the questionnaires was made by the Japanese ARIA and GINA Committee, Prof. Ohta, Chair. The rhinitis questionnaire included four symptoms of rhinitis, an evaluation of conjunctivitis, four questions on environmental factors affecting symptoms, and questions on duration and severity of the disease and impact on quality of life. This questionnaire made it possible to classify rhinitis according to ARIA (1). The asthma questionnaire included eight questions on asthma control and eight questions on environmental factors affecting asthma control. This questionnaire made it possible to assess asthma control based on GINA criteria (15) although pulmonary function tests were not performed as previously published (17). The working definition of asthma control is given in Table S3.

  •  Questionnaire I explains about the pathophysiology of the disease (Rhinitis or asthma) to patients. (Please refer to Table S1‘What is rhinitis?’ or Table S2‘What is asthma’.)
  •  Questionnaire II in the rhinitis questionnaire asks about symptoms highly specific to rhinitis. (Please refer to Table S1‘Could I have rhinitis?’.)
  •  Questionnaire II in the asthma questionnaire asks specific questions to assess control of asthma (Table S2‘What is asthma’.)
  •  Questionnaire III asks about the environmental factors affecting rhinitis or asthma symptoms (Please refer to Table S1‘What is rhinitis?’ or Table S2‘What is asthma’.)
Diagnosis of rhinitis

The physician made the diagnosis of rhinitis based on symptoms of rhinitis, nasal physical examination, serum allergen-specific IgE, skin prick tests, and/or a nasal provocation test, although not every diagnostic evaluation was carried out during all of these examinations.

Visual Analog Scale

Visual analog scales have been used in rhinitis (18, 19) and asthma (20, 21) to assess the impairment induced by these diseases. Two VAS were recorded by the patient before physician’s examination: one for asthma and one for rhinitis. Scores ranged from not at all bothersome (0 cm) to extremely bothersome (10 cm).

Study size

To have the study population be representative of the asthma population in Japan, almost 2000 physicians were selected to enroll up to 30 patients each. According to the report by the Japanese Census and Statistics Department of the Ministry of Internal Affairs and Communications in August 2008, the Japanese population over 15 years of age was about 110 million. With a sample size of 30 000 patients, and an estimated asthma prevalence rate in Japan as 3% (22), the study should include about 1% of the total population of patients with asthma.

Statistical methods

The frequencies and numbers were shown, and chi-square tests were analyzed for subjects with and without rhinitis. An odds ratio and its 95% confidence (OR, 95% CI) interval were calculated for subjects with and without rhinitis.

For continuous data, summary statistics were calculated, and a Mann–Whitney U-test was conducted for subjects with and without rhinitis. Bonferroni’s correction was applied when multiple data were studied. Age data have been converted to appropriate categories for analysis, the frequencies and proportions for each category were calculated. The correlation between age and the co-morbid rate was analyzed by the Pearson product-moment correlation coefficient method. OR and 95% CI were calculated for subjects with and subjects without rhinitis. Missing data were not replaced.

The study was sufficiently large to analyze two sets of data: self-administered and physician’s administered questionnaire with over 13 000 questionnaires in each analysis. Data were analyzed using the software sas ver. 8.2 (SAS Institute Japan Ltd., Tokyo, Japan).

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Source of funding
  9. Author contributions
  10. Conflict of interest
  11. References
  12. Supporting Information

Participants

Thousand nine hundred and ten physicians enrolled 29 518 asthmatics (15.45 patients per physician); 15 051 (51.0%) questionnaires were physician administered. A complete evaluation (diagnosed subjects with no missing answers on the diagnostic sheet or questionnaires) was available for 19 385 patients (65.67%). However, as the primary outcome is the physician’s diagnosis of rhinitis, some questions were not essential for this evaluation (Table S4) and the total number of patients evaluated was 26 680 (90.4%). The disposition of study subjects is shown in Fig. 2.

image

Figure 2.  Flow diagram of the study.

Download figure to PowerPoint

Descriptive data

The demographic characteristics of the patients are presented in Table 2. Rhinitis was present in 67.3% of the total evaluable patients. In this study, 68.5% of patients who used the self-administered questionnaire and 66.2% of patients who used the physician-administered had rhinitis. Rhinitis diagnosis was made on symptoms (92.3%), physical examination (39.1%), and more rarely on serum-specific IgE (27.9%) (Table S5). There was no significant difference for patients with self-administered and physician-administered questionnaires.

Table 2.   Demographic data
 Total population (n = 26 680)Questionnaire administrator
Self-administered (n = 13 024)Physician’s administered (n = 13 656)
Age (years) (OR: per year increase)
 Mean (SD)52.2 (18.7)50.6 (17.8)53.8 (19.4)
Sex, n (%)
 Male10 976 (41.1)5271 (40.5)5705 (41.8)
 Female15 704 (58.9)7753 (59.5)7951 (58.2)
VAS for rhinitis (cm)
 Mean (SD)4.00 (3.41)4.20 (3.40)3.82 (3.41)
 Data missing, n (%)766 (2.9)500 (3.8)266 (1.9)
ARIA classification, n (%)
 Mild intermittent10 763 (40.3)4889 (37.5)5874 (43.0)
 Moderate/severe intermittent9232 (34.6)5230 (40.2)4002 (29.3)
 Mild persistent357 (1.3)129 (1.0)228 (1.7)
 Moderate/severe persistent6328 (23.7)2776 (21.3)3552 (26.0)
VAS for asthma (cm)
 Mean (SD)4.27 (3.04)4.26 (3.05)4.28 (3.04)
 Data missing, n (%)674 (2.5)504 (3.9)170 (1.2)
Control of asthma based on GINA, n (%)
 Controlled8742 (32.8)4394 (33.7)4347 (31.8)
 Partly controlled11 200 (42.0)5626 (43.2)5574 (40.8)
 Uncontrolled6739 (25.3)3004 (23.1)3735 (27.4)
Existence of rhinitis
 n (%)17 945 (67.3)8910 (68.4)9035 (66.2)
 95% CI66.7–67.867.6–69.265.4–67.0

Main results

Main results are presented in Table 3. For most results, self- and physician-administered questionnaires gave similar results although the magnitude of the differences between self- and physician-administered questionnaires differed. Patients with physician’s diagnosed rhinitis were significantly younger than those without rhinitis.

Table 3.   Main results in the 26 680 selected patients
 Questionnaire administrator
Self-administered (n = 13 024)Physician’s administered (n = 13 656)
Existence of rhinitisOR (95% CI)Existence of rhinitisOR (95% CI)
Yes (n = 8910)No (n = 4114)Yes (n = 9035)No (n = 4621)
Age (years)
 Mean (SD)47.4 (17.2)56.8 (17.6)0.970 (0.968–0.973)50.5 (18.8)60.2 (18.8)0.973 (0.971–0.975)
Sex, n (%)
 Male3450 (38.7)1821 (44.3)0.80 (0.74–0.86)3649 (40.4)2056 (44.5)0.85 (0.79–0.91)
 Female5460 (61.3)2293 (55.7)5386 (59.6)2565 (55.5)
Rhinitis questionnaire, n (%)
 Watery rhinorrhea
  Yes5252 (58.9)475 (11.5)11.00 (9.91–12.21)6481 (71.7)273 (5.9)40.42 (35.47–46.05)
  No3638 (41.1)3639 (88.5)2554 (28.3)4348 (94.1)
 Any nasal symptom without watery rhinorrhea
  Yes2157 (24.2)519 (12.6)2.21 (1.99–2.46)1667 (18.5)288 (6.2)3.40 (2.99–3.88)
  No6753 (75.8)3595 (87.4)7368 (81.5)4333 (93.8)
Asthma questionnaire, n (%)
 Wheezing at night
  Yes4024 (45.2)1514 (36.8)1.41 (1.31–1.53)4848 (53.7)2041 (44.2)1.46 (1.36–1.57)
  No4886 (54.8)2600 (63.2)4187 (46.3)2580 (55.8)
 More than twice a week
  Yes1912 (21.6)690 (16.8)1.36 (1.24–1.50)2263 (25.0)1006 (21.8)1.20 (1.10–1.31)
  No6989 (78.4)3424 (83.2)6772 (75.0)3615 (78.2)
 Wheezing during activities or exercise
  Yes3972 (44.6)1500 (36.5)1.40 (1.30–1.51)4256 (47.1)1848 (40.0)1.34 (1.24–1.44)
  No4938 (55.4)2614 (63.5)4779 (52.9)2773 (60.0)
 Cough, dyspnea at night
  Yes3206 (36.0)1073 (26.1)1.59 (1.47–1.73)3815 (42.2)1422 (30.8)1.64 (1.53–1.77)
  No5704 (64.0)3041 (73.9)5220 (57.8)3199 (69.2)
 Dyspnea during daytime of activities
  Yes2728 (30.6)978 (23.8)1.42 (1.30–1.54)3156 (34.9)1356 (29.3)1.29 (1.18–1.40)
  No6182 (69.4)3136 (76.2)5879 (65.1)3265 (70.7)
 Need for rescue inhaler
  Yes3313 (37.2)1165 (28.3)1.50 (1.38–1.62)3506 (38.8)1273 (27.5)1.67 (1.54–1.80)
  No5597 (62.8)2949 (71.7)5529 (61.2)3348 (72.5)
 Need for rescue inhaler over twice a week
  Yes1701 (19.1)671 (16.3)1.21 (1.10–1.34)1680 (18.6)698 (15.1)1.28 (1.17–1.41)
  No7209 (80.9)3443 (83.7)7355 (81.4)3923 (84.9)

In the 26 680 evaluable patients, rhinitis was present in 68.5% of patients who used the self-administered questionnaire and in 66.2% of those who received the physician-administered questionnaire (Table 3). However, 994 (7.6%) patients with the self-administered questionnaire and 561 (5.2%) patients with physician-administered questionnaire had rhinitis symptoms on questionnaire without a physician’s diagnosis of rhinitis.

The majority of patients with a physician’s diagnosis of rhinitis had moderate/severe rhinitis; 74.7% and 76.2% (self- and physician-administered questionnaires respectively) of patients had bothersome symptoms. Some patients without a diagnosis of rhinitis had mild rhinitis as determined by ARIA, but only 887 (6.8%) and 342 (2.5%) of these patients had indicated that they had bothersome symptoms of rhinitis on their questionnaires (self- and physician-administered questionnaires respectively). The median VAS value for rhinitis was 5.49 [2.51–7.90 (25–75%)] and 5.6 (2.75–7.85) cm in patients with a physician’s diagnosis of rhinitis vs 0.38 (0.0–2.32) and 0.07 (0.0–0.42) cm in patients without a physician’s diagnosis of rhinitis (self- and physician-administered questionnaires respectively).

For the vast majority of analyses comparing the presence or absence of rhinitis, the significance of the results was identical in self-administered and physician-administered questionnaires. However, the magnitude of the differences between patients with and without physician’s diagnosed rhinitis differed (Table 3). Patients with physician’s diagnosed rhinitis were significantly younger than those without rhinitis.

Asthma control was significantly worse in patients with a physician’s diagnosis of rhinitis by comparison with those without rhinitis for all criteria except exacerbations requiring systemic corticosteroid in past year. There were significantly more patients with uncontrolled asthma as defined by GINA in those with a physician’s diagnosis of rhinitis (25.4 self-administered and 29.7% physician-administered) by comparison with those without rhinitis (18.0% self-administered and 22.8% physician-administered). The VAS value for asthma was 4.75 (1.85–7.00) and 4.79 (1.90–7.18) cm in patients with a physician’s diagnosis of rhinitis vs 2.90 (0.83–5.78) and 2.98 (0.81–6.10) cm in patients without rhinitis (self- and physician-administered questionnaires respectively)

Other analyses

The cumulative prevalence of rhinitis in asthmatics differs depending on the age of the patient (Fig. 3A,B). Under the age of 60 years, over 75% of asthmatics have physician’s diagnosed rhinitis. Watery rhinorrhea was present in around 60% of the patients with physician’s diagnosed rhinitis before the age of 60 years. After the age of 60 years, the prevalence of watery rhinorrhea decreased whereas the prevalence of rhinitis without rhinorrhea was similar in all age groups. Watery rhinorrhea was less reported by patients than by physicians according to the self- and physician-administered questionnaires (r = −0.238, P < 0.0001). The repartition of VAS for asthma in patients with and without a physician’s diagnosis of rhinitis is presented in Fig. S2.

image

Figure 3.  Cumulative prevalence of rhinitis in asthmatics depending on age. (A) Self-administered questionnaire. (B) Physician’s administered questionnaire.

Download figure to PowerPoint

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Source of funding
  9. Author contributions
  10. Conflict of interest
  11. References
  12. Supporting Information

Key results

Using the most used guidelines on rhinitis and asthma (ARIA and GINA), in a large nation-wide study of asthmatics in Japan, 67.3% of patients present with physician-diagnosed rhinitis. Some patients without physician’s diagnosed rhinitis have nasal symptoms suggestive of rhinitis and up to 73.1% of asthmatics may be assumed to suffer from rhinitis. This study is the first to show (i) an age-dependent prevalence of rhinitis, (ii) that most asthmatics have moderate/severe rhinitis as defined by ARIA, and (iii) that patients with physician’s diagnosed rhinitis have poorer asthma control, as defined by GINA, than those without rhinitis. The study included two sets of over 13 000 patients each using identical questionnaires for asthma and rhinitis. Similar results have been obtained in both populations showing the validity of results.

Limitations

The subjects included in this study were prediagnosed with asthma. The diagnosis of asthma was made according to the Japanese guidelines (16). These guidelines have been used by the vast majority of physicians in Japan for the past 15 years (23) and have been frequently updated. However, it is possible that, after 60 years of age, some COPD patients may have been diagnosed as asthmatics (24).

The same questionnaire was self-administered and physician-administered. The questions were based on the two most widely used asthma [GINA (15)] and rhinitis [ARIA (1)] guidelines. All questions were filled in, and 26 680 (90.3%) patients had an evaluable questionnaire for the study purpose. Results of both questionnaires were similar. The severity and persistence of rhinitis was based on all ARIA questions (1). The control of asthma was based on GINA questions (15) but did not include pulmonary function (17). It is, therefore, possible that some patients were classified as ‘controlled’ whereas they were not. However, most asthma control questionnaires do not use pulmonary function tests (25), and the ACQ (asthma control questionnaire) is more reliable without including data of pulmonary function tests than with them (26). Some questions of GINA control are not fully defined, and we needed to use a specific wording. This is the case for the duration of the survey (4 weeks).

Treatment of patients for asthma or rhinitis was not defined, as, in this sample it appeared very difficult to assess the exact treatment. Moreover, asthma control is independent of treatment (25). On the other hand, some patients receiving treatment for rhinitis may not have had a physician’s diagnosis of rhinitis as they may have been asymptomatic.

Visual analog scales are used in many diseases and are of interest in rhinitis (18, 19). The present study confirms the potential importance of VAS in rhinitis as asthmatics without rhinitis have a median level of 0.07–0.38 cm whereas those with physician-diagnosed rhinitis have a median value of 5.49–5.6 cm. These levels are similar to those reported in European populations of rhinitis patients (18, 19). However, for asthma, VAS is not validated yet and it was used as an exploratory outcome.

Allergic and nonallergic rhinitis cannot be differentiated by questionnaire and a structured allergy history may be insufficient for the diagnosis of allergy (27). Around 20% of asthmatics had nasal obstruction without rhinorrhea, and these patients may have nonallergic rhinitis (5). Smoking was not studied and this exposure may have helped to differentiate asthma and COPD in the older population group of the study (24).

The study is a nation-wide survey with an adequate repartition of patients throughout the country. The duration of the study may have been extended to one year to control climatic parameters. However, in autumn and winter, many patients could have viral nasal infections which can mimic rhinitis. We, therefore, reduced the length of the study to around 6 months.

Interpretation

The primary outcome was the rate of rhinitis in asthmatics assessed using physician-diagnosis of rhinitis. As previously reported, rhinitis is common in asthma (1–3). However, this study is unique owing to the diagnosis of rhinitis by physicians in a very large sample, the questionnaire based on GINA and ARIA. No study of this size has ever been published. It appears that physicians may not diagnose rhinitis accurately as a subset of asthmatics without diagnosis of rhinitis had nasal symptoms, and some of them had moderate/severe nasal symptoms. The vast majority of patients without diagnosed rhinitis had intermittent symptoms. Thus, it is likely that the rate of rhinitis was greater than that diagnosed by physicians. In subsequent analyses, it will be important to assess differences between primary care physicians and allergy specialists.

Another novel finding is the age-dependent prevalence of rhinitis. The size of the study allows comparisons between age groups and 1891 patients were over 80 years. Rhinitis prevalence decreases from around 75% below the age of 60 years to 45% after 80 years. Less than 30% of asthmatics over 80 years had rhinorrhea. In older patients, there may be differences in perception of rhinitis or different phenotypes of asthma and/or rhinitis and their interaction (28). These data prompt new studies in elderly to better understand and control rhinitis and asthma and their interaction.

Asthma control is impaired in patients with rhinitis. This is a novel finding as no study included a full questionnaire on GINA in patients with rhinitis and many studies are post hoc analyses (29, 30). All GINA clinical criteria (except exacerbations in past year) and VAS levels are consistent. Moreover, the results of self-questionnaire and physician-administered questionnaires show similar results. Patients report fewer criteria of poor control than physicians. It is possible that differences in asthma treatment exist between asthmatics with and without rhinitis.

Generalizability

This study used the same methods in two sets of subjects and experimenters. It may be, therefore, seen as a replication study to determine generalizability to different subjects, age groups, and locations. The results are reliable and valid, and extraneous variables did not modify results. Underreporting of rhinitis symptoms and asthma control was observed when the questionnaires were applied by the patients. This is common in allergy and respiratory fields (31). The sample group is truly representative of the whole Japanese population.

The size of the group allows the statistics to be safely extrapolated to the entire population of Japan and give clues for the expansion outside Japan as many of the outcomes are similar in Japanese and European populations (18, 19).

Conclusions

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Source of funding
  9. Author contributions
  10. Conflict of interest
  11. References
  12. Supporting Information

Asthma is a highly prevalent disease worldwide and although links between asthma and rhinitis have been extensively studied, no large study has been made using the most widely used questionnaires for both asthma and rhinitis. Thus, although the study has been exclusively made in Japan, it can be generalized. This study shows that rhinitis should be examined in all patients with asthma and that rhinitis is a marker of lack of control of the disease.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Source of funding
  9. Author contributions
  10. Conflict of interest
  11. References
  12. Supporting Information

No medical writer was involved in writing or reviewing of the paper. Especially, we would like to express our thanks to Keisuke Tobe of Banyu Pharmaceuticals for his contribution to the statistical analysis of the manuscript. Jean Bousquet supported by EU Framework programme for research, contract no. FOOD-CT-2004-506378.

Source of funding

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Source of funding
  9. Author contributions
  10. Conflict of interest
  11. References
  12. Supporting Information

The study was sponsored by Banyu Pharmaceutical Co, Ltd (Kitanomaru Square, 1-13-12, Kudan-kita, Chiyoda-ku, Tokyo 102-8667, Japan). The authors designed the protocol and wrote the paper without help from a medical writer. They were aware of the results and proposed the statistical analysis which was made by EPS Co., Ltd (2-3-19, Koraku, Bunkyo-ku, Tokyo, Japan) entrusted by Banyu.

Author contributions

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Source of funding
  9. Author contributions
  10. Conflict of interest
  11. References
  12. Supporting Information

Ken Ohta designed the protocol and was involved in the writing and analysis. Jean Bousquet was involved in the design of the protocol, the analysis, and writing. Philippe J. Bousquet was involved on the methodology part and writing of the paper. Lawrence Grouse was involved in the protocol design and the writing of the paper. The other Japanese authors participated in the design of the protocol, recruitment of patients, and drafting of the paper.

Conflict of interest

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Source of funding
  9. Author contributions
  10. Conflict of interest
  11. References
  12. Supporting Information

Ken Ohta has received honorarium for boards, scientific expertize, lectures from AstraZeneca, GSK, Kyorin, Novartis, MSD. Philippe Jean Bousquet has received honorarium for lectures and scientific expertize from Schering Plough and Stallergènes. Jean Bousquet has received honorarium for boards, scientific expertize, lectures from ALK, AstraZeneca, Banyu, Chiesi, GSK, Merck, Novartis, Schering Plough, Stallergènes, UCB. Hisamichi Aizawa has received honorarium for lectures from Boehringer Ingelheim, GSK. Sankei Nishima has received honorarium for scientific expertize from Teijin Pharma. The following authors have no conflict to declare, Kazuo Akiyama, Mitsuru Adachi, Masakazu Ichinose, Motohiro Ebisawa, Gen Tamura, Atsushi Nagai, Takeshi Fukuda, Akihiro Morikawa, Yoshitaka Okamoto, Yoichi Kohno, Hirohisa Saito, Hiroshi Takenaka, Lawrence Grouse.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Source of funding
  9. Author contributions
  10. Conflict of interest
  11. References
  12. Supporting Information
  • 1
    Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008;63(Suppl. 86):8160.
  • 2
    Shaaban R, Zureik M, Soussan D, Neukirch C, Heinrich J, Sunyer J et al. Rhinitis and onset of asthma: a longitudinal population-based study. Lancet 2008;372:10121014.
  • 3
    Ait-Khaled N, Odhiambo J, Pearce N, Adjoh KS, Maesano IA, Benhabyles B et al. Prevalence of symptoms of asthma, rhinitis and eczema in 13- to 14-year-old children in Africa: the International Study of Asthma and Allergies in Childhood Phase III. Allergy 2007;62:247258.
  • 4
    Walker S, Sheikh A. Self reported rhinitis is a significant problem for patients with asthma. Prim Care Respir J 2005;14:8387.
  • 5
    Bousquet J, Fokkens W, Burney P, Durham SR, Bachert C, Akdis CA et al. Important research questions in allergy and related diseases: nonallergic rhinitis: a GA2LEN paper. Allergy 2008;63:842853.
  • 6
    Dobashi K, Nakazawa T, Mori M. [Report on the questionnaire study of actual status of adult bronchial asthma patients in gunma prefecture]. Nisshoku Kan A J 2003;10:226.
  • 7
    Okada M, Names PF. [Frequency of seasonal allergic rhinitis, bronchial asthma and atopic dermatitis in adult females in the Area of Osaka, Rinsho to Kenkyu]. J Clin Pract Res 2009;79:134137.
  • 8
    Bresciani M, Paradis L, Des Roches A, Vernhet H, Vachier I, Godard P et al. Rhinosinusitis in severe asthma. J Allergy Clin Immunol 2001;107:7380.
  • 9
    ten Brinke A, Grootendorst DC, Schmidt JT, De Bruine FT, van Buchem MA, Sterk PJ et al. Chronic sinusitis in severe asthma is related to sputum eosinophilia. J Allergy Clin Immunol 2002;109:621626.
  • 10
    Bousquet J, Gaugris S, Kocevar VS, Zhang Q, Yin DD, Polos PG et al. Increased risk of asthma attacks and emergency visits among asthma patients with allergic rhinitis: a subgroup analysis of the improving asthma control trial. Clin Exp Allergy 2005;35:723727.
  • 11
    Price D, Zhang Q, Kocevar VS, Yin DD, Thomas M. Effect of a concomitant diagnosis of allergic rhinitis on asthma-related health care use by adults. Clin Exp Allergy 2005;35:282287.
  • 12
    Sole D, Camelo-Nunes IC, Wandalsen GF, Melo KC, Naspitz CK. Is rhinitis alone or associated with atopic eczema a risk factor for severe asthma in children? Pediatr Allergy Immunol 2005;16:121125.
  • 13
    Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108 (5 Suppl.):S147S334.
  • 14
    Ciprandi G, Cirillo I, Vizzaccaro A, Tosca M, Passalacqua G, Pallestrini E et al. Seasonal and perennial allergic rhinitis: is this classification adherent to real life? Allergy 2005;60:882887.
  • 15
    Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, Fitzgerald M et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008;31:143178.
  • 16
    Nishima S. [New approach and recommendation in JAGL2007 (Japanese guideline for the diagnosis and treatment of allergic diseases 2007)]. Nippon Rinsho 2009;67:20392042.
  • 17
    Thomas M, Kay S, Pike J, Williams A, Rosenzweig JR, Hillyer EV et al. The Asthma Control Test (ACT) as a predictor of GINA guideline-defined asthma control: analysis of a multinational cross-sectional survey. Prim Care Respir J 2009;18:4149.
  • 18
    Bousquet PJ, Combescure C, Neukirch F, Klossek JM, Mechin H, Daures JP et al. Visual analog scales can assess the severity of rhinitis graded according to ARIA guidelines. Allergy 2007;62:367372.
  • 19
    Bousquet PJ, Combescure C, Klossek JM, Daures JP, Bousquet J. Change in visual analog scale score in a pragmatic randomized cluster trial of allergic rhinitis. J Allergy Clin Immunol 2009;123:13491354.
  • 20
    Flood EM, De Cock E, Mork AC, Revicki DA. Evaluating preference weights for the Asthma Symptom Utility Index (ASUI) across countries. Health Qual Life Outcomes 2006;4:51.
  • 21
    Laforest L, El Hasnaoui A, Pribil C, Ritleng C, Schwalm MS, Van Ganse E. Asthma patients’ perception of their ability to influence disease control and management. Ann Allergy Asthma Immunol 2009;102:378384.
  • 22
    Nakagawa T, Miyamoto T, Ito K, Ohta K. Prevalence of bronchial asthma in adult habitants in Fujieda city. Nihon Kyobu Shikkan Gakkai Zasshi 1987;25:873879.
  • 23
    Makino S, Furusho K, Ohta K, Mukoyama T. A survey on awareness and utilization of new asthma management guidelines in Japan. J Asthma 2003;40:701708.
  • 24
    Jenkins CR, Thompson PJ, Gibson PG, Wood-Baker R. Distinguishing asthma and chronic obstructive pulmonary disease: why, why not and how? Med J Aust 2005;183(1 Suppl.):S35S37.
  • 25
    Humbert M, Holgate S, Boulet LP, Bousquet J. Asthma control or severity: that is the question. Allergy 2007;62:95101.
  • 26
    Juniper EF, Bousquet J, Abetz L, Bateman ED. Identifying ‘well-controlled’ and ‘not well-controlled’ asthma using the Asthma Control Questionnaire. Respir Med 2006;100:616621.
  • 27
    Smith HE, Hogger C, Lallemant C, Crook D, Frew AJ. Is structured allergy history sufficient when assessing patients with asthma and rhinitis in general practice? J Allergy Clin Immunol 2009;123:646650.
  • 28
    Busse PJ, Kilaru K. Complexities of diagnosis and treatment of allergic respiratory disease in the elderly. Drugs Aging 2009;26:122.
  • 29
    Zhang Q, Thomas M, Wisniewski T, Sazonov Kocevar V, Price D. Treatment and outcomes in patients with asthma and allergic rhinitis in the United Kingdom. Int Arch Allergy Immunol 2006;142:318328.
  • 30
    Haughney J, Price D, Kaplan A, Chrystyn H, Horne R, May N et al. Achieving asthma control in practice: understanding the reasons for poor control. Respir Med 2008;102:16811693.
  • 31
    Holgate S, Bisgaard H, Bjermer L, Haahtela T, Haughney J, Horne R et al. The Brussels Declaration: the need for change in asthma management. Eur Respir J 2008;32:14331442.

Supporting Information

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. Acknowledgments
  8. Source of funding
  9. Author contributions
  10. Conflict of interest
  11. References
  12. Supporting Information

Figure S1. Distribution of Institutions across Japan.

Figure S2. VAS on asthma.

Table S1. Questionnaire on rhinitis in asthmatics.

Table S2. Questionnaire on asthma control with rhinitis.

Table S3. Working definition of GINA classification employed in SACRA to assess asthma control.

Table S4. Number of participants with missing data.

Table S5. Diagnosis of rhinitis.

Table S6. Rhinitis deteriorates asthma control assessed by VAS and GINA criteria.

Table S7. Other results.

FilenameFormatSizeDescription
ALL_2676_sm_supplement.doc1903KSupporting info item

Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.