To cite this article: Valero A, Ferrer M, Baró E, Sastre J, Navarro AM, Martí-Guadaño E, Dávila I, del Cuvillo A, Colás C, Antépara I, Alonso J, Mola O, Izquierdo I, Mullol J. Discrimination between moderate and severe disease may be used in patients with either treated or untreated allergic rhinitis. Allergy 2010; 65: 1609–1613.
Background: Allergic rhinitis (AR) is a common disease with major socioeconomic burden and a significant impact on quality of life.
Objective: The aim of this study was to discriminate between moderate and severe AR patients whether receiving treatment or not, using a modified criterion of allergic rhinitis and its impact on asthma (ARIA) classification.
Methods: The modified ARIA severity classification (J Allergy Clin Immunol, 120, 2007, 359) categorizes AR as mild (no items affected), moderate (1–3 items affected), and severe (all four items affected). We applied these criteria to 1666 treated and 1058 untreated AR patients and compared their symptoms total four-symptom score (T4SS) and quality of life (ESPRINT-15), according to their clinical severity.
Results: Allergic rhinitis clinical status was significantly worse (P < 0.001) in treated than in untreated patients. For both treated and untreated patients, T4SS and ESPRINT-15 Quality of life scores were significantly worse (P < 0.001) in severe than in moderate patients.
Conclusions: The modified ARIA severity classification is a useful clinical tool to discriminate moderate from severe AR among both treated and untreated patients.
allergic rhinitis and its impact on asthma
EStudio de la calidad de vida enPacientes conRINoconjunTivitis (Quality of Life Study in Patients with Rhinoconjunctivitis)
health-related quality of life
intermittent allergic rhinitis
persistent allergic rhinitis
rhinoconjunctivitis quality of life questionnaire
severe chronic upper airway disease
total four-symptom score
Allergic rhinitis (AR) is a common and increasingly prevalent disease that generates an important socioeconomic burden and a significant impact on quality of life (QoL) (1). Allergic rhinitis has traditionally been classified as perennial or seasonal depending on the allergen responsible of symptoms (2, 3). The allergic rhinitis and its impact on asthma (ARIA) document developed a new classification based on symptom duration: intermittent (IAR) and persistent (PER) rhinitis. The ARIA classification also introduced a system for assessing AR severity based on the impairment of four health-related quality of life (HRQL) items: sleep, daily activities/sport and leisure, work or school performance, and troublesome symptoms.
According to the ARIA workshop group, AR is mild when there is no impairment of any of these items, while moderate/severe when one or more of these items are impaired (1). Moreover, the large prevalence of moderate/severe rhinitis (69–90%) (4–6) suggests an important heterogeneity in this disease severity group (7). Bousquet et al. (2) have proposed the replacement of the term ‘moderate/severe’ by ‘severe’ as a result of the high proportion of patients reporting impaired activities, while Van Hoecke et al. (8) have proposed to discriminate between moderate and severe rhinitis by reducing the number of the ARIA severity criteria in two: impact on sleep and impact on daily activities, sport and leisure, and work or school performance. Our group has recently proposed a modification of the ARIA severity classification, by maintaining the original severity items, which allows to discriminate between AR patients with different levels of severity: mild (not affected items), moderate (1–3 affected items), and severe (four affected items) (9).
Because ARIA recommends the use of its severity classification in untreated patients, the modified criterion proposed was only validated among untreated patients. However, as most AR patients attended in outpatient clinics are already treated (10, 11), recent studies have started to use the ARIA severity classification also in treated AR patients (2, 8, 12, 13).
The objective of the study was to validate the modified ARIA criterion (9) in a large sample population of patients with AR, allowing to discriminate between moderate and severe status among patients either receiving or not receiving treatment.
Study design and population
The study was performed using a pre-existing database from a cross-sectional, population-based study. The study was a survey conducted from April to June 2005 to evaluate a large representative data on adult outpatient population suffering from AR in Spain. Patient’s characteristics have been published elsewhere (14). Participants were older than 18 years, with a confirmed diagnosis of AR and currently visiting their physician for AR, either under current treatment or untreated. The study investigators (N = 539) mainly were general practitioners (69%), ENT specialists (18.2%), or allergologists (8.4%) from primary care and hospital-based settings distributed throughout Spain (data were not available for 4.4% of the study investigators). Patients with AR (N = 2756) were recruited by a quota sampling procedure: 16 quotas of 170 patients each were performed to ensure representative sampling of age, gender, and ARIA classification (duration and severity) from the studied population. This study has been approved by the Ethics Committee of Hospital Clinic de Barcelona (Spain).
Patient’s clinical evaluation
In addition to sociodemographic characteristics of patients (age, gender, and educational level), data about the type of AR rhinitis (persistent or intermittent, according to ARIA definition) (1) and the treatment regime were collected.
Different outcome measures were administered:
- • Allergic rhinitis severity classification. AR severity was assessed by the four ARIA items (sleep, daily activities/sport, work/school performance, and troublesome symptoms) to classify patients on different levels of disease severity (1): mild (no affected items) and moderate/severe (one or more affected items), as well as distinguishing between moderate (1–3 affected items) and severe (four affected items), based on the modified criterion (9).
- • Total Four-Symptom Score (T4SS ). The T4SS was computed as the sum of the four main nasal symptoms of rhinitis: nasal congestion, rhinorrhea, nasal itching, and sneezing. Symptoms were scored from 0 to 3 (0, no symptoms; 1, mild; 2; moderate; and 3, severe).
- • ESPRINT-15 questionnaire. This is an AR-specific QoL questionnaire, validated in Spain, which contains 15 items covering five domains: symptoms (five items), daily activities (three items), sleep (three items), psychological affectation (three items), and wellness (one item). Items were answered using a six-point Likert scale. Both global and domain scores are computed, ranging from 0 to 6 (the worst QoL) (15, 16).
Group comparisons were performed using unpaired Student’s t-test, nonparametric Mann–Whitney U-test, and Chi-square or Fisher’s exact statistics, when appropriate. Chi-square statistics were also used to examine differences in the T4SS (asymptomatic, mild, moderate and severe) among different AR severity levels, in both treated and untreated patients. Comparisons of ESPRINT-15 between subjects with or without treatment and their AR severity were carried out by anova test for lineal trend. Tukey’s studentized range was calculated for post hoc comparisons if a statistical difference was found among groups. All hypothesis tests were two tailed, and statistical significance was assessed at the 0.05 levels. All statistical procedures were performed using an spss package version 13 for Windows (SPSS Inc, Chicago, IL, USA).
The analysis included 2.724 patients with AR either treated (N = 1666) or untreated (N = 1058). Clinical severity according to T4SS, disease severity, and HRQL outcomes of AR was significantly worse (P < 0.001) for treated than for untreated patients (Table 1), suggesting that more severe symptoms lead patients to seek treatment. In addition, significant differences were found in the distribution of T4SS scores among the different severity groups, using both original and modified ARIA criterion classifications, for both treated (P < 0.001) and untreated (P < 0.001) patients (Table 2).
|Global (N = 2724)||Treated patients (N = 1666)||Untreated patients (N = 1058)||P-value|
|Age, years (mean ± SD)||47.5 ± 16.8||47.6 ± 16.4||47.2 ± 17.5||NS|
|Gender, women, N (%)||1427 (52.4)||899 (54.0)||528 (50.0)||0.041*|
|Type of AR duration (%)|
|AR severity (ARIA original) (%)|
|AR severity (New Criterion) (%)|
|ESPRINT questionnaire, mean ± SD|
|Global score||2.3 ± 1.4||2.5 ± 1.3||2.0 ± 1.4||<0.001†|
|Symptoms domain||2.5 ± 1.4||2.7 ± 1.3||2.2 ± 1.4||<0.001†|
|Daily activities domain||2.2 ± 1.5||2.4 ± 1.4||1.9 ± 1.5||<0.001†|
|Sleep domain||2.2 ± 1.6||2.4 ± 1.6||2.0 ± 1.6||<0.001†|
|Psychological impact domain||2.2 ± 1.5||2.4 ± 1.5||1.9 ± 1.5||<0.001†|
|ESPRINT- item 15 (%)|
|AR severity||Treated patients||Untreated patients|
|N||T4SS median, interquartile range||N||T4SS median, interquartile range|
|T4SS score mean by ARIA original severity classification|
|Mild||142||0, 0–1||184||0, 0–1|
|Moderate/Severe||1449||2, 1–3||846||2, 1–2|
|Severity intragroup analysis (Kruskal–Wallis)||P < 0.001||P < 0.001|
|T4SS score mean by ARIA new criterion severity classification|
|Mild||142||0, 0–1||184||0, 0–1|
|Moderate||990||2, 1–2||648||1, 1–2|
|Severe||459||3, 2–3||198||2, 2–3|
|Severity intragroup analysis (Kruskal–Wallis)||P < 0.001||P < 0.001|
Using ARIA original severity classification, ESPRINT-15 HRQL global scores were significantly higher (worse) for moderate/severe patients than for mild patients (Figs 1A and 2A). When using the modified ARIA classification, ESPRINT-15 HRQL global scores also significantly discriminated between moderate and severe patients (Figs 1B and 2B). These differences were observed in both untreated (Fig. 1) and treated (Fig. 2) patients with AR.
A significant trend on global scores of ESPRINT-15 among groups of treated and untreated patients defined by different levels of disease severity (mild/moderate/severe) was demonstrated. Higher scores (worse QoL) were observed through AR severity groups. Tests for pair wise comparisons showed significant differences between mild and moderate patients and between moderate and severe patients (Figs 1 and 2).
The main findings of this study were: first, the New Criterion of ARIA to discriminate between moderate and severe disease was validated in a large population of patients with AR. Severe patients showed significantly worse symptom and QoL scores than moderate patients. Second, the application of the modified criterion was valid not only for the untreated but also for the treated AR patient population, where differences among moderate and severe disease on symptoms and QoL were significant as well.
The excessive proportion of patients with AR classified in the moderate/severe group (69–90%) (2, 4, 6) clearly justifies the need of differentiating among moderate and severe rhinitis patients, if progression of disease is to be adequately monitored. This discrimination between moderate and severe patients would be useful to obtain more homogeneous populations of patients, according to their severity, to better design epidemiological studies and clinical trials, and to develop disease management strategies in both treated and untreated patients (2, 17–19).
Until present, the ARIA document has recommended the application of ARIA classification only in patients with untreated rhinitis, although most patients with AR evaluated in outpatient clinics are receiving treatment (10, 11). Following the results of this study, we are now able to classify the severity of AR also in patients with treated rhinitis and thereby monitor the response to different therapeutic strategies. Nevertheless, the development of rhinitis control tools to evaluate the response to treatment and to generate adequate therapeutic strategies should be strongly encouraged. The analysis of both control and clearly defined severity phenotypes may also help to develop new epidemiological, clinical, and pharmacoeconomic studies under the umbrella of the new concept of Severe Chronic Upper Airway Disease (20).
In conclusion, we have shown that modified ARIA severity classification can validly discriminate between moderate and severe AR in a large population of both treated and untreated patients with AR. Using the number of affected ARIA severity items: mild (no item affected), moderate (one to three affected items), and severe (four affected items), we have achieved a more efficient and valid grouping of patients whose symptoms and QoL are clearly different.
This study was sponsored by an unrestricted educational grant from Grupo Uriach SA, Barcelona, Spain. We also thank all the investigators participating in the different phases of the ESPRINT project.
We are extremely grateful to the 539 investigators who made this study possible.