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Keywords:

  • allergic rhinitis;
  • children;
  • modified ARIA criterion;
  • severity

Abstract

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. Conflict of interest
  8. References

Background

A modified allergic rhinitis and its impact on asthma (ARIA) (m-ARIA) criterion to classify the severity of allergic rhinitis (AR) has recently been validated in both treated and untreated adult patients; however, such information in children is lacking. The aim of this study was to validate this m-ARIA severity criterion, which allows for discrimination between moderate and severe AR, in a large pediatric patient sample population.

Methods

The m-ARIA classification categorizes AR severity into mild (no affected items), moderate (1–3 affected items), and severe (all four affected items). We applied this modified criterion to untreated AR pediatric patients aged 6–12 years, through an observational, cross-sectional, and multicenter study. AR symptoms were assessed using the Total Four Symptom Score (T4SS), and the severity was evaluated by both ARIA severity items and visual analogue scale (VAS).

Results

Allergic rhinitis pediatric patients (= 1269) from 271 centers were included. Among them, 59.5% had intermittent and 40.5% persistent disease; 89.9% had moderate/severe AR using the original ARIA (o-ARIA) classification and 59.5% had moderate, while 30.5% had severe AR using the m-ARIA criterion. Using the m-ARIA, significantly higher T4SS and VAS scores were obtained when comparing severe with moderate AR.

Conclusions

The m-ARIA severity classification is a useful clinical tool to discriminate moderate from severe AR among untreated pediatric patients.

Abbreviations
AR

allergic rhinitis

ARIA

allergic rhinitis and its impact on asthma

HRQL

health-related quality of life

m-ARIA

modified ARIA

o-ARIA

original ARIA

QoL

quality of life

RQLQ

rhinoconjunctivitis quality of life questionnaire

SCUAD

severe chronic upper airway disease

TSS

total symptom score

VAS

visual analogue scale

Allergic rhinitis (AR) is a common and increasingly prevalent disease that generates a significant socioeconomic burden and impact on the quality of life (QoL). The Allergic Rhinitis and its Impact on Asthma (ARIA) document shows that AR is the most frequent allergic chronic disease in the pediatric population and is often associated with other allergic diseases [1]. In Spain, almost a half of AR pediatric patients suffer from bronchial asthma (44.9%), the onset of rhinitis being significantly associated with the development of asthma [2]. The ISAAC study has shown an increasing prevalence of AR in Spain and other countries [3]. In the Spanish pediatric population, AR prevalence ranges from 8.2% (6–7 years) to 15.5% (13–14 years) [4]. Children suffering from AR also have a measurable impairment in health-related QoL (HRQL), demonstrated by decreased school performance, sleep disturbance, emotional, and other psychosocial problems [5-8].

The ARIA document developed a new classification based on symptom duration: intermittent and persistent allergic rhinitis, and introduced a system for assessing AR severity based on the impairment of four HRQL items: sleep, daily activities/sport/leisure, work productivity/school performance, and troublesome symptoms [1]. ARIA document is on continuous updating process involving different areas like clinical symptoms, diagnostic procedures, and its interpretation, treatment, encouraging physicians, and patients to understand and use ARIA guidelines in order to raise the optimal care and increase the control of the AR in adult and pediatric patients [9, 10].

According to the original ARIA classification (o-ARIA), AR is mild when there is no impairment of any of these items, whereas it is moderate/severe when one or more of these items are impaired [1]. Moreover, the large prevalence of moderate/severe rhinitis (89.9% of patients in our study) suggests an important heterogeneity in this disease severity group that should be eliminated in order to achieve a better evaluation of AR [11-13]. Valero et al. [14] have recently proposed a modification of the o-ARIA severity classification, by maintaining the original four items that allow for discrimination between AR patients with different levels of severity: mild (no affected items), moderate (1–3 affected items), and severe (all four affected items). Jáuregui et al. [15] have recently validated the o-ARIA classifications in a pediatric population. Total Four Symptom Score (T4SS) was significantly different among diverse categories and visual analogue scale (VAS) adequately correlated with severity according to ARIA items, concluding that o-ARIA classification by itself is able to discriminate severity grades in children aged 6–12 years.

The objective of the present study was, for the first time, to validate the m-ARIA severity classification [14] in a large sample population of AR pediatric patients, allowing for discrimination between moderate and severe status. Following ARIA recommendations, our study only includes untreated patients and no current ARIA severity item has been deleted or modified.

Material and methods

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. Conflict of interest
  8. References

Study design and population

The study was a multicenter, epidemiological, cross-sectional population-based registry. The survey was conducted between May and July 2008 in order to evaluate a large representative data on pediatric outpatient population suffering from AR in Spain. Participants were aged 6–12 years, with a confirmed diagnosis of AR, currently visiting their physician for AR, untreated in the 2 weeks prior to inclusion, and whose legal guardians had given written consent. A total of 271 centers and 334 investigators distributed throughout Spain to avoid any geographic or seasonal influence participated in this study: 23.9% were allergologists, 12.8% otorhinolaryngologists, 61.8% pediatricians, and 1.5% allergic pediatricians. Patients with AR (= 1269) were recruited if they fulfilled the following inclusion criteria: (i) 6–12 years old, (ii) a previous diagnosis of AR made by an allergist, (iii) a signed parental consent form, and (iv) not having received any treatment for their AR for at least the two weeks preceding inclusion in the study. Patients were considered to suffer from AR if they had (i) suggestive symptoms of rhinoconjunctivitis within one or more preceding years and (ii) at least one positive skin prick test and/or specific IgE to a clinically relevant aeroallergen. The study was approved by the Ethics Committee of Hospital Clínic of Barcelona (Spain).

Study outcomes

Demographic data (age, sex, height, and weight), place of residence, and household characteristics, skin allergen sensitization, mean duration of AR, and severity of AR according to m-ARIA criterion were obtained. The presence of comorbidities including asthma, atopic dermatitis, acute and chronic urticaria, rhinosinusitis, drug allergy, food allergy, seromucous otitis, and adenoid hypertrophy was also evaluated.

The duration of AR was classified according to ARIA guidelines as persistent (symptoms appearing for more than 4 days a week and more than four consecutive weeks) or intermittent (symptoms appearing up to 4 days a week or up to four consecutive weeks) [1].

Three different outcomes were used to evaluate the disease:

  • AR severity classification. AR severity was assessed by the four ARIA items (sleep, daily activities/sport/leisure, school performance, and troublesome symptoms) to classify patients on different levels [1]: mild (no affected items) and moderate/severe (one or more affected items) using o-ARIA classification, as well as discriminating between moderate (1–3 affected items) and severe (all of four affected items), using the m-ARIA criterion [14]. Each of the items was evaluated by VAS.
  • T4SS. The T4SS was calculated 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; 3, severe), resulting in a T4SS ranging from 0 to 12.
  • VAS. Severity was also assessed by patients using VAS, from 0 to 100 mm [16].

Statistical methods

A descriptive analysis of the studied population was performed in terms of demographic characteristics and distribution of patients according to o-ARIA and m-ARIA classifications. Statistical analysis included a comparison between the different degrees of severity according to ARIA classification, T4SS, and VAS.

Statistical analysis was carried out using sas (Statistical Analysis System, Chicago, IL, USA) program, version 9.1.3. Continuous variables were analyzed by means of number (N), mean, standard deviation, median, and extreme values. Variables with asymmetric frequency distribution were described using medians and 25th–75th interquartiles. Categorical variables were described by means of N and percentages in every category. Comparisons were made using the Kruskal–Wallis and chi-square tests. A P-value lower than 0.05 was considered statistically significant.

Results

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. Conflict of interest
  8. References

A total of 1269 pediatric patients were included in the study, 59.5% of them showing intermittent and 40.5% persistent AR. Mean age of the patients was 9.05 ± 1.93 years (girls 41.3%). The most frequent allergen sensitizers were pollens (53.5%) and house dust mites (43.5%). The most frequent comorbidities were conjunctivitis (53.6%), asthma (49.5%), and atopic dermatitis (40%). The mean duration of AR was 2.5 ± 2.4 years. The severity of persistent allergic rhinitis was greater than that of intermittent allergic rhinitis (< 0.004) (Table 1). Asthma (< 0.001) and seromucous otitis (< 0.001) were significantly related to the grade of severity of AR using m-ARIA, in contrast to the rest of the comorbidities studied. No differences (< 0.05) in gender were observed related to age, duration and severity of symptoms using the o-ARIA classification and the m-ARIA criterion (Table 2).

Table 1. Severity of allergic rhinitis (AR) according to modified- allergic rhinitis and its impact on asthma criterion
VariableIntermittentPersistentP-valuea
  1. a

    P-value calculated using chi-square test.

Total734 (100.0%)506 (100.0%)0.0038
Mild88 (12.0%)40 (7.9%) 
Moderate445 (60.6%)289 (57.1%) 
Severe201 (27.4%)177 (35.0%) 
Table 2. Characteristics of the allergic rhinitis study population
 TotalTotalFemaleMaleP-valuea
1269 (100.0%)524 (41.3%)745 (58.7%)
  1. a

    P-value calculated using chi-square test.

Age N 12445127320.1403
Mean (SD)9.05 (1.93)8.95 (1.96)9.11 (1.91)
Median9.09.09.0
(P25; P75)(7.0; 11.0)(7.0; 11.0)(7.0; 11.0)
Duration of ARTotal1265 (100.0%)523 (100.0%)742 (100.0%)0.2574
Intermittent754 (59.5%)302 (57.7%)452 (60.9%)
Persistent511 (40.5%)221 (42.3%)290 (39.1%)
Severity according to o-ARIATotal1238 (100.0%)513 (100.0%)725 (100.0%)0.3609
Mild126 (10.1%)57 (11.1%)69 (9.5%)
Moderate/severe1112 (89.9%)456 (88.9%)656 (90.5%)
Severity according to m-ARIATotal1238 (100.0%)513 (100.0%)725 (100.0%)0.6579
Mild126 (10.1%)57 (11.1%)69 (9.5%)
Moderate735 (59.5%)301 (58.7%)434 (59.9%)
Severe377 (30.4%)155 (30.2%)222 (30.6%)

Using the o-ARIA classification, 10.1% of patients had mild and 89.9% had moderate/severe AR, while m-ARIA criterion was able to discriminate between moderate (59.5%) and severe (30.4%) AR patients.

Statistically significant differences were found in the distribution of T4SS and VAS scores among the different severity groups, using m-ARIA criterion classification (Figs 1 and 2). These significant differences were also witnessed in the global analysis of T4SS individualized parameters and of the ARIA severity items measured by VAS (Table 3).

image

Figure 1. Nasal symptoms were assessed by T4SS (0–12) children using the modified allergic rhinitis and its impact on asthma (ARIA) severity classification in both intermittent (IAR) and persistent (PER) allergic rhinitis. Data are expressed in median and 25th – 75th interquartiles (boxes) and mean and standard deviation (diamonds and error bars).

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image

Figure 2. Allergic rhinitis severity assessed using visual analogue scale (VAS; 0–100) in children classified by modified allergic rhinitis and its impact on asthma (ARIA). Data are expressed in median and 25th – 75th interquartiles (boxes) and mean and standard deviation (diamonds and error bars).

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Table 3. Global analysis of individualized parameters of T4SS in children with allergic rhinitis (AR) according to modified allergic rhinitis and its impact on asthma (ARIA) guideline
 Intermittent/MildIntermittent/ModerateIntermittent/SeverePersistent/MildPersistent/ModeratePersistent/Severe
Sneezing
 N 7541018937283174
 Arithmetic mean (SD)0.80 (0.96)1.66 (0.93)a1.72 (0.94)a0.95 (0.97)1.75 (0.89)b1.86 (0.88)b
Rhinorrhea
 N 8743919840286176
 Arithmetic mean (SD)0.83 (0.65)1.54 (0.85)a1.60 (0.86)a1.05 (0.75)1.67 (0.87)b1.85 (0.86)b
Nasal itching
 N 8843919740288177
Arithmetic mean (SD)0.80 (0.78)1.42 (0.82)a1.53 (0.83)a0.93 (0.76)1.61 (0.86)b1.70 (0.84)b
Nasal obstruction
 N 8643720139285177
 Arithmetic mean (SD)0.71 (0.78)1.50 (0.92)a1.66 (0.89)a0.87 (0.77)1.82 (0.91)b2.18 (0.81)b
Global analysis of ARIA severity items measured by visual analogue scale (VAS) in children with AR according to modified ARIA guideline
  1. SD, standard deviation; T4SS, Total Four Symptom Score.

  2. P-value calculated using Kruskal–Wallis test.

  3. a

    < 0.001 Intermittent Mild vs Moderate and Moderate vs Severe

  4. b

    < 0.001 Persistent Mild vs Moderate and Moderate vs Severe.

Sleep disturbance
 N 32372011164176
Arithmetic mean (SD)0.00 (0.00)18.07 (19.61)a26.61 (23.94)a0.00 (0.00)26.90 (25.10)b38.26 (26.60)b
Impairment of daily activities, leisure, and/or sport
 N 22892010187176
 Arithmetic mean (SD)0.00 (0.00)23.55 (20.63)a32.51 (23.71)a0.00 (0.00)27.37 (22.35)b38.36 (24.31)b
Impairment of school performance
 N 21762001110176
 Arithmetic mean (SD)0.00 (0.00)12.53 (18.29)a23.68 (22.03)a0.00 (0.00)16.31 (20.72)b31.35 (24.37)b
Troublesome symptoms
 N 14131992264177
Arithmetic mean (SD)0.00 (0.00)33.34 (22.25)a39.59 (25.43)a0.00 (0.00)41.94 (23.03)b47.85 (25.55)b

Discussion

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. Conflict of interest
  8. References

The main finding of the present study was that the m-ARIA criterion for discrimination between moderate and severe diseases was validated for the first time in a large population of untreated AR pediatric patients. Severe patients showed significantly worse symptoms than moderate patients.

The excessive proportion of AR patients classified in the moderate/severe group (89.9%) in our study clearly justifies the need for differentiation between moderate (59.5%) and severe (30.4%) rhinitis patients to adequately monitor the progression of disease. These increased percentages, between 80% and 93%, have been obtained in previous studies, with the vast majority of patients classified into the moderate–severe group, in both untreated [14, 17] and treated [17, 18] adult patients.

Regarding the comorbidities, asthma and seromucous otitis showed significant correlation (< 0.001) with greater severity of AR using m-ARIA. Recent studies reflected a significant correlation among greater severity of AR not only with the presence of bronchial asthma [18], as in our study, but also with an impairment of asthma control [19]. Seromucous otitis has been associated with nasal allergy, as in this study, and a highly significant correlation with obstructive nasal symptoms has been described because AR can cause Eustachian tube dysfunction [20].

The Multi-center Allergy Study (MAS) was initiated in 1990 to investigate respiratory allergy and allergic sensitization in a population-based birth cohort from 3- to 13-year-olds. A recent study [21] designed with the aim to examine the application of the o-ARIA classification in the population of the MAS, using only two severity categories, mild and severe (instead of moderate and severe) and persistent and intermittent, showed that in general, 50–70% of children with persistent AR had severe symptoms, reflecting the importance of AR in this age group. The use of the m-ARIA criterion would have been more useful in achieving an accurate classification of the patients. According to this result, our study showed a greater severity of symptoms in persistent AR than in intermittent (< 0.004).

The broad overlap between moderate to severe AR on the VAS but also on T4SS could be interpreted as a limitation of the study. Different grades of severity of AR have been selected for this study, but it is necessary to take into account that these grades are not completely different between them and that if the vast majority of patients are included in the moderate/severe group, then overlap may occur. In our study, in spite of this possible limitation, statistically significant differences were found among moderate and severe groups using m-ARIA.

Patients with AR managed through a scheme based on international guidelines have a better outcome than those evaluated and treated with a nonstandardized scheme [22]. Only a structured allergy history is not sufficient to assess patients with respiratory allergy in general practice, resulting in false-positive rates for different aeroallergens and inaccurate diagnosis [23]. In this context, ARIA guidelines are necessary to provide in primary care the best assessment to improve diagnosis and treatment in these patients. With pediatric patients, ARIA develops a similar stepwise approach to therapy as in adults, but with adjusted doses for them [24]. Given the special attention that physicians pay on the children's therapy in order to maximize drug's efficacy and minimize the adverse effects, our validation in pediatric population of the m-ARIA criterion should be useful to achieve a better control of the severity and the treatment of the symptoms of AR in patients aged 6–12 years.

This discrimination between patients with clearly defined severity phenotypes would be useful to obtain more homogeneous populations of patients, according to their severity, in order to better design epidemiological and pharmaco-economic studies, and to define new strategies for therapy and follow-up, both for clinical practice and for clinical trials, under the umbrella of the new concept of severe chronic upper airway disease (SCUAD) [25].

In conclusion, we have shown, for the first time, that m-ARIA severity classification can discriminate between moderate and severe AR in a large population of untreated pediatric patients. Further studies should be carried out in order to optimize the treatment strategies according to this modified ARIA severity classification in children with AR.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. Conflict of interest
  8. References

This study was supported in part by an educational grant from UCB Pharma.

References

  1. Top of page
  2. Abstract
  3. Material and methods
  4. Results
  5. Discussion
  6. Acknowledgements
  7. Conflict of interest
  8. References