REVIEW

Quality of life in allergic rhinitis and impact of high-dose sublingualimmunotherapy: a real-life studyR. Ariano�, S. Amorosow, C. Astaritaz, M. Bassi‰, P. Bonadonnaz, P. Campik , M. DiGioacchino��, A. Musarraww, O. Querciazz, M. Russello‰‰,A. Venutizz, M. Zambitokk , G. DiCara���, C. Incorvaiawww, P. Puccinellizzz and F. Fratizzz�ASL 1 Imperiese, Allergy Department, Bordighera, Italy, wAllergy Unit, Ospedale Civico, Palermo, Italy, z2nd University, Allergy and Clinical Immunology, Naples, Italy,‰Rho Hospital, Pediatrics, Rho, Italy, zBorgo Trento Hospital, Allergy Service, Verona, Italy, kS. Giovanni di Dio Hospital, Allergy Clinic, Florence, Italy, ��University of

Chieti, Allergy and Clinical Immunology, Chieti, Italy,wwASL, Allergy Unit, Reggio Calabria, Italy, zzFaenza Hospital, Allergy Unit, Faenza, Italy, ‰‰Sant’Anna Hospital,

Allergy Unit, Como, Italy, zzUniversita Cattolica del Sacro Cuore, Rome, Italy, k kASL 6, Allergy Unit, Palermo, Italy, ���University Hospital, Department of Pediatric

Sciences, Perugia, Italy, wwwAllergy/Pulmonary rehabilitation, Istituti Clinici di Perfezionamento, Milan, Italy and zzzScientific Department, Stallergenes, Milan, Italy

Clinical andExperimental

Allergy Reviews

Correspondence:Cristoforo Incorvaia, Viale Molise, Milan69 20137, Itay.E-mail: cristoforo.incorvaia@fastwebnet.it

SummaryAllergic rhinitis (AR) may significantly impair quality of life (QoL), and therefore it isimportant to evaluate the effectiveness of the available treatments on such a parameter. Westudied QoL by a real-life model in a large group of patients with rhinitis caused by the mostcommon aeroallergens and assessed the effects of high-dose sublingual immunotherapy(SLIT). An overall number of 452 subjects (229 males, 223 females, mean age 25� 13 years)was included in the study. Of them, 208 were allergic to house dust mites, 196 to grass pollen,104 to Parietaria pollen, 48 to olive pollen, 28 to ragweed pollen, and two to cypress pollen.QoL was measured before and after SLIT with the specific questionnaire RhinoconjunctivitisQuality-of Life-Questionnaire (RQLQ) introduced and validated by Juniper. At the same time,patients evaluated their clinical status by visual analogue scale (VAS) from 0 (worst) to 10(best). SLIT was performed by extracts from Stallergenes standardized in index of reactivity(IR) by a build-up phase in 11 days and a maintenance phase with 300 IR three times a weekfor the duration of the study. All side-effects were registered. The mean RQLQ was 2.93� 1.04before SLIT and 1.50� 0.98 after SLIT (Po 0.001), with comparable improvement in thedifferent allergen treatments. The respective mean VAS score was 4.47� 2.11 and 6.92� 1.64(Po 0.001). SLIT was completely tolerated in 395 patients (87.4%), while in 57 (12.6%) it gaverise to slight reactions, mostly at the local level in the mouth or in the gastrointestinal tract.High dose SLIT, administered in a clinical model comparable with routine application,provides significant improvement of both clinical status and QoL in patients with AR causedby common aeroallergens.

Keywords quality of life, sublingual immunotherapy, real-life study

Introduction

The efficacy of sublingual immunotherapy (SLIT) in aller-gic rhinitis (AR) is currently supported by meta-analysis [1]and its safety is defined by both post-marketing surveysand analysis of published studies [2–5]. This good char-acterization was made possible by a large number ofdouble-blind, placebo-controlled studies, while little atten-tion was given, thus far, to real-life studies.

Such surveys have the advantage to evaluate patients ina clinical situation very similar to routine treatment,distinct from the rigid organization of a controlled study.To do this, parameters different from daily symptom–

medication scores — the hallmark of controlled studies —are generally used. For example, the subjective evaluationof their clinical status made by patients by the visualanalogue scale (VAS) has long been known as a valid tool[6]. Also, the assessment of quality of life (QoL) hasoptimal characteristics in this view, but thus far was rarelyused in studies on allergen immunotherapy, and particu-larly in SLIT [7].

This study was aimed at evaluating the clinicaleffects of SLIT in a large group of patients with ARtreated for the most common inhalant allergensusing QoL measurement by a specific questionnaire andVAS scores.

Clinical and Experimental Allergy Reviews, 6, 71–73 doi: 10.1111/j.1472-9725.2006.00103.x

�c 2006 Blackwell Publishing Ltd

Materials and methods

Patients

Patients were included from those presenting with rhinitissymptoms at the Allergy centres participating in the study.Inclusion criteria were presence of rhinitis from at least2 consecutive years and age from 6 to 60 years, andexclusion criterion was current allergen immunotherapyin any form.

Methods

The kind of sensitization of patients was assessed byperforming skin prick tests (SPTs) with a standard panelof environmental allergens (Stallergenes, Antony, France).Positivity of SPT was established according to the guide-lines of the European Academy of Allergology and Clin-ical Immunology [8].

SLIT was conducted with allergen extracts standardizedin index of reactivity (IR) from Stallergenes, using thebuild-up phase in 11 days suggested by the manufacturerwith a top dose of 300 IR and a maintenance treatmentwith administration of 300 IR three times a week for theduration of the study. Treatment was started at least3 months before the respective pollen seasons in patientsallergic to pollens, and at any time in mite-allergicpatients.

All side-effects were recorded in specifically designedcharts.

QoL was measured by the questionnaire Rhinitis Qualityof Life Questionnaire (RQLQ) by Juniper and Guyatt [9]validated for the Italian language, and at the same timethe subjective evaluation of clinical status was assessed byVAS, scoring from 0 (very bad) to 10 (very good). RQLQand VAS were obtained in patients suffering from polli-nosis in the respective pollination periods (February forcypress, March for birch, May for grasses and olive, Julyfor Parietaria, and September for ragweed) before andafter SLIT. In patients allergic to house dust mites (HDMs),RQLQ and VAS were recorded at inclusion and 1 year after.

Statistical analysis

The Wilcoxon signed-rank test for paired data was usedfor intragroup analysis and the Mann–Whitney U-test wasused for intergroup analysis. Values of P lower than 0.05were considered statistically significant. All statisticalanalysis was made by means of the standard statisticalsoftware SPSS 13.0.

Results

An overall number of 452 patients (229 males, 223females, mean age 25� 13 years) entered the study.

According to their sensitization, 206 were treated withHDMs extract, 196 with grass pollen, 104 with Parietariapollen, 48 with olive pollen, 28 with ragweed pollen, andtwo with cypress pollen.

SLIT was tolerated without any side-effect in 395patients (87.4%), while in 57 (12.6%), adverse reactionswere reported, consisting of 23 reactions (5.1%) with oralitching or burning, 18 reactions (4%) with gastrointestinalsymptoms, such as pain, nausea, vomiting or diarrhoea,10 reactions (2.2%) with both oral and gastrointestinalsymptoms, two reactions (0.4%) with rhinitis, two (0.4%)with cough, and two (0.4%) with asthma. No severesystemic reaction was reported. There were 28 withdra-wals of SLIT (6%), three for side-effects, three for non-compliance, and 22 for reasons unrelated to treatment.

The mean VAS score was 4.47� 2.11 before SLIT and6.92� 1.64 after SLIT (Po 0.001), and the mean RQLQscore was 2.93� 1.04 before SLIT and 1.50� 0.98 afterSLIT (Po 0.001). This is shown in Fig. 1.

A comparison of the RQLQ score was made at baselineto assess whether different sensitizations could associatewith different QoL. The comparison regarded the threemain subgroups, i.e. dust mites, grass pollen, and Parie-taria pollen, with mean scores of, respectively, 2.72�1.13, 2.95� 1.05, and 3.18� 0.99: these differences arestatistically not significant.

Discussion

Despite the current consideration of the importance ofQoL in medicine and particularly in evaluating the out-come of medical treatments, little attention has been paidthus far to such an issue in allergen immunotherapy. Inparticular, only one controlled study addressed QoL — bythe generic questionnaire SF-20 — as an outcome measure

0

4

8

Before SLIT After SLIT

VASRQLQ

Fig. 1. Changes in RQLQ and VAS before and after SLIT. RQLQ, Rhino-conjuctivitis Quality-of-Life Questionnaire; VAS, visual analogue scale;SLIT, sublingual immunotherapy.

�c 2006 Blackwell Publishing Ltd, Clinical and Experimental Allergy Reviews, 6 : 71–73

72 R. Ariano et al

of SLIT, and found that in patients with mite-inducedasthma the active treatment achieved QoL scores signifi-cantly better than those achieved with placebo, attainingat the same time significant improvement in respiratoryfunction and a significant decrease of anti-asthmaticdrugs [7]. No data are available on QoL changes with SLITin patients with AR, which however was reported asassociated, because of troublesome symptoms, with aQoL even worse than in patients with asthma [10].

A number of QoL questionnaires are availablefor rhinitis, and the RQLQ introduced by Juniper andGuyatt [9] was demonstrated as a valid instrument toassess clinical changes in response to drug treatment forAR [11, 12].

In the present study, using a real-life model on aquite large number of patients, we found that high-doseSLIT significantly improved the RQLQ score in bothseasonal pollen-induced and perennial mite-inducedrhinitis, and the improvement was confirmed by thescores on patients’ clinical status obtained by VAS.It is interesting to note that no significant difference inRQLQ score was detected at baseline between the differentkinds of sensitization, and thus it may be argued thatimpairment in QoL is comparable to pollinosis fromgrasses or Parietaria and in mite-induced rhinitis. Regard-ing at least pollen-induced rhinitis, a recent studyreported instead that female gender, a lower educationlevel, and living in the countryside were associated withpoorer QoL [13].

Considering that health-related QoL is defined by theeffects not only of a given illness but also of its treatment,the very good tolerability of SLIT has surely concurred tothe benefit. In fact, the side-effects of the treatment weremild, self-remitting, and mostly consisting in localreaction in the mouth or in the gastroenteric tract oncethe extract was swallowed. This safety profile offersconfirmation to previous reports and analyses on such anissue [2–5].

In conclusion, QoL as measured by RQLQ appears as avaluable tool to monitor patients with AR undergoingSLIT as a routine treatment, in which parameters, such assymptoms–medication diaries or functional evaluation,are generally not employed.

Acknowledgements

We thank all colleagues who participated this study:A. Berra, D. Berra, M. Bevilacqua, G. Capocasale,

S. Capretti, A. M. Carbonara, R. Caruso, S. Casa, G. Casino,C. Castagneto, V. Castella, F. Castellano, N. Castiglione,G. Castiglioni, E. Cavallucci, M. Cervone, M. Cilia,C. Colangelo, L. G. Cremonte, F. Cucinelli, E. Cupaiolo, G.M. D’Ippolito, L. D’Ancona, S. Daniele, E. De Benedictis,

M. Gregori, M. De Simone, M. R. Della Penna, A. DiPastena, P. Di Rocco, G. Dragotto, F. Emiliani, G. Errico,C. Fazio, E. Ferrarini, G. Feyles, A. Fiorina, P. Gambardella,F. Gani, I. Grasso, R. M. Grasso, A. Ingrassia, D. Lietti,L. Muratore, R. Longo, G. Manzotti, M. A. Moschella,F. Murzilli, F. Nebiolo, S. Nenna, R. Niniano, M. Nuccilli,F. Orlando, F. Paolini, R. Pellegrino, S. Ramando,A. Rapetti, L. Rossi, E. Serpe, M. Sforza, V. Sillano,M. Sugamiele, T. Truffelli, L. Vaccari, M. Verini, N. Verna,F. Vitale, G. Vitale, U. Viviani, M. Zanca, and G. Zucchini.

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