Inflamm. Res. (2015) 64:373–375 DOI 10.1007/s00011-015-0826-9
Inflammation Research
SHORT COMMUNICATION
Allergic rhinitis phenotypes based on mono-allergy or poly-allergy Matteo Gelardi1 • Giorgio Ciprandi2 • Cristoforo Incorvaia3 • Serena Buttafava4 Eleonora Leo1 • Lucia Iannuzzi1 • Nicola Quaranta1 • Franco Frati4
•
Received: 20 April 2015 / Revised: 21 April 2015 / Accepted: 23 April 2015 / Published online: 3 May 2015 Ó Springer Basel 2015
Abstract Background Allergic rhinitis (AR) is characterized by typical symptoms that are dependent on inflammation. Poly-allergy is a frequent phenomenon. Phenotyping AR represents an up-to-date issue. Objective The aim of this study was to evaluate whether the number of allergies is able to define different phenotypes in patients with AR. Methods 83 patients (43 males, mean age 34.7 years) suffering from AR were evaluated. Sensitization, VAS for nasal symptoms perception, and nasal cytology were evaluated. Results Poly-allergic patients perceived more severe nasal obstruction than mono-allergic ones (p = 0.0006) as well as they had more frequent sneezing (p \ 0.0001). Moreover, poly-allergic patients had a more intense inflammatory infiltrate, concerning both eosinophils (p = 0.0005) and mast cells (p = 0.0001), than mono-allergic patients. Conclusions The present study demonstrates that the presence of poly-allergy could define a distinct AR phenotype in comparison with mono-allergy. It could be
Responsible Editor: John Di Battista. & Giorgio Ciprandi [email protected] 1
Section of Otolaryngology, Department of Neuroscience and Sensory Organs, University of Bari, Bari, Italy
2
Department of Medicine, IRCCS-A.O.U. San Martino, Viale Benedetto XV 6, 16132 Genoa, Italy
3
Allergy/Pulmonary Rehabilitation, ICP Hospital, Milan, Italy
4
Medical and Scientific Department, Stallergenes, Milan, Italy
clinically relevant as poly-allergic patients have more intense inflammation and more severe symptoms than monoallergic ones. Keywords Allergic rhinitis Mono-allergy Poly-allergy Nasal cytology Symptom perception Phenotypes
Introduction Allergic rhinitis (AR) is characterized by an IgE-mediated inflammation. Nasal mucosa is infiltrated by a typical cellular pattern, mainly constituted by eosinophil and mast cell [1]. Allergic inflammation is responsible for symptom occurrence. In this regard, it has been evidenced a relevant association between inflammation grade and symptom severity [1]. On the other hand, sensitization to more allergens (such as poly-sensitization) represents a very common issue in the clinical practice [2]. This phenomenon has practical consequences, mainly concerning the diagnosis of true allergy and the prescription of the allergen extract for allergen immunotherapy (AIT). Therefore, the task of the allergist is to discriminate between simple sensitization and true allergy. Allergy is defined by the consistence between exposure to sensitizing allergen and concurrent symptom occurrence [3]. In the clinical practice, it should be preferred the term poly-allergy instead poly-sensitization, as it may generate confusion in this particularly complicated matter. As phenotyping allergic rhinitis could be clinically relevant, a hypothesis to be tested is whether two possible distinct AR phenotypes may exist considering the presence of mono-allergy or poly-allergy.
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M. Gelardi et al.
Materials and methods
Discussion
This cross-sectional study included 83 patients (43 males, mean age 34.7 years), suffering from allergic rhinitis. They were consecutively visited in the rhino-allergology clinic of the Department of Otorhinolaryngology of the University of Bari. The subjects were enrolled in the study on the basis of the first diagnosis of AR according to validated criteria [3]. Exclusion criteria were: diagnosis of non-allergic rhinitis, presence of acute or chronic upper respiratory infections, nasal polyps, clinically relevant septal deviation, previous or current specific immunotherapy, and use of nasal or oral corticosteroids, nasal or oral vasoconstrictors, antileukotrienes, and antihistamines during the previous 4 weeks. Clinical examination, visual analog scale (VAS) assessment of nasal obstruction perception [4], skin prick test [5], and nasal cytology [1] were performed during the spring of 2013. Parametric tests (ANOVA) and non-parametric tests (U Mann–Whitney) were used. A Chi-square (v2 ) test or Yates test were used for contingency tables. Statistical analysis was computed using Statistical Package for Social Science (SPSS version 20, IBM, USA). All statistical tests were two-sided, and the significance level was set at 0.05.
Sensitization to more allergens in the same patient, such as poly-sensitization, is a phenomenon that may characterize the natural history of many allergic patients, representing a typical evolution of allergy [6]. Poly-sensitization matter assumes a clinical relevance mainly for deciding the choice of allergen extracts for AIT. Many doctors prefer medications to AIT in these patients. However, the concept of poly-sensitization is substantially misleading as sensitization per se does not mean true allergy. In other words, the term sensitization defines a mere production of allergen-specific IgE, such as a relevant part of sensitized patients are not allergic. In fact, allergy is defined by the symptom appearance following the exposure to sensitizing allergen. Thus, this reasoning should be ever considered in all poly-sensitized patients. On the other hand, it has been reported that poly-allergic patients perceive more severe symptoms than mono-allergic ones [7]. This study, conducted in a large AR cohort, concluded that mono-allergic and poly-allergic AR patients could constitute two different categories. The present study addressed this relevant issue: assessing inflammation and symptoms in mono-allergic and poly-allergic AR patients. Two main inflammatory cells were evaluated: eosinophil and mast cell. Eosinophil is the main effector cell in allergic inflammation: allergic inflammation may be excluded if there is no eosinophil in nasal cytology. Eosinophil infiltrate grade is closely related with symptom severity [1]. Mast cell is the inflammatory cell involved in the early phase reaction, as it is capable of releasing mediators (when activated by allergen exposure) responsible of symptoms occurrence. Also, nasal obstruction was considered assessing the patient’s perception by VAS. Nasal obstruction represents the symptom more reflective for allergic inflammation. The present study demonstrated that poly-allergic patients had more intense inflammation and more severe symptoms than mono-allergic ones. This finding suggests a relevant clinical information: poly-allergic patients may define an AR phenotype different from mono-allergy. This matter might suggest also a practical implication about AIT prescription. However, further studies should be conducted to investigate to confirm these results in more representative cohort also measuring immunologic parameters. In conclusion, this study demonstrated that the presence of poly-allergy could define a distinct AR phenotype in comparison with mono-allergic patients.
Results Globally, 83 AR patients were investigated: 48 (57.8 %) were poly-allergic and 35 (42.2 %) were mono-allergic. Figure 1 reports the relevant findings. Poly-allergic patients perceived a significantly (p = 0.0006) more severe nasal obstruction (VAS value 6.02 ± 3.17) than mono-allergic ones (3.51 ± 3.2). Sneezing symptom was significantly (p \ 0.0001) more frequent in poly-allergic patients (85.4 %) than in monoallergic ones (37.1 %), as well as watery rhinorrhea: 77.1 % of poly-allergic patients and 48.6 % of mono-allergic ones (p = 0.014). Poly-allergic patients had a significantly (p = 0.0005) more abundant eosinophil infiltrate (1.77 ± 1.43) than mono-allergic ones (0.71 ± 0.99). Similarly, mast cell infiltrate was significantly (p = 0.0001) more numerous in poly-allergic patients (0.96 ± 1.17) than in mono-allergic ones (0.14 ± 0.43).
123
Allergic rhinitis phenotypes based on mono-allergy or poly-allergy
375
Fig. 1 Upper left quadrant mean VAS score for nasal obstruction in the two sub-groups; upper right quadrant percentage of patients with sneezing in the two sub-groups. Central quadrant percentage of patients with watery rhinorrhea in the two sub-groups. Upper left
quadrant mean of eosinophil classes in the sub-groups; upper right quadrant mean of mast cells classes in the two sub-groups. *p \ 0.05; ***p \ 0.001
F. Frati and S. Buttafava are Stallergenes Italy
update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63(Suppl 86):8–160. Bousquet PJ, Combescure C, Neukirch F, Klossek JM, Mechin H, Daures JP, Bousquet J. Visual analog scales can assess the severity of rhinitis graded according to ARIA guidelines. Allergy. 2007;62:367–72. Dreborg S (ed). EAACI subcommittee on skin tests. Skin tests used in type I allergy testing. Position paper. Allergy. 1989;44:S22–S31. Baatenburg de Jong A, Dikkeschel LD, Brand PL. Sensitization patterns to food and inhalant allergens in childhood: a comparison of non-sensitized, monosensitized, and polysensitized children. Pedatr Allergy Immunol. 2011;22:166–71. Ciprandi G, Cirillo I. Monosensitization and polysensitization in allergic rhinitis. Eur J Intern Med. 2011;22:e75–9.
Conflict of interest employees.
4.
References 1. Gelardi M, Maselli del Giudice A, Candreva T, Fiorella ML, Allen M, Klersy K, Marseglia GL, Ciprandi G. Nasal resistance and allergic inflammation depend on allergen type. Int Arch Allergy Immunol. 2006;141:384–9. 2. Ciprandi G, Incorvaia C, Puccinelli P, Soffia S, Scurati S, Frati F. The polysensitization as a challenge for the allergist: the suggestions provided by the POLISMAIL studies. Expert Opin Biol Ther. 2011;11:715–22. 3. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008
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Inflammation Research
SHORT COMMUNICATION
Allergic rhinitis phenotypes based on mono-allergy or poly-allergy Matteo Gelardi1 • Giorgio Ciprandi2 • Cristoforo Incorvaia3 • Serena Buttafava4 Eleonora Leo1 • Lucia Iannuzzi1 • Nicola Quaranta1 • Franco Frati4
•
Received: 20 April 2015 / Revised: 21 April 2015 / Accepted: 23 April 2015 / Published online: 3 May 2015 Ó Springer Basel 2015
Abstract Background Allergic rhinitis (AR) is characterized by typical symptoms that are dependent on inflammation. Poly-allergy is a frequent phenomenon. Phenotyping AR represents an up-to-date issue. Objective The aim of this study was to evaluate whether the number of allergies is able to define different phenotypes in patients with AR. Methods 83 patients (43 males, mean age 34.7 years) suffering from AR were evaluated. Sensitization, VAS for nasal symptoms perception, and nasal cytology were evaluated. Results Poly-allergic patients perceived more severe nasal obstruction than mono-allergic ones (p = 0.0006) as well as they had more frequent sneezing (p \ 0.0001). Moreover, poly-allergic patients had a more intense inflammatory infiltrate, concerning both eosinophils (p = 0.0005) and mast cells (p = 0.0001), than mono-allergic patients. Conclusions The present study demonstrates that the presence of poly-allergy could define a distinct AR phenotype in comparison with mono-allergy. It could be
Responsible Editor: John Di Battista. & Giorgio Ciprandi [email protected] 1
Section of Otolaryngology, Department of Neuroscience and Sensory Organs, University of Bari, Bari, Italy
2
Department of Medicine, IRCCS-A.O.U. San Martino, Viale Benedetto XV 6, 16132 Genoa, Italy
3
Allergy/Pulmonary Rehabilitation, ICP Hospital, Milan, Italy
4
Medical and Scientific Department, Stallergenes, Milan, Italy
clinically relevant as poly-allergic patients have more intense inflammation and more severe symptoms than monoallergic ones. Keywords Allergic rhinitis Mono-allergy Poly-allergy Nasal cytology Symptom perception Phenotypes
Introduction Allergic rhinitis (AR) is characterized by an IgE-mediated inflammation. Nasal mucosa is infiltrated by a typical cellular pattern, mainly constituted by eosinophil and mast cell [1]. Allergic inflammation is responsible for symptom occurrence. In this regard, it has been evidenced a relevant association between inflammation grade and symptom severity [1]. On the other hand, sensitization to more allergens (such as poly-sensitization) represents a very common issue in the clinical practice [2]. This phenomenon has practical consequences, mainly concerning the diagnosis of true allergy and the prescription of the allergen extract for allergen immunotherapy (AIT). Therefore, the task of the allergist is to discriminate between simple sensitization and true allergy. Allergy is defined by the consistence between exposure to sensitizing allergen and concurrent symptom occurrence [3]. In the clinical practice, it should be preferred the term poly-allergy instead poly-sensitization, as it may generate confusion in this particularly complicated matter. As phenotyping allergic rhinitis could be clinically relevant, a hypothesis to be tested is whether two possible distinct AR phenotypes may exist considering the presence of mono-allergy or poly-allergy.
123
374
M. Gelardi et al.
Materials and methods
Discussion
This cross-sectional study included 83 patients (43 males, mean age 34.7 years), suffering from allergic rhinitis. They were consecutively visited in the rhino-allergology clinic of the Department of Otorhinolaryngology of the University of Bari. The subjects were enrolled in the study on the basis of the first diagnosis of AR according to validated criteria [3]. Exclusion criteria were: diagnosis of non-allergic rhinitis, presence of acute or chronic upper respiratory infections, nasal polyps, clinically relevant septal deviation, previous or current specific immunotherapy, and use of nasal or oral corticosteroids, nasal or oral vasoconstrictors, antileukotrienes, and antihistamines during the previous 4 weeks. Clinical examination, visual analog scale (VAS) assessment of nasal obstruction perception [4], skin prick test [5], and nasal cytology [1] were performed during the spring of 2013. Parametric tests (ANOVA) and non-parametric tests (U Mann–Whitney) were used. A Chi-square (v2 ) test or Yates test were used for contingency tables. Statistical analysis was computed using Statistical Package for Social Science (SPSS version 20, IBM, USA). All statistical tests were two-sided, and the significance level was set at 0.05.
Sensitization to more allergens in the same patient, such as poly-sensitization, is a phenomenon that may characterize the natural history of many allergic patients, representing a typical evolution of allergy [6]. Poly-sensitization matter assumes a clinical relevance mainly for deciding the choice of allergen extracts for AIT. Many doctors prefer medications to AIT in these patients. However, the concept of poly-sensitization is substantially misleading as sensitization per se does not mean true allergy. In other words, the term sensitization defines a mere production of allergen-specific IgE, such as a relevant part of sensitized patients are not allergic. In fact, allergy is defined by the symptom appearance following the exposure to sensitizing allergen. Thus, this reasoning should be ever considered in all poly-sensitized patients. On the other hand, it has been reported that poly-allergic patients perceive more severe symptoms than mono-allergic ones [7]. This study, conducted in a large AR cohort, concluded that mono-allergic and poly-allergic AR patients could constitute two different categories. The present study addressed this relevant issue: assessing inflammation and symptoms in mono-allergic and poly-allergic AR patients. Two main inflammatory cells were evaluated: eosinophil and mast cell. Eosinophil is the main effector cell in allergic inflammation: allergic inflammation may be excluded if there is no eosinophil in nasal cytology. Eosinophil infiltrate grade is closely related with symptom severity [1]. Mast cell is the inflammatory cell involved in the early phase reaction, as it is capable of releasing mediators (when activated by allergen exposure) responsible of symptoms occurrence. Also, nasal obstruction was considered assessing the patient’s perception by VAS. Nasal obstruction represents the symptom more reflective for allergic inflammation. The present study demonstrated that poly-allergic patients had more intense inflammation and more severe symptoms than mono-allergic ones. This finding suggests a relevant clinical information: poly-allergic patients may define an AR phenotype different from mono-allergy. This matter might suggest also a practical implication about AIT prescription. However, further studies should be conducted to investigate to confirm these results in more representative cohort also measuring immunologic parameters. In conclusion, this study demonstrated that the presence of poly-allergy could define a distinct AR phenotype in comparison with mono-allergic patients.
Results Globally, 83 AR patients were investigated: 48 (57.8 %) were poly-allergic and 35 (42.2 %) were mono-allergic. Figure 1 reports the relevant findings. Poly-allergic patients perceived a significantly (p = 0.0006) more severe nasal obstruction (VAS value 6.02 ± 3.17) than mono-allergic ones (3.51 ± 3.2). Sneezing symptom was significantly (p \ 0.0001) more frequent in poly-allergic patients (85.4 %) than in monoallergic ones (37.1 %), as well as watery rhinorrhea: 77.1 % of poly-allergic patients and 48.6 % of mono-allergic ones (p = 0.014). Poly-allergic patients had a significantly (p = 0.0005) more abundant eosinophil infiltrate (1.77 ± 1.43) than mono-allergic ones (0.71 ± 0.99). Similarly, mast cell infiltrate was significantly (p = 0.0001) more numerous in poly-allergic patients (0.96 ± 1.17) than in mono-allergic ones (0.14 ± 0.43).
123
Allergic rhinitis phenotypes based on mono-allergy or poly-allergy
375
Fig. 1 Upper left quadrant mean VAS score for nasal obstruction in the two sub-groups; upper right quadrant percentage of patients with sneezing in the two sub-groups. Central quadrant percentage of patients with watery rhinorrhea in the two sub-groups. Upper left
quadrant mean of eosinophil classes in the sub-groups; upper right quadrant mean of mast cells classes in the two sub-groups. *p \ 0.05; ***p \ 0.001
F. Frati and S. Buttafava are Stallergenes Italy
update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63(Suppl 86):8–160. Bousquet PJ, Combescure C, Neukirch F, Klossek JM, Mechin H, Daures JP, Bousquet J. Visual analog scales can assess the severity of rhinitis graded according to ARIA guidelines. Allergy. 2007;62:367–72. Dreborg S (ed). EAACI subcommittee on skin tests. Skin tests used in type I allergy testing. Position paper. Allergy. 1989;44:S22–S31. Baatenburg de Jong A, Dikkeschel LD, Brand PL. Sensitization patterns to food and inhalant allergens in childhood: a comparison of non-sensitized, monosensitized, and polysensitized children. Pedatr Allergy Immunol. 2011;22:166–71. Ciprandi G, Cirillo I. Monosensitization and polysensitization in allergic rhinitis. Eur J Intern Med. 2011;22:e75–9.
Conflict of interest employees.
4.
References 1. Gelardi M, Maselli del Giudice A, Candreva T, Fiorella ML, Allen M, Klersy K, Marseglia GL, Ciprandi G. Nasal resistance and allergic inflammation depend on allergen type. Int Arch Allergy Immunol. 2006;141:384–9. 2. Ciprandi G, Incorvaia C, Puccinelli P, Soffia S, Scurati S, Frati F. The polysensitization as a challenge for the allergist: the suggestions provided by the POLISMAIL studies. Expert Opin Biol Ther. 2011;11:715–22. 3. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008
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