The effects of climate conditions on allergic rhinitis prevalence and latest epidemiologic data from Western Thrace/NE Greece region

ORIGINAL ARTICLE / ΕΡΕΥΝΗΤΙΚΗ ΕΡΓΑΣΙΑ The effects of climate conditions on allergic rhinitis prevalence and latest epidemiologic data from Western Thrace/NE Greece region Η επίδραση των κλιματικών συνθηκών στον επιπολασμό της αλλεργικής ρινίτιδας και νεότερα επιδημιολογικά δεδομένα από την περιοχή της Δυτικής Θράκης/Βόρειο Ανατολική Ελλάδα Katotomichelakis M 1, MD, PhD Nikolaidis C 2, PhD Katsimpris P 1, MD Tsirogianni O 1, MD Hilmi N 1, MD Riga M 1, MD, PhD Danielides V 1, MD, PhD 1 Department of Otorhinolaryngology, Medical School, Democritus University of Thrace, Alexandroupolis, Evros, Greece 2 Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Alexandroupolis, Evros, Greece Hellenic Otorhinolaryngology, Volume 35 - Issue 4, 2014 Correspondence to: Professor Vassilios Danielides, MD, PhD Department of Otorhinolaryngology, University Hospital of Alexandroupolis, Alexandroupolis 68100, Greece E-mail: vdanielidis@hotmail.com Κατωτομιχελάκης Μ 1 Νικολαίδης Χ 2 Κατσιμπρής Π 1 Τσιρογιάννη Ο 1 Χιλμί Ν 1 Ρήγα Μ 1 Δανιηλίδης Β 1 1 Πανεπιστημιακή Ωτορινολαρυγγολογική Κλινική, Ιατρική Σχολή, Δημοκρίτειο Πανεπιστήμιο Θράκης, Αλεξανδρούπολη, Έβρος, Ελλάδα. 2 Εργαστήριο Υγιεινής και Περιβαντολλογικής προστασίας, Ιατρική Σχολή, Δημοκρίτειο Πανεπιστήμιο Θράκης, Αλεξανδρούπολη, Έβρος, Ελλάδα. Ελληνική Ωτορινολαρυγγολογία, Τόμος 35 - Τεύχος 4, 2014 A b s t r a c t Introduction: Although allergic sensitivities to common inhaled aero-allergens present significant differences among places, there is no recent data from Greece that correlate climate conditions with prevalence of allergic rhinitis (AR). The aim of this epidemiologic study is the comparative investigation of differences in allergic sensitivities in a population from areas of Evros with different climate conditions. Materials and methods: Seven hundred and forty one subjects with nasal complaints were participated during an annual (2013) period. Among them 369 patients of both sexes were diagnosed with AR. 168 lived in warm Mediterranean climate conditions of South Evros (SE) and 201 lived in the cold-humid climate conditions of North Evros (NE). Division was based on their living place in the last 5 years. Meteorological data were obtained from the regional station of the Hellenic National Meteorological Service. Daily mean temperature ( C), relative humidity (%), rainfall (mm), wind speed (km/h) and wind direction were recorded. Results: Overall, the most prevalent sensitizations in SE patients were found to: Dermatophagoides (55%), Grasses mix (52%), Olive (33.3%), Parietaria (16%) and Alternaria alternate (7.2%), whereas NE patients sensitizations were as followed: Dermatophagoides (57.2%), Grasses mix (42.3%), Alternaria alternata (26.9%), Parietaria and Olive (13.9%). Among AR patients there was only a percentage of 26.3% who had knowledge for being allergic. Significant correlations between specific allergen sensitivities and climate conditions were found for olive for SE patients and for Alternaria alternata for NE patients. Conclusions: Sensitivities to common aero-allergens vary according to climate conditions. In hot, Mediterranean climate conditions, there is a domination of sensitivities to grasses, olive and parietaria allergens, whereas in cold-humid conditions there is a prevalence of mold sensitivities and mainly to Alternaria alternata. Moreover most AR patients were not aware of their sensitivities, a finding that stresses the need for SPTing in every day clinical practice. Key words: Allergic rhinitis; sensitivities; aero-allergens; skin prick test; climate conditions. Π Ε Ρ Ι Λ Η Ψ Η Εισαγωγή: Μολονότι η εμφάνιση αλλεργικών ευαισθησιών στα κοινά εισπνεόμενα αλλεργιογόνα παρουσιάζει σημαντικές διαφορές ανάμεσα στις περιοχές, δεν υπάρχουν πρόσφατα δεδομένα από την Ελλάδα που να συσχετίζουν τις κλιματικές συνθήκες με την εμφάνιση της αλλεργικής ρινίτιδας (ΑΡ). Σκοπός της παρούσης επιδημιολογικής μελέτης αποτελεί η συγκριτική έρευνα των διαφορών στις αλλεργικές ευαισθησίες σε έναν πληθυσμό από περιοχές του Έβρου με διαφορετικές κλιματικές συνθήκες. Υλικό και Μέθοδος: Στην παρούσα μελέτη συμμετείχαν 741 άτομα με ρινικές διαταραχές κατά την διάρκεια του έτους 2013. Μεταξύ αυτών 369 ασθενείς και των δύο φύλων διαγνώστηκαν με ΑΡ. Οι 168 ζούσαν στο ζεστό-μεσογειακό κλίμα του Νοτίου Έβρου (ΝΕ) και οι 201 183

The effects of climate conditions on allergic rhinitis prevalence and latest epidemiologic data from Western Thrace/NE Greece region Διεύθυνση αλληλογραφίας: Καθηγητής Βασίλειος Δανιηλίδης Πανεπιστημιακή Ωτορινολαρυγγολογική Κλινική, Πανεπιστημιακό Νοσοκομείο Αλεξανδρούπολης, Αλεξανδρούπολη 68100, Ελλάδα E-mail: vdanielidis@hotmail.com στις κρύες-υγρές κλιματικές συνθήκες του Βορείου Έβρου (ΒΕ). Η κατανομή βασίστηκε στην διαμονή των ασθενών τα τελευταία 5 χρόνια. Τα Μετεωρολογικά δεδομένα ελήφθησαν από το περιφερειακό σταθμό της Εθνικής Μετεωρολογικής Υπηρεσίας. Καταγράφηκαν η ημερήσια μέση θερμοκρασία ( C), η σχετική υγρασία (%), οι βροχοπτώσεις (mm), η ταχύτητα του ανέμου (km/h), καθώς και η διεύθυνση του ανέμου. Αποτελέσματα: Συνολικά, τα πιο σημαντικά ποσοστά ευαισθητοποίησης στους ασθενείς από το Νότιο Έβρο βρέθηκαν στα ακόλουθα αλλεργιογόνα: ακάρεα (55%), αγρωστώδη (52%), ελιά (33,3%), περδικάκι (16%) και alternaria alternata (7,2%), ενώ στους ασθενείς από τον Βόρειο Έβρο τα αντίστοιχα ποσοστά ευαισθητοποίησης ήταν τα ακόλουθα: ακάρεα (57,2%), αγρωστώδη (42,3%), alternaria alternata (26,9%), περδικάκι και ελιά (13,9%). Από το σύνολο των ασθενών με ΑΡ μόνο ένα ποσοστό της τάξης του 26,3% γνώριζε την ευαισθησία. Στατιστικά σημαντική συσχέτιση βρέθηκε για την αλλεργική ευαισθησητοποίηση στην ελιά στους ασθενείς από τον ΝΕ και στον μύκητα alternaria alternata στους ασθενείς από τον ΒΕ. Συμπεράσματα: Οι αλλεργικές ευαισθησίες στα πιο συνήθη εισπνεόμενα αλλεργιογόνα παρουσιάζουν σημαντικές διαφορές ανάλογα με τις κλιματικές συνθήκες. Σε πιο θερμές, μεσογειακές κλιματικές συνθήκες, παρατηρείται κυριαρχία των αλλεργικών ευαισθησιών στα αγρωστώδη, την ελιά και το περδικάκι, σε αντίθεση με τα πιο υγρά κλίματα στα οποία παρατηρείται μία αυξημένη επίπτωση στους μύκητες και κυρίως στην alternaria alternata. Είναι επίσης σημαντικό το γεγονός ότι οι περισσότεροι ασθενείς με ΑΡ δεν είχαν γνώση των ευαισθησιών τους, ένα εύρημα που υπογραμμίζει την ανάγκη για την εκτέλεση δερματικών δοκιμασιών νυγμού στην καθημερινή κλινική πράξη. Λέξεις κλειδιά: Αλλεργική ρινίτιδα, ευαισθησίες, αερο-αλλεργιογόνα, δερματικές δοκιμασίες νυγμού, κλιματικές συνθήκες. 184 INTRODUCTION Allergic rhinitis (AR) is defined as a symptomatic disorder of the nose induced after allergen exposure by an immunoglobulin E (IgE)-mediated inflammation of the membranes lining the nose. 1 It represents a disease of modern society with a considerable increase in recent years. 2-7 At European level, it is believed that 25%-40% of the population suffers, but only 1 in 2 patients are being diagnosed and only 1 in 4 patients receive proper treatment. 4-8 This means that AR is frequently ignored, underdiagnosed, misdiagnosed, and mistreated, which not only is detrimental to health but has also a significant social cost. 2,6,9 Symptomatology includes nasal obstruction, sneezing, rhinorrhea, itchy nose and itchy eyes. 2 Allergic rhinitis symptoms occurs when sensitized individuals inhale airborne allergens, such as typically tree, grass, weed pollens and some molds, as well as animal danders, 2,10,11 with the intensity of symptoms depending on the density of aeroallergen circulation and on the duration of exposure. 12,13 Atmosphere allergenic content varies not only between countries but even in the same country, according to climate (temperature, winds, rain, humidity), geography, vegetation and other factors. 14-17 This means that pollen monitoring is very important for the management of respiratory allergy, for the development of preventive measures for allergic patients, as well as for enabling clinicians to more effective selection of allergens for skin prick testing (SPT), promoting diagnosis and finally better treatment management (immunotherapy, drug use etc). Although there are differences in prevalence among regions, there is no recent data from Greece related to epidemiology and to the relationship between climatic conditions and prevalence of allergic rhinitis. The purpose of this epidemiologic study is a comparative investigation of differences in allergic sensitivities in a sample population from areas of Evros with different climatic conditions. The clinical importance besides presentation of a significant data from a wide region with extremely different climate conditions is also to stress the importance of the construction of pollen calendars for preventive and therapeutical reasons. This should be a cost effective program that has to be implemented all over Greece. Materials and methods In this epidemiologic study seven hundred and forty one subjects were participated during an annual (2013) period. All subjects were examined in the rhinologic clinic of the tertiary Academic Hospital of Alexandroupolis, due to nasal complaints. According to their living place in the last 5 years, they were divided into two groups. The first one included 378 participants who lived in the warm Mediterranean climate conditions of South Evros (SE) and 363 who lived in the cold-humid climate con-

Katotomichelakis M, Nikolaidis C, Katsimpris P, Tsirogianni O, Hilmi N, Riga M, Danielides V Fig. 1. Sensitizations to one (mono-sensitization) or more (polysensitization) aeroallergens in SE (South Evros) and NE (North Evros). Fig. 2. Sensitizations to most common aeroallergens in AR patients from SE and NE regions. 185 ditions of North Evros (NE). Allergic sensitizations to registered pollens were detected in a group of 369 patients of both sexes. 168 patients from SE and 201 patients from NE. Diagnosis of AR was based on clinical examination that included history, nasal endoscopy, skin prick testing (SPT) with a battery of common aeroallergens. Clinical examination also included olfactory evaluation by sniffin sticks test and pulmonary function assessment by spirometry. Only subjects with a positive SPT who fulfilled the criteria of AR according to ARIA guidelines 18 were included in the study group. All patients lived for a minimum of the last 5 years in the study area. Criteria for exclusion were history of chronic urticaria/angioedema and/or symptomatic dermographism, immunotherapy treatment during the last 5 years, recent usage of oral or nasal corticosteroids 4 weeks prior to inclusion and oral H1 antihistamines 1 week prior to inclusion. Symptoms evaluation was made by the Total 5 Symptoms Score (T5SS) that includes the symptoms of nasal discharge (rhinorrhea), nasal congestion, itchy nose, sneezing, and itchy eyes. All symptoms were graded from 0 (absent) to 3 (very troublesome), with total scores ranging from 0 15. 18 Olfactory function was evaluated using Sniffin Sticks test package (Burghart, Wedel, Germany). Sniffin Sticks test included specific tests for odor threshold (OT), odor discrimination (OD), and odor identification (OI). 19 Results of each one of the three tests were combined to a Threshold Discrimination Identification-TDI-score. TDI score ranges from 0 to 48 (values of 15 or less represent anosmia, values between 16 and 34.5 represent hyposmia and values over 34.5 represent normosmia for the mild climate conditions in Greece). 20 SPT s were performed and evaluated as described by the European Academy of Allergy and Clinical Immunology. 21 The allergen panel (Sublivac/HAL/The Nederlands) consisted of the Pan European GA2LEN panel 22 which contains antigens of Dermatophagoides farinae and Dermatophagoides pteronyssinus, cat and dog epithelium, Grasses mix, Parietaria, Olive tree, Poplar, Alternaria alternata, Cladosporium, Aspergillus, Cypress, and Pine. The study protocol was approved by the local Institutional Review Board. All subjects signed an informed consent. The study was performed in accordance with the Declaration of Helsinki/Hong Kong. Meteorological data were obtained from the regional station of the Hellenic National Meteorological Service (http://www.hnms. gr). Daily mean temperature ( C), relative humidity (%), rainfall (mm), wind speed (km/h) and wind direction were recorded. Differences between SE and NE areas were assessed by means of Odds Ratio (OR) and 95% Confidence Intervals (CI) in 2x2 contingency tables. All statistical analyses were performed in SPSS v.19. A p value of <0.05 was considered to be statistically significant. RESULTS The total study group included 741 subjects (mean age 40.1±4.3, range 6-70 years). 378 subjects lived in SE areas (mean age 35.4±5.2, range 6-70 years) and 363 in NE areas (mean age 43.5±3.9, range 6-70 years). In total, 369 individuals (49.8%) were diagnosed with AR; 179 (48.5%) males of mean age 36.4±4.9 years and 190 (51.5%) females of mean age 35.7±5.1 years. Accordingly, 168 (45.5%) of them lived in SE and 201 (54.5%) lived in NE areas. There were no significant differences among groups related to sex and age. According to SPT s results, mono-sensitization was found in 52 patients (31%) from SE compared to 99 patients (49.3%) from NE. Similarly, polysensitized were 116 patients (69%) and 102 patients (50.7%) respectively (Fig. 1). Overall, the most prevalent sensitizations in patients who lived in SE were to: Dermatophagoides (55%), Grasses mix (52%), Olive (33.3%), Parietaria (16%) and Alternaria alternate (7.2%), whereas in NE patients sensitizations were as followed: Dermatophagoides (57.2%), Grasses mix (42.3%), Alternaria alternata (26.9%), Parietaria and Olive (13.9%) (Fig. 2). Among AR patients from SE a percentage of 38.1% had knowledge for being allergic, by contrast to a 16.4% of patients from NE. Correlations between sensitizations to common inhaled aeroallergens and climate conditions in the two regions are given in

The effects of climate conditions on allergic rhinitis prevalence and latest epidemiologic data from Western Thrace/NE Greece region Table 1. Correlations between sensitizations to common inhaled aero-allergens and climate conditions between the two regions (South Evros-SE- versus North Evros-NE). Allergen Sensitized individuals (SE) Sensitized individuals (NE) Odds ratio (95% C.I.) Dermatophagoides 92 115 0.91 (0.6-1.37) Grasses 87 85 1.47 (0.97-2.21) Olive 56 28 3.1 (1.85-5.15) *** Parietaria 27 28 1.18 (0.67-2.1) Alternaria 12 54 0.21 (0.11-0.41)*** Table 1. Patients who lived in mild-mediterranean climates were 3 times more likely to be sensitized to olive antigen compared to those who lived in colder and more humid climate conditions. On the contrary the latter s were 5 times more likely to be sensitized in Alternaria alternata mold. DISCUSSION It is widely known that differences in climate may result alone or in concert with other parameters in different aero-allergenic patterns among regions, which in turn, impacts the prevalence or severity of allergic illness via sensitization and response pathways. 12-15,23 The unique aerobiological conditions of an area clearly affect the clinical manifestations of respiratory allergy and explain the number of studies for pollen concentrations, even within the same country. 24-27 This study represents the first epidemiologic study for Western Thrace/NE Greece that clearly states differences in epidemiology of AR between places with different climate conditions even in the same prefecture. Although the sample tested in both areas was about the same, the results of our study indicate that 44.4% of the examined patients from SE suffered from AR, as opposed to 55.4% from NE. The difference in prevalence among places could be explained by the fact that allergic rhinitis has been proved to be more frequent in colder areas with respect to temperate ones. 5 The first clinically important finding of this study was the differences presented in sensitizations between the different populations. We found that except of Dermatophagoides sensitizations that were similar and common to both populations the most prevalent sensitizations for SE patients were grasses, olive and wall pellitory allergens. On the contrary molds and especially Alternaria alteranata, a fungus that has been closely related to asthma, 28 is very common to AR patients who live in the cold-humid climate conditions of NE. Sensitizations in SE patients are in accordance to previous studies from patients who lived in similar Mediterranean climate conditions. 24,29 Similarities are evident between Greece and other Mediterranean countries, especially Southern Italy and Spain. Olive and grass pollens have been proved to be the most important causes of inhalant allergy in Mediterranean countries. 30 This is explained by the fact that the most prevalent allergenic plants in these areas with known clinical significance are grasses, Olea europaea and Parietaria species 25. This means that vegetation reflects pollen calendar and this leads to sensitization in AR patients. Additionally similar findings for Alternaria alteranata prevalence in humid climates have also been published. 31-37 Moulds, particularly Alternaria alternata, deserve attention because they are considered to be both indoor and outdoor risk factors for asthma and asthma-like symptoms 28. Moulds thrive in humid climates, and the release of the spores is elicited by sunny and windy weather. 37 Although similarities in overall findings, clinically important differences in sensitization prevalences among AR patients who live in different places are described. 24,25,29,30-38 This is the reason that explains the importance of such epidemiologic studies. Another important finding of this study is the large percentage of AR patients (73.7%) who ignored their sensitivities. This finding comes to confirm previous studies that show 50% of AR patients to be under-diagnosed and accordingly, 75% of patients to be either un- or miss-treated. 4-8 In our study cohort, the percentage is even higher, namely 73.7% of patients are not aware of their sensitivities. This is very alarming and emphasizes the need for preventive strategies that include National programs of SPTing in the population, as well as the need for pollen calendars construction. Early diagnosis and proper treatment for AR will lead to less cost and better quality of life for people, especially for children. CONCLUSIONS In this study we found that sensitivities to common aero-allergens vary according to climate conditions. Significant correlations between sensitizations to common inhaled aero-allergens and climate conditions were found for olive in SE patients who lived in hot, Mediterranean climate conditions compared to Al- 186

Katotomichelakis M, Nikolaidis C, Katsimpris P, Tsirogianni O, Hilmi N, Riga M, Danielides V ternaria alternata sensitizations in NE patients who lived in humid regions. It is also important to mention the significant percentage of patients, who were not aware of their sensitivities, finding that emphasizes the need for SPT in every day clinical practice. Therefore with this study we confirmed the influence of climatic conditions on AR patients sensitization and stress the importance of the construction of pollen maps on a national basis for better management. R e f e r e n c e s 1. Bousquet J, Khaltaev N, Cruz AA, et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 Update. Allergy 2008;63:8-160. 2. Greiner AN, Hellings PW, Rotiroti G, Scadding GK. Allergic rhinitis. Lancet 2011; 378:2112-22. 3. Settipane RA, Schwindt C. Chapter 15: Allergic rhinitis. Am J Rhinol Allergy 2013;27 (Suppl 1):S52-5. 4. Björkstén B, Clayton T, Ellwood P, et al. ISAAC Phase III Study Group. 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