EPIDEMIOLOGICAL OUTCOMES RHINITIS AND ASTHMA: UNITED AIRWAY DISEASE EPIDEMIOLOGICAL OUTCOMES Dr. İ.Kıvılcım Oğuzülgen Gazi University School of Medicine, Department of Pulmonary Medicine Ankara, Turkey

ASTHMA ασθμα İlk defa Homer tarafından kullanılan, ağrılı ve zor nefes almayı tarifleyen bu sözcük ilk defa Hipokrat zamanında klinik bir anlam kazanmıştır ve o dönemin yazılarında bir hastalıktan çok bir semptomu tariflemek için kullanılmıştır.

Asthma in history ... A disease, emphasizing the wheezing, the dry, often non productive cough, and the inability to sleep in a prone position. The disease called ortopnoia is also called asthma ..... ....They eagerly go into the open air, since no house sufficieth for their respiration...... ...cough incessant and laborious, expectoration small, thin, cold, resembling the efflorescence of foam..... ...if these symptoms increase, they sometimes produce suffocation...... First recognizable clinic description of asthmatic paroxysm was provided by Aretaeus, a Greek physician born in Cappadocia. Aretaeus of Cappadocia was a physician who followed the pneumatic school of medicine and Hippocrate's teachings. He is credited with describing such chronic conditions as pleurisy, diphtheria, tetanus, pneumonia, asthma, and epilepsy. He gave diabetes its name, from the Greek word meaning "siphon". He is the second physician known to describe ulcerative colitis (the first being Soranus).  This was translated into Latin and printed in Venice in 1552. Aretaeus of Cappadocia 81-131 AD

Aretaeus of Cappadocia described asthma with care, attributing it to thick and viscid phlegm caused by coldness and humidity suffered by the patient. Aretaeus of Cappadocia (81­131) De Causis et Signis Acutorum et Diuturnorum Morborum, Liber Primus (Of the Causes and Signs of Acute and Morbid Disease) Oxford, 1723 1552 ‘de çevrilmiş.

The prevalance of asthma in world 3.4 6.9 5.8 – 6.7 2.7 7.2 12 7.1 4 4 4 2.9 10.5 9.5-18.9 GINA, updated 2004.

The prevalance of asthma in Turkey 5.5-7.9 5.6-7.6 7.1-8.9 9.5-11.2 8.1-10.8 TC ortalaması 6.9-8.8 9.6-8.1 5.8-7.4 2.2-2.5 5.9-7.3 9.4 5.9-7.3 8.2-11.0 8.5-11.0 5.7-7.7 Kurt E et al. PARTFAIT study. Unpublished data Dinmezel S et al. Allergy Asthma Proc 2005; 26:403-409 Kalyoncu AF et al. Allergol Immunopathol 2001; 29:264-271

Rhinitis in history About the beginning or middle of the June every year.... ... a sensation of heat and fulness is experienced in the eyes... ... to this succeeds irritation of the nose producing sneezing To the sneezing are added a further sensation of thightness of the chest, a difficulty of breathing 1819 - Dr. John Bostock first accurately described hay fever as a disease that affected the upper respiratory tract. Although of unknown origin, oddly enough it had nothing to do with either hay or having a fever. Hay fever, or in medical terms, seasonal allergic rhinitis, is the most widespread form of allergy, affecting more than 15 million Americans. Common symptoms include sneezing, a runny or stuffed nose, red, itchy, swollen or watery eyes and itching in the nose and throat. Dr. John Bostock Med Chir Trans 1819; 10: 161

The prevalance of rhinitis in world 10 19-23.4 14 4.4 – 14.2 6.6 22.7 14.9 – 29 10.2 – 21.1 10.6 4.1 13.3 4.5 ARIA Workshop Report. J Allergy Clin Immunol 2001;108: S153-S161.

The prevalance of rhinitis in Turkey 13.3-17.5 12.9-17.8 13.1-18.5 17.5-22.9 13.4-18.4 Türkiye oratalaması 13.5-18.6 15.7-20.6 12.2-17.8 12.7-14.5 12.2-16.1 27.7 5.9-7.3 15.2-20.3 13.6-19.4 10.7-16.4 Kurt E et al. PARTFAIT study. Unpublished data Dinmezel S et al. Allergy Asthma Proc 2005; 26:403-409 Kalyoncu AF et al. Allergol Immunopathol 2001; 29:264-271

Allergic Rhinitis Asthma Epidemiologic Links between Allergic Rhinitis and Asthma Allergic Rhinitis and Asthma Have Similar Prevalence Patterns (ISAAC) Allergic Rhinitis Asthma UK Australia Canada Brazil USA South Africa Germany France Argentina Algeria China Russia UK Australia Canada Brazil USA South Africa Germany France Argentina Algeria China Russia Study of worldwide prevalence of atopic diseases in 463,801 children 13–14 years of age. Children self-reported symptoms over 12 months using questionnaires. International Study of Asthma and Allergies in Childhood (ISAAC) 5 10 15 20 25 30 35 40 5 10 15 20 25 30 35 40 % prevalence % prevalence ISAAC Steering Committee Lancet 1998;351:1225–1232.

Epidemiologic Links between Allergic Rhinitis and Asthma Allergic Rhinitis and Asthma Have Similar Trends in Prevalence Asthma Allergic Rhinitis 3.5 3.0 2.5 2.0 1.5 1.0 0.5 9 8 7 6 5 4 3 2 1 % of men % of men Fllandiyada askerlik muayenesi sırasında int. Classification of disease codlarından yola çıkarak 1966-2003 arasında 1.4 milyon insanın kayıtlarının incelenmesinden çıkan sonuçlar, her iki durumun prevalansındaki değişmelerin paralelliğini göstermketedir. 1960 1970 1980 1990 2000 1960 1970 1980 1990 2000 Year Year Latvala J et al. 2005;3301186–1187.

First published papers in PubMed about the relation between rhinitis and asthma RANDOLPH TG, ROLLINS JP. Adrenocorticotropic hormone (ACTH) its effect in bronchial asthma and ragweed hay fever. Ann Allergy. 1950 Mar-Apr;8(2):149-62. CUERVO TRUJILLO C. [Bronchial asthma in children consecutive to allergic rhinitis.] Rev Colomb Pediatr Pueric. 1952 Jun;11(5):221-40. VUKOBRATOVIC S. [The relation between allergic rhinitis and bronchial asthma and the reaction of sensitized tissue to histamine.] Med Glas. 1954 Sep;8(9):310-3.

Approximately 60% of the patients experience rhinitis symptoms before asthma symptoms AR semptomları olguların çoğunda çocukluk vya adölesan dönemde,%70’inde 30 yaşından önce başlamaktadır. Erişkinlerde semptomlar kolayca fark edilirken çocuklarda genellikle tanı gözden kaçırılmaktadır.

60-80% of asthmatics have coexisting allerjic rhinitis, Epidemiologic Links between Allergic Rhinitis and Asthma 60-80% of asthmatics have coexisting allerjic rhinitis, 20% - 38% of patients who have allergic rhinitis have coexisting asthma. Braman SS et al.Chest 1987; 1:671-74 Grossman J. CHEST 1997; 111:11S-16S.

Asthma and rhinitis might interact each other? Asthma and rhinitis might be two different manifestations of the same atopic disease? Asthma and rhinitis might interact each other? Upper and lower airways might be influenced by a common inflammatory process, which might be sustained and amplified by intertwined mechanisms. AR and A:Astma are manifestations of the same disease entity and they represent a continuum of disease. In this way, subjects with less severe disease express both rhinitis and asthma. This concept has been labeled “one airway-one disease”, allerjik rhinobronchitis or united airway disease. According to this concept allergic rhinitis should ubiquitously present in subjects with allergic asthma. However, epidemiological studies have not been able to demonstrate this convincingly Pedersen PA et al. Allergy 1983; 38:25-29 Leynaert B et al. J Allergy Clin Immunol 2004; 113:86-93

Epidemiologic evidence for the link between rhinitis and asthma Asthma prevalence is increased in allergic and non-allergic rhinitis Rhinitis is almost always present in asthma Rhinitis may be a risk factor for asthma Non-spesific bronchial hyperresponsiveness is increased in persistent rhinitis Adopted from ARIA (www.whiar.com)

Epidemiologic evidence for the link between rhinitis and asthma Asthma prevalence is increased in allergic and non-allergic rhinitis Rhinitis is almost always present in asthma Rhinitis may be a risk factor for asthma Non-spesific bronchial hyperresponsiveness is increased in persistent rhinitis Asthma prevalence is increased in allergic and non-allergic rhinitis Rhinitis is almost always present in asthma Rhinitis may be a risk factor for asthma Non-spesific bronchial hyperresponsiveness is increased in persistent rhinitis

ECRHS Swedish results (n:9325) Asthma prevalence is increased in allergic and non-allergic rhinitis ECRHS Swedish results (n:9325) Rhinitis (+) Rhinitis (-) 19.5% had asthma related disease 2.3% had asthma related disease İsveçin 3 şehrinde yapılan bir kesitsel anket çalışmasında astma related disease: Son 12 ayda astım atağı geçirmek veya astım ilacı kullanıyor olmak. ECRHS Swedish results of the first part of the study. OR=10.1 (95% CI 8.4-12.2) p<0.001 E. Björnsson et al. Eur Respir J 1994; 7,:2146–2153.

ECRHS results OR=19.9 (95%CI 14.6-27.2) Asthma prevalence is increased in allergic and non-allergic rhinitis ECRHS results 1412 perennial rhinitis and 5198 control subjects Rhinitis (+) Rhinitis (-) Asthma 16.2% Asthma 1.0% OR=19.9 (95%CI 14.6-27.2) Leynaert B et al.J Allergy Clin Immunol 1999; 104:301-304.

ECRHS results-2 (1412 perennial rhinitis and 5198 control subjects) Asthma prevalence is increased in allergic and non-allergic rhinitis ECRHS results-2 (1412 perennial rhinitis and 5198 control subjects) Nonatopic subjects Atopic subjects Rhinitis (+) Asthma 7.8%, Rhinitis (-) Asthma 0.5% OR=11.6 (95%CI 6.2-21.9, p=0.001) Rhinitis (+) Asthma 19.1% Rhinitis (-) Asthma 2.3% OR=8.1 (95%CI 5.4-12.1, p=0.001) Leynaert B et al.J Allergy Clin Immunol 1999; 104:301-304.

ECRHS results (31 centers) Asthma prevalence is increased in allergic and non-allergic rhinitis ECRHS results (31 centers) % with asthma 20 18 16 14 12 10 8 6 4 2 Rhinitis (+) Rhinitis (-) 31 ülkenin stage II sonuçları. Spain Italy France Benelux UK Scandinavia US The proportion of of subjects with asthma was 2.0% in subjects without rhinitis and 13.4% in subjects with rhinitis, OR=6.63 (95%CI 5.44-8.08), p<0.001. Leynaert B et al. J Allergy Clin Immunol 2004; 113: 86-93

Epidemiologic evidence for the link between rhinitis and asthma Asthma prevalence is increased in allergic and non-allergic rhinitis Rhinitis is almost always present in asthma Rhinitis may be a risk factor for asthma Non-spesific bronchial hyperresponsiveness is increased in persistent rhinitis Asthma prevalence is increased in allergic and non-allergic rhinitis Rhinitis is almost always present in asthma Rhinitis may be a risk factor for asthma Non-spesific bronchial hyperresponsiveness is increased in persistent rhinitis

Data from Finnish Twin Cohort (n:11540) Rhinitis is almost always present in asthma Data from Finnish Twin Cohort (n:11540) 1975 1990 Hay fever (men) Hay fever (women) 18-45 yaşa arası 11540 kişi 1975-1981-1990 anketlerle değerlendirilmiş. 15 yılda astım insidansı erkeklerde 2.3%, kadınlarda 2.6%. Hay fever erkeklerde 9.4%, kadınlarda 13.4%. Hay fever in 219 subjects with incident asthma Huovinen E et al. Chest 1999;115;928-936

The Copenhagen Allergy Study Rhinitis is almost always present in asthma The Copenhagen Allergy Study 1990 1998 Takipte yeni gelişen 28 polene karşı AA’lının 18’inin (%64.2) başlangıçta polene karşı AR (+), 10 ‘u takipte polene karşı AR (+) olmuş. Hayvana karşı AA gelişen 10 olgunun 5’i baştan AR, 4’ü takipte AR olmuş, Mite’a karşı AA gelişen 10 olgunun 5’i baştan AR, 5’i takipte (+) olmuş. Thus AR appeared to be present among nearly all subjects with AA. Patients who developed allergic asthma during the follow-up Linneberg A et al. Allergy 2002; 57: 1048-1052

ISAYA 2005 (n:17666) Reported allergic rhinitis prevalence is 18.7%. Rhinitis is almost always present in asthma ISAYA 2005 (n:17666) Reported allergic rhinitis prevalence is 18.7%. The prevalence of allergic rhinitis in subjects reporting asthma was about 60%. Italian study of asthma in young adults, 20-44 yaş, 9 merkez. 1999-2000 arası. ECRHS satge 1benzeri anket çalışması Bugiani M et al. Allergy 2005: 60: 165–170

Data from asthmatic children aged 3-16 years (n:369) Rhinitis is almost always present in asthma Data from asthmatic children aged 3-16 years (n:369) 68.8% (254) of asthmatics (87.9% of allergic asthmatics) were diagnosed with allergic rhinitis. Retrospective evaluation of their file records showed that only 23.8% and 57.7% of this group had received a diagnosis of allergic rhinitis and treatments for allergic rhinitis, respectively. HÜTF çocuk kliniğinde yapılan çalışma, anket çalışması, daha önce kullanılna standart anketlerin modifikasyonu Kocabas CN et al. Pediatr Pulmonol. 2005; 40:235–240.

Epidemiologic evidence for the link between rhinitis and asthma Asthma prevalence is increased in allergic and non-allergic rhinitis Rhinitis is almost always present in asthma Rhinitis may be a risk factor for asthma Non-spesific bronchial hyperresponsiveness is increased in persistent rhinitis Asthma prevalence is increased in allergic and non-allergic rhinitis Rhinitis is almost always present in asthma Rhinitis may be a risk factor for asthma Non-spesific bronchial hyperresponsiveness is increased in persistent rhinitis

23-years follow-up study Rhinitis may be a risk factor for asthma 23-years follow-up study 12 10 8 6 4 2 % of patients who developed asthma 10.5 Allergic rhinitis at baseline (n=162) 3.6 No allergic rhinitis at baseline (n=528) p<0.002 Allergic rhinitis increased the risk of asthma about threefold Settipane RJ et al. Allergy Proc 1994;15:21–25.

Rhinitis may be a risk factor for asthma Birth 6 years n:747 Sağlıklı çocukların ilk 6 yılındaki takip sonuçları 42% had allergic rhinitis / 58% was non-rhinitic Wright AL et al. Pediatrics 1994; 94: 895-901

Data from Finnish Twin Cohort Rhinitis may be a risk factor for asthma Data from Finnish Twin Cohort 1975 1990 Subjects Subjects at risk Cases Incidence of asthma 1976-1990 IRR (95%CI) Hay fever 1975 No 4554 86 1.9 1.0 Yes 301 25 8.3 4.3 (2.8-6.6) 5487 107 2.0 355 43 12.1 6.0 (4.2-8.3) 18-45 yaşa arası 11540 kişi 1975-1981-1990 anketlerle değerlendirilmiş. IRR: incident rate ratio Hay fever significantly icreased the risk of asthma ! Huovinen E et al. Chest 1999; 115;928-936

Data from ECRHS stage III Rhinitis may be a risk factor for asthma Data from ECRHS stage III 1990 1993 n:1370 (20-44 yr) A.Rhinitis (+) A.Rhinitis (-) Hem atopik hem nonatopiklerde rinit varlığı multivaryant analizde astımın ortaya çıkmasında anlamlı bağımsız risk faktörü olarak bulunmuş. ECRHS protokolündeki hastalar 3rd stage. ( 1. evre anket, 2. evre seçilenlere tetkik, 3. evre yeni anket) 13.1% 1.6% had new onset of asthma OR= 4.9 (95% CI 2.3-10.4) Plaschke P et al. Am J Respir Crit Care Med 2000;162:920–924

Tucson Epidemiologic Study of Obstructive Lung Disease Rhinitis may be a risk factor for asthma Tucson Epidemiologic Study of Obstructive Lung Disease 1972 1992 173 Incident asthmatic patients 2177 Subjects without asthma Subjects who reported the presence of rhinitis before the onset of asthma Bu longitudinal kohorttan vaka kontrollü çalışma çıkarılmış. 76.3% 43.8% p<0.001 Rhinitis had a strong predictive value for the onset of asthma (OR=3.81; 95%CI 2.50-5.79) irrespective of whether subjects had positive or negative skin test responses Guerra S et al. J Allergy Clin Immunol 2002; 109: 419-425

Data from ECRHS (n:10210, 31 centers) Rhinitis may be a risk factor for asthma Data from ECRHS (n:10210, 31 centers) Barcelona Galdako Albacete Oviedo Huelvo Pavia Turin Verona Bordeaux Grenoble Montpellier Paris Antwerp-South Antwerp-City Groningen Bergen-op-Zoom Geleen Dublin Cambridge Ipswich Norwich Reykjavik Bergen Göteborg Umea Uppsala Wellington Christchurch Hawkes-Bay Melbourne Portland Combined ECRHS stage II tamamlayan 31 merkezin sonuçları 0.5 1 2 5 10 The risk of asthma was strongly associated with rhinitis in all centers (combined OR=7.03; 95% CI 6.25-7.91, p<0.001) Leynaert B et al. J Allergy Clin Immunol 2004; 113: 86-93)

Epidemiologic evidence for the link between rhinitis and asthma Asthma prevalence is increased in allergic and non-allergic rhinitis Rhinitis is almost always present in asthma Rhinitis may be a risk factor for asthma Non-spesific bronchial hyperresponsiveness is increased in persistent rhinitis Asthma prevalence is increased in allergic and non-allergic rhinitis Rhinitis is almost always present in asthma Rhinitis may be a risk factor for asthma Non-spesific bronchial hyperresponsiveness is increased in persistent rhinitis

Seasonal increase of bronchial reactivity in allergic rhinitis Non-spesific bronchial hyperresponsiveness is increased in persistent rhinitis Seasonal increase of bronchial reactivity in allergic rhinitis 27 patients with hay fever without a history of asthma had inhalation challenge test: Out of pollen season During pollen season BPT (+) 11% (n:3) 48.1% (n:13) Madonini E et al. J Allergy Clin Immunol. 1987; 79:358-63.

ECRHS results (1412 perennial rhinitis and 5198 control subjects) Non-spesific bronchial hyperresponsiveness is increased in persistent rhinitis ECRHS results (1412 perennial rhinitis and 5198 control subjects) Among Non-asthmatic subjects Rhinitis (+) BHR 22.5% Without rhinitis BHR 7.5% OR=3.6 (95% CI 3.0-4.3) ECRHS 22 ülke, 48 merkez, 22-44 y arası 140.000 kişi taranmış. Cevap verenlerden 34 merkezden randomize seçilen bir gruba tetkikler yapılmış. ANket, SFT, BPT, cilt testi, spes IgE, total IgE. (The frequency of current astma was 16.2% among individuals with rhinitis vs 1.0% among control subjects OR=19.9; 95% CI 14.6-27.2) Leynaert B et al. J Allergy Clin Immunol 1999; 104:301-304.

ECRHS results (1412 perennial rhinitis and 5198 control subjects) Non-spesific bronchial hyperresponsiveness is increased in persistent rhinitis ECRHS results (1412 perennial rhinitis and 5198 control subjects) Nonatopic subjects Atopic subjects Rhinitis (+) BHR 11.6%, Rhinitis (-) BHR 6.6% (OR=1.5, 95%CI 1.0-2.2, p=0.001) Rhinitis (+) BHR 26.7% Rhinitis (-) BHR 10.0% (OR= 3.3, 95%CI 2.6-4.2,p=0.001) Leynaert B et al. J Allergy Clin Immunol 1999; 104:301-304.

Possible pathophysiological mechanisms for the association between rhinitis and asthma Nasal obstruction leading to mouth breathing, causing impaired warming and humidification of the inspired air and increased deposition of inhaled allergens in lower airways; Nasal–bronchial reflex; Aspiration of nasal secretions; Increased bronchial hyperresponsiveness.

Epidemiological data show that there is a strong link between rhinitis and asthma... Thank you!