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Asthma Rhinitis

  1. 1. Asthma Rhinitis link
  2. 2. By Dr . Ashraf El-Adawy Consultant Chest Physcian TB TEAM Expert - WHO
  3. 3. Asthma and allergic Rhinitis are common health problems that cause major illness and disability world wide. Both are common chronic diseases that affect the quality of life of patients and have a significant economic impact European Respiratory Disease 2006
  4. 4. The prevalence of asthma and rhinitis varies all over the world with allergic Rhinitis being two times more prevalent than asthma. The worldwide incidence of allergic Rhinitis and asthma has been on the rise . European Respiratory Disease 2006
  5. 5. Australia asthma 18% rhinitis 25% Canada asthma 13% rhinitis 25% Sweden asthma 8% rhinitis 15% China asthma 5% rhinitis 10% Worldwide prevalence Brasil asthma 10% rhinitis 22% Kenya asthma 8% rhinitis 13% ISAAC study, Lancet 1998
  6. 6. Using a conservative estimate, it is proposed that allergic rhinitis occurs in around 500 million people Studies suggest that there are more than 300 million persons worldwide who are affected by asthma
  7. 7. Co-Existence of Asthma and Allergic Rhinitis: A 23-Year follow- Up Study of College Students William A. Greinsner, Robert J. Settipane and Guy A. Settipane Allergy and Asthma Proc 1998
  8. 8. Allergic Rhinitis and Asthma frequently occur together 40% of allergic rhinitis patients have asthma 80% of asthma patients have concomitant Rhinitis symptoms European Respiratory Disease 2006
  9. 9. Most Patients with Asthma Have Allergic Rhinitis • Approximately 80% of asthmatics have allergic rhinitis Asthma alone Allergic rhinitis alone Allergic rhinitis + asthma Adapted from The Workshop Expert Panel. Management of Allergic Rhinitis and its Impact on Asthma (ARIA) Pocket Guide. A Pocket Guide for Physicians and Nurses. 2001; Bousquet J and the ARIA Workshop Group J Allergy Clin Immunol 2001;108(5):S147- S334; Sibbald B, Rink E Thorax 1991;46:895-901; Leynaert B et al Am J Respir Crit Care Med 2000;162:1391-1396.
  10. 10. IMPACT OF ASTHMA AND ALLERGIC RHINITIS ON EACH • Epidemiologic • Anatomic • Physiologic • Immunopathologic • Therapeutic
  11. 11. Allergic Rhinitis is a risk factor for asthma Allergic Rhinitis increased the risk of asthma ~3-fold 12 10 8 6 4 2 0 Subjects with asthma at 23- year follow-up (%) 10.5 Allergic rhinitis at baseline (n=162) 3.6 No allergic rhinitis at baseline (n=528) p<0.002 23-year follow-up of college freshmen undergoing allergy testing; data based on 738 individuals (69% male) with average age of 40 years. Adapted from Settipane RJ et al Allergy Proc 1994;15:21-25.
  12. 12. Rhinitis as an independent risk factor for adult-onset asthma (atopic and non-atopic) (European Community Respiratory Health Survey) Asthma (%) Atopic Non atopic 25 20 15 10 5 Adapted from Leynaert B et al. J Allergy Clin Immunol 1999; no rhinitis, N=5198 rhinitis, N=1412 OR=11 OR=17 0
  13. 13. Prevalence of asthma (physician diagnosed) in Rhinitis - 591 patients - 502 controls - allergic to pollens, mite, -epithelia Bousquet, CEA 2005 35 30 25 20 % subjects 15 10 5 0 contr mild severe mild severe intermittent persistent % pazienti
  14. 14. The prevalence of asthma in subjects without Rhinitis is usually less than 2%. The prevalence of asthma in patients with Rhinitis varies from 10 to 40% depending on studies Patients with moderate/severe persistent Rhinitis may be more likely to suffer from asthma than those with an intermittent and/or a milder form of the disease
  15. 15. BHR was found in 24% to 40% of patients with active Rhinitis (In the general population the BHR prevalence is 10-20%) Di Lorenzo G. et al. “ Non-specific airway responsiveness in mono-sensitive Sicilian patients with allergic rhinitis: its relationship to total serum IgE levels and blood eosinophils during and out of the pollen season” Clin Exp Allergy 1997; 27: 1052-59 Ramsdale EH et al. “ Asymptomatic bronchial hyperresponsiveness in rhinitis” J Allergy Clin Immunol 1985; 75: 573-577 Annesi I. et al. “ Relationship of upper airways disorders to FEV1 and bronchial hyperresponsiveness in an epidemiological study” Eur Respir J 1992; 5: 1104-1110
  16. 16. Several studies suggested that patients with allergic Rhinitis and BHR are at higher risk of developing asthma Braman SS et al. “ Airway hyperresponsiveness in allergic rhinitis: a risk factor for asthma” Chest 1987; 91: 671-674 Laprise C. et al. “ Asymptomatic airway hyperresponsiveness: A three-year follow-up” Am J Respir Crit Care Med 1997; 156: 403-9
  17. 17. The current concept is that AR precedes Rhinitis asthma Disease severity time Togias, Allergy 1999 asthma in most patients
  18. 18. The Allergy March: A Progression of Seemingly Unrelated Diseases CHDs CHDs Atopic Dermatitis GI Distress Recurrent Otitis Media Allergic Asthma Allergic Rhinitis Food Sensitivity Inhalant Sensitivity Time (~years) Genetic Predispositi on
  19. 19. Links between Rhinitis and asthma Epidemiologic evidence Rhinitis is a significant risk factor for adult-onset asthma in both atopic and non-atopic subjects increased the risk by about 3 times. 76% asthmatic patients reported presence of Rhinitis before onset asthma.
  20. 20. Links between Rhinitis and asthma Epidemiologic evidence Patients with moderate/severe persistent Rhinitis may be more likely to suffer from asthma than those with an intermittent and/or mild Rhinitis Asthma prevalence is increased in allergic and non-allergic Rhinitis Non-specific bronchial hyperreactivity is increased in persistent Rhinitis
  21. 21. Allergic Rhinitis and Asthma Share Common Triggers
  22. 22. • . Allergic Rhinitis and asthma share similar inflammatory processes Common triggers Similar inflammatory cascade on exposure to allergen Similar pattern of early- and late-phase responses Infiltration by the same inflammatory cells (e.g.eosinophils) Several potential connecting pathways including systemic transmission of inflammatory mediators
  23. 23. Allergic asthma and allergic Rhinitis are characterized by a similar inflammatory process Eosinophils in airway mucosa are regarded as the hallmark of allergic Rhinitis and asthma Eosinophilic inflammation has been found in the lower airways of allergic Rhinitis patients without asthma and in the upper airways of asthmatic patients without nasal complaints
  24. 24. Bronchial biopsioes after Specific provocation in patients with rhinitis or asthma ASTHMA Crimi E et al, JAP 2001 RHINITIS ALONE Same inflammation
  25. 25. Nasal allergen challenge Increases bronchial reactivity Induces bronchial inflammation Littell NT, Changes in airways resistance following nasal provocation. Am Rev Respir Dis 1990 Corren J Changes in bronchial responsiveness following nasal provocation with allergens. JACI 1992 Small P ET AL The effects of allergen-induced nasal provocation on pulmonary function in patients with perennial allergic rhinitis. Am J Rhinol 1989
  26. 26. Induces nasal inflammation Bronchial endoscopic challenge With allergen
  27. 27. Mechanisms of pathologic relationships between upper and lower airways. Togias A Allergy 1999;54(suppl 57):94.. Aspiration of Inflammatory Material Oral breathing Nasopharyngo-bronchial reflex Systemic Propagation of Nasal Inflammation
  28. 28. Naso-bronchial reflex Allergen INFLAMMATION nose Cytokines bone marrow bronchi Bronchial hyperreactivity physical filter function adhesion molecules viral infection
  29. 29. The relationships between Rhinitis and asthma can be viewed under the concept that the 2 conditions are manifestations of one syndrome, in 2 parts of the respiratory tract , the upper and lower airways, respectively At the low end of the severity spectrum, Rhinitis may occur alone , in the middle range of the spectrum, Rhinitis and AHR may be present and, at the high end, Rhinitis and asthma may both be present, with the severity of each condition tracking in parallel. . Togias A, J Allergy Clin Immunol Jun2003
  30. 30. Chronic Allergic Inflammatory Airway Syndrome Allergic Rhinitis Allergic rhinitis + Bronchial Hyperreactivity Allergic Rhinitis + Asthma
  31. 31. Allergic Rhinitis and Asthma: Two Related Conditions Linked by One Common Airway The United Airways Disease
  32. 32. The allergic Rhinitis and asthma frequently co-exist leading to the concept that these seemingly separate disorders are manifestations of the same disease expressed to a greater or lesser extent in either the upper or the lower airways. In some patients Rhinitis predominates and asthma is undiagnosed or sub-clinical, in others it is reversed, while in many both are clinically expressed. Togias A, J Allergy Clin Immunol Jun2003
  33. 33. The nose-lung interaction in allergic rhinitis and asthma: united airways disease G.Passalacqua, G.Ciprandi & G.W.Canonica 2004 Asthma and Rhinitis as different Aspects of a sinlge disorder
  34. 34. Clinical links
  35. 35. Influence of comorbid conditions on asthma Boulet LP, ERJ 2009
  36. 36. Risk factors of frequent exacerbation in difficult-to-treat asthma Ten Brinke A et al Eur Resp J 2005 51
  37. 37. Clinical aspects of the link between chronic sinonasal diseases and asthma. Dursun et al. Allergy Asthma Proc 2006
  38. 38. The coexistence of sinusitis and asthma, especially in children, is known, and infection of the paranasal sinuses is frequently implicated in the development of disease of the lower respiratory tract in allergic patients. Sinusitis and/or adenoiditis have been shown by endoscopic assessment to occur in more than 50% of children with asthma. ARIA 2008
  39. 39. Infected sinuses are a reservoir of proliferating bacteria and are frequently associated with worsening of asthma. Endotoxins from the cell walls of gram-negative bacteria have potent pro-inflammatory properties, and inhalation of endotoxin has been shown to induce airway narrowing and hyperresponsiveness in patients with asthma.
  40. 40. Good correlation among abnormal sinus x-rays, blood eosinophilia and asthma symptoms Steroid-dependent asthmatics usually have abnormal sinus computed tomography The sinonasal inflammation is a risk for asthma exacerbation Treatment of sinusitis improves asthma
  41. 41. Cruz, Allergy 2008
  42. 42. Untreated rhinitis increases the risk of asthma attacks. Asthma Asthma + rhinitis Bousquet, Clin Exp Allergy 2005
  43. 43. Treatment of Rhinitis reduces emergency visits for asthma Baena-Cagnani et al, Int Arch Allergy Immunol 2003 Nelson HS, JACI 2003 Crystal-Peters, JACI 2002 Fuhlbrigge, Curr Opin Allergy Immunol 2003 Adams et al. J.A.C.I. 2002
  44. 44. Treating allergic rhinitis cuts asthma costs • 61% fewer hospitalisations in treated patients 0.9 2.3 p<0.01 Patients hospitalised over 1-year period (%) Patients untreated for AR (n=1357) Patients treated for AR (n=3587) 2.5 2.0 1.5 1.0 0.5 0.0
  45. 45. • therapeutic Therapeutic aspects
  46. 46. The severity of allergic rhinitis was shown to be directly correlated with asthma severity. Those patients whose allergic rhinitis was severe or poorly controlled had worse asthma control and tended to have more persistent asthma than those with mild or well controlled rhinitis. In addition, bronchial hyperresponsiveness can be present in patients with allergic rhinitis without clinical evidence of asthma ARIA 2008
  47. 47. Prompt and effective treatment of nasal disease can have a marked effect on preventing the development of asthma, and on existing asthma symptoms. The World Allergy Organization IAACI, 2003 Treatment of rhinitis has the potential to reduce asthma symptoms to such an extent that treatment with prophylactic anti-asthma drugs may be unnecessary in some patients with a diagnosis of mild asthma. Curr Opin Allergy Clin Immunol 2003
  48. 48. Among a population with co-existing asthma and allergic rhinitis, treatment for allergic rhinitis was associated with a decrease in the risk of subsequent asthma-related events by one-third to one-half compared with persons who did not receive treatment for this disorder. Fuhlbrigge A, Curr Opin Allergy Clin Immunol 2003
  49. 49. The recommended clinical approach is to manage the two disorders discretely but simultaneously. You should treat each disease separately; that even though it's 1 disease, you can't just treat the nose and take care of the asthma,or treat the asthma and take care of the nose. Each one has to be treated appropriately. Asthma Management: An Expert Interview With Harold Nelson, MD 4/1/2005 Harold Nelson, MD, Professor of Medicine at National Jewish Medical and Research Center, discusses data presented at AAAAI 2005 in asthma management.
  50. 50. Asthma Pathophysiology Symptoms The tip of the iceberg Airflow obstruction Bronchial hyperresponsiveness Airway inflammation
  51. 51. Minimal persistent inflammation is also Present in patients with seasonal allergic rhinitis V. Ricca, M.Landi, P.Ferrero, A.Bairo, C.Tazzer,G.W.Canonica and G.Ciprandi gw111199 J.A.C.I. 2001
  52. 52. Concept of "minimal persistent inflammation" Threshold level for symptoms 100 10 1 0,1 0 2 4 6 8 10 12 Months mite allergen (μg/g of dust) Minimal persistent inflammation Symptoms inflammation Ciprandi et al, J Allergy Clin Immunol 1996
  53. 53. Instead of considering allergic rhinitis as a disease of acute symptoms, it needs to be understood as a chronic inflammatory disease. Even in the absence of symptoms, continuous exposure to low levels of allergen results in an inflammatory infiltration and ICAM-1 expression, which is known as "minimal persistent inflammation" (MPI).
  54. 54. The concept of minimal persistent inflammation suggests a different approach to therapy in which symptoms can be considered the “tip of the iceberg” of the allergic reaction with inflammation and hyper-responsiveness representing the submerged iceberg Therefore, any optimal therapeutic strategy for AR should focus on minimizing inflammatory phenomena rather than only on alleviating acute symptoms.
  55. 55. Therapeutic implications of minimal persistent inflammation The intranasal corticosteroids (INCSs) are the current first-line therapy for moderate to severe cases of seasonal and perennial AR Regular persistent use of INCSs has been effective in reducing all symptoms nasal congestion, rhinorrhoea, sneezing, and nasal itching in both adults and children. They also suppress multiple mediators and several stages of the inflammatory process.
  56. 56. INCS are the most effective drug In A.R. ICS are the milestone asthma treatment • ICS+INCS in the same UAD patients???????
  57. 57. Taramarcaz, Cochrane 2008
  58. 58. Conclusions: Treatment of nasal conditions, particularly with intranasal steroids, confers significant protection against exac-erbations of asthma leading to ED visits for asthma. These results support the use of intranasal steroids by individuals with asthma and upper airways conditions. J Allergy Clin Immunol. 2002 Apr;109(4):636-42
  59. 59. mild intermittent TREATMENT OF ALLERGIC RHINITIS ARIA -Allergic Rhinitis and its Impact on Asthma Mild persistent Moderate-severe intermittent Moderate-severe persistent Antileukotrienes (if asthma) Nasal steroid Cromones 2nd Generation antihistamine Decongestant (<10 days) Allergen avoidance Im immunotherapy
  60. 60. Treatment of comorbid Rhinitis & asthma
  61. 61. "integrated" therapeutic approach in patients with rhinitis and asthma.
  62. 62. Treatment of rhinitis and asthma using a single approach ● Oral H1-antihistamines are not recommended, but not contraindicated in the treatment of asthma. ● Intranasal glucocorticosteroids are at best moderately effective in asthma. ● Intranasal glucocorticosteroids may be effective in reducing asthma exacerbations and hospitalizations. ● The role of intrabronchial glucocorticosteroids in rhinitis is unknown. ARIA 2008
  63. 63. ● Montelukast is effective in the treatment of allergic rhinitis and asthma in patients over 6 years of age. ● Subcutaneous immunotherapy is recommended in both rhinitis and asthma in adults, but it is burdened by side effects, in particular in asthmatics. ● Anti-IgE monoclonal antibody is effective for both rhinitis and asthma. ARIA 2008
  64. 64. combined simultaneous treatment of co-existing asthma & rhinitis Pulmonary steroid Twice daily & Pulmonary bronchodilator Rescue medication Oral Anti-histamine Once daily Or Oral Anti-leukotriene Once daily + + & Nasal steroid Once daily Or Pulmonary combination : ICS+LABA Twice daily + +
  65. 65. When to Consider Immunotherapy Mild Moderate ± conjunctivitis Allergen avoidance when possible RHINITIS Pharmacotherapy Severe ± conjunctivitis Consider immunotherapy Intermittent Mild persistent Pharmacotherapy Moderate persistent Consider immunotherapy Severe persistent
  66. 66. Final Remarks “Allergic rhinitis and asthma are chronic inflammatory disorders that have been linked epidemiologically, pathophysiologically, and therapeutically as “one airway disease.”
  67. 67. Final Remarks 1-Patients with persistent Rhinitis should be evaluated for asthma 2-Patients with persistent asthma should be evaluated for Rhinitis 3-A combined strategy should be used in the treatment of upper and lower airways
  68. 68. Thank you for staying awake!