The Role of Sinus Disease and Reflux in the Pathogenesis of Asthma. Anne Dixon, MA, BM, BCh

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1 The Role of Sinus Disease and Reflux in the Pathogenesis of Asthma Anne Dixon, MA, BM, BCh

2 Outline GERD and asthma Epidemiology Mechanistic relationship Effect of GERD on asthma control Effect of GERD treatment on asthma control Rhinitis/sinusitis and asthma Epidemiology Mechanistic relationship Effect of rhinitis and sinusitis on asthma control Effect of treatment on asthma control

3 GERD and Asthma: Epidemiology Prevalence reported between 32 and 84% About half have asymptomatic reflux

4 GERD symptoms precede asthma onset Gunnbjornsdottir ERJ 2004

5 GERD may cause bronchospasm Direct micoaspiration of acid causes bronchospasm Acid in esophagus causes vagally mediated bronchoconstriction

6 Asthma may aggravate GERD Negative intra-thoracic pressure during asthmatic episode Effect of medications on lower esophageal sphincter tone. Hyperinflation causes descent of diaphragm into stomach herniation of lower esophageal sphincter into chest

7 Pathophysiological Relationship may be bi-directional GERD? Asthma

8 Effect of GERD on asthma severity and control

9 Effect of GERD on asthma severity ph probe positive ph probe negative p n 160 (53%) 144 (47%) age asthma onset 16 yrs 17 yrs 0.14 β agonist 2x per week 81% 78% 0.55 ACQ % 91% 0.54 oral steroids in last year (%) 56% 43% 0.03 nocturnal awakenings 18% 10% 0.08 Mean ASUI Mean AQLQ fev % predicted fvc % predicted pc20 to methacholine Dimango, 2009, AJRCCM

10 Effect of GERD treatment on asthma

11 Treatment of symptomatic reflux Kiljander 2010 AJRCCM

12 Improvement in morning peak flow in patients with nocturnal asthma symptoms Kijlander AJRCCM 2006

13 Treatment of GERD placebo esomperazole p n episodes of poorly controlled asthma oral steroid use nocturnal awakenings change in fev (liters) change in fvc (liters) change in ASUI Mean AQLQ change in ACQ change in pc Mastronarde: NEJM, 2009

14 %2Fconte Relative+R Laheij%2C 2004+%3 jamav292 true 292/16/19 http%3a% View as a PowerPoint Slide Risk of Pneumonia with PPI Laheij 2004 JAMA

15 Increased Risk of Fracture and Osteoporosis Gray 2010, Archives of Internal Medicine

16 GERD and Asthma Treat only if clinical indications to treat GERD Treatment is not risk free Unlikely to see significant improvements in asthma control?

17 Asthma and the Nose

18 Galen: A.D. Secretions from brain drip into airway and cause asthma?

19 Prevalence of Upper Airways Disease in Asthmatics Rhinitis and Sinusitis both common in asthmatics Allergic rhinitis reported by 50-80% of asthmatics Allergy history commonly noted in patients with sinusitis Mucosal thickening noted by sinus CT in 70% asthmatics

20 Rhinitis a risk factor for future development of Asthma Concept of the Allergic March (begins with eczema) Burgess JACI 2007

21 What is the Nature of the Relationship Two manifestations of the same disease process? One continuous airway, sharing common mucosal layer Common immune mediators affect both allergic rhinitis and asthma

22 Pathology of allergic rhinitis and asthma Concept of one airway, unified airway disease

23 Differences in lower airway inflammation between asthmatics with and without rhinitis Dixon, Lung 2008

24 Common manifestations of the same disease? Can disease in one compartment, the nose alter disease in another compartment, the lung?

25 Changes in nasal mucosa in response to segmental bronchoscopic challenge. Braunstahl AJRCCM 2001

26 Bronchial changes in response to nasal challenge pre post ICAM-1 VCAM-1 E-Selectin CD31 Braunstahl, JACI 2001

27 Nature of connection between lung and nose Nasobronchial reflex? Post nasal drip of inflammatory mediators? Activation of systemic mediators?

28 Allergen challenge induces systemic response

29 Rhinitis/sinusitis and asthma Common pathology Asthmatics without rhinitis likely represent a different phenotype of disease Disease in one portion of the airway may effect disease in a distant part of the airway

30 Sinonasal Disease and Asthma Severity and Control

31 Rhinitis/sinusitis associated with worse symptoms, but better lung function Dixon, Chest 2006

32 Sinus disease associated with risk of asthma exacerbation Adjusted OR (95% CI) Psychological dysfunctioning 10.8 ( ) Recurrent respiratory infections 6.9 ( ) Severe chronic sinus disease 3.7 ( ) Obstructive sleep apnea 3.4 ( ) OR adjusted for age and asthma duration Ten Brinke, ERJ 2005

33 Is there any evidence that treating upper airways disease effects the course of asthma?

34 Treating Allergic Rhinitis in Allergy Season retrospective subgroup analysis of 58 asthmatics (14) (14) (19) (11) Welsh et al 1987, Mayo Clin Proc

35 Treating Allergic Rhinitis in Allergy Season 18 patients randomized to placebo or nasal beclamethasone no change in asthma Corren 1992, JACI

36 Participants n Age (yrs) Trial design Intervention PAR & Asthma Double-Blind Cross-Over AR & Asthma 25 adults RCT PAR and asthma 74 adults 3 group, RCT SAR and asthma 863 adults 3 group, RCT AR, no asthma 23 adults RCT SAR & Asthma 262 adults Nasal and MDI steroid versus anti-histamine and montelukast Nasal steroid Placebo Nasal steroid MDI steroid Both Nasal steroid Montelukast Placebo Nasal steroid Placebo 4 group Nasal steroid RCT MDI steroid Nasal & MDI steroid Placebo Duration (wks) 8 weeks 2 weeks 120 days Outcome Decreased bronchial hyperreactivity and eno in steroid group only Decreased cysteinyl leukotrienes in exhaled breath condensate Decreased asthma symptoms all groups ref Barnes Failla Stelchma 4 weeks No effect on asthma outcomes Nathan 4 weeks Decreased eno Sandrini 6 weeks No effect of nasal steroid on bronchial hyperreactivity or peak flow SAR & Asthma Aug RCT Nasal steroid, placebo 6 weeks No effect bronchial hyperreactivity Thio AR & Asthma 11 adults Double-Blind Cross-Over Nasal steroids MDI steroid 2 weeks Nasal steroid only improved bronchial hyperreactivity SAR & asthma 21 adults RCT Nasal steroid, placebo 4 weeks Improved bronchial hyperreactivity Watson SAR & asthma 18 adults RCT Nasal steroid, placebo 4 weeks Improved bronchial hyperreactivity Corren PAR & asthma 16 Adults RCT Nasal steroid, placebo 4 weeks Decreased exhaled NO Sandrini PAR & asthma 40 Children RCT Nasal steroid, placebo 4 weeks No change exhaled NO Pedroletti Dahl Aubier

37 Efficacy of nasal steroid for asthma control Nathan Chest 2005

38 Effect of treating sinusitis on asthma control

39 Treatment of Sinusitis Slavin 1980 JACI

40 Treatment of Sinusitis Rachelefsky 1984, Pediatrics 73:

41 Participants CRS & Asthma CRS & Asthma CRS & Asthma CRS & Asthma CRS & Asthma n Age (yrs) 43 adults Trial design* Intervention Duration of Trial Asthma Outcome ref Observational : two arms Observational 41 Mean age 9 28 adults Cross Over Observational : Surgery or Medical Treatment Antibiotic + Nasal steroid + Systemic steroid Nasal Saline or antibiotics Endoscopic sinus surgery (ESS) 12 months eno symptoms FEV1, (medical treatment did better) Ragab 57 6 weeks symptoms Tosca weeks Pre and post surgery Improved bronchial hyperreactivity after antibiotics symptoms Peak Flow Tsao 59 Dejima adults Observational ESS 12 months symptoms Dunlop 61 CRS & Asthma 19 adults Observational ESS Pre and post surgery symptoms Dhong 62 CRS & Asthma CRS & Asthma 17 Adult Observational ESS months symptoms Batra Adult Observational ESS 33 months No change Goldstein 64 CRS & Asthma 15 Adult Observational ESS 6 months peak flow Ikeda 65

42 Treating severe/acute sinonasal disease s is indicated regardless of asthma What about perennial or chronic disease? How do you diagnose perennial rhinitis/chronic sinusitis?

43 Sino-nasal Questionnaire (SNQ) Dixon, CHEST 2009

44 Sinonasal questionnaire (SNQ)

45 Sinonasal questionnaire (SNQ)

46 Study of Asthma and Nasal Steroids (STAN) HL & HL children and adults chronic sinonasal disease Primary Outcome: asthma control

47 Take Home Treat if GERD/sinus disease severe enough to warrant treatment by itself Treating GERD does not have major effect on asthma control Effect of treating chronic sinonasal disease on asthma is not known.

48

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