A Review of the Current Guidelines for the Diagnosis and Treatment of Adult Rhinosinusitis

1. A Review of the Current Guidelines for the Diagnosis and Treatment of Adult Rhinosinusitis Jamie Tibbo, PGY-5 Department of Otolaryngology University of Ottawa September 3, 2008

2. Objectives • To review the recent clinical guidelines for the management of adult sinusitis (AAO-HNS). • To compare the AAO-HNS guidelines with the European (EPOS) Guidelines. • To summarize the clinical guidelines so that clinicians can have an accurate and concise overview. • After reviewing the guidelines, to gain a sense of consensus among the department members on management of sinusitis.

4. Original Article: European Academy of Allerology & Clinical Immunology (EAACI)

5. Rhinosinusitis Background • Sinusitis affects 1 in 7 adults in the U.S. • 31 million diagnosed per year • Estimated health care cost $3 - 5.8 Billion • Mainly due to ambulatory and ER services • 500 000 sinus surgeries performed • > 20% of antibiotic Rx are for sinusitis • 5th most common Dx which Abx prescribed • 73 million days restricted activity/year

6. Rhinosinusitis Background • Chronic Rhinosinusitis (CRS) affects 14-16% of U.S. population • Peak age of 20-59 yrs • More common in females • Accompanied by nasal polyps in 19-36%

7. Classification • Duration: • Acute (<4weeks) • Subacute (4-12 wks) • Chronic (>12 weeks)-with or w/out acute exacerbations • Symptom Pattern/Etiology: • Acute Bacterial Rhinosinusitis (ABRS) • Viral Rhinosinusitis (VRS) • 4 or more episodes ABRS = Recurrent Acute Rhinosinusitis

8. The AAO-HNS Guidelines • Focus on diagnosis and management of ABRS • Primary Purposes: • Improve diagnostic accuracy for Adult Rhinosinusitis • Reduce inappropriate use of radiographic imaging • Promote appropriate use of ancillary tests (eg. CT, FNL, allergy testing) • Based on literature up to January 2007

9. Interventions Considered in Rhinosinusitis Guideline Development

10. AAO-HNS Guidelines:Quality for Grades of Evidence

11. EPOS: Categories of Evidence • Ia: meta-analysis of RCTS, RCTs • Ib: at least 1x RCT • IIa: at least 1x controlled study w/out randomization • III: non-experimental descriptive studies • IV: expert opinion

12. Definitions:Guideline for Evidence-Based Statements

13. EPOS: Strength of Recommendations • A = directly based on category I evidence • B = directly based on category II evidence, or extrapolated from category I evidence • C = directly based on category III evidence or extrapolated from category I or II evidence • D = directly based on category IV evidence or extrapolated from category I, II or III evidence

14. Outline of Evidence-Based Statements

15. Statement 1a.Diagnosis of Acute Rhinosinusitis • Clinicians should distinguish presumed acute bacterial rhinosinusitis (ABRS) from acute rhinosinusitis (ARS) caused by viral upper respiratory infections and non-infectious conditions. • Level of Evidence = A • Strong Recommendation

16. Definitions: Acute Rhinosinusitis

17. EPOS Definitions • EPOS: Definition of Rhinosinusitis • inflammation of nose and paranasal sinuses with 2 or more symptoms, one of which should be either nasal obstruction or nasal discharge, +/- Facial pain, +/- reduction in smell • EPOS: Definition of Acute Rhinosinusitis • Symptoms lasting <12 wks • Subdivided: • Acute Viral RS: symptoms < 10 days • Acute Non-Viral RS: increase of symptoms after five days or persistent symptoms after 10 days with < 12 wks duration

18. Transition from Viral to Bacterial Infection • Up to 2% of VRS complicated by bacterial infection • Day 1-10: Can be difficult to distinguish VRS from ABRS. • “Double Sickening” Pattern • Pt initially gets better then gets worse • Consistent with ABRS

19. Cardinal Symptoms of Acute Rhinosinusitis • Fever (not included) • Present in some patients with VRS • Does not predict bacterial infection as an isolated diagnostic criterion • 50% sensitivity and specificity for ABRS • Therefore was not included as a cardinal sign • Important in decision to treat with antibiotics • AAO-HNS: >38.3 °C • EPOS: >38.0 °C • Sputum colorshould not be used to assess the need for antibiotic therapy • color is related to presence of neutrophils, not bacteria.

20. 2005 Canadian Rhinosinusitis Review Paper Wright & Frankel Based on: American Academy of Otolaryngology- Head and Neck Surgery task force criteria

21. Statement 1b.Radiographic Imaging and Acute Rhinosinusitis • Clinicians should not obtain radiographic imaging for patients who meet diagnostic criteria for acute rhinosinusitis, unless a complication or alternative diagnosis is suspected. • Recommendation against based on diagnostic studies with minor limitations and a preponderance of benefit over harm.

22. Radiographic Imaging and Acute Rhinosinusitis • Lau et al. 1999 • Meta-analysis of 6 studies showed that sinus radiography has moderate sensitivity (76%) and specificity (79%) compared with sinus puncture in diagnosing ABRS. • Engels et al. 2000 • Prospective series looking at antral puncture results as the gold standard. Showed complete opacification, and airfluid level, or both, on plain film radiography to have a sensitivity of 73% and specificity of 80% for acute rhinosinusitis. • Sensitivity and specificity for ethmoid and frontal sinusitis are lower on plain film radiography. • Gwaltney et al. 1994 • Sinus involvement is common in documented viral URIs, making it impossible to distinguish ABRS from VRS based solely on imaging studies.

23. Radiographic Imaging and Acute Rhinosinusitis • Radiographic imaging may be obtained: • When a complication of ARS or an alternative diagnosis is suspected. • When a pt has modifying factors or co-morbidities that predispose to complications • i.e. diabetes, immune compromised state, past history of facial trauma or surgery • Limitations of CT: • Radiation may be 10x that of plain films • lack of specificity for bacterial infection

24. Statement 2.Symptomatic Relief of Viral Rhinosinusitis (VRS) • Clinicians may prescribe symptomatic relief in managing VRS. • Option based on randomized trials with limitations and cohort studies with an unclear balance of benefit and harm that varies by patient.

25. Symptomatic Relief of Viral Rhinosinusitis (VRS) • Symptomatic Management: • Anti-pyretics • Analgesics • Decongestants (topical more effective systemic) • Steroids • Systemic- not shown effective • Topical- weak evidence for effectiveness • Anti-histamines • No proven effect on outcome • Nasal Irrigation- not mentioned

26. Statement 3a.Pain Assessment of Acute Bacterial Rhinosinusitis • The management of ABRS should include an assessment of pain. The clinician should recommend analgesic treatment based on the severity of pain. • Strong recommendation based on randomized controlled trials of general pain relief in non-ABRS populations with a preponderance of benefit over harm.

27. Score > 5 shown To adversely Affect QOL EPOS: Disease Symptom Score • Define disease severity: • Mild: VAS 0-3 • Moderate: VAS 4-7 • Severe: VAS 8-10

28. Statement 3b.Symptomatic Relief of Acute Bacterial Rhinosinusitis • Clinicians may prescribe symptomatic relief in managing ABRS. • Option based on randomized trials with heterogeneous populations, diagnostic criteria, and outcome measures with a balance of benefit and harm.

29. Grade D recommend. [Level Ib (-) #] Grade A recommend. [Level Ib] Grade D recommend. [Level Ib (-) #] No evidence or recommendations Symptomatic Relief of Acute Bacterial Rhinosinusitis • Adjunctive treatments for rhinosinusitis that may aid in symptomatic relief include • decongestants (-adrenergic) • corticosteroids (topical?) • saline irrigation • Mucolytics • **None of these products have been specifically approved by the FDA for use in acute rhinosinusitis (as of February 2007), and few have data from controlled clinical studies supporting this use. EPOS Guidelines: EPOS Guidelines recommend Oral Corticosteroid: Grade A, Level Ib

30. Symptomatic Relief of Acute Bacterial Rhinosinusitis • Topical Corticosteroids • Most clinical trials for ABRS are industry supported and include studies of mometasone, fluticasone,flunisolide,and beclomethasone. • Meltzer et al. 2000 • Showed significantly reduced mean symptom scores during days 2 to 15 of treatment for patients with non-severe ABRS who received mometasone furoate (Nasonex) nasal spray twice daily compared with patients who received amoxicillin or placebo. • Dolor et al. 2001 • Patients with ABRS and a history of recurrent or chronic sinusitis benefited from adding fluticasone propionate (Flonase) nasal spray to cefuroxime axetil twice daily for 10 days, and xylometazoline hydrochloride (Otrivin) for 3 days. • No controlled clinical trials of systemic steroids for treating ABRS have been published

31. Symptomatic Relief of Acute Bacterial Rhinosinusitis • Nasal Saline Irrigation • may improve quality of life, decrease symptoms, and decrease medication use for ABRS, particularly in patients with frequent sinusitis. • Buffered hypertonic (3%-5%) saline irrigation showed a modest benefit for acute rhinosinusitis in 2 clinical trials (Inanli et al. 2002; Rabago et al. 2002). • Compared with isotonic saline, hypertonic saline may have a superior antiinflammatory effect and better ability to thin mucus and transiently improve mucociliary clearance.79-81 • RCT of patients with the common cold and acute rhinosinusitis, found no difference in outcomes for hypertonic saline, normal saline, or observation (Adam et al. 1998)

32. Symptomatic Relief of Acute Bacterial Rhinosinusitis • Topical & Systemic Decongestants • No RCTs that specifically study the efficacy of decongestants for ABRS • but two small studies have shown that xylometazoline nasal spray reduces congestion of sinus and nasal mucosa on imaging studies 51,66and is superior to a single orally administered dose of pseudoephedrine.66 • It just makes sense

33. Symptomatic Relief of Acute Bacterial Rhinosinusitis • Antihistamines • No role in the symptomatic relief of ABRS in non-atopic patients. • No studies support their use in an infectious setting, and antihistamines may worsen congestion by drying the nasal mucosa. • Braun et al. 1997 • RCT in allergic patients with ABRS showed reduced sneezing and nasal congestion for loratadine (Claritin) vs. placebo when used as an adjunct to antibiotics and oral corticosteroids.89 • Antihistamine therapy can be considered in patients with ABRS whose symptoms suggestive of a significant allergic component. • EPOS Guidelines: • recommend oral antihistamines in allergic patients only: Grade B, Level Ib

34. Statement 4.Watchful Waiting for Acute Bacterial Rhinosinusitis • Observation without use of antibiotics is an option for selected adults with uncomplicated ABRS who have mild illness (mild pain and temperature <38.3°C or 101°F) and assurance of follow-up. • Option based on double-blind randomized controlled trials with heterogeneity in diagnostic criteria and illness severity, and a relative balance of benefit and risk.

35. EPOS Guidelines: • Abx started after 5 days of symptoms or in severe cases • T >38 °C significant Observation for Non-Severe ABRS • Abx deferred in selected patients for up to 7 days after diagnosis and limiting management to symptomatic relief. • Previous guidelines stated 7 days after symptoms began • Patients with non-severe illness (mild pain, temperature < 38.3°C ) at presentation can be observed if follow-up is assured, and a system is in place that permits re-evaluation if the illness persists or worsens. • Antibiotics are started if: • the patient’s condition fails to improve by 7 days or • worsens at any time • Patients with severe illness(moderate to severe pain or temperature 38.3°C or 101°F) are treated initially with oral antibiotics. • Should consider general health and comorbid conditions.

36. Score > 5 shown To adversely Affect QOL EPOS: Disease Symptom Score • Define disease severity: • Mild: VAS 0-3 • Moderate: VAS 4-7 • Severe: VAS 8-10

37. Observation for Non-Severe ABRS • High percentage of spontaneous improvement when patients receive placebo in RCTs, plus only a modest benefit from antibiotics • Three meta-analyses (Ip et al. 2005; de Ferrant et al., 1998; Williams et al., 2003)compared antibiotic vs. placebo for acute rhinosinusitis • spontaneous improvement in 62% to 69% of patients after 7 to 14 days • spontaneous cure in 19% to 39%, and an absolute increase of 13% to 19% in favorable outcomes when antibiotics are used. • Results limited by restricted subsets of included articles and failure to include several RCTs that were subsequently published.

38. Placebo vs. Antibiotics in ABRS • Systematic review of MEDLINE and the Cochrane Trial Registry through January 2007 revealed 13 double-blind, placebo-controlled, randomized trials.

39. Double-Blind RCT s of Abx vs. Placebo

40. Meta-analysis of Abx. Vs. Placebo

41. NNT = 7 patients NNH = 9 patients Meta-analysis of Abx. Vs. Placebo • Clinical outcomes: • “Cured” = absence or near-absence of all presenting signs and symptoms of ARS • “Improved” = partial or complete relief of presenting signs and symptoms • By 3 to 5 days after starting treatment: • less than one third of patients receiving placebo are cured or improved, and the impact of antibiotics on outcomes is not significant. • By 7 to 12 days after starting treatment: • 35% of patients are cured • 73% are improved (or cured) • with an absolute increase in positive outcomes (rate difference, RD) of 14% to 15% when antibiotics are given (number needed to treat [NNT] of about 7 patients. • By 14 to 15 days after starting treatment: • cure rate in the placebo group is 45% and the impact of antibiotics becomes nonsignificant • Adverse events • occur more often with antibiotics than placebo with about one additional event for every 9 patients treated (number needed to harm, or NNH). • Most adverse events are gastrointestinal, but other reported side effects include skin rash, vaginal discharge, headache, dizziness, and fatigue.

42. Applying Clinical Trial Data to Patients • Nearly all placebo-controlled trials recruited subjects from a primary care setting • results may not apply to patients with more severe or persistent symptoms seen by specialists or emergency physicians • Evidence-base for severe illness limited

43. Time-related Outcomes in RCTs

44. Summary of Recommendation • Recommend limiting observation of ABRS to patients with non-severe illness at presentation, with assurance of follow-up so that antibiotics can be started if patients fail to improve by 7 days after diagnosis or have worsening at any time. • Should it be 7 days after onset of symptoms? • Also consider patient preference

45. Statement 5. Choice of Antibiotic for ABRS • If a decision is made to treat ABRS with antibiotics, the clinician should prescribe amoxicillin as first-line therapy for most adults. • Recommendation based on randomized controlled trials with heterogeneity and non-inferiority design with a preponderance of benefit over harm.

46. Choice of Antibiotic for ABRS • Justification for amoxicillin as first-line therapy for most patients with ABRS relates to: • safety • efficacy • low cost • narrow microbiologic spectrum • Dozens of RCTs assessed efficacy of antibiotics in patients with ABRS • most trials either funded by pharmaceutical companies or conducted by authors associated with the pharmaceutical industry

47. Choice of Antibiotic for ABRS • Review by Ip et. al. 2005 • no differences in 11 comparative meta-analyses • found small decrease in failure rates for amoxicillin-clavulanate vs cephalosporins (NNT 30). • Amoxicillin increases rates of clinical cure or improvement compared with placebo (Table 9) • evidence is weak

48. Combined effect is significant Clinical Efficacy of Amoxil vs. Placebo

49. Choice of Antibiotic for ABRS • For penicillin-allergic patients, folate inhibitors (trimethoprim-sulfamethoxazole) are a cost-effective alternative • Macrolides may also be used for patients with penicillin allergy

50. Choice of Antibiotic for ABRS Wright & Frankel