Maximum Medical Therapy of Chronic Rhinosinusitis. Riyadh Alhedaithy R5 ENT Resident, Combined KSUF and SB. 30/12/2015

Transcription

1 Maximum Medical Therapy of Chronic Rhinosinusitis Riyadh Alhedaithy R5 ENT Resident, Combined KSUF and SB. 30/12/2015

2 ARTICLE REVIEW

3 INTRODUCTION Chronic rhinosinusitis (CRS) is a common, debilitating, and expensive chronic inflammatory disease. Despite appropriate medical therapy, a subset of patients with CRS will have persistent symptoms and be considered candidates for endoscopic sinus surgery (ESS). ESS is associated with improvements in patient symptoms, quality of life, and is the economically wise choice compared to continued medical therapy alone.

4 INTRODUCTION The decision on when to offer surgery is poorly defined. There is no consensus on what the appropriate or maximal medical therapy (MMT) should be provided to patients prior to considering them candidates for ESS. In order to improve the appropriateness and value of care for CRS, it is important to define appropriate evidencebased indications for ESS.

5 OBJECTIVES To define the MMT criteria used as an indication for ESS in patients with persistent symptoms of CRS.

6 MATERIALS AND METHODS Databases (Jan 2009-Dec 2014): Ovid MEDLINE, EM-BASE, Cochrane Central register of Controlled Trials, Cochrane Database of Systematic Reviews, Science Citation Index, Database of Abstracts and Reviews of Effects, CAB Abstracts, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL)

7 MATERIALS AND METHODS Inclusion criteria: Adult patient population (>18 years of age) with a diagnosis of CRS and received ESS. Exclusion criteria: CF, granulomatous and autoimmune disease, immotile ciliary diseases, acute complications of rhinosinusitis, or other non-crs indications for ESS.

8 MATERIALS AND METHODS Extracted Data: Type of medical therapies Mean duration of use for each therapy Disease characteristics (including polyp status) Diagnostic criteria utilized, Subjective patient outcomes criteria used (if any)

9 MATERIALS AND METHODS Primary outcome: MMT criteria was defined as the medical therapy protocol that must have been trialed and failed prior to being considered a candidate for ESS. Duration of each therapy involved in the MMT criteria was synthesized in a quantitative manner by calculating means with standard deviations and 95% confidence intervals.

10 RESULTS

11 RESULTS 1041 Articles 82 Articles 4 (5%) Not mentioned 3 (4%) CRSsNP 19 (24%) CRSwNP 60 (73%) CRSwNP CRSsNP

12 RESULTS MMT Criteria: None of the studies specified the type of topical corticosteroid therapy used in the MMT criteria. Selection of oral antibiotic was typically described as broad spectrum or culture-directed antibiotic, 4 studies (5%) specified amoxicillin/clavulanate. Prednisone and methylprednisolone were the steroid agents used in the MMT criteria.

13 RESULTS Of the 19 studies that evaluated CRSwNP patients, 14 (74%) included systemic corticosteroids as part of MMT criteria. Of the 3 studies that evaluated CRSsNP patients, All 3 (100%) included systemic corticosteroids in the MMT criteria. Of the 60 studies that evaluated both CRSwNP and CRSsNP patients, 31 (52%) included systemic corticosteroids.

14 Only 26 of the 82 studies reporting the MMT criteria prior to ESS (32%) provided an explicit definition on what was considered failed MMT. RESULTS

15 DISCUSSION In the 82 studies that explicitly reported MMT criteria prior to ESS: The most common MMT criteria were: 8-week course of topical intranasal corticosteroids (91%) and 3-week course of broad-spectrum or culture-directed oral antibiotic (89%). The use of systemic corticosteroids was often included (61%), with the mean duration being a 2-week course. Evidence supports the use of systemic corticosteroids in CRSwNP, but remains less conclusive for CRSsNP.

16 DISCUSSION Majority of studies (65%) considered failure of MMT to involve persistence of CRS symptoms alone, without the need for repeat radiologic imaging As there is currently a lack of a uniform definition of what constitutes a failure of MMT, we feel authors need to include this information in future studies evaluating ESS for CRS.

17 DISCUSSION Several mailed surveys have been performed in an attempt to characterize which therapies are included in MMT

18 DISCUSSION In 2007, a survey study by Dubin et al. was selectively mailed to members of the American Rhinologic Society (ARS) and obtained 308 responses: The most common response indicated that practitioners would always include topical nasal corticosteroids and oral antibiotics in their MMT regimen. Saline irrigations and systemic corticosteroids were usually included.

19 DISCUSSION 67% of respondents considered failure to involve an persistent symptoms with unchanged CT 24% considered a failure to involve persistent abnormal CT despite complete resolution of symptoms.

20 DISCUSSION The most recent survey study mailed questionnaires to all members of ENT-UK ( in 2012: Majority (61%) of the 167 respondents self-identified as rhinologists. Majority of respondents would always include topical corticosteroid sprays (61%, 0-5 months duration) and oral antibiotics (92%, 1-2 weeks duration). Systemic corticosteroids (0-5 days duration) were rarely included.

21 DISCUSSION Clarithromycin and amoxicillin-clavulanate were the most broad-spectrum antibiotics used, in that order. Majority of respondents would also consider routine allergy testing with use of oral antihistamines, if indicated by a positive test.

22 CONCLUSION A minority of studies explicitly report MMT criteria before considering a patient with CRS a candidate for ESS. When reported, the MMT criteria varied widely with the majority of protocols involving a minimum 8-week course of topical intranasal corticosteroids and 3-week course of oral antibiotics. A 2-week course of systemic corticosteroids was also included as part of MMT in more than one-half of the reviewed studies.

23 ARTICLE REVIEW

24 OBJECTIVE Evaluate the effects of oral glucocorticoids and doxycycline on symptoms and objective clinical and biological parameters in patients with CRSwNP.

25 MATERIALS AND METHODS Double-blind, placebo-controlled, multicenter trial. Randomly assigned 47 patients with bilateral nasal polyps to receive either (for 20 days): Methylprednisolone in decreasing doses (32 8 mg once daily) Doxycycline (200 mg on the first day, followed by 100 mg once daily) Placebo

26 MATERIALS AND METHODS Patients were followed for 12 weeks and were assessed for: 1. Symptoms and signs by nasal endoscopy. 2. Nasal peak inspiratory flow. 3. Markers of inflammation in nasal secretions (eosinophilic cationic protein (ECP), IL-5, myeloperoxidase, matrix metalloproteinase 9, and IgE). 4. Peripheral blood level concentrations of (eosinophils, ECP, and soluble IL-5 receptor)

27 MATERIALS AND METHODS

28 MATERIALS AND METHODS

29 RESULTS

30 RESULTS Methylprednisolone Group: Significant reduction of polyp size after one week compared to placebo p= Maximal reduction was after two weeks P<

31 RESULTS Methylprednisolone Group: Polyps began to recur after 2 weeks, but still has significant reduction in polyp score compared with the placebo until month 2.

32 RESULTS Methylprednisolone Group: After 3 months, NO significant effect of methylprednisolone on polyp size was observed compared with placebo and baseline values.

33 RESULTS Doxycycline Group: Significant reduction in polyp size starting at week two compared with placebo and remained significantly reduced upto 3 months after dosing.

34 RESULTS Effect of Methylprednisolone on patients symptoms compared to placebo: Significant decrease in nasal congestion, PND and hyposmia after 1 week until 4 week. Symptoms scores worsened progressively after week 4 and returned to baseline values. No significant effect on rhinorrhea

35 RESULTS Effect of Doxycycline on patients symptoms compared to placebo: Significant reduction in PND at week 2 and significant reduction in rhinorrhea at week 8.

36 RESULTS Anti-inflammatory effects of Methylprednisolone: Significant decrease of eosinophils in blood samples compared with placebo starting at week 1, with a maximal decrease at 2 weeks. Blood eosinophils counts returned to baseline levels at month 1. Rebound eosinophilia (above baseline level) observed levels at month 2 and 3. Significant reduction in IL-5 and IgE at weeks 1,2,and 4. No change in MMP-9 levels in nasal secretion

37 RESULTS Anti-inflammatory effects of Doxycycline : No effect on eosinophils level in blood samples. No effect on IL-5 level in nasal secretions. Significant reduction in IgE at weeks 1,2,and 4. Significant decrease in levels of myeloperoxidase and MMP-9 in nasal secretions.

38 CONCLUSION Methylprednisolone and doxycycline each significantly decreased nasal polyp size compared with placebo. Oral doxycycline causes a long-term reduction in nasal polyp size (lasting for 12 weeks), whereas methylprednisolone causes an initial reduction in polyp size (maximal after week 2) but complete recurrence after 2 months. Treatment of CRSwNP with oral corticosteroids is of limited value unless it is associated with surgery or therapy with intra nasal corticosteroids.