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Current conservative treatments in chronic rhinosinusitis with or without nasal polyps : review and analysis of reports on controlled clinical trials

Defense Thèse de privat-docent : Univ. Genève, 2010
Abstract Background: Chronic rhinosinusitis (CRS) implies inflammation of the nose and paranasal sinuses which may or may not have an infectious component and includes nasal polyposis (NP). Chronic rhinosinusitis signs and symptoms persist over 12 weeks and may involve acute exacerbations. It affects around 15% of the population and causes significant reduction in quality of life. The diagnosis is based largely on symptoms with confirmation by nasendoscopy. Computerized tomography scans may confirm mucosal abnormalities in the paranasal sinuses. Various underlying conditions such as infections, anatomical variations, immunodeficiency, aspirin intolerance, mucociliary impairment and allergic fungal rhinosinusitis may present as CRS. Recently found Staphylococcus aureus enterotoxin superantigens, their intracellular long-term persistence, and the production of biofilms may contribute to the pathogenesis of CRS with and without NP. No one single causative factor has been identified that fully accounts for all CRS variations. Various inflammatory processes are involved in the pathogenesis of CRS. Characteristic histomorphological features of CRS without NP are a neutrophilic inflammation and goblet cell hyperplasia, thickening of the basement membrane, limited subepithelial oedema, and prominent fibrosis. Nasal polyps show a predominant eosinophilic inflammation and the destruction of connective tissue. Recent research has focused on cytokines, chemokines, growth factors and metalloproteinases to explain these features, but the aetiology of NP remains largely unclear. Because of the complex pathogenesis of CRS and the multiplicity of factors playing a role in the aetiology, the current management of CRS remains a challenge. The evidence of a few good quality trials in this area suggests that treatment is primarily medical, involving corticosteroids, antibiotics, saline douching, antileukotrienes, and antihistamines and that surgery should be considered for complications, anatomical variations causing local obstruction, allergic fungal disease or for patients who remain very symptomatic despite maximal medical treatment. Objectives: To review the literature on conservative, non-surgical treatments for CRS with or without NP, to evaluate their effectiveness and safety, and to analyse their strength of evidence, recommendations and clinical usefulness in the management of these chronic disease. A succinct update of CRS definition and classification and its pathophysiology is provided. Search strategy: The search included MEDLINE (1950 – 2009) and THE COCHRANE LIBRARY. The date of the last search was June 2009. Selection criteria: Randomised controlled and prospective, clinically-relevant trials in which any non-surgical treatment was evaluated in patients with CRS with or without NP, and after surgery to prevent disease recurrence. The diagnosis of seasonal or perennial allergic rhinitis was an exclusion criterion. Data collection and analysis: Trials were graded for methodological quality and assigned an evidence level based on the modified Sekelle's evidence scale. Each category of articles was then assigned an overall grade for the strength of evidence [I (strongest) to IV (weakest)], a grade for recommendation [A (strongest: consistent level I studies) to D (weakest: level IV evidence or extrapolated recommendation from any level)], and the clinical relevance. Results: Two hundred and eight trials were identified that satisfied the inclusion criteria. The retained studies could be grouped as followed: antibiotics (22 trials), antifungal agents (10 trials), antihistamines (11 trials), antileukotrienes (11 trials), aspirin desensitisation and maintenance (16 trials), bacterial lysate preparations (3 trials), capsaicin (12 trials), corticosteroids (36 trials), cromolyn sodium (5 trials), decongestants (4 trials), furosemide (4 trials), gastroesophageal reflux therapy (4 trials), immunotherapy (4 trials), ipratropium bromide (21 trials), nasal irrigation (20 trials), mucoactive agents (7 trials), phytopreparations (7 trials), homeopathies (2 trials), acupuncture (6 trials) and immunomodulatory agents (3 trials). There is strong evidence [Ib-evidence] that long-term intranasal steroids are beneficial in the treatment of the signs and symptoms of CRS with and without NPs and for the prevention of disease recurrence after surgery. Short-course systemic corticosteroids should only be used as rescue medication in cases of severe NP [Ibevidence]. Strong evidence also exists in favour of systemic long-term macrolides in CRS without [Ib-evidence] and with NPs [III-evidence], long-term saline irrigation's in CRS without NPs [Ib-evidence] and less, of topical capsaicin [Ib/III-evidence] in CRS with and without NPs. Strong evidence has been demonstrated for the long-term systemic antileukotriene [Ib-evidence], and aspirin desensitisation/ maintenance [Ibevidence] treatments in the management of the aspirin exacerbated respiratory disease (asthma, NPs and aspirin or non-steroidal anti-inflammatory drug intolerance); a specific subgroup of CRS with NPs. Antileukotrienes seem evidently prevent NP recurrence after surgery [Ib-evidence]. Short-course systemic treatment of decongestants and mucoactive agents show evidently an improvement of CRS symptoms [Ib-evidence]. Good evidence also exists in favour of long-term courses of topical and systemic antihistamines [Ib-evidence] and intranasal ipratropium bromide [Ib-evidence] in the treatment of rhinorrhea and less, nasal congestion in non-allergic, non-infectious perennial rhinitis (vasomotor rhinitis); a subclass of CRS without NPs. Bacterial lysate preparations show good evidence in the treatment of symptoms and particularly reduce the frequency of acute infectious episodes in CRS without NPs [Ib-evidence]. Studies dealing with olfaction and QoL outcome are rare, demonstrating significant improvement in the treatment groups of AS desensitisation and topical / systemic steroids, and in the treatment groups of long-term macrolides, antileukotrienes, systemic steroids, topical ipratropium bromide and saline irrigations, respectively. An excellent safety profile could be demonstrated for these drug categories. Intranasal antibiotics [Ib(-)-evidence], topical and systemic antifungal agents [Ib(-)-evidence], intranasal cromolyn sodium [Ib(-)-evidence], topical decongestants [Ib(-)-evidence], topical mucoactive agents [Ib(-)-evidence], homeopathy [Ib(-)- evidence], and acupuncture [Ib(-)-evidence] cannot be recommended due to evidenced negative outcome in randomized trials or bad safety profile. Due to the lack of randomized, placebo controlled studies or unclear outcome, the other treatment categories like topical furosemide, gastroesophageal reflux therapy, immunotherapy, topical and systemic phytopreparations and immunomodulators cannot be retained as first-choice therapy options or are not clinically relevant in the management of CRS with or without NPs. Conclusions: The often imprecise definitions of CRS, complex pathogenesis and uncertainties regarding the precise role played by the involved processes and a lack of well designed trials render an analysis of the retained data difficult. The initial management of CRS is medically with endoscopic sinus surgery reserved for refractory CRS. First-choice drug treatment in CRS with or without NPs comprises long-term topical steroids and short-term systemic corticosteroids for severe disease. Intranasal steroids also prevent NP recurrences after surgery. Long-term systemic, low-dose macrolides with their anti-inflammatory, immunomodulatory, anti-mucous and less, antimicrobial actions seem to be a good alternative treatment modality in steroid non-responders. Long-term saline irrigation's may be used singly or as adjunct therapy. Antileukotriene and aspirin desensitisation / maintenance therapy can be considered for aspirin exacerbated respiratory disease. Promising antiinflammatory agents include topical capsaicin and systemic bacterial lysate preparations. Topical and systemic antihistamines and intranasal ipratropium bromide demonstrated improvement in the treatment of rhinorrhea and less, nasal congestion in vasomotor rhinitis; a specific subclass of non-allergic, non-infectious perennial rhinitis. New approaches are currently evolving, specifically targeting eosinophilic recruitment (chemokine receptor 3, eotaxins) and inflammation (interleukin-4, -5, -13), immunoglobulin E, or tissue remodelling by reducing the activity of metalloproteinases. Better uniform definitions and classifications of CRS with and without NPs and further well conducted trials in clearly defined patient groups are needed to progress in the management of this chronic and complex inflammatory disease.
Keywords Chronic rhinosinusitisNasal polyps
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Deposited on : 2010-10-18

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