Oral antifungal therapy for chronic rhinosinusitis and its subtypes: a systematic review

Thanasumpun, Thunchai; Batra, Pete S.

doi:10.1002/alr.20088

Cited by 15 publications

(9 citation statements)

References 49 publications

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“…In a recent meta-analysis including 6 randomized controlled trials in CRS patients, evidence was against the effectiveness of either topical or systemic antifungal therapy 31 . However, in a select subgroup of AFRS patients, oral itraconazole and ketoconazole had a more positive response, although most of these studies were uncontrolled 32 . Oral itraconazole yielded positive effects in a subset of asthmatic patients with fungal sensitivity 10 and the majority of asthma or ABPA patients that cannot tolerate itraconazole appear to benefit from either posaconazole or voriconazole 11 .…”

Section: Discussionmentioning

confidence: 97%

Airway surface mycosis in chronic TH2-associated airway disease

Porter

Lim

Maskatia

et al. 2014

Journal of Allergy and Clinical Immunology

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Background Environmental fungi have been linked to T helper type 2 (Th2) cell-related airway inflammation and the Th2-associated chronic airway diseases asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. Objective To determine the frequency of fungus isolation and fungus-specific immunity in Th2-associated and non-associated airway disease patients. Methods Sinus lavage fluid and blood were collected from sinus surgery patients (n=118) including CRS patients with and without nasal polyps and AFRS and non-CRS/non-asthmatic control patients. Asthma status was deteremined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. Peripheral blood mononuclear cells were restimulated with fungal antigens in an enzyme linked immunocell spot (ELISpot) assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared to fungus-specific IgE levels measured from plasma by ELISA. Results Filamentous fungi were significantly more commonly cultured from Th2-associated airway disease subjects (asthma, CRSwNP, or AFRS: n=68) compared to non-Th2-associated control patients (n=31); 74% vs 16% respectively, p<0.001. Both fungus-specific IL-4 ELISpot (n=48) and specific IgE (n=70) data correlated with Th2-associated diseases (sensitivity 73% and specificity 100% vs. 50% and 77%, respectively). Conclusions The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with Th2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients. Clinical Implications Airway fungi may contribute to the expression of sinusitis with nasal polyps and asthma, suggesting that efforts to eradicate fungi from the airways and environments of these patients should be considered.

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Section: Discussionmentioning

confidence: 97%

Airway surface mycosis in chronic TH2-associated airway disease

Porter

Lim

Maskatia

et al. 2014

Journal of Allergy and Clinical Immunology

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“…275,283,284 There is also the potential for inducing fungal resistance due to the low concentrations used in topical formulations. Multiple trials used concentrations of amphotericin B at 100 µg/mL, a concentration that has been documented to not impede fungal growth in vitro compared with true inhibition at 200 and 300 µg/mL.…”

Section: Role Of Fungi In Crsmentioning

confidence: 99%

“…Every systematic review that was limited to RCTs 255,258,275 concluded that there was no beneficial effect from either oral or topical antifungal therapy in CRS. The only potential benefits of oral antifungal therapies were found in a systematic review of observational studies with nonvalidated outcome measures, 283 which carry a risk of bias that makes conclusions impossible. In the Cochrane review, 275 which included both oral and topical antifungals and had strict inclusion criteria, there was no evidence of benefit for topical antifungals.…”

Section: Rhinosinusitis Guideline Evidence-based Statementsmentioning

confidence: 99%

Clinical Practice Guideline (Update): Adult Sinusitis

Rosenfeld

Piccirillo

Chandrasekhar³

et al. 2015

Otolaryngol.--head neck surg.

931

1,303

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The update group made strong recommendations that clinicians (1) should distinguish presumed ABRS from acute rhinosinusitis (ARS) caused by viral upper respiratory infections and noninfectious conditions and (2) should confirm a clinical diagnosis of CRS with objective documentation of sinonasal inflammation, which may be accomplished using anterior rhinoscopy, nasal endoscopy, or computed tomography. The update group made recommendations that clinicians (1) should either offer watchful waiting (without antibiotics) or prescribe initial antibiotic therapy for adults with uncomplicated ABRS; (2) should prescribe amoxicillin with or without clavulanate as ﬁrst-line therapy for 5 to 10 days (if a decision is made to treat ABRS with an antibiotic); (3) should reassess the patient to confirm ABRS, exclude other causes of illness, and detect complications if the patient worsens or fails to improve with the initial management option by 7 days after diagnosis or worsens during the initial management; (4) should distinguish CRS and recurrent ARS from isolated episodes of ABRS and other causes of sinonasal symptoms; (5) should assess the patient with CRS or recurrent ARS for multiple chronic conditions that would modify management, such as asthma, cystic fibrosis, immunocompromised state, and ciliary dyskinesia; (6) should confirm the presence or absence of nasal polyps in a patient with CRS; and (7) should recommend saline nasal irrigation, topical intranasal corticosteroids, or both for symptom relief of CRS. The update group stated as options that clinicians may (1) recommend analgesics, topical intranasal steroids, and/or nasal saline irrigation for symptomatic relief of viral rhinosinusitis; (2) recommend analgesics, topical intranasal steroids, and/or nasal saline irrigation) for symptomatic relief of ABRS; and (3) obtain testing for allergy and immune function in evaluating a patient with CRS or recurrent ARS. The update group made recommendations that clinicians (1) should not obtain radiographic imaging for patients who meet diagnostic criteria for ARS, unless a complication or alternative diagnosis is suspected, and (2) should not prescribe topical or systemic antifungal therapy for patients with CRS.

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“…Given the hepatotoxic effects and potential cardiotoxic effects of the medication and its cost, as well as our inability to predict the small subset who will respond, itraconazole should be utilized sparingly and usually as a last resort. A review of the literature on oral antifungal therapy in the treatment of CRS was performed in 2011 and suggested some potential benefi t from using itraconazole and ketoconazole, but the level of evidence was low [ 21 ].…”

Section: Systemic Antifungalsmentioning

confidence: 99%