Berrylin J. Ferguson

Adult chronic rhinosinusitis: definitions, diagnosis, epidemiology, and pathophysiology.

Abstract Chronic rhinosinusitis Chronic rhinosinusitis (CRS) is a term that has been used to describe a number of entities characterized by chronic symptoms of nasal and sinus inflammation or infection. There has been a lack of consensus regarding definitions and treatments because CRS may be a spectrum of diseases with a range of appropriate treatments. The absence of widely accepted definitions for CRS has resulted in a paucity of research directed at understanding its pathophysiology and has hampered efforts to improve treatment. A Task Force was convened by the Sinus and Allergy Health Partnership to summarize much of the current and important information available regarding the prevalence, economic impact, pathophysiology, common inflammatory mediators, and the role of infectious microbes such as bacteria and fungi in CRS. The goal is to establish a standard and usable definition. Through this thorough review of the literature and the expert input from Task Force members, a definition was developed that serves to create a consistent baseline so that many of the currently debated or unanswered questions may be addressed. The new and more-specific Task Force definition is that “ Chronic rhinosinusitis is a group of disorders characterized by inflammation of the mucosa of the nose and paranasal sinuses of at least 12 weeks duration.” Recommended criteria for making the diagnosis of CRS for both clinical care and research were also outlined.

Rhinosinusitis: Establishing definitions for clinical research and patient care

Background There is a need for more research on all forms of rhinosinusitis. Progress in this area has been hampered by a lack of consensus definitions and the limited number of published clinical trials. Objectives To develop consensus definitions for rhinosinusitis and outline strategies useful in clinical trials. Methods Five national societies, The American Academy of Allergy, Asthma and Immunology; The American Academy of Otolaryngic Allergy; The American Academy of Otolaryngology Head and Neck Surgery; The American College of Allergy, Asthma and Immunology; and the American Rhinologic Society formed an expert panel from multiple disciplines. Over two days, the panel developed definitions for rhinosinusitis and outlined strategies for design of clinical trials. Results Committee members agreed to adopt the term “rhinosinusitis” and reached consensus on definitions and strategies for clinical research on acute presumed bacterial rhinosinusitis, chronic rhinosinusitis without polyposis, chronic rhinosinusitis with polyposis, and classic allergic fungal rhinosinusitis. Symptom and objective criteria, measures for monitoring research progress, and use of symptom scoring tools, quality-of-life instruments, radiologic studies, and rhinoscopic assessment were outlined for each condition. Conclusion The recommendations from this conference should improve accuracy of clinical diagnosis and serve as a starting point for design of rhinosinusitis clinical trials.

Eosinophilic Mucin Rhinosinusitis: A Distinct Clinicopathological Entity

Background Allergic fungal sinusitis (AFS) was recognized in 1981. Since 1983, a form of sinusitis histologically similar to AFS except for the absence of fungal hyphae has also been noted. The designation “eosinophilic mucin rhinosinusitis (EMRS)” is proposed. Its relationship to AFS is controversial and problematic.

Fungal Rhinosinusitis: A Categorization and Definitional Schema Addressing Current Controversies

Fungal (rhino‐) sinusitis encompasses a wide spectrum of immune and pathological responses, including invasive, chronic, granulomatous, and allergic disease. However, consensus on terminology, pathogenesis, and optimal management is lacking. The International Society for Human and Animal Mycology convened a working group to attempt consensus on terminology and disease classification.

Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial

IMPORTANCE Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases. OBJECTIVE To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up. INTERVENTIONS Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks. MAIN OUTCOMES AND MEASURES Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0-110; higher scores indicating worse quality of life; minimal clinically important difference ≥8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety. RESULTS Among the 60 patients who were randomized (mean [SD] age, 48.4 years [9.4 years]; 34 men [56.7%]; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was -0.3 (95% CI, -1.0 to 0.4) with placebo and -1.9 (95% CI, -2.5 to -1.2) with dupilumab (LS mean difference, -1.6 [95% CI, -2.4 to -0.7]; P < .001). The LS mean difference between the 2 groups for the Lund-Mackay CT total score was -8.8 (95% CI, -11.1 to -6.6; P < .001). Significant improvements with dupilumab were also observed for the 22-item SinoNasal Outcome Test (LS mean difference between groups, -18.1 [95% CI, -25.6 to -10.6]; P < .001) and sense of smell assessed by UPSIT (LS mean difference, 14.8 [95% CI, 10.9 to 18.7]; P < .001). The most common adverse events were nasopharyngitis (33% in the placebo group vs 47% in the dupilumab group), injection site reactions (7% vs 40%, respectively), and headache (17% vs 20%). CONCLUSIONS AND RELEVANCE Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01920893.

Demonstration of biofilm in human bacterial chronic rhinosinusitis.

Background Bacterial biofilms may explain why some patients with bacterial chronic rhinosinusitis (CRS) improve while on antibiotics but relapse after completion of the antibiotic. In the human host, biofilms exist as a community of bacteria surrounded by a glycocalyx that is adherent to a foreign body or a mucosal surface with impaired host defense. Biofilms generate planktonic, nonadherent bacterial forms that may metastasize infection and generate systemic illness. These planktonic bacteria are susceptible to antibiotics, unlike the adherent biofilm. Methods We reviewed four cases of CRS using transmission electron microscopy (TEM) to assay for typical colony architecture of biofilms. Bacterial communities surrounded by a glycocalyx of inert cellular membrane materials consistent with a biofilm were shown in two patients. Results In the two patients without biofilm, a nonbacterial etiology was discovered (allergic fungal sinusitis) in one and in the other there was scant anaerobic growth on culture and the Gram stain was negative. Culture of the material from the biofilm grew Pseudomonas aeruginosa in both patients. Pseudomonas from the biofilm showed a glycocalyx, not present in Pseudomonas cultured for 72 hours on culture media. Both patients’ symptoms with bacterial biofilms were refractory to culture-directed antibiotics, topical steroids, and nasal lavages. Surgery resulted in cure or significant improvement. Conclusion Biofilms are refractory to antibiotics and often only cured by mechanical debridement. We believe this is the first TEM documentation of bacterial biofilms in CRS in humans.

Mucormycosis of the nose and paranasal sinuses

Rhinocerebral mucormycosis is an invasive fungal infection initiated in the paranasal sinuses that frequently progresses to orbital and brain involvement. If recognized early, involvement is limited to the nasal cavity and paranasal sinuses. Diabetics in poor control are at greatest risk, however, any immunocompromised individual may be infected. The mainstays of therapy are reversal of immunosuppression, systemic amphortericin B, and surgical débridement. Survival has improved dramatically, yet deaths still occur if the infection is not recognized and not treated early in its course or if the source of immunocompromise is not reversible. Several case examples illustrate the clinical course of this unusual, but potentially fatal, fungal infection. Taxonomy, clinical presentation, diagnosis, and management of mucormycosis of the paranasal sinuses are reviewed in detail.

Definitions of fungal rhinosinusitis

Classification of fungal rhinosinusitis is important for the accurate prediction of prognosis and direct therapy. The most important distinction is between invasive and noninvasive fungal rhinosinusitis. Within the invasive division are acute invasive and chronic invasive (granulomatous and nongranulomatous forms) rhinosinusitis. Within the noninvasive division are saprophytic colonization, fungus balls, and allergic fungal rhinosinusitis. This article briefly outlines the definition and management of each of these manifestations.

Geographic variation in allergic fungal rhinosinusitis

Allergic fungal rhinosinusitis (AFRS) has a worldwide distribution. This survey of 20 otolaryngologic practices throughout the United States confirmed a variation in the frequency of AFRS relative to endoscopic sinus procedures performed for all other diagnoses. The highest incidence occurred in Memphis, Tennessee at 23%, with three other southern practices reporting a frequency of at least 10%. In the northern locations the frequency ranged from 0 to 4%. No correlation with mould counts was demonstrated, possibly because of incomplete mould data relative to most of the surgical locations.

Fungus balls of the paranasal sinuses.

Fungus balls of the paranasal sinuses represent a noninvasive manifestation of fungal sinusitis. Patients are immunocompetent but no more allergic than the general population. There is little tissue reaction to the tangled mat of hyphae. If the patient becomes immunocompromised, then the fungus ball may become invasive, as illustrated by an included case report. One hundred sixty-three additional cases of patients with paranasal sinus fungus balls are reviewed from the literature.