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Objectives: (1) To describe the existing literature on procalcitonin (PCT) as a biomarker in patients with acute rhinosinusitis (ARS), (2) to analyze outcomes in ARS patients who were treated with PCT-guided therapy versus traditional management, and (3) to compare PCT to other biomarkers used in diagnosis of bacterial ARS. Data Sources: PubMed and Embase. Review Methods: A systematic search in the PubMed and Embase databases was performed to identify studies related to PCT as a biomarker in ARS. After critical appraisal of validity by 2 authors, 6 studies with a total of 313 patients were selected for data extraction and analysis. We identified 2 randomized control trials (RCTs) of PCT-based guidelines for antibiotic management of ARS in outpatient settings and 4 observational studies that compared PCT to other biomarkers in patients with ARS., Results: The 2 RCTs demonstrated a reduction (41.6% in 1 study and 71% in the other) in antibiotic prescription rate in the PCT-guided group versus the control group with no change in the number of days with impaired activity due to illness (9.0 vs 9.0 days [ P = .96]; 8.1 vs 8.2 days [95% confidence interval -0.7 to 0.7]), number of days of work missed, and percentage of patients with persistent symptoms at 28 days. In the observational cohort studies, PCT did not consistently correlate with C-reactive protein, body temperature, and/or white blood cell counts., Conclusions: The limited existing literature on the role of PCT in diagnosis, management, and prediction of clinical outcomes in ARS suggests that PCT-based guidelines for antibiotic prescription are a safe and effective method of minimizing unnecessary antibiotic use.

Chronic rhinosinusitis (CRS) affects 12.5% of the U.S., Population: CRS can be divided into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps. Some individuals with CRSwNP do not respond to standard-of-care medical and surgical management. For these individuals, targeted biologic agents are emerging as an important therapeutic alternative. In this review, we described the most-relevant studies that addressed the use of anti-immunoglobulin E (omalizumab), anti-interleukin 5 (mepolizumab and reslizumab), and anti-interleukin 4/interleukin 13 (dupilumab) monoclonal antibodies for the treatment of CRSwNP. In addition, we discussed the importance of some of these clinical trials in identifying new CRS endotypes based on distinct inflammatory profiles.

Background: Chronic rhinosinusitis (CRS) is a common disease in the United States. There are a significant number of patients with CRS who are refractory to standard medical and surgical therapy. Many of these patients also have comorbid allergic rhinitis (AR) and asthma, although the underlying pathophysiology that connects these three conditions remains unclear., Objective: The goal of this article is to review the relationships among CRS, AR and asthma., Methods: Scientific literature that addresses the prevalence of AR and asthma in CRS populations, the effect of AR and asthma on CRS disease severity, and whether treatment of AR and asthma can affect CRS outcomes was reviewed., Results: The literature supports the relationship between AR and CRS, but there is no direct evidence of causality the between the two conditions. There is a high prevalence of CRS in patients with asthma and the presence of CRS is associated with worse asthma outcomes. There is weak evidence that treatment of CRS may improve asthma outcomes. Targeting type 2 inflammation via biologics is being investigated in the treatment of asthma and CRS., Conclusion: AR, asthma, and CRS are closed related and understanding the associations among these comorbid diseases will have significant clinical implication.

Chronic rhinosinusitis (CRS) is estimated to affect over 35 million people. However, not all patients with the diagnosis respond to standard medical and surgical treatments. Although there are a variety of reasons a patient may be refractory to therapy, one possible etiology is the presence of an underlying immunodeficiency. This review will focus on the description, recognition, and treatment of several antibody deficiencies associated with CRS, including common variable immunodeficiency (CVID), selective IgA deficiency, IgG subclass deficiency, and specific antibody deficiency (SAD). The diagnosis of antibody deficiency in patients with CRS is important because of the large clinical implications it can have on sinus disease management. CVID is treated with immunoglobulin replacement, whereas SAD may be managed symptomatically and sometimes with prophylactic antibiotics and/or immunoglobulin replacement.

Nasal polyps occur in 1-4% of the population, usually occurring in the setting of an underlying local or systemic disease. The most common associated condition is chronic rhinosinusitis (CRS). A high prevalence of nasal polyps is also seen in allergic fungal rhinosinusitis, aspirin-exacerbated respiratory disease, Churg-Strauss syndrome, and cystic fibrosis. In the setting of CRS, nasal polyps are not likely to be cured by either medical or surgical therapy; however, control is generally attainable. The best medical evidence supports the use of intranasal corticosteroids for maintenance therapy and short courses of oral corticosteroids for exacerbations. The evidence for short- and long-term antibiotics is much less robust. For patients with symptomatic nasal polyposis nonresponsive to medical therapies, functional endoscopic sinus surgery provides an adjunctive therapeutic option.

Chronic rhinosinusitis (CRS) is the second most common chronic medical condition in the United States. It represents a group of disorders characterized by inflammation of the nasal mucosa and paranasal sinuses of at least 12 weeks duration. CRS with or without nasal polyps is defined as inflammation of the nose characterized by two or more symptoms, one of which should be either nasal blockage, obstruction, congestion, or nasal discharge (anterior/posterior nasal drip); with or without facial pain/pressure; and/or with or without reduction or loss of smell. Symptomatology should be supported by obvious disease evident in either nasal endoscopy or computed tomography imaging. Although CRS is not likely to be cured by either medical or surgical therapy, it can generally be controlled. Best medical evidence supports maintenance therapy with intranasal corticosteroids and saline irrigation. For exacerbations, short to intermediate courses of antibiotics (up to 4-weeks) with or without oral corticosteroids are recommended. For patients with difficult-to-treat CRS, functional endoscopic sinus surgery provides an adjunctive therapeutic option.

Chronic rhinosinusitis (CRS) is the second most common chronic medical condition in the United States. It represents a group of disorders characterized by inflammation of the nasal mucosa and paranasal sinuses of at least 12 weeks duration. CRS with or without nasal polyps is defined as inflammation of the nose characterized by two or more symptoms, one of which should be either nasal blockage, obstruction, congestion, or nasal discharge (anterior/posterior nasal drip); with or without facial pain/pressure; and/or with or without reduction or loss of smell. Symptomatology should be supported by obvious disease evident in either nasal endoscopy or computed tomography imaging. Although CRS is not likely to be cured by either medical or surgical therapy, it can generally be controlled. Best medical evidence supports maintenance therapy with intranasal corticosteroids and saline irrigation. For exacerbations, short to intermediate courses of antibiotics (up to 4-weeks) with or without oral corticosteroids are recommended. For patients with difficult-to-treat CRS, functional endoscopic sinus surgery provides an adjunctive therapeutic option.

IgE hypersensitivity is important to the pathogenesis of allergic diseases and the development and persistence of airway inflammation. Allergic immunomodulation encompasses various therapies that attempt to suppress or modify the immune mechanisms responsible for IgE-mediated disease. These include allergy immunotherapy (AIT) in the forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), as well as the emergence of biological agents, such as anti-IgE, for allergic respiratory disease. Clinical evidence strongly supports the efficacy and safety of AIT for the treatment of allergic rhinitis, allergic conjunctivitis, and allergic asthma, but for chronic rhinosinusitis evidence is lacking. In allergic rhinitis, the decision to initiate AIT depends on the degree to which symptoms can be reduced by avoidance and medication, the amount and type of medication required to control symptoms, the adverse effects of medication, the severity and duration of symptoms, and their effect on quality of life. AIT has the potential to produce sustained long-lasting immune modulation and possibly avoid or reduce lifelong requirements for medical therapy. Although SLIT is currently being evaluated, SCIT remains the preferred form of AIT in the United States because of robust efficacy data, availability of allergen extracts, and current Food and Drug Administration approval. However, SLIT holds the potential for greater patient safety and convenience. Other immunomodulators such as anti-IgE also hold promise, but require further investigation.

The contributing role of specific IgE sensitization in the pathophysiology of sinonasal diseases including rhinitis, chronic rhinosinusitis (CRS), and nasal polyps is explored. Although it is estimated that sensitization to environmental allergens is present in 75% of patients with rhinitis, the role of allergy in CRS and nasal polyps is less certain. However, when atopy is present in the setting of nasal polyps, it is associated with worse quality of life and a higher incidence of asthma. Several theories have been put forth whereby inhalant aeroallergen exposure could drive the inflammatory response that occurs both in the nose and in the sinuses. Tools available to determine the presence of allergic sensitization include skin tests for immediate hypersensitivity, in vitro testing for allergen-specific IgE, and nasal allergen provocation testing. Whether by skin testing or in vitro testing, the identification of specific IgE requires clinical correlation with the history and physical exam.

Nasal polyps occur in 1-4% of the population, usually occurring in the setting of an underlying local or systemic disease. The most common associated condition is chronic rhinosinusitis (CRS). A high prevalence of nasal polyps is also seen in allergic fungal rhinosinusitis, aspirin-exacerbated respiratory disease, Churg-Strauss syndrome, and cystic fibrosis. In the setting of CRS, nasal polyps are not likely to be cured by either medical or surgical therapy; however, control is generally attainable. The best medical evidence supports the use of intranasal corticosteroids for maintenance therapy and short courses of oral corticosteroids for exacerbations. The evidence for short- and long-term antibiotics is much less robust. For patients with symptomatic nasal polyposis nonresponsive to medical therapies, functional endoscopic sinus surgery provides an adjunctive therapeutic option.

The contributing role of specific IgE sensitization in the pathophysiology of sinonasal diseases including rhinitis, chronic rhinosinusitis (CRS), and nasal polyps is explored. Although it is estimated that sensitization to environmental allergens is present in 75% of patients with rhinitis, the role of allergy in CRS and nasal polyps is less certain. However, when atopy is present in the setting of nasal polyps, it is associated with worse quality of life and a higher incidence of asthma. Several theories have been put forth whereby inhalant aeroallergen exposure could drive the inflammatory response that occurs both in the nose and in the sinuses. Tools available to determine the presence of allergic sensitization include skin tests for immediate hypersensitivity, in vitro testing for allergen-specific IgE, and nasal allergen provocation testing. Whether by skin testing or in vitro testing, the identification of specific IgE requires clinical correlation with the history and physical exam.

IgE hypersensitivity is important to the pathogenesis of allergic diseases and the development and persistence of airway inflammation. Allergic immunomodulation encompasses various therapies that attempt to suppress or modify the immune mechanisms responsible for IgE-mediated disease. These include allergy immunotherapy (AIT) in the forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), as well as the emergence of biological agents, such as anti-IgE, for allergic respiratory disease. Clinical evidence strongly supports the efficacy and safety of AIT for the treatment of allergic rhinitis, allergic conjunctivitis, and allergic asthma, but for chronic rhinosinusitis evidence is lacking. In allergic rhinitis, the decision to initiate AIT depends on the degree to which symptoms can be reduced by avoidance and medication, the amount and type of medication required to control symptoms, the adverse effects of medication, the severity and duration of symptoms, and their effect on quality of life. AIT has the potential to produce sustained long-lasting immune modulation and possibly avoid or reduce lifelong requirements for medical therapy. Although SLIT is currently being evaluated, SCIT remains the preferred form of AIT in the United States because of robust efficacy data, availability of allergen extracts, and current Food and Drug Administration approval. However, SLIT holds the potential for greater patient safety and convenience. Other immunomodulators such as anti-IgE also hold promise, but require further investigation.

Background: A subset of patients with chronic rhinosinusitis (CRS) has refractory disease. The risk factors for refractory CRS include atopy, a disrupted mucociliary transport system, medical conditions affecting the sinonasal tract mucosa, and immunodeficiency., Methods: We review four primary immunodeficiencies reported in individuals with CRS: common variable immune deficiency (CVID), selective IgA deficiency, IgG subclass deficiency, and specific antibody deficiency. We also review treatment options for individuals with both CRS and a concomitant immune defect., Results: There is a high prevalence of CRS in individuals with CVID and selective IgA deficiency. While many reports describe IgG subclass deficiency in individuals with CRS, the clinical relevance of this is unclear. Specific antibody deficiency may play a more significant role in the pathogenesis of refractory CRS., Conclusion: Screening for a primary immunodeficiency should be part of the diagnostic workup of refractory CRS, as its identification may allow for more effective long-term therapeutic options.

Background: Chronic rhinosinusitis (CRS) is a common inflammatory condition of the paranasal sinuses and nasal passages. CRS with nasal polyp (CRSwNP) is a subtype of CRS, and the pathogenesis of CRSwNP remains largely unclear., Methods: This article reviews the literature regarding the pathophysiology of CRSwNP., Results: Evidence suggests that altered innate immunity, adaptive immunity, tissue remodeling, and/or effects of microorganisms may play a role in the development of CRSwNP. Aberrant arachidonic acid metabolism may also contribute to the pathogenesis of CRSwNP in patients with aspirin-exacerbated respiratory disease., Conclusion: There have been significant advances in the understanding pathophysiology of CRSwNP. Additional research is needed to elucidate these mechanisms and to determine their relative importance in the pathogenesis of CRSwNP.

Background: Specific antibody deficiency may predispose patients to recurrent respiratory tract infections. There is limited literature assessing specific antibody deficiency in chronic rhinosinusitis (CRS). This study evaluated the role of specific antibody deficiency in patients with CRS who have failed medical therapy., Methods: We performed a retrospective chart review of patients with CRS who underwent functional endoscopic sinus surgery and had prior assessment for humoral immunodeficiency. Each patient's record was reviewed for serum quantitative immunoglobulin G (IgG) and IgA and anti-Streptococcus pneumoniae antibody titers measured at baseline and 6 weeks postvaccination with the 23-valent unconjugated pneumococcal vaccine. Clinical characteristics, including asthma, atopy, and nasal polyps, were recorded., Results: Of the 129 CRS patients who met inclusion criteria, 93 (72%) had low baseline antipneumococcal titers. Fifteen (11.6%) patients were diagnosed with specific antibody deficiency based on an inadequate response to the pneumococcal polysaccharide vaccine. The group of patients with specific antibody deficiency had significantly lower serum IgA levels when compared with those patients with normal preimmunization titers (138 ± 67.3 versus 330 ± 356; p < 0.05). Patients with specific antibody deficiency had a significantly lower number of preimmunization protective antipneumococcal titers when compared with vaccine responders (1.41 versus 2.72; p < 0.0005)., Conclusion: This retrospective study indicates that patients with medically refractory CRS may have a high prevalence of low preimmunization antipneumococcal titers and specific antibody deficiency. Furthermore, lower serum IgA levels identified in these specific antibody deficiency patients suggests that a prospective study to further characterize this relationship is warranted.

Background: There is a clinical association between asthma and chronic rhinosinusitis (CRS). This study was designed to determine whether severity of coexistent asthma affects the clinical presentation of CRS., Methods: Cross-sectional analysis was performed of prospectively collected data in 187 patients with CRS who were evaluated in a large, tertiary academic nasal and sinus center. Patients were stratified into three groups based on asthma status using National Institutes of Health criteria: (1) nonasthmatic, (2) intermittent/mild asthma, (3) or moderate/severe asthma., Results: Mean Lund-Mackay scores were 9.7, 11.6, and 15.6, respectively. ANOVA testing with post-hoc Tukey analysis revealed that Lund-MacKay scores were significantly greater in group 3 than either group 1 (p < 0.05) or group 2 (p < 0.01). The prevalence of allergic sensitization was 72.4, 82.8, and 100% in groups 1, 2, and 3, respectively (p = 0.03). The prevalence of nasal polyposis was 31.4% in group 1, 48.3% in group 2, and 94.4% in group 3 (p < 0.0001). No differences were observed regarding demographic factors or the incidence of the triad of aspirin sensitivity, asthma, and nasal polyposis among those with different severities of asthma., Conclusion: Increasing severity of asthma is associated with advancing radiological severity of CRS and a greater prevalence of allergic sensitization and nasal polyposis. This large adult series shows that asthma severity may have a significant correlation with the presentation of CRS. This study adds to the growing support for the unified airway theory.