Dupilumab provides early and durable improvement of symptoms in patients with chronic rhinosinusitis with nasal polyps.

Objectives: To evaluate within-patient symptom improvement in the dupilumab SINUS-24/-52 studies in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) (NCT02912468/NCT02898454). Methods: Patients received dupilumab 300 mg or placebo every 2 weeks for 24 (SINUS-24) or 52 weeks (SINUS-52) on background intranasal corticosteroids. Patients daily reported symptoms of nasal congestion (NC), loss of smell (LoS) and rhinorrhoea on a scale of 0-3 (0 - no symptoms, 1 - mild, 2 - moderate, 3 - severe symptoms). The proportions of patients with moderate-to-severe symptoms (score ≥ 2) at baseline who improved to no-to-mild symptoms (score ≤ 1) were determined at Weeks 2, 24 (pooled studies) and 52 (SINUS-52). Subgroups with prior sinonasal surgery and coexisting asthma were analysed. Results: At baseline in the pooled intention-to-treat population (n = 724), the proportions of patients with scores ≥ 2 for NC, LoS and rhinorrhoea were 87, 94 and 64%, respectively. Significantly, more patients achieved scores ≤ 1 (no/mild symptoms) with dupilumab vs placebo for each symptom at each time point {Week 2 NC 12% vs 2% [odds ratio 8.9 (95% CI 3.0-26.3)], LoS 5% vs 1% [4.6 (1.3-16.8)], rhinorrhoea 9% vs 2% [4.8 (1.5-15.4)], all P < 0.05; Week 24 NC 54% vs 14% [8.7 (5.6-13.5)], LoS 43% vs 6% [14.4 (7.9-26.0)], rhinorrhoea 53% vs 16% [6.6 (4.1-10.9)], all P < 0.0001}. Results were similar in subgroups with prior surgery and coexisting asthma. Conclusion: Significantly, more patients achieved improvement from moderate-to-severe symptoms to no-to-mild symptoms with dupilumab than placebo, regardless of prior surgery or coexisting asthma. Improvement was observed as early as Week 2 and continued through to Week 52.

Chapter 4: Chronic rhinosinusitis.

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.

Chapter 6: Nasal polyps.

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.

Chapter 14: Nonallergic rhinitis.

Rhinitis is characterized by one or more of the following nasal symptoms: congestion, rhinorrhea (anterior and posterior), sneezing, and itching. It is classified as allergic or nonallergic, the latter being a diverse syndrome that is characterized by symptoms of rhinitis that are not the result of IgE-mediated events. Excluding infectious rhinitis and underlying systemic diseases, clinical entities that can be classified among the disorders that make up the nonallergic rhinitis syndromes include gustatory rhinitis, nonallergic rhinitis with eosinophilia syndrome (NARES), atrophic, drug-induced (rhinitis medicamentosa), hormone induced, senile rhinitis (of the elderly), rhinitis associated with chronic rhinosinusitis with or without nasal polyps, and the idiopathic variant formerly known as vasomotor rhinitis but more accurately denoted as nonallergic rhinopathy (NAR). The prevalence of nonallergic rhinitis has been observed to be one-third that of allergic rhinitis, affecting ~7% of the U.S. population or ~22 million people. NAR is the most common of the nonallergic rhinitis subtypes, comprising at least two-thirds of all nonallergic rhinitis sufferers. Although certain precipitants such as perfume, strong odors, changes in temperature or humidity, and exposure to tobacco smoke are frequently identified as symptom triggers, NAR may occur in the absence of defined triggers. The diagnosis of nonallergic rhinitis is purely clinical and relies on a detailed history and physical exam. Skin testing or in vitro testing to seasonal and perennial aeroallergens is required to make the diagnosis of nonallergic rhinitis. Because of the heterogeneous nature of this group of disorders, treatment should be individualized to the patient's underlying pathophysiology and/or symptoms and is often empiric.

Chapter 15: Allergic rhinitis.

Allergic rhinitis affects 60 million of the U.S. population, 1.4 billion of the global population, and its prevalence appears to be increasing. The duration and severity of allergic rhinitis symptoms place a substantial burden on patient's quality of life, sleep, work productivity, and activity. The health impact of allergic rhinitis is compounded by associated complications and comorbidities including asthma, otitis media, sinusitis, and nasal polyps. Allergic rhinitis symptoms result from a complex, allergen-driven mucosal inflammatory process, modulated by immunoglobulin E (IgE), and caused by interplay between resident and infiltrating inflammatory cells and a number of vasoactive and proinflammatory mediators, including cytokines. This allergic response may be characterized as three phases: IgE sensitization, allergen challenge, and elicitation of symptoms. A thorough allergic history is the best tool for the diagnosis of allergic rhinitis, the establishment of which is achieved by correlating the patient's history and physical exam with an assessment for the presence of specific IgE antibodies to relevant aeroallergens determined by skin testing or by in vitro assay. Management of allergic rhinitis includes modifying environmental exposures, implementing pharmacotherapy, and, in select cases, administering allergen-specific immunotherapy. Intranasal therapeutic options include antihistamines, anticholinergic agents, corticosteroids (aqueous or aerosol), mast cell stabilizers, saline, and brief courses of decongestants. Selection of pharmacotherapy is based on the severity and chronicity of symptoms with the most effective medications being intranasal corticosteroids and intranasal antihistamines, which can be used in combination (separately or in fixed dose) for more difficult to control allergic rhinitis.

Chapter 16: Determining the role of allergy in sinonasal disease.

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.

Chapter 4: Chronic rhinosinusitis.

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.

Chapter 6: Nasal polyps.

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.

Chapter 14: Nonallergic rhinitis.

Rhinitis is characterized by one or more of the following nasal symptoms: congestion, rhinorrhea (anterior and posterior), sneezing, and itching. It is classified as allergic or nonallergic, the latter being a diverse syndrome that is characterized by symptoms of rhinitis that are not the result of IgE-mediated events. Excluding infectious rhinitis and underlying systemic diseases, clinical entities that can be classified among the disorders that make up the nonallergic rhinitis syndromes include gustatory rhinitis, nonallergic rhinitis with eosinophilia syndrome (NARES), atrophic, drug-induced (rhinitis medicamentosa), hormone induced, senile rhinitis (of the elderly), rhinitis associated with chronic rhinosinusitis with or without nasal polyps, and the idiopathic variant formerly known as vasomotor rhinitis but more accurately denoted as nonallergic rhinopathy (NAR). The prevalence of nonallergic rhinitis has been observed to be one-third that of allergic rhinitis, affecting ∼7% of the U.S. population or ∼22 million people. NAR is the most common of the nonallergic rhinitis subtypes, comprising at least two-thirds of all nonallergic rhinitis sufferers. Although certain precipitants such as perfume, strong odors, changes in temperature or humidity, and exposure to tobacco smoke are frequently identified as symptom triggers, NAR may occur in the absence of defined triggers. The diagnosis of nonallergic rhinitis is purely clinical and relies on a detailed history and physical exam. Skin testing or in vitro testing to seasonal and perennial aeroallergens is required to make the diagnosis of nonallergic rhinitis. Because of the heterogeneous nature of this group of disorders, treatment should be individualized to the patient's underlying pathophysiology and/or symptoms and is often empiric.

Chapter 15: Allergic rhinitis.

Allergic rhinitis affects 60 million of the U.S. population, 1.4 billion of the global population, and its prevalence appears to be increasing. The duration and severity of allergic rhinitis symptoms place a substantial burden on patient's quality of life, sleep, work productivity, and activity. The health impact of allergic rhinitis is compounded by associated complications and comorbidities including asthma, otitis media, sinusitis, and nasal polyps. Allergic rhinitis symptoms result from a complex, allergen-driven mucosal inflammatory process, modulated by immunoglobulin E (IgE), and caused by interplay between resident and infiltrating inflammatory cells and a number of vasoactive and proinflammatory mediators, including cytokines. This allergic response may be characterized as three phases: IgE sensitization, allergen challenge, and elicitation of symptoms. A thorough allergic history is the best tool for the diagnosis of allergic rhinitis, the establishment of which is achieved by correlating the patient's history and physical exam with an assessment for the presence of specific IgE antibodies to relevant aeroallergens determined by skin testing or by in vitro assay. Management of allergic rhinitis includes modifying environmental exposures, implementing pharmacotherapy, and, in select cases, administering allergen-specific immunotherapy. Intranasal therapeutic options include antihistamines, anticholinergic agents, corticosteroids (aqueous or aerosol), mast cell stabilizers, saline, and brief courses of decongestants. Selection of pharmacotherapy is based on the severity and chronicity of symptoms with the most effective medications being intranasal corticosteroids and intranasal antihistamines, which can be used in combination (separately or in fixed dose) for more difficult to control allergic rhinitis.

Chapter 16: Determining the role of allergy in sinonasal disease.

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.

Appropriate use of epinephrine in anaphylaxis.

We are submitting a case-based presentation illustrating medical errors in the use of epinephrine for the treatment of anaphylaxis. Readers will learn from mistakes made by other emergency caregivers in treating anaphylaxis. The article will specifically review the recommended use of epinephrine in the management of anaphylaxis. Four patients are presented who were seen in consultation by our outpatient allergy service. In all 4 cases, the history was suggestive of an episode of anaphylaxis in which emergency care providers mismanaged treatment. In 2 cases, the patients required ICU care after improperly receiving intravenous epinephrine. In the remaining 2 cases, epinephrine use was either omitted or significantly delayed in its administration. Our presentation includes a review of consensus statements regarding the treatment of anaphylaxis with particular regard to the use of epinephrine. We hope that this information will help prevent similar errors from harming other patients.