Rhinitis 2020: A practice parameter update.

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.

Drug Hypersensitivity Reactions.

Drug hypersensitivity reactions (DHRs) may be classified based on timing (immediate vs delayed), mechanisms, and pattern of clinical manifestations. Management may include selection of alternative, non-cross reactive agents, drug allergy testing, graded challenge and/or desensitization. Immediate skin testing only identifies risk for immediate-type allergic DHR and has a negative predictive value for only a limited number of drugs (eg, penicillin). Desensitization induces a temporary state of tolerance that is maintained only so long as the drug is continued. This article discusses special considerations about antibiotics, angiotensin-converting enzyme inhibitors, anesthetic agents, aspirin and nonsteroidal antiinflammatory drugs, radiocontrast media, and chemotherapeutic agents.

Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology.

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.

ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy": AIRWAYS ICPs initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration project.

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.

Allergic fungal rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) is a subset of chronic rhinosinusitis with nasal polyps (CRSwNP) characterized by antifungal IgE sensitivity, eosinophil-rich mucus (ie, allergic mucin), and characteristic computed tomographic and magnetic resonance imaging findings in paranasal sinuses. AFRS develops in immunocompetent patients, with occurrence influenced by climate, geography, and several identified host factors. Molecular pathways and immune responses driving AFRS are still being delineated, but prominent adaptive and more recently recognized innate type 2 immune responses are important, many similar to those established in patients with other forms of CRSwNP. It is unclear whether AFRS represents merely a more extreme expression of pathways important in patients with CRSwNP or whether there are other disordered immune responses that would define a distinct endotype or endotypes. Although AFRS and allergic bronchopulmonary aspergillosis share some analogous immune mechanisms, the 2 conditions do not occur commonly in the same patient. Treatment of AFRS almost always requires surgical debridement of the involved sinuses. Oral corticosteroids decrease recurrence after surgery, but other adjunctive pharmacologic agents, including topical and oral antifungal agents, do not have a firm evidence basis for use. There is good rationale for use of biologic agents that target eosinophilic inflammation or other type 2 responses, but studies in patients with AFRS are required.

Monocyte chemotactic protein-induced protein 1 controls allergic airway inflammation by suppressing IL-5-producing TH2 cells through the Notch/Gata3 pathway.

BACKGROUND: Asthmatic and allergic inflammation is mediated by TH2 cytokines (IL-4, IL-5, and IL-13). Although we have learned much about how TH2 cells are differentiated, the TH2 checkpoint mechanisms remain elusive. OBJECTIVES: In this study we investigate how monocyte chemotactic protein-induced protein 1 (MCPIP1; encoded by the Zc3h12a gene) regulates IL-5-producing TH2 cell differentiation and TH2-mediated inflammation. METHODS: The functions of Zc3h12a-/- CD4 T cells were evaluated by checking the expression of TH2 cytokines and transcription factors in vivo and in vitro. Allergic airway inflammation of Zc3h12a-/- mice was examined with murine asthma models. In addition, antigen-specific CD4 T cells deficient in MCPIP1 were transferred to wild-type recipient mice, challenged with ovalbumin (OVA) or house dust mite (HDM), and accessed for TH2 inflammation. RESULTS: Zc3h12a-/- mice have spontaneous severe lung inflammation, with an increase in mainly IL-5- and IL-13-producing but not IL-4-producing TH2 cells in the lung. Mechanistically, differentiation of IL-5-producing Zc3h12a-/- TH2 cells is mediated through Notch signaling and Gata3 independent of IL-4. Gata3 mRNA is stabilized in Zc3h12a-/- TH2 cells. MCPIP1 promotes Gata3 mRNA decay through the RNase domain. Furthermore, deletion of MCPIP1 in OVA- or HDM-specific T cells leads to significantly increased TH2-mediated airway inflammation in OVA or HDM murine models of asthma. CONCLUSIONS: Our study reveals that MCPIP1 regulates the development and function of IL-5-producing TH2 cells through the Notch/Gata3 pathway. MCPIP1 represents a new and promising target for the treatment of asthma and other TH2-mediated diseases.

Pharmacologic Treatment of Seasonal Allergic Rhinitis: Synopsis of Guidance From the 2017 Joint Task Force on Practice Parameters.

DESCRIPTION: The Joint Task Force on Practice Parameters, which comprises representatives of the American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI), formed a workgroup to review evidence and provide guidance to health care providers on the initial pharmacologic treatment of seasonal allergic rhinitis in patients aged 12 years or older. METHODS: To update a prior systematic review, the workgroup searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 18 July 2012 to 29 July 2016 to identify studies that addressed efficacy and adverse effects of single or combination pharmacotherapy for seasonal allergic rhinitis. In conjunction with the Joint Task Force, the workgroup reviewed the evidence and developed recommendations about initial treatment approaches by using the Grading of Recommendations Assessment, Development and Evaluation approach. Members of the AAAAI, the ACAAI, and the general public provided feedback on the draft document, which the Joint Task Force reviewed before finalizing the guideline. RECOMMENDATION 1: For initial treatment of seasonal allergic rhinitis in persons aged 12 years or older, routinely prescribe monotherapy with an intranasal corticosteroid rather than an intranasal corticosteroid in combination with an oral antihistamine. (Strong recommendation). RECOMMENDATION 2: For initial treatment of seasonal allergic rhinitis in persons aged 15 years or older, recommend an intranasal corticosteroid over a leukotriene receptor antagonist. (Strong recommendation). RECOMMENDATION 3: For treatment of moderate to severe seasonal allergic rhinitis in persons aged 12 years or older, the clinician may recommend the combination of an intranasal corticosteroid and an intranasal antihistamine for initial treatment. (Weak recommendation).

Seasonal Allergic Rhinitis: A focused systematic review and practice parameter update.

PURPOSE OF REVIEW: The review compares and contrasts seven major United States and international allergic rhinitis guidelines from 2008 to 2017. RECENT FINDINGS: Despite many treatment options for allergic rhinitis, patients often report lack of therapeutic control and a reduced quality of life. Guidelines intended to improve allergic rhinitis care have been evolving into evidence based, systematic reviews, with less reliance on consensus of expert opinion characteristic of more traditional guidelines. The first Grading of Recommendations Assessment, Development, and Evaluation-based guideline developed in the United States for seasonal allergic rhinitis was first published in 2017. SUMMARY: When critically analyzing the allergic rhinitis guidelines that use the rigorous Grading of Recommendations Assessment, Development, and Evaluation methodology, different groups of expert authors, using the same reference articles, will, at times, reach different conclusions regarding the quality of the evidence and the strength of the recommendation. Factors potentially contributing to these divergent determinations include: lack of objective primary outcome measures in allergic rhinitis, poorly defined Minimal Clinically Important Difference, failure to include all interested parties in guideline development, for example, patients, and subjectivity inherent in the expert panel.

Health care resource use and associated costs among patients with seasonal versus perennial allergic rhinitis.

BACKGROUND: Health care resource use (HRU) and costs among patients with seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) have not been widely studied. OBJECTIVE: To develop an algorithm to classify patients with SAR and patients with PAR, and to evaluate treatment patterns, HRU, and costs among these patients. METHODS: Patients with allergic rhinitis (AR) were identified retrospectively by using electronic medical records and administrative claims data, with an index date as the earlier of the date of AR diagnosis or allergy medication use. Patients with AR were followed-up from 12 months before the index date through 12 months after the index date (follow-up) and were classified as SAR or PAR based on medication patterns during follow-up. AR-related HRU, allergy immunotherapy administration, and costs per patient per year during follow-up were compared between patients with SAR and those with PAR, with analyses stratified by asthma diagnosis before the index date and by physician specialty (primary care physician versus specialist). RESULTS: Approximately 23% of patients with AR were classified as having PAR and 77% as having SAR. During follow-up, the patients with PAR had more allergy medication prescriptions versus the patients with SAR (8.0 versus 2.4 prescriptions), higher prescription medication costs ($1551 versus $313), higher allergy immunotherapy cost ($180 versus. $118), and higher total AR-related costs ($1944 versus $643); all with p < 0.001. Patients with asthma had higher costs than those without asthma. Patients seen by a specialist has higher costs than those treated by a primary care physician. CONCLUSION: Patients with PAR experienced more AR-related prescription drug use and higher health care costs than patients with SAR, with prescription drug costs being the main cost driver. Treatments that reduce the need for ongoing prescription medication use have the potential to be cost saving.

The spectrum of allergic fungal diseases of the upper and lower airways.

Fungi cause a wide spectrum of fungal diseases of the upper and lower airways. There are three main phyla involved in allergic fungal disease: (1) Ascomycota (2) Basidiomycota (3) Zygomycota. Allergic fungal rhinosinusitis (AFRS) causes chronic rhinosinusitis symptoms and is caused predominantly by Aspergillus fumigatus in India and Bipolaris in the United States. The recommended treatment approach for AFRS is surgical intervention and systemic steroids. Allergic bronchopulmonary aspergillosis (APBA) is most commonly diagnosed in patients with asthma or cystic fibrosis. Long term systemic steroids are the mainstay treatment option for ABPA with the addition of an antifungal medication. Fungal sensitization or exposure increases a patient's risk of developing severe asthma and has been termed severe asthma associated with fungal sensitivity (SAFS). Investigating for triggers and causes of a patient's asthma should be sought to decrease worsening progression of the disease.

Clinical practice guideline: Allergic rhinitis.

OBJECTIVE: Allergic rhinitis (AR) is one of the most common diseases affecting adults. It is the most common chronic disease in children in the United States today and the fifth most common chronic disease in the United States overall. AR is estimated to affect nearly 1 in every 6 Americans and generates $2 to $5 billion in direct health expenditures annually. It can impair quality of life and, through loss of work and school attendance, is responsible for as much as $2 to $4 billion in lost productivity annually. Not surprisingly, myriad diagnostic tests and treatments are used in managing this disorder, yet there is considerable variation in their use. This clinical practice guideline was undertaken to optimize the care of patients with AR by addressing quality improvement opportunities through an evaluation of the available evidence and an assessment of the harm-benefit balance of various diagnostic and management options. PURPOSE: The primary purpose of this guideline is to address quality improvement opportunities for all clinicians, in any setting, who are likely to manage patients with AR as well as to optimize patient care, promote effective diagnosis and therapy, and reduce harmful or unnecessary variations in care. The guideline is intended to be applicable for both pediatric and adult patients with AR. Children under the age of 2 years were excluded from the clinical practice guideline because rhinitis in this population may be different than in older patients and is not informed by the same evidence base. The guideline is intended to focus on a limited number of quality improvement opportunities deemed most important by the working group and is not intended to be a comprehensive reference for diagnosing and managing AR. The recommendations outlined in the guideline are not intended to represent the standard of care for patient management, nor are the recommendations intended to limit treatment or care provided to individual patients. ACTION STATEMENTS: The development group made a strong recommendation that clinicians recommend intranasal steroids for patients with a clinical diagnosis of AR whose symptoms affect their quality of life. The development group also made a strong recommendation that clinicians recommend oral second-generation/less sedating antihistamines for patients with AR and primary complaints of sneezing and itching. The panel made the following recommendations: (1) Clinicians should make the clinical diagnosis of AR when patients present with a history and physical examination consistent with an allergic cause and 1 or more of the following symptoms: nasal congestion, runny nose, itchy nose, or sneezing. Findings of AR consistent with an allergic cause include, but are not limited to, clear rhinorrhea, nasal congestion, pale discoloration of the nasal mucosa, and red and watery eyes. (2) Clinicians should perform and interpret, or refer to a clinician who can perform and interpret, specific IgE (skin or blood) allergy testing for patients with a clinical diagnosis of AR who do not respond to empiric treatment, or when the diagnosis is uncertain, or when knowledge of the specific causative allergen is needed to target therapy. (3) Clinicians should assess patients with a clinical diagnosis of AR for, and document in the medical record, the presence of associated conditions such as asthma, atopic dermatitis, sleep-disordered breathing, conjunctivitis, rhinosinusitis, and otitis media. (4) Clinicians should offer, or refer to a clinician who can offer, immunotherapy (sublingual or subcutaneous) for patients with AR who have inadequate response to symptoms with pharmacologic therapy with or without environmental controls. The panel recommended against (1) clinicians routinely performing sinonasal imaging in patients presenting with symptoms consistent with a diagnosis of AR and (2) clinicians offering oral leukotriene receptor antagonists as primary therapy for patients with AR. The panel group made the following options: (1) Clinicians may advise avoidance of known allergens or may advise environmental controls (ie, removal of pets; the use of air filtration systems, bed covers, and acaricides [chemical agents formulated to kill dust mites]) in patients with AR who have identified allergens that correlate with clinical symptoms. (2) Clinicians may offer intranasal antihistamines for patients with seasonal, perennial, or episodic AR. (3) Clinicians may offer combination pharmacologic therapy in patients with AR who have inadequate response to pharmacologic monotherapy. (4) Clinicians may offer, or refer to a surgeon who can offer, inferior turbinate reduction in patients with AR with nasal airway obstruction and enlarged inferior turbinates who have failed medical management. (5) Clinicians may offer acupuncture, or refer to a clinician who can offer acupuncture, for patients with AR who are interested in nonpharmacologic therapy. The development group provided no recommendation regarding the use of herbal therapy for patients with AR.

Clinical practice guideline: allergic rhinitis executive summary.

The American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) has published a supplement to this issue featuring the new Clinical Practice Guideline: Allergic Rhinitis. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 14 recommendations developed address the evaluation of patients with allergic rhinitis, including performing and interpretation of diagnostic testing and assessment and documentation of chronic conditions and comorbidities. It will then focus on the recommendations to guide the evaluation and treatment of patients with allergic rhinitis, to determine the most appropriate interventions to improve symptoms and quality of life for patients with allergic rhinitis.

The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) survey: provider practices and beliefs about allergen immunotherapy.

BACKGROUND: The practices and beliefs of the provider specialties that treat allergic rhinoconjunctivitis (ARC) with allergen immunotherapy (AIT) may vary. METHODS: A telephone survey of 500 randomly selected health care practitioners in 7 specialties, conducted in 2012. RESULTS: AIT was provided as a subcutaneous injection (SCIT) by 91% of allergist/immunologists, 54% of otolaryngologists, and 18% to 24% of other specialties. Otolaryngologists were the most frequent providers of sublingual drops of AIT (SLIT; 33%), compared to 2% to 10% of other specialties. AIT was recommended for adults with allergic rhinoconjunctivitis by 100% of allergist/immunologists vs 62% to 84% of the other specialties (p < 0.001). The primary reason for recommending AIT for adults (52%) or children (46%) was that other therapies did not work. Between 48% (nurse practitioners/physician assistants) and 93% (allergist/immunologists) of practitioners always or often decreased symptomatic medications over the course of AIT treatment. Most practitioners in all specialties (82-100%) thought that AIT was appropriate for patients with severe allergy symptoms. Significantly more allergist/immunologists and otolaryngologists than other specialists thought AIT was appropriate for mild allergy symptoms (p < 0.001 and p = 0.004, respectively, vs other specialties). Significantly more allergist/immunologists than other specialists thought that AIT was more effective than symptomatic medications (p < 0.001), could reduce the further development of allergies (p = 0.03), and could prevent the development of asthma. CONCLUSION: SCIT was more frequently provided than SLIT by all the specialties. Otolaryngologists were the most likely to offer SLIT, while very few allergist/immunologists offered SLIT. Allergist/immunologists differed from other specialties in some beliefs about the effectiveness of AIT.

Ocular and nasal allergy symptom burden in America: the Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) surveys.

Previous nationwide surveys of allergies in the United States have focused on nasal symptoms, but ocular symptoms are also relevant. This study determines the effects of ocular and nasal allergies on patients' lives. Telephone surveys of randomly selected U.S. households (the patient survey) and health care providers (provider survey) were conducted in the United States in 2012. Study participants were 2765 people ≥5 years of age who had ever been diagnosed with nasal or ocular allergies and 500 health care providers in seven specialties. Respondents to the patient survey reported a bimodal seasonal distribution of allergy symptoms, with peaks in March to May and September. Nasal congestion was the most common of the symptoms rated as "extremely bothersome" (39% of respondents), followed by red, itchy eyes (34%; p = 0.84 for difference in extreme bothersomeness of nasal and ocular symptoms). Twenty-nine percent of respondents reported that their or their child's daily life was impacted "a lot" when allergy symptoms were at their worst. Workers rated their mean productivity at 29% lower when allergy symptoms were at their worst (p < 0.001 compared with no symptoms). Providers reported that itchy eyes was the symptom causing most patients to seek medical treatment by pediatricians (73%), ophthalmologist/optometrists (72%), and nurse practitioners or physician assistants (62%), whereas nasal congestion was the symptom causing most patients to seek treatment from otolaryngologists (85%), allergist/immunologists (79%), and family medicine practitioners (64%). Ocular and nasal allergy symptoms substantially affected patients' lives and were comparable in their impact.

The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) survey: patients' experience with allergen immunotherapy.

Allergen immunotherapy (AIT) is used for the treatment of allergic rhinoconjunctivitis as a subcutaneous injection (subcutaneous immunotherapy [SCIT]). Extracts used for SCIT are also used off-label to formulate a liquid delivered as sublingual drops (sublingual immunotherapy [SLIT]). This study was designed to survey patients' experiences and beliefs regarding SCIT and SLIT. People who had ever been diagnosed with nasal and/or ocular allergies were identified in a 2012 telephone survey of U.S. households. Respondents were asked questions about their or their child's use of SCIT and SLIT and their beliefs about AIT. Of 2765 respondents, 46.5% had ever heard of AIT and 22.7% had ever initiated it: 20.9% with SCIT and 1.8% with SLIT (p < 0.0001). The most frequently cited reason for beginning AIT was that symptoms were unresolved with other medications (SCIT, 32.1%; SLIT, 14.0%). Some or full symptom relief was reported by 74.9% of respondents treated with SCIT and 66.0% of those treated with SLIT (p = 0.17 for SCIT versus SLIT). Approximately one-third of respondents who had ever heard of or had been treated with AIT said "don't know" when asked if immunotherapy controls allergy symptoms for years (33.6%), is a very safe treatment (29.3%), or can cure allergy symptoms (27.5%). Effective relief of allergy symptoms was cited most often as the primary benefit of SCIT (37.8%) and convenience was the primary benefit of SLIT (14%). Only one-fifth of respondents had ever been treated with AIT, largely with SCIT. More than one-half of respondents had never heard of AIT and respondents' beliefs indicated a need for educational efforts.

Diagnosis and treatment of nasal and ocular allergies: the Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) surveys.

BACKGROUND: Allergic rhinoconjunctivitis (ARC) is managed by a number of health care professional specialties, whose practice styles may vary. OBJECTIVE: To survey patients and health care professionals about the diagnosis and treatment of ARC. METHODS: The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) surveys were telephone surveys of randomly selected patients and health care professionals in the United States in 2012. Participants were 2,765 people ever diagnosed as having nasal and/or ocular allergies and 500 practitioners in 7 specialties who were treating ARC. RESULTS: Adult respondents to the patient survey reported that their allergies had been diagnosed most often by physicians in family practice (46%) rather than by allergists/immunologists (17%) or otolaryngologists (11%). Children's allergies had been diagnosed most often by pediatricians (41%) and family practitioners (22%). Most respondents with conditions diagnosed by an allergist/immunologist (94.9%) or otolaryngologist (62.7%) had been given an allergy test, but the test was not given to most patients with conditions diagnosed by family practitioners (61.3%) or pediatricians (64.9%). Most patients (75.8%) were treating their allergies with over-the-counter medications, and 53.5% were taking prescription medications. Allergen immunotherapy was being used by 33% (adult) or 28% (child) patients of allergist/immunologists, 25% (adult) or 24% (child) patients of otolaryngologists, and 8% and 10% of patients of family practitioners and pediatricians, respectively. CONCLUSION: Most patients took nonprescription medications for their allergy symptoms or were treated by general practitioners, who did not use allergy testing when diagnosing ARC. Most patients seen by allergist/immunologists and otolaryngologists were evaluated with allergy tests, and most allergen immunotherapy was provided by allergy specialists.

Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology.

Chronic rhinosinusitis (CRS) is a complex disease consisting of several disease variants with different underlying pathophysiologies. Limited knowledge of the mechanisms of these disease subgroups is possibly the greatest obstacle in understanding the causes of CRS and improving treatment. It is generally agreed that there are clinically relevant CRS phenotypes defined by an observable characteristic or trait, such as the presence or absence of nasal polyps. Defining the phenotype of the patient is useful in making therapeutic decisions. However, clinical phenotypes do not provide full insight into all underlying cellular and molecular pathophysiologic mechanisms of CRS. Recognition of the heterogeneity of CRS has promoted the concept that CRS consists of multiple groups of biological subtypes, or "endotypes," which are defined by distinct pathophysiologic mechanisms that might be identified by corresponding biomarkers. Different CRS endotypes can be characterized by differences in responsiveness to different treatments, including topical intranasal corticosteroids and biological agents, such as anti-IL-5 and anti-IgE mAb, and can be based on different biomarkers that are linked to underlying mechanisms. CRS has been regarded as a single disease entity in clinical and genetic studies in the past, which can explain the failure to identify consistent genetic and environmental correlations. In addition, better identification of endotypes might permit individualization of therapy that can be targeted against the pathophysiologic processes of a patient's endotype, with potential for more effective treatment and better patient outcomes.

Management of rhinitis: guidelines, evidence basis, and systematic clinical approach for what we do.

Whereas very mild rhinitis may be simply and successfully self-managed by patients using medications available over the counter, most patients with rhinitis who present to medical offices have more severe rhinitis that may need a more comprehensive diagnostic and therapeutic approach. Optimal care may require special diagnostic studies and combination therapies that are arrived at only after trying multiple different medication and therapeutic options. This article presents a systematic approach to office care of rhinitis from the perspective of an allergist-immunologist. More emphasis is given to discussion of dilemmas that face the specialist or more involved considerations that have been highlighted in recently published guidelines.