RESUMO
Nonsteroidal antiinflammatory drug-exacerbated respiratory disease (NERD) is a unique and often clinically severe disease affecting a subgroup of adults with asthma, chronic rhinosinusitis with nasal polyposis, and respiratory reactions with exposure to all cyclooxygenase 1-inhibiting nonsteroidal antiinflammatory drugs. NERD has a high disease burden and is estimated to affect 7% of adults with asthma and 30% of patients who have both asthma and nasal polyps. The disease is underdiagnosed and underrecognized by physicians on a routine basis, which leads to a delay in appropriate management. The goal of this review is to focus on the disease recognition, diagnosis, and different modes of uptodate therapies, including medical management, surgical intervention, aspirin desensitization, and biologic therapy.
Assuntos
Asma , Pólipos Nasais , Transtornos Respiratórios , Adulto , Humanos , Aspirina/uso terapêutico , Anti-Inflamatórios não Esteroides/efeitos adversos , Transtornos Respiratórios/tratamento farmacológico , Pólipos Nasais/terapia , Pólipos Nasais/tratamento farmacológico , Asma/tratamento farmacológico , Doença CrônicaRESUMO
PURPOSE OF REVIEW: The aim is to describe why this review is timely and relevant. Acetylsalicylic acid exacerbated respiratory disease (AERD) is a clinically significant disease affecting approximately 7% of all asthmatics or around 1,400,000 persons in the United States alone. A large portion of these patients remain undiagnosed. This review summarizes up to date knowledge on the pathophysiology, treatment opinions and provides an expert opinion on how to approach the AERD patient. RECENT FINDINGS: Findings describe the main themes in the literature covered by the article. Review of the current knowledge in terms of the key cells, cytokines/chemokines contributing to the acquired disease state of AERD. It also provides clinical approach toward the AERD patient with regards to current treatment options. SUMMARY: Summary describes the implications of the findings for clinical practice or research. This is an up-to-date review of the current literature, with insight into how to approach the management of an AERD patient.
Assuntos
Asma Induzida por Aspirina , Asma , Sinusite , Aspirina/efeitos adversos , Asma Induzida por Aspirina/diagnóstico , Asma Induzida por Aspirina/epidemiologia , Asma Induzida por Aspirina/terapia , Citocinas , HumanosRESUMO
BACKGROUND: Periplaneta americana and Blattella germanica cockroaches are widespread, and risk of sensitization increases in urban environments where these roaches thrive as household pests. There are no prior reports of Blaptica dubia cockroach allergy, though human exposure to B. dubia is increasing through commercial breeding as feeder insects. CASE PRESENTATION: A 50-year-old B. dubia cockroach breeder presented with progressively worsening upper and lower respiratory symptoms in recent years. Symptoms were worse with exposure to her B. dubia roach colony. Skin prick testing (SPT) to B. dubia cast skin, internal organs, and feces was performed in both the subject and a human control. Testing for P. americana and B. germanica sensitization was also performed in the subject. SDS-Polyacrylamide gel electrophoresis (PAGE), immunoblots, and enzyme-linked immunosorbent assays (ELISA) studies were performed using the subject and control serums to explore for specific IgE binding to B. dubia as well as P. americana. Our results showed SPT was positive to B. dubia internal organs in the subject and negative in the control. In the subject, SPT was negative to P. americana though intradermal (ID) testing was positive and serum specific IgE (sIgE) testing was negative to B. germanica. Immunoblotting of the subject's serum to B. dubia internal organ extract showed several distinct bands of IgE binding at 47 kilodaltons (kD), 68 kD, 74 kD, 83 kD, and 118 kD. The strongest band was at 118 kD on B. dubia immunoblotting, which was absent in P. americana on SDS-PAGE. ELISA studies showed an increased IgE response to both B. dubia and P. americana in the subject versus the control. CONCLUSIONS: This case confirmed the first reported allergy to B. dubia cockroaches. There may be cross-reactivity between B. dubia and P. americana, though our case suggests SPT and sIgE testing using P. americana and B. germanica extract has potential to miss a B. dubia cockroach allergy. This allergy is likely underreported, and further study is needed to explore the natural history of B. dubia cockroach allergy.
RESUMO
PURPOSE OF REVIEW: The aim of this study was to highlight the phenotypes and endotypes of asthma as a tool for selection of the Food and Drug Administration approved biologic therapies. RECENT FINDINGS: An evolving concept of asthma has led to the identification of distinct phenotypes and endotypes in this disease. Asthma endotypes are defined as the biological mechanism and are often categorized as T2-high and T2-low based on the influence of T helper type 2 (T2) cells and type 2 cytokines, including interleukin (IL)-4, IL-5, IL-9 and IL-13. Biomarkers such as peripheral blood absolute eosinophil count, total IgE, specific IgE and fractional exhaled nitric oxide may be used as indicators of asthma endotypes and help predict response to biologic therapies. There are currently five biologic therapies approved as a treatment option for T2-high asthma: omalizumab, benralizumab, mepolizumab, reslizumab and dupilumab. SUMMARY: Here, we explore the current understandings of asthma endotypes and review their associated phenotypes. We provide practical and evidence-based guidance for clinicians considering a biologic for asthma add-on maintenance therapy.
Assuntos
Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Produtos Biológicos/farmacologia , Células Th2/efeitos dos fármacos , Antiasmáticos/uso terapêutico , Asma/sangue , Asma/classificação , Asma/diagnóstico , Produtos Biológicos/uso terapêutico , Biomarcadores/sangue , Humanos , Fenótipo , Índice de Gravidade de Doença , Células Th2/imunologia , Células Th2/metabolismo , Resultado do TratamentoRESUMO
Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) characterized by a type 2 immune signature often have severe and recurrent disease. Lower airway conditions such as asthma are common comorbidities and share similar pathophysiology. CRSwNP with asthma is characterized by tissue eosinophilia and high local IgE levels. Clinically, CRSwNP with comorbid asthma is associated with more severe sinonasal symptoms and worse quality of life, and it is more difficult to treat both medically and surgically. Asthma in the presence of nasal polyposis is also more difficult to control, being more exacerbation prone, with increased airway obstruction and more extensive eosinophilic inflammation. Aspirin/nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (AERD) is a recognized phenotype of CRSwNP with comorbid asthma. Patients with CRSwNP with comorbid AERD are among those with the most severe and difficult-to-treat disease, and tend to have severe NP. The shared pathophysiology of the upper and lower airways has important implications for both the diagnosis and management of respiratory comorbidities. However, in clinical practice, the nose and lungs are often treated as separate entities. The underlying systemic inflammatory link between CRSwNP and asthma provides a compelling rationale for systemic treatment with novel biologics targeting shared underlying type 2 inflammatory pathways.
Assuntos
Asma , Pólipos Nasais , Rinite , Sinusite , Asma/epidemiologia , Doença Crônica , Humanos , Pólipos Nasais/epidemiologia , Qualidade de Vida , Rinite/epidemiologia , Sinusite/epidemiologiaRESUMO
Aspirin-exacerbated respiratory disease (AERD) is frequently diagnosed in patients with severe type 2 airway inflammation presenting with nasal polyps and severe asthma. It has been associated with a recalcitrant course with high medical and surgical requirements. The advent of recent biological and other targeted treatments show promise in the medical management of patient with AERD. The goal of complete disease control where patients no longer require recurrent surgical procedures, systemic corticosteroid exposure and may live with a stable and relatively normal quality of life is now within reach. Further work is necessary to identify biomarkers predictive of treatment response.
Assuntos
Asma/epidemiologia , Depressão/epidemiologia , Psicoterapia/métodos , Estresse Psicológico/epidemiologia , Adulto , Antidepressivos/uso terapêutico , Asma/psicologia , Asma/terapia , Terapia Cognitivo-Comportamental , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Otimismo , Testes de Função Respiratória , Estados Unidos/epidemiologiaRESUMO
Background Aspirin-exacerbated respiratory disease (AERD), also known as Samter's triad or aspirin (ASA)-intolerant asthma, affects 7% of asthmatics and has a higher prevalence in those with chronic rhinosinusitis and concomitant nasal polyposis. ASA desensitization with daily ASA therapy is a uniquely beneficial treatment for this disease entity and has been shown to have a significant impact on symptom scores, polyp disease, and need for systemic corticosteroids. However, no long-term studies have demonstrated whether or not ASA therapy remains safe and beneficial for these patients beyond 5-10 years. Objective This study was designed to determine the clinical course of AERD patients desensitized between 1995 and 2010. Methods A 20-question survey was distributed to patients who successfully completed ASA desensitization between January 1995 and April 2010. The questions were designed to assess ASA safety and longitudinal effects of ASA therapy in AERD. Results Of the 285 patients contacted, 92 (32%) completed the questionnaire. Average length of follow-up was 15 years. Of survey responders, 35 patients had discontinued ASA therapy. Although adverse reactions occurred, many also discontinued due to lack of efficacy or need for surgery. For those remaining on ASA (62%), significant improvement in sense of smell, asthma, sinus, and allergic rhinitis scores were noted ( P ≤ .001). The majority of ASA patients (68%) had a positive response to treatment and did not require further sinus surgery. However, ASA therapy did not delay the time to next sinus/polyp surgery ( P = .27) or reduce total number of sinus surgeries ( P = .56) compared to those who stopped treatment. Nearly 85% of AERD patients on ASA therapy found it to be helpful in improving airway disease and quality of life. Conclusion Aspirin desensitization followed by daily maintenance ASA therapy appears to be safe and effective even after 10+ years of continuous use.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Asma Induzida por Aspirina/terapia , Dessensibilização Imunológica/métodos , Pólipos Nasais/terapia , Rinite/terapia , Sinusite/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma Induzida por Aspirina/epidemiologia , Doença Crônica , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/epidemiologia , Rinite/epidemiologia , Sinusite/epidemiologia , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) are widely used in the United States and throughout the world for a variety of indications. Several unique hypersensitivity syndromes exist to this class of medications, making them one of the common reasons for consultation to the allergist. The lack of any laboratory-based diagnostic studies to assist in identifying the culprits in these reactions make evaluation of aspirin and NSAID hypersensitivity challenging. Identifying patients appropriate for oral challenge and/or desensitization protocols is the standard pragmatic approach to this issue when it arises.
Assuntos
Alérgenos/imunologia , Anti-Inflamatórios não Esteroides/imunologia , Aspirina/imunologia , Hipersensibilidade a Drogas/terapia , Urticária/terapia , Administração Oral , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Dessensibilização Imunológica , Hipersensibilidade a Drogas/diagnóstico , Humanos , Terapia de Alvo Molecular , Urticária/diagnósticoRESUMO
BACKGROUND: Prostaglandin E2 (PGE2) is an anti-inflammatory compound that inhibits 5-lipoxygenase activity. Diminished PGE2 regulation in aspirin-exacerbated respiratory disease (AERD) leads to respiratory reactions on cyclooxygenase 1 inhibition. In vitro studies have found that exogenous PGE2 stabilizes inflammatory mediator release. OBJECTIVE: To examine whether misoprostol (oral prostaglandin E1 analogue) use during aspirin challenge and desensitization might decrease the severity of aspirin-induced symptoms and make desensitization safer for patients with AERD. METHODS: Forty-five patients undergoing aspirin challenge and/or desensitization were randomized to misoprostol (n = 30) or placebo (n = 15) and compared with a group of historical controls (n = 31). Misoprostol (200 µg) was administered at 30 minutes, 90 minutes, and 4 hours after the first dose of nasal ketorolac. Measured end points included change in forced expiratory volume in 1 second (FEV1), peak nasal inspiratory flow rate (PNIF), number of treatments received for induced reactions, and adverse gastrointestinal effects. RESULTS: A difference in FEV1 and PNIF reduction was detected between misoprostol and placebo (P = .03) and misoprostol and historical controls (P = .01), respectively, during nasal ketorolac challenge. No difference was detected among aspirin reactors. Among all reactors, no difference in magnitude was found for FEV1 (P = .13) or PNIF (P = .07) reduction across all 3 groups. Total treatment requirement was similar (P = .14). Patients receiving misoprostol were more likely to report adverse gastrointestinal effects (P = .02). CONCLUSION: The addition of misoprostol to current aspirin challenge and/or desensitization protocols reveals no protective effect in reducing the intensity of nonsteroidal anti-inflammatory drug-induced symptoms and is not recommended based on the findings in this study.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Dessensibilização Imunológica , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/terapia , Misoprostol/uso terapêutico , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/terapia , Adolescente , Adulto , Antiasmáticos/administração & dosagem , Antiasmáticos/uso terapêutico , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Hipersensibilidade a Drogas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Hipersensibilidade Respiratória/diagnóstico , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Aspirin-exacerbated respiratory disease is characterized by asthma, chronic rhinosinusitis, nasal polyposis, and sensitivity to aspirin and other nonsteroidal anti-inflammatory drugs. Confirmation of the diagnosis requires provocation challenge with resulting upper and/or lower airways reactivity. Currently, determination of a positive challenge result is based solely on clinical judgment that synthesizes subjective symptoms and objective measures, as a concomitant increase in nasal or bronchial airways resistance is measured in only half of patients. OBJECTIVE: To describe a quantitative scoring system, based on symptoms typically reported during provocation challenge, used to identify a positive challenge result. METHODS: A total of 115 patients were asked to record 10 symptoms, rated on a scale from 1 (mild) to 10 (most severe), at regular intervals during intranasal ketorolac with modified oral aspirin challenge performed in our office. Composite scores, a simple sum of all individual scores, were calculated at each time point and compared with baseline, prechallenge values. RESULTS: One hundred of the 115 patients were determined to have a positive challenge result. A statistically significant difference in composite scores was observed in reactors vs nonreactors. All nonreactors recorded an increase in composite score of less than 5, whereas 69% of reactors recorded an increase of 5 or more. CONCLUSION: Our 10-symptom composite score provides a quantitative and comparable measure of symptoms that typically present during a challenge with a positive result. Although an external validation is needed to confirm its diagnostic performance characteristics, a change in composite score of 5 or more appears to be specific to reactors.
Assuntos
Aspirina/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/imunologia , Fenótipo , Hipersensibilidade Respiratória/diagnóstico , Hipersensibilidade Respiratória/imunologia , Adulto , Idoso , Feminino , Humanos , Imunização , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Testes de Provocação Nasal , Testes de Função Respiratória , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto JovemRESUMO
Aspirin-exacerbated respiratory disease (AERD) is an acquired disease characterized by chronic eosinophilic airway inflammation with underlying dysregulation of arachidonic acid metabolism. The purpose of this paper is to review the latest developments in our understanding of the underlying pathophysiology including the role of eosinophils, mast cells, innate lymphoid cells (ILC2), and platelets. Clinical features such as respiratory reactions induced by alcohol, aggressive nasal polyposis, and anosmia will allow for earlier recognition of these patients in clinical practice. The current state of the art management of AERD will be addressed including the ongoing central role for aspirin desensitization and high-dose aspirin therapy.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Asma Induzida por Aspirina/terapia , Animais , Asma Induzida por Aspirina/imunologia , Asma Induzida por Aspirina/patologia , HumanosRESUMO
Nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, are among the most commonly used drugs worldwide. They account for a large number of adverse drug reactions (ADRs). The prevalence of NSAID-induced reactions is increasing. Distinguishing between a predicted side effect of a drug and a potentially life-threatening hypersensitivity reaction is essential to manage the affected patient. However, most clinicians find it difficult to diagnose these types of reactions despite published classification schemes. In this overview, we provide an in-depth review of NSAID classification, types of NSAID reactions, diagnostic tactics, and management strategies to provide the reader with a greater understanding of NSAID-induced reactions.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/terapia , Anti-Inflamatórios não Esteroides/classificação , Gerenciamento Clínico , HumanosRESUMO
Nonsteroidal anti-inflammatory drug (NSAID)-induced urticarial and angioedema reactions are among the most commonly encountered drug hypersensitivity reactions in clinical practice. Three major clinical phenotypes of NSAID-induced acute skin reactions manifesting with angioedema, urticaria, or both have been distinguished: NSAID-exacerbated cutaneous disease, nonsteroidal anti-inflammatory drug-induced urticaria/angioedema (NIUA), and single NSAID-induced urticaria and angioedema. In some patients clinical history alone might be sufficient to establish the diagnosis of a specific type of NSAID hypersensitivity, whereas in other cases oral provocation challenges are necessary to confirm the diagnosis. Moreover, classification of the type of cutaneous reaction is critical for proper management. For example, in patients with single NSAID-induced reactions, chemically nonrelated COX-1 inhibitors can be safely used. However, there is cross-reactivity between the NSAIDs in patients with NSAID-exacerbated cutaneous disease and NIUA, and thus only use of selective COX-2 inhibitors can replace the culprit drug if the chronic treatment is necessary, although aspirin desensitization will allow for chronic treatment with NSAIDs in some patients with NIUA. In this review we present a practical clinical approach to the patient with NSAID-induced urticaria and angioedema.
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Angioedema/diagnóstico , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Pele/efeitos dos fármacos , Angioedema/induzido quimicamente , Angioedema/tratamento farmacológico , Angioedema/imunologia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Dessensibilização Imunológica/métodos , Gerenciamento Clínico , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/imunologia , Humanos , Pele/imunologia , Pele/patologia , Fatores de TempoRESUMO
PURPOSE OF REVIEW: The use of aspirin in coronary artery disease and address the unmet need of aspirin therapy in patients with history of hypersensitivity reactions to aspirin (acetylsalicylic acid; ASA) or other nonsteroidal inflammatory drugs (NSAIDs). RECENT FINDINGS: Aspirin hypersensitivity is reported in 1.5% of patients with cardiovascular disease. However, many of those labeled as allergic to aspirin had experienced side-effects and could be safely treated with aspirin. Those with true hypersensitivity reactions were often not placed on appropriate antiplatelet therapy. A number of protocols of varying complexity exist in the literature for aspirin desensitization. The focus of this review is to identify the types of aspirin reactions that can occur and provide a rational approach to oral aspirin challenge and desensitization. SUMMARY: In summary, with rare exceptions, patients with a history of 'aspirin/NSAID allergy' who need ASA for cardiovascular issues will be able to safely take aspirin either after a graded challenge or desensitization providing a central role of the allergist in the management of these patients.
Assuntos
Anti-Inflamatórios não Esteroides , Aspirina , Doença da Artéria Coronariana/tratamento farmacológico , Dessensibilização Imunológica , Hipersensibilidade a Drogas/terapia , Inibidores da Agregação Plaquetária , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Doença da Artéria Coronariana/complicações , Hipersensibilidade a Drogas/complicações , Hipersensibilidade a Drogas/diagnóstico , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêuticoAssuntos
Asma Induzida por Aspirina/terapia , Ciclo-Oxigenase 1/metabolismo , Dessensibilização Imunológica/métodos , Pólipos Nasais/terapia , Administração Oral , Adulto , Algoritmos , Alérgenos/imunologia , Anti-Inflamatórios não Esteroides/imunologia , Asma Induzida por Aspirina/diagnóstico , Asma Induzida por Aspirina/imunologia , Medicina Baseada em Evidências , Humanos , Leucotrienos/metabolismo , Masculino , Pólipos Nasais/diagnóstico , Pólipos Nasais/imunologia , RecidivaRESUMO
Nonsteroidal anti-inflammatory drugs (NSAIDs) are cyclooxygenase inhibitors with analgesic, anti-inflammatory, antipyretic, and antithrombotic effects. NSAIDs have been implicated in a variety of drug-induced reactions that are proved as or suspected of being mediated through a host immune response. Single-drug-induced reactions are the hallmark of these types of reactions. The types of single-drug-induced reactions are the confluence of 2 variables, the structure of the drug and the specific types of immune responses. This article identifies reactions patterns and the NSAIDs most likely to elicit each immune response.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Anafilaxia/etiologia , Angioedema/etiologia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Humanos , Hipersensibilidade Tardia/diagnóstico , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Tardia/etiologia , Urticária/etiologiaRESUMO
Aspirin is an important antiplatelet agent in the treatment of cardiovascular disease. Aspirin "allergy" often directs the physician away from this potentially life-saving modality. The majority of patients with a history of "reactions to aspirin" have aspirin/nonsteroidal anti-inflammatory drug (NSAID)-induced gastritis, easy bruisability, or other side effects. The minority of these patients has a "true allergy," referred to as a hypersensitivity reaction. The former group can be started on aspirin without the need for special challenge. Adding a proton-pump inhibitor can often mitigate the gastrointestinal side effects. Patients with aspirin hypersensitivity can be safely challenged with aspirin.