Asunto(s)
Aspirina , Asma Inducida por Aspirina , Humanos , Aspirina/efectos adversos , Aspirina/administración & dosificación , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/administración & dosificaciónAsunto(s)
Anticuerpos Monoclonales Humanizados , Asma Inducida por Aspirina , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Asma Inducida por Aspirina/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Anciano , Esquema de Medicación , Aspirina/efectos adversos , Aspirina/administración & dosificaciónAsunto(s)
Antiinflamatorios no Esteroideos , Asma Inducida por Aspirina , Hipersensibilidad a las Drogas , Humanos , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Hipersensibilidad a las Drogas/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Aspirina/efectos adversos , Aspirina/inmunología , Aspirina/uso terapéutico , Adulto , Dolor/tratamiento farmacológico , Anciano , Manejo del Dolor/métodosRESUMEN
Background: Olfactory dysfunction (OD) and smell loss affects aspects of patients' everyday life and lowers their quality of life. OD questionnaires are considered one of the core-outcome measures in chronic rhinosinusitis, but many existing smell loss questionnaires contained pandemic-prohibitive questions on social gatherings or restaurant visits, were too culture specific or gender specific, or were overly long and cumbersome. Objective: We aimed to develop a new brief questionnaire to assess the impact and consequences of smell loss and its burden on daily life. This study validates this new, short, multicultural, dichotomized questionnaire in an international population that has aspirin-exacerbated disease (AERD). Methods: The Consequences of Smell Loss (COSL) questionnaire was developed and content validity was assessed by experts and patients at Brigham and Women's Hospital. The questionnaire, along with other validated quality-of-life surveys, was answered by 853 patients with AERD. We evaluated the factor structure, reliability, validity, and discriminative ability of the COSL questionnaire. Results: The final version of the COSL questionnaire consisted of 13 items divided into three subdomains (emotional distress, food and safety, and physical health) through factor analysis. The Cronbach α for internal consistency was 0.82. Convergent and discriminant validity with the 22-item Sinonasal Outcome Test (SNOT-22), Healthy Days Core Module-4, Patient Health Questionnaire-4, and a specific question on taste and smell were high (p < 0.0001 for all). The COSL questionnaire score was associated with SNOT-22 categories (p < 0.001) and was categorized as follows: normal, 0-1 points; very few consequences, 2-3 points; few, 4 points; moderate, 5-6 points; and severe, 7-13 points. Conclusion: The COSL questionnaire is a new, brief, valid, reliable tool that can effectively screen for a high burden of OD in patients with AERD and has the potential to be used in other patient populations with OD as well.
Asunto(s)
Asma Inducida por Aspirina , Sinusitis , Humanos , Femenino , Calidad de Vida , Anosmia , Reproducibilidad de los Resultados , Aspirina/efectos adversos , Asma Inducida por Aspirina/diagnóstico , Encuestas y Cuestionarios , Sinusitis/epidemiología , Enfermedad CrónicaAsunto(s)
Asma Inducida por Aspirina , Pólipos Nasales , Enfermedades Respiratorias , Rinitis , Humanos , Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Enfermedades Respiratorias/tratamiento farmacológico , Pólipos Nasales/tratamiento farmacológico , Desensibilización Inmunológica , Asma Inducida por Aspirina/diagnóstico , Asma Inducida por Aspirina/tratamiento farmacológico , Enfermedad Crónica , Rinitis/tratamiento farmacológicoAsunto(s)
Asma Inducida por Aspirina , Pólipos Nasales , Sinusitis , Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales Humanizados , Aspirina/efectos adversos , Asma Inducida por Aspirina/tratamiento farmacológico , Asma Inducida por Aspirina/epidemiología , Niño , Humanos , Pólipos Nasales/epidemiología , PrevalenciaRESUMEN
BACKGROUND: The impact of anosmia on quality-of-life (QoL) for patients with aspirin-exacerbated respiratory disease (AERD) is poorly understood. We aimed to investigate how the severity of smell loss and olfactory dysfunction (OD) in patients with AERD affects their QoL, mental health and physical well-being. METHODS: Five validated QoL questionnaires (Sinonasal Outcome Test-22, Asthma Control Test, Healthy Days Core Module-4, Short Form-36 and Patient Health Questionnaire-4) and two newly developed questionnaires assessing severity and consequences of OD were electronically sent to all 2913 patients in the Brigham and Women's Hospital AERD registry. Responses were received from 853 participants for analysis. RESULTS: Overall, 85% of participants reported a present diminished sense of smell and/or taste, and 30% categorized their OD severity was, "as bad as it can be." There were significant relationships between the severity of self-reported OD and both psychological distress and general health scores, even after adjusting for asthma control. Additionally, incidence rates for physically and mentally unhealthy days in the prior month were higher for patients with moderate or severe OD than for normosmic patients. Patients with diminished smell responded that they could not identify spoiled food (86%), did not enjoy food (71%), felt unsafe (63%) and had encountered dangerous situations (51%) as consequences of their OD. CONCLUSIONS: Anosmia and hyposmia severely impact the physical, emotional and mental health of AERD patients, and lead to safety concerns in their daily lives. The importance of olfaction and the relevance of OD to patients' QoL should be acknowledged and evaluated by clinicians caring for these patients.
Asunto(s)
Asma Inducida por Aspirina , Sinusitis , Humanos , Femenino , Calidad de Vida , Anosmia , Salud Mental , Sinusitis/epidemiología , Asma Inducida por Aspirina/epidemiología , Aspirina/efectos adversosRESUMEN
BACKGROUND: Dupilumab, a mAb targeting IL-4Rα, improves upper and lower airway symptoms in patients with aspirin-exacerbated respiratory disease (AERD), but the mechanisms leading to clinical improvement are not fully elucidated. OBJECTIVE: Our aim was to identify the mechanistic basis of clinical improvement in patients with AERD treated with dupilumab. METHODS: A total of 22 patients with AERD were treated with dupilumab for 3 months for severe asthma and/or chronic rhinosinusitis with nasal polyps. Clinical outcomes were assessed at baseline and at 1 and 3 months after initiation of dupilumab. Nasal fluid, urine, blood, and inferior turbinate scrapings were collected at the 3 time points for determination of mediator levels, cellular assays, and RNA sequencing. RESULTS: Participants had rapid improvement in clinical measures, including sense of smell, sinonasal symptoms, and lung function after 1 month of treatment with dupilumab; the improvements were sustained after 3 months of dupilumab. Baseline severity of smell loss was correlated with lower nasal prostaglandin E2 levels. Dupilumab increased nasal prostaglandin E2 level and decreased levels of nasal albumin, nasal and urinary leukotriene E4, and serum and nasal IgE. Transcripts related to epithelial dysfunction and leukocyte activation and migration were downregulated in inferior turbinate tissue after treatment with dupilumab. There were no dupilumab-induced changes in nasal eosinophilia. CONCLUSION: Inhibition of IL-4Rα in AERD led to rapid improvement in respiratory symptoms and smell, with a concomitant improvement in epithelial barrier function, a decrease in inflammatory eicosanoid levels, and an increase in the anti-inflammatory eicosanoid prostaglandin E2 level. The therapeutic effects of dupilumab are likely due to decreased IL-4Rα signaling on respiratory tissue granulocytes, epithelial cells, and B cells.
Asunto(s)
Asma Inducida por Aspirina , Pólipos Nasales , Rinitis , Sinusitis , Aspirina/efectos adversos , Asma Inducida por Aspirina/diagnóstico , Enfermedad Crónica , Eicosanoides , Humanos , Pólipos Nasales/inducido químicamente , Pólipos Nasales/tratamiento farmacológico , Prostaglandinas , Rinitis/inducido químicamente , Rinitis/tratamiento farmacológico , Sinusitis/inducido químicamente , Sinusitis/tratamiento farmacológicoAsunto(s)
Asma Inducida por Aspirina , Pólipos Nasales , Rinitis , Sinusitis , Anticuerpos Monoclonales Humanizados/efectos adversos , Artralgia/tratamiento farmacológico , Aspirina/efectos adversos , Asma Inducida por Aspirina/tratamiento farmacológico , Enfermedad Crónica , Humanos , Pólipos Nasales/complicaciones , Rinitis/complicaciones , Sinusitis/complicacionesRESUMEN
BACKGROUND: Patterns of medication use and efficacy in aspirin-exacerbated respiratory disease (AERD) have not been well characterized, especially since the advent of respiratory biologics. Aspirin therapy after desensitization (ATAD) is efficacious for upper and lower respiratory symptoms for patients with AERD, though aspirin-related adverse effects can limit therapy. The optimal coordination of ATAD and respiratory biologics for the treatment of AERD remains unclear. OBJECTIVE: We aimed to characterize patterns of medication use and treatment experience with biologics and ATAD in AERD. METHODS: We surveyed 98 patients with AERD recruited from the Brigham and Women's Hospital AERD registry. Patients completed an online questionnaire describing their medication history and treatment experience. RESULTS: A total of 52 (53.0%) patients reported a history of use of one or more respiratory biologics (omalizumab, mepolizumab, reslizumab, benralizumab, or dupilumab), and 84 (85.7%) reported undergoing aspirin desensitization. There were 24 patients (24.4%) who reported concurrent use of a biologic and ATAD. Compared with those taking ATAD alone, patients taking a biologic and ATAD concurrently were less likely to report that aspirin was effective for their AERD symptoms (odds ratio, 0.161 [95% confidence interval, 0.03-0.76]; P =.02). Whereas patients reported varying efficacy with biologics, dupilumab had the highest odds of patients reporting it worked "very well" (odds ratio, 17.58 [95% confidence interval, 5.68-54.35]; P < .001). CONCLUSION: Biologics are emerging as a treatment option for AERD and are generally well tolerated. Biologic efficacy in AERD is variable by agent, though most patients taking dupilumab found it to be effective. Patients on a biologic in conjunction with ATAD may represent a more severe subset of AERD for which ATAD alone is insufficient.
Asunto(s)
Asma Inducida por Aspirina , Productos Biológicos , Sinusitis , Aspirina/efectos adversos , Asma Inducida por Aspirina/diagnóstico , Asma Inducida por Aspirina/tratamiento farmacológico , Productos Biológicos/efectos adversos , Desensibilización Inmunológica , Femenino , Humanos , Evaluación del Resultado de la Atención al PacienteAsunto(s)
Asma Inducida por Aspirina , Pólipos Nasales , Sinusitis , Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Aspirina/efectos adversos , Asma Inducida por Aspirina/tratamiento farmacológico , Humanos , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/cirugíaRESUMEN
BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) outpatient challenge protocols are not standardized. They vary in clinical practice and can be time- and resource-intensive to perform. OBJECTIVE: To investigate the safety and outcomes of two-step outpatient NSAID challenges to evaluate patients with non-aspirin-exacerbated respiratory disease (AERD)-related NSAID hypersensitivity. METHODS: We conducted a retrospective study of patients with a history of NSAID allergy who underwent outpatient NSAID challenges under allergist supervision. Individuals with AERD were excluded. Patient demographics, NSAID reaction history, and drug challenge details and outcomes were collected. RESULTS: A total of 249 patients (mean age, 51.6 years; 63.5% female) underwent 262 NSAID challenges. Of these, 224 challenges were negative (85.5%). Thirty challenges resulted in an immediate reaction during the challenge procedure (11.5%) and eight resulted in delayed reactions (3.1%). Three individuals with immediate reactions required treatment with intramuscular epinephrine. Factors associated with a positive NSAID challenge included a prior reaction occurring within 5 years of drug challenge (odds ratio [OR] = 3.66; 95% confidence interval [CI], 1.67-8.44), a prior immediate reaction within 3 hours of NSAID ingestion (OR = 2.45; 95% CI, 1.12-5.57), a history of cross-reactive NSAID hypersensitivity to multiple NSAIDs (OR = 2.97; 95% CI, 1.23-6.91), and the presence of comorbid chronic spontaneous urticaria (OR = 2.95; 95% CI, 1.35-6.41). CONCLUSIONS: More than 85% of two-step non-AERD NSAID drug challenges were negative for an immediate or delayed reaction, which allowed patients to use at least one clinically indicated NSAID. Challenge reactions were generally mild. Two-step NSAID challenge protocols can be safely performed in the outpatient setting.
Asunto(s)
Asma Inducida por Aspirina , Hipersensibilidad a las Drogas , Hipersensibilidad , Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Asma Inducida por Aspirina/tratamiento farmacológico , Hipersensibilidad a las Drogas/terapia , Femenino , Humanos , Hipersensibilidad/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Estudios RetrospectivosRESUMEN
BACKGROUND: Eosinophilic asthma and nasal polyposis are hallmarks of aspirin-exacerbated respiratory disease (AERD), and IL-5 inhibition has been shown to provide therapeutic benefit. However, IL-5Rα is expressed on many cells in addition to eosinophils, and the mechanisms by which IL-5 inhibition leads to clinical benefit in eosinophilic asthma and nasal polyposis are unlikely to be due exclusively to antieosinophil effects. OBJECTIVE: We sought to identify the mechanisms by which anti-IL-5 treatment with mepolizumab improves respiratory inflammation in AERD. METHODS: The clinical characteristics, circulating granulocytes, nasal scraping transcripts, eosinophilic cationic protein, tryptase, and antibody levels, and urinary and nasal eicosanoid levels were measured for 18 subjects with AERD who were taking mepolizumab and compared with those of 18 matched subjects with AERD who were not taking mepolizumab. RESULTS: Subjects taking mepolizumab had significantly fewer peripheral blood eosinophils and basophils, and those cells that remained had higher surface CRTH2 expression than did the cells from subjects not taking mepolizumab. Nasal prostaglandin F2α, prostaglandin D2 metabolites, leukotriene B4, and thromboxane levels were lower in subjects taking mepolizumab, as were urinary levels of tetranor-prostaglandin D2 and leukotriene E4. The nasal epithelial cell transcripts that were overexpressed among subjects with AERD who were taking mepolizumab were enriched for genes involved in tight junction formation and cilium organization. Nasal and urinary prostaglandin E2, tryptase, and antibody levels were not different between the 2 groups. CONCLUSION: IL-5 inhibition in AERD decreases production of inflammatory eicosanoids and upregulates tight junction-associated nasal epithelial cell transcripts, likely due to decreased IL-5 signaling on tissue mast cells, eosinophils, and epithelial cells. These direct effects on multiple relevant immune cells contribute to the mechanism of benefit afforded by mepolizumab.
Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Asma Inducida por Aspirina , Basófilos , Eosinófilos , Pólipos Nasales , Adolescente , Adulto , Anciano , Asma Inducida por Aspirina/tratamiento farmacológico , Asma Inducida por Aspirina/inmunología , Asma Inducida por Aspirina/orina , Basófilos/inmunología , Basófilos/patología , Eicosanoides/inmunología , Eicosanoides/orina , Eosinófilos/inmunología , Eosinófilos/patología , Femenino , Humanos , Interleucina-5/inmunología , Subunidad alfa del Receptor de Interleucina-5/inmunología , Masculino , Persona de Mediana Edad , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/inmunología , Pólipos Nasales/orinaRESUMEN
BACKGROUD: Aspirin-exacerbated respiratory disease (AERD) is a difficult-to-treat syndrome where timely diagnosis and initiation of disease-specific therapies are pertinent to improved patient outcomes. OBJECTIVE: To characterize the most common timeline for development of the clinical triad [asthma, nasal polyposis, and reactions to nonsteroidal anti-inflammatory drugs (NSAIDs)], identify barriers to prompt diagnosis of AERD, and describe indications for an aspirin challenge to facilitate accurate diagnosis. METHODS: Six hundred ninety-seven patients with diagnosed AERD and history of at least one sinus surgery to remove nasal polyps were identified in the Brigham and Women's Hospital AERD registry. Patient reported age at disease onset of asthma, nasal polyposis, and age of first NSAID reaction were obtained from 2013 to 2019 at enrollment. RESULTS: Of the 697 patients identified, diagnosis of asthma preceded diagnosis of nasal polyposis and first NSAID reaction, although there was considerable variability between patients. CONCLUSIONS: Prompt diagnosis of AERD is important for patient and provider education and improved care of this difficult-to-treat population of patients. Consider diagnostic aspirin challenge in patients without historical reactions to NSAIDs who have an otherwise compatible clinical history, specifically in patients who take daily low-dose aspirin, leukotriene modifiers, avoid NSAIDs, or who are severely symptomatic at baseline where it would be difficult to identify an acute worsening of symptoms.
RESUMEN
Antibodies are key immune effectors that confer protection against pathogenic threats. The nature and longevity of the antibody response to SARS-CoV-2 infection are not well defined. We charted longitudinal antibody responses to SARS-CoV-2 in 92 subjects after symptomatic COVID-19. Antibody responses to SARS-CoV-2 are unimodally distributed over a broad range, with symptom severity correlating directly with virus-specific antibody magnitude. Seventy-six subjects followed longitudinally to â¼100 days demonstrated marked heterogeneity in antibody duration dynamics. Virus-specific IgG decayed substantially in most individuals, whereas a distinct subset had stable or increasing antibody levels in the same time frame despite similar initial antibody magnitudes. These individuals with increasing responses recovered rapidly from symptomatic COVID-19 disease, harbored increased somatic mutations in virus-specific memory B cell antibody genes, and had persistent higher frequencies of previously activated CD4+ T cells. These findings illuminate an efficient immune phenotype that connects symptom clearance speed to differential antibody durability dynamics.