RESUMEN
BACKGROUND: The aim was to identify risk factors for severe adult-onset asthma. METHODS: We used data from a population-based sample (Adult Asthma in Finland) of 1350 patients with adult-onset asthma (age range 31-93 years) from Finnish national registers. Severe asthma was defined as self-reported severe asthma and asthma symptoms causing much harm and regular impairment and ≥ 1 oral corticosteroid course/year or regular oral corticosteroids or waking up in the night due to asthma symptoms/wheezing ≥ a few times/month. Sixteen covariates covering several domains (personal characteristics, education, lifestyle, early-life factors, asthma characteristics and multiple morbidities) were selected based on the literature and were studied in association with severe asthma using logistic regressions. RESULTS: The study population included 100 (7.4%) individuals with severe asthma. In a univariate analysis, severe asthma was associated with male sex, age, a low education level, no professional training, ever smoking, ≥ 2 siblings, ≥ 1 chronic comorbidity and non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) (p < 0.05), and trends for association (p < 0.2) were observed for severe childhood infection, the presence of chronic rhinosinusitis with nasal polyps, and being the 1st child. The 10 variables (being a 1st child was removed due to multicollinearity) were thus entered in a multivariate regression model, and severe asthma was significantly associated with male sex (OR [95% CI] = 1.96 [1.16-3.30]), ever smoking (1.98 [1.11-3.52]), chronic comorbidities (2.68 [1.35-5.31]), NERD (3.29 [1.75-6.19]), and ≥ 2 siblings (2.51 [1.17-5.41]). There was a dose-response effect of the total sum of these five factors on severe asthma (OR [95% CI] = 2.30 [1.81-2.93] for each one-unit increase in the score). CONCLUSIONS: Male sex, smoking, NERD, comorbidities, and ≥ 2 siblings were independent risk factors for self-reported severe asthma. The effects of these factors seem to be cumulative; each additional risk factor gradually increases the risk of severe asthma.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Asma Inducida por Aspirina/epidemiología , Asma/epidemiología , Pólipos Nasales/epidemiología , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Asma Inducida por Aspirina/etiología , Estudios de Casos y Controles , Enfermedad Crónica , Comorbilidad , Estudios Transversales , Femenino , Finlandia/epidemiología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Rinitis/epidemiología , Factores de Riesgo , Factores Sexuales , Hermanos , Sinusitis/epidemiología , Fumar/efectos adversosRESUMEN
BACKGROUND: AERD (aspirin-exacerbated respiratory disease) is the combination of asthma, chronic rhinosinusitis/nasal polyposis (CRSwNP) and acute respiratory reactions after intake of NSAIDs (cyclooxygenase-1-inhibitors). It is characterized by chronic eosinophilic airway inflammation which is exacerbated by NSAIDs. Despite guideline-based treatment for asthma and CRSwNP and avoidance of NSAIDs, the disease is often progressive. Long-term aspirin treatment after desensitization can be effective. CASE DESCRIPTION: A 60-year old man with a history of polyposis nasi and pansinusitis was admitted for sinus surgery. Prior to the surgery he developed hypoxemic failure after taking diclofenac. He was diagnosed with acute asthma exacerbation due to diclofenac. After treatment with oxygen, nebulized bronchodilators and prednisolone he recovered within one day. AERD was diagnosed based on patient's comorbidity and sensitivity to diclofenac. CONCLUSION: Patients with rhinosinusitis, nasal polyps or asthma have a high risk of NSAID hypersensitivity. Therefore routinely treatment with NSAIDs should be avoided in these patients.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Asma Inducida por Aspirina/etiología , Diclofenaco/efectos adversos , Sinusitis/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/complicaciones , Periodo Preoperatorio , Rinitis/complicaciones , Sinusitis/cirugíaRESUMEN
OBJECTIVE: To phenotype patients with aspirin-exacerbated respiratory disease (AERD) according to the presence of atopy, urticaria and level of peripheral eosinophils. METHODS: This study included adult asthmatic patients with AERD followed up at a tertiary hospital. They were classified according to atopy and/or urticaria, assessing clinical and laboratorial differences among the groups in order to identify possible aggravating factors of the disease. RESULTS: We included 73 patients, 78.1% being female with a mean age of 54.0 years. Severe asthma was observed in 68.5% and respiratory exacerbation with dipyrone in 67.1% of these patients. They had median total serum IgE of 191.6 IU/mL, mean peripheral eosinophils of 718.5 cells/mm3, and 50.7% were atopic. Urticaria was observed in 32.9% of them, and exacerbations were more often triggered by dipyrone (p = .016). Atopic patients were younger than nonatopic patients (p = .023), and had, on average, higher total serum IgE levels (p = .022). We observed a good correlation between asthma severity and peripheral eosinophils count (r2 = 026; p = .021). CONCLUSIONS: In this study, severe asthma was highly prevalent in AERD patients. Likewise, urticaria was quite prevalent and its presence was associated with dipyrone induced hypersensitivity reaction. Atopy was found in half of the patients, with no association with asthma severity. Patients with higher levels of peripheral eosinophils had more severe asthma. Dypirone hypersensitivity may be a marker for concomitant respiratory and cutaneous hypersensitivity reactions.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Asma Inducida por Aspirina/etiología , Dipirona/efectos adversos , Dipirona/inmunología , Hipersensibilidad a las Drogas/complicaciones , Hipersensibilidad Inmediata/complicaciones , Urticaria/complicaciones , Asma Inducida por Aspirina/inmunología , Progresión de la Enfermedad , Hipersensibilidad a las Drogas/inmunología , Eosinófilos , Femenino , Humanos , Hipersensibilidad Inmediata/inmunología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
Rationale: Aspirin-exacerbated respiratory disease is characterized by severe asthma, nonsteroidal antiinflammatory drug hypersensitivity, nasal polyposis, and leukotriene overproduction. Systemic corticosteroid therapy does not completely suppress lifelong aspirin hypersensitivity. Omalizumab efficacy against aspirin-exacerbated respiratory disease has not been investigated in a randomized manner.Objectives: To evaluate omalizumab efficacy against aspirin hypersensitivity, leukotriene E4 overproduction, and symptoms during an oral aspirin challenge in patients with aspirin-exacerbated respiratory disease using a randomized design.Methods: We performed a double-blind, randomized, crossover, placebo-controlled, single-center study at Sagamihara National Hospital between August 2015 and December 2016. Atopic patients (20-79 yr old) with aspirin-exacerbated respiratory disease diagnosed by systemic aspirin challenge were randomized (1:1) to a 3-month treatment with omalizumab or placebo, followed by a >18-week washout period (crossover design). The primary endpoint was the difference in area under logarithm level of urinary leukotriene E4 concentration versus time curve in the intent-to-treat population during an oral aspirin challenge.Measurements and Main Results: Sixteen patients completed the study and were included in the analysis. The area under the logarithm level of urinary leukotriene E4 concentration versus time curve during an oral aspirin challenge was significantly lower in the omalizumab phase (median [interquartile range], 51.1 [44.5-59.8]) than in the placebo phase (80.8 [interquartile range, 65.4-87.8]) (P < 0.001). Ten of 16 patients (62.5%) developed oral aspirin tolerance up to cumulative doses of 930 mg in the omalizumab phase (P < 0.001).Conclusions: Omalizumab treatment inhibited urinary leukotriene E4 overproduction and upper/lower respiratory tract symptoms during an oral aspirin challenge, resulting in aspirin tolerance in 62.5% of the patients with aspirin-exacerbated respiratory disease.
Asunto(s)
Antialérgicos/uso terapéutico , Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Asma Inducida por Aspirina/tratamiento farmacológico , Omalizumab/uso terapéutico , Adulto , Anciano , Área Bajo la Curva , Asma Inducida por Aspirina/etiología , Asma Inducida por Aspirina/fisiopatología , Asma Inducida por Aspirina/orina , Estudios Cruzados , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado , Humanos , Leucotrieno E4/orina , Masculino , Persona de Mediana Edad , Prostaglandina D2/análogos & derivados , Prostaglandina D2/orina , Adulto JovenRESUMEN
INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (NERD) is defined by intolerance to cyclooxygenase 1 inhibitors, chronic rhinosinusitis with recurrent nasal polyps, and/or intrinsic bronchial asthma. Long-term administration of acetylsalicylic acid (ASA) after desensitization has been used to mitigate these sequelae, but the optimal dose and balancing symptom relief and side effects remain unsettled. METHODS: Retrospective data analysis of 85 patients with NERD receiving maintenance therapy of 300 mg ASA was followed by questionnaires (our own, not validated and the Sino-Nasal Outcome Test-20). We received responses from 55 patients and examined 30 of them clinically. RESULTS: Patients with no ASA-associated side effects were 56.4% (56 of 85 patients) of the cohort. In this study, 60% (33 of 55 patients) continued prophylaxis of 300 mg ASA daily for an average of 34.7 months. Elective surgery was the most frequent cause of discontinuation of ASA (21.8%; 12 of 55 patients). Rhinomanometry values were significantly improved with ASA (P < .05; Wilcoxon), but there was no significant reduction in nasal polyposis or improvement in olfaction at the time of follow-up examination. CONCLUSIONS: Minor clinical improvements were identified. Side effects were well tolerated by most patients, and no serious sequelae occurred. The indications for long-term ASA therapy in NERD patients remain unsettled.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Asma Inducida por Aspirina/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Pólipos Nasales/tratamiento farmacológico , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Asma Inducida por Aspirina/etiología , Enfermedad Crónica , Desensibilización Inmunológica , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/epidemiología , Estudios Retrospectivos , Rinitis/epidemiología , Sinusitis/epidemiología , Resultado del TratamientoRESUMEN
Asthma induced by ingestion of aspirin occurs when symptoms arise within 30 minutes to three hours after aspirin consumption. Previous data indicate that sensitivity to aspirin may be associated with poorly controlled asthma. This study aims to evaluate the frequency of aspirin sensitivity in patients with moderate to severe asthma receiving conventional asthma therapy. This clinical trial was conducted on 65 patients aged 18 to 65 years with moderate to severe asthma from February 2015 to February 2016 at the Allergy Department, Hazrat-e-Rasoul Hospital, Iran University of Medical Sciences, Tehran. To assess treatment responses in patients, forced expiratory volume in the first second (FEV1) and asthma control test (ACT) scores were measured at baseline and after 3 months. The results of the oral aspirin challenge revealed a prevalence of 35.38% for sensitivity to aspirin. Hypersensitivity reactions to aspirin were detected in 60.9% of the patients with moderate asthma and 39.1% of the patients with severe asthma. All patients with positive aspirin challenge tests suffered from rhinosinusitis and in 56.5% of cases, history of previous hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) was detected. No meaningful differences were found between those patients with aspirin sensitivity and those with aspirin tolerance neither in mean pre-bronchodilator FEV1 nor in ACT scores pre- and post-treatment. To conclude, aspirin sensitivity was not found to have an association with an unfavorable response to conventional treatment in patients with uncontrolled asthma.
Asunto(s)
Aspirina/efectos adversos , Asma Inducida por Aspirina/diagnóstico , Asma Inducida por Aspirina/etiología , Adolescente , Adulto , Anciano , Antiasmáticos/administración & dosificación , Antiasmáticos/uso terapéutico , Antiinflamatorios no Esteroideos/efectos adversos , Asma Inducida por Aspirina/tratamiento farmacológico , Susceptibilidad a Enfermedades , Femenino , Humanos , Inmunización , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: To assess the safety and efficacy of Aspirin desensitization combined with long-term Aspirin therapy in patients with Aspirinexacerbated respiratory disease (AERD). METHODS: We searched the PubMed, Ovid, Cochrane Library, and Google Scholar databases from inception to October 2018 for articles in English. We only included randomized controlled trials and parallel or cross-over studies in which adults with AERD were randomly assigned to undergo Aspirin desensitization and receive long-term Aspirin therapy or placebo. RESULTS: A total of 869 citations were retrieved, and 6 studies met the criteria for analysis. All studies indicated that nasal symptoms, asthma symptoms, or both improved significantly after Aspirin desensitization. In addition, most studies reported a decline in corticosteroid dosage (oral and inhaled). The 4 studies that reported nasal polyps did not demonstrate a change in nasal polyps with Aspirin therapy compared with placebo. The dropout rates in all studies reviewed ranged from 5.8% to 55.7%, and the most common adverse events were gastrointestinal symptoms. CONCLUSIONS: Clearly, Aspirin desensitization and treatment are beneficial for AERD patients, with relief of nasal symptoms, improvement in asthma control, decrease in daily corticosteroid use, and no fatal adverse events. However, the long-term adverse effects of Aspirin desensitization and optimal dosage of Aspirin merit further investigation.
Asunto(s)
Aspirina/efectos adversos , Asma Inducida por Aspirina/etiología , Asma Inducida por Aspirina/terapia , Desensibilización Inmunológica , Adulto , Aspirina/administración & dosificación , Asma Inducida por Aspirina/diagnóstico , Desensibilización Inmunológica/efectos adversos , Desensibilización Inmunológica/métodos , Duración de la Terapia , Endoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/patología , Evaluación de Síntomas , Resultado del TratamientoRESUMEN
PURPOSE: Aspirin-exacerbated respiratory disease (AERD) is a severe form of chronic rhinosinusitis with nasal polyps (CRSwNP) accompanied by asthma and an aspirin intolerance. The underlying pathomechanism of AERD still remains unclear, recent data suggest a complex inflammatory imbalance. In the present study, we investigated the cytokine patterns in AERD, CRSwNP and healthy control patients. Furthermore, we describe the change in cytokine level in the course of aspirin desensitization (AD) with continuous intake of aspirin. METHODS: The study included a total of 104 participants, 48 healthy controls, 45 patients with nasal polyps and 11 patients with AERD undergoing AD. Nasal secretions were analyzed for IL-1ß, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, THF-α, IFN-γ, eotaxin and ECP using Bio-Plex Human Cytokine Assay and Uni-CAP FEIA. Baseline measurements of cytokine levels were performed in all 104 patients; in patients with AERD, follow-up was performed 1-6 and 6-24 months after the initiation of AD. RESULTS: Our preliminary results show a TH2 dominated, eosinophilic milieu in AERD patients, which decreased in the first weeks of AD. However, after 6 months of AD, proinflammatory cytokines show a tendency to increase again. Also, TH1 as well as Treg associated cytokine seem to increase over time. CONCLUSIONS: For the first time, the present work shows the cytokine pattern in nasal secretions of AERD patients before and during AD. Further investigation of the complex interaction of inflammatory cytokines during AD might reveal important insights into the disease entity of AERD and open up new horizons for a targeted therapy.
Asunto(s)
Aspirina/efectos adversos , Asma Inducida por Aspirina/inmunología , Asma Inducida por Aspirina/terapia , Citocinas/inmunología , Desensibilización Inmunológica/métodos , Adulto , Aspirina/administración & dosificación , Asma Inducida por Aspirina/etiología , Secreciones Corporales/química , Secreciones Corporales/inmunología , Enfermedad Crónica , Citocinas/análisis , Citocinas/biosíntesis , Femenino , Humanos , Interleucina-13 , Masculino , Persona de Mediana Edad , Pólipos Nasales/inmunología , Nariz , Datos Preliminares , Rinitis/inmunología , Sinusitis/inmunología , Adulto JovenAsunto(s)
Asma Inducida por Aspirina/terapia , Anticuerpos Monoclonales/uso terapéutico , Asma Inducida por Aspirina/etiología , Bronquiectasia/diagnóstico , Bronquiectasia/epidemiología , Enfermedad Crónica , Comorbilidad , Desensibilización Inmunológica , Humanos , Antagonistas de Leucotrieno/uso terapéutico , Lavado Nasal (Proceso) , Pólipos Nasales/complicaciones , Pólipos Nasales/diagnóstico , Rinitis/diagnóstico , Rinitis/epidemiología , Sinusitis/diagnóstico , Sinusitis/epidemiología , Base del Cráneo/cirugía , Esteroides/uso terapéuticoRESUMEN
PURPOSE OF REVIEW: NSAID-Exacerbated Disease (N-ERD) is a chronic eosinophilic inflammatory disorder of the respiratory tract occurring in patients with asthma and/or rhinosinusitis with nasal polyps, whose symptoms are exacerbated by NSAIDs. The purpose of this review is to provide an update on clinical characteristics, pathophysiology, and management of N-ERD, and to emphasize heterogeneity of this syndrome. RECENT FINDINGS: Growing evidence indicates that N-ERD, which has been considered a separate asthma phenotype, is heterogenous, and can be divided in several subphenotypes varying in clinical characteristics. Pathophysiology of N-ERD is complex and extends beyond abnormalities in the arachidonic acid metabolism. Heterogeneity of pathophysiological mechanisms underlying development of airway inflammation seems to be associated with variability in response to both anti-inflammatory and disease-specific treatments (e.g., with aspirin after desensitization). SUMMARY: Progress in understanding of the pathophysiology of N-ERD leads to discovery and validation of new biomarkers facilitating diagnosis and predicting the response to treatment of the chronic inflammation underlying upper (CRSwNP) and lower airway (asthma) symptoms. Better characterization of the immunophysiopathological heterogeneity of N-ERD (identification of endotypes) may allow more personalized, endotype-driven approach to treatment in the future.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Asma Inducida por Aspirina/diagnóstico , Asma Inducida por Aspirina/etiología , Rinitis/inducido químicamente , Sinusitis/inducido químicamente , Asma Inducida por Aspirina/inmunología , Asma Inducida por Aspirina/prevención & control , Biomarcadores , Enfermedad Crónica , Humanos , Pólipos Nasales/complicaciones , FenotipoRESUMEN
BACKGROUND: Aspirin challenge and desensitization remains the criterion standard in diagnosis and treatment for patients with aspirin-exacerbated respiratory disease (AERD), but the protocols can be time and resource intensive. OBJECTIVE: To provide evidence that oral aspirin challenge and desensitization can be safely performed in an outpatient setting in 1 day. METHODS: Forty-four patients with a confirmed diagnosis of AERD, stable asthma, and baseline FEV1 value greater than or equal to 70% of predicted completed an oral aspirin challenge and desensitization protocol. The starting dose was 40.5 mg with escalating doses of aspirin (81, 162.5, 325 mg) at 90-minute intervals until symptoms were provoked. Desensitization was defined as tolerating a repeated administration of the provocative aspirin dose and at least 1 subsequent dose, bringing the total aspirin ingested during the in-clinic desensitization to 325 mg or more. RESULTS: Ninety-three percent of patients completed the challenge and desensitization in 1 day, with an average protocol completion time of 9 hours and 29 minutes. Two patients (4.6%) chose to complete the protocol over 2 days. One patient (2.3%) was discontinued from the protocol because of ongoing abdominal discomfort and diarrhea. No patient required epinephrine, emergency department visit, or hospitalization. CONCLUSIONS: Patients with AERD on a stable asthma regimen and with a baseline FEV1 value greater than or equal to 70% can be safely desensitized to aspirin using a 90-minute dose escalation protocol, starting at a dose of 40.5 mg, and defining desensitization as tolerance of the repeated provocation dose and at least 1 subsequent aspirin dose, bringing total cumulative daily dose to 325 mg or more. This protocol can routinely be completed in 1 day.
Asunto(s)
Aspirina/administración & dosificación , Asma Inducida por Aspirina/terapia , Inhibidores de la Ciclooxigenasa/administración & dosificación , Desensibilización Inmunológica/métodos , Pólipos Nasales/terapia , Rinitis/terapia , Sinusitis/terapia , Aspirina/efectos adversos , Aspirina/inmunología , Asma Inducida por Aspirina/etiología , Asma Inducida por Aspirina/inmunología , Asma Inducida por Aspirina/fisiopatología , Enfermedad Crónica , Inhibidores de la Ciclooxigenasa/efectos adversos , Inhibidores de la Ciclooxigenasa/inmunología , Relación Dosis-Respuesta a Droga , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/inducido químicamente , Pólipos Nasales/inmunología , Rinitis/inducido químicamente , Rinitis/inmunología , Sinusitis/inducido químicamente , Sinusitis/inmunologíaAsunto(s)
Asma Inducida por Aspirina/epidemiología , Esofagitis Eosinofílica/epidemiología , Aspirina/administración & dosificación , Aspirina/efectos adversos , Asma Inducida por Aspirina/etiología , Asma Inducida por Aspirina/terapia , Inhibidores de la Ciclooxigenasa/administración & dosificación , Inhibidores de la Ciclooxigenasa/efectos adversos , Desensibilización Inmunológica/métodos , Esofagitis Eosinofílica/inducido químicamente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/inducido químicamente , Pólipos Nasales/epidemiología , Pólipos Nasales/terapia , Estudios Retrospectivos , Rinitis/inducido químicamente , Rinitis/epidemiología , Rinitis/terapia , Sinusitis/inducido químicamente , Sinusitis/epidemiología , Sinusitis/terapiaRESUMEN
OBJECTIVE: Aspirin exacerbated respiratory disease (AERD) patients are challenging to manage with sinonasal and pulmonary symptoms refractory to maximal medical and surgical therapies. Our objective was to comprehensively examine objective and validated, disease-specific subjective sinonasal and pulmonary outcomes of aspirin (ASA) desensitization therapy in this patient population. METHODS: Prospective cohort study at an academic tertiary center. AERD patients with a history of chronic rhinosinusitis with nasal polyposis (CRSwNP), prior diagnosis of asthma, and a history of ASA sensitivity were eligible for inclusion. Patients underwent ASA desensitization using an established institutional protocol and continued on a 650mg twice daily maintenance dose. Baseline Sinonasal Outcome Test (SNOT-22) and Asthma Control Questionnaire (ACQ) responses, acoustic rhinometry, peak flow readings, and endoscopic scoring of nasal polyps were recorded prior to desensitization and after 6months of maintenance therapy. RESULTS: Twelve patients were recruited for participation and underwent desensitization. Eight patients continued maintenance therapy and follow up at 6months. Prior to desensitization, patients reported bothersome sinonasal symptoms with a median SNOT-22 score of 30.0±34.5 (interquartile range (IQR)). There was significant improvement after 6months of maintenance therapy to a median SNOT-22 score of 18.5±17.3 (p=0.025, Wilcoxon signed rank test). Acoustic rhinometry, endoscopic scores, ACQ and forced expiratory volume values remained stable at 6months. CONCLUSIONS: AERD patients may benefit from ASA desensitization with subjective sinonasal symptom improvement at 6months and stable asthma and objective sinonasal measures. Further discussion is needed in the otolaryngology community regarding ASA desensitization in AERD management.
Asunto(s)
Aspirina/uso terapéutico , Asma Inducida por Aspirina/terapia , Desensibilización Inmunológica , Pólipos Nasales/terapia , Rinitis/terapia , Sinusitis/terapia , Anciano , Aspirina/efectos adversos , Asma Inducida por Aspirina/etiología , Enfermedad Crónica , Estudios de Cohortes , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/inducido químicamente , Estudios Prospectivos , Rinitis/inducido químicamente , Rinometría Acústica , Prueba de Resultado Sino-Nasal , Sinusitis/inducido químicamenteRESUMEN
BACKGROUND: Aspirin desensitization (AD) has been the only available modifying treatment in aspirin-exacerbated respiratory disease (AERD). The mechanisms of AD are nonetheless poorly understood. Though very effective, AD is limited by its risks and side-effects. OBJECTIVE: Moving forward to the targeted biologicals era, the aim of this study was to characterize the airway inflammatory response to long-term AD, including TSLP dynamics, in order to assess potential new targets in AERD. PATIENTS AND METHODS: Adult patients with aspirin challenge-confirmed AERD underwent an oral AD followed by daily ingestion of aspirin for at least 6 months. Clinical data and inflammatory biomarkers were measured and compared, before and after AD. Induced sputum analyses were performed at baseline, one and six months after AD (differential cell count and levels of sputum supernatant leukotriene C4, prostaglandin D2 and E2, and TSLP). RESULTS: AD was followed by significant clinical improvement, as quantified by all monitored parameters. The good clinical outcomes of AD in our study are supported by overall changes observed in the arachidonic acid metabolites (decreased PGD2 over a constant LTC4/PGE2). TSLP increased (mean baseline 0.1⯱â¯0.03; 1 month 3.68⯱â¯7; 6 months 212.2⯱â¯44â¯pg/ml; pâ¯<â¯0.01). CONCLUSIONS: Our findings suggest that new biologicals blocking TSLP might have a clinical benefit in AERD, by cutting down the TSLP-induced PGD2 generation.
Asunto(s)
Aspirina/efectos adversos , Aspirina/inmunología , Asma Inducida por Aspirina/etiología , Asma Inducida por Aspirina/terapia , Desensibilización Inmunológica/métodos , Adulto , Anciano , Aspirina/administración & dosificación , Asma Inducida por Aspirina/inmunología , Citocinas/antagonistas & inhibidores , Citocinas/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Prostaglandina D2/antagonistas & inhibidores , Prostaglandina D2/metabolismo , Adulto Joven , Linfopoyetina del Estroma TímicoRESUMEN
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic eosinophilic rhinosinusitis, nasal polyps, asthma, and respiratory sensitivity to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). In addition to sensitivity to aspirin and NSAIDs, the majority of patients with AERD have been reported to have respiratory intolerance associated with the consumption of alcohol. METHODS: A multicenter prospective cohort study was performed. Patients with AERD confirmed by aspirin challenge were eligible to participate. Those who described themselves as able to tolerate alcohol consumption were excluded. Patients underwent aspirin desensitization following endoscopic sinus surgery. A questionnaire was distributed to patients before and after desensitization to determine pre-desensitization and post-desensitization symptoms associated with alcohol ingestion. RESULTS: Forty-five patients were enrolled and 37 patients completed the study. The most common pre-desensitization symptoms were nasal congestion (95.6%), rhinorrhea (46.7%), and wheezing (40%). Improvement in the ability to tolerate alcohol was noted in 86.5% of participants (95% confidence interval [CI], 75.5% to 97.5%) and 70.3% of participants (95% CI, 55.5% to 85.0%) described desensitization to be "very helpful" or "extremely helpful" for their ability to tolerate alcohol. CONCLUSION: The majority of patients with AERD who experience respiratory symptoms with alcohol consumption describe improvement in this domain following aspirin desensitization.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Antiinflamatorios no Esteroideos/administración & dosificación , Aspirina/administración & dosificación , Asma Inducida por Aspirina/prevención & control , Desensibilización Inmunológica , Hipersensibilidad a los Alimentos/prevención & control , Adulto , Anciano , Asma Inducida por Aspirina/etiología , Asma Inducida por Aspirina/patología , Desensibilización Inmunológica/normas , Femenino , Hipersensibilidad a los Alimentos/etiología , Hipersensibilidad a los Alimentos/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Aspirin desensitization has been associated with benefit in management of aspirin-exacerbated respiratory disease (AERD). An intervention that would encourage aspirin desensitization to be performed more frequently has substantial potential for improving outcomes and quality of life in patients with AERD. OBJECTIVE: We investigated whether omalizumab administration would be associated with attenuation of aspirin-provoked bronchospasm in patients with AERD undergoing aspirin desensitization. METHODS: We carried out a randomized, double-blind, placebo-controlled study in which subjects with AERD who fulfilled label criteria for omalizumab received omalizumab or placebo for 16 weeks, and then underwent aspirin desensitization. RESULTS: Eleven subjects completed aspirin desensitization. Of the 7 who were randomized to omalizumab, 5 had no respiratory reaction during aspirin desensitization. Compared with placebo, omalizumab was associated with a significantly greater likelihood for subjects with AERD to have no respiratory reaction during desensitization (P = .04, Fisher exact test). There was an overall difference in urinary leukotriene E4 (LTE4) levels in subjects who received omalizumab and did not have a respiratory reaction during desensitization compared with subjects randomized to placebo (P = .035, mixed model with interaction). Urinary LTE4 levels were significantly higher with respiratory reaction in placebo subjects compared with levels obtained after the 100-mg dose in AERD subjects who had no respiratory reaction (P < .001, mixed model with interaction). CONCLUSION: In atopic AERD subjects, omalizumab administration for 16 weeks was associated with "clinically silent" desensitization. Further studies to investigate the therapeutic utility of omalizumab in patients with AERD who are candidates for aspirin desensitization are warranted based on these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00555971.
Asunto(s)
Antiasmáticos/uso terapéutico , Aspirina/efectos adversos , Asma Inducida por Aspirina/tratamiento farmacológico , Espasmo Bronquial/prevención & control , Desensibilización Inmunológica/métodos , Omalizumab/uso terapéutico , Adulto , Asma Inducida por Aspirina/etiología , Asma Inducida por Aspirina/inmunología , Asma Inducida por Aspirina/orina , Biomarcadores/orina , Espasmo Bronquial/etiología , Espasmo Bronquial/inmunología , Espasmo Bronquial/orina , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Leucotrieno E4/orina , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Aspirin desensitization is an appropriate procedure for many patients with aspirin-exacerbated respiratory disease (AERD). Patients can require aspirin re-dosing, which prolongs the desensitization process. The frequency of this is not widely reported, nor is it known which patients will require multiple re-dosing. OBJECTIVE: To determine the frequency of and factors associated with repeat aspirin re-dosing during desensitization. METHODS: Charts of aspirin desensitization procedures from 2011 to 2016 at the University of Michigan Allergy/Immunology Clinic were reviewed. Reactions with provoking doses and number of dose repetitions were characterized. Previous AERD history, medical history, medications, and baseline spirometry were also recorded. Bivariate correlation and multivariate logistic regression were used to analyze associations between patient characteristics and need for repeated dosing of aspirin. RESULTS: A total of 84 positive-reacting patients during desensitization were identified. Of these patients, 33% required 2 or more aspirin dose repetitions during desensitization. Requiring 2 or more repeat doses during desensitization was associated with male gender (odds ratio = 6.194, P = .008), forced expiratory volume in 1 second (FEV1) decrease during desensitization (odds ratio = 1.075 per percent point drop, P = .021), and initial aspirin provoking dose during desensitization of 81 mg or lower (odds ratio = 11.111, P = .003). No association was found with pre-desensitization medications, asthma severity, AERD duration, or number/character of reported previous aspirin reactions. CONCLUSION: During aspirin desensitization for AERD, approximately one third of our patients require multiple repeat doses. Risk factors for multiple repeated doses include male gender, drop in FEV1, and lower aspirin provoking doses during desensitization. This information can help inform which patients may require multiple re-dosing for desensitization.
Asunto(s)
Aspirina/administración & dosificación , Asma Inducida por Aspirina/tratamiento farmacológico , Desensibilización Inmunológica/métodos , Administración Oral , Adulto , Anciano , Asma Inducida por Aspirina/etiología , Asma Inducida por Aspirina/inmunología , Esquema de Medicación , Cálculo de Dosificación de Drogas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Estudios Retrospectivos , Factores SexualesAsunto(s)
Aspirina/efectos adversos , Asma Inducida por Aspirina/diagnóstico , Espasmo Bronquial/diagnóstico , Síndrome de Dificultad Respiratoria/diagnóstico , Piel/efectos de los fármacos , Administración Cutánea , Corticoesteroides/uso terapéutico , Adulto , Albuterol/uso terapéutico , Aspirina/administración & dosificación , Asma Inducida por Aspirina/tratamiento farmacológico , Asma Inducida por Aspirina/etiología , Asma Inducida por Aspirina/fisiopatología , Espasmo Bronquial/inducido químicamente , Espasmo Bronquial/tratamiento farmacológico , Espasmo Bronquial/fisiopatología , Broncodilatadores/uso terapéutico , Femenino , Humanos , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/fisiopatología , Pruebas de Función Respiratoria , Piel/inmunología , Piel/metabolismoAsunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Asma Inducida por Aspirina/diagnóstico , Ibuprofeno/efectos adversos , Asma Inducida por Aspirina/etiología , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Olfato/inducido químicamente , Ruidos Respiratorios/etiología , Sinusitis/inducido químicamenteRESUMEN
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is an asthma phenotype that involves high costs and significant burden for health systems. OBJECTIVE: To determine the level of knowledge and attitudes towards AERD among Ecuadorian physicians. METHODS: Descriptive, observational study. A questionnaire about knowledge on the disease and attitude towards it (confidence in the treatment and importance of AERD, measured with a Likert scale) was developed. The answers about knowledge were dichotomized into right and wrong; attitude was rated as high or low. Means and percentages were obtained; the answers of doctors with or without specialty were compared using the chi-square test. RESULTS: One-hundred eighteen physicians participated. The age was 41.3 ± 11.7 years; 48.3 % were specialists. Less than 50% answered correctly the questions about knowledge. Specialist physicians obtained more correct answers regarding first symptoms, prevalence and leukotriene overproduction (67.9 %, 46.3% and 90.7 %), when compared with general practitioners (45.0 %, 25% and 74.6 %) (p < 0.05). More than 70 % of physicians indicated high confidence in the identification of patients with AERD. There were no significant differences in attitudes (p > 0.05). CONCLUSION: Medical education programs should be developed in order to improve the level of knowledge about AERD.
Antecedentes: La enfermedad respiratoria exacerbada por aspirina (EREA) es un fenotipo de asma que conlleva un alto costo e importante carga para los sistemas de salud. Objetivo: Determinar los conocimientos y actitudes hacia la EREA en médicos ecuatorianos. Métodos: Estudio observacional descriptivo. Se elaboró un cuestionario acerca de los conocimientos sobre la enfermedad y la actitud hacia ella (confianza en el tratamiento e importancia de la EREA, medidas con una escala de Likert). Las respuestas sobre conocimiento se dicotomizaron en correctas e incorrectas; la actitud se calificó como alta o baja. Se obtuvo media y porcentaje; con c2 se compararon las respuestas de los médicos con o sin especialidad. Resultados: Participaron 118 médicos. La edad fue de 41.3 ± 11.7 años; 48.3 % era especialista. Menos de 50 % contestó correctamente las preguntas sobre conocimiento. Los especialistas obtuvieron más respuestas correctas respecto a los primeros síntomas, prevalencia y sobreproducción de leucotrienos (67.9, 46.3 y 90.7 %), al compararlos con los médicos generales (45, 25 y 74.6 %) (p < 0.05). Más de 70 % de los médicos indicó alta confianza en la identificación de pacientes con EREA. No hubo diferencias significativas en las actitudes (p > 0.05). Conclusión: Se deben desarrollar programas de educación médica para mejorar el conocimiento acerca de la EREA.