RESUMO
Respiratory allergies affect humans worldwide, causing extensive morbidity and mortality. They include allergic rhinitis (AR), asthma, pollen food allergy syndrome (PFAS), aspirin-exacerbated respiratory disease (AERD), and nasal polyps (NPs). The study of respiratory allergic diseases requires new technologies for early and accurate diagnosis and treatment. Omics technologies provide the tools required to investigate DNA, RNA, proteins, and other molecular determinants. These technologies include genomics, transcriptomics, proteomics, and metabolomics. However, proteomics is one of the main approaches to studying allergic disorders' pathophysiology. Proteins are used to indicate normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. In this field, the principal goal of proteomics has been to discover new proteins and use them in precision medicine. Multiple technologies have been applied to proteomics, but that most used for identifying, quantifying, and profiling proteins is mass spectrometry (MS). Over the last few years, proteomics has enabled the establishment of several proteins for diagnosing and treating respiratory allergic diseases.
Assuntos
Asma , Proteômica , Genômica/métodos , Humanos , Espectrometria de Massas , Metabolômica/métodos , Proteômica/métodosRESUMO
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a syndrome characterised by chronic rhinosinusitis, nasal polyps, asthma and aspirin intolerance. An imbalance of eicosanoid metabolism with anover-production of cysteinyl leukotrienes (CysLTs) has been associated with AERD. However, the precise mechanisms underlying AERD are unknown. OBJECTIVE: To establish the transcriptome of the nasal polyp airway epithelial cells derived from AERD patients to discover gene expression patterns in this disease. METHODS: Nasal airway epithelial cells were isolated from 12 AERD polyps and 8 AERD non-polyp nasal mucosa samples as controls from the same subjects. Utilising the Illumina HiSeq 2500 platform, RNA samples were sequenced. Potential gene candidate DMRT3 was selected from the differentially-expressed genes for validation. RESULTS: Comparative transcriptome profiling of nasal epithelial cells was accomplished in AERD. A total of 20 genes had twofold mean regulation expression differences or greater. In addition, 8 genes were upregulated, including doublesex and mab-3 related transcription factor 3 (DMRT3), and 12 genes were downregulated. Differentially regulated genes comprised roles in inflammation, defence and immunity. Metabolic process and embryonic development pathways were significantly enriched. Enzyme-linked immune sorbent assay (ELISA) results of DMRT3 in AERD patients were significantly upregulated compared to controls (p = 0.03). Immunohistochemistry (IHC) of AERD nasal polyps localised DMRT3 and was predominantly released in the airway epithelia. CONCLUSION: Findings suggest that DMRT3 could be potentially involved in nasal polyp development in AERD patients. Furthermore, several genes are downregulated, hinting at the dedifferentiation phenomenon in AERD polyps. However, further studies are imperative to confirm the exact mechanism of polyp formation in AERD patients.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Pólipos Nasais/metabolismo , Transtornos Respiratórios/tratamento farmacológico , Transtornos Respiratórios/metabolismo , Fatores de Transcrição TFII/metabolismo , Transcriptoma , Adulto , Aspirina/efeitos adversos , Asma Induzida por Aspirina/genética , Asma Induzida por Aspirina/metabolismo , Doença Crônica , Células Epiteliais/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Leucotrienos/metabolismo , Masculino , Pessoa de Meia-Idade , Lavagem Nasal , Pólipos Nasais/imunologia , RNA-Seq , Sinusite/imunologia , Sinusite/metabolismo , Testes CutâneosRESUMO
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is an aggressive respiratory tract inflammatory disorder manifesting as asthma, chronic rhinosinusitis with nasal polyposis, and a respiratory sensitivity to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Corticosteroids, both systemic and topical/inhaled, are used to treat inflammation of the upper and lower airways. Our objective was to examine the potential impact of complete endoscopic sinus surgery (ESS) and aspirin desensitization (AD) on short-term and long-term corticosteroid use. METHODS: For this pilot study, a retrospective chart review of all patients with AERD who underwent ESS followed by AD was performed. Daily prednisone use, average daily prednisone dose, and inhaled corticosteroid use were analyzed at the following time points: preoperative, postoperative/pre-AD, and 2 to 3 months, 4 to 6 months, 7 to 12 months, and 13 to 24 months following AD. RESULTS: A total of 125 patients underwent ESS followed by AD. Compared to preoperatively, patients who underwent ESS and AD were less likely to be on daily prednisone at all time points and upon long-term follow-up (32% preoperatively vs 10% at 13 to 24 months, McNemar's test = 9.00, p = 0.009). Average daily prednisone dose decreased from 10.6 ± 7.9 mg preoperatively to 3.8 ± 2.6 mg at 13 to 24 months following AD (Mann-Whitney U; W = 122, p = 0.01). Similarly, high-dose and medium-dose inhaled corticosteroid use decreased from 18% to 7% and from 36% to 22% respectively (Pearson's chi-square = 8.06, p = 0.05). CONCLUSION: In our AERD cohort who underwent ESS followed by AD, there was an observed decrease in overall systemic and topical/inhaled corticosteroid use. These findings can have implications for treatment given the potentially hazardous side effects of corticosteroid use.
Assuntos
Asma Induzida por Aspirina , Pólipos Nasais , Anti-Inflamatórios não Esteroides , Aspirina/efeitos adversos , Dessensibilização Imunológica , Humanos , Pólipos Nasais/cirurgia , Projetos Piloto , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Previous work has shown that chronic rhinosinusitis (CRS) severity may be associated with particulate matter 2.5 (PM2.5 ) and black carbon (BC) in CRS patients without nasal polyps (CRSsNP). Data regarding occupational exposures, however, are lacking. We assessed the impact of PM2.5 , BC, as well as occupational airborne exposure on CRS disease severity. METHODS: Patients with CRS with nasal polyps (CRSwNP), CRSsNP, and aspirin-exacerbated respiratory disease (AERD) were identified from an institutionwide database. Spatial modeling from 37 pollutant monitoring sites in Allegheny County was used to estimate exposures. Patient occupations using the 2010 Standard Occupation Classification (SOC10) and airborne occupation exposures to vapors, gases, dusts, fumes, fibers and mists (VGDFFiM) or diesel fumes were recorded. Disease severity was measured by modified Lund-Mackay score (LMS), systemic corticosteroid therapy, and incidence of functional endoscopic sinus surgery (FESS). RESULTS: Two hundred thirty-four patients were included (CRSwNP, n = 113; CRSsNP, n = 96; AERD, n = 25). The prevalence of AERD among those with CRSwNP was 18%. Patients exposed to VGDFFiM or diesel fumes required higher steroid doses vs nonexposed patients (p = 0.015 and p = 0.03, respectively); patients with VGDFFiM levels >5% were more likely to undergo FESS vs nonexposed patients (p = 0.0378). There was no difference in PM2.5 and BC with regard to disease severity and FESS between CRSwNP, CRSsNP, and AERD patients. Steroid use was significantly higher in CRSwNP and AERD vs CRSsNP (p = 0.001). LMS was significantly higher in AERD as compared with CRSwNP and CRSsNP (p = 0.001). CONCLUSION: Occupational airborne exposure to VGDFFiM correlated with increased prevalence of FESS and need for corticosteroids in CRS patients. There was no difference in PM2.5 and BC levels and disease severity outcome measures between CRS subtypes in this subset.
Assuntos
Poluentes Ocupacionais do Ar/análise , Asma Induzida por Aspirina/epidemiologia , Doença Crônica/epidemiologia , Pólipos Nasais/epidemiologia , Rinite/epidemiologia , Sinusite/epidemiologia , Aerossóis/análise , Monitoramento Ambiental , Feminino , Gases/análise , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Material Particulado/análise , Pennsylvania/epidemiologia , Prevalência , Índice de Gravidade de Doença , Emissões de Veículos/análiseRESUMO
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.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Asma Induzida por Aspirina/prevenção & controle , Dessensibilização Imunológica , Hipersensibilidade Alimentar/prevenção & controle , Adulto , Idoso , Asma Induzida por Aspirina/etiologia , Asma Induzida por Aspirina/patologia , Dessensibilização Imunológica/normas , Feminino , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
Introdução: A doença respiratória exacerbada por aspirina (DREA), caracterizada por asma, rinossinusite, polipose nasal e hipersensibilidade à aspirina, pode ser sugerida pela história, porém, o teste de provocação oral com a aspirina é o padrão ouro para o diagnóstico, e a dessensibilização com aspirina, uma boa opção terapêutica. O objetivo do trabalho foi avaliar as características clínicas e os resultados dos procedimentos de provocação e/ou de dessensibilização com aspirina nos pacientes com suspeita de DREA, bem como observar se houve correlação com a literatura. Métodos: Neste estudo retrospectivo, foram avaliados prontuários de pacientes adultos com suspeita de DREA, em acompanhamento em um hospital terciário e que foram submetidos à provocação e/ ou dessensibilização com aspirina. Dois protocolos foram utilizados para o teste de provocação: (a) cetorolaco nasal/aspirina oral, e (b) apenas aspirina oral. Foram avaliados: características clínicas, a positividade do teste e da dessensibilização e a comparação deste resultado com a história prévia. Resultados: Participaram do estudo 24 pacientes, com média de idade de 50,8 anos, sendo 54,2% do sexo feminino. Treze pacientes (54,2%) tinham asma grave, e seis (25%), asma alérgica. Média do volume expiratório forçado no primeiro segundo (VEF1) foi de 81,5% do valor predito. Dezenove pacientes (79,2%) referiam broncoespasmo e/ou urticária com anti-inflamatórios não esteroidais. Cinco pacientes não faziam associação com essas medicações. Independente do protocolo usado, onze pacientes (45,8%) apresentaram teste positivo, confirmando a DREA, sendo que seis pacientes (25%) foram submetidos à dessensibilização com aspirina. Oito pacientes (33,3%) apresentaram provocação negativa, e cinco (20,8%) não conseguiram completar a investigação devido à presença de urticária. Conclusões: Pacientes com suspeita de DREA deveriam ser submetidos à provocação com aspirina para confirmar o diagnóstico. Um quarto dos pacientes foi submetido à dessensibilização, entretanto, para a maioria dos pacientes não foi possível confirmar o diagnóstico ou o teste foi negativo.
Introduction: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, rhinosinusitis, nasal polyps, and aspirin hypersensitivity. The condition may be suggested by the patient's medical history; however, oral provocation test with aspirin is the gold standard for diagnosis, and desensitization with aspirin, a good therapeutic option. The aim of this study was to evaluate the clinical characteristics and results obtained with aspirin provocation tests and/or desensitization in patients with suspected AERD, as well as to correlate these data with the literature available. Methods: In this retrospective study, the medical records of adult patients with suspected AERD followed at a tertiary hospital who underwent aspirin challenge and/or desensitization were evaluated. Two protocols were used for the challenge test: (a) nasal ketorolac/ oral aspirin; and (b) oral aspirin alone. Clinical characteristics and both test and desensitization positivity were evaluated, and the results were compared with data from the patient's history. Results: Twenty-four patients participated in the study, with a mean age of 50.8 years; 54.2% were female. Thirteen patients (54.2%) had severe asthma, and six (25%) had allergic asthma. Mean forced expiratory volume in 1 second (FEV1) was 81.5% of the predicted value. Nineteen patients (79.2%) reported bronchospasm and/or urticaria with nonsteroidal anti-inflammatory drugs. Five patients had no association with these medications. Regardless of the protocol used, eleven patients (45.8%) presented positive tests, confirming the diagnosis of AERD, and six patients (25%) underwent aspirin desensitization. Eight patients (33.3%) had negative results in the provocation test, and five (20.8%) failed to complete the investigation due to the presence of urticaria. Conclusions: Patients with suspected AERD should undergo aspirin challenge to confirm the diagnosis. One-fourth of our patients underwent desensitization, but for most patients, either it was not possible to confirm the diagnosis or the test resulted negative.
Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Asma , Anti-Inflamatórios não Esteroides , Aspirina , Pólipos Nasais , Diagnóstico , Hipersensibilidade , Pacientes , Terapêutica , Volume Expiratório Forçado , Estudos Retrospectivos , Asma Induzida por AspirinaRESUMO
Aspirin-exacerbated respiratory disease is a chronic and treatment-resistant disease, characterized by the presence of eosinophilic rhinosinusitis, nasal polyposis, bronchial asthma, and nonsteroidal anti-inflammatory drugs hypersensitivity. Alterations in arachidonic acid metabolism may induce an imbalance between pro-inflammatory and anti-inflammatory substances, expressed as an overproduction of cysteinyl leukotrienes and an underproduction of prostaglandin E2. Although eosinophils play a key role, recent studies have shown the importance of other cells and molecules in the development of the disease like mast cells, basophils, lymphocytes, platelets, neutrophils, macrophages, epithelial respiratory cells, IL-33 and thymic stromal lymphopoietin, making each of them promissory diagnostic and treatment targets. In this review, we summarize the most important clinical aspects of the disease, including the current topics about diagnosis and treatment, like provocation challenges and aspirin desensitization. We also discuss recent findings in the pathogenesis of the disease, as well as future trends in diagnosis and treatment, including monoclonal antibodies and a low salicylate diet as a treatment option.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Asma Induzida por Aspirina/imunologia , Asma/induzido quimicamente , Pólipos Nasais/induzido quimicamente , Doenças Respiratórias/induzido quimicamente , Rinite/induzido quimicamente , Sinusite/induzido quimicamente , Adulto , Anticorpos Monoclonais/uso terapêutico , Ácido Araquidônico/metabolismo , Asma/terapia , Asma Induzida por Aspirina/diagnóstico , Asma Induzida por Aspirina/epidemiologia , Asma Induzida por Aspirina/terapia , Cisteína/metabolismo , Citocinas/metabolismo , Dessensibilização Imunológica/métodos , Dinoprostona/metabolismo , Progressão da Doença , Síndrome de Hipersensibilidade a Medicamentos , Eosinófilos/metabolismo , Feminino , Humanos , Leucotrienos/metabolismo , Masculino , Mastócitos/metabolismo , Pólipos Nasais/terapia , Doenças Respiratórias/diagnóstico , Doenças Respiratórias/epidemiologia , Doenças Respiratórias/terapia , Rinite/terapia , Sinusite/terapia , Linfopoietina do Estroma do TimoRESUMO
BACKGROUND: In this study we assessed patient outcomes after complete endoscopic sinus surgery (ESS) and aspirin desensitization for patients with aspirin-exacerbated respiratory disease (AERD). METHODS: A retrospective chart review was conducted for patients with aspirin challenge-proven AERD who underwent complete ESS followed by aspirin desensitization. Outcomes assessed included need for revision surgery and quality-of-life measures using the 22-item Sino-Nasal Outcomes Test (SNOT-22). Data were collected preoperatively, postoperatively prior to desensitization, and then at intervals post-desensitization through 30 months after aspirin desensitization. A longitudinal linear mixed-effects model was used for data analysis. RESULTS: Thirty-four patients met the inclusion criteria for this study. Thirty-two patients successfully completed aspirin desensitization and were subsequently followed for 30 months after desensitization. Two patients were unable to complete desensitization. Five patients discontinued aspirin maintenance therapy due to gastrointestinal and respiratory side effects. Within the follow-up period, there were only 3 (9.4%) revision sinus surgeries. Notably, 1 of these revision cases occurred in a patient who had discontinued aspirin maintenance therapy. After surgical treatment and prior to desensitization patients had significant reductions in SNOT-22 scores. Our results demonstrate that total SNOT-22 scores remained statistically unchanged from immediate post-desensitization throughout the 30-month follow-up period. CONCLUSION: Complete sinus surgery followed by timely aspirin desensitization and maintenance therapy is an effective combination in the long-term management of sinus disease in patients with AERD.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Asma Induzida por Aspirina/terapia , Dessensibilização Imunológica , Endoscopia , Seios Paranasais/cirurgia , Humanos , Reoperação , Índice de Gravidade de Doença , Sinusite/cirurgia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: The aspirin exacerbated respiratory disease (AERD) shows a prevalence of 7% among asthmatics and increases to 14% in patients with difficult to control asthma. Treatment includes the use of inhibitors of leukotriene receptor (), intranasal steroids, polypectomy, asthma management according to the severity and avoid taking nonsteroidal anti-inflammatory drugs (NSAIDs). In some patients it is necessary desensitization protocol to it. CLINICAL CASES: Two patients diagnosed with respiratory disease exacerbated by aspirin, with poor asthma control and need for multiple polypectomies, despite optimal pharmacological management, carrying out protocol desensitization to aspirin (AAS) successful, now after 4 years of having carried out, they have adequate asthma control without need for polypectomies with a maintenance dose of aspirin 150 mg/day.
Antecedentes: la prevalencia de enfermedad respiratoria exacerbada por aspirina es de 7% en pacientes asmáticos y se incrementa, incluso, a 14% en pacientes con asma de difícil control. El tratamiento incluye la prescripción de inhibidores de los receptores de leucotrienos, esteroides intranasales, polipectomías, tratamiento del asma según su severidad y evitar los antiinflamatorios no esteroides. En algunos pacientes es necesario realizar el protocolo de desensibilización a la aspirina. Casos clínicos: se describen 2 mujeres con diagnóstico de enfermedad respiratoria exacerbada por la administración de aspirina, con escaso control de los cuadros de asma y a quienes fue necesario realizar múltiples polipectomías, a pesar del manejo farmacológico óptimo. Se llevó a cabo protocolo de desensibilización a aspirina (AAS); la respuesta fue positiva. Después de cuatro años, las pacientes presentan adecuado control del asma, con una dosis de mantenimiento de AAS de 150 mg/ día y no han requerido polipectomías.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Asma Induzida por Aspirina/terapia , Dessensibilização Imunológica/métodos , Pólipos Nasais/cirurgia , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/imunologia , Aspirina/efeitos adversos , Aspirina/imunologia , Asma Induzida por Aspirina/imunologia , Humanos , Quimioterapia de Manutenção , Pólipos Nasais/imunologia , Pólipos Nasais/terapiaRESUMO
BACKGROUND: Systemic reactions are related to the pathogenesis of Aspirin Exacerbated Respiratory Disease (AERD). With this work we wanted to study the changes in the systemic levels of inflammatory mediators in both baseline and after oral aspirin challenge in patients with and without AERD. METHODS: Patients with nasal polyposis and asthma with AERD (n=20) and without (n=18) were orally challenged with aspirin in a single-blind placebo controlled study. Serum samples and urine were collected before and 6h after placebo and aspirin oral challenges. Serum levels of inflammatory mediators were assayed by using the Luminex technology and ELISA. The concentrations of 9-alpha, 11-beta prostaglandin F2, and leukotriene E4 (uLTE4) were measured in urine samples by ELISA. The expression of T-cell surface markers was analyzed in peripheral blood mononuclear cells isolated before and after the challenges. RESULTS: AERD patients showed significantly higher baseline levels of s-IL-5R-alpha, uLTE4 and percentage of CD4(+)CD25(+)CD127(pos) and CD4(+)CD45RA(-)CD45RO(+) but decreased levels of TGF-ß1 and number of CD4(+)CD25(+)CD127(neg) cells. Aspirin challenge induced the release of uLTE4, IL-6 and increased the number of CD4(+)CD45RA(-)CD45RO(+) memory T-cells only in AERD patients but failed to reduce the levels of sCD40L as observed in non-AERD subjects. Further, IL-8 and sIL-5R-alpha levels directly correlated with the PD20ASA and the effects of aspirin on IL-6 and number of memory T-cells was more pronounced in subjects showing more strong reaction (bronchial and nasal). CONCLUSIONS: AERD patients have a differential baseline inflammatory pattern that supports the role inflammation as underlying mechanism of the disease. Systemic response to oral aspirin challenge was related to an increase in serum IL-6 and the number of circulating memory T-cells in AERD patients.