Reações respiratórias agudas desencadeadas por AINEs nos pacientes com urticária crônica espontânea exacerbada por AINEs / Acute respiratory reactions triggered by NSAIDs in patients with NSAID-exacerbated chronic spontaneous urticaria

Introdução: Até 30% dos pacientes com urticária crônica espontânea (UCE) exacerbam com anti-inflamatório não esteroidal (AINE). Estas são reações de hipersensibilidade não imunológicas atribuídas a propriedades farmacológicas destes medicamentos. A hipersensibilidade aos AINEs pode estar associada a uma urticária mais grave ou mais prolongada. Aproximadamente 10% dos pacientes com UCE exacerbada por AINEs também apresentam sintomas respiratórios após a exposição aos AINEs (chamadas de reações mistas). Objetivo: Avaliar a presença de manifestações respiratórias após o uso de AINE nos pacientes com UCE exacerbada por AINEs. Métodos: Neste estudo retrospectivo, os prontuários eletrônicos de pacientes com UCE exacerbada por AINEs atendidos em um hospital terciário foram revisados. Os pacientes sem história de exacerbação ou que não sabiam referir o uso ou a piora dos sintomas com AINEs foram excluídos. Foram avaliados sintomas respiratórios agudos desencadeados pelos AINEs e sintomas respiratórios crônicos, concomitante a UCE. Resultados: Foram avaliados 92 pacientes, sendo 90% do sexo feminino, média de idade de 52 anos e tempo de doença de 12,9 anos. Os AINEs mais comuns foram a dipirona (65,2%) e o diclofenaco (33,7%). A história de sintomas respiratórios agudos associados ao quadro cutâneo, após a exposição ao AINE, estava presente em 13% dos pacientes. Quarenta pacientes (43,5%) apresentavam rinite crônica e, destes, 13 pacientes (32,5%) possuíam também diagnóstico de asma, e 2 (5%) apresentavam pólipos nasais. Os sintomas respiratórios agudos foram mais frequentes nos pacientes com rinite crônica (22,5%) quando comparados com os pacientes sem doença respiratória crônica (5,8%). Conclusões: O presente estudo mostrou que 13% dos pacientes com UCE exacerbada por AINEs também apresentavam sintomas respiratórios agudos após o uso de AINEs, sendo denominados pacientes com reações de hipersensibilidade mista ou "blended reactions". Destes, 75% apresentavam doença respiratória crônica de base.

Introduction: Up to 30% of patients with chronic spontaneous urticaria (CSU) exacerbate with non-steroidal anti-inflammatory drugs (NSAIDs). These are non-immunological hypersensitivity reactions attributed to the pharmacological properties of these drugs. Hypersensitivity to NSAIDs may be associated with more severe or long-lasting urticaria. Approximately 10% of patients with NSAID-exacerbated CSU also present respiratory symptoms after exposure to NSAIDs (the so-called "blended reactions"). Objective: To evaluate the presence of respiratory manifestations after the use of NSAIDs in patients with NSAID-exacerbated CSU. Methods: In this retrospective study, the electronic medical records of patients with NSAID-exacerbated CSU seen at a tertiary hospital were reviewed. Patients without a history of exacerbation or who did not know whether they had used NSAIDs or whether their symptoms worsened after the use of NSAIDs were excluded. Acute respiratory symptoms triggered by NSAIDs and chronic respiratory symptoms coexisting with CSU were assessed. Results: A total of 92 patients were evaluated; 90% were female, mean age was 52 years, and disease duration was 12.9 years. The NSAIDs most commonly used were dipyrone (65.2%) and diclofenac (33.7%). History of acute respiratory symptoms associated with the cutaneous condition after exposure to NSAIDs was present in 13% of the patients. Forty patients (43.5%) had chronic rhinitis; of these, 13 patients (32.5%) also had a diagnosis of asthma, and 2 (5%) presented nasal polyps. Acute respiratory symptoms were more frequent in patients with chronic rhinitis (22.5%) when compared to patients without any chronic respiratory disease (5.8%). Conclusions: The present study showed that 13% of the patients with NSAID-exacerbated CSU also presented acute respiratory symptoms after the use of NSAIDs, i.e., they were patients with mixed hypersensitivity reactions or "blended reactions." Of these, 75% presented an underlying chronic respiratory disease.

Aspirin attenuates the anti-inflammatory effects of theophylline via inhibition of cAMP production in mice with non-eosinophilic asthma

Theophylline is commonly used to treat severe asthma and chronic obstructive pulmonary disease (COPD) characterized by non-eosinophilic inflammation. Acetyl salicylic acid (ASA) is one of the most widely used medications worldwide, but up to 20% of patients with asthma experience aggravated respiratory symptoms after taking ASA. Here we evaluated the adverse effect of ASA on the therapeutic effect of theophylline in mice with non-eosinophilic asthma. A non-eosinophilic asthma mouse model was induced by airway sensitization with lipopolysaccharide-containing allergen and then challenged with allergen alone. Therapeutic intervention was performed during allergen challenge. Theophylline inhibited lung inflammation partly induced by Th1 immune response. ASA attenuated the beneficial effects of theophylline. However, co-administration of the ASA metabolite salicylic acid (SA) showed no attenuating effect on theophylline treatment. The therapeutic effect of theophylline was associated with increase in cAMP levels, which was blocked by co-treatment of theophylline and ASA. ASA co-treatment also attenuated the anti-inflammatory effects of a specific phosphodiesterase 4 inhibitor. These results demonstrate that ASA reverses anti-inflammatory effects of theophylline, and that ASA exerts its adverse effects through the inhibition of cAMP production. Our data suggest that ASA reverses lung inflammation in patients taking theophylline, although clinical evidence will be needed.

Airway Responsiveness to Inhaled Aspirin is Influenced by Airway Hyperresponsiveness in Asthmatic Patients

BACKGROUND/AIMS: Many patients with aspirin-induced asthma have severe methacholine airway hyperresponsiveness (AHR), suggesting a relationship between aspirin and methacholine in airway response. This study was performed to determine whether methacholine AHR affects the response of asthmatics to inhaled aspirin. METHODS: The clinical records of 207 asthmatic patients who underwent inhalation challenges with both aspirin and methacholine were reviewed retrospectively. An oral aspirin challenge was performed in patients with a negative inhalation response. The bronchial reactivity index (BRindex) was calculated from the percent decrease in lung function divided by the last dose of the stimulus. RESULTS: Forty-one (20.9%) and 14 (7.1%) patients showed a positive response to aspirin following an inhalation and oral challenge, respectively. Only 24.3 and 14.3% of the responders had a history of aspirin intolerance, respectively. The methacholine BRindex was significantly higher in the inhalation responders (1.46 +/- 0.02) than in the oral responders (1.36 +/- 0.03, p < 0.01) and in non-responders (n = 141, 1.37 +/- 0.01, p < 0.001). The aspirin BRindex was significantly correlated with the methacholine BRindex (r = 0.270, p < 0.001). Three of four patients who received the oral challenge, despite a positive inhalation test, showed negative responses to the oral challenge. Two of these patients had severe AHR. CONCLUSIONS: A considerable number of asthmatic patients with no history of aspirin intolerance responded to the inhalation aspirin challenge. The airway response to aspirin was significantly correlated with methacholine-AHR, and a false-positive response to aspirin inhalation test seemed to occur primarily in patients with severe AHR.