RESUMO
OBJECTIVE: It has been hypothesized that some patients with chest tightness of unknown origin can be successfully treated with a bronchodilator and that they should be diagnosed with chest pain variant asthma. We conducted a prospective study to characterize newly diagnosed patients with chest tightness relieved with bronchodilator use and without characteristic bronchial asthma attacks. METHODS: Eleven patients were registered following recurrent positive responses of chest tightness to inhalation of a ß2-agonist. These patients underwent assessments of airway responsiveness to methacholine, bronchial biopsy and bronchial lavage under fiber-optic bronchoscopy before receiving treatment. RESULTS: For the patients with chest tightness relieved with bronchodilator use, the bronchial biopsy specimens exhibited significant increases in lymphocyte and macrophage infiltration (p < 0.05) and no significant increase in eosinophils (p = 0.2918) compared with the control subjects. The bronchial responsiveness to methacholine was increased in two of the patients with chest tightness, and it was not increased in seven; in addition, increased percentages of eosinophils were detected in bronchial lavage fluid (5% or more) from two patients, but no increase was detected in eight patients. CONCLUSIONS: We suspect that the chest tightness was induced by airway constriction in these patients, but further study is necessary to validate this hypothesis. We propose that the chest tightness relieved with bronchodilator use was attributed to airway constriction resulting from inflammation with lymphocytes and macrophages and/or that the chest tightness was directly attributed to airway inflammation. This clinical trial is registered at www.umin.ac.jp (UMIN13994 and UMIN 16741).
Assuntos
Broncodilatadores/farmacologia , Broncodilatadores/uso terapêutico , Dor no Peito/tratamento farmacológico , Dor no Peito/imunologia , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Adulto , Idoso , Obstrução das Vias Respiratórias/tratamento farmacológico , Obstrução das Vias Respiratórias/imunologia , Asma/tratamento farmacológico , Asma/imunologia , Hiper-Reatividade Brônquica , Testes de Provocação Brônquica , Líquido da Lavagem Broncoalveolar/citologia , Broncoscopia , Doença Crônica , Eosinófilos/metabolismo , Feminino , Fluticasona/farmacologia , Fluticasona/uso terapêutico , Humanos , Linfócitos/metabolismo , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Procaterol/farmacologia , Procaterol/uso terapêutico , Estudos Prospectivos , Testes de Função RespiratóriaRESUMO
BACKGROUND: Attenuation of ischemia reperfusion injury (IRI) is important in lung transplantation. Our group previously reported that ß2-adrenoreceptor agonist inhalation during the period before procurement successfully attenuated IRI in donated lungs after cardiac death. We therefore hypothesized that ß2-adrenoreceptor agonist inhalation during ex vivo lung perfusion (EVLP) after procurement might also have a protective effect. METHODS: Cardiac-dead beagles were left at room temperature for 210 minutes, and all lungs were subsequently procured and subjected to EVLP for 240 minutes. The beagles were allocated to 2 groups: the ß2 group (receiving an aerosolized ß2-adrenoreceptor agonist 20 minutes after initiation of EVLP; n = 7) and the control group (receiving an aerosolized control solvent at the same time point; n = 6). Physiologic data, including lung function, were evaluated during EVLP. RESULTS: The ß2 group showed significantly lower peak airway pressure and pulmonary artery pressure than the control group. Dynamic pulmonary compliance was higher, pulmonary vascular resistance (PVR) was lower, and the wet-to-dry lung weight ratio was lower in the ß2 group than in the control group. Cyclic adenosine monophosphate (cAMP) and total adenosine nucleotide (TAN) levels in lung tissue after EVLP were higher in the ß2 group than in the control group. The ß2 group also showed more cystic fibrosis transmembrane conductance regulator (CFTR) gene expression. CONCLUSIONS: After procurement, ß2-adrenoreceptor agonist inhalation during EVLP attenuates lung injury in a canine model of organ donation after cardiac death.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Pulmão/irrigação sanguínea , Procaterol/administração & dosagem , Traumatismo por Reperfusão/prevenção & controle , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Animais , Cães , Técnicas In Vitro , Perfusão , Procaterol/uso terapêuticoRESUMO
Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of many respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). To evaluate the treatment responses of procaterol and CD38 inhibitors in an ozone-induced AHR mice model, we hypothesized that procaterol and two synthetic CD38 inhibitors (Compounds T and H) might have therapeutic effects on the ozone-induced AHR mice model, and the nuclear factor-kappaB (NF-κB) pathway and the CD38 enzymatic activity might be involved in the mechanisms. With the exception of the Control group, ozone exposure was used to establish an AHR model. Male Kunming mice in the Procaterol and CD38 inhibitors groups were treated with an emulsifier of procaterol hydrochloride, Compound T or H. Results indicated that (1) no drug showed severe toxicity in this study; (2) ozone exposure induced airway inflammation and AHR; (3) intragastric treatment with procaterol and Compound T achieved potent therapeutic effects, but Compound H did not show any therapeutic effect; (4) the NF-κB pathway was involved in both the pathogenic mechanisms of ozone and therapeutic mechanisms of procaterol and Compound T; (5) however, the in vivo effect of Compound T was not caused by its inhibitory activity on CD38. Taken together, procaterol and Compound T are potentially good drugs to treat asthma and COPD complicated with ozone exposure.
Assuntos
Antiasmáticos/uso terapêutico , Benzoatos/uso terapêutico , Hiper-Reatividade Brônquica/tratamento farmacológico , Indóis/uso terapêutico , Procaterol/uso terapêutico , ADP-Ribosil Ciclase 1/antagonistas & inibidores , Animais , Antiasmáticos/farmacologia , Benzoatos/farmacologia , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/patologia , Hiper-Reatividade Brônquica/fisiopatologia , Testes de Provocação Brônquica , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Indóis/farmacologia , Contagem de Leucócitos , Pulmão/imunologia , Pulmão/patologia , Masculino , Glicoproteínas de Membrana/antagonistas & inibidores , Cloreto de Metacolina , Camundongos , NF-kappa B/imunologia , Ozônio , Procaterol/farmacologiaRESUMO
A 24-year-old Japanese man presented with a complaint of chest pressure. He began to have severe chest pressure several times a day. The attack was frequently induced by smoking. During an attack, we gave him an inhalation with procaterol hydrochloride, and his chest tightness disappeared. He was suspected to have chest pain variant asthma. We asked him to stop smoking, and gave him corticosteroid, and his chest pressure did not reappear. This disease is relatively unknown. There is a need for a better dissemination of knowledge about this disease.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Asma/complicações , Dor no Peito/tratamento farmacológico , Procaterol/uso terapêutico , Fumar/efeitos adversos , Adulto , Dor no Peito/etiologia , Humanos , MasculinoRESUMO
A 39-year-old man consulted our hospital because of severe constrict pain at the sternal area and heavy sensation in chest. His chest pain improved with procaterol hydrochloride, he was diagnosed as having chest pain variant asthma. His symptoms improved with corticosteroid and cysteinyl leukotriene antagonist. Not so many articles have been reported that concerned with this disease. There is a need for a better dissemination of knowledge about this disease.
Assuntos
Asma/complicações , Dor no Peito/etiologia , Acetatos/uso terapêutico , Adulto , Androstadienos/uso terapêutico , Asma/tratamento farmacológico , Dor no Peito/tratamento farmacológico , Ciclopropanos , Quimioterapia Combinada , Fluticasona , Humanos , Antagonistas de Leucotrienos/uso terapêutico , Masculino , Proteínas de Membrana/antagonistas & inibidores , Prednisolona/uso terapêutico , Procaterol/uso terapêutico , Quinolinas/uso terapêutico , Receptores de Leucotrienos , SulfetosRESUMO
Intraabdominal sepsis can lead to acute respiratory failure, and concomitant diaphragmatic dysfunction may be aggravated by sepsis-induced airway hyperreactivity. We previously reported that isoproterenol, a nonselective beta-adrenoceptor agonist, increased diaphragmatic contractility and accelerated recovery from fatigue during sepsis. The purpose of this study was to demonstrate the direct inotropic effect of a potent bronchodilator and beta(2)-selective adrenoceptor agonist, procaterol, on fatigued diaphragmatic contractility in an intraabdominal septic model. Rats were divided into two groups: a cecal ligation and perforation (CLP) group and a sham group. CLP was performed in the CLP group whereas laparotomy alone was performed in the sham group. The left hemidiaphragm was removed at 16 h after the operation. The diaphragmatic tissues were exposed to procaterol (10(-8)-10(-6) M), and muscle contractility was assessed. Intracellular cyclic AMP levels were also measured in the CLP model. Procaterol caused an upward shift in the force-frequency curves in the CLP group whereas it had no effect on the curves in the sham group. Procaterol significantly increased cyclic AMP levels in the CLP model. We conclude that the potent bronchodilator procaterol had a direct and positive inotropic effect on the diaphragm in an intraabdominal septic model.
Assuntos
Broncodilatadores/uso terapêutico , Diafragma/fisiopatologia , Procaterol/uso terapêutico , Sepse/tratamento farmacológico , Sepse/fisiopatologia , Antagonistas Adrenérgicos beta/uso terapêutico , Animais , AMP Cíclico/metabolismo , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Propranolol/uso terapêutico , Ratos , Ratos WistarAssuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Músculo Liso/efeitos dos fármacos , Canais de Potássio/efeitos dos fármacos , Potássio/metabolismo , Antagonistas de Receptores Adrenérgicos beta 1 , Antagonistas de Receptores Adrenérgicos beta 2 , Antagonistas Adrenérgicos beta/farmacologia , Albuterol/farmacologia , Albuterol/uso terapêutico , Animais , Antiasmáticos/farmacologia , Asma/metabolismo , Broncodilatadores/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Charibdotoxina/farmacologia , Cobaias , Humanos , Transporte de Íons/efeitos dos fármacos , Isoproterenol/farmacologia , Isoproterenol/uso terapêutico , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/metabolismo , Nifedipino/farmacologia , Peptídeos/farmacologia , Procaterol/farmacologia , Procaterol/uso terapêutico , Terbutalina/farmacologia , Terbutalina/uso terapêuticoRESUMO
Objective of the study: To determine the maximal bronchodilator dose of procaterol and pirbuterol administered by inhalation with an without an aerochamber (Aerocâmera) to children with acute brinchial asthma attacks. Type of study: Prospective. 18 children (6-15 years of age) with acute bronchial asthma attacks (FEV1 < 80 per cents of the predicted value) received pirbuterol (N = 10) or procaterol (N = 8) by metered-dose inhaler, one puff every 5 minutes, for a total of five doses. During another acute attack, the same patient received the same medication with the aid of a spacer (Aerocâmera). Clinical evaluation and pulmonary function tests were performed 5 minutes after each inhaled dose. Results: For both drugs, maximal bronchodilation was obtained after the second dose. No significant side effects were observed even after procaterol doses of 50 µg or pirbuterol doses of 1000 µg. The results were unaffected by the use of the spacer. Conclusions: The doses that induced maximal bronchodilation were 400 µg pirbuterol and 20 µg procaterol Although the spacer did not change the results, it is a valuable aid for patients who have difficulty in using the metered-dose inhaler (M.D.I.)