RESUMO
PURPOSE: To evaluate fluticasone propionate/formoterol (FP/FORM) in COPD. PATIENTS AND METHODS: COPD patients with forced expiratory volume in 1 s (FEV1) ≤50% predicted and ≥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 µg bid, or formoterol (FORM) 12 µg bid for 52 weeks. The primary outcome was the annualized rate of moderate/severe COPD exacerbations. RESULTS: In total, 1,765 patients were randomized. There were fewer discontinuations with FP/FORM 500/20 µg (20.6%) and 250/10 µg (24.0%) compared with FORM (26.1%). None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; P≤0.402). There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 µg versus FORM in patients with ≥2 exacerbations in the preceding year (RR: 0.79; P=0.084). Pre- and post-dose FEV1 and forced vital capacity were greater with FP/FORM 500/20 µg versus FORM (P≤0.039). There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 µg versus FORM (RR: 0.87; P=0.077). There were more St George's Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 µg than FORM (odds ratios [OR] at weeks 6, 23 and 52 ≥1.28; P≤0.054). EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 µg and 250/10 µg versus FORM (P≤0.066). Acute ß2-agonist-induced effects and 24-hour Holter findings were similar for all treatments. Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses. Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 µg, FP/FORM 250/10 µg and FORM-treated patients, respectively. Adverse events were otherwise similar across treatment groups. CONCLUSION: FP/FORM did not reduce exacerbation rates versus FORM. Numerical benefits were observed with FP/FORM 500/20 µg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores. Few efficacy differences were evident between FP/FORM 250/10 µg and FORM. Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low. Adverse events were otherwise similar between treatments.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Androstadienos/uso terapêutico , Broncodilatadores/uso terapêutico , Etanolaminas/uso terapêutico , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Adulto , Idoso , Androstadienos/efeitos adversos , Broncodilatadores/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Combinação de Medicamentos , Etanolaminas/efeitos adversos , Europa (Continente) , Feminino , Fluticasona , Volume Expiratório Forçado , Fumarato de Formoterol , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , República da Coreia , Índice de Gravidade de Doença , África do Sul , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Capacidade VitalRESUMO
University Pulmology and Allergy Clinic was founded in 1975 when the Depertment of Internal Medicine, directed by Prof. Dr. Dimitar Arsov, later member of the Macedonian Academy of Sciencies and Arts, was divided into eight separate and independent clinics. The first head of the Pulmonology and Allergy Clinic was Prof. Dr. Ljubomir Kotevski. He had a very difficult goal: to establish and further develop the newly formed clinic. The Clinic flourished and became one of the leading Clinics in the Clinical Centre during the directorship of Prof. dr. Dejan Dokic.. He completely rebuilt and refurbished the Clinic, which became a modern Clinic providing excellent working conditions for the employees and, most importantly, provided a first class service to the patients. During his mandate he obtained a grant from the Japanese Government worth $1,000,000 which was used to obtain a new, modern and sophisticated medical equipment. Since the establishment of the clinic, many national and international scientific projects were carried out and many scientific papers were published as well as many monographs, and chapters in scientific books. As a result of continuous education, of the total number of 24 doctors there are 16 subspecialists in respiratory medicine and 4 specialists in internal medicine. There are 9 professors in internal medicine at the University of Pulmonology and Allergy Clinic lecturing at the Medical Faculty in Skopje. The University Pulmonology and Allergy Clinic has an international reputation due to many contacts with famous European Institutions. All these international interrelations have resulted in honouring 3 professors: Prof. Dr. Gert Kunkel from Berlin, Germany, Prof. Dr. Robert Loddenkemper from Berlin, Germany and Prof. Dr. Peter Howard from Southampton, UK.
Assuntos
Centros Médicos Acadêmicos/organização & administração , Alergia e Imunologia/organização & administração , Prestação Integrada de Cuidados de Saúde/organização & administração , Hipersensibilidade , Ambulatório Hospitalar/organização & administração , Pneumologia/organização & administração , Doenças Respiratórias , Centros Médicos Acadêmicos/história , Alergia e Imunologia/educação , Alergia e Imunologia/história , Prestação Integrada de Cuidados de Saúde/história , Técnicas de Diagnóstico do Sistema Respiratório , Educação Médica/organização & administração , História do Século XX , História do Século XXI , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/história , Hipersensibilidade/terapia , Ambulatório Hospitalar/história , Pneumologia/educação , Pneumologia/história , República da Macedônia do Norte , Doenças Respiratórias/diagnóstico , Doenças Respiratórias/história , Doenças Respiratórias/terapiaRESUMO
A double-blind randomised trail design was used to address the effect of ambient ozone on the nasal airways and to evaluate the effects of ozone on allergic mucosa. Ten grass pollen allergic rhinitics were exposed for 2 hours at rest on 2 separate occasions to 400 ppb ozone and filtered air respectively. The exposure to 400 ppb ozone and filtered air was performed prior to the grass pollen season and again during the season. Baseline nasal lavage in which histamine, eosinophil cationic protein (ECP), myeloperoxidase (MPO), total proteins, and albumin were measured and neutrophils, eosinophils and epithelial cells were counted, was made immediately prior to exposure (-120 min). After 2 h of exposure to ozone/filtered air repeated measurements were performed at 0, 30, 60, 120, 240, 360 minutes post exposure. Significant increases were observed when exposed to ozone versus filtered air during the pollen season for histamine (AUC1; p=0.05), MPO (AUC2; p=0.05), ECP (AUC2; p=0.008), total proteins (AUC, p=0.02; AUC1, p=0.007; AUC2, p=0.05), and albumin (AUC, p=0.007; AUC1, p=0.02; AUC2, p=0.005). There was also a significant increase in the total protein level (AUC, p=0.05; AUC1, p=0.02; AUC2 p=0.05) and albumin (AUC, p=0.03; AUC1, p=0.03; AUC2, p=0.04) after ozone exposure versus air out of season. Significant increase of the neutrophils (p=0.01 and p=0.007) in the nasal lavage fluid (NLF) at time points 0 min and 360 min respectively were observed, while eosinophils and epithelial cells significantly increased only at time point 360 min (p=0.02 and p=0.02 respectively) all of them after ozone exposure versus filtered air during the season. Neutrophils also significantly increased in the NLF at time point 0 min and 360 min (p=0.03 and p=0.01) while epithelial cells increased only at time point 360 min (p=0.01) after ozone exposure versus filtered air out of season. We can conclude that ozone induces neutrophil and eosinophil recruitment into the nose and this is accompanied by activation, as evidenced by release of MPO and ECP in NAL. Pre-existing allergic mucosal inflammation during the pollen season, exaggerates the response to ozone, particularly in relationship to the recruitment of eosinophils and neutrophils 6h following exposure.
Assuntos
Poluentes Ambientais/efeitos adversos , Mucosa Nasal/efeitos dos fármacos , Ozônio/efeitos adversos , Poaceae , Rinite Alérgica Sazonal/imunologia , Adulto , Biomarcadores/metabolismo , Método Duplo-Cego , Proteína Catiônica de Eosinófilo/imunologia , Proteína Catiônica de Eosinófilo/metabolismo , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Eosinófilos/metabolismo , Feminino , Histamina/imunologia , Histamina/metabolismo , Humanos , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Exposição por Inalação/efeitos adversos , Masculino , Lavagem Nasal , Líquido da Lavagem Nasal/imunologia , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Peroxidase/imunologia , Peroxidase/metabolismo , Rinite Alérgica Sazonal/metabolismo , Estações do Ano , Fatores de TempoRESUMO
After exposure to ozone, humans develop neutrophil infiltration of the nasal mucosa. To investigate the events contributing to inflammatory cell recruitment in the nasal mucosa we exposed 10 healthy nonsmoking volunteers to 400 ppb ozone or filtered air for 2h at rest on two separate occasions. Nasal biopsies were performed 6h after ozone/filtered air exposure. The nasal biopsies were embedded in glycol mathacrylate and immunostained for inflammatory cells, including neutrophils, mast cells, total T-cells (CD3), T-cell subsets CD8 and CD4, macrophages, eosinophils adhesion molecules (P-selectin, E-selectin, ICAM-1, VCAM-1), cytokines (TNF-α, IL-1ß, GM-CSF, IL-6), chemokines (IL-8 and RANTES), and nuclear factor NF-κB. No significant changes were seen in the number of T-cells, and T-cell subsets, eosinophils, macrophages, or percentages of vessels expressing P-selectin, VCAM-1, GM-CSF, IL-6 and RANTES in the biopsies. The number of neutrophils and mast cells in the submucosa was significantly higher after ozone exposure (p=0.009 and p=0.005 respectively). The percentage of vessels expressing E-selectin (p=0.01), ICAM-1 (p=0.005), IL-8 (p=0.02), TNF-α (p=0.02), IL-1ß (p=0.009), and NF-κB (p=0.05) increased significantly after ozone exposure as compared to filtered air exposure. Exposure of normal subjects to ozone increases the expression of proinflammatory cytokines resulting in upregulation of IL-8 and adhesion molecules via activation of NF-κB, leading to neutrophil inflitration in the nasal mucosa.
Assuntos
Moléculas de Adesão Celular , Citocinas , Inflamação , NF-kappa B/metabolismo , Mucosa Nasal , Infiltração de Neutrófilos , Ozônio , Subpopulações de Linfócitos T/efeitos dos fármacos , Adulto , Biópsia , Moléculas de Adesão Celular/classificação , Moléculas de Adesão Celular/metabolismo , Citocinas/classificação , Citocinas/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Imuno-Histoquímica , Inflamação/imunologia , Inflamação/patologia , Exposição por Inalação/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Infiltração de Neutrófilos/efeitos dos fármacos , Infiltração de Neutrófilos/imunologia , Ozônio/efeitos adversos , Ozônio/metabolismo , Subpopulações de Linfócitos T/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Regulação para CimaRESUMO
OBJECTIVES: Acoustic rhinometry is used to objectively measure the minimal cross sectional area and volumes of nasal cavities. However, no data for healthy subjects has been reported in Macedonia. Therefore, we wanted to establish the normal range among healthy adults and to evaluate the changes after nasal decongestion. METHODS: We included 50 males and 50 females in this study (mean age: 23.2 years; age range: 19 to 40 years). An acoustic rhinometer was used to evaluate the first minimal cross-sectional area (MCA1), the distance from the tip of the probe to the first minimal cross-sectional area (D1), the second minimal cross sectional area (MCA2), the distance from the tip of the probe to the second minimal cross sectional area (D2), the volume between the tip of the nosepiece and 3 cm into the nasal cavity (V03), the volume of the nasal cavity between 2 to 5 cm from the tip of the nosepiece (V25), the volume of the nasal cavity between 4 to 7 cm from the tip of the nosepiece (V47), and the volume between the tip of the nosepiece and 7 cm into the nasal cavity (V07). These measurements were taken before and after nasal decongestion. RESULTS: Data acquired from the male group before decongestion were as follows: MCA1 L: 0.71+/-0.07 (cm2); D1 L: 0.34+/-0.05 (cm); MCA2 L: 0.46+/-0.13 (cm2); D2 L: 2.46+/-0.11 (cm); MCA1 R: 0.73+/-0.06 (cm2); D1 R: 0.35+/-0.05 (cm); MCA2 R: 0.47+/-0.11 (cm2); D2 R: 2.41+/-0.18 (cm); V03 L 2.59+/-0.82 (cm3); V25 L; 4.83+/-1.93 (cm3); V47 L; 7.82+/-2.94 (cm3); V07 L: 11.48+/-4.23 (cm3); V03 R 2.55+/-0.72 (cm3); V25 R; 4.71+/-1.76 (cm3); V47 R; 7.60+/-2.30 (cm3); V07 R: 12.03+/-3.65 (cm3); data acquired from the female group before decongestion were: MCA1 L: 0.65+/-0.12 (cm2); D1 L: 0.35+/-0.05 (cm); MCA2 L: 0.50+/-0.12 (cm2); D2 L: 2.36+/-0.15 (cm); MCA1 R: 0.65+/-0.11 (cm2); D1 R: 0.35+/-0.04 (cm); MCA2 R: 0.49+/-0.13 (cm2); D2 R: 2.41+/-0.13 (cm); V03 L 2.64+/-0.58 (cm3); V25 L; 5.11+/-1.17 (cm3); V47 L; 8.30+/-2.20 (cm3); V07 L: 12.38+/-3.19 (cm3); V03 R 2.42+/-0.56 (cm3); V25 R; 4.43+/-1.34 (cm3); V47 R; 7.35+/-2.29 (cm3); V07 R: 11.06+/-3.19 (cm3) The increase in MCA1 and MCA2 after nasal decongestion was significant (p<0.001), both in females and males. The increases in V03, V25, V47 and V07 after nasal decongestion were statistically significant both in the female and male groups as well (p<0.001). CONCLUSION: Acoustic rhinometry is a convenient method for assessing the geometry of the nasal cavity. The maximal effect of decongestion is found in the anterior and middle parts of the nasal cavity, at the level of the inferior and middle turbinates.
Assuntos
Cavidade Nasal/anatomia & histologia , Rinometria Acústica , Adulto , Feminino , Humanos , Masculino , Tamanho do Órgão , Valores de Referência , Adulto JovemRESUMO
Ozone is a significant public health concern worldwide. Despite increasing evidence for the role of the bronchial epithelial cells in the generation of proinflammatory cytokines there is little information on the biological relevance of ozone induced release of cytokines in nasal airway inflammation. We have investigated the effect of ozone on the nasal mucosa using immunohistochemical staining of nasal biopsies taken 6h after exposure to either 400 ppb ozone or filtered. We found that ozone significantly increases the number of neutrophils in the epithelium (p=0.03), and expression of NF-kB (p<0.03), TNF-a (p<0.05), IL-1b (p<0.03), IL-8 (p<0.007), IL-6 (p<0.02), GM-CSF (p<0.02) and ICAM-1 (p <0.01) in the epithelial cells 6h after exposure. Furthermore, we found a significant correlations between IL-8 expression and number of neutrophils (r=0.85, p< 0.002) and NF-kB and TNF-a expression (r=0.77, p<0.009) in the epithelium. These results suggest that ozone-induced inflammation of the nasal mucosa may be a consequence of increased synthesis and release of epithelial cell-derived cytokines and adhesion molecules which influence the activity of inflammatory cells.
Assuntos
Mucosa Nasal/efeitos dos fármacos , Oxidantes Fotoquímicos/efeitos adversos , Ozônio/efeitos adversos , Adulto , Citocinas/metabolismo , Método Duplo-Cego , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Epitélio/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Mucosa Nasal/patologiaRESUMO
BACKGROUND: A new depot allergoid of house dust mite (Dermatophagoides pteronyssinus - D.pt) has been created in line with the principles and methodology established in the successful development of pollen allergoids. A two-year double-blind placebo-controlled clinical trial, with one further follow-up year of active treatment, has been conducted to assess clinical efficacy and tolerance. METHODS: 40 patients (20 verum and 20 placebo) with IgE-mediated mite allergy and a history of moderate to severe perennial symptoms of rhinoconjunctivitis with or without asthma participated in a 2-year randomized, double-blind, placebo-controlled trial. Actively treated patients were included in a follow-up year. Active treatment was performed with an aluminium hydroxide adsorbed house dust mite allergoid. Parameters for baseline data and clinical efficacy: nasal challenge, quantitative skin prick testing, Visual Analog Scale (VAS), patients' diaries, physician's assessment of patients? health condition, symptoms and use of anti-allergic medication as well as adverse reactions and changes in specific IgG4 and IgE antibodies. RESULTS: The trial detected superiority (p < 0.05) of mite depot allergoid versus placebo with regard to VAS and symptom intensity sum score in patients who needed anti-allergic medication in the baseline period. Significant differences (p < 0.05) between verum and placebo groups were also seen for patients' reactivities to nasal challenges and prick tests with allergen. The blinded assessment by the physician documented a significant difference (p < 0.05) between the groups in favour of active treatment. After reaching the maximum dose as well as after 12 and 24 months, specific IgG4 antibody concentrations were significantly elevated in the verum group (p < 0.05) by comparison with placebo. Local reactions were less frequent in the verum group and no systemic adverse reactions occurred. A third year of active treatment resulted in further improvement and documented the advantage of booster therapy to stabilize the clinical success. CONCLUSION: Specific immunotherapy with a mite depot allergoid induced significant clinical improvements versus placebo. Safety was assessed as excellent, and no systemic adverse reactions occurred.
Assuntos
Dermatophagoides pteronyssinus/imunologia , Dessensibilização Imunológica , Extratos Vegetais/administração & dosagem , Rinite Alérgica Perene/terapia , Adolescente , Adulto , Alérgenos/imunologia , Alergoides , Animais , Método Duplo-Cego , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Rinite Alérgica Perene/etiologia , Rinite Alérgica Perene/imunologiaRESUMO
Allergic rhinitis is an inflammatory disorder of the nasal mucosa typified by the symptoms of nasal itch, sneeze, anterior nasal secretions, and nasal blockage. These symptoms arise from the interaction between mediators and neural, vascular, and glandular structures within the nose. Nasal itch, sneezes, and rhinorrhoea are predominantly neural in origin, while nasal obstruction is predominantly vascular. Nasal biopsy studies show accumulation of eosinophils within the lamina propria and epithelium and an increase in tissue and cell surface basophils in both seasonal and perennial allergic rhinitis. These cells are in an activated state. Within the epithelium, increased numbers of mast cells, T cells and Langerhans' cells, which induce T-cell activation, are found. The accumulation of these cells can be linked to chemokine and cytokine generation by the epithelial cells themselves. Thus, the tissue cell recruitment is orchestrated by activated mast cells, T cells, and epithelial cells, with the recruited tissue eosinophils also contributing to their persistence at this site through autocrine mechanisms. Mast cells generate an array of mediators including histamine, tryptase, leukotrienes, and prostaglandins. Histamine is also generated by basophils. Eosinophils and basophils contribute to the leukotriene synthesis within the tissue. Histamine nasal insufflation induces nasal itch, sneeze, and rhinorrhoea as well as nasal blockage, thereby reproducing all the symptoms of allergic rhinitis. These effects are primarily mediated by H1-receptors, and H1-receptor antagonists are a prominent treatment. Antagonism of histamine at these receptors reduces symptoms by about 40-50%, with the greatest effect on the neurally mediated responses. Thus, histamine is a major mediator of allergic rhinitis, but not the sole contributor. Nasal insufflation with leukotrienes, prostaglandins, or kinins is associated with the development of nasal blockage. These mediators act primarily on the nasal vasculature and, in this respect, leukotrienes are potent mediators. Leukotrienes also induce plasma protein exudation, which contributes to the anterior nasal secretions. Studies with combination products have suggested that modifying the effects of both leukotrienes and histamine has complementary effects in relieving nasal symptoms, indicating that both these mediators are relevant to disease expression.
Assuntos
Mucosa Nasal/imunologia , Rinite Alérgica Perene/imunologia , Rinite Alérgica Sazonal/imunologia , Eosinófilos/imunologia , Histamina/imunologia , Humanos , Células de Langerhans/imunologia , Leucotrienos/imunologia , Mastócitos/imunologia , Receptores Histamínicos H1/imunologia , Linfócitos T/imunologiaRESUMO
BACKGROUND: Nasal provocation with adenosine 5'-monophosphate (AMP) elicits nasal symptoms in subjects with rhinitis. Histamine released from mast cells may play a part in AMP induced nasal responses. METHODS: Symptoms of rhinitis were recorded and histamine release in the fluid obtained by nasal lavage after AMP, guanosine 5'-monophosphate (GMP), and placebo instillations was measured in nine subjects with allergic rhinitis and nine non-allergic controls in a double blind, randomised, placebo controlled study. RESULTS: No symptoms or significant increases in histamine were observed after GMP and placebo challenge. Significantly higher levels of histamine were seen in the nasal lavage fluids of allergic subjects following AMP challenge than in nonallergic controls, the median (range) histamine concentration increasing from the baseline value of 1.62 (0.44-6.99) ng/ml to 6.45 (0.81-16.17) ng/ml at three minutes. No increase in histamine levels was seen in the non-allergic subjects in whom the median histamine concentration was 1.13 (0.29-4.25) ng/ml at baseline and 0.97 (0.31-5.89) ng/ml three minutes after AMP challenge. CONCLUSIONS: AMP elicits an immediate rise in histamine levels in the nasal lavage fluid of allergic subjects compared with non-allergic individuals. These findings indicate that the exaggerated nasal response to adenosine may reflect mast cell priming in vivo, thus supporting its application as a potential new marker of allergic inflammation.
Assuntos
Monofosfato de Adenosina , Histamina/metabolismo , Rinite/diagnóstico , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Líquido da Lavagem Nasal/química , Testes de Provocação Nasal/métodosRESUMO
UNLABELLED: We investigated the interrelationship and the influence of thyroid-stimulating antibodies (TSAb), TSH-blocking antibodies (TSHBAb), and of radioiodine (131I)-induced thyroid damage in the early (within 1 yr) outcome of thyroid function in hyperthyroid patients with Graves' disease (GD) treated with 131I. TSAb, TSHBAb, and ultrasound thyroid volume (as an index of thyroid damage) were simultaneously measured before and at 1, 3, 6, and 12 months after 131I in 31 GD patients. One year after radioiodine, 9.7% of patients were hyperthyroid (Hyper-group), requiring methimazole; 12.9% were euthyroid (Eu-group); and 77.4% were hypothyroid (Hypo-group). Pretreatment thyroid volume in the Eu-group and Hyper-group was significantly greater (P = 0.009) than in the Hypo-group. Pre-131I TSAb levels were higher in the Hyper-group vs. the Hypo-group (P = 0.01) or the Eu-group (P = 0.03). A significant post-131I increase in TSAb levels occurred in 66% of patients developing hypothyroidism but not in those remaining hyperthyroid. After 131I, TSHBAb appeared in 7 patients, in all but one associated with high levels of TSAb. One year after radioiodine: 1) the mean percent reduction in thyroid volume was greater in the Hypo-group (80.7%) or the Eu-group (83.5%) than in the Hyper-group (35.7%) (P = 0.007 and 0.0033 respectively); 2) hypothyroid patients had smaller (P = 0.0058) post-131I thyroids than hyperthyroid patients; and 3) TSAb were still elevated in 75% hypothyroid patients, but all of them had a thyroid volume < or = 8 mL, indicating major postradioiodine gland damage. IN CONCLUSION: 1) the early outcome of thyroid function after 131I for GD is mainly related to pretreatment thyroid volume and to the degree of its reduction after therapy; 2) high TSAb levels before 131I are associated with a relative resistance to therapy; 3) a postradioiodine increase in TSAb levels is related to the development of hypothyroidism; and 4) the concomitant appearance of TSHBAb and disappearance of TSAb are not frequent after 131I and play a role in the development of early postradioiodine hypothyroidism only in a minority of patients.
Assuntos
Autoanticorpos/sangue , Doença de Graves/radioterapia , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Radioisótopos do Iodo/uso terapêutico , Glândula Tireoide/efeitos da radiação , Tireotropina/sangue , Adulto , Idoso , Antitireóideos/uso terapêutico , Feminino , Seguimentos , Doença de Graves/diagnóstico por imagem , Doença de Graves/fisiopatologia , Humanos , Hipertireoidismo/tratamento farmacológico , Hipertireoidismo/epidemiologia , Hipotireoidismo/epidemiologia , Radioisótopos do Iodo/efeitos adversos , Masculino , Metimazol/uso terapêutico , Pessoa de Meia-Idade , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/fisiopatologia , Tireotropina/imunologia , Fatores de Tempo , UltrassonografiaRESUMO
BACKGROUND: Bradykinin, a potent inflammatory mediator, is released during allergic and non-allergic rhinitis and asthma in man. Nasal bradykinin challenge induces a dose-dependent plasma leakage into the nasal cavity and relevant symptoms of rhinitis. OBJECTIVE: We now report on substance P generation during nasal bradykinin challenge in vivo. METHODS: The effect of locally applied bradykinin on substance P generation was studied in nine individuals, allergic to grass pollen and six non-allergic controls. In the allergics TAME-esterase activity, histamine and substance P concentrations were measured in nasal lavages and correlated to the clinical symptoms. RESULTS: Substance P concentrations in nasal lavages increased in a dose-dependent fashion during nasal bradykinin challenge in both groups. In the allergic group Substance P-increases correlated with the production of TAME-esterase activity (r = 0.9, P < 0.05) whereas these allergic individuals did not produce any histamine increases. The generation of substance P and the increase of TAME-esterase activity was associated with the onset of clinical symptoms. Correlation of oedema and hypersecretion to substance P were significant by linear regression analysis (r = 0.88, P < 0.005 and r = 0.89, P < 0.02, respectively). Bradykinin induced irritations like burning and itching were short-term and rare. Serial dilutions of nasal washes produced Substance P-RIA displacement curves that paralleled the standard curve and recovery of standard substance P that was added to nasal washes was 76 +/- 4% (mean +/- SEM), n = 8. CONCLUSION: Bradykinin induces in vivo a dose-dependent plasma leakage into the nasal cavity without affecting mast cells, but stimulates nerve endings resulting in the release of the neuropeptide substance P.
Assuntos
Bradicinina , Hipersensibilidade Imediata/diagnóstico , Mucosa Nasal/efeitos dos fármacos , Substância P/biossíntese , Adolescente , Adulto , Feminino , Humanos , Hipersensibilidade Imediata/patologia , Masculino , Pessoa de Meia-Idade , Líquido da Lavagem Nasal/química , Mucosa Nasal/metabolismo , Testes de Provocação Nasal , Peptídeo Hidrolases/análise , Substância P/análiseRESUMO
In recent years, it has been possible to demonstrate mediator release into the nasal secretion after nasal allergen challenge in patients with allergic rhinitis. Using the nasal provocation model, we determined whether the mediator release was altered in immunotherapy-treated patients. Seventeen grass-pollen-allergic patients were examined under controlled, reproducible conditions. Serial challenges with increasing doses of grass pollen produced increasing numbers of clinical symptoms and release of mediators such as kinins, TAME-esterase activity, and histamine. Ten patients received a semidepot perennial grass-pollen extract for 4 years. Seven patients served as controls and did not receive immunotherapy during the observation period. Data from the group of patients receiving immunotherapy over the first year already showed a partially significant decline in the maximal mediator release after nasal allergen challenges compared to the results of pretreated challenges, whereas controls did not show any significant changes. Nasal allergen challenges after termination of 4 years' immunotherapy significantly modified the mediator release compared to pretreatment values (TAME-esterase activity P < 0.05, kinins P < 0.01, and histamine P < 0.01). Decrease of mediator release paralleled the symptom-medication scores and quantitative skin prick test. Finally, we could demonstrate a significant correlation between specific IgG increase and mediator decrease in the treated group.
Assuntos
Hidrolases de Éster Carboxílico/metabolismo , Liberação de Histamina , Imunoterapia , Cininas/metabolismo , Pólen/imunologia , Rinite Alérgica Sazonal/terapia , Adolescente , Adulto , Relação Dose-Resposta Imunológica , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Imunoglobulina E/análise , Imunoglobulina G/análise , Testes de Provocação Nasal , Teste de Radioalergoadsorção , Testes CutâneosRESUMO
The purpose of our study was to evaluate the effects of laser turbinectomy on local allergic inflammation by measuring the secretion of mediators (histamine, bradykinin, and TAME-esterase activity) in nasal lavage fluid after nasal provocation with different allergen concentrations. Our study included 15 patients, aged 15-35 years, who displayed perennial housedust-mite rhinitis (positive prick test, RAST class > 2, and positive nasal provocation with Dermatophagoides pteronyssinus (D.p.) extract) and hypertrophic inferior turbinates. Rhinomanometry (Rhino-test 441, Allergopharma, Germany) and nasal provocation with D.p. extract (Allergopharma, Germany) followed by lavage were performed in all patients. The procedure was repeated three and 12 months after Neodynium:YAG laser turbinectomy. Three and 12 months after laser turbinectomy, we found a significant improvement of nasal flow (p < 0.01 and p < 0.05, respectively) and resistance (p < 0.1 and p < 0.01, respectively) with a tendency towards airway blockage in the long-term follow-up, but no changes in mediator levels of nasal lavages after allergen provocation, suggesting that laser turbinectomy has no effects on local allergic inflammation.
Assuntos
Terapia a Laser , Ácaros/imunologia , Líquido da Lavagem Nasal/química , Rinite Alérgica Perene/imunologia , Rinite Alérgica Perene/cirurgia , Conchas Nasais/cirurgia , Adolescente , Adulto , Resistência das Vias Respiratórias , Alérgenos , Animais , Bradicinina/análise , Poeira/efeitos adversos , Feminino , Seguimentos , Histamina/análise , Humanos , Masculino , Manometria , Testes de Provocação Nasal , Peptídeo Hidrolases/análise , Fatores de TempoRESUMO
The purpose of our study was to evaluate the effects of laser turbinectomy on local allergic inflammation by measuring the secretion of mediators (histamine, bradykinin, and TAME-esterase activity) in nasal lavage fluid after nasal provocation with different allergen concentrations. Our study included fifteen patients, aged fifteen to 35, who displayed perennial house-dust-mite rhinitis (positive prick test, RAST class > 2 and positive nasal provocation with Dermatophagoides pteronyssinus [D.p.] extract) and hypertrophic inferior turbinates. Rhinomanometry (Rhino-Test 441, Allergopharma, Reinbeck, Germany) and nasal provocation with D.p. extract (Allergopharma, Germany) followed by lavage were performed in all patients. The procedure was repeated three and twelve months after neodymium:YAG laser turbinectomy. Three and twelve months after laser turbinectomy, we found a significant improvement of nasal flow (p < 0.01, p < 0.05) and resistance (p < 0.01, p < 0.01) but no change of mediator levels in nasal lavage after allergen provocation, suggesting that laser turbinectomy has no effects on local allergic inflammation.
Assuntos
Terapia a Laser , Rinite Alérgica Perene/cirurgia , Conchas Nasais/cirurgia , Adolescente , Adulto , Bradicinina/metabolismo , Feminino , Liberação de Histamina/fisiologia , Humanos , Masculino , Testes de Provocação Nasal , Peptídeo Hidrolases/metabolismo , Rinite Alérgica Perene/patologia , Resultado do Tratamento , Conchas Nasais/patologiaRESUMO
Twenty-five patients with perennial rhinitis and a positive skin prick test (SPT) for Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df) were submitted to nasal provocation and the radioimmunosorbent test (RAST) for specific IgE-antibodies. We found a significant correlation in the reaction to both allergen extracts for all parameters examined. In addition, there was a significant correlation among the SPT, the RAST and the nasal provocation for Dp and between the SPT and the RAST for Df. In patients with perennial rhinitis we recommend the combination of all three methods to differentiate unspecific rhinitis from an allergic rhinitis. Only the patients with proved allergic rhinitis could benefit from a specific hyposensitisation.