RESUMO
The evidence base for the benefit of quitting smoking as regards morbidity and mortality outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) is limited. The present article is a review of the existing literature. A systematic literature search in medical databases was performed until March 2006, and subsequently until September 1, 2007. The outcomes examined were COPD-related morbidity and mortality (including all-cause mortality) in COPD patients in connection with smoking cessation. A total of 21 and 27 published articles on morbidity and mortality, respectively, were identified and reviewed. For both outcomes, only a few of the studies included patients with severe COPD. Most of the studies reported a beneficial effect of smoking cessation compared with continued smoking, whereas a few found no improvement. Methodological problems, including small study sizes, poor data quality, possibility of reverse causality and incomplete ascertainment of cause of death, limit interpretation of some of the studies. The evidence as a whole supports the conclusion that, even in severe chronic obstructive pulmonary disease, smoking cessation slows the accelerated rate of lung function decline and improves survival compared with continued smoking.
Assuntos
Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/terapia , Abandono do Hábito de Fumar , Adolescente , Adulto , Idoso , Aterosclerose , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Risco , Fumar , Resultado do TratamentoRESUMO
Non-invasive mucosal sampling (nasosorption and nasal curettage) was used following nasal allergen challenge with grass pollen in subjects with allergic rhinitis, in order to define the molecular basis of the late allergic reaction (LAR). It was found that the nasal LAR to grass pollen involves parallel changes in pathways of type 2 inflammation (IL-4, IL-5 and IL-13), inflammasome-related (IL-1ß), and complement and circadian-associated genes. A grass pollen nasal spray was given to subjects with hay fever followed by serial sampling, in which cytokines and chemokines were measured in absorbed nasal mucosal lining fluid, and global gene expression (transcriptomics) assessed in nasal mucosal curettage samples. Twelve of 19 subjects responded with elevations in interleukin (IL)-5, IL-13, IL-1ß and MIP-1ß/CCL4 protein levels in the late phase. In addition, in these individuals whole-genome expression profiling showed upregulation of type 2 inflammation involving eosinophils and IL-4, IL-5 and IL-13; neutrophil recruitment with IL-1α and IL-1ß; the alternative pathway of complement (factor P and C5aR); and prominent effects on circadian-associated transcription regulators. Baseline IL-33 mRNA strongly correlated with these late-phase responses, whereas a single oral dose of prednisone dose-dependently reversed most nasal allergen challenge-induced cytokine and transcript responses. This study shows that the LAR to grass pollen involves a range of inflammatory pathways and suggests potential new biomarkers and therapeutic targets. Furthermore, the marked variation in mucosal inflammatory events between different patients suggests that in the future precision mucosal sampling may enable rational specific therapy.
Assuntos
Proteínas do Sistema Complemento/metabolismo , Hipersensibilidade/imunologia , Inflamassomos/metabolismo , Mucosa Nasal/imunologia , Células Th2/imunologia , Adulto , Alérgenos/imunologia , Antígenos de Plantas/imunologia , Feminino , Humanos , Hipersensibilidade/dietoterapia , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade Tardia , Interleucina-13/metabolismo , Interleucina-1beta/metabolismo , Interleucina-5/metabolismo , Masculino , Pessoa de Meia-Idade , Poaceae/imunologia , Pólen/imunologia , Prednisona/uso terapêutico , Adulto JovemRESUMO
A simple method is described for the isolation of human peripheral blood eosinophils by an immunomagnetic procedure. Superparamagnetic particles were coupled to a monoclonal antibody against CD16, a molecule present on neutrophils but not on eosinophils. A peripheral blood granulocyte preparation, containing neutrophils and eosinophils, was incubated with these anti-CD16 particles. In the magnetic field of a permanent magnet, magnetically labelled neutrophils were then retained on columns with a ferromagnetic matrix. By this negative selection procedure, eosinophils of 99.5% purity were obtained from normal individuals and 99.6% purity from patients with eczema. A comparison was made between the immunomagnetic method and eosinophil isolation after N-formyl-methionyl-leucyl-phenyl-alanine treatment. Even in the case of individuals with very low eosinophil counts, the immunomagnetic method permits the efficient isolation of highly purified and functionally active eosinophils.
Assuntos
Separação Celular/métodos , Eosinófilos/citologia , Glicoproteínas de Membrana , Antígenos CD/análise , Antígenos de Diferenciação/imunologia , Eczema/fisiopatologia , Eosinófilos/imunologia , Eosinófilos/fisiologia , Humanos , Magnetismo , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/citologia , Neutrófilos/imunologia , Receptores Fc/imunologia , Receptores de IgG , Superóxidos/metabolismo , Tetraspanina 29RESUMO
A simple method for isolating highly purified eosinophils from human blood is described. Buffy coats from normal individuals (eosinophil counts less than 0.4 x 10(9)/litre) were centrifuged through a two layer Percoll density gradient, to produce a granulocyte fraction containing neutrophils and eosinophils. Neutrophils were extracted from this fraction using a monoclonal antibody (CLB FcR gran 1) against CD 16 (Fc gamma R III) in a direct or indirect selection procedure using immunomagnetic beads (Dynabeads). This negative immunoselection produced eosinophils of greater purity and with a superior capacity to mount a respiratory burst than eosinophils isolated by a method employing metrizamide.
Assuntos
Separação Celular/métodos , Eosinófilos , Técnicas Imunológicas , Antígenos de Diferenciação/imunologia , Centrifugação com Gradiente de Concentração , Eosinófilos/imunologia , Humanos , Medições Luminescentes , Magnetismo , Metrizamida , Neutrófilos/imunologia , Povidona , Receptores Fc/imunologia , Receptores de IgG , Dióxido de SilícioRESUMO
A range of low molecular weight chemicals have been developed to antagonise the eotaxin receptor, cysteine-cysteine chemokine receptor-3 (CCR3), with the aim of selectively inhibiting eosinophil recruitment into tissue sites. However, the results of recent clinical trials with monoclonal antibodies directed against interleukin-5 (IL-5) question the role of eosinophils in mediating the symptoms of asthma and allergic disease. For this reason, the plans for clinical development of certain CCR3 antagonists have been halted. However, eotaxin 1-3 and a variety of other chemokines interact with CCR3; and this receptor is expressed not only on eosinophils but also on basophils, mast cell subpopulations, activated Th2 cells, macrophages, and airway epithelial cells. Hence, CCR3 is closely associated with asthma and allergy and blockade of this receptor may have pronounced beneficial effects in these diseases. We consider the chemical structures of CCR3 antagonist molecules from a range of pharmaceutical companies, and present an early clinical development plan for a hypothetical CCR3 antagonist. CCR3 antagonists are likely to be safe and effective therapies for allergic diseases, and their clinical pharmacology can readily be defined within phase I/II studies in patients with allergy and asthma.
Assuntos
Antialérgicos/farmacologia , Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Receptores de Quimiocinas/antagonistas & inibidores , Animais , Antialérgicos/química , Antiasmáticos/química , Quimiocina CCL11 , Quimiocinas/fisiologia , Quimiocinas CC/fisiologia , Humanos , Receptores CCR3 , Receptores de Quimiocinas/químicaRESUMO
The incidence of chronic obstructive pulmonary disease (COPD) is increasing throughout the world. Much less is known about the pathogenesis of COPD than that of asthma and there is little response to current therapy. Most patients with COPD have acquired their lung disease through smoking cigarettes, and the major step in management is to minimise further damage by stopping this habit. A number of therapies are being developed for the treatment of COPD; including new bronchodilators such as tiotropium bromide, agents to block inflammation induced by neutrophils and macrophages, as well as strategies to combat proteases and oxidants. The long-term goal is to provide therapy that retards the accelerated loss of lung function occurring in COPD. Development of novel therapies for COPD requires reliable Phase II decision making before entering large scale Phase III studies. The patient with COPD is often overlooked compared to their asthmatic counterpart, who benefit from an urgent need to identify novel targets and better therapy.
Assuntos
Drogas em Investigação , Pneumopatias Obstrutivas/tratamento farmacológico , Medicamentos para o Sistema Respiratório , Agonistas Adrenérgicos beta , Animais , Antibacterianos , Antioxidantes , Broncodilatadores , Quimiocinas/antagonistas & inibidores , Antagonistas Colinérgicos , Citocinas/antagonistas & inibidores , Inibidores Enzimáticos , Expectorantes , Glucocorticoides , Humanos , Antagonistas de Leucotrienos , Pneumopatias Obstrutivas/epidemiologia , Pneumopatias Obstrutivas/etiologia , Pneumopatias Obstrutivas/prevenção & controle , Oxigenoterapia , Receptores de Taquicininas , Medicamentos para o Sistema Respiratório/farmacologia , Medicamentos para o Sistema Respiratório/uso terapêutico , Abandono do Hábito de Fumar , TeofilinaRESUMO
The health burden of asthma is increasing globally at an alarming rate, providing a strong impetus for the development of new therapeutics. Currently available inhaled bronchodilators and anti-inflammatory drugs are effective in most asthmatics, but this palliative therapy requires long-term daily administration. Despite considerable efforts by the pharmaceutical industry, it has been difficult to develop novel therapeutic agents; the leukotriene antagonists and synthesis inhibitors being the only new class of asthma treatments to have been licensed in the last 30 years. It is clearly important to understand more about the underlying mechanisms of asthma and about how current drugs work before rational improvements in therapy can be expected. There are numerous therapies in clinical development that combat the inflammation found in asthma, specifically targeting eosinophils, IgE, adhesion molecules, cytokines and chemokines, inflammatory mediators and cell signalling. In particular, there is the obvious need for new therapy for severe asthma that is poorly controlled by high doses of corticosteroids, as well as agents to counter acute emergency asthma. A long-term goal is to develop disease-modifying immunotherapy, that could be introduced in childhood to alter the natural history of asthma. Thanks to the extensive efforts of the pharmaceutical industry, in the near future we can expect the introduction of a range of novel therapies for asthma.
Assuntos
Antiasmáticos , Asma/tratamento farmacológico , Drogas em Investigação , Adjuvantes Imunológicos , Antagonistas Adrenérgicos beta , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Anti-Inflamatórios , Antivirais , Asma/epidemiologia , Asma/etiologia , Asma/prevenção & controle , Broncodilatadores , Quimiocinas/antagonistas & inibidores , Citocinas/antagonistas & inibidores , Inibidores Enzimáticos , Terapia Genética , Glucocorticoides , Humanos , Imunossupressores , Imunoterapia , Antagonistas de Leucotrienos , Fitoterapia , Proteínas RecombinantesRESUMO
The leucocyte antigen CD23 is expressed by B lymphocytes following activation by a number of stimuli and functions as an IgE receptor, and in its soluble form, as a putative B cell growth factor. The expression of CD23 on the surface of lymphocytes in paraffin wax sections of synovial biopsy specimens was studied using a novel mouse monoclonal antibody, BU38. Specimens were investigated from nine cases of rheumatoid arthritis, six cases of osteoarthritis, and eight cases of chronic inflammation in articular and non-articular tissues. CD23 was expressed on a high proportion of lymphocytes in all forms of chronic inflammation and was not specific for rheumatoid arthritis. It may be a characteristic feature of any chronic inflammatory response. As CD23 was found on the surface of lymphocytes in many cases of these arthritides, sCD23 in serum or synovial fluid may yet prove a useful marker for the severity of the inflammatory infiltrate.
Assuntos
Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos B/análise , Artrite Reumatoide/imunologia , Linfócitos B/imunologia , Receptores Fc/análise , Sinovite/imunologia , Adolescente , Adulto , Idoso , Criança , Doença Crônica , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Osteoartrite/imunologia , Receptores de IgE , Membrana Sinovial/imunologiaRESUMO
The first 2001 meeting of the Society for Medicines Research, held in London on March 14, was devoted to emerging treatments for chronic obstructive pulmonary disease, commonly referred to as smoking-related lung disease or COPD. As COPD afflicts more and more people around the world, the dual need for preventative measures and therapeutic approaches will also continue to grow. During this sobering yet inspiring symposium, researchers looked at compounds that are currently in phase III clinical studies; reactive oxidant species, proteases and neutrophil chemotactics as therapeutic targets; and finally, the potential of monoclonal antibodies and retinoids.
RESUMO
The ocular findings in three brothers with Bruton's disease are reported. All three boys had purulent conjunctivitis, but the two older brothers also developed marked corneal scarring with visual impairment. Haemophilus influenzae was cultured from conjunctival swabs; it was resistant to neomycin but sensitive to chloramphenicol. Tear analysis showed that the three subjects had normal levels of lysozyme but no detectable IgA.
Assuntos
Agamaglobulinemia/genética , Conjuntivite Bacteriana/complicações , Doenças da Córnea/complicações , Infecções por Haemophilus/complicações , Agamaglobulinemia/complicações , Criança , Cloranfenicol/uso terapêutico , Conjuntivite Bacteriana/tratamento farmacológico , Infecções por Haemophilus/tratamento farmacológico , Humanos , Imunoglobulinas/análise , Lactente , Masculino , Muramidase/análise , Componente Secretório/análise , Lágrimas/imunologiaRESUMO
During the Phase I/II assessment of new therapies with the potential to suppress eosinophil and neutrophil inflammation, there is a need to assess the peripheral blood pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the drug. This has relevance in respiratory disease since drugs that target eosinophillic inflammation are in development for asthma; whereas neutrophil-directed therapies are being introduced for treatment of chronic obstructive airways disease (COPD). Pharmacokinetic evaluation is required to determine the concentration of drug substance (and possibly metabolites) in peripheral blood at intervals following single or repeated dosing. Pharmacodynamic assessment is also required since many drug substances have a duration of action which is prolonged beyond the time when drug substance is detectable in the blood (see Fig. 1). Fig. 1. Whole blood pharmacodynamics. In preclinical studies, animal or human blood is treated with test agents. In clinical studies, human subjects are treated with drug and blood removed for analysis. GAFS, gated autofluorescence forward scatter; PK, pharmacokinetics; PD, pharmacoldynamics.
RESUMO
Thirteen patients suffering from primary hypogammaglobulinaemia receiving intravenous immunoglobulin replacement therapy underwent computerized tomography of the paranasal sinuses. The CT scans were evaluated and related to clinical data from the patients, who were selected for study on the basis of having symptoms of rhinosinusitis. The scans varied from normal to demonstrating widespread sinus abnormality. There was no relationship between the scan findings and duration of ENT symptoms, range of current symptoms, or the interval between the onset of ENT symptoms and the start of intravenous immunoglobulin replacement therapy. It is nevertheless possible that prompt institution of replacement therapy, after correct diagnosis early in the course of the disease, may prevent the development of sinus disease refractory to such treatment.
Assuntos
Agamaglobulinemia/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Doenças dos Seios Paranasais/diagnóstico por imagem , Seios Paranasais/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Agamaglobulinemia/complicações , Idoso , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças dos Seios Paranasais/etiologia , Estudos Retrospectivos , Rinite/etiologia , Sinusite/etiologia , Fatores de TempoRESUMO
BACKGROUND: beta-Tryptase is a multifunctional mast cell serine protease released during mast cell degranulation and tryptase/trypsin inhibitors are a novel potential therapeutic approach for allergic inflammatory diseases. OBJECTIVES: This study was performed to assess the effects of RWJ-58643 on nasal symptoms, eosinophil influx, and cytokine and chemokine release following nasal allergen challenge (NAC). METHODS: Male patients with grass pollen allergic rhinitis (n=16) out of season received single doses of RWJ-58643 (100, 300, 600 microg) or matched placebo given 30 min before NAC in a double-blind, randomized crossover design. A single dose of 200 microg budesonide was studied in an open-label extension phase. NAC was performed with Timothy grass pollen (ALK) via a nasal device, and nasal lavage was performed at times 0 (pre-drug, pre-allergen), 0.5 (30 min post-drug, pre-NAC) 1.5, 2.5, 4.5, 6.5, 8.5, and 24 h after drug administration. Nasal lavage mediators were analysed using a sensitive multiplexed bead immunoassay system. RESULTS: Low-dose RWJ-58643 (100 microg) and budesonide (200 microg) significantly reduced symptoms, eosinophils and levels of IL-5 following NAC. However, higher doses of RWJ-58643 (300 and 600 microg) caused a late eosinophilia and preceding increases in IL-5 compared with placebo. CONCLUSIONS: This study suggests that combined beta-tryptase and trypsin inhibition has therapeutic potential in allergic inflammation, however, this property is dose responsive and higher doses are ineffective and may cause eosinophilia.
Assuntos
Pirrolidinas/imunologia , Rinite Alérgica Sazonal/imunologia , Serina Endopeptidases/imunologia , Tiazóis/imunologia , Inibidores da Tripsina/imunologia , Administração Intranasal , Adulto , Alérgenos/imunologia , Benzotiazóis , Budesonida/administração & dosagem , Budesonida/imunologia , Quimiocina CCL11 , Quimiocina CCL2/análise , Quimiocinas CC/análise , Fatores Quimiotáticos de Eosinófilos/imunologia , Estudos Cross-Over , Método Duplo-Cego , Eosinófilos/imunologia , Feminino , Humanos , Mediadores da Inflamação/imunologia , Interleucina-5/análise , Interleucina-8/análise , Contagem de Leucócitos , Masculino , Mastócitos/imunologia , Pessoa de Meia-Idade , Pirrolidinas/administração & dosagem , Tiazóis/administração & dosagem , Inibidores da Tripsina/administração & dosagem , Triptases , Fator de Necrose Tumoral alfa/análiseRESUMO
There is variability in the distribution of inflammatory cells in bronchial tissue in chronic obstructive pulmonary disease (COPD). Better strategies for biopsy sampling of the airway mucosa may improve the capacity to show a difference between study populations where variability in distribution exists. The current authors have examined sources of biological variability in the quantification of inflammatory cells in endobronchial biopsies using immunostained samples taken from 51 subjects with COPD, with a mean forced expiratory volume in one second of 1.71 L, 55% predicted. The distribution of variance contributed by different sources was similar for different inflammatory cell types. For CD8+ cells, a key inflammatory cell in COPD, the largest contribution to intra-subject variability (39%) was time (i.e. 10 weeks between biopsies of placebo-treated subjects), followed by airway generation (23%), biopsy (2.5%), zone (within section; 1.4%) and section (0.4%). Power calculations demonstrated that examining one section from one biopsy, from each of two airway generations, would require a sample size of 32 subjects per group to show a difference of one doubling or halving in CD8+ cells, compared with 47 subjects per group if only one airway generation was sampled. Therefore, biopsies from more than one airway generation should be examined in order to maximise statistical power to detect a difference between study groups.
Assuntos
Brônquios/patologia , Doença Pulmonar Obstrutiva Crônica/patologia , Adulto , Idoso , Biópsia , Brônquios/imunologia , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Projetos de Pesquisa , Testes de Função Respiratória , Estatísticas não ParamétricasRESUMO
BACKGROUND: Cytokines and chemokines produced by allergen-reactive T-helper type 2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders. OBJECTIVE: This study was performed to assess the effect of 7 days of topical corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils, cytokines and chemokines obtained by nasal lavage and filter paper methods. METHODS: Patients with grass pollen seasonal-allergic rhinitis (n = 13) out of season received nasal challenge following matched placebo (twice daily into each nostril for 7 days) and fluticasone propionate (100 microg twice daily into each nostril for 7 days). Chemokine and cytokine levels were analysed using a sensitive automated bead immunoassay system at intervals up to 8 h after NAC. RESULTS: Levels of cytokines and chemokines from filter paper were generally higher than from nasal lavage. Fluticasone propionate caused a reduction in symptoms, total leukocyte counts and eosinophils, and abrogation of IL-4, IL-5, IL-6 and IL-13 responses in the filter paper taken in the late phase (P < 0.05 for IL-4 and IL-13, P < 0.01 for IL-5 and IL-6). Levels of chemokines (eotaxin, RANTES, MCP-1, MIP-1alpha, IL-8 and IP-10) were also reduced in the late phase (P < 0.01 at 8 h). However, levels of IL-2, IL-3, IL-7, IL-12 (p40 and p70), -15, TNF-alpha, IFN-gamma and GM-CSF were not affected. CONCLUSION: Fluticasone propionate has selective inhibitory effects on Th2 cytokine synthesis following nasal challenge, while also decreasing release of chemokines, but not affecting levels of Th1 cytokines.
Assuntos
Corticosteroides/administração & dosagem , Alérgenos , Androstadienos/administração & dosagem , Interleucinas/metabolismo , Mucosa Nasal/imunologia , Rinite Alérgica Sazonal/imunologia , Corticosteroides/uso terapêutico , Adulto , Análise de Variância , Androstadienos/uso terapêutico , Feminino , Fluticasona , Humanos , Interleucina-13/análise , Interleucina-13/metabolismo , Interleucina-4/análise , Interleucina-4/metabolismo , Interleucina-5/análise , Interleucina-5/metabolismo , Interleucinas/análise , Masculino , Líquido da Lavagem Nasal/química , Mucosa Nasal/efeitos dos fármacos , Testes de Provocação Nasal , Poaceae , Pólen , Rinite Alérgica Sazonal/tratamento farmacológico , Método Simples-CegoRESUMO
BACKGROUND: Nasal lavage is a noninvasive method of obtaining inflammatory exudates following nasal allergen challenge (NAC), and permits cells and released mediators to be evaluated. OBJECTIVE: To determine the effects of a single dose of topical steroid on eosinophils and levels of chemokines and cytokines in nasal lavage fluid following NAC in patients with allergic rhinitis. METHODS: Patients with grass pollen seasonal allergic rhinitis (n = 32) out of the allergy season received either nasal budesonide (100 microg per nostril) or matched placebo before allergen challenge in a double blind two-way crossover design. A semi-automated mixed bead array system was employed to measure multiple chemokines and cytokines in small volumes (50 microl) of nasal lavage supernatants. RESULTS: Following NAC there was a rapid onset of nasal symptoms together with nasal eosinophilia, and the appearance of IL-5 and IL-13 in lavages between 4 and 8 h. Elevated levels of eotaxin, RANTES, IL-8 and MCP-1 were also detected following allergen challenge. A single dose of nasal budesonide caused a decrease in symptoms (P < 0.05) and nasal eosinophils (P < 0.05) with selective abrogation of IL-5 and IL-13 responses (P < 0.05), but a lack of effect on levels of eotaxin, RANTES, IL-8 and MCP-1. CONCLUSION: This study suggests that a single dose of nasal steroid has the capacity to selectively abolish IL-5 and IL-13 responses following NAC. This model should be convenient for testing novel anti-inflammatory and immunoregulatory agents intended for the treatment of allergic rhinitis.
Assuntos
Anti-Inflamatórios/administração & dosagem , Budesonida/administração & dosagem , Interleucina-13/antagonistas & inibidores , Interleucina-5/antagonistas & inibidores , Phleum/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/tratamento farmacológico , Administração Intranasal , Adulto , Alérgenos/efeitos adversos , Alérgenos/imunologia , Anti-Inflamatórios/uso terapêutico , Budesonida/uso terapêutico , Feminino , Humanos , Interleucina-13/metabolismo , Interleucina-5/metabolismo , Masculino , Pessoa de Meia-Idade , Líquido da Lavagem Nasal/imunologia , Testes de Provocação Nasal , Phleum/efeitos adversos , Pólen/efeitos adversos , Rinite Alérgica Sazonal/etiologia , Rinite Alérgica Sazonal/metabolismo , Rinite Alérgica Sazonal/fisiopatologia , Resultado do TratamentoRESUMO
Inhaled beta 2-agonists continue to be the mainstay of asthma therapy, along with inhaled corticosteroids (ICS). A recent advance has been the recognition that 'add-on' or adjunctive therapies to ICS, such as long-acting beta 2-agonists and leukotriene antagonists, are a superior option to increased doses of ICS. Traditionally, inhaled beta 2-agonists and ICS have been administered via separate devices, but combined administration of a long-acting inhaled beta 2-agonist and an ICS by a single inhaler has recently become available in clinical practice. For the future, biotechnology is providing a number of potential therapies for asthma that are directed against some of the inflammatory mediators, such as immunoglobulin E and interleukin-4 and -5, thought to be involved in the pathophysiology of the disease. These biotechnological therapies may eventually provide the opportunity to tailor treatment to the needs of individual patients, and to manipulate the immune system away from allergic responses.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Asma/tratamento farmacológico , Imunoglobulina E/imunologia , Interleucina-5/imunologia , Receptores de Interleucina-4/uso terapêutico , Agonistas Adrenérgicos beta/administração & dosagem , Anticorpos Anti-Idiotípicos/fisiologia , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais/fisiologia , Quimioterapia Combinada , Previsões , Humanos , Nebulizadores e Vaporizadores , Receptores de Interleucina-4/fisiologiaRESUMO
The health burden of asthma is increasing globally at an alarming rate, providing a strong impetus for the development of new therapeutics, particularly drugs that may prevent development of the disease. Currently available inhaled bronchodilators and anti-inflammatory drugs are effective in most asthmatic patients, but this palliative therapy requires long-term daily administration. Despite considerable efforts by the pharmaceutical industry, it has been difficult to develop novel therapeutic agents, the leukotriene antagonists being the only new class of asthma treatments to be licensed in the past 30 years. It is clearly important to understand more about the underlying mechanisms of asthma and about how currently used drugs work before rational improvements in therapy can be expected. There are numerous therapies in clinical development that combat the inflammation found in asthma, specifically targeting eosinophils, IgE, adhesion molecules, cytokines (interleukin-4, -5, -13) and chemokines, inflammatory mediators, and cell signaling (kinase inhibitors). In particular, there is the obvious need for new therapy for severe asthma that is poorly controlled by high-dose corticosteroids as well as agents to counter acute emergency asthma. A long-term goal is to develop disease-modifying immunotherapy that could be introduced in childhood to alter the natural history of asthma. Thanks to the extensive efforts of the pharmaceutical industry, we can expect the introduction of a range of novel therapies for asthma in the near future.