RESUMO
BACKGROUND AND OBJECTIVE: There are still gaps in the knowledge regarding the effectiveness of house dust mite (HDM) sublingual immunotherapy (SLIT) on allergic rhinitis (AR) and asthma (AA)-associated sleep disorders. A non-interventional study was conducted to assess the effect of the Standardized quality (SQ) HDM SLIT-tablet on safety and symptoms in adults with HDM respiratory allergies. The aim was to describe the status of insomnia and daytime sleepiness in AR and/or AA patients treated with the SQ HDM SLIT-tablet. METHODS: This was a 12-month multicenter, longitudinal and prospective study. Participants started the SQ HDM SLIT-tablet for moderate-to-severe HDM AR, persistent despite the use of symptom-relieving medication; or HDM AA not well controlled by inhaled corticosteroids and associated with mild-to-severe HDM AR. Sleep symptoms were measured using the Insomnia Severity Index (ISI) questionnaire and the Epworth Sleepiness Scale (ESS). RESULTS: A total of 1,526 adult patients were enrolled and 1,483 were included in the analysis. At baseline, 41.5% of patients reported sleep disorders: 77.0% of them had insomnia and 28.9% suffered from excessive daytime sleepiness. Insomnia was significantly more frequent among patients with uncontrolled AR (83.1%) than those with controlled AR (52.6%) (p<0.0001). Over time, 48.3% and 59.7% of patients reported an improvement greater than the minimal clinically important difference on the ISI and ESS scales respectively. CONCLUSION: In patients with HDM AR and/or asthma associated sleep disorders, an improvement in subjective insomnia and sleepiness was observed after one year of treatment with the SQ HDM SLIT-tablet in a real-life setting.
RESUMO
This document is the outcome of a group of experts brought together at the request of the French Society of Sleep Research and Medicine to provide recommendations for the management of obstructive sleep apnea syndrome type 1 (OSA1) in children. The recommendations are based on shared experience and published literature. OSA1 is suspected when several nighttime respiratory symptoms related to upper airway obstruction are identified on clinical history taking. A specialist otolaryngologist examination, including nasofibroscopy, is essential during diagnosis. A sleep study for OSA1 is not mandatory when at least two nighttime symptoms (including snoring) are noted. Therapeutic management must be individualized according to the location of the obstruction. Ear, nose, and throat (ENT) surgery is often required, as hypertrophy of the lymphoid tissues is the main cause of OSA1 in children. According to clinical findings, orthodontic treatment generally associated with specialized orofacial-myofunctional therapy might also be indicated. Whatever treatment is chosen, follow-up must be continuous and multidisciplinary, in a network of trained specialists.
Assuntos
Apneia Obstrutiva do Sono , Tonsilectomia , Criança , Humanos , Adolescente , Consenso , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/terapia , Ronco , Tonsilectomia/efeitos adversos , Polissonografia/efeitos adversosRESUMO
Most of the continuous positive airway pressure (CPAP) devices currently in use allow telemonitoring of observance, leaks and the apnoea-hypopnoea index (AHI). La Société française de recherche et de médecine du sommeil (SFRMS) and La Société de pneumologie de langue française (SPLF) workgroup offer to CPAP prescribers and to home care providers a scientific document which has the following purposes: to underline the relevance of the telemonitoring of leaks and the AHI, to define alert thresholds, to describe the principal mechanisms generating excessive leaks and high AHI, and to propose a diagnostic algorithm.
Assuntos
Algoritmos , Pressão Positiva Contínua nas Vias Aéreas , Monitorização Fisiológica , Pneumologia/normas , Apneia Obstrutiva do Sono/terapia , Telemedicina/normas , Pressão Positiva Contínua nas Vias Aéreas/instrumentação , Pressão Positiva Contínua nas Vias Aéreas/métodos , Pressão Positiva Contínua nas Vias Aéreas/normas , França , Serviços de Assistência Domiciliar/organização & administração , Humanos , Sistemas de Registro de Ordens Médicas/organização & administração , Sistemas de Registro de Ordens Médicas/normas , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Cooperação do Paciente , Prognóstico , Pneumologia/métodos , Pneumologia/organização & administração , Valores de Referência , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Sociedades Médicas/organização & administração , Sociedades Médicas/normas , Telemedicina/métodosRESUMO
OBJECTIVE: Obstructive sleep apnea (OSA) is a high prevalent disorder with severe consequences including sleepiness, metabolic, and cardiovascular disorders. The aim of this study was to assess the effect of an individualized exercise-training (IET) program with educational sessions vs educational sessions alone on severity markers of OSA over an eight-week duration. METHODS: This was a randomised, controlled, parallel-design study. In sum, 64 patients with moderate-to-severe OSA (apnea-hypopnea index AHI 15-45/hour), low physical activity level (Voorrips<9), body-mass index (BMI) <40 kg/m2 were included in intervention group (IG) or control group (CG), and 54 patients finished the study. All underwent polysomnography (PSG), multiple sleep latency test (MSLT), constant workload exercise test, blood samples and fulfilled questionnaires twice. The primary endpoint was the change in apnea-hypopnea (AHI) at eight weeks from baseline. Main secondary endpoints were daytime sleepiness assessed by questionnaire and objective tests. RESULTS: No significant between-group differences were found for changes in AHI. A reduction in AHI was found in IG only (p = 0.005). Compared to CG, exercise training leads to a greater decrease in AHI during REM sleep (p = 0.0004), with a significant increase in mean daytime sleep latency (p = 0.02). Between-group differences were significant for weight reduction, severity of fatigue, insomnia and depressive symptoms with trend for sleepiness symptoms. CONCLUSIONS: In adult patients with moderate-to-severe OSA, IET did not decrease AHI compared to the control group but improved markers of severity of OSA, in particular AHI in rapid eye movement (REM) sleep and objective daytime sleepiness. Adding personalized exercise training to the management of patients with OSA should be considered. CLINICALTRIALS. GOV IDENTIFIER: NCT01256307.
Assuntos
Distúrbios do Sono por Sonolência Excessiva , Terapia por Exercício , Apneia Obstrutiva do Sono , Adulto , Exercício Físico , Humanos , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia , Sono REMRESUMO
BACKGROUND: Histamine H1-receptor antagonists are used to relieve the symptoms of an immediate allergic reaction. They have additional anti-inflammatory effects that could result from an inhibition of the transcription factors activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB). The implication of the H1-receptor in these effects is controversial. Diphenhydramine is a first-generation H1-receptor antagonist while mizolastine and desloratadine are second-generation compounds. Mizolastine is also an inhibitor of 5-lipoxygenase (5-LO), an enzyme that has been involved in NF-kappaB activation. OBJECTIVE: We measured the ability of antihistamines to reverse histamine-induced smooth muscle contraction, an effect that involves the H1-receptor. We then investigated whether these drugs affect NF-kappaB and AP-1 activities in A549 lung epithelial cells, and whether this potential regulation involves H1-receptor and 5-LO. METHODS: Muscle tone was measured on tracheal segments of guinea-pigs. The H1-receptor was overexpressed by transfection and detected by Western blotting and immunofluorescence microscopy. NF-kappaB and AP-1 activities were assessed by reporter gene assays in cells overexpressing or not overexpressing the H1-receptor. Production of regulated upon activation, normal T cell expressed andsecreted (RANTES), a chemokine whose expression is induced through NF-kappaB, was measured using an immunoassay. RESULTS: H1-receptor antagonists reversed histamine-induced contraction in a dose-dependent manner. Induction of AP-1 and NF-kappaB activities by histamine and the down-regulatory effect of antihistamines required overexpression of the H1-receptor. In contrast, when tumour necrosis factor-alpha and a phorbol ester were used to stimulate NF-kappaB and AP-1 activities, respectively, repression of these activities did not involve the H1-receptor. Indeed, repression was triggered only by a subset of H1-receptor antagonists and was not stronger after overexpression of the H1-receptor. Mizolastine and desloratadine dose-dependently decreased tumour necrosis factor-alpha-induced production of RANTES. Diphenhydramine, H2- and H3-receptor antagonists as well as selective inhibitors of 5-LO were ineffective in this assay. CONCLUSION: Repression of NF-kappaB and AP-1 activities by H1-receptor antagonists involves H1-receptor-dependent and -independent mechanisms but not 5-LO.
Assuntos
Antagonistas dos Receptores Histamínicos H1/farmacologia , NF-kappa B/metabolismo , Receptores Histamínicos H1/metabolismo , Fator de Transcrição AP-1/metabolismo , Análise de Variância , Animais , Araquidonato 5-Lipoxigenase/metabolismo , Linhagem Celular , Quimiocina CCL5/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Técnicas Genéticas , Cobaias , Histamina/farmacologia , Humanos , Inibidores de Lipoxigenase/farmacologia , Pulmão/citologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Músculo Liso/efeitos dos fármacos , Plasmídeos/genética , Receptores Histamínicos H1/genética , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Traqueia/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
The glucocorticoids (GC) betamethasone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone and triamcinolone acetonide are currently used in the treatment of inflammatory diseases. Through a process called trans-activation, GC activate gene expression and produce various physiological and pharmacological effects. In particular, by inducing gluconeogenic enzymes, long-term GC treatment may cause diabetes. Using three different assays, we have extensively compared the capacity of the above GC to activate gene expression. trans-Activation of a GC inducible luciferase gene was assessed in HeLa and A549 cells after stable and transient transfection, respectively. In hepatoma tissue culture cells, we measured trans-activation of the endogenous gene encoding tyrosine aminotransferase, a gluconeogenic enzyme. Half-maximal effective concentrations of GC were determined by dose-response analyses. Results obtained with these assays were highly correlated and GC were ranked in three groups according to their trans-activation potency: betamethasone, dexamethasone, and triamcinolone acetonide > methylprednisolone and prednisolone > hydrocortisone. Potencies were not strictly related to receptor binding affinities and not significantly affected by the amount of endogenous GC receptor.
Assuntos
Glucocorticoides/genética , Ativação Transcricional/efeitos dos fármacos , Relação Dose-Resposta a Droga , Genes Reporter , Glucocorticoides/farmacologia , Humanos , Concentração Inibidora 50 , Luciferases/genética , Reprodutibilidade dos Testes , Células Tumorais Cultivadas , Tirosina Transaminase/genéticaRESUMO
Nebulization therapy is an approach for the treatment of respiratory diseases such as asthma which was not anticipated in the international recommendations for the treatment of asthma and which merits study. Even if the place of nebulizers in the treatment of asthma exacerbations has been validated, this is not the case for adult asthmatic subjects with chronic asthma. While asthma control for most patients can be achieved using metered-dose inhaler and dry powder inhaler therapy, some patients may require regular home nebulized therapy. Before determining the objectives and therapeutic characteristics of nebulization in the treatment of chronic asthma in the adult patient, we shall first describe the pathophysiological elements involved in the treatment of asthma and of the couple 'nebulized substance-nebulizer' leading to an optimal nebulization.
Assuntos
Asma/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Nebulizadores e Vaporizadores , Adulto , Anti-Inflamatórios/administração & dosagem , Glucocorticoides/administração & dosagem , Humanos , Autoadministração , EsteroidesRESUMO
BACKGROUND: Glucocorticoids are used as anti-inflammatory, immuno-modulatory, anti-proliferative and cytotoxic drugs, but they also trigger important side-effects. These hormones bind to glucocorticoid receptor alpha (GRalpha), an intracellular protein, which acts essentially in the nucleus. MAIN POINTS: GRalpha is a ligand-activated transcription factor that positively or negatively regulates gene expression by distinct mechanisms. Stimulation of gene transcription occurs after direct binding of the receptor to specific responsive DNA elements. Gene activation by glucocorticoids is mainly responsible for certain adverse effects. In contrast, the therapeutic effects of glucocorticoids are predominantly mediated through repression of genes encoding inflammatory mediators. Inhibitory protein-protein interaction between the hormone-activated receptor and the transcription factors NF-kappaB and AP-1 was found to be the underlying mechanism. However, inhibition of other transcription factors may account for deleterious effects of glucocorticoids, such as adrenal suppression and osteoporosis. GRalpha also mediates rapid non-genomic effects of glucocorticoids. Side-effects are reduced by using topical glucocorticoids which have a low systemic bioavailability. Moreover, it is important to determine the lowest effective maintenance dose of systemic and topical glucocorticoids to further decrease the risk of adverse effects. This is particularly justified because inhibition of AP-1 and NF-kappaB activities, that is the anti-inflammatory effect, occurs at much lower hormone concentrations than transactivation. PERSPECTIVES: Clinical use of glucocorticoids is limited by occurrence of severe adverse effects. Therefore, the current aim is to design GRalpha ligands that retain only the anti-inflammatory activities of GC.
Assuntos
Anti-Inflamatórios , Glucocorticoides , Receptores de Glucocorticoides , Administração Tópica , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ritmo Circadiano , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Camundongos , Camundongos Transgênicos , Mineralocorticoides/administração & dosagem , Mineralocorticoides/efeitos adversos , Mineralocorticoides/farmacologia , Mineralocorticoides/uso terapêutico , Osteoporose/induzido quimicamente , Receptores de Glucocorticoides/efeitos dos fármacos , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/fisiologia , Fatores de Transcrição , Transcrição GênicaRESUMO
DRUG PRESCRIPTION: Many pregnant women have asthma and/or rhinitis. Particular attention is required when prescribing drugs in this situation. Medication can be prescribed during pregnancy when the apparent benefit is greater than the apparent risk. Usually at least one drug of each major class used to control these disease can be given safely. In addition, physiological changes associated with pregnancy could affect the upper and lower pathways. CAREFUL MANAGEMENT: Ideally, drug prescription for asthma and/or rhinitis in pregnant women should be part of a global process implicating obstetricians, primary care physicians, and allergy, rhinology or lung specialists. The only way to improve the mother's comfort and avoid complications for both mother and child is to perfectly control the disease. Indeed, it would be regrettable to be too prudent and deprive symptomatic patients of active treatments. Patients should be clearly informed of the benefits and risks of drug therapy.
Assuntos
Asma/tratamento farmacológico , Complicações na Gravidez/induzido quimicamente , Rinite/tratamento farmacológico , Adulto , Broncodilatadores/efeitos adversos , Feminino , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Humanos , Descongestionantes Nasais/efeitos adversos , Gravidez , Complicações na Gravidez/prevenção & controleRESUMO
Asthma is regarded as a disease with a complex interaction between genetic and environmental factors. Since the end of the 1970s and during the 80s the world has seen an increase in the prevalence, morbidity and mortality linked to asthma. The rapidity of progress of this phenomenon means that it cannot be explained only by modification of genetic factors and stresses the preponderance of exogenous factors. The purpose of this review is to examine the epidemiological knowledge of these environmental factors and of the genetic factors in asthma in order to underline how these genetic and exogenous factors interact and modulate the occurrence of the asthmatic disease. In the first part of this general review we discussed the epidemiology of asthma in terms of prevalence, incidence, mortality, cost and socio-professional and scholastic repercussions and underlined for each environmental factor its causal role and/or exacerbation in asthma as well as its contribution in the increased prevalence and severity of asthma. In the second part of this general view we touch on the epidemiological knowledge of the genetics of asthma and of atopy.
Assuntos
Asma/epidemiologia , Asma/genética , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/genética , Epidemiologia Molecular , Asma/economia , Asma/imunologia , Asma/mortalidade , Hiper-Reatividade Brônquica/epidemiologia , Hiper-Reatividade Brônquica/genética , Hiper-Reatividade Brônquica/imunologia , Efeitos Psicossociais da Doença , Custos e Análise de Custo , Suscetibilidade a Doenças/imunologia , Meio Ambiente , Genes MHC da Classe II/genética , Predisposição Genética para Doença , Antígenos HLA/genética , Humanos , Hipersensibilidade Imediata/imunologia , Imunoglobulina E/sangue , Incidência , Prevalência , Receptores de Antígenos de Linfócitos T/genética , Fatores SocioeconômicosRESUMO
BACKGROUND: Acute descending posterior mediastinitis is a very serious condition which can develop after common ear-nose-throat infections. Clinical manifestations are typical and must be recognized rapidly for early diagnosis. CASE REPORTS: We report two cases. In the first case, a 28-year-old man had a retropharyngeal abscess which fistulized into the left pleural cavity. Three operations were necessary to achieve cure and favorable outcome. In the second case, mediastinitis was diagnosed in a 39-year-old patient following a throat infection. Despite early surgery, outcome was fatal due to development of pericarditis and tamponnade. DISCUSSION: These two cases illustrate the variable course of descending mediastinitis and emphasize the importance of early medicosurgical cure. Treatment is based on intravenous antibiotics using a combination of 2 or 3 drugs at high doses in association with emergency surgery and extensive mediastinal washings. Despite well-conducted treatment, descending necrotizing mediastinitis may lead to a fatal outcome.
Assuntos
Mediastinite/diagnóstico , Adulto , Infecções Bacterianas , Tamponamento Cardíaco/etiologia , Evolução Fatal , Fístula/complicações , Fístula/cirurgia , Infecção Focal/complicações , Infecção Focal/cirurgia , Humanos , Masculino , Mediastinite/etiologia , Mediastinite/cirurgia , Necrose , Pericardite/etiologia , Doenças Faríngeas/microbiologia , Pleura/microbiologia , Pleura/cirurgia , Doenças Pleurais/complicações , Doenças Pleurais/cirurgia , Abscesso Retrofaríngeo/complicações , Abscesso Retrofaríngeo/cirurgia , Resultado do TratamentoRESUMO
Many different forms of nebulizer treatment for asthma have been developed over the last few years, including several which have reached international concensus. Nevertheless, there are no widely recognized recommendations concerning the role of nebulization in the treatment of asthma in adults. We present here the main elements on the pathophysiological basis of nebulization treatment of asthma, the physical and chemical parameters of nebulization, the different nebulizers and the substances which can be administered and their costs. The indications for home nebulizer treatment of asthma in adults include asthma with chronic sinusitis or nasosinus polyposis, asthma with hypersecretion with or without bronchial dilatation, severe poorly controlled asthma, corticodependent asthma. The aim of this discussion on nebulizer administration is to reduce the amount of systemic corticosteroid delivery and underline the need for quality research in this area.
Assuntos
Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Administração por Inalação , Adulto , Aerossóis , Asma/fisiopatologia , Broncodilatadores/administração & dosagem , HumanosRESUMO
While on the basis of clinical studies glucocorticoids (GC) became the first-line therapy for asthma, the molecular basis of GC action has been extensively studied. Glucocorticoids exert their effects by binding to the glucocorticoid receptor (GR), which then inhibits or increases gene transcription through processes known as transrepression and transactivation, respectively. Transrepression results from the inhibitory interaction between the GR and other transcription factors like AP-1 and NF-kappa B. Since AP-1 and NF-kappa B DNA binding sites have been mapped to the promoter regions of many genes coding for proinflammatory mediators (IL-1, 2, 5, 6, 8, 13, TNF-alpha, RANTES, Eotaxin, GM-CSF, metalloproteinases, ICAM-1 ...), this interaction may be an important aspect of the GC anti-inflammatory properties. Transactivation is mediated through binding of the GC-activated GR to a DNA sequence called glucocorticoid response element (GRE) and may result in some benefits and side effects since GRE has been mapped to the promoter regions of genes coding for lipocortin, beta 2-adrenergic receptor, and for genes involved in the onset of metabolic effects (diabetes, hypokaliemia, hydrosodic retention) and glaucoma. Other molecular mechanisms may also be involved like the binding to the GR to a negative GRE (nGRE), the interaction with the basal transcriptional machinery, and the post transcriptional modulation of mRNA stability. In asthma, the relative importance of each mechanism remains to be studied, but both mechanisms may probably be involved.
Assuntos
Asma/tratamento farmacológico , Glucocorticoides/farmacologia , Receptores de Glucocorticoides/fisiologia , Asma/genética , Asma/imunologia , Glucocorticoides/imunologia , Humanos , Inflamação , Regiões Promotoras Genéticas , RNA Mensageiro/efeitos dos fármacos , Receptores de Glucocorticoides/efeitos dos fármacos , Fatores de Transcrição/farmacologia , Transcrição GênicaRESUMO
Asthma is regarded as a disease with a complex interaction between genetic and environmental factors. Since the end of the 1970s and during the 80s the world has seen an increase in the prevalence, morbidity and mortality linked to asthma. The rapidity of progress of this phenomenon means that it cannot be explained only by modification of genetic factors and stresses the preponderance of exogenous factors. The purpose of this review is to examine the epidemiological knowledge of these environmental factors and of the genetic factors in asthma in order to underline how these genetic and exogenous factors interact and modulate the occurrence of the asthmatic disease. In the first part of this general review we will discuss the epidemiology of asthma in terms of prevalence, incidence, mortality, cost and socio-professional and scholastic repercussions and will underline for each environmental factor its causal role and/or exacerbation in asthma as well as its contribution in the increased prevalence and severity of asthma. In the second part of this general view we touch on the epidemiological knowledge of the genetics of asthma and of atopy.
Assuntos
Asma/epidemiologia , Asma/genética , Meio Ambiente , Absenteísmo , Adulto , Alérgenos/efeitos adversos , Asma/economia , Asma/mortalidade , Criança , Efeitos Psicossociais da Doença , Poluição Ambiental/efeitos adversos , Humanos , Incidência , Prevalência , Infecções Respiratórias/epidemiologiaRESUMO
The efficacy of corticosteroids in asthma has been recognized over 40 years ago. Since that time, the advent of inhaled forms has further improved the therapeutic of these drugs which are now recognized as the fundamental treatment for asthma, and described in detail by national and international consensus. Based on a large body of literature, it can now be recommended to prescribe inhaled corticosteroids for symptomatic asthma patients. Long-term treatment is required and dosage not exceeding 1000 micrograms/d (beclometasone dipropionate equivalent) in adults are safe. Differences in the pharmacological characteristics of the various systematic and inhaled corticosteroids can be used to adapt treatment and administration route to each patient and achieve good patient compliance with optimal therapeutic efficacy.
Assuntos
Asma/tratamento farmacológico , Glucocorticoides/administração & dosagem , Administração por Inalação , Administração Oral , Adulto , Asma/metabolismo , Glucocorticoides/farmacocinética , HumanosRESUMO
The development of fibreoptic bronchoscopy has enabled significant progress in the understanding of the pathogenesis of asthma. It has brought to the fore the importance of bronchial inflammation even in asymptomatic patients and/or in patients who have only mild disease. The practice of bronchial biopsy in vivo is an excellent method of studying bronchial inflammation. The purpose of this general review is to recall the value of bronchial biopsies in the understanding of the effects of steroids on asthma: effects on the epithelium, the basement membrane and the blood vessels. Their cellular contents consist equally of cytokines, enzymes and adhesion molecules. At the level of the bronchial epithelium steroid therapy engenders a diminution in eosinophils, mast cells an lymphocytes. It restores the ratio of ciliated to other cells back to normal and increases the number of nerve synapses. Regarding the interstitium the corticoids diminish the number of eosinophils, mast cells and T lymphocytes. The effect on different lymphocyte subtypes is controversial, as is the effect of the basal membrane. Steroid therapy diminishes the proteins, GM-CSF.RANTES and IL-8 as well as the messengers IL-4, IL-13 and IL-5. It seems to increase the messengers for IFN-gamma and IL-12 and favourably modulates the vascular composition to inflammation in asthma. Nevertheless it is to be regretted that too few studies have looked at the correlations between histological changes and clinical and respiratory function improvement engendered by steroid therapy.
Assuntos
Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Biópsia , Brônquios/patologia , Bronquite/tratamento farmacológico , Asma/patologia , Membrana Basal/efeitos dos fármacos , Vasos Sanguíneos/efeitos dos fármacos , Brônquios/efeitos dos fármacos , Brônquios/enzimologia , Bronquite/patologia , Broncoscopia , Moléculas de Adesão Celular/efeitos dos fármacos , Quimiocina CCL5/metabolismo , Eosinófilos/efeitos dos fármacos , Epitélio/efeitos dos fármacos , Tecnologia de Fibra Óptica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos dos fármacos , Humanos , Interferon gama/efeitos dos fármacos , Interleucinas/metabolismo , Subpopulações de Linfócitos/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Linfócitos T/efeitos dos fármacosRESUMO
A CONTROVERSIAL DEFINITION: The current definition of corticosteroid-resistant asthma is a spirometry definition. There is however, no consensus on dose, treatment duration, steroid administration route and the degree of FEV1 non-reversibility allowing the diagnosis of corticosteroid-resistant asthma. Finally, the beneficial effect of steroids in clinical terms (symptom frequency, number of hospitalizations, quality of life) is not taken into consideration, thus nearly one-half al all patients included in studies on corticosteroid resistance are taking long-term oral steroids. This subgroup of patients must be considered individually when examining these studies. COMPLEX PATHOGENESIS: There are a wide range of anomalies described in the literature involving: glucocorticoid pharmacokinetics, cytokine regulation, cell function (monocytes, lymphocytes, eosionophils), and transcription factors (glucocorticoid and AP-1 receptors). DIFFICULT THERAPEUTIC MANAGEMENT: There are several prerequisites before proposing exceptional regimens using cyclosporine, gold salts, methotrexate, or immunoglobulins: i) certain diagnosis of asthma (with CT scan and ultrasonographic explorations if needed, ii) proper control of environmental factors and good compliance, iii) proof of the absence of clinical benefit with long-term corticosteroids. These exceptional therapeutic schemes have their disadvantages and are only warranted by clinically patent corticosteroid resistance (whatever the "biological" cause).