Airway inflammatory effect of hydrogen peroxide in guinea pigs

Reactive oxygens are now considered to be important substances in promoting inflammatory process. Recently, airway inflammation has attracted attention closely linked to bronchial asthma. The present study was undertaken to examine whether hydrogen peroxide, one of the reactive oxygens, could produce airway inflammation. Airway inflammation was assessed by airway vascular permeability in terms of pontamine sky blue (PSB) exudation. Airway resistance was measured with a modified Konzett-R?ssler method and was expressed as a change in ventilation overflow. Inhalation of hydrogen peroxide (0.01-1.0 M) markedly caused a PSB exudation in a concentration-dependent manner in all of the trachea, main bronchus, and lungs. The hydrogen peroxide-induced PSB exudation effect was attenuated was attenuated by pretreatment with catalase, although heat-inactivated catalase had no inhibitory effect. Deferoxamine, which inhibits conversion of hydrogen peroxide into hydroxyl radical, decreased the PSB exudation induced by hydrogen peroxide. On the other hand, inhalation of hydrogen peroxide (1.0 M) caused a significant and biphasic increase in ventilation overflow. This airway constriction was suppressed by pretreatment with inhaled catalase, but not by inhaled deferoxamine. These results indicate that hydrogen peroxide causes an intense airway inflammation; this inflammatory effect may be mediated not only by hydrogen peroxide itself but also by hydroxyl radical. Hydrogen peroxide and hydroxyl radical may thus play an important role in bronchial asthma and bronchitis through inducing airway inflammation.     

Use of induced sputum to examine airway inflammation in childhood asthma

Airway inflammation is important in the pathogenesis of asthma, during which it may lead to symptomatic exacerbations and increases in asthma severity, as well as contribute to future decline in asthma status. The use of induced sputum has emerged as an important and useful technique to study airway inflammation. It has particular advantages in the study of childhood asthma because it is noninvasive and allows samples to be collected on repeated occasions in children over 7 years of age. The results of cell counts are reliable when the sputum is processed in a standardized manner involving selection from saliva, cell dispersion, and quantitative cytology. Children with asthma have increased eosinophils and mast cells, which may persist even with high doses of inhaled corticosteroid therapy. During a severe exacerbation of asthma, there is an intense and heterogeneous inflammatory response involving eosinophil and neutrophil accumulation and activation. Characterization of the relevance of airway inflammation in children with asthma is important.     

Induction of airway mucus production By T helper 2 (Th2) cells: a critical role for interleukin 4 in cell recruitment but not mucus production

Airway inflammation is believed to stimulate mucus production in asthmatic patients. Increased mucus secretion is an important clinical symptom and contributes to airway obstruction in asthma. Activated CD4 Th1 and Th2 cells have both been identified in airway biopsies of asthmatics but their role in mucus production is not clear. Using CD4 T cells from mice transgenic for the OVA-specific TCR, we studied the role of Th1 and Th2 cells in airway inflammation and mucus production. Airway inflammation induced by Th2 cells was comprised of eosinophils and lymphocytes; features found in asthmatic patients. Additionally, there was a marked increase in mucus production in mice that received Th2 cells and inhaled OVA, but not in mice that received Th1 cells. However, OVA-specific Th2 cells from IL-4-deficient mice were not recruited to the lung and did not induce mucus production. When this defect in homing was overcome by administration of TNF-alpha, IL-4 -/- Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells. These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes. These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.     

Regulation of airway neurogenic inflammation by neutral endopeptidase

Airway neurogenic inflammation is caused by tachykinins released from peripheral nerve endings of sensory neurons within the airways, and is characterized by plasma protein extravasation, airway smooth muscle contraction and increased secretion of mucus. Tachykinins are degraded and inactivated by neutral endopeptidase (NEP), a membrane-bound metallopeptidase, which is located mainly at the surface of airway epithelial cells, but is also present in airway smooth muscle cells, submucosal gland cells and fibroblasts. The key role of NEP in limiting and regulating the neurogenic inflammation provoked by different stimuli has been demonstrated in a large series of studies published in recent years. It has also been shown that a variety of factors, which are relevant for airway diseases, including viral infections, allergen exposure, inhalation of cigarette smoke and other respiratory irritants, is able to reduce NEP activity, thus enhancing the effects of tachykinins within the airways. On the basis of these observations, the reduction of neutral endopeptidase activity may be regarded as a factor that switches neurogenic airway responses from their physiological and protective functions to a detrimental role that increases and perpetuates airway inflammation. However, further studies are needed to assess the role of neutral endopeptidase down regulation in the pathogenesis of asthma and other inflammatory airway diseases.     

Methods of evaluating airway inflammation

Airway inflammation is a feature of bronchial asthma and can be quantified invasively with bronchial mucosal biopsy and bronchoalveolar lavage. The induction of sputum by the inhalation of hypertonic saline however is safer and more noninvasive when compared with such methods. Evidence of airway inflammation may be revealed by examining hypertonic saline-induced sputum for eosinophils, cytokines and eosinophil cationic protein. There is a clear need however to develop further noninvasive discriminant measurement of airway inflammation.     

Preparing nurse leaders for the future: views from Canada

Airway responsiveness assessed using histamine and methacholine is safe, reproducible and relatively easily undertaken in adults and children. Results are similar for methacholine and histamine although methacholine is better tolerated. Responsiveness is increased in children and the elderly, and in women compared to men, possibly due to body size effects. Baseline lung function confounds the interpretation of airway responsiveness and may explain the effect of smoking in most studies. Results are most usefully expressed as the provocative dose producing a 20% fall in FEV1 (PD20FEV1) or the dose-response slope (DRS). When technical factors are controlled the reproducibility of the test is from one to two doubling doses. Measurements of airway responsiveness have been widely used in clinical and research practice. However, assessing their value in diagnosing asthma is limited by the lack of a gold standard for the definition of asthma. Using a cut-off value of 8 mg/mL or 8 mumol for PD20, the tests will discriminate asthmatic from non-asthmatic subjects (based on questionnaire definitions of asthma) with a sensitivity of around 60% and a specificity of around 90%. These properties of the test result in positive and negative predictive values of 86% and 69% when the prevalence of asthma is high (50%-as in the clinical setting) and 40% and 95% when the prevalence of asthma is low (10%, as in general population studies). In the usual clinical setting, assessing the significance of atypical or non-specific symptoms, the tests are of intermediate value in predicting the presence of asthma and less useful in excluding asthma. The additional benefit of testing airway responsiveness to measuring peak flows or to a trial of therapy has yet to be fully assessed. Testing of airway responsiveness may be of value in assessing occupational asthma, asthma severity and the effects of potential sensitizers or treatments. In research, tests of airway responsiveness are more useful for excluding cases of asthma. In population studies, they serve as an objective marker of abnormal airway function which may be genetically determined and, like allergy, are strongly associated with asthma. The predictive value of airway hyperresponsiveness for the development of airway disease is yet to be clearly established. In epidemiology the benefits of measuring airway responses must be weighed against the added inconvenience and cost that is incurred.     

Patterns in children''s fruit and vegetable consumption by meal and day of the week

Seasonal bronchial asthma causally connected with the exposure to pollen allergens is a chronic, eosinophilic mucosal inflammation of airway. This inflammation is the basis for the development of nonspecific bronchial hyperreactivity which is the most typical but mutable feature of asthma. Bronchial hyperreactivity often determines asthma intensity and the need of asthma treatment. The nonspecific bronchial hyperreactivity over two consecutive years was evaluated in 11 patients (2 women and 9 men) with seasonal bronchial asthma, sensitized to grass, remaining under the conditions of natural allergen exposure and out of this period. Bronchial reactivity to histamine was measured by Cockcroft's at all method. So called histamine threshold (PC20H) in mg/ml was assessed. The values of ventilatory parameters (FVC, FEV1) and asthma symptom scores were also measured. It was showed that nonspecific bronchial hyperreactivity significantly increased in subjects with seasonal bronchial asthma during natural pollen exposure. PC20H in two studies performed during this period decreased 3 and 6 times when compared to preseasonal values. The majority part of patients (80%) has the increased bronchial reactivity to histamine also beyond the of grass season when clinical symptoms of asthma and rhinitis are not observed. This postseasonal hyperreactivity could be the effect of the chronic inflammation process persisted from the period of natural allergen exposure. Continuous subthreshold, which means asymptomatic exposure to perennial allergens to which most of patients are sensitized, could be another reason of this hyperreastivity. The possibility of exposure to the activity of seasonal allergens the whole year in persons with asthma can not omitted, as the presence of pollens in the sample of the house dust in patient's flat is observed during the yield of pollen season. Nonspecific bronchial hyperreactivity in individual patients is fluctuated, which probably is not dependent on the intensity of natural allergen exposure.     

Non-invasive monitoring of bronchial inflammation in asthma

The present consensus on the diagnosis and treatment of asthma relies on symptoms and lung function measurements for the monitoring of disease severity. Even though this probably remains the cornerstone of asthma management, the rapidly increasing insight into the pathogenesis and pathophysiology of the disease is presently leading to the development of more direct measurements of airway inflammation, which may provide potentially relevant information on its clinical course and prognosis. However, at present none of these has sufficiently been validated for current use in monitoring patients with asthma. First, there are new ways of looking at symptoms and lung function. Careful measurements of symptoms by visual analogue scale (VAS) are suggesting that inflammatory activity within the airways can be subjectively perceived, a sensitivity which may be blunted in patients with brittle asthma. In addition, modern physiological parameters, such as the degree of bronchodilatation following a deep breath (M/P-ratio), are strongly associated with airway inflammation. Second, there are multiple cellular and/or soluble markers of inflammation in peripheral blood (using PCR, in situ hybridization, flow cytometry, or circulating mediators and cytokines) and in urine (LTE4, EPX). Recently this has been extended by similar measurements in hypertonic saline-induced sputum (cell differentials and specific stainings on cytospins, flow cytometry, and levels of e.g. ECP, IL-5, IL-8). Finally, mediators and cytokines in the condensate of exhaled air (H2O2, leukotrienes, IL-5?) as well as exhaled NO are currently under evaluation. Adding such markers of airway inflammation as guides in asthma therapy is potentially useful. As a first step towards such a new approach we have recently shown that adding the reduction of airway hyperresponsiveness to the aims of asthma therapy leads to a better clinical as well as histological outcome after two years of treatment. In conclusion, there are new and exciting perspectives in the monitoring of disease severity in asthma in the future. Longitudinal studies presently ongoing will elucidate which parameter is potentially most useful in guiding asthma management.     

Airway autonomic nervous system dysfunction and asthma

Airways are richly innervated by 4 nervous systems: adrenergic, cholinergic, inhibitory nonadrenergic noncholinergic (i-NANC), and excitatory NANC (e-NANC) nervous systems. Dysfunction or hyperfunction of these systems may be involved in the inflammation or airway hyperresponsiveness observed in asthmatic patients. The cholinergic nervous system is the predominant neural bronchoconstrictor pathway in humans. Airway inflammation results in exaggerated acetylcholine release from cholinergic nerves via dysfunction of the autoreceptor, muscarinic M2, which is possibly caused by a major basic protein or IgE. Vasoactive intestinal peptide (VIP) and nitric oxide (NO) released from i-NANC nerves act as an airway smooth muscle dilator. The effects of VIP and NO are diminished after allergic reaction by inflammatory cell-mediated tryptase and reactive oxygen species. Thus, in asthmatic airways, the inflammatory change-mediated neural imbalance may result in airway hyperresponsiveness. Tachykinins derived from e-NANC nerves have a variety of actions including airway smooth muscle contraction, mucus secretion, vascular leakage, and neutrophil attachment; and they may be involved in the pathogenesis of asthma. Since tachykinin receptor antagonists are effective for bradykinin- and exercise-induced bronchoconstriction in asthmatic patients, these drugs may be useful for asthma therapy.     

Implications of early inflammation and infection in cystic fibrosis: a review of new and potential interventions

Airway infection and inflammation occur early in cystic fibrosis (CF) lung disease, suggesting the need for early treatment. Our current approach to routine management of CF includes a comprehensive, CF center-directed program that aims at maintaining normal nutrition and delaying the progression of lung disease. Regular secretion clearance, frequent antibiotics, and bronchodilators are commonly used. However, despite this early, aggressive comprehensive management, airway inflammation and infection progress. Several other recent approaches such as the use of corticosteroids and ibuprofen to decrease inflammation, as well as dornase alfa to thin secretions and improve pulmonary function, are under investigation in young children. Other potential treatments include amiloride/uridine triphosphate and hypertonic saline aerosol. Early treatment offers the promise of reducing morbidity as well as delaying the progression of later disease.     

Oral administration of L-arginine potentiates allergen-induced airway inflammation and expression of interleukin-5 in mice

The role of nitric oxide in the airway hyperresponsiveness and inflammation of bronchial asthma has not yet been established. However, L-arginine, the substrate for nitric oxide synthases, reportedly alleviates airway hyperresponsiveness caused by parainfluenza virus and reduces granulocytic inflammation induced by ischemia-reperfusion. We investigated the effects of L-arginine on a murine model of allergic asthma that included airway hyperresponsiveness, eosinophilic inflammation and expression of interleukin (IL)-5 in the lung. The mice received drinking water with or without L-arginine for 9 weeks. Histologic evaluation and cellular profiles in bronchoalveolar lavage fluid showed that p.o. administration of L-arginine (72 micromol/kg/day) significantly enhanced eosinophilic airway inflammation and goblet cell proliferation that were associated with intratracheal instillation of ovalbumin. L-Arginine also increased protein levels of IL-5 and IL-2 in supernatants from the lung exposed to ovalbumin. The number of eosinophils in bronchoalveolar lavage fluid correlated significantly with the expression of IL-5. L-Arginine did not reverse ovalbumin-associated airway hyperresponsiveness to inhaled ACh. These results suggest that p.o. administration of L-arginine aggravates allergen-induced eosinophilic airway inflammation via expression of IL-5, and in this model it does not show therapeutic efficacy against airway hyperresponsiveness associated with allergen exposure. Oral administration of L-arginine, the precursor of nitric oxide, may not be an effective intervention in allergic asthma.     

Interleukin-9 promotes allergen-induced eosinophilic inflammation and airway hyperresponsiveness in transgenic mice

Human atopic asthma is a complex heritable inflammatory disorder of the airways associated with clinical signs of allergic inflammation and airway hyperresponsiveness. Recent studies demonstrate that the degree of airway responsiveness is strongly associated with interleukin (IL)-9 expression in murine lung. To investigate the contribution of IL-9 to airway hyperresponsiveness, and to explore directly its relationship to airway inflammation, we studied transgenic mice overexpressing IL-9. In this report we show that IL-9 transgenic mice (FVB/N-TG5), in comparison with FVB/NJ mice, display significantly enhanced eosinophilic airway inflammation, elevated serum total immunoglobulin E, and airway hyperresponsiveness following lung challenge with a natural antigen (Aspergillus fumigatus). These data support a central role for IL-9 in the complex pathogenesis of allergic inflammation.     

Natural killer cells determine development of allergen-induced eosinophilic airway inflammation in mice

The earliest contact between antigen and the innate immune system is thought to direct the subsequent antigen-specific T cell response. We hypothesized that cells of the innate immune system, such as natural killer (NK) cells, NK1.1(+) T cells (NKT cells), and gamma/delta T cells, may regulate the development of allergic airway disease. We demonstrate here that depletion of NK1.1(+) cells (NK cells and NKT cells) before immunization inhibits pulmonary eosinophil and CD3(+) T cell infiltration as well as increased levels of interleukin (IL)-4, IL-5, and IL-12 in bronchoalveolar lavage fluid in a murine model of allergic asthma. Moreover, systemic allergen-specific immunoglobulin (Ig)E and IgG2a levels and the number of IL-4 and interferon gamma-producing splenic cells were diminished in mice depleted of NK1.1(+) cells before the priming regime. Depletion of NK1.1(+) cells during the challenge period only did not influence pulmonary eosinophilic inflammation. CD1d1 mutant mice, deficient in NKT cells but with normal NK cells, developed lung tissue eosinophilia and allergen-specific IgE levels not different from those observed in wild-type mice. Mice deficient in gamma/delta T cells showed a mild attenuation of lung tissue eosinophilia in this model. Taken together, these findings suggest a critical role of NK cells, but not of NKT cells, for the development of allergen-induced airway inflammation, and that this effect of NK cells is exerted during the immunization. If translatable to humans, these data suggest that NK cells may be critically important for deciding whether allergic eosinophilic airway disease will develop. These observations are also compatible with a pathogenic role for the increased NK cell activity observed in human asthma.     

Persistence of sputum eosinophilia in children with controlled asthma when compared with healthy children

We aimed to describe induced sputum cell counts in healthy nonasthmatic children, and to compare these to children with controlled and uncontrolled asthma. Following clinical assessment and spirometry, ultrasonically nebulized hypertonic saline was used to induce sputum from children with asthma (n=50) and without asthma (n=72). Sputum was dispersed and cell counts performed to yield total and differential cell counts. Specific stains were used for eosinophil and mast cell counts. All of the children with asthma were receiving inhaled and/or oral corticosteroids. Current asthma control was assessed in terms of symptoms and lung function. Children were classified as controlled on inhaled corticosteroids (no current symptoms, normal lung function n=15), current symptomatic asthma (n=16) and asthma exacerbation (n=11). It was found that eosinophils comprised a median 0.3% (interquartile range (IQR): 0, 1.05) of cells in sputum from healthy children. Sputum eosinophils (4.3% (IQR: 15, 14.1) p=0.0005) and epithelial cells (14% (IQR: 6, 19.4) p=0.0005) were significantly higher in children with asthma than in nonasthmatic children. Children whose asthma was controlled, as well as those with symptoms, had more sputum eosinophils and epithelial cells than the nonasthmatics. Mast cells were found in the sputum of only four of the 42 children with asthma. This study demonstrates that eosinophilic airway inflammation and epithelial damage can occur in children with asthma. Airway inflammation persists even in those children who are receiving inhaled corticosteroids, have normal lung function and good symptomatic control of their disease.     

Airway epithelium: more than just a barrier!

Airway hyper-responsiveness and epithelial cell damage are associated commonly with asthma. The airway epithelium is a physical barrier that protects sensory nerves and smooth muscle from stimulation by inhaled irritants. In addition, epithelial cells release mediators that can inhibit bronchoconstriction by relaxing the underlying smooth muscle: so-called 'epithelium-derived relaxing factors' (EpiDRFs). Clear functional evidence for EpiDRFs is provided by experiments where different endogenous mediators induce the relaxation of tracheas containing epithelium, but cause a contraction in preparations lacking this layer. Here, Gert Folkerts and Frans Nijkamp describe the pharmacological relevance of the putative EpiDRFs, prostaglandin E2 and NO, in the modulation of airway tone under basal conditions in vitro and in vivo. Special attention is paid to the role of both EpiDRFs in the development of airway hyper-responsiveness in animal models and in patients with asthma.     

The role of rhinovirus in allergic airway inflammation

Epidemiological data demonstrate that viral infections are the most important trigger for acute asthma symptoms in children, and this association persists in many adults with asthma. Studies on volunteers experimentally infected with rhinoviruses (RV) suggest that atopy alone does not predispose to unusually severe symptoms. In contrast, experimental models combining viral infection and allergen exposure have identified potential links between virus-induced and allergen-induced inflammation. While in vitro studies suggest that cytokines may be an important part of this association, their role must be verified by sampling lower airway fluids and tissues in vivo after experimental and/or natural rhinovirus infections. Although it has long been recognized that the common cold is a potent trigger for symptoms of asthma, the mechanisms underlying the association between upper respiratory infection and increased lower airway obstruction remain obscure. The use of experimental infection of volunteers with or without respiratory allergies has enabled direct comparisons of common cold symptoms in these two groups. Furthermore, techniques such as bronchoalveolar lavage and segmental antigen challenge have been used to directly sample lower airway fluids and tissues during acute viral infection.     

Mitogen-activated signaling in cultured airway smooth muscle cells

Airway hyperresponsiveness and excess smooth muscle mass coexist in patients with asthma and bronchopulmonary dysplasia. This increase in airway smooth muscle mass, which in part relates to smooth muscle proliferation, may increase bronchoconstrictor-induced airway narrowing, even in the absence of excessive force generation. Thus, there is need for a precise understanding of the events involved in airway smooth muscle mitogenesis. This review examines the inflammatory substances and growth factors that induce airway smooth muscle proliferation, and the signaling pathways that may be involved in the transduction of these extracellular signals to the cell nucleus. Also discussed are various antimitogenic substances and potential mechanisms underlying the inhibition of cell proliferation. Central to the discussion are the extracellular signal regulated kinases (ERKs), serine/threonine kinases of the mitogen-activated protein kinase (MAP kinase) superfamily, which upon activation, translocate from the cytoplasm to the nucleus after mitogenic stimulation. Insight gained from studies of cultured airway smooth muscle growth and mitogen-activated signaling may shed light on parallel mechanisms that may operate in asthma and in bronchopulmonary dysplasia, and may lead to therapeutic interventions against airway remodeling.     

Airway remodeling: potential contributions of subepithelial fibrosis and airway smooth muscle hypertrophy/hyperplasia to airway narrowing in asthma

Recently, much attention has been focused on the airway structural changes accompanying chronic, severe asthma, and the potential ramifications of these changes for airway function and medical management. Airway remodeling may exaggerate airway narrowing by: (i) thickening of the airway wall internal to the smooth muscle, thereby increasing the luminal obstruction generated by a given degree of smooth muscle shortening; (ii) increasing the amount of smooth muscle, thereby increasing shortening; and/or (iii) reducing the load on the smooth muscle, either by increasing the compliance of the airway wall or by reducing airway-parenchymal interdependence. The possibility also exists that airway remodeling represents a protective mechanism against excessive airway narrowing. The major airway structural changes occurring in asthma are subepithelial protein deposition and increased airway smooth muscle mass (hypertrophy, hyperplasia, or both). Several investigators have found correlations between the magnitudes of subepithelial thickening and smooth muscle hypertrophy/hyperplasia and the severity of airways disease, though interpretation has been made difficult by study differences in patient population, treatment, indices of disease severity, and morphometric technique. Taken together, these data suggest that increases in airway remodeling may contribute significantly to the airflow obstruction observed in patients with asthma. However, data proving a causal relationship between airway remodeling and asthma severity remain elusive.     

Budesonide affects allergic mucociliary dysfunction

Airway inflammation characterized by neutrophils and free elastase contributes to allergic mucociliary dysfunction. Glucocorticosteroids are the most important anti-inflammatory agents used in the treatment of asthma, but their effect on allergic mucociliary dysfunction is not known. Therefore, we assessed both the prophylactic and therapeutic effects of the glucocorticosteroid budesonide on antigen-induced mucociliary dysfunction in sheep. Tracheal mucus velocity (TMV), a marker of mucociliary clearance, was measured by using a roentgenographic technique. When budesonide was administered either 30 min before or 1 h after airway challenge with Ascaris suum, the antigen-induced fall in TMV at 6 h was prevented. The effects on TMV at 8 and 24 h after challenge were also determined when budesonide and, for comparative purposes, alpha1-protease inhibitor were given 6 h after antigen challenge. Budesonide treatment improved TMV at 8 h, but TMV was not significantly different from antigen alone at 24 h. Treatment with alpha1-protease inhibitor, however, caused only a significant reversal of the antigen-induced fall in TMV at 24 h after challenge; this indicates a more prolonged effect than budesonide. Our results suggest that antiproteases may have a potential role as a therapeutic approach to mucociliary dysfunction in asthma and provide evidence for another means by which glucocorticosteroids contribute to the control of the disease.     

Apheresis platelets: emerging issues related to donor platelet count, apheresis platelet yield, and platelet transfusion dose

The prevalence of atopic dermatitis and other allergic diseases is increasing in industrialized countries. Today we know that atopy is conditioned genetically, but the development of the atopic phenotype requires environmental factors. It is believed that the genetic factors have not changed and that the increased prevalence is due to the increase in exposure to allergenic and non-specific environmental factors. The potential for sensitization is greater in the early years of life, so it is necessary to reduce harmful environmental exposure at these ages. Atopic clinical manifestations develop sequentially, in many cases beginning with atopic dermatitis in the early months of life. We know that children with atopic dermatitis present non-specific bronchial hyperreactivity (58 to 82%), which is a risk factor for the later development of asthma. The presence of specific bronchial hyperreactivity for mites in atopic dermatitis with mite sensitization also has been described, and it has been demonstrated that signs of eczema can develop or become exacerbated by airway exposure during bronchial challenge tests. The evolution from atopic dermatitis to asthma is a possibility that must be kept in mind. Patients should be followed-up and study of hyperreactivity and sensitization to allergens should be carried out in order to prevent the development of clinical symptoms. Prevention should include pneumoallergens, food allergens, and non-specific environmental risk factors, such as parental smoking (particularly mothers), pollution inside and outside the home, etc. Prevention is particularly important in children at risk of allergy, as determined by a family history among first-degree relatives, as well as the presence of atopic dermatitis, particularly of early onset, because these patient are most at risk of developing bronchial asthma in later years. At present, pharmacological prevention is being studied, without overlooking environmental prevention, in children at high risk of atopic disease for the purpose of preventing chronic inflammations that will condition their future as adults. In our daily clinical experience, atopic dermatitis is responsible for 8% of visits to a pediatric allergology unit. We emphasize that 62.5% of our patients with dermatitis are referred when they already have bronchial asthma, which represents an important delay in diagnosis with respect to the onset of symptoms.