The role of viruses in development or exacerbation of atopic asthma

Respiratory viral infections in early childhood have been linked to the development of persistent wheezing and asthma. Epidemiologic data indicate that, for the majority of children, virus-induced wheezing is a self-limited condition, with no long-term consequences. For a substantial minority, however, virus-induced wheezing is associated with persistent asthma and the potential for enhanced allergic sensitization. For the most part, this subset of patients is genetically predisposed; they are atopic children in whom respiratory viral infections trigger the early development of asthma by mechanisms that have not been fully elucidated. Both inflammatory and noninflammatory mechanisms may be involved. It does not appear that viral infection per se in early life is responsible for the induction of atopic asthma. Data from animal models provide support for the concept that enhanced allergic sensitization caused by increased uptake of allergen during infection may play a critical role, as well as T-cell-mediated immune responses to viral infection, which may favor eosinophilic inflammatory responses and the development of altered airway function to inhaled methacholine. Recent advances in our understanding of the interactions between respiratory viruses and the development of reactive airway disease offer new possibilities for preventive treatment in children at risk for developing persistent wheezing and asthma exacerbation as a result of viral infection.     

Persistent airflow obstruction in young adult asthma patients

Background: Lung function determined by spirometry and the severity of dyspnea correlate weakly in asthma patients. We attempted to determine the risk factors in asthma patients having persistent airway obstruction despite of having only mild subjective symptoms, and to examine the possibility of improving FEV1 by treating asthma on the basis of the bronchodilator change in FEV1.Methods: We examined asthma patients in their 20s and who visited Sagamihara National Hospital for the first time over a period of four years, by reviewing their clinical records. They underwent tests on the bronchodilator change in FEV1 and a test of airway hyperresponsiveness to histamine dihydrochloride.Results: One hundred thirty-eight subjects (mean age, 25.6 years; 51 males, 87 females; current smoking, 30.4%; history of childhood asthma, 48.6%) were enrolled. Among them, 18.8% (26/138) showed persistent airway obstruction (postbronchodilator FEV1/FVC (%) < 80%). Using the multiple logistic regression model, we found that history of childhood asthma and smoking history were the significant isolated risk factors for persistent airway obstruction. Moreover, we determined that the factors associated with the reversibility of airway obstruction in asthma patients without subjective symptoms were history of childhood asthma.Conclusions: In this study, patients not undergoing treatment for asthma were examined. History of childhood asthma and smoking history may be the risk factors for persistent airway obstruction in the asthma patients with mild subjective symptoms. Tests on the bronchodilator change in FEV1 should be performed in patients with history of childhood asthma and smoking history, even if they have only mild subjective symptoms.     

Impact of Innate and Environmental Factors on Wheezing Persistence During Childhood

Background. Persistent asthma in adults starts often early in childhood and is associated with alterations in respiratory function that occur early in life. Objectives. The aim of this study was to evaluate the importance of innate and environmental factors associated with occurrence of asthma during childhood in a population of recurrent wheezing infants followed prospectively. Methods. A cohort of infants less than 30 months old with recurrent wheezing was established in order to assess severity of respiratory symptoms and to look for the presence of atopy and environmental risk factors. At the age of 6 years, they were reevaluated with respect to remission or persistence of wheezing over the previous 12-month period. Results. Data were available for 219 subjects aged 15 ± 5 months. In 27% of the infants with recurrent wheeze, wheezing persisted until the age of 6 years. In multivariate analysis, stepwise logit analysis showed that the risk factors for persistent wheezing are eosinophilia ≥470/mm³, allergenic sensitization, and a father with asthma. Environmental factors present during the first year of life that protect from persistence of wheezing are () breastfeeding for longer than 3 months, () pets at home, and () ≥3 siblings. The detection rate for persistent wheezing in this model is 72%. The persistence score showed good specificity 91% but low sensitivity 35%. Conclusion. This study confirms the role of atopic host factors on wheezing persistence during childhood and detected protective environmental factors.     

Quoi de neuf en allergologie pédiatrique en 2000 ?Revue de la littérature internationale dˈoctobre 1999 à octobre 2000

The relation between maternal and childhood atopy may result from an increased intrauterine Th2 environment and high levels of Th2 cytokines in the milk of atopic mothers. The value of in vitro tests for early prediction of atopy is low, but high levels of eosinophil-derived proteins in nasal secretions of neonates may predict respiratory allergy. The prevalence of respiratory allergy has decreased in children living in rural areas, especially on farms. This may be related to exposure to mycobacterias, but the development of allergic conditions is independent of tuberculin reactivity and history of tuberculosis infection; however, the prevalence of asthma is decreased in young adults infected by Mycobacterium tuberculosis during childhood. High levels of eosinophils in the blood of children with bronchiolitis predict the development of persistent wheezing and asthma. Inhaled, oral and intravenous corticosteroids do not prevent relapses of bronchiolitis and persistent wheezing, but early hyposensitization has long-term beneficial effects on asthmatic symptoms. Results of prick-tests and specific IgE determinations are correlated with the severity of food allergy, and several studies confirm the diagnostic value of patch-tests with foods in children with atopic dermatitis associated with food allergy. Interesting cases of unexpected food allergies are reported (carob-induced anaphylaxis, and exercise-induced anaphylaxis to snails). Finally, children with spina bifida demonstrate a progressive sensitization to latex, in spite of a latex-free environment after the first surgical procedure(s), and the gelatin included in vaccines is highly immunogenic and allergenic.     

The role of respiratory tract infections and the microbiome in the development of asthma: A narrative review

Asthma is a common disease in childhood, and might predispose for chronic obstructive respiratory morbidity in adolescence and adulthood. Various early‐life risk factors might influence the risk of wheezing, asthma, and lower lung function in childhood. Cohort studies demonstrated that lower respiratory tract infections in the first years of life are associated with an increased risk of wheezing and asthma, while the association with lung function is less clear. Additionally, the gut and airway microbiome might influence the risk of wheezing and asthma. The interaction between respiratory tract infections and the microbiome complicates studies of their associations with wheezing, asthma, and lung function. Furthermore, the causality behind these observations is still unclear, and several other factors such as genetic susceptibility and the immune system might be of importance. This review is focused on the association of early‐life respiratory tract infections and the microbiome with wheezing, asthma, and lung function, it is possible influencing factors and perspectives for future studies.

     

Clinical phenotypes of asthma

PURPOSE OF REVIEW: Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic mechanisms, but in particular to ascertain the specific genes associated with these phenotypes. RECENT FINDINGS: In children, three asthma phenotypes are now well defined: transient infant wheezing, nonatopic wheezing of the toddler, and IgE-mediated wheezing/asthma. Recently, a fourth phenotype, late-onset childhood asthma has been added to this list. In adults, asthma persisting from childhood into adulthood should be distinguished from asthma starting in adulthood. The phenotypes of adult-onset asthma are still poorly defined. Until now, phenotypic classification has been based primarily on etiologic factors (eg, aspirin sensitivity, persistent respiratory infections, occupational factors, or toxic exposures) or clinical characteristics of the disease (eg, mild, severe, brittle, near fatal, with fixed airflow obstruction, steroid resistant). Novel noninvasive techniques to assess the type and severity of airway inflammation and dysfunction are increasingly used to identify better the different phenotypes. SUMMARY: The classic phenotype of IgE-mediated asthma starting in childhood is now clearly defined. However, many other phenotypes of asthma in childhood as well in adulthood are being recognized. In particular, asthma starting in adulthood and noneosinophilic asthma constitute an important part of the adult asthma population, and are still poorly defined. A precise definition of these asthma phenotypes is urgently needed because they are likely to be associated with different genotypes, responses to treatment, and prognoses.     

Consequences of long-term inflammation. The natural history of asthma

Although asthma is classically defined as reversible airflow obstruction, and often remits in younger subjects with milder disease, the natural history of asthma is that various degrees of airflow obstruction may persist and, in the long-term, asthma may become moderately to fully irreversible. Severe, irreversible airflow obstruction may develop despite apparently appropriate therapy and in the absence of other risk factors, such as smoking and environmental insults. All studies of subjects with persisting asthma show increased decline in lung function compared with normal subjects. Persistent abnormal physiology is reflected both in reduced airflow rates and in increased airway responsiveness. The cellular and molecular mechanisms of airway remodeling are described elsewhere in this issue. Questions not yet clearly answered are the reasons for these persistent abnormalities in some asthmatics, and which subjects are most at risk. Factors that adversely impact the outcome as adults identified relatively consistently among many longitudinal studies of the natural history of asthma include: Female gender. Environmental tobacco smoke exposure in childhood. Personal tobacco smoking in adolescence and adulthood. Age of onset of symptoms. Severity of childhood asthma. Duration of asthma. Severity of lung function abnormality in childhood. Bronchodilator reversibility. Degree of airway hyperresponsiveness. Delay in initiating anti-inflammatory therapy. Remission among adult asthmatics is uncommon, but is associated with better initial lung function, young age, male gender, and lesser degrees of airway responsiveness. The role of atopy remains controversial. Conversely, risk factors for death from asthma include older age, smoking, atopy, impaired lung function, and moderate to high reversibility. Treatment can improve lung function, reduce airway responsiveness, and improve quality of life. The overall effect of treatment on the natural history of the disease is not yet clear, despite significant short-term improvements from effective anti-inflammatory therapy.     

Issues and unmet needs in pediatric asthma

Asthma is common and becoming more so in childhood. Although mild asthma may incur low average annual costs per child, these estimates need to be viewed in the context of the very large numbers of affected individuals. Whereas asthma and wheezing illness in childhood had in the past been broadly subdivided into asthma (often associated with atopy) and wheezy bronchitis (wheeze only, with associated upper respiratory tract infection), this distinction was lost during the 1970s in view of the demonstrated underdiagnosis and undertreatment of symptomatic school-age children. The acceptance of asthma as a chronic inflammatory disease and evidence for airway remodeling and progressive deterioration in airway function in association with symptoms and atopy have led to earlier use of topical steroids at higher starting doses delivered by improved age-appropriate devices. Treating all children as if they were destined to become atopic asthmatics and at risk of airway remodeling may not be rational, particularly in those whose symptoms will subsequently resolve. However, there are as yet no screening tests which can clearly identify individuals at risk of long-term chronic airway inflammation and airway remodeling. The large number of infants and young children with current symptoms suggestive of asthma and in whom resolution is likely in the majority poses problems for the clinician in deciding the best initial therapy. There is an urgent need to develop simple and reliable measures that can identify the early manifestations of atopic airway sensitisation and to establish the place of early intervention with nonsteroidal drugs, including leukotriene antigonists.     

Asthma,exercise and metabolic dysregulation in paediatrics

Asthma is the most frequent chronic disease in childhood. Chest tightness, cough, wheezing and dyspnoea during or after exercise may be unique manifestations of asthma in up to 90% of subjects. Physical activity may be reduced by uncontrolled asthma symptoms and parental beliefs, impairing physical fitness of asthmatic children. Clinicians working in the field of allergy are aware of evidence supporting the benefits of physical activity for patients with asthma. Treatment of asthma is required in order to obtain its control and to avoid any limitation in sports and active play participation. As exercise performance in children with controlled asthma is not different from that of healthy controls, any exercise limitation cannot be accepted. Overweight and obesity may interfere with asthma and exercise, leading to dyspnoea symptoms. Evidences on the effect of insulin resistance on airway smooth muscle and on bronchial hyperactivity are presented.

Neutrophilic airway inflammation and association with bacterial lipopolysaccharide in children with asthma and wheezing

Asthma is a leading chronic childhood illness in the US. To gain further insight into the pathophysiology of childhood asthma, we studied markers of airway inflammation and possible triggers such as bacterial lipopolysaccharide (LPS) in 18 children with chronic asthma and persistent wheezing who underwent clinically indicated bronchoscopy and bronchoalveolar lavage (BAL). We predominantly found neutrophilic airway inflammation associated with increased levels of IL-8, metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP-1) and MMP-9/TIMP-1 ratio. A significant correlation was found between levels of LPS in BAL and airway neutrophils in BAL from a subgroup of children who had a tendency of increased levels of MMP-9 and TIMP-1, suggesting that increased LPS levels in BAL may contribute to chronic airway inflammation and early remodeling. Our data highlight the importance of defining chronic triggers of early airway inflammation in children and characterizing their inflammation, considering the use of bronchoscopy and BAL. Increased knowledge of airway inflammation in children may help prevent a more severe asthma phenotype and lead to environmental control measures and new treatment strategies to intervene against the establishment of irreversible inflammation.     

Development of Bronchial Hyperresponsiveness During Childhood

Bronchial hyperresponsiveness (BHR) produces the characteristic pathological abnormalities seen in asthma and clearly plays a central role in the pathophysiology of asthma. The presence of BHR has been demonstrated in infants with asthma, as has the possibility of BHR persisting through the childhood period. The level of BHR may not only reflect the state of the airways, as a marker of airway dysfunction, but may also predict the persistent prognosis of the disease. Thus, measurement of BHR may provide important information about the symptoms and lung function in children with asthma. In view of multiple pathophysiological mechanisms, BHR does not seem to have a single cause. Many potential confounding variables, such as age, gender, and genetic status, and some environmental factors, such as allergens, infections, and pollutants, could be responsible for the establishment of childhood BHR. There may be differences between the mechanisms that induce transient BHR and the mechanisms that induce persistent BHR. Also, there may be differences between the causes that induce BHR in the infantile period and the causes that maintain persistent BHR during childhood asthma. There is also disagreement as to the most suitable method to measure BHR in children, especially in infants. The assessment of BHR in young children has not been uniformly successful, and measurements of BHR changes over the childhood period are associated with a number of problems. To resolve these problems, there may be two ways to study childhood BHR. One is to use age-matched specific techniques to clarify the precise BHR in each age group; the other is to use simple techniques that can be performed over the childhood period on a large number of subjects. In studies of infantile respiratory dysfunction the ultimate goal is to establish a simple, noninvasive method by which measurements of respiratory function may be obtained in infants. Further investigations and acceptable methods will be needed to clarify the mechanisms involved in the establishment of asthma throughout the childhood period.     

The connection between early life wheezing and subsequent asthma: The viral march

Several new lines of evidence suggest that alterations in immune responses which predispose to bronchial obstruction during acute respiratory infection, especially with rhinoviruses, may explain to a considerable extent the link between early life wheezing and subsequent asthma; above all among those schoolchildren who are prone to having recurrent asthma exacerbations. The nature of these alterations is currently the subject of considerable scrutiny, but cross-sectional studies suggest that deficits in innate immune responses mediated by interferon type I and III are present in lung macrophages and epithelial cells of adult asthmatics. Similarly, long-term follow-up studies suggest that deficits in interferon gamma responses in the first year of life predispose to recurrent episodes of wheezing from the preschool years and into early adolescence. A better understanding of the “viral march” could yield new therapeutic approaches for the prevention and treatment of acute severe airway obstruction during childhood.     

Respiratory viral infections and early asthma in childhood.

Respiratory viral infections profoundly influence the disease activity of wheezing illnesses and asthma in early childhood. Viral bronchiolitis shares many features with asthma and a subset of children develop recurrent wheezing after their initial illness. Recently mechanisms for virus-induced exacerbations of childhood asthma are beginning to be focused on and defined. Viruses cause systemic immune activation and also produce local inflammation. These factors are likely to affect airway pathogenesis leading to airway narrowing, an increase in mucus production, and eventually bronchospasm, and airway obstruction. These new insights related to the pathogenesis and disease activity are likely to provide new targets for the therapy and prevention of early asthma in childhood.     

Viral "bronchitis" in childhood: relationship to asthma and obstructive lung disease

Lower respiratory tract infections in children, including group, bronchiolitis, and bronchitis are frequently associated with recurrent episodes of wheezing. Different respiratory viruses assume greater importance at different ages of children. Respiratory syncytial virus is the most prevalent viral respiratory infection in preschool children, while rhinovirus is of increasing importance in older children. Asymptomatic virus shedding and mild respiratory infections do not provoke asthma symptoms nor do bacteria, except in association with sinusitis. Furthermore, epidemiologic studies strongly suggest that viral lower respiratory tract illness in early childhood is associated with pulmonary abnormalities, including bronchial hyperreactivity and peripheral airway obstruction that may persist for many years, and is possibly a cause of chronic airway obstruction in adulthood. Several different mechanisms have been identified by which respiratory viruses provoke asthma. No one single mechanism, however, adequately explains virus-induced asthma. Nonetheless, a common thread to these various proposed mechanisms is the ability of respiratory viruses to cause airway inflammation, either directly, through cytopathic effects, or indirectly, by increasing the inflammatory processes of respiratory cells. The consequence of these effects causes increased airway responsiveness and asthma.     

Normal airway responsiveness to methacholine in cardiac asthma

Cardiac asthma has been used as a synonym for episodes of cough, dyspnea, and wheezing caused by left ventricular dysfunction. The similarity of the terms bronchial asthma and cardiac asthma, and the observed symptoms of each disease implies a common pathophysiology. Bronchial asthma is characterized pathologically by airway narrowing, inflammation, edema, and obstruction by mucus. Bronchial asthma is defined as increased responsiveness of the tracheobronchial tree, which is manifested clinically as reversible expiratory airflow obstruction. The classic symptoms of bronchial asthma are cough, dyspnea, and wheezing. Cardiac asthma produces the same symptoms, but the pathophysiology producing these symptoms is not well described. We describe two patients with cardiac asthma who failed to demonstrate airway hyperresponsiveness to nonspecific bronchoprovocation testing and we postulate that these patients' symptoms were produced exclusively by left ventricular failure.     

Diagnostic value of flexible bronchoscopy in children with persistent and recurrent wheezing.

Episodes of wheezing are very common in infancy. In pediatrics, indications for flexible bronchoscopy include prolonged wheezing, where airway abnormalities such as malacia disorders, tracheobronchial abnormalities, and vascular ring may be found. The study was performed to determine the diagnostic use of flexible bronchoscopy in wheezy patients who were previously administered bronchodilators and steroids for asthma and whose symptoms recurred or were not improved at all. Infants with wheezing were identified and collected over a 3-year period at the pediatric pulmonology unit. Flexible bronchoscopy was performed for diagnostic purposes in 34 (24 boys and 10 girls) patients with wheezing who were previously treated for asthma. The mean age for the onset of the symptoms was 2.5 months (0-12 months), and the mean age of bronchoscopic assessment was 9 months (45 days-48 months). A definitive diagnosis was made by bronchoscopy in 29 (85%) patients. Functional abnormalities in 15 patients (malacia in 9, tracheal dyskinesia in 3, and both in 3 patients), structural abnormalities in 5 patients (bronchial abnormality in 2, subglottic stenosis in 2, and obliterative-like lesion at the orifice of right bronchus in 1), and coexistent structural and functional abnormalities in 9 patients were present. Bronchoscopy revealed normal findings in five patients. Structural and functional airway abnormalities are commonly found in children with wheezing and should be considered in the differential diagnosis of persistent and prolonged wheezing. Bronchoscopy should be performed in patients who remain symptomatic despite treatment for asthma.     

Effects of glutathione S-transferase M1, maternal smoking during pregnancy,and environmental tobacco smoke on asthma and wheezing in children

The rise in childhood asthma prevalence suggests a role for environmental factors in the etiology of this evolving epidemic; however, genetics also influence the occurrence of asthma. Glutathione S-transferase (GST) M1 may play a role in asthma and wheezing occurrence among those exposed to tobacco smoke, as it functions in pathways involved in asthma pathogenesis such as xenobiotic metabolism and antioxidant defenses. Effects of GSTM1 genotype, maternal smoking during pregnancy, and childhood environmental tobacco smoke (ETS) exposure on asthma and wheezing were investigated in 2,950 children enrolled in 4th, 7th, and 10th grade classrooms in 12 Southern California communities. The effects of in utero exposure to maternal smoking on asthma and wheezing occurrence were largely restricted to children with GSTM1 null genotype. Among GSTM1 null children, in utero exposure was associated with increased prevalence of early onset asthma (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.0-2.5), asthma with current symptoms (OR 1.7, 95% CI 1.1-2.8), persistent asthma (OR 1.6, 95% CI 1.1-2.4), lifetime history of wheezing (OR 1.8, 95% CI 1.3-2.5), wheezing with exercise (OR 2.1, 95% CI 1.3-3.3), wheezing requiring medication (OR 2.2, 95% CI 1.4-3.4), and emergency room visits in the past year (OR 3.7, 95% CI 1.9-7.3). Among children with GSTM1 (+) genotype, in utero exposure was not associated with asthma or wheezing. Our findings indicate that there are important long-term effects of in utero exposure in a genetically susceptible group of children.     

Relación entre las infecciones respiratorias de vías bajas durante el primer año de vida y el desarrollo de asma y sibilancias en niños

Introduction

There is limited knowledge on the relationship between lower respiratory tract infections (LRTI) and asthma and wheezing during infancy, as there are few studies with prospective design, birth cohort and in non selected population. The objectives of the present study were to determine the prevalence of asthma and recurrent wheezing in childhood and to analyse the relationship between LTRI during the first year of life and the development of asthma and/or wheezing in childhood.

Patients and Methods

Prospective birth cohort study conducted in the Hospital del Mar (Barcelona). We recruited 487 children, followed up from the pregnancy to the 6th year of life. As outcomes we studied: the presence of asthma and wheezing. As independent variables we studied: LTRI occurring during the first year of life, and some covariables including, among others: prematurity, birth weight, maternal history of asthma and atopy, breastfeeding, prenatal exposure to tobacco.

Results

The asthma prevalence at 6 year of age was 9.3%. The variables associated with the development of asthma were LTRI, prematurity, atopic mother and formula breastfeeding. LTRI during the first year of life were also related with early recurrent wheezing and persistent wheezing.

Conclusions

Our results confirm that LTRI during the first year of life are related to the diagnosis of asthma and with the clinical phenotypes of early wheezing and persistent wheezing. These results are in accordance with the concept that LTRI occurring during a critical period of development, as are the first years of life, have an important role on in the later development of asthma and recurrent wheezing.     

Eosinophilic airway disorders associated with chronic cough

Chronic cough is a major clinical problem. The causes of chronic cough can be categorized into eosinophilic and noneosinophilic disorders, the former being comprised of asthma, cough variant asthma (CVA), atopic cough (AC) and non-asthmatic eosinophilic bronchitis (NAEB).Cough is one of the major symptoms of asthma. Cough in asthma can be classified into three categories; 1) CVA: asthma presenting solely with coughing, 2) cough-predominant asthma: asthma predominantly presenting with coughing but also with dyspnea and/or wheezing, and 3) cough remaining after treatment with inhaled corticosteroid (ICS) and β2-agonists in patients with classical asthma, despite control of other symptoms. There may be two subtypes in the last category; one is cough responsive to anti-mediator drugs such as leukotriene receptor antagonists and histamine H1 receptor antagonists, and the other is cough due to co-morbid conditions such as gastroesophageal reflux.CVA is one of the commonest causes of chronic isolated cough. It shares a number of pathophysiological features with classical asthma with wheezing such as atopy, airway hyperresponsiveness (AHR), eosinophilic airway inflammation and various features of airway remodeling. One third of adult patients may develop wheezing and progress to classical asthma. As established in classical asthma, ICS is considered the first-line treatment, which improves cough and may also reduce the risk of progression to classical asthma.AC proposed by Fujimura et al. presents with bronchodilator-resistant dry cough associated with an atopic constitution. It involves eosinophilic tracheobronchitis and cough hypersensitivity and responds to ICS treatment, while lacking in AHR and variable airflow obstruction. These features are shared by non-asthmatic eosinophilic bronchitis (NAEB). However, atopic cough does not involve bronchoalveolar eosinophilia, has no evidence of airway remodeling, and rarely progresses to classical asthma, unlike CVA and NAEB. Histamine H1 antagonists are effective in atopic cough, but their efficacy in NAEB is unknown. AHR of NAEB may improve with ICS within the normal range. Taken together, NAEB significantly overlaps with atopic cough, but might also include milder cases of CVA with very modest AHR. The similarity and difference of these related entities presenting with chronic cough and characterized by airway eosinophilia will be discussed.     

Assessing the risk of asthma in infants and pre-school children

Childhood asthma is a heterogeneous inflammatory disease with several wheezing phenotypes (transient, atopic, nonatopic, and obese) and various clinical expressions of multifactorial origin. All forms, however, follow a similar course characterized by recurrent episodes of airway obstruction. Studies have shown that the onset of disease occurs early in life for the great majority of asthmatics, that airway inflammation and remodeling are present in schoolchildren with asthma, and that even infants with persistent wheezing present airway inflammation. The difficulty lies in the early identification of infants with recurrent wheezing who are at risk of suffering persistent asthma later in life. The Asthma Predictive Index, a simple tool validated in a longitudinal study, has been suggested for early identification of infants with recurrent wheezing who are at risk of developing asthma and whose lung function has undergone major irreversible damage during the first years of life.