Advances in pediatric asthma in 2008: Where do we go now?
2009; Elsevier BV; Volume: 123; Issue: 1 Linguagem: Inglês
10.1016/j.jaci.2008.11.002
ISSN1097-6825
Autores Tópico(s)Occupational exposure and asthma
ResumoThis year's summary focuses on recent advances in pediatric asthma as reported in Journal publications in 2008. New National Asthma Education and Prevention Program asthma guidelines were released in 2007 with a special emphasis on asthma control. Attention was redirected to methods that could reduce impairment, specifically symptom control, and minimize risk, including exacerbations. Journal theme issues in 2008 focused on several relevant asthma topics including asthma exacerbations, exercise-induced bronchospasm, asthma and obesity, and occupational asthma. This review highlights Journal articles and related articles that reinforce principles of the guidelines and also direct us to new information that will advance asthma care for children. A major step forward will be finding ways to implement the asthma guidelines. This year's summary focuses on recent advances in pediatric asthma as reported in Journal publications in 2008. New National Asthma Education and Prevention Program asthma guidelines were released in 2007 with a special emphasis on asthma control. Attention was redirected to methods that could reduce impairment, specifically symptom control, and minimize risk, including exacerbations. Journal theme issues in 2008 focused on several relevant asthma topics including asthma exacerbations, exercise-induced bronchospasm, asthma and obesity, and occupational asthma. This review highlights Journal articles and related articles that reinforce principles of the guidelines and also direct us to new information that will advance asthma care for children. A major step forward will be finding ways to implement the asthma guidelines. Last year, this Advances in Pediatric Asthma review included a summary of key features in the updated asthma guidelines and discussed new findings related to pediatric asthma.1Szefler S.J. Advances in pediatric asthma in 2007.J Allergy Clin Immunol. 2008; 121: 614-619Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar The asthma guidelines emphasized the importance of asthma control, a stepwise approach to asthma management, and the importance of early diagnosis and intervention.2National Institutes of Health. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma. August 2007. NIH publication no. 07-4051. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/index.htm. Accessed November, 10, 2008.Google Scholar, 3Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma—summary report 2007.J Allergy Clin Immunol. 2007; 120: S94-S138Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar This review highlights 2008 Journal publications that reinforce principles in the current guidelines and add new information to consider for future guidelines and observations that advance our ability to adapt personalized medicine to the management of childhood asthma (Table I).Table IKey advances in pediatric asthma in 20081. For asthma guidelines to be effective, clinicians must incorporate key messages into practice, specifically application of spirometry and appropriate use of long-term controller therapy.2. Careful identification of asthma phenotypes combined with biomarkers and genetics will lead to new insights into the mechanisms of this complex, heterogeneous disease.3. Attention must now be directed to reducing health disparities with better understanding of methods that lead to poor asthma control in susceptible populations.4. Risk profiles are developing that will lead to early identification of children susceptible to persistent asthma and prompt early intervention strategies.5. Asthma and obesity represent growing epidemics that often coexist with beginnings in early childhood. Open table in a new tab Implementing the asthma guidelinesSeveral key terms were introduced with the new National Asthma Education and Prevention Program asthma guidelines, including severity, control, responsiveness, impairment, and risk.2National Institutes of Health. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma. August 2007. NIH publication no. 07-4051. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/index.htm. Accessed November, 10, 2008.Google Scholar, 3Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma—summary report 2007.J Allergy Clin Immunol. 2007; 120: S94-S138Abstract Full Text Full Text PDF PubMed Scopus (0) Google ScholarSeverity is defined as the intrinsic intensity of the disease process and can be measured most readily and directly in patients who are not receiving long-term controller therapy. Control is the degree to which the manifestations of asthma (symptoms, functional impairment, and risks of untoward events) are minimized and the goals of therapy are achieved. Responsiveness is the ease with which control is achieved by therapy.Asthma severity and asthma control are both divided into 2 domains: impairment and risk. Impairment is the assessment of the frequency and intensity of symptoms, as well as the functional limitations that the patient is experiencing now or in the past because of asthma. Risk is the estimate of the likelihood of an asthma exacerbation, progressive loss of pulmonary function over time caused by asthma, or an adverse event from medication or even death. The assessment of severity and control provides guidance for the direction to take in stepping up or stepping down medications. In a recent theme issue on asthma in The Lancet, McIvor and Chapman4McIvor R.A. Chapman K.R. The coming of age of asthma guidelines.Lancet. 2008; 372: 1021-1022Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar provide an overview of the past 20 years of asthma guidelines by pointing out some of the challenges in addressing the appropriate target audience and assuring application of these principles to improve outcomes. They point to the many ways that clinicians have ignored key messages in these reports and support the new direction in making guidelines practical and implementable. There are ways to do this, but it will require cooperation from all stakeholders including patients, health care providers, and clinicians, to name a few.Asthma controlNow that attention is redirected to achieving well controlled asthma, we must carefully monitor asthma control to evaluate the benefits and risks of interventions. Asthma is a complex disease, and key to understanding individual patients is the careful assessment of control to guide treatment and help anticipate and thus prevent exacerbations and progression of the disease.5Frey U. Suki B. Complexity of chronic asthma and chronic obstructive pulmonary disease: implications for risk assessment and disease progression and control.Lancet. 2008; 372: 1088-1099Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 6Spahn J.D. Covar R.A. Clinical assessment of asthma progression in children and adults.J Allergy Clin Immunol. 2008; 121: 548-557Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar Careful identification of asthma phenotypes will lead to new insights into the mechanisms of this complex, heterogeneous disease.7Anderson G.P. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease.Lancet. 2008; 372: 1107-1119Abstract Full Text Full Text PDF PubMed Scopus (729) Google ScholarHolt et al8Holt E.W. Cook E.F. Covar R.A. Spahn J.D. Fuhlbrigge A.L. Identifying the components of asthma health status in children with mild to moderate asthma.J Allergy Clin Immunol. 2008; 121: 1175-1180Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar applied factor analysis to explore the relationships between measures of asthma morbidity and to identify heterogeneous components of asthma health status in children age 5 to 12 years. They identified 5 factors—(1) inflammatory markers, (2) symptom/medication use, (3) asthma exacerbations, measures of lung function based on (4) FEV1 and forced vital capacity, and (5) bronchodilator response and FEV1/forced vital capacity—that appear to provide independent information in the assessment of asthma. Bender and Zhang9Bender B. Zhang L. Negative affect, medication adherence, and asthma control in children.J Allergy Clin Immunol. 2008; 122: 490-495Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar examined adherence and asthma control and concluded that although negative affect and adherence were predictive of asthma control, the relationship of each to asthma control was distinctly different. They observed that the accuracy of symptom perception may be influenced by patient and parent affect characteristics.ManagementAsthma management in children carries with it concern for adverse effects of commonly used medications. A brief report by Pelkonen et al10Pelkonen A. Kari O. Selroos O. Nikander K. Haahtela T. Turpeinen M. Ophthalmologic findings in children with asthma receiving inhaled budesonide.J Allergy Clin Immunol. 2008; 122: 832-834Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar provided reassuring information that short courses of high-dose inhaled corticosteroid (ICS) and long-term use of low-dose to medium-dose ICS, specifically budesonide, was not associated with the development of lens opacities or clinically important increases in intraocular pressure.The recent report of an adolescent suicide attributed to initiation of montelukast has raised concern regarding psychological adverse effects associated with leukotriene modifiers. Holbrook and Harik-Khan11Holbrook J.T. Harik-Khan R. Montelukast and emotional well-being as a marker for depression: results from three randomized double-masked clinical trials.J Allergy Clin Immunol. 2008; 122: 828-829Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar examined data from 3 controlled trials conducted within the American Lung Association Asthma Clinical Research Centers and did not find evidence of a negative effect of montelukast on emotional well being, but additional studies will be needed to examine the potential for idiosyncratic reactions.Questions continue to be raised regarding the benefits of early intervention with ICS. Based on analysis from an early intervention study with budesonide (Inhaled Steroid Treatment As Regular Therapy in Early Asthma study) conducted in 7241 patients age 5 to 66 years with recent-onset, mild persistent asthma, Busse et al12Busse W.W. Pedersen S. Pauwels R.A. Tan W.C. Chen Y.Z. Lamm C.J. et al.START Investigators Group. The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5-year follow-up: effectiveness of early intervention with budesonide in mild persistent asthma.J Allergy Clin Immunol. 2008; 121: 1167-1174Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar concluded that this form of early intervention improved asthma control including significantly lower risk of severe asthma-related events with less additional medication use.Managed careNow that revised guidelines are available, it will be important to assess ways to integrate these principles into managed care systems. These systems can be used to examine the efficacy of treatment strategies. For example, Zeiger et al13Zeiger R.S. Hay J.W. Contreras R. Chen W. Quinn V.P. Seal B. et al.Asthma costs and utilization in a managed care organization.J Allergy Clin Immunol. 2008; 121: 885-892Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar examined the effect of single controller ICS compared with other drug regimens and concluded that total direct costs and asthma-related utilizations were meaningfully less in the year after being dispensed single controller ICS compared with single controller leukotriene modifiers or most combination controllers.Despite significant advances in care that have seen the reduction in asthma mortality over the last 10 years, certain patient populations still experience greater morbidity, and this disparity must be addressed. Stingone and Claudio14Stingone J.A. Claudio L. Disparities in allergy testing and health outcomes among urban children with asthma.J Allergy Clin Immunol. 2008; 122: 748-753Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar examined allergy care in urban children and found that many children do not receive comprehensive asthma treatment that includes management of allergies and education on avoidance of household allergens. This might indicate lower access to medical care among families ineligible for public programs. Alternatively, perhaps unique programs will have to be applied to reduce health disparities. Canino et al15Canino G. Vila D. Normand S.T. Acosta-Pérez E. Ramírez R. García P. et al.Reducing asthma health disparities in poor Puerto Rican children: the effectiveness of a culturally tailored family intervention.J Allergy Clin Immunol. 2008; 121: 665-670Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar evaluated the effectiveness of a culturally adapted family asthma management intervention and found that this home-based program tailored to cultural needs of low-income Puerto Rican families resulted in a number of improved asthma control measures and improved parents' confidence in managing their child's asthma.New insights that could affect future asthma managementAlthough the asthma guidelines summarize a significant amount of information about asthma, there is much that we do not know about the susceptibility, variability, recovery, and mechanisms of the disease.16Reed C.E. What the 21st century does not know about asthma—yet.J Allergy Clin Immunol. 2008; 121: 601-602Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar This section highlights new findings that should receive attention in revising future asthma guidelines.Early indicators associated with asthmaOur ability to prevent the development of asthma is strongly linked to our ability to identify characteristics that are associated with a high likelihood of developing the disease. Some studies have pointed to prenatal indicators, and others have examined postnatal factors. In regard to prenatal factors, Pistiner et al17Pistiner M. Gold D.R. Abdulkerim H. Hoffman E. Celedón J.C. Birth by cesarean section, allergic rhinitis, and allergic sensitization among children with a parental history of atopy.J Allergy Clin Immunol. 2008; 122: 274-279Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar reported that cesarean delivery was not associated with the development of asthma but was associated with allergic rhinitis and atopy among children with a parental history of asthma or allergies. On the other hand, Kumar et al18Kumar R. Yu Y. Story R.E. Pongracic J.A. Gupta R. Pearson C. et al.Prematurity, chorioamnionitis, and the development of recurrent wheezing: A prospective birth cohort study.J Allergy Clin Immunol. 2008; 121: 878-884Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar reported a relationship of prematurity and chorioamnionitis on early childhood wheezing, an effect that was stronger in African Americans. These observations require confirmation to set up risk profiles for features that signal a child at risk for persistent asthma.Several studies reported on features associated with developing asthma in children. McDonald et al,19McDonald K.L. Huq S.I. Lix L.M. Becker A.B. Kozyrskyj A.L. Delay in diphtheria, pertussis, tetanus vaccination is associated with a reduced risk of childhood asthma.J Allergy Clin Immunol. 2008; 121: 626-631Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar in a longitudinal study in Manitoba, found a negative association between delay in administration of the first dose of whole-cell diphtheria-tetanus-pertussis immunization in childhood and the development of asthma, with the association greater with delays in all of the first 3 doses.Kim et al20Kim J.S. Ouyang F. Pongracic J.A. Fang Y. Wang B. Liu X. et al.Dissociation between the prevalence of atopy and allergic disease in rural China among children and adults.J Allergy Clin Immunol. 2008; 122: 929-935Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar sought to describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population. They noted that although atopic sensitization was common in this rural farming population, particularly to shellfish, peanut, dust mite, and cockroach, the prevalence of allergic disease was quite low. However, Donohue et al21Donohue K.M. Al-alem U. Perzanowski M.S. Chew G.L. Johnson A. Divjan A. et al.Anti-cockroach, mouse IgE is associated with early wheeze and atopy in an inner-city birth cohort.J Allergy Clin Immunol. 2008; 122: 914-920Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar observed in an inner-city population that children age 2 to 3 years who develop anticockroach, mouse IgE are at increased risk of wheeze and atopy with a dose-response relationship between higher IgE class and prevalence of wheeze, rhinitis, or atopic dermatitis. Thus, the pattern of specific sensitization could be important in determining the disease course.Interesting observations in select populations can also help our understanding of pathways to asthma. Foster et al22Foster S.B. McIntosh K. Thompson B. Lu M. Yin W. Rich K.C. et al.Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study.J Allergy Clin Immunol. 2008; 122: 159-165Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar noted an increased incidence of asthma in HIV+ children treated with highly active antiretroviral therapy (HAART) than HIV+ children not receiving HAART and hypothesized that this might be driven by immunoreconstitution of CD4+ T cells. Burgess et al23Burgess J.A. Dharmage S.C. Byrnes G.B. Matheson M.C. Gurrin L.C. Wharton C.L. et al.Childhood eczema and asthma incidence and persistence: a cohort study from childhood to middle age.J Allergy Clin Immunol. 2008; 122: 280-285Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar examined the association between childhood eczema and asthma and concluded that childhood eczema increased the likelihood of childhood asthma, of new-onset asthma in later life, and of asthma persisting into middle age; however, this finding was no longer evident when adjusted for allergic rhinitis. Shaaban et al24Shaaban R. Zureik M. Soussan D. Neukirch C. Heinrich J. Sunyer J. et al.Rhinitis and onset of asthma: a longitudinal population-based study.Lancet. 2008; 372: 1049-1057Abstract Full Text Full Text PDF PubMed Scopus (441) Google Scholar using the European Community Respiratory Health Survey investigated the onset of asthma in patients with allergic and nonallergic rhinitis in an adult population. They noted a relationship of allergic rhinitis, especially with sensitization to mite, was associated with increased risk of asthma independently of other allergens. These observations prompt studies of early intervention for allergic rhinitis or eczema either directly for these allergic disorders or as indicators for initiating treatment of asthma to determine their effect on altering the course of asthma. Lowe et al25Lowe A.J. Carlin J.B. Bennett C.M. Hosking C.S. Abramson M.J. Hill D.J. et al.Do boys do the atopic march while girls dawdle?.J Allergy Clin Immunol. 2008; 121: 1190-1195Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar also studied the relationship of eczema to asthma and reported that eczema in the first 2 years of life is associated with an increased risk of childhood asthma in boys, but there was no evidence of this relationship in girls. Beasley et al,26Beasley R. Clayton T. Crane J. von Mutius E. Lai C.K.W. Montefort S. et al.ISAAC Phase Three Study GroupAssociation between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6-7 years: Analysis from Phase Three of the ISAAC programme.Lancet. 2008; 372: 1039-1048Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar based on observations in the International Study of Asthma and Allergies in Childhood program, reported that use of paracetamol (acetaminophen) in the first year of life and in later childhood is associated with risk of asthma at age 6 to 7 years and might be a risk factor or signal for the development of asthma in childhood.Tepper et al27Tepper R.S. Llapur C.J. Jones M.H. Tiller C. Coates C. Kimmel R. et al.Expired nitric oxide and airway reactivity in infants at risk for asthma.J Allergy Clin Immunol. 2008; 122: 760-765Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar reported that atopic characteristics of the infant could be important determinants of airway physiology based on observations that infants sensitized to egg or milk compared with infants sensitized to neither egg or milk had lower flows and greater airway reactivity but no difference in exhaled nitric oxide. However, infants with total serum IgE levels >20 IU/mL had higher exhaled nitric oxide levels compared with infants with IgE levels ≤20 IU/mL but no difference in forced flows or airway reactivity.Elliott et al28Elliott L. Henderson J. Northstone K. Chiu G.Y. Dunson D. London S.J. Prospective study of breast-feeding in relation to wheeze, atopy, and bronchial responsiveness in the Avon Longitudinal Study of Parents and Children (ASPAC).J Allergy Clin Immunol. 2008; 122: 49-54Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar examined the relationship between breast-feeding and later asthma and allergy outcomes using a large birth cohort in the United Kingdom and did not find a relationship. This is consistent with other reports that suggest breast-feeding may be helpful in reducing the likelihood of wheezing in young children but does not affect the course of later outcomes.29Sicherer S.H. Burks A.W. Maternal and infant diets for prevention of allergic diseases: understanding menu changes in 2008.J Allergy Clin Immunol. 2008; 122: 29-33Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Finally, Stern et al30Stern D.A. Morgan W.J. Halonen M. Wright A.L. Martinez F.D. Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study.Lancet. 2008; 372: 1058-1064Abstract Full Text Full Text PDF PubMed Scopus (303) Google Scholar examined the contribution of sex and early life factors to asthma diagnosed in young adults. They concluded that asthma with onset in early adulthood has its origins in childhood. Factors associated with chronic asthma at 22 years of age included onset at 6 years of age and persistent wheezing in early life, sensitization to Alternaria alternata, low airway function at age 6 years, and bronchial hyperresponsiveness at 6 years. In a comprehensive review of the literature, Sly et al31Sly P.D. Boner A.L. Bjorksten B. Bush A. Custovic A. Eigenmann P.A. et al.Early identification of atopy in the prediction of persistent asthma in children.Lancet. 2008; 372: 1100-1106Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar concluded that objective assessment of atopy by quantitating allergen-specific IgE in serum against common food allergens and local aeroallergens by 2 years of age in conjunction with the presence of other atopic manifestations can help identify the wheezing children at high risk of developing persistent asthma. Nicolaou et al32Nicolaou N.C. Simpson A. Lowe L.A. Murray C.S. Woodcock A. Custovic A. Day-care attendance, position in sibship, and early childhood wheezing: a population-based birth cohort study.J Allergy Clin Immunol. 2008; 122: 500-506Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar noted that day care attendance was associated with a reduced risk of current wheezing in 5-year-old children. The protective effect appeared strongest for children who entered day care between the ages of 6 and 12 months.This information helps set the stage for early identification of children at risk for developing asthma and for designing trials to develop methods to modify the course of asthma. Indeed, some of these risk factors have already been used to design trials for intervention in young children at high risk for developing asthma.33Guilbert T.W. Morgan W.J. Zeiger R.S. Mauger D.T. Boehmer S.J. Szefler S.J. et al.Two year inhaled corticosteroid treatment on subsequent asthma in high-risk toddlers.N Engl J Med. 2006; 354: 1985-1997Crossref PubMed Scopus (869) Google ScholarAsthma and obesityNational attention has been directed to the growing epidemic of obesity. The May 2008 theme issue was devoted to asthma and obesity. Litonjua and Gold34Litonjua A.A. Gold D.R. Asthma and obesity: common early-life influences in the inception of disease.J Allergy Clin Immunol. 2008; 121: 1075-1084Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar comment that the prevalence of both asthma and obesity has increased, and both have their beginnings in early childhood. Therefore, common exposures that predispose individuals to both conditions may explain the association. They discuss some common factors, such as common genetic predictors, prenatal exposure to specific nutrients and overall maternal nutrition, patterns of colonization of the neonatal and infant gut, birth weight and infant weight gain, sedentary behaviors, and levels of adipokines in early life, as features to explore.Shore35Shore S.A. Obesity and asthma: possible mechanisms.J Allergy Clin Immunol. 2008; 121: 1087-1093Abstract Full Text Full Text PDF PubMed Scopus (346) Google Scholar extends this discussion by presenting several mechanisms associated with obesity that contribute to asthma, including reduced lung volume and tidal volume in obesity that promote airway narrowing; low-grade inflammation that may act on the lungs to exacerbate asthma; obesity-related changes in adipose-derived hormones including leptin and adiponectin; and comorbidities of obesity, such as dyslipidemia, gastroesophageal reflux, sleep-disordered breathing, type 2 diabetes, or hypertension that may provoke or worsen asthma. Therefore, novel therapeutic strategies for treatment of the obese patient with asthma may result from a better understanding of the mechanisms that contribute to both disorders.Mehra and Redline36Mehra R. Redline S. Sleep apnea: a proinflammatory disorder that coaggregates with obesity.J Allergy Clin Immunol. 2008; 121: 1096-1102Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar identified a coaggregated relationship between obesity and sleep apnea that may affect asthma control through augmented inflammation and oxidative stress affecting cardiopulmonary disease. Mosen et al37Mosen D.M. Schatz M. Magid D.J. Camargo C.A. The relationship between obesity and asthma severity and control in adults.J Allergy Clin Immunol. 2008; 122: 507-511Abstract Full Text Full Text PDF PubMed Scopus (246) Google Scholar demonstrate that obesity is associated with worse asthma outcomes, especially an increased risk of asthma-related hospitalization. Although this relationship between asthma and worse outcomes has not been clearly demonstrated in children, the pattern is set because infants with higher weight-for-length scores at 6 months of age have a greater risk of recurrent wheezing by age 3 years.38Taveras E.M. Rifas-Shiman S.L. Camargo C.A. Gold D.R. Litonjua A.A. Oken E. et al.Higher adiposity in infancy associated with recurrent wheeze in a prospective cohort of children.J Allergy Clin Immunol. 2008; 121: 1161-1166Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar Therefore, early interventions to prevent excess infant adiposity might help reduce children's risk of asthma-related symptoms.Asthma exacerbationsThe revised asthma guidelines also redirect attention to assessing and preventing asthma exacerbations. The October 2008 theme issue was focused on asthma exacerbations.39Szefler S.J. Asthma exacerbations: putting a lid on the volcano.J Allergy Clin Immunol. 2008; 122: 697-699Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Sears40Sears M.R. Epidemiology of asthma exacerbations.J Allergy Clin Immunol. 2008; 122: 662-668Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar provides an excellent review on the epidemiology of asthma exacerbations, indicating that exacerbations are often, but not always, associated with viral infection, especially rhinovirus, with significant interaction with allergen sensitization and exposure. Seasonal patterns of exacerbations are seen especially in children, and may be aggravated by lack of adequate maintenance anti-inflammatory treatment during the high-risk viral season, especially that reflected in the Northern Hemisphere in the month of September after returning to school. Therefore, recognizing these risk factors can be used to design prevention measures to reduce morbidity and mortality associated with asthma exacerbations. Sykes and Johnston41Sykes A. Johnston S.L. Etiology of asthma exacerbations.J Allergy Clin Immunol. 2008; 122: 685-688Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar and Kelly and Busse42Kelly J.T. Busse W.W. Host immune responses to rhinovirus: mechanisms in asthma.J Allergy Clin Immunol. 2008; 122: 671-682Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar provide detailed discussions on the mechanisms of asthma exacerbations, es
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