- Email: [email protected]
The Editors' Choice
The Editors’ Choice Donald Y.M. Leung, MD, PhD Harold S. Nelson, MD Stanley J. Szefler, MD
THE JOURNAL OF
Allergy Clinical Immunology AND
VOLUME 119
NUMBER 3
Key role for TNF in a mouse model of asthma Using various mutant mice on the C57BL/6 background, Nakae et al (p 680) show that the soluble form of TNF importantly contributes to antigen-induced bronchial hyperreactivity (AHR) to methacholine and the associated pulmonary inflammation (see Figure) in a model of ovalbumin (OVA)–induced bronchial allergic inflammation. Earlier work by this group indicates that mast cells play an important role in the expression of this model of allergic inflammation, which omits the use of alum to elicit antigen sensitization. As noted by the authors, one should use great caution in attempting to extrapolate to clinical medicine conclusions that are based on studies of mouse models of airway allergic inflammation. However, as noted by the authors, 2 different pilot studies have already provided evidence that 10 to 12 weeks of treatment with the soluble TNFR-IgG1 Fc fusion protein etanercept improved airway function, reduced AHR to methacholine, and reduced
Inhaled corticosteroids prevent accelerated loss of lung function in some patients with asthma In studies of populations of patients with asthma, there is an accelerated decline in pulmonary function measured by FEV1. It is not certain whether this accelerated decline in lung function is prevented by control of airway inflammation through use of inhaled corticosteroids (ICSs). In this issue of the Journal, de Marco and coauthors (p 611) report relevant data obtained from 667 young adult patients with asthma who were studied twice (1991 to 1993 and 1999 to 2002) as participants in the European Community Respiratory Health Survey. At baseline, the subjects’ mean age was 33.9 years, the mean duration of asthma 15.6 years,
Prednisolone in rhinovirus-associated first wheezing episode It has been difficult to demonstrate the beneficial effects of corticosteroids in early wheezing illnesses, although these agents are clearly effective in the management of childhood asthma. In this issue of the Journal, Lehtinen and coworkers (p 570) report 1-year follow-up of the first wheezing episode in children less than 3 years of age. The children were randomized to receive either prednisolone or placebo. The efficacy of prednisolone was studied post hoc in relation to risk factors for recurrent wheezing, including rhinovirus infection, which has been suggested as a new
J ALLERGY CLIN IMMUNOL
Diminished lung inflammation ()) in OVA-sensitized, OVA-challenged C57BL/6J-TNF–/– mice versus wild-type mice.
symptom scores in patients with refractory, steroid-resistant asthma. The findings of Nakae et al in mice support the hypothesis that TNF can promote the allergic inflammation and AHR observed in some subjects with asthma. and the mean FEV1 3.4 L. On follow-up (average 9 years), there was a significant trend for less loss of pulmonary function with longer use of inhaled corticosteroids: 34 mL/year in nonusers, 28 mL/year in those using ICSs for less than 8.7 months, 24 mL/year for those using ICSs from 8.7 to less than 48 months, and 20 mL/year for those using ICSs for 48 months or more. Decline in lung function was significantly greater in males (35 mL/year) than in females (24 mL/year) and for older subjects, but it was not associated with smoking history. Furthermore, the protective effect of ICSs on loss of lung function was limited to those participants with total serum IgE of more than 100 kU/L. The authors advise that their findings should not be interpreted as indicating that ICSs should be prescribed only in patients with IgE of more than 100 kU/L, inasmuch as only 1 outcome of corticosteroid use was investigated in this study. major risk factor. The study confirmed in a general population that rhinovirus-associated early wheezing is a major viral risk factor for recurrent wheezing. It was a more important predictor than respiratory syncytial virus–induced disease. An unexpected and provocative finding was that a 3day prednisolone treatment for the first episode of wheezing associated with rhinovirus infection showed benefit for up to 12 months. Eczema also influenced the response to prednisolone. The authors found the findings understandable given that susceptibility to rhinovirus-induced early wheezing and eczema is known to predict recurrent wheezing in children. A prospective clinical trial is needed to test the hypothesis that prednisolone reduces recurrent wheezing associated with rhinovirus infection or eczema.
March 2007 Page 527
Eosinophilic esophagitis in children: When does it begin and where does it end? To patients and their families, eosinophilic esophagitis (EE) seems an enigma. When a diagnosis is made, there is relief that a biological reason for the persistent symptoms has finally been found. However, the diagnosis comes with a multitude of questions. How did my child get EE? How long will it take before the EE resolves? How widespread is the intestinal involvement? Assa’ad et al (p 731) made an unprecedented long-term examination of pediatric EE. The authors studied an 8-year follow-up of 89 patients with EE. They report that patients are mainly atopic Caucasian males who frequently develop gastrointestinal pathology in segments of the gastrointestinal tract outside the esophagus. The distribution of the affected segments varies from patient to patient (see Figure), as does the severity of coexisting gastrointestinal pathology. In addition, the authors describe the clinical course of EE as typically involving 3 years of symptoms before a diagnostic endoscopy is performed and as being associated with chronicity, 1 to 3 years being needed for the disease to resolve. Even then, the majority of the patients relapse; hence, long-term follow-up is indicated.
German Infant Nutritional Intervention Study proves nutritional intervention effective for prevention of atopic dermatitis Protein hydrolysates are recommended for infants at risk for allergic diseases if breast-feeding is insufficient. However, the preventive potential of the different types— for example, partially or extensively whey or casein hydrolysates—has not been fully established. Therefore, von Berg et al (p 718) compared, in a prospective, randomized, double-blind fashion, the allergy-preventive effect of 3 hydrolyzed infant formulas with a standard cow’s milk
Cat and dust mite allergen levels, specific IgG and IgG4, and respiratory symptoms in adults Controversy continues to exist regarding the role of animal exposure and the development of allergy. Childhood exposure to high levels of cat dander has been reported to cause an increase in specific IgG4, no IgE response, and little clinical disease. In this issue of the Journal, Jarvis and coauthors (p 697) examine the association of IgG4 levels with allergen exposure and allergic respiratory symptoms in approximately 2500 adult participants in the European Community Respiratory Health Survey. Neither sensitization to cat nor sensitization to house dust mites correlated with mattress levels of the respective major allergens (Fel d 1
Page 528 March 2007
Patients with EE separated into groups according to the gastrointestinal segment(s) with pathologic abnormalities.
formula supplementary to breast-feeding in 2252 high-risk infants. The investigators found a significantly reduced risk for atopic dermatitis, but not for asthma, over 3 years with the extensively hydrolyzed casein and also with the partially hydrolyzed whey hydrolysate, but not with the extensively hydrolyzed whey formula used in this study. This suggests that the preventive potential of a particular hydrolysate is not dependent on the extent of hydrolysis alone and thus can be proved only in clinical trials. Furthermore, the results of a stratified analysis lead to the hypothesis that the phenotype— here, the presence of atopic dermatitis in the infant’s immediate family—might modify the preventive potential of the formulas. In total, this study might be of relevance to further feeding recommendations for high-risk infants. and Der 1). On the other hand, levels of IgG and IgG4 increased with increasing Fel d 1 exposure, particularly in those with specific IgE. No similar relation between Der 1 levels and IgG or IgG4 was observed. Prevalence of symptoms on exposure to cats, dogs, or horses was higher in subjects who were IgE-sensitized to cats. There was no evidence that higher levels of cat-specific IgG4 were associated with less wheeze, asthma, or symptoms on exposure, even when the analyses were stratified by IgE sensitization or for Fel 1 exposure. In subjects with IgE sensitization to house dust mites, the prevalence of asthma was significantly higher in those with the highest IgG4 levels, an association that persisted after adjustment for Der 1 levels. The authors conclude that in this community-based sample of adults, high IgG4 levels to cat or house dust mites were not associated with a lower risk of allergic respiratory symptoms.
J ALLERGY CLIN IMMUNOL
THE JOURNAL OF
Allergy Clinical Immunology AND
VOLUME 119
NUMBER 3
Key role for TNF in a mouse model of asthma Using various mutant mice on the C57BL/6 background, Nakae et al (p 680) show that the soluble form of TNF importantly contributes to antigen-induced bronchial hyperreactivity (AHR) to methacholine and the associated pulmonary inflammation (see Figure) in a model of ovalbumin (OVA)–induced bronchial allergic inflammation. Earlier work by this group indicates that mast cells play an important role in the expression of this model of allergic inflammation, which omits the use of alum to elicit antigen sensitization. As noted by the authors, one should use great caution in attempting to extrapolate to clinical medicine conclusions that are based on studies of mouse models of airway allergic inflammation. However, as noted by the authors, 2 different pilot studies have already provided evidence that 10 to 12 weeks of treatment with the soluble TNFR-IgG1 Fc fusion protein etanercept improved airway function, reduced AHR to methacholine, and reduced
Inhaled corticosteroids prevent accelerated loss of lung function in some patients with asthma In studies of populations of patients with asthma, there is an accelerated decline in pulmonary function measured by FEV1. It is not certain whether this accelerated decline in lung function is prevented by control of airway inflammation through use of inhaled corticosteroids (ICSs). In this issue of the Journal, de Marco and coauthors (p 611) report relevant data obtained from 667 young adult patients with asthma who were studied twice (1991 to 1993 and 1999 to 2002) as participants in the European Community Respiratory Health Survey. At baseline, the subjects’ mean age was 33.9 years, the mean duration of asthma 15.6 years,
Prednisolone in rhinovirus-associated first wheezing episode It has been difficult to demonstrate the beneficial effects of corticosteroids in early wheezing illnesses, although these agents are clearly effective in the management of childhood asthma. In this issue of the Journal, Lehtinen and coworkers (p 570) report 1-year follow-up of the first wheezing episode in children less than 3 years of age. The children were randomized to receive either prednisolone or placebo. The efficacy of prednisolone was studied post hoc in relation to risk factors for recurrent wheezing, including rhinovirus infection, which has been suggested as a new
J ALLERGY CLIN IMMUNOL
Diminished lung inflammation ()) in OVA-sensitized, OVA-challenged C57BL/6J-TNF–/– mice versus wild-type mice.
symptom scores in patients with refractory, steroid-resistant asthma. The findings of Nakae et al in mice support the hypothesis that TNF can promote the allergic inflammation and AHR observed in some subjects with asthma. and the mean FEV1 3.4 L. On follow-up (average 9 years), there was a significant trend for less loss of pulmonary function with longer use of inhaled corticosteroids: 34 mL/year in nonusers, 28 mL/year in those using ICSs for less than 8.7 months, 24 mL/year for those using ICSs from 8.7 to less than 48 months, and 20 mL/year for those using ICSs for 48 months or more. Decline in lung function was significantly greater in males (35 mL/year) than in females (24 mL/year) and for older subjects, but it was not associated with smoking history. Furthermore, the protective effect of ICSs on loss of lung function was limited to those participants with total serum IgE of more than 100 kU/L. The authors advise that their findings should not be interpreted as indicating that ICSs should be prescribed only in patients with IgE of more than 100 kU/L, inasmuch as only 1 outcome of corticosteroid use was investigated in this study. major risk factor. The study confirmed in a general population that rhinovirus-associated early wheezing is a major viral risk factor for recurrent wheezing. It was a more important predictor than respiratory syncytial virus–induced disease. An unexpected and provocative finding was that a 3day prednisolone treatment for the first episode of wheezing associated with rhinovirus infection showed benefit for up to 12 months. Eczema also influenced the response to prednisolone. The authors found the findings understandable given that susceptibility to rhinovirus-induced early wheezing and eczema is known to predict recurrent wheezing in children. A prospective clinical trial is needed to test the hypothesis that prednisolone reduces recurrent wheezing associated with rhinovirus infection or eczema.
March 2007 Page 527
Eosinophilic esophagitis in children: When does it begin and where does it end? To patients and their families, eosinophilic esophagitis (EE) seems an enigma. When a diagnosis is made, there is relief that a biological reason for the persistent symptoms has finally been found. However, the diagnosis comes with a multitude of questions. How did my child get EE? How long will it take before the EE resolves? How widespread is the intestinal involvement? Assa’ad et al (p 731) made an unprecedented long-term examination of pediatric EE. The authors studied an 8-year follow-up of 89 patients with EE. They report that patients are mainly atopic Caucasian males who frequently develop gastrointestinal pathology in segments of the gastrointestinal tract outside the esophagus. The distribution of the affected segments varies from patient to patient (see Figure), as does the severity of coexisting gastrointestinal pathology. In addition, the authors describe the clinical course of EE as typically involving 3 years of symptoms before a diagnostic endoscopy is performed and as being associated with chronicity, 1 to 3 years being needed for the disease to resolve. Even then, the majority of the patients relapse; hence, long-term follow-up is indicated.
German Infant Nutritional Intervention Study proves nutritional intervention effective for prevention of atopic dermatitis Protein hydrolysates are recommended for infants at risk for allergic diseases if breast-feeding is insufficient. However, the preventive potential of the different types— for example, partially or extensively whey or casein hydrolysates—has not been fully established. Therefore, von Berg et al (p 718) compared, in a prospective, randomized, double-blind fashion, the allergy-preventive effect of 3 hydrolyzed infant formulas with a standard cow’s milk
Cat and dust mite allergen levels, specific IgG and IgG4, and respiratory symptoms in adults Controversy continues to exist regarding the role of animal exposure and the development of allergy. Childhood exposure to high levels of cat dander has been reported to cause an increase in specific IgG4, no IgE response, and little clinical disease. In this issue of the Journal, Jarvis and coauthors (p 697) examine the association of IgG4 levels with allergen exposure and allergic respiratory symptoms in approximately 2500 adult participants in the European Community Respiratory Health Survey. Neither sensitization to cat nor sensitization to house dust mites correlated with mattress levels of the respective major allergens (Fel d 1
Page 528 March 2007
Patients with EE separated into groups according to the gastrointestinal segment(s) with pathologic abnormalities.
formula supplementary to breast-feeding in 2252 high-risk infants. The investigators found a significantly reduced risk for atopic dermatitis, but not for asthma, over 3 years with the extensively hydrolyzed casein and also with the partially hydrolyzed whey hydrolysate, but not with the extensively hydrolyzed whey formula used in this study. This suggests that the preventive potential of a particular hydrolysate is not dependent on the extent of hydrolysis alone and thus can be proved only in clinical trials. Furthermore, the results of a stratified analysis lead to the hypothesis that the phenotype— here, the presence of atopic dermatitis in the infant’s immediate family—might modify the preventive potential of the formulas. In total, this study might be of relevance to further feeding recommendations for high-risk infants. and Der 1). On the other hand, levels of IgG and IgG4 increased with increasing Fel d 1 exposure, particularly in those with specific IgE. No similar relation between Der 1 levels and IgG or IgG4 was observed. Prevalence of symptoms on exposure to cats, dogs, or horses was higher in subjects who were IgE-sensitized to cats. There was no evidence that higher levels of cat-specific IgG4 were associated with less wheeze, asthma, or symptoms on exposure, even when the analyses were stratified by IgE sensitization or for Fel 1 exposure. In subjects with IgE sensitization to house dust mites, the prevalence of asthma was significantly higher in those with the highest IgG4 levels, an association that persisted after adjustment for Der 1 levels. The authors conclude that in this community-based sample of adults, high IgG4 levels to cat or house dust mites were not associated with a lower risk of allergic respiratory symptoms.
J ALLERGY CLIN IMMUNOL