2. Asthma phenotypes

8. Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program Moore AJRCCM 2010;181:315 Using three variables (baseline FEV 1 [with a bronchodilator withhold], maximal "Max" FEV 1 after six to eight puffs of albuterol, and age of onset of asthma), subjects can be assigned to the five clusters that range from milder asthma (Cluster 1) to more severe disease (Clusters 4 and 5).

9. Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program Moore AJRCCM 2010;181:315 50 – 40 – 30 – 20 – 10 – 0 5 – 0 % Sputum: Eosinophils , Neutrophils 1 2 3 4 5 23.3% 33.3% 37.6% 34.7% 48.3% 0.7% 0.7% 1.9% 1.5% 1.2% Cluster

11. Background: Clinicians have difficulty in diagnosing asthma in preschool children with suggestive symptoms. Objective: We sought to develop a clinical asthma prediction score for preschool children who have asthma-like symptoms for the first time. Predicting the long-term prognosis of children with symptoms suggestive of asthma at preschool age Caudri JACI 2009;124:903

14. Predicting the long-term prognosis of children with symptoms suggestive of asthma at preschool age Caudri JACI 2009;124:903 MALE SEX 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 1.7 POST-TERM DELIVERY MEDIUM/LOW PARENTAL EDUCATION ECZEMA 3 ≥ 4 2.5 1.5 2.1 1.5 2.3 OR FOR ASTHMA AT AGE 7-8 YEARS WHEEZING FREQUENCY TIMES/Y

22. 55% Percentages of remitting, periodic, and persistent asthma evaluated in the follow-up phase in CAMP were similar for the budesonide, nedocromil, and placebo–treated groups. Predictors of remitting, periodic, and persistent childhood asthma Covar JACI 2010;125:359

23. 55% Percentages of remitting, periodic, and persistent asthma evaluated in the follow-up phase in CAMP were similar for the budesonide, nedocromil, and placebo–treated groups. Predictors of remitting, periodic, and persistent childhood asthma Covar JACI 2010;125:359 Remission of asthma in adolescence is infrequent and not affected by 4 years of anti-inflammatory controller therapy.

24. FEATURES AT ENTRY INTO CAMP ASSOCIATED WITH REMITTING VERSUS PERSISTENT ASTHMA ( OR ) 3.23 lack of allergen sensitization and less exposure to indoor allergens milder asthma higher FEV 1 1.05 1.39 less BHR 3.5 - 3.0 - 2.5 - 2.0 - 1.5 - 1.0 - 0.5 - 0 2.01 P<0.0001 P=0.03 P=0.03 P<0.02 Predictors of remitting, periodic, and persistent childhood asthma Covar JACI 2010;125:359

25. 55% Distribution of CAMP participants with remitting ( blue ), periodic ( purple ), and persistent ( red ) course by age at the end of the observational phase (N=the number within the bars). The percentage of participants having remitting asthma did not increase with age , although the numbers of older adolescents were low. Predictors of remitting, periodic, and persistent childhood asthma Covar JACI 2010;125:359

27. Values for the cumulative dose of methacholine at the inflection point of respiratory resistance (Dmin) and the slope of the methacholine respiratory resistance dose-response curve (Sm) in 4 groups. Relationship between bronchial hyperreactivity and asthma remission during adolescence Mochizuki Ann Allergy Asthma Immunol 2009;103:201 Dmin = bronchial sensitivity Sm = speed of bronchial constriction (bronchial reactivity) adolescent asthma adolescent asthma

28. Values for the cumulative dose of methacholine at the inflection point of respiratory resistance (Dmin) and the slope of the methacholine respiratory resistance dose-response curve (Sm) in 4 groups. Adolescents with asthma remission showed no change in Dmin, whereas a significant decrease of Sm was observed (symptom-free but bronchial hyperresponsive asthma). Dmin = bronchial sensitivity Sm = speed of bronchial constriction (bronchial reactivity) adolescent asthma adolescent asthma

29. Values for the cumulative dose of methacholine at the inflection point of respiratory resistance (Dmin) and the slope of the methacholine respiratory resistance dose-response curve (Sm) in 4 groups. Relationship between bronchial hyperreactivity and asthma remission during adolescence Mochizuki Ann Allergy Asthma Immunol 2009;103:201 Sm = speed of bronchial constriction (bronchial reactivity) adolescent asthma

30. Asthma Origins

33. OR for FEV 1 /FVC ≤ 70% 1.7 6.3 1 1 7.2 ≥ 3 1.6 ≥ 3 n°FACTORS IN MEN n°FACTORS IN WOMEN 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 Early life origins of chronic obstructive pulmonary disease Svanes Thorax 2010;65:14–20

34. OR for FEV 1 /FVC ≤ 70% 1.7 6.3 1 1 7.2 ≥ 3 1.6 ≥ 3 n°FACTORS IN MEN n°FACTORS IN WOMEN 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 COPD increased with increasing childhood disadvantage Early life origins of chronic obstructive pulmonary disease Svanes Thorax 2010;65:14–20

35. Associations of chronic obstructive pulmonary disease (COPD)* with (A) individual childhood disadvantage factors and (B) with the number of childhood disadvantage factors. COPD defined as FEV 1 /FVC < 0.70 and FEV 1 < 80% predicted (A) (B) Early life origins of chronic obstructive pulmonary disease Svanes Thorax 2010;65:14–20

38. Birth weight and risk of asthma in 3-9-year-old twins: exploring the fetal origins hypothesis Kindlund Thorax 2010;65:146 Birth characteristics of subjects with and without asthma in a sample of Danish twin pairs, 3-9 years of age.

39. Birth weight and risk of asthma in 3-9-year-old twins: exploring the fetal origins hypothesis Kindlund Thorax 2010;65:146 Birth characteristics of subjects with and without asthma in a sample of Danish twin pairs, 3-9 years of age. This finding lends support to the “fetal origins hypothesis” suggesting undisclosed prenatal determinants for the risk of asthma.

42. Non-atopic intrinsic asthma and the 'family tree' of chronic respiratory disease syndromes Holt CEA 2009;39:807 Chronic respiratory inflammatory diseases – a 'family tree' Inset A : Key Inset B : Proposed partial overlap between disease risk genotypes

43. Non-atopic intrinsic asthma and the 'family tree' of chronic respiratory disease syndromes Holt CEA 2009;39:807 Chronic respiratory inflammatory diseases – a 'family tree' Inset A : Key Inset B : Proposed partial overlap between disease risk genotypes Early respiratory tract infections and atopic sensitization during the preschool years are both independently associated with risk for asthma development, but the highest risk for persistent asthma is observed in children who experience both .

44. Non-atopic intrinsic asthma and the 'family tree' of chronic respiratory disease syndromes Holt CEA 2009;39:807 Chronic respiratory inflammatory diseases – a 'family tree' Inset A : Key Inset B : Proposed partial overlap between disease risk genotypes Severe exacerbations of NAA, similar to the situation in AA, are almost invariably triggered by virus infection but requiring a longer time scale to reach a similar clinical end point.

45. Non-atopic intrinsic asthma and the 'family tree' of chronic respiratory disease syndromes Holt CEA 2009;39:807 Chronic respiratory inflammatory diseases – a 'family tree' Inset A : Key Inset B : Proposed partial overlap between disease risk genotypes Inheritance of reduced lung function is a risk factor for severe, early onset COPD.

46. Perinatal Risk factors

51. Asthma and viruses

52. Recurrent wheezing after respiratory syncytial virus or non-respiratory syncytial virus bronchiolitis in infancy: a 3-year follow-up. Valkonen Allergy 2009:64:1359 Background: Recent studies have suggested that rhinovirus -associated early wheezing is a greater risk factor for development of recurrent wheezing in children than is early wheezing associated with respiratory syncytial virus (RSV). We determined the development of recurrent wheezing in young children within 3 years after hospitalization for RSV or non-RSV bronchiolitis.

56. In vitro susceptibility to rhinovirus infection is greater for bronchial than for nasal airway epithelial cells in human subjects Lopez-Souza JACI 2009;123:1384 Background: Human rhinoviruses (HRVs) characteristically cause upper respiratory tract infection, but they also infect the lower airways, causing acute bronchitis and exacerbating asthma. Objective: Our purpose was to study ex vivo the differences in the response to HRV infection of nasal and bronchial epithelial cultures from the same healthy and asthmatic individuals using conditions favoring development of fully differentiated, pseudostratified mucociliary epithelium.

58. Immunocytochemistry for rhinovirus RNA (HRV-16) Micrograph of noninfected control HBE cells showing no HRV-16. Micrograph of infected HBE cells showing a high number of HRV-16–infected cells, some with condensed chromatin/nuclei (bright green). In vitro susceptibility to rhinovirus infection is greater for bronchial than for nasal airway epithelial cells in human subjects Lopez-Souza JACI 2009;123:1384

63. Asthma and bacteria, atypical bacteria

64. A low dose of Mycoplasma pneumoniae infection enhances an established allergic inflammation in mice: the role of the prostaglandin E 2 pathway Wu , CEA 2009;39:1754 Background: Over 40% of chronic stable asthma patients have evidence of respiratory Mycoplasma pneumoniae (Mp) infection as detected by PCR, but not by serology and culture, suggesting that a low-level Mp is involved in chronic asthma. However, the role of such a low-level Mp infection in the regulation of allergic inflammation remains unknown. Objective: To determine the impact of a low-level Mp infection in mice with established airway allergic inflammation on allergic responses such as eosinophilia and chemokine eotaxin-2, and the underlying mechanisms [i.e. the prostaglandin E2 (PGE2) pathway] since PGE2 inhalation before an allergen challenge suppressed the eosinophil infiltration in human airways.

65. A low dose of Mycoplasma pneumoniae infection enhances an established allergic inflammation in mice: the role of the prostaglandin E 2 pathway Wu, CEA 2009;39:1754 Ovalbumin induced asthma IL-4 expression, bronchoalveolar lavage (BAL) eosinophil, eotaxin-2 and PGE 2 levels.

66. A low dose of Mycoplasma pneumoniae infection enhances an established allergic inflammation in mice: the role of the prostaglandin E 2 pathway Wu, CEA 2009;39:1754 Ovalbumin induced asthma Low-dose Mp in allergic mice significantly enhanced IL-4 and eotaxin-2, and lung eosinophilia. IL-4 expression, bronchoalveolar lavage (BAL) eosinophil, eotaxin-2 and PGE 2 levels.

67. Ovalbumin induced asthma Low-dose Mp in allergic mice significantly enhanced IL-4 and eotaxin-2, and lung eosinophilia. IL-4 expression, bronchoalveolar lavage (BAL) eosinophil, eotaxin-2 and PGE 2 levels. High-dose Mp significantly reduced lung eosinophilia and tended to decrease IL-4 and eotaxin-2. A low dose of Mycoplasma pneumoniae infection enhances an established allergic inflammation in mice: the role of the prostaglandin E 2 pathway Wu, CEA 2009;39:1754

68. A low dose of Mycoplasma pneumoniae infection enhances an established allergic inflammation in mice: the role of the prostaglandin E 2 pathway Wu, CEA 2009;39:1754 CFU, colony-forming unit; Mp, Mycoplasma pneumoniae; Sal, saline.

73. Is intrinsic asthma synonymous with infection? Dahlberg Clinical & Experimental Allergy 2009;39:1324 Rackemann described the ‘intrinsic asthma’ population over 50 years ago as a unique subgroup that was characterized by onset of progressive loss of lung function beginning later in life , possibly after a respiratory infection. It has also been associated with a female predominance , aspirin-sensitive bronchospasm , and nasal polyposis . While the aetiology is not understood, we propose that persistent respiratory infections play a central role in the development of intrinsic asthma .

74. Is intrinsic asthma synonymous with infection? Dahlberg Clinical & Experimental Allergy 2009;39:1324 Respiratory tract infections incite established asthma and likely participate in the initiation of chronic allergic pulmonary inflammation in both infancy and adulthood

75. Is intrinsic asthma synonymous with infection? Dahlberg Clinical & Experimental Allergy 2009;39:1324 Intrinsic asthma may develop in individuals who are unable to eliminate an acute respiratory infection due to previously acquired subtle immune impairments .

77. Cleaning Indoor and Outdoor pollution as Risk factors

82. la prevalenza misura la proporzione di &quot;eventi&quot; presenti in una popolazione in un dato momento . l'incidenza misura la proporzione di &quot;nuovi eventi&quot; che si verificano in una popolazione in un dato lasso di tempo.

90. TWO REPRESENTATIVE HOUSEHOLD KITCHEN MEXICO Patsari chimney wood stove Open wood fire Improved Biomass Stove Intervention in Rural Mexico Romieu Am. J. Respir. Crit. Care Med 2009;180:649

94. Background: Ambient fine particles (particular matter <2.5 µm diameter [PM 2.5 ]) and ozone exacerbate respiratory conditions including asthma. There is little documentation determining whether children are more vulnerable to the effects of ambient pollution than adults , or whether pollution causes life-threatening episodes requiring intensive care unit (ICU) admission . Objective: We investigate the relationship between severe asthma morbidity and PM 2.5 and ozone in the warm season, and determine whether there is an age-related susceptibility to pollution. Age-related association of fine particles and ozone with severe acute asthma in New York City Silverman JACI 2010;125:367

106. Asthma red-ox

107. Role of Oxidative Stress in Ultrafine Particle–induced Exacerbation of Allergic Lung Inflammation Alessandrini Am J Respir Crit Care Med 2009;179:984 Exposed to elemental carbon ultrafine particles (EC-UFPs) Exposed to filtered air immediately before allergen challenge and systemically treated with N-acetylcysteine or vehicle. In sensitized and challenged mice EC-UFP inhalation increased allergen-induced lung lipid peroxidation and NF- κ B activation in addition to inflammatory infiltrate, cytokine release, and airway hyperresponsiveness. Ovalbumin-sensitized mice

108. Role of Oxidative Stress in Ultrafine Particle–induced Exacerbation of Allergic Lung Inflammation Alessandrini Am J Respir Crit Care Med 2009;179:984 Exposed to elemental carbon ultrafine particles (EC-UFPs) Exposed to filtered air immediately before allergen challenge and systemically treated with N-acetylcysteine or vehicle. N-acetylcysteine treatment significantly reduced the adjuvant activity of EC-UFPs. In sensitized and challenged mice EC-UFP inhalation increased allergen-induced lung lipid peroxidation and NF- κ B activation in addition to inflammatory infiltrate, cytokine release, and airway hyperresponsiveness. Ovalbumin-sensitized mice

109. Role of Oxidative Stress in Ultrafine Particle–induced Exacerbation of Allergic Lung Inflammation Alessandrini Am J Respir Crit Care Med 2009;179:984 ( A ) Nonsensitized mice exposed for 24 hours to EC-UFPs (NS/UFP); ( B ) Sensitized and challenged mice exposed to filtered air (S/OVA); A B

110. Role of Oxidative Stress in Ultrafine Particle–induced Exacerbation of Allergic Lung Inflammation Alessandrini Am J Respir Crit Care Med 2009;179:984 C D ( C ) sensitized mice exposed to EC-UFP 24 hours before OVA challenge (S/UFP/OVA); ( D ) sensitized mice exposed to EC-UFP 24 hours before OVA challenge and treated with NAC (S/NAC/UFP/OVA).

119. Histone deacetylase-2 and airway disease. Barnes PJ. Ther Adv Respir Dis. 2009;3:235-43. The increased expression of inflammatory genes in inflammatory lung diseases is regulated by acetylation of core histones , whereas histone deacetylase-2 (HDAC2) suppresses inflammatory gene expression . increased expression of inflammatory genes suppresses inflammatory gene expression

120. Histone deacetylase-2 and airway disease. Barnes PJ. Ther Adv Respir Dis. 2009;3:235-43. The increased expression of inflammatory genes in inflammatory lung diseases is regulated by acetylation of core histones , whereas histone deacetylase-2 (HDAC2) suppresses inflammatory gene expression . The reduction in HDAC2 appears to be secondary to increased oxidative stress in the lungs. Antioxidants such as curcumin may therefore restore corticosteroid sensitivity

123. The predicted probability of current asthma at age 10 among boys and girls based on risk calculation [odds ratio (OR)] per increase in cat allergen exposure at age 2. asthma Childhood asthma and early life exposure to indoor allergens, endotoxin and β (1,3)-glucans Bertelsen CEA 2010;40:307 per 10 µg/g dust increase in cat allergen exposure at 2 years of age OR for 2 – 1 – 0 1.20 BHR 1.22

124. The predicted probability of current asthma at age 10 among boys and girls based on risk calculation [odds ratio (OR)] per increase in cat allergen exposure at age 2. asthma Childhood asthma and early life exposure to indoor allergens, endotoxin and β (1,3)-glucans Bertelsen CEA 2010;40:307 per 10 µg/g dust increase in cat allergen exposure at 2 years of age OR for 2 – 1 – 0 1.20 BHR 1.22 No association was seen with allergic sensitization.

125. The predicted probability of current asthma at age 10 among boys and girls based on risk calculation [odds ratio (OR)] per increase in cat allergen exposure at age 2. asthma Childhood asthma and early life exposure to indoor allergens, endotoxin and β (1,3)-glucans Bertelsen CEA 2010;40:307 per 10 µg/g dust increase in cat allergen exposure at 2 years of age OR for 2 – 1 – 0 1.20 BHR 1.22 In a community with a low prevalence of pet keeping and low mite allergen levels, exposure to cat allergens early in life increased the risk of late childhood asthma and BHR, but not the risk of allergic sensitization.

133. House Dust Mite–Promoted Epithelial-to-Mesenchymal Transition in Human Bronchial Epithelium Heijink AJRCMB 2010;42:69 Human bronchial epithelium (16HBE cells) Fibrogenic cytokine TGF-β and protease-containing aeroallergen house dust mite induce epithelial-to-mesenchymal transition (EMT), a key process in tissue repair and remodeling +TGF- β TGF- β +

134. House Dust Mite–Promoted Epithelial-to-Mesenchymal Transition in Human Bronchial Epithelium Heijink AJRCMB 2010;42:69 Mesenchymal stem cells , or MSCs , are multipotent stem cells that can differentiate into a variety of cell types . Cell types that MSCs have been shown to differentiate in ex vivo cultures and in vitro or in vivo include: - osteoblasts (bone cells), - chondrocytes (cartilage cells) and - adipocytes (fat cells). Mesenchymal stem cells

135. The non-proteolytic house dust mite allergen Der p2 induce NF- κ B and MAPK dependent activation of bronchial epithelial cells . Österlund C EA 2010;39:1199 Der p2, a major non-proteolytic allergen of Dermatophagoides pteronyssinus , Human bronchial epithelial cell line BEAS-2B Dose-dependent up-regulation of: - granulocyte-macrophage colony-stimulating f factor (GMC-SF), - IL-6, IL-8, - monocyte-chemotactic protein-1 (MCP-1) - macrophage inflammatory protein-3 α - intercellular adhesion molecule (ICAM)-1.

136. The non-proteolytic house dust mite allergen Der p2 induce NF- κ B and MAPK dependent activation of bronchial epithelial cells . Österlund C EA 2010;39:1199 Der p2, a major non-proteolytic allergen of Dermatophagoides pteronyssinus , Human bronchial epithelial cell line BEAS-2B This non-proteolytic allergen, in addition to its immunogenic properties, can aggravate respiratory airway disease by adjuvant-like activation of the lung epithelium. Dose-dependent up-regulation of: - granulocyte-macrophage colony-stimulating f factor (GMC-SF), - IL-6, IL-8, - monocyte-chemotactic protein-1 (MCP-1) - macrophage inflammatory protein-3 α - intercellular adhesion molecule (ICAM)-1.

137. The non-proteolytic house dust mite allergen Der p2 induce NF- κ B and MAPK dependent activation of bronchial epithelial cells . Österlund C EA 2010;39:1199 Der p 2 ( μ g/mL) Der p 2 ( μ g/mL) Der p 2 ( μ g/mL)

139. Obesity

164. 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 23% 0% 0% 60% 33% Children with metabolic syndrome Snoring Obese Non obese Obese Non obese Obesity and obesity related co-morbidities in a referral population of children with asthma Ross, Ped Pul 2009;44:877

165. 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 23% 0% 0% 60% 33% Children with metabolic syndrome Snoring Obese Non obese Obese Non obese Obesity and obesity related co-morbidities in a referral population of children with asthma Ross, Ped Pul 2009;44:877 Insufficient sleep and nocturnal desaturations tended to be more prevalent among obese subjects.

171. Comparison of anthropometric measures of obesity in childhood allergic asthma: Central obesity is most relevant. Musaad JACI 2009;123:1321 Health risks for obesity are most associated with fat distribution rather than body weight. Alternative measures that account for fat distribution include waist circumference, a measure of abdominal (central) obesity that, compared with BMI percentiles, better predicts risk for some diseases, such as cardiovascular disease. Similarly, waist/height ratio and the conicity index have been found to be more sensitive than BMI in predicting the risk for cardiovascular disease.

172. Obesity, waist size and prevalence of current asthma in the California Teachers Study cohort Von Behren Thorax 2009;64:889–893 Background: Obesity is a risk factor for asthma, particularly in women, but few cohort studies have evaluated abdominal obesity which reflects metabolic differences in visceral fat known to influence systemic inflammation. A study was undertaken to examine the relationship between the prevalence of asthma and measures of abdominal obesity and adult weight gain in addition to body mass index (BMI) in a large cohort of female teachers.

176. Asthma other risk factors

180. Asthma protective factors

183. Beneficial effects of high dose of L-arginine on airway hyperresponsiveness and airway inflammation in a murine model of asthma Mabalirajan JACI 2010;125:626 Ovalbumin–sensitized and challenged mice. L-arginine significantly reduced AHR and airway inflammation including bronchoalveolar lavage fluid eosinophilia, T H 2 cytokines, TGF- β 1, goblet cell metaplasia, and subepithelial fibrosis. Different doses of L-arginine.

184. Beneficial effects of high dose of L-arginine on airway hyperresponsiveness and airway inflammation in a murine model of asthma Mabalirajan JACI 2010;125:626 Ovalbumin–sensitized and challenged mice. L-arginine significantly reduced AHR and airway inflammation including bronchoalveolar lavage fluid eosinophilia, T H 2 cytokines, TGF- β 1, goblet cell metaplasia, and subepithelial fibrosis. Different doses of L-arginine. Further, L-arginine increased exhaled nitric oxide levels and reduced the markers of nitro-oxidative stress such as nitrotyrosine, 8-isoprostane, and 8-hydroxy-2’-deoxyguanosine.

185. Beneficial effects of high dose of L-arginine on airway hyperresponsiveness and airway inflammation in a murine model of asthma Mabalirajan JACI 2010;125:626 Ovalbumin–sensitized and challenged mice. L-arginine significantly reduced AHR and airway inflammation including bronchoalveolar lavage fluid eosinophilia, T H 2 cytokines, TGF- β 1, goblet cell metaplasia, and subepithelial fibrosis. Different doses of L-arginine. This was associated with reduced activity and expression of arginase 1, increased expression of endothelial NOS, and reduction of inducible NOS in bronchial epithelia.

189. ASTHMA BHR

190. Asthma pathogenesis

191. The airway smooth muscle cell , as well as contracting and relaxing, produces myriad inflammatory and growth factors as well as extracellular matrix proteins and adhesion molecules, which enable interactions with inflammatory cells. Asthma may arise from an intrinsic defect in the smooth muscle cell, which could then be the primary driver of inflammation and remodelling . Intrinsic asthma: is it intrinsic to the smooth muscle? Black CEA 2010;39:962

192. The airway smooth muscle cell , as well as contracting and relaxing, produces myriad inflammatory and growth factors as well as extracellular matrix proteins and adhesion molecules, which enable interactions with inflammatory cells. Asthma may arise from an intrinsic defect in the smooth muscle cell, which could then be the primary driver of inflammation and remodelling . Intrinsic asthma: is it intrinsic to the smooth muscle? Black CEA 2010;39:962 An abnormality in the airway smooth muscle cell, which is capable of producing inflammatory, immunological and growth factors as well as molecules, which facilitate interaction with inflammatory cells, is the primary or instigating event.

193. Intrinsic asthma: not so different from allergic asthma but driven by superantigens? Barnes C EA 2010;39:1145 Invasion of airway epithelial cells by Staphylococcus aureus (and other microorganisms) causes the release of Staphylococcal superantigens (Sag) (and other superantigens), which act on airway B lymphocytes to cause class-switching with the local production of polyclonal IgE, together with IgE directed against SSa (which acts as a 'superallergen'). This causes mast cell activation and release of bronchoconstrictor mediators .

195. Stimulated airway smooth muscle supernatant (ASMS) elicited an eosinophilopoietic response by blood progenitors from (a) normals (n=11) and (b) atopic asthmatics (n=12), optimal at 1/10 dilution. Eosinophil/basophil colony forming unit (Eo/B CFU) numbers. Human airway smooth muscle promotes eosinophil differentiation Fanat CEA 2010;39:1009

196. Plasmacytoid dendritic cells during infancy are inversely associated with childhood respiratory tract infections and wheezing Upham JACI 2009;124:707 DCs are a family of bone marrow–derived cells that can be separated into 2 major subgroups: conventional or myeloid DCs (mDCs) and plasmacytoid DCs (pDC). Animal models have highlighted the importance of mDCs in the pathogenesis of allergic airway inflammation, whereas pDCs appear to play a specialized role in host defense against viral infections at mucosal surfaces and in some circumstances might mediate immune tolerance.

201. Regulatory cells, cytokine pattern and clinical risk factors for asthma in infants and young children with recurrent wheeze Borrego C EA 2010;39:1160 HC, healthy children; LRC, low risk for asthma wheezing children; HRC, high risk for asthma wheezing children.

202. Background: Asthma phenotypes are well described among children. However, there are few studies comparing airway inflammation in different clinical presentations of pediatric asthma. We tested the hypothesis that nonatopic asthma is associated with a predominant noneosinophilic inflammation in the airways, as assessed by induced sputum. The objective of this study was to evaluate the cytological characteristics of induced sputum (IS) in atopic (AA), nonatopic asthmatics (NAA) and nonatopic nonasthmatic children (NANA). Neutrophilic airway inflammation is a main feature of induced sputum in nonatopic asthmatic children Drews Allergy 2009:64:1597

205. AA, atopic asthma; NAA, nonatopic asthma; NANA, no asthma/no atopy. * Data expressed as median (minimum–maximum).  Significant difference when compared with NANA, P < 0.001. ‡ Significant difference when compared with AA, P < 0.001. § Significant difference when compared with NAA and NANA, P < 0.001. ¶ Eosinophilia = if sputum eosinophils ≥3%. Differential cell counts * from induced sputum in the three clinical phenotypes Cell viability, % 86 (64–95) 84 (50–95) 88 (66–93) TCC†×10 6 /mg 3.4 (1.2–13.0) 4.0 (1.5–7.6) 2.2 (1.8–8.0) Neutrophils % 11.0 (7.0–16) 18.0 (7.0–31) ‡ 13.0 (8.0–22.0) Eosinophils % 9.0 (0.2–64.0) § 1.0 (0–66.0) 0.5 (0–1.8) Macrophages % 76.4 (29–86) 78.0 (24–84) 81.0 (74–87) Lymphocytes % 0.8 (0–4) 1.0 (0–5.0) 0.8 (0–2.0) Sputum eosinophilia ¶ , n (%) 17 (81)  5 (23.8) 0 (0) Neutrophilic airway inflammation is a main feature of induced sputum in nonatopic asthmatic children Drews Allergy 2009:64:1597

206. Relationship Between Amphiregulin and Airway Inflammation in Children With Asthma and Eosinophilic Bronchitis Won Kim Chest 2009;136:805 Background: Amphiregulin , a member of the epidermal growth factor family , has been shown to promote the growth of fibroblasts, to be associated with the T-helper type 2 cell adaptive immune response, and to up-regulate mucin gene expression. We aimed to determine whether sputum amphiregulin is expressed at elevated levels in patients with asthma or eosinophilic bronchitis (EB), and whether it is associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children.

210. Tissue remodeling induced by hypersecreted epidermal growth factor and amphiregulin in the airway after an acute asthma attack Enomoto JACI 2009;124:913 Backgroun