The first thousand days – intestinal microbiology of early life: establishing a symbiosis

1. 1. 
      

Pediatric Allergy and Immunology

1. Volume 25, Issue 5, pages 428–438, August 2014

Article first published online: 5 JUN 2014

DOI: 10.1111/pai.12232

1. Harm Wopereis^1,2, 
2. Raish Oozeer¹, 
3. Karen Knipping¹, 
4. Clara Belzer² and
5. Jan Knol^1,2,*

Abstract

The development of the intestinal microbiota in the first years of life is a dynamic process significantly influenced by early-life nutrition. Pioneer bacteria colonizing the infant intestinal tract and the gradual diversification to a stable climax ecosystem plays a crucial role in establishing host–microbe interactions essential for optimal symbiosis. This colonization process and establishment of symbiosis may profoundly influence health throughout life. Recent developments in microbiologic cultivation-independent methods allow a detailed view of the key players and factors involved in this process and may further elucidate their roles in a healthy gut and immune maturation. Aberrant patterns may lead to identifying key microbial signatures involved in developing immunologic diseases into adulthood, such as asthma and atopic diseases. The central role of early-life nutrition in the developmental human microbiota, immunity, and metabolism offers promising strategies for prevention and treatment of such diseases. This review provides an overview of the development of the intestinal microbiota, its bidirectional relationship with the immune system, and its role in impacting health and disease, with emphasis on allergy, in early life.

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Oral Immunotherapy in Children With IgE-Mediated Wheat Allergy: Outcome and Molecular Changes

P Rodríguez del Río,1 A Díaz-Perales,2 S Sanchez-García,1 C Escudero,1 Patricia do Santos,2,3 M Catarino,2,3 MD Ibañez1

1Allergy Department, Hospital Infantil Niño Jesús, Madrid, Spain 2Centro de Biotecnologia y Genómica de Plantas (UPM-INIA), Madrid, Spain 3Pharmacy School, University of Lisbon, Lisbon, Portugal

J Investig Allergol Clin Immunol 2014; Vol. 24(4): 240-248

Abstract Background: IgE-mediated wheat allergy affects around 0.5% of the population, and current management is based on avoidance. We propose an active intervention to promote tolerance in wheat-allergic children. Objectives: To investigate the efficacy and safety of an oral immunotherapy (OIT) protocol with wheat to treat IgE-mediated wheat-allergic children. Methods: Six wheat allergic patients assessed in a double-blind, placebo-controlled food challenge (DBPCFC) underwent wheat OIT with an up-dosing phase until 100 g of wheat was tolerated, followed by a 6-month maintenance phase. Tolerance to rye and oat was evaluated, as were specific IgE (sIgE) to wheat and other cereals and sIgE, sIgG4, and sIgG1 to a panel of wheat proteins (α-amylase and trypsin inhibitors, wheat lipid transfer proteins, gliadins, and glutenins). Results: Threshold doses in the wheat DBPCFC ranged from 6.6 g to 96.6 g. Five out of 6 (83%) patients successfully finished the updosing phase in 3 to 24 days; after a 6-month maintenance phase, all the patients maintained good tolerance of 100 g of wheat daily. Only 6.25% of doses in the up-dosing phase elicited mild adverse reactions. All 5 patients who successfully finished the up-dosing phase tolerated rye after OIT, and all but 1 tolerated oat as well. The median baseline wheat sIgE was 47.5 kUA/L, increasing to 84.55 kUA/L after up-dosing and decreasing to 28.75 kUA/L after 6 months of follow-up. None of the patients showed sIgE to 5-ω-gliadin, but α-amylase inhibitors were recognized by all patients. Specific IgG4 and sIgG1 increased in all patients. Conclusions: Our wheat OIT protocol was safe, efficient, and rapid. In our population, α-amylase was the major allergen. Key words: Food allergy. Immunotherapy. Food immunotherapy. Oral immunotherapy. Wheat allergy. Gluten. α-Amylase inhibitors. 5-ω-gliadin. Children. LTP.   Free Full-Text (PDF)   How to use PDF documents

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The Journal of Allergy and Clinical Immunology

J Allergy Clin Immunol. May 2014; 133(5): 1317–1329.

doi:  10.1016/j.jaci.2013.12.1082

PMCID: PMC4024198

Preterm birth, infant weight gain, and childhood asthma risk: A meta-analysis of 147,000 European children

Agnes M.M. Sonnenschein-van der Voort, PhD,a,b,c Lidia R. Arends, PhD,d,e,f Johan C. de Jongste, MD, PhD,c Isabella Annesi-Maesano, MD, PhD,g,h S. Hasan Arshad, DM,i Henrique Barros, MD, PhD,j Mikel Basterrechea, MD,k,l Hans Bisgaard, MD, DMSci,m,n Leda Chatzi, MD, PhD,o Eva Corpeleijn, PhD,p Sofia Correia, PharmD, MSc,j Leone C. Craig, MD, PhD,q Graham Devereux, MD, PhD,q Cristian Dogaru, MD, PhD,r Miroslav Dostal, MD, DSc,s Karel Duchen, MD,tMerete Eggesbø, MD, PhD,u C. Kors van der Ent, MD, PhD,v Maria P. Fantini, MD,w Francesco Forastiere, MD, PhD,xUrs Frey, MD, PhD,y Ulrike Gehring, PhD,z Davide Gori, MD,w Anne C. van der Gugten, MD, PhD,v Wojciech Hanke, MD, PhD,aa A. John Henderson, MD, PhD,bb Barbara Heude, PhD,cc,dd Carmen Iñiguez, PhD,l,ee,ff Hazel M. Inskip, MSc, PhD,gg Thomas Keil, MD, MScPH,hh,ii Cecily C. Kelleher, MD, MPH,jj Manolis Kogevinas, MD, PhD,kk Eskil Kreiner-Møller, MD,m,n Claudia E. Kuehni, MD, PhD,r Leanne K. Küpers, MSc,p Kinga Lancz, PhD,ll Pernille S. Larsen, MSc,mm Susanne Lau, MD, PhD,nn Johnny Ludvigsson, MD, PhD,t Monique Mommers, PhD,oo Anne-Marie Nybo Andersen, MD, PhD,mm Lubica Palkovicova, MD, PhD,ll Katharine C. Pike, MD, PhD,pp Costanza Pizzi, MSc,qq Kinga Polanska, PhD,aa Daniela Porta, MSc,x Lorenzo Richiardi, MD, PhD,qq Graham Roberts, DM,i Anne Schmidt, MD,rrRadim J. Sram, MD, DSc,s Jordi Sunyer, MD, PhD,l,ss,tt,uu Carel Thijs, MD, PhD,oo Maties Torrent, MD, PhD,vv Karien Viljoen, MBChB, MSc,jj Alet H. Wijga, PhD,ww Martine Vrijheid, PhD,l,ss,tt Vincent W.V. Jaddoe, MD, PhD,a,b,xx andLiesbeth Duijts, MD, PhDb,c,yy,

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Abstract

Background

Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results.

Objectives

We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years).

Methods

First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 and="" asthma="" birth="" childhood="" g="" low="" outcomes.="" p="" weeks="" weight="" with="">

Results

Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27).

Conclusion

Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.

Key words: Gestational age, low birth weight, infant growth, wheezing, asthma, children, cohort studies, epidemiology

Abbreviations used: BMI, Body mass index; ISAAC, International Study on Asthma and Allergy in Childhood; OR, Odds ratio; pOR, Pooled odds ratio; SDS, Standard deviation scores

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Abstract

Background

Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results.

Objectives

We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years).

Methods

First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 and="" asthma="" birth="" childhood="" g="" low="" outcomes.="" p="" weeks="" weight="" with="">

Results

Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27).

Conclusion

Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.

Key words: Gestational age, low birth weight, infant growth, wheezing, asthma, children, cohort studies, epidemiology

Abbreviations used: 

Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications

• NIHPA Author Manuscripts
• PMC4047642

J Allergy Clin Immunol. Author manuscript; available in PMC Jun 6, 2014.

Published in final edited form as:

J Allergy Clin Immunol. May 2014; 133(5): 1289–130112.

PMCID: PMC4047642

NIHMSID: NIHMS579247

Judie A. Howrylak, MD,a Anne L. Fuhlbrigge, MD,b,c,d Robert C. Strunk, MD,e Robert S. Zeiger, MD,f Scott T. Weiss, MD,b,c,d and Benjamin A. Raby, MDb,c,d, for the Childhood Asthma Management Program Research Group*

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Abstract

Background

Although recent studies have identified the presence of phenotypic clusters in asthmatic patients, the clinical significance and temporal stability of these clusters have not been explored.

Objective

Our aim was to examine the clinical relevance and temporal stability of phenotypic clusters in children with asthma.

Methods

We applied spectral clustering to clinical data from 1041 children with asthma participating in the Childhood Asthma Management Program. Posttreatment randomization follow-up data collected over 48 months were used to determine the effect of these clusters on pulmonary function and treatment response to inhaled anti-inflammatory medication.

Results

We found 5 reproducible patient clusters that could be differentiated on the basis of 3 groups of features: atopic burden, degree of airway obstruction, and history of exacerbation. Cluster grouping predicted long-term asthma control, as measured by the need for oral prednisone (P < .0001) or additional controller medications (P = .001), as well as longitudinal differences in pulmonary function (P < .0001). We also found that the 2 clusters with the highest rates of exacerbation had different responses to inhaled corticosteroids when compared with the other clusters. One cluster demonstrated a positive response to both budesonide (P = .02) and nedocromil (P = .01) compared with placebo, whereas the other cluster demonstrated minimal responses to both budesonide (P = .12) and nedocromil (P = .56) compared with placebo.

Conclusion

Phenotypic clustering can be used to identify longitudinally consistent and clinically relevant patient subgroups, with implications for targeted therapeutic strategies and clinical trials design.

Keywords: Childhood asthma, asthma phenotypes, inhaled corticosteroids, cluster analysis, asthma classification, longitudinal study

Abstract

Background

Although recent studies have identified the presence of phenotypic clusters in asthmatic patients, the clinical significance and temporal stability of these clusters have not been explored.

Objective

Our aim was to examine the clinical relevance and temporal stability of phenotypic clusters in children with asthma.

Methods

We applied spectral clustering to clinical data from 1041 children with asthma participating in the Childhood Asthma Management Program. Posttreatment randomization follow-up data collected over 48 months were used to determine the effect of these clusters on pulmonary function and treatment response to inhaled anti-inflammatory medication.

Results

We found 5 reproducible patient clusters that could be differentiated on the basis of 3 groups of features: atopic burden, degree of airway obstruction, and history of exacerbation. Cluster grouping predicted long-term asthma control, as measured by the need for oral prednisone (P < .0001) or additional controller medications (P = .001), as well as longitudinal differences in pulmonary function (P < .0001). We also found that the 2 clusters with the highest rates of exacerbation had different responses to inhaled corticosteroids when compared with the other clusters. One cluster demonstrated a positive response to both budesonide (P = .02) and nedocromil (P = .01) compared with placebo, whereas the other cluster demonstrated minimal responses to both budesonide (P = .12) and nedocromil (P = .56) compared with placebo.

Conclusion

Phenotypic clustering can be used to identify longitudinally consistent and clinically relevant patient subgroups, with implications for targeted therapeutic strategies and clinical trials design.

Keywords: Childhood asthma, asthma phenotypes, inhaled corticosteroids, cluster analysis, asthma classification, longitudinal study

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Toll-Like Receptors Required for Dermatophagoides farinae to Activate NF-κB

J-STAGE Home  >  Publications - Top  > Bibliographic Information

Biological and Pharmaceutical Bulletin
Vol. 37 (2014) No. 1 p. 74-80

http://dx.doi.org/10.1248/bpb.b13-00595

 

DN/JST.JSTAGE/bpb/b13-00595

Regular Articles

Takaaki Kitajima¹⁾, Masashi Muroi¹⁾, Naomi Yamashita¹⁾, Ken-ichi Tanamoto¹⁾

1) Research Institute of Pharmaceutical Sciences, Musashino University

 Released on J-STAGE 20140101  

Keywords: house dust mite, allergen, innate immunity

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• Abstract:
• Body and excrement extracts from Dermatophagoides farinae were used to study stimulation of Toll-like receptors (TLRs). The excrement extract stimulated nuclear factor (NF)-κB-dependent reporter activity to an extent similar to lipopolysaccharide (LPS) in a mouse macrophage cell line, J774A.1, but the activity of the body extract was negligible. The excrement extract also activated NF-κB in HEK293 cells expressing TLR1/TLR2, TLR2/TLR6 and CD14/TLR4/MD-2, whereas no activation was observed in cells expressing TLR3, TLR5, TLR7, TLR8 or TLR9. Although the excrement extract required co-expression of CD14, TLR4 and MD-2 in HEK293 cells to activate NF-κB, efficient activation was still observed in I-13.35 cells, a bone-marrow macrophage cell line established from LPS-hypo-responsive C3H/HeJ mice. The excrement extract activated NF-κB in HEK293 cells expressing TLR2 alone, but the activation was significantly increased by co-expression of CD14. Polymyxin B inhibited CD14/TLR4/MD-2- and CD14/TLR2-mediated activation of NF-κB but not the activation in I-13.35 cells. These results indicate that CD14/TLR4/MD-2-dependent and CD14/TLR2-dependent mechanisms are involved in the activation of NF-κB by the excrement extract of D. farinae and suggest that the extract also contains substances that activate NF-κB through non-TLR-mediated mechanisms.

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Copyright © 2014 The Pharmaceutical Society of Japan

Prostaglandin E2 receptors in asthma and in chronic rhinosinusitis/nasal polyps with and without aspirin hypersensitivity

Review

Liliana Machado-Carvalho^123*, Jordi Roca-Ferrer¹²³ and César Picado¹²³

• *Corresponding author: Liliana Machado-Carvalho lsmachad@clinic.ub.es

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Respiratory Research 2014, 15:100  doi:10.1186/s12931-014-0100-7

Published: 26 August 2014

Abstract (provisional)

Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma frequently coexist and are always present in patients with aspirin exacerbated respiratory disease (AERD). Although the pathogenic mechanisms of this condition are still unknown, AERD may be due, at least in part, to an imbalance in eicosanoid metabolism (increased production of cysteinyl leukotrienes (CysLTs) and reduced biosynthesis of prostaglandin (PG) E2), possibly increasing and perpetuating the process of inflammation. PGE2 results from the metabolism of arachidonic acid (AA) by cyclooxygenase (COX) enzymes, and seems to play a central role in homeostasis maintenance and inflammatory response modulation in airways. Therefore, the abnormal regulation of PGE2 could contribute to the exacerbated processes observed in AERD. PGE2 exerts its actions through four G-protein-coupled receptors designated E-prostanoid (EP) receptors EP1, EP2, EP3, and EP4. Altered PGE2 production as well as differential EP receptor expression has been reported in both upper and lower airways of patients with AERD. Since the heterogeneity of these receptors is the key for the multiple biological effects of PGE2 this review focuses on the studies available to elucidate the importance of these receptors in inflammatory airway diseases.

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Tattoo-Associated Skin Reaction: The Importance of an Early Diagnosis and Proper Treatment

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Abstract

Biomed Res Int. 2014; 2014: 354608.

Published online Jul 23, 2014. doi:  10.1155/2014/354608

PMCID: PMC4132403

Andrea Bassi, ^{1 ,*} Piero Campolmi, ¹ Giovanni Cannarozzo, ¹ Rossana Conti, ¹ Nicola Bruscino, ¹ Massimo Gola, ¹Stefano Ermini, ² Daniela Massi, ³ and Silvia Moretti ¹

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Abstract

Tattoo is going to be a very common practice especially among young people and we are witnessing a gradual increase of numerous potential complications to tattoo placement which are often seen by physicians, but generally unknown to the public. The most common skin reactions to tattoo include a transient acute inflammatory reaction due to trauma of the skin with needles and medical complications such as superficial and deep local infections, systemic infections, allergic contact dermatitis, photodermatitis, granulomatous and lichenoid reactions, and skin diseases localized on tattooed area (eczema, psoriasis, lichen, and morphea). Next to these inflammatory skin reactions we have to consider also the possibility of the development of cutaneous conditions such as pseudolymphomatous reactions and pseudoepitheliomatous hyperplasia. The aim of this study is to underline the importance of an early diagnosis by performing a histological examination especially when we are in front of suspected papulonodular lesions arising from a tattoo, followed by a proper treatment, since cutaneous neoplastic evolution is known to be a rare but possible complication.

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