Serum angiopoietin is associated with lung function in patients with asthma: a retrospective cohort study

Research article

Kuk-Young Moon, PuReun-HaNeul Lee, Sung-Woo Park, Choon-Sik Park and An-Soo Jang

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BMC Pulmonary Medicine 2014, 14:143  doi:10.1186/1471-2466-14-143

Published: 2 September 2014

Abstract (provisional)

Background

Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis that establishes vascular integrity, and angiopoietin-2 (Ang-2) acts as its natural inhibitor. We considered that angiopoietin might be important in bronchial asthma.

Methods

In total, 35 patients with asthma and 20 healthy subjects were studied.

Results

The serum Ang-1 levels were significantly elevated in patients with asthma compared to control subjects (293.9 +/- 13.8 pg/mL vs. 248.3 +/- 16.2 pg/mL, respectively, p = 0.04). The serum Ang-2 levels were not different between the two groups. The areas under the curve (AUC) for serum angiopoietins revealed that the serum level of Ang-1 (0.68) was more sensitive and specific than the serum Ang-2 level (0.55) for differentiating between patients with asthma and control subjects. The serum Ang-1/Ang-2 ratio was correlated with the FEV1/FVC ratio (r = -0.312, p = 0.02), while serum Ang-2 was correlated with body mass index.

Conclusions

Our results indicate that the serum Ang-1 levels were higher in asthma patients compared with healthy subjects. As the Ang-1/Ang-2 ratio was related to lung function, the data suggest that serum angiopoietin is associated with lung function in patients with asthma.

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Specific IgE to fish extracts does not predict allergy to specific species within an adult fish allergic population

Research

Karlijn JG Schulkes, Rob JB Klemans, Lidy Knigge, Marjolein de Bruin-Weller, Carla AFM Bruijnzeel-Koomen, Åsa Marknell deWitt, Jonas Lidholm and André C Knulst

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Clinical and Translational Allergy 2014, 4:27  doi:10.1186/2045-7022-4-27

Published: 1 September 2014

Abstract (provisional)

Background

Fish is an important cause of food allergy. Studies on fish allergy are scarce and in most cases limited to serological evaluation. Our objective was to study patterns of self-reported allergy and tolerance to different commonly consumed fish species and its correlation to IgE sensitization to the same species.

Methods

Thirty-eight adult fish allergic patients completed a questionnaire regarding atopy, age of onset and symptoms to 13 commonly consumed fish species in the Netherlands (pangasius, cod, herring, eel, hake, pollock, mackerel, tilapia, salmon, sardine, tuna, plaice and swordfish). Specific IgE to these fish extracts were analyzed by ImmunoCAP.

Results

Median age of onset of fish allergy was 8.5 years. Severe reactions were reported by the majority of patients (n = 20 (53%) respiratory and of these 20 patients, 6 also had cardiovascular symptoms). After diagnosis, 66% of the patients had eliminated all fish from their diet. Allergy to all species ever tried was reported by 59%. In relation to species ever tried, cod (84%) and herring (79%) were the most frequently reported culprit species while hake (57%) and swordfish (55%) were the least frequent. A positive sIgE (value >= 0.35 kUA/L) to the culprit species ranged between 50% (swordfish) and 100% (hake). In tolerant patients, a negative sIgE (value - 0.35 kUA/L) ranged from 0% (hake, pollock and swordfish) to 75% (sardine). For cod, the agreement between sIgE test results and reported allergy or tolerance was 82% and 25%, respectively. Sensitization to cod parvalbumin (Gad c 1) was present in 77% of all patients.

Conclusion

Serological cross-reactivity between fish species is frequent, but in a significant proportion of patients, clinical relevance appears to be limited to only certain species. A well-taken history or food challenge is required for discrimination between allergy to the different fish species.

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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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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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