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Tuesday, June 11, 2013

Restoring health

The rise in non-communicable, inflammatory diseases (NCD), and in particular allergic and atopic illnesses, has begun to redirect the efforts of the clinical research community toward early prevention in addition to supportive intervention.   This is in light of the significant burden on healthcare created by NCD as well as the realization of the limitations of pharmacotherapies to affect underlying causes. 

This month’s review article by Pfefferle, Prescott and Kopp (J Allergy Clin Immunol 2013; 131(6): 1453-1463) assesses the practical application of findings that commensal gut microbes are critical partners in the evolution of environmental tolerance.   They focus on the accumulating evidence supporting a disrupted human microbiome that has led researchers to propose the use of pro- and pre-biotic therapies as means to prevent inflammatory immune processes that create chronic allergic and atopic diseases.

Pfefferle et al. review briefly the current knowledge on the collaboration of the gut and the immune system in developing tolerance, pointing out the importance of maternal exposure to both pathogenic and non-pathogenic microbes in directing fetal immunity.  They note that high prenatal exposure has been shown to have an independent protective effect on allergic outcomes and that these effects are epigenetic.  Citing a study that compared the immune status and responsiveness of urban Australian children with native Papua New Guinea children, Pfefferle discuss the higher immune activation but lower reactivity of the Papua New Guinea children compared to their urban counterparts, an observation that points to highly divergent microbial exposure of the mothers and their children.

The authors go on to cover the research on maternal pro- and prebiotic interventions for eczema and food allergies.  At least half of the maternal probiotic intervention studies for eczema and food allergy showed positive results, but conflicting results were presented in the remainder.  Maternal prebiotic studies also showed positive effects in both animal models and human subjects, with offspring having greatly diminished expression of eczema.  The observed variability of trial results is analyzed with respect to study design, dosing, population and environmental region. 

Mechanically prepared bacterial lysates (BL) for protection against respiratory illness is also discussed in Pfefferle et al.  Observations that BL push upper airway responses toward Th1 maturation were the basis for studies that examined the effect of BL in reducing the incidence of acute respiratory tract infections (ARTI).  Results showed a protective effect of BL, especially in high risk children.  The authors comment that ARTI and recurrent wheeze in childhood is associated with the development of asthma and suggest that BL may be a future focus of asthma prevention research. 

Pfefferle et al. concludes noting that both the intrinsic and extrinsic microbial environment are implicated in almost all inflammatory NCD and suggest that methods of microbial manipulation are an important focus of future research aimed at prevention strategies. 

Early life BMI progression and asthma incidence

Results from an interesting epidemiological investigation based on data from eight birth cohorts collected under the Global Allergy and Asthma European Network [GA2LEN] research initiatives are presented this month in Rzehak et al (J Allergy Clin Immunol 2013; 131(6): 1528-1536).  Risk of “incident asthma,” defined as first reported physician diagnosis, for 3 age brackets up to 6 years old is analyzed.

Using a novel growth curve analysis method to identify classes of BMI trajectories normalized according to WHO standards [BMI-SDS], the authors identify three classes, a normative class [Class 1], an early rapid growth only up to 2 years class [Class 2], and a persistent rapid growth to 6 years class [Class 3].  Survival analysis of the three BMI-SDS trajectories assessed the hazard ratio [HR] for incident asthma in each. 

Rzehak et al. report that children in the Class 2 trajectory had a significant increased risk of incident asthma within their first 6 years.  Class 3 children had similar risk that did not achieve significance.  Hazard ratios were similar between Class 2 and 3, the latter class having a greater prevalence of excess weight and obesity, suggesting that there is an association of early rapid weight gain with incident asthma, independent of overweight or obesity.

Rzehak et al. conclude that rapid weight gain during the first two years of life increases the risk of incident asthma by the age of 6 years.