Diet and asthma: looking back,moving forward

Asthma is an increasing global health burden, especially in the western world. Public health interventions are sought to lessen its prevalence or severity, and diet and nutrition have been identified as potential factors. With rapid changes in diet being one of the hallmarks of westernization, nutrition may play a key role in affecting the complex genetics and developmental pathophysiology of asthma. The present review investigates hypotheses about hygiene, antioxidants, lipids and other nutrients, food types and dietary patterns, breastfeeding, probiotics and intestinal microbiota, vitamin D, maternal diet, and genetics. Early hypotheses analyzed population level trends and focused on major dietary factors such as antioxidants and lipids. More recently, larger dietary patterns beyond individual nutrients have been investigated such as obesity, fast foods, and the Mediterranean diet. Despite some promising hypotheses and findings, there has been no conclusive evidence about the role of specific nutrients, food types, or dietary patterns past early childhood on asthma prevalence. However, diet has been linked to the development of the fetus and child. Breastfeeding provides immunological protection when the infant''s immune system is immature and a modest protective effect against wheeze in early childhood. Moreover, maternal diet may be a significant factor in the development of the fetal airway and immune system. As asthma is a complex disease of gene-environment interactions, maternal diet may play an epigenetic role in sensitizing fetal airways to respond abnormally to environmental insults. Recent hypotheses show promise in a biological approach in which the effects of dietary factors on individual physiology and immunology are analyzed before expansion into larger population studies. Thus, collaboration is required by various groups in studying this enigma from epidemiologists to geneticists to immunologists. It is now apparent that this multidisciplinary approach is required to move forward and understand the complexity of the interaction of dietary factors and asthma.     

Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: proof of concept

Antioxidant-rich diets are associated with reduced asthma prevalence. However, direct evidence that altering intake of antioxidant-rich foods affects asthma is lacking. The objective was to investigate changes in asthma and airway inflammation resulting from a low antioxidant diet and subsequent use of lycopene-rich treatments. Asthmatic adults (n=32) consumed a low antioxidant diet for 10 days, then commenced a randomized, cross-over trial involving 3×7 day treatment arms (placebo, tomato extract (45 mg lycopene/day) and tomato juice (45 mg lycopene/day)). With consumption of a low antioxidant diet, plasma carotenoid concentrations decreased, Asthma Control Score worsened, %FEV₁ and %FVC decreased and %sputum neutrophils increased. Treatment with both tomato juice and extract reduced airway neutrophil influx. Treatment with tomato extract also reduced sputum neutrophil elastase activity. In conclusion, dietary antioxidant consumption modifies clinical asthma outcomes. Changing dietary antioxidant intake may be contributing to rising asthma prevalence. Lycopene-rich supplements should be further investigated as a therapeutic intervention.     

West Sweden Asthma Study: Prevalence trends over the last 18 years argues no recent increase in asthma

Asthma prevalence has increased over the last fifty years, but the more recent changes have not been conclusively determined. Studies in children indicate that a plateau in the prevalence of asthma may have been reached, but this has not yet been confirmed in adults. Epidemiological studies have suggested that the prevalence of asthma in adults is approximately 7-10% in different parts of the western world.We have now performed a large-scale epidemiological evaluation of the prevalence of asthma and respiratory symptoms in adults between the ages of 16-75 in West Sweden. Thirty thousand randomly chosen individuals were sent a detailed questionnaire focusing on asthma and respiratory symptoms, as well possible risk factors. Sixty-two percent of the contacted individuals responded to the questionnaire. Asthma prevalence, defined as asthma diagnosed by a physician, was 8.3%. Moreover, the prevalence of respiratory symptoms was lower compared to previous studies. The most common respiratory symptom was any wheeze (16.6%) followed by sputum production (13.3%). In comparison with studies performed 18 years ago, the prevalence of asthma has not increased, and the prevalence of most respiratory symptoms has decreased. Therefore, our data argues that the continued increase in asthma prevalence that has been observed over the last half century is over.     

Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: Proof of concept

Antioxidant-rich diets are associated with reduced asthma prevalence. However, direct evidence that altering intake of antioxidant-rich foods affects asthma is lacking. The objective was to investigate changes in asthma and airway inflammation resulting from a low antioxidant diet and subsequent use of lycopene-rich treatments. Asthmatic adults (n=32) consumed a low antioxidant diet for 10 days, then commenced a randomized, cross-over trial involving 3×7 day treatment arms (placebo, tomato extract (45 mg lycopene/day) and tomato juice (45 mg lycopene/day)). With consumption of a low antioxidant diet, plasma carotenoid concentrations decreased, Asthma Control Score worsened, %FEV₁ and %FVC decreased and %sputum neutrophils increased. Treatment with both tomato juice and extract reduced airway neutrophil influx. Treatment with tomato extract also reduced sputum neutrophil elastase activity. In conclusion, dietary antioxidant consumption modifies clinical asthma outcomes. Changing dietary antioxidant intake may be contributing to rising asthma prevalence. Lycopene-rich supplements should be further investigated as a therapeutic intervention.     

Chronic obstructive pulmonary disease, asthma and protective effects of food intake: from hypothesis to evidence?

Evidence for a role of diet in asthma and chronic obstructive pulmonary disease (COPD) has been accumulating rapidly over the past decade. Associations have been reported between the intake of fruit, fish, antioxidant vitamins, fatty acids, sodium or magnesium, and indicators of asthma and COPD. Several issues need to be addressed before causality of these associations can be established. The role of diet in the development of disease and the induction time and reversibility of the effect needs further investigation. The role of smoking habits in the relation of diet and respiratory disease also needs to be elucidated. Nevertheless, based on the available evidence, dietary guidelines could be proposed for the primary and secondary prevention of asthma and COPD that are in line with existing dietary guidelines for the prevention of coronary heart disease and cancer.     

Range-Finding Study of Risk Factors for Childhood Asthma Development and National Asthma Prevalence

This review explores the recent epidemiological literature to identify possible risk factors for childhood asthma development, as well as the proportion of cases that might be attributable to each factor. Tobacco smoke and house-dust-mite allergy are the only environmental risk factors with firmly established roles in asthma development. Together with genetics, these risk factors probably account for much of childhood asthma development. Suggestive risk factors include cockroach, pet, and mold allergens; low birth weight; small family size; and viral infection. More theoretical risk factors include insufficient breastfeeding, obesity/inactivity, ambient ozone, and living in non-farm settings. National/international trends suggest several risk factors that could play major roles in the rising prevalence of asthma. The “tighter” building construction of modern housing and the increasing time that children spend indoors has undoubtedly increased indoor allergen exposures. Children also spend more time in sedentary activities, with a concomitant decrease in physical activity and increase in obesity. Modern “hygiene” and the changing nature of childhood infection may have also increased asthma prevalence. Mechanisms have been suggested implicating ambient air pollution in asthma development, and there is limited epidemiological evidence supporting this hypothesis. However, this evidence does not resolve why pollution levels have been decreasing throughout the period that asthma rates have risen     

Examining the temporal relationships between childhood obesity and asthma

Childhood obesity has become an issue of increasing concern to health researchers and policymakers in the United States. One important chronic health condition linked to obesity is pediatric asthma. Although researchers have speculated that both conditions may have common origins, the majority of research in this area has focused on a unidirectional relationship between obesity and later asthma. However, much of the literature is limited by its reliance on cross-sectional data and its failure to examine the possibility that asthma may influence weight fluctuations through changes in physical and sedentary activity. Using data from the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K), I explore the bidirectional relationships between childhood obesity and asthma. The results in this paper suggest that past asthma levels are positively correlated with changes in BMI and the onset of obesity. However, only new onset asthma is positively correlated with subsequent changes in BMI. The potential mechanisms are unclear, as I find little evidence that asthma is structurally related to changes in physical or sedentary activity over time. When testing the prevailing hypothesis that obesity is related to subsequent asthma, I find that lagged weight status is strongly related to asthma prevalence levels but that the onset of overweight or obesity is not associated with the subsequent onset of asthma. These results suggest that the onset of asthma may be related to subsequent weight gain over time.     

Changes to airborne pollen counts across Europe

A progressive global increase in the burden of allergic diseases has affected the industrialized world over the last half century and has been reported in the literature. The clinical evidence reveals a general increase in both incidence and prevalence of respiratory diseases, such as allergic rhinitis (common hay fever) and asthma. Such phenomena may be related not only to air pollution and changes in lifestyle, but also to an actual increase in airborne quantities of allergenic pollen. Experimental enhancements of carbon dioxide (CO[Formula: see text]) have demonstrated changes in pollen amount and allergenicity, but this has rarely been shown in the wider environment. The present analysis of a continental-scale pollen data set reveals an increasing trend in the yearly amount of airborne pollen for many taxa in Europe, which is more pronounced in urban than semi-rural/rural areas. Climate change may contribute to these changes, however increased temperatures do not appear to be a major influencing factor. Instead, we suggest the anthropogenic rise of atmospheric CO[Formula: see text] levels may be influential.     

Trends in prevalence of allergic rhinitis and correlation with pollen counts in Switzerland

In recent decades, a large number of epidemiological studies investigating the change of prevalence of hay fever showed an increase in the occurrence of this disease. However, other studies carried out in the 1990s yielded contradictory results. Many environmental factors have been hypothesized to contribute to the increasing hay fever rate, including both indoor and ambient air pollution, reduced exposure to microbial stimulation and changes in diets. However, the observed increase has not convincingly been explained by any of these factors and there is limited evidence of changes in exposure to these risk factors over time. Additionally, recent studies show that no further increase in asthma, hay fever and atopic sensitisation in adolescents and adults has been observed during the 1990s and the beginning of the new century. As the pattern of pollen counts has changed over the years, partly due to the global warming but also as a consequence of a change in the use of land, the changing prevalence of hay fever might partly be driven by this different pollen exposure. Epidemiological data for hay fever in Switzerland are available from 1926 until 2000 (with large gaps between 1926 and 1958 and 1958 to 1986) whereas pollen data are available from 1969 until the present. This allows an investigation as to whether these data are correlated provided the same time spans are compared. It would also be feasible to correlate the pollen data with meteorological data which, however, is not the subject of our investigation. Our study focuses on analyzing time series of pollen counts and of pollen season lengths in order to identify their trends, and to ascertain whether there is a relationship between these trends and the changes in the hay fever prevalence. It is shown in this paper that the pollen exposure has been decreasing in Basel since the beginning of the 1990s whereas the rate of the hay fever prevalence in Switzerland remained approximately unchanged in this period but with a slight tendency to decrease. In Locarno, most of the pollen species also show a decreasing trend, while in Zurich, the development is somewhat different as the pollen counts of most of the pollen types have been increasing. It is interesting, however, that some of the pollen counts of this station (grass, stinging nettle, mugwort and ragweed) have been decreasing in the period 1982–2007.     

Diet and endothelial function

Endothelial dysfunction is one of the earliest events in atherogenesis. A consequence of endothelial damage is a lower availability of nitric oxide (NO), the most potent endogenous vasodilator. NO inhibits platelet aggregation, smooth muscle cell proliferation and adhesion of monocytes to endothelial cells. Endothelial dysfunction is present in patients with cardiovascular disease and/or coronary risk factors, such as hypertension, dyslipidemia, diabetes, smoking or hyperhomocysteinemia. At present, soluble markers and high resolution ultrasound of the brachial artery, have provided simple tools for the study of endothelial function and the effects of several interventions. It has been demonstrated that dietary factors may induce significant changes on vascular reactivity. Nutrients, such as fish oil, antioxidants, L-arginine, folic acid and soy protein have shown an improvement in endothelial function that can mediate, at least partially, the cardioprotective effects of these substances. Attention has been focused on dietary patterns in populations with lower prevalence of cardiovascular disease. There is some evidence suggesting that Mediterranean diet characterized by high consumption of vegetables, fish, olive oil and moderate wine consumption may have a positive effect on endothelial function. These results give us evidence on the significant role of diet on endothelial function and its impact on the pathogenesis of atherosclerosis.     

Nutrient sensing in the gastrointestinal tract: Possible role for nutrient transporters

Although it is well established that the presence of nutrients in the gut lumen can bring about changes in GI function, the mechanisms and pathways by which these changes occur has not been fully elucidated. It has been known for many years that luminal nutrients stimulate the release of hormones and regulatory peptides from gut endocrine cells and that luminal nutrients activate intrinsic and extrinsic neural pathways innervating the gut. Activation of gut endocrine cells and neural pathways by nutrients in the gut lumen is key in coordination of postprandial GI function and also in the regulation of food intake. Recent evidence suggests that these pathways can be modified by long term changes in diet or by inflammatory processes in the gut wall. Thus it is important to determine the cellular and molecular mechanisms underlying these processes not only to increase our understanding of as part of basic physiology but also to understand changes in these pathways that occur in the presence of pathophysiology and disease. This review summarizes some of the latest data that we have obtained, together with information from the other laboratories, which have elucidated some of the mechanisms involved in nutrient detection in the gut wall. The focus is on monosaccharides and protein hydrolysates as there is some evidence for a role for nutrient transporters in detection of these nutrients.     

Mr. de la Roche replies

Review of the literature reveals sporadic but true increases in the prevalence and death rates for asthma over the past 25 years. Although changes in hereditary, allergic and environmental factors must be considered as possible causes of this increase, its suddenness points to risk factors that change rapidly. Such is the case with atmospheric pollutants, notably nitrogen dioxide and particles, both of which have been shown to have adverse effects on the tracheobronchial tree. These pollutants tend to concentrate inside homes, especially since the early 1980s, when the energy crisis brought about changes in the home environment.     

Probable evidence of scurvy in subadults from archeological sites in Peru

Subadult scurvy is not well documented in archeological human remains despite the existence of many biomedical references indicating that bone changes do occur in some cases and, because of this, should be observable in human burials. There are several potential reasons for this gap in our knowledge of scurvy. Not all children who suffered from scurvy died of the disease or from other causes when they had scurvy. Scurvy may not leave characteristic bone changes in every case of the disease. Some of the pathological conditions associated with scurvy have been known for many years, but these features may be rare or difficult to differentiate from other pathological conditions. Recently a lesion of the skull has been described that is probably pathognomonic for scurvy, specifically porous and sometimes hypertrophic lesions of the greater wing of the sphenoid. This lesion is bilateral and highly associated with evidence of inflammation at other anatomical sites in the skull. A survey of subadult skulls (N = 363) in the human skeletal collection from Peru at the National Museum of Natural History, Smithsonian Institution, reveals a prevalence of 10% of skulls that exhibit plausible evidence of scurvy. Some cases of scurvy also have cribra orbitalia that has been attributed to anemia. In most of the Peruvian scurvy cases, anemia is an unlikely possibility because there is no evidence of marrow hyperplasia. This highlights the need for caution in using lesions of the orbit as an indicator of anemia when there is no other evidence of this disease elsewhere in the skeleton. Anatomical evidence of scurvy offers the potential of providing new and important evidence of diet in archeological human populations.     

School Variation in Asthma: Compositional or Contextual?

Background

Childhood asthma prevalence and morbidity have been shown to vary by neighborhood. Less is known about between-school variation in asthma prevalence and whether it exists beyond what one might expect due to students at higher risk of asthma clustering within different schools. Our objective was to determine whether between-school variation in asthma prevalence exists and if so, if it is related to the differential distribution of individual risk factors for and correlates of asthma or to contextual influences of schools.

Methods

Cross-sectional analysis of 16,640 teens in grades 7–12 in Wave 1 (data collected in 1994–5) of the National Longitudinal Study of Adolescent Health. Outcome was current diagnosis of asthma as reported by respondents'' parents. Two-level random effects models were used to assess the contribution of schools to the variance in asthma prevalence before and after controlling for individual attributes.

Results

The highest quartile schools had mean asthma prevalence of 21.9% compared to the lowest quartile schools with mean asthma prevalence of 7.1%. In our null model, the school contributed significantly to the variance in asthma ( = 0.27, CI: 0.20, 0.35). Controlling for individual, school and neighborhood attributes reduced the between-school variance modestly ( = 0.19 CI: 0.13–0.29).

Conclusion

Significant between-school variation in current asthma prevalence exists even after controlling for the individual, school and neighborhood factors. This provides evidence for school level contextual influences on asthma. Further research is needed to determine potential mechanisms through which schools may influence asthma outcomes.     

Observations on recent increase in mortality from asthma.

The mortality attributed to asthma has increased annually in England and Wales from 1960 to 1965. The increase is more pronounced at ages 5 to 34 years than at older ages and is most pronounced at ages 10 to 14 years. In this last age group the mortality increased nearly eight times in seven years, and in 1966 asthma accounted for 7% of all deaths. No comparable increase has been observed in any other country, but smaller increases at ages 10 to 19 years have been observed in Australasia, Japan, western Europe, and the United States. There is no evidence to suggest that there has been any change in diagnostic habits, certification of deaths, or methods of classification which could account for the increase in Great Britain, and it is concluded that the increase is real. General practitioners'' records provide no evidence of an increase in prevalence and it seems probable that there has been an increase in case fatality. No environmental hazards are known which could have increased the severity of the disease, and the possibility has to be considered that the increase may be due to new methods of treatment. Corticosteroids have been used increasingly since 1952, and in Great Britain the use of pressurized aerosols containing sympathomimetics has increased rapidly since 1960.     

Epithelium-fibroblast interactions in response to airway inflammation

Dramatic changes to the architecture of the airway walls have been commonly described in the airways of patients with asthma, cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Much research has focused on how airway inflammation drives these structural changes, particularly in terms of the mechanisms/mediators that are involved, and a number of parallels are observed between the disease phenotypes. For example, the increased deposition of extracellular matrix (ECM) at focal sites in the airway wall is seen in asthma and all interstitial lung diseases that involve fibrosis. In addition, increased expression of a number of well characterized cytokines and growth factors, such as TGF-beta and epidermal growth factor (EGF) have been demonstrated in these diseases. However, the role of the lesser-known cytokines, including the leukaemia inhibitory factor (LIF) and other members of the IL-6 family of cytokines in the pathogenesis of airway remodelling and fibrosis is largely unknown. However, the use of genetic manipulation in vivo and more specific inhibitors/antibodies in vitro has now provided increasing evidence to support the hypothesis that a complex interaction exists between these cytokines, ECM and integrins in regulating the function of both epithelial cells and fibroblasts.     

Epidemiology of dust-mite-related disease

For many years it has been suggested that allergens derived from the house dust mite played a major role in the pathogenesis of asthma, eczema and some cases of allergic rhinitis. Recently, house dust mite allergens have been purified and specific immunoassays developed with which exposure to house dust mites and their allergens can be more easily determined. Using these tools, epidemiological studies have provided confirmatory evidence that not only is house dust mite exposure associated with the majority of cases of asthma in children and young adults, but that it is causally related to the development of asthma.     

Secular trend in the occurrence of asthma among children and young adults: critical appraisal of repeated cross sectional surveys.

OBJECTIVES: To review repeated surveys of the rising prevalence of obstructive lung disease among children and young adults and determine whether systematic biases may explain the observed trends. DESIGN: Review of published reports of repeated cross sectional surveys of asthma and wheezing among children and young adults. The repeated surveys used the same sampling frame, the same definition of outcome variables, and equivalent data collection methods. SETTING: Repeated surveys conducted anywhere in the world. SUBJECTS: All repeated surveys whose last set of results were published in 1983 or later. MAIN OUTCOME MEASURES: Lifetime and current prevalences of asthma and current prevalence of wheezing. The absolute increase (yearly percentage) in the prevalences of asthma and wheezing was calculated and compared between studies. RESULTS: 16 repeated surveys fulfilled the inclusion criteria. 12 reported increases in the current prevalence of asthma (from 0.09% to 0.97% a year) and eight reported increases in the current prevalence of wheezing (from 0.14% to 1.24% a year). Changes in labelling are likely to have occurred for the reporting of asthma, and information biases may have occurred for the reporting of wheezing. Only one study reported an increase in an objective measurement. CONCLUSIONS: The evidence for increased prevalences of asthma and wheezing is weak because the measures used are susceptible to systematic errors. Until repeated surveys incorporating more objective data are available no firm conclusions about increases in obstructive lung disease among children and young adults can be drawn.     

Genetic variants on 17q21 are associated with asthma in a Han Chinese population

A genome-wide study has shown an association between SNPs located on 17q21 and asthma. Such associations have been identified in several populations, but little is known about the Han Chinese population. We conducted a case-control study in a Han Chinese population to investigate the relationship between SNPs located on 17q21 and asthma; 241 asthmatic patients and 212 healthy controls were recruited from the outpatient clinics of the Nanfang Hospital, Guangdong Province, southern China. We genotyped six SNPs (rs8067378, rs8069176, rs2305480, rs4795400, rs12603332, and rs11650680) located on 17q21 with the Sequenom MassARRAY iPLEX platform. For two of these six loci (rs2305480 and rs8067378), there was evidence of association with asthma, and there was a weak association of asthma with rs8069176. We confirm that genetic variants on 17q21 are associated with asthma in the Han Chinese population.