KEY POINTS
• The development and persistence of asthma are driven by gene–environment interactions. For children, a ‘window of opportunity’ exists in utero and in early life, but intervention studies are limited.
• For intervention strategies that include allergen avoidance:
o Strategies directed at a single allergen have not been effective
o Multifaceted strategies may be effective, but the essential components have not been identified.
• Current recommendations, based on high quality evidence or consensus, include:
o Avoid exposure to environmental tobacco smoke during pregnancy and the first year of life o Encourage vaginal delivery
o Advise breast-feeding for its general health benefits (not necessarily for asthma prevention)
o Where possible, avoid use of paracetamol (acetaminophen) and broad-spectrum antibiotics during the first year of life.
FACTORS CONTRIBUTING TO THE DEVELOPMENT OF ASTHMA
Asthma is generally believed to be a heterogeneous disease whose inception and persistence is driven by gene–
environment interactions. The most important of these interactions may occur in early life and even in-utero. There is consensus that a ‘window of opportunity’ exists during pregnancy and early in life when environmental factors may influence asthma development. Multiple environmental factors, both biological and sociological, may be important in the development of asthma. Data supporting the role of environmental risk factors for the development of asthma include a focus on: nutrition, allergens (both inhaled and ingested), pollutants (particularly environmental tobacco smoke), microbes, and psychosocial factors. Additional information about factors contributing to the development of asthma, including occupational asthma, is found in Appendix Chapter 2.
‘Primary prevention’ refers to preventing the onset of disease. This chapter focuses on primary prevention in children.
See p.66 and review articles30 for strategies for preventing occupational asthma.
PREVENTION OF ASTHMA IN CHILDREN Nutrition
Maternal diet and weight gain during pregnancy
For some time, the mother’s diet during pregnancy has been a focus of concern relating to the development of allergy and asthma in the child. There is no firm evidence that ingestion of any specific foods during pregnancy increases the risk for asthma. However, a recent study of a pre-birth cohort observed that maternal intake of foods commonly considered allergenic (peanut and milk) was associated with a decrease in allergy and asthma in the offspring.489 Similar data have been shown in a very large Danish National birth cohort, with an association between ingestion of peanuts, tree nuts and/or fish during pregnancy and a decreased risk of asthma in the offspring.490,491 No dietary changes during pregnancy are therefore recommended for prevention of allergies or asthma.
Data suggest that maternal obesity and weight gain during pregnancy pose an increased risk for asthma in children. A recent meta-analysis492 showed that maternal obesity in pregnancy was associated with higher odds of ever asthma or wheeze or current asthma or wheeze; each 1 kg/m2 increase in maternal BMI was associated with a 2% to 3% increase in the odd of childhood asthma. High gestational weight gain was associated with higher odds of ever asthma or wheeze. However, no recommendations can be made at present, as unguided weight loss in pregnancy should not be encouraged.
Breast-feeding
Despite the existence of many studies reporting a beneficial effect of breast-feeding on asthma prevention, results are conflicting,279 and caution should be taken in advising families that breast-feeding will prevent asthma.493 Breast-feeding decreases wheezing episodes in early life; however, it may not prevent development of persistent asthma (Evidence D).
Regardless of its effect on development of asthma, breast-feeding should be encouraged for all of its other positive benefits (Evidence A).
Vitamin D
Intake of vitamin D may be through diet, dietary supplementation or sunlight. A systematic review of cohort, case control and cross-sectional studies concluded that maternal intake of vitamin D, and of vitamin E, was associated with lower risk of wheezing illnesses in children.494
Delayed introduction of solids
Beginning in the 1990s, many national pediatric agencies and societies recommended delay of introduction of solid food, especially for children at a high risk for developing allergy. Current guidelines do not recommend strict avoidance of high-risk foods,279 but carefully controlled, prospective studies are needed to conclusively resolve this controversy.
Probiotics
A meta-analysis provided insufficient evidence to recommend probiotics for the prevention of allergic disease (asthma, rhinitis, eczema or food allergy).495
Inhalant allergens
Sensitization to indoor, inhaled aero-allergens is generally more important than sensitization to outdoor allergens for the presence of, and/or development of, asthma. While there appears to be a linear relationship between exposure and sensitization to house dust mite,496,497 the relationship for animal allergen appears to be more complex.279 Some studies have found that exposure to pet allergens is associated with increased risk of sensitization to these allergens,498,499 and of asthma and wheezing.500,501 By contrast, other studies have demonstrated a decreased risk of developing allergy with exposure to pets.502,503 A review of over 22,000 school-age children from 11 birth cohorts in Europe found no correlation between pets in the homes early in life and higher or lower prevalence of asthma in children.504 For children at risk of asthma, dampness, visible mold and mold odor in the home environment are associated with increased risk of developing asthma.505 Overall, there are insufficient data to recommend efforts to either reduce or increase pre-natal or early-life exposure to common sensitizing allergens, including pets, for the prevention of allergies and asthma.
Birth cohort studies provide some evidence for consideration. A meta-analysis found that studies of interventions focused on reducing exposure to a single allergen did not significantly affect asthma development, but that multifaceted interventions such as in the Isle of Wight study,506 the Canadian Asthma Primary Prevention Study,507 and the Prevention of Asthma in Children study508 were associated with lower risk of asthma diagnosis in children younger than 5 years.509 Two multifaceted studies that followed children beyond 5 years of age demonstrated a significant protective effect both before and after the age of 5 years.506,510 The Isle of Wight study has shown a continuing positive benefit for early-life intervention through to 18 years of age;511 however, exactly which components of the intervention were important and which specific mechanistic changes were induced remain elusive.
Pollutants
Maternal smoking during pregnancy is the most direct route of pre-natal environmental tobacco smoke exposure.512 A meta-analysis concluded that pre-natal smoking had its strongest effect on young children, whereas post-natal maternal smoking seemed relevant only to asthma development in older children.513
Exposure to outdoor pollutants, such as living near a main road, is associated with increased risk of asthma,514 but one study suggested that this may only be important for children also exposed to tobacco smoke in-utero and in infancy.515
Comment [A27]: Brozek 2010 ARIA review added
Deleted: In summary,
Microbial effects
The ‘hygiene hypothesis’, and the more recently coined ‘microflora hypothesis’ and ‘biodiversity hypothesis’,516 suggest that human interaction with microbiota may be beneficial in preventing asthma. For example, there is a lower risk of asthma among children raised on farms with exposure to stables and consumption of raw farm milk than among children of non-farmers.517 The risk of asthma is also reduced in children whose bedrooms have high levels of bacterial-derived lipopolysaccharide endotoxin.518,519 Similarly, children in homes with ≥2 dogs or cats are less likely to be allergic than those in homes without dogs or cats.503 Exposure of an infant to the mother’s vaginal microflora through vaginal delivery may also be beneficial; the prevalence of asthma is higher in children born by Caesarian section than those born vaginally.520 This may relate to differences in the infant gut microbiota according to their mode of delivery.521 Medications and other factors
Antibiotic use during pregnancy and in infants and toddlers has been associated with the development of asthma later in life,522-524 although not all studies have shown this association.525 Intake of the analgesic, paracetamol (acetaminophen), may be associated with asthma in both children and adults,526 although exposure during infancy may be confounded by use of paracetamol for respiratory tract infections.526 Frequent use of paracetamol by pregnant women has been associated with asthma in their children.527
There is no evidence that vaccinations increase the risk of a child developing asthma.
Psychosocial factors
The social environment to which children are exposed may also contribute to the development and severity of asthma.
Maternal distress that persists from birth through to early school age has been associated with an increased risk of the child developing asthma.522
ADVICE ABOUT PRIMARY PREVENTION OF ASTHMA
Based on the results of cohort and observational studies, and a GRADE-based analysis for the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines,279 parents enquiring about how to reduce the risk of their children developing asthma can be provided with the advice summarized in Box 7-1.
There is interest in investigating other strategies for prevention of asthma, based on known associations. For example, respiratory syncytial virus infection is associated with subsequent recurrent wheeze, and preventative treatment of premature infants with monthly injections of the monoclonal antibody, palivizumab, (prescribed for prophylaxis of respiratory syncytial virus) is associated with a reduction in recurrent wheezing in the first year of life.528
Possibly the most important factor is the need to provide a positive, supportive environment that decreases stress, and which encourages families to make choices with which they feel comfortable.
Box 7-1. Advice about primary prevention of asthma in children 5 years and younger
Parents enquiring about how to reduce the risk of their child developing asthma can be provided with the following advice:
• Children should not be exposed to environmental tobacco smoke during pregnancy or after birth
• Vaginal delivery should be encouraged where possible
• Breast-feeding is advised, for reasons other than prevention of allergy and asthma
• The use of broad-spectrum antibiotics during the first year of life should be discouraged.
Comment [A28]: Previous reference 487 (Thavagnanam et al 2008) has been replaced with a newer meta-analysis, Huang et al 2015
Comment [A29]: Previous reference 493 Etminan et al 2009 has been replaced with a newer meta-analysis, Cheelo et al 2016
SECTION 3. TRANSLATION INTO CLINICAL PRACTICE