Atopy is not a single phenotype, the idea of an “atopic march” from infantile eczema through food allergy to asthma and rhinitis is way too simplistic. Early interventions have been disappointing. Curiously, food allergies and eczema often improve through childhood – this seems less common with asthma.
There are different risk groups. Environmental exposure to allergens and microbes in early life is one factor. Farm environment protects (exposures and/or dietary).
Most studies show dog ownership protective. Weaker evidence for cats. House dust mite sensitisation in early life predicts asthma in school age. Primary prevention of HDM sensitisation has conflicting evidence – Isle of Wight study showed mite avoidance prevented sensitisation and asthma; Canada study showed effectiveness but Dutch study did not. Manchester study reduced early wheezing but had higher rates of sensitisation. Australian study no effect overall but depended on age.
Reduced bacterial diversity is a risk factor for asthma and atopic wheeze – certain bacteria esp bacteroides and firmacutes seem to be protective.
Viruses also play a role. RSV is associated with later asthma regardless of existing atopy or not, although perhaps not with asthma persisting into adulthood; rhinovirus wheezing in first 3yrs is similarly associated with persistent wheeze, especially in atopic persons. So impact of more RSV and other vaccines could be fascinating.
Heritability of asthma accounts for less than 50% of patients so gene-environment interactions are at least as important. A gene has been found that is associated with early childhood asthma with severe exacerbations (CDHR3). TSLP gene on chromosome 5q22 encodes for a master regulator for TH2 processes. But another well recognised gene region on chromosome 17q12-21 (including ORMDL3 and GSDMB) seems to be involved in airway dysregulation after virus infection, rather than allergy.
Increasing evidence that respiratory health is influenced by parental exposures that occur long before conception. The strongest evidence relates adolescent tobacco smoking and overweight in future fathers to increased asthma and lower lung function in their offspring, supported by evidence on parental preconception occupational exposures and air pollution. Antenatal and postnatal (passive) smoking important. Role of breast feeding vs formula still controversial.
No evidence for asthma preventer treatment as an early intervention – cf JIA and other inflammatory conditions.
Grass immunotherapy for rhinitis in children reduces the incidence of later asthma and need for asthma medication. Presumably house dust mite immunotherapy would help too? HDM antigens have allergenic but also endotoxin and enzymatic effects! Jurgen’s study of HDM SLIT in infancy found reduced sensitisation (to anything, but def HDM – but only 11% difference and active group had more pets…); at 3 yrs, no difference in clinical outcomes, unfortunately – in fact, more wheeze…
Spanish RCT of oral bacterial extracts (6 different ones for 6 months) significantly reduced number of wheeze episodes (40%) for up to 1 year. Animal experiments have already shown that oral administration of bacterial extracts prevents bronchial hyperreactivity.
We should therefore encourage less Caesarean sections, more breast feeding, less antibiotic use, more green spaces, more “natural” food preparation and distribution (ie less plastic!).