Third, in PARSIFAL dust from children’s mattresses were collected by vacuuming — it is not very likely that many helminthic eggs were transported from stable to bedroom. In GABRIELA, only airborne dust samples were collected which again may miss helminth eggs although being certainly present in stable dust.
Fourth, more microbial exposure and more fungal taxa on farms are a trivial finding.
The inverse associations of the diversity scores with asthma were not confounded by status with respect to living on a farm because adjustment did not change the respective point estimates for asthma (Table 2), although the associations became nonsignificant.
Small sample size, borderline p-values even after a long fishing expedition?
What do these strange “probability” plots really show – the probability of asthma or the probability to live on a farm?
The plots are misleading if adjustment for farm living does not change the parameter estimates for bacterial/fungal diversity.
Sixth – even many years later, the main findings of this study have not been independently replicated. There is not any single study that shows listeriosis (Listeria) or diphtheria (Corynebacterium) to be protective.
A recent study in the NEJM found remarkable differences in the asthma prevalence between Amish and Hutterite populations. The lifestyle of both communities is similar but their farming practice is distinct as the Amish follow a more traditional style of outdoor grazing whereas the Hutterities use industrialized farming practices. Gene expression data in the Amish children have been interpreted as „intense exposure to microbes“ because protection of experimental asthma by Amish derived house dust was nearly abrogated in mice deficient for MyD88.
Any helminth exposure has been excluded due to low IgE and eosinophil counts in the children while I still think that this could be an explanation in particular as the attempt to show an effect of bacterial exposure was unsuccessful since the discovery of the farming effect.
One difference between conventional stable (Hutterites) and outdoor grazing (Amish) is the higher helminthic infection rate on pasture, mainly with Fasciola, Ostertagia, Eimeria, Cooperia, Dictyocaulus and Trichostrongylos species.
Infected cattle rarely demonstrate clinical disease, while it is known that Fasciola (as for example Schistosome) has numerous immunosuppressive functions in the host. IgE is not always raised as Fasciola can degrade human immunoglobulin or even induce eosinophil apoptosis.
When starting in the asthma field in 1989, the textbooks told me that asthma is a disease of the lung. Some years later, asthma turned out to be a disease of the bone marrow cells. More recently, I raised the question if asthma could be even a disease of the gut – our largest immunological organ being frequently exposed to allergen & plenty of immunological active substances. Although on the different track (vitamin A) also other authors now think of an early impaired immune gut response.
Rather unexpected for me was a study in J Steroid Biochem Mol Biol that 1,25(OH)2D3 inhibits in vitro and in vivo intracellular growth of the parasite Toxoplasma gondii. yea, yea.