Environmental factors such as inhaling toxic fumes and cigarette smoking are not believed to play a role in DPB, and unknown environmental and other non-genetic causes—such as unidentified bacteria or viruses—have not been ruled out.Cystic fibrosis (CF), a progressive multi-system lung disease, has been considered in the search for a genetic cause of DPB. This is for a number of reasons. CF, like DPB, causes severe lung inflammation, abundant mucus production, infection, and shows a genetic predominance among Caucasians of one geographic group to the rarity of others; whereas DPB dominates among East Asians, CF mainly affects individuals of European descent. While no gene has been implicated as the cause of DPB, mutation in a specific gene—much more likely to occur in Europeans—causes CF. This mutation in the CF-causing gene is not a factor in DPB, but a unique polymorphism (variation) in this gene is known to occur in many Asians not necessarily affected by either disease. It is being investigated whether this gene in any state of mutation could contribute to DPB. Pathophysiology
Inflammation is a normal part of the human immune response, whereby leukocytes (white blood cells), including neutrophils (white blood cells that specialize in causing inflammation), gather, and chemokines (proteins released from certain cells, which activate or elicit a response from other cells) accumulate at any location in the body where bacterial or viral infections occur. Inflammation interferes with the activity of bacteria and viruses, and serves to clear them from the body.
Additionally, when a food substance, supplement or medicine containing a precursor (choline or carnitine) is ingested, bacteria in the gut convert a portion of those precursors to TMA. Moderate amounts of precursor are absorbed in the small intestine before reaching the gut, however if precursor rich food saturates the transport capacity of the intestine, excess precursor ends up in the gut. The proportion of precursor converted to TMA is related to the amount of specific bacteria in the gut.TMA in the gut is absorbed through the intestinal lining and enters the bloodstream, where it is filtered by the liver. The liver usually produces an abundance of the enzyme FMO3, which neutralises the TMA by oxidising it to odourless TMAO, and passes it through to the bladder. If FMO3 enzyme production is compromised, or there is too much TMA for the amount of enzyme, then TMA will continue to circulate in the bloodstream until enough enzyme is produced. While TMA is in the bloodstream, it is slowly exits the body via bodily fluids; urine, sweat, saliva, reproductive fluids and breath (See fluid balance for rates of fluid loss). TMA has no known interactions with any known internal or organ function. Although lecithin, creatinine and betaine are technically precursors to TMA, studies have shown no significant effect on the production of excess TMA/TMAO in urinary analysis at normal dietary levels of consumption. Symptoms and signs
Trimethylamine is most noticeable in urine, as it is captured, concentrated and released in intervals.