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This sounds to me like classic VCM induced plug fouling. If you change the plugs and the problem goes away for 3-5 months, comes back with dirty plugs again, then that screams oil fouling caused by VCM. You need to disable the VCM (ECO mode) that turns off the 3 rear cylinders for fuel economy. I would install a VCMTunerII, replace the plugs again (use only NGK from a reputable authorized reseller--not Amazon or eBay,) and hope you've escaped the need to have the pistons re-ringed.

At your mileage, I'd also replace all four O2's. This could be the cause of your occasional roughness. After replacing mine at 170K it ran like a brand new car. They don't last forever. Be sure and use NTK sensors, which are the OEM.

As mentioned, if you have oil on the coils when you remove them then that's a valve cover/spark plug seal issue and you should do a valve cover gasket replacement. At your mileage you should also do a valve adjustment if it hasn't been done already, as well.
 
On Gen 3 the "ECO" mode only indicates cylinder pause. Since this is the gen 3 forum, and his post was in regards to a gen 3 van, I didn't go into nuances of the newer models.
 
Good. We now know the Eco light tells a different story on different generation Odysseys. The next question is - is there really any reason to "Muzzler" the newer Odysseys where the cylinder deactivation is imperceptible when it activates? Supposedly, Honda has now fixed the cylinder durability issue on these newer Odysseys, right?
My 08 Touring cylinder pause was always imperceptible--still is, though I've been muzzled since 135K and am now using a VCMTunerII which prevents VCM from activating altogether. The problems have not been fixed. The entire system is flawed and no matter what they do it will eventually give problems. GM has the same issue with their DoD engines with AFM. In that engine it damages the lifters which requires cylinder head removal to get the lifters out of the block. Often times it means a new engine. It's just a bad idea.

There are reports here all the time of gen 4 vans with carbon fouling causing misfires. I would Muzzle every engine that has this dumb system.
 
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