How to avoid letters while searching pubmed portal? I am retrieving disease related articles from pPMC. Some of the articles contain letters starting with "Dear friends" , "Dear Editor", etc. Can these be considered valid articles? How to filter the search results so as to avoid letters while searching for research articles? 

PS: I have tried filtering by publication type. Options include 'letter' and 'comment' etc. but they don't seem to be working.
You are really asking two questions, a technical and a principal. As for the technical, let us assume your search is #1, then you can exclude letters by searching:

#1 NOT (letter[PT] OR comment*[PT])


Note the asterisk to also include the commentary publication type.

As to the other question; "Can these be considered valid articles?" - yes, they can! And in some cases, the information provided in comments can be as important or perhaps even more important than what is provided in the article commented on. So whether you should include them in your search highly depends on what the purpose of your search is. Are you getting a rough idea of the available literature? Then fine, exclude them. Are you doing a systematic literature review? Include them! There might be crucial information regarding data or conflicting findings. It should be possible to quickly (manually) exclude irrelevant letters.