What do you regard as the lowest depth of misery? (Just to give you an idea, Proust's reply was 'To be separated from Mama.') I think that the lowest depth of misery ought to be distinguished from the highest pitch of anguish. In the lower depths come enforced idleness, sexual boredom, and/or impotence. At the highest pitch, the death of a friend or even the fear of the death of a child.
Impotence is one of the major hazards of cigarette smoking.
Intolerance is evidence of impotence.