These disturbing revelations have tarnished Dr. Selye’s legacy as a major scientific investigator. His reputation is irrevocably stained. History would prove his tobacco-stress theories wrong. By the time of his death in 1982, mounting evidence proved that the scientific links between smoking and cancer and cardiovascular disease were irrefutable.
Smoke in the Rheum
There are few odors more noxious than the reek of cigarettes on a patient’s clothing, especially for those of us who toil in windowless spaces. So why do people smoke?
Among the 6,000 components of inhaled smoke is the highly addictive drug, nicotine. Inhaled nicotine quickly binds to acetylcholine type receptors leading to the release of significant amounts of the neurotransmitter dopamine in the nucleus accumbens, a key area of the brain that triggers dependency behavior.8 Dopamine appeared very early in the course of evolution and is involved in many functions that are essential for survival of the organism, such as attentiveness, motivation, learning and memorization. But most of all, dopamine is a key element in identifying natural rewards for the organism, so the urge to keep puffing can be overwhelming. One cigarette begets another. The habit becomes an addiction, with dire consequences for the smoker.
Although oncogenesis and vascular damage are considered to be the major hazards of smoking, there are other very significant effects that rheumatologists have recently identified. The first association between smoking and rheumatoid arthritis (RA) was a serendipitous finding in a study examining oral contraceptive use in RA patients.9 Subsequent studies demonstrated a two to fourfold increased risk of RA among smokers.
Work done in Sweden and duplicated elsewhere has demonstrated that smoking is strongly associated with an increased risk of RA in those patients expressing anticyclic citrullinated peptide (anti-CCP).10 Smoking increased the risk of RA in those subjects with disease-associated susceptibility genes (DRB1 shared epitope [SE] alleles) through a mechanism involving the generation of disease-specific autoantibodies (anti-CCP antibodies), because smoking has an effect only in those patients in whom immune tolerance to citrullinated peptides is lost. In fact, smoking had no effect on RA risk in anti-CCP-negative patients even if they bore a double copy of the DRB1 SE allele. This raises an intriguing question: Can the incidence of RA in individuals at high risk for developing the disease be reduced by convincing them to never smoke or to quit smoking altogether? The efficacy of this behavior modification is currently being probed in a long-term study led by several colleagues of mine at Brigham and Women’s Hospital in Boston.
