Reversing smoke-induced damage and disease in the lung

"It has not been very clear what causes the disease and there has been no therapy to stop or reverse lung destruction in emphysema," said Norbert Weissman of the University of Giessen Lung Center in Germany. "There have really been no new concepts about therapy in the last 20 years."

COPD, including chronic bronchitis and emphysema, is expected to become the third-greatest cause of death worldwide by the year 2020.

In addition to airway inflammation and decreased of respiratory function, COPD is often accompanied by pulmonary hypertension, which is essentially high blood pressure in the lungs. Whether this condition was a cause or a consequence of COPD was not known.

Now, with powerful mouse models of COPD, Weissman and colleagues provide evidence that changes to the pulmonary blood vessels and the development of high blood pressure precede the development of emphysema. They further trace those effects to an inducible form of an enzyme known as nitric oxide synthase (iNOS), which catalyzes the formation of nitric oxide.

Nitric oxide (NO) and the nitric oxide system are important for opening up blood vessels and maintaining vascular tone. When nitric oxide levels grow too high, however, the molecule can undergo a chemical reaction forming aggressive peroxynitrite.

"Simply put, peroxynitrite can modify protein functions, leading to the destruction of lung tissue," Weissman said.

It appears this is exactly what happens in the development of emphysema. Mice lacking the iNOS enzyme were protected from both emphysema and pulmonary hypertension. Importantly, existing pharmacological agents can block iNOS activity, and mice treated with one of these drugs were protected from COPD-like changes to their lung vasculature. Treatment with the inhibitor also successfully reversed the course of the disease in the mice.

I have also been diagnosed with COPD and asthma and told the PF is not far off the horizon with everything I have gone through the last 50+ yrs, and I stuck with the occasional cigar and shot every once in a great while.

IPF is bizarre because they don't know what causes it and are grasping at straws to find out.

A few years ago a study was done on people like me with IPF and heavy smokers with known PF an they conclude the heavy smokers generally live longer.

I have been on ESBRIET(pirfenidone) for 4 years and I am doing OK at 84,inspite of a lot of other medical problems.

Everybody have a Merry Christmas. I intend too, and am looking forward to a family gathering tonight. -Tom

The answer is apparently at least a small “yes.” My tea, chocolate powder, grape seed extract, etc. could be encouraging an overproduction of NO that readily combines with Superoxide when in close proximity in the bloodstream, creating a super oxidant called “peroxynitrite.” From a study link I posted in an earlier post states:

“Neither superoxide nor NO is particularly toxic in vivo because there are efficient means to minimize their accumulation (72, 74). Superoxide is rapidly removed by high concentrations of scavenging enzymes called superoxide dismutases (SOD) with distinct isoenzymes located in the mitochondria, cytoplasm, and extracellular compartments. NO is rapidly removed by its rapid diffusion through tissues into red blood cells (161, 639), where it is rapidly converted to nitrate by reaction with oxyhemoglobin (Fig. 1). This limits the biological half-life of NO in vivo to less than a second, whereas the concentrations of NO relevant for cellular signaling can persist in phosphate-buffered saline for an hour (79). However, when both superoxide and NO are synthesized within a few cell diameters of each other, they will combine spontaneously to form peroxynitrite by a diffusion-limited reaction (583). In essence, every time NO and superoxide collide, they form peroxynitrite. No enzyme is required to form peroxynitrite because no enzyme can possibly catalyze any reaction as fast. NO is the only known biological molecule that reacts faster with superoxide and is produced in high enough concentrations to outcompete endogenous levels of superoxide dismutase. Consequently, the kinetics and thermodynamics of the reaction of superoxide with NO make the formation of peroxynitrite inevitable in vivo.”

In essence, having “more” NO means a higher than “normal” conversion rate of NO to peroxynitrite, which is the truly concerning problem, and not NO under normal circumstances.

Interesting.

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