Smoker’s cough, bronchitis and chronic obstructive pulmonary disease (COPD) – what else do you reckon are the typical manifestations of chronic cigarette smoking? You now want to add “reduced tendency of lungs to self-heal” to the list as well because this is what the latest study from German Center for Lung Research (DZL) proves.

About 10-12% of adults in Germany suffer from the smoking-induced COPD. COPD is an umbrella term for lung diseases that make it difficult to breathe. Unlike asthma, which is almost never progressive, COPD is always progressive and is characterized by the gradual damage to the air sacs (emphysema), chronic inflammation of bronchi (bronchitis) and some degree of permanent damage and enlargement of bronchi (bronchiectasis).

Per experts, COPD costs six billion euros to the country. Scientists in Europe and around the world are investigating the factors that contribute to and aggravate COPD and the measures and adjustments that can be made to prevent damage.

One such approach is the lungs’ ability to self-heal, which, unfortunately, does not occur in COPD.

Dr. Melanie Königshoff, head of the Lung Repair and Regeneration (LRR) Research Unit at the Comprehensive Pneumology Center (CPC) at Helmholtz Zentrum München says,

“In healthy patients, the so-called WNT/beta-catenin signaling pathway is responsible for the lung’s homeostasis. Until now, it was not clear why it was silenced in patients with COPD.”

Dr. Melanie and colleagues have been investigating the role of lung self-healing in COPD for years and have found Frizzled molecules (Frizzled-4) to play the key role.

“Frizzled 4 is a receptor molecule that sits on the surface of lung cells, where it regulates their self-renewal via WNT/beta-catenin,” says Wioletta Skronska-Wasek, doctoral candidate at the LRR and the leading author of the study. “However if the cells are exposed to cigarette smoke, Frizzled 4 disappears from the surface and cell growth comes to a halt.”

The study typically began with the observation that the lung tissue of COPD patients, particularly those who are smokers, have fewer Frizzled-4 molecule receptors.

In the next step, the researchers studied the observation in cell culture and model systems and noticed that the inhibition of Frizzled-4 signaling led to reduced WNT/beta-catenin activity. A reduced number of Frizzled-4 molecules meant reduced repair capacity and wound healing.

The researchers further noticed that if Frizzled-4 molecule receptors were completely absent, it would result in the loss of certain proteins that constitute lung tissue, including the essential IGF1, fibulin and elastin. In fact, a lack of receptors means the lungs cannot repair themselves and it would result in reduced lung elasticity.

The lung’s elasticity is essential for normal breathing process. If the lung’s elasticity is damaged, the respiratory system gets badly affected making it difficult for the patient to breathe. Shortness of breath is the typical manifestation of asthma and COPD.

To validate their finding, the researchers artificially stimulated production of Frizzled-4 levels in cell culture. The increase in the molecule receptors led to the production of proteins essential for lung function. An increase in the essential proteins reversed the blocked repair process.

The researchers concluded that activation of Frizzled-4 can lead to lung repair in smokers who are COPD patients by restoring WNT/beta-catenin signaling pathway.

Interesting as the finding is, it is the first step in the right direction. Further research is warranted to confirm the findings of the study as well as to develop new therapies for irreversible and lethal COPD.

The study was published on March 2, 2017 in the American Journal of Respiratory and Critical Care Medicine.