Zinc reverses lung damage and greatly improves patient survival.

Researchers have found that zinc, a common mineral, can reverse lung damage and improve patient survival. (CREDIT: Creative Commons)

Researchers at the Women’s Guild Lung Institute in Cedars-Sinai have found that zinc, a common mineral, can reverse lung damage and improve survival for patients with a fatal age-related disease known as idiopathic pulmonary fibrosis (IPF).

Their findings, published in The Journal of Clinical Investigation, could change the way we treat patients with this disease, which most often affects people over 50 years of age.

“This study could be a game-changer,” said Paul Noble, MD, chair of medicine, director of the Women’sGuild Lung Institute and co-author of the study. “We have identified the underlying cause of IPF-associated lung injury and a potential therapeutic target that could restore the lung’s ability to heal itself.”

Idiopathic pulmonary fibrosis, or IPF, affects 100,000 people in the US and has no known cause. The condition, which leads to scarring of the lungs, called fibrosis, and progressive difficulty in breathing is incurable, and most patients die or need a lung transplant within three to five years of diagnosis. The incidence of IPF increases dramatically with age and affects men more often than women.

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In this study, Cedars-Sinai researchers found that the stem cells that line the air sacs in the lungs of IPF patients lose their ability to process zinc, which is known to play a role in cell growth and healing of damaged tissues.

Zinc deficiency impairs the ability of cells called alveolar epithelial cells type 2 (AEC2) to regenerate. Restoring this ability through a molecular pathway that the researchers traced in their experiments could lead to a therapy that reverses IPF-related lung damage. The research team also created a model of IPF in lab mice that can be used to develop new treatments.

The researchers first analyzed the AEC2 of healthy lungs as well as those of patients with IPF. They found that lung cells with IPF lack a protein called zinc transporter 8 (ZIP8), which draws zinc into the cell.

In experiments with organoids — miniature, simplified versions of organs grown in a dish from patient tissues — they also found that cells lacking the ZIP8 protein could not regenerate and form colonies as healthy cells should.

“Organoids with AEC2 cells that had the ZIP8 transporter were able to attract zinc into the cells and then were able to regenerate and form more colonies,” said Carol Liang, MD, assistant professor of medicine and first author of the study. “Cells without ZIP8 couldn’t take in zinc, so they formed fewer colonies. So we determined that it is ZIP8 that allows cells to use zinc.”

The researchers also used drugs and deletion of the ZIP8 gene in AEC2 mice to mimic IPF in lab mice. When they fed these mice a diet that included zinc supplements, their fibrosis improved.

Graphical abstract of how zinc works in the lungs. In young and healthy AEC2, a sufficient amount of ZIP8 provides sufficient levels of intracellular zinc, SIRT1 activity, and the ability to renew AEC2. However, in old AEC2 and AEC2 IPF, ZIP8 downregulation leads to intracellular zinc deficiency and defective SIRT1 activity, which impairs AEC2 turnover. In addition, enzymes that regulate NAD+ synthesis were downregulated in IPF AEC2, which further exacerbated the disruption of SIRT1. Therefore, optimal combinations of zinc activation, NAD+ and SIRT1 can restore AEC2 integrity and mitigate fibrosis. MT, metallothionein. (TEACHING: Journal of Clinical Research)

“There have been few detailed studies on how zinc works in the lungs,” said Dianhua Jiang, MD, professor of medicine at Cedars-Sinai and co-author of the study. “Our company is the first to define in detail the role of zinc in lung biology, especially in IPF. It was particularly interesting to find that zinc regulates the production of two other key tissue regeneration molecules, nicotinamide adenine dinucleotide (NAD+) and sirtuin1. These molecules are involved in tissue regeneration and aging.”

More research is needed to determine why ZIP8 loss occurs in lung cells and whether zinc supplementation, alone or in combination with NAD+ and Sirtuin1 activators, will help activate the lung repair response, reverse lung damage in patients with this disease. Liang said, adding that answering these questions could help thousands of patients.

The role of zinc dysregulation in lung diseases. (Credit: MDPI.com)

The aim is to design a clinical trial to determine if intervention in the ZIP8/NAD+/Sirtuin1 pathway can improve lung function in IPF.

“The cause of IPF is unknown, but aging is an important factor,” Liang said. “The population as a whole is aging and the incidence is increasing. We need to find a cure because we have more and more patients every year.”

What are the stages of lung cancer?

According to the Cleveland Clinic, the stage of cancer is usually determined by the size of the initial tumor, how far or deep it has invaded surrounding tissues, and whether it has spread to the lymph nodes or other organs. Each type of cancer has its own staging guidelines.

Staging of lung cancer

Each stage has several combinations of size and distribution that can fall into this category. For example, the primary tumor in stage III cancer may be smaller than in stage II cancer, but other factors place it at a more advanced stage. General stage of lung cancer:

• Stage 0 (in-situ): The cancer is in the upper lining of the lung or bronchi. It has not spread to other parts of the lung or beyond the lung.

• Stage I: The cancer has not spread beyond the lung.

• Stage II: The cancer is larger than stage I, has spread to lymph nodes inside the lung, or has more than one tumor in one lobe of the lung.

• Stage III: The cancer is larger than stage II, has spread to nearby lymph nodes or structures, or has more than one tumor in different lobes of the same lung.

• Stage IV: Cancer has spread to another lung, fluid around the lung, fluid around the heart, or distant organs.

Limited or extensive stage

Although health care providers currently use stages I through IV to treat small cell lung cancer, you may also hear it described as limited or extensive stage. This is based on whether the area can be treated with a single radiation field.

• Limited stage SCLC is limited to one lung and can sometimes be in lymph nodes in the middle of the chest or above the collarbone on the same side.

• Extensive stage SCLC spreads to one lung or spreads to the other lung, lymph nodes on the opposite side of the lung, or to other parts of the body.

What are the symptoms of lung cancer?

According to the Cleveland Clinic, most of the symptoms of lung cancer are similar to those of other, less serious diseases. Many people do not have symptoms until the disease has developed, but some people develop symptoms early. For those who experience symptoms, it may be just one or more of these:

• A cough that doesn’t go away or gets worse over time.

• Difficulty breathing or shortness of breath (shortness of breath).

• Pain or discomfort in the chest.

• Wheezing breath.

• Coughing up blood (hemoptysis).

• Hoarseness.

• Loss of appetite.

• Unexplained weight loss.

• Unexplained tiredness (fatigue).

• Shoulder pain.

• Swelling of the face, neck, arms, or upper chest (superior vena cava syndrome).

• Small pupil and drooping eyelid in one eye with little or no sweating on that side of the face (Horner’s syndrome).

Lung Cancer Risk Factors

While there are many factors that can increase your risk of developing lung cancer, smoking any type of tobacco product, including cigarettes, cigars, or pipes, is the biggest risk factor. Experts estimate that 80% of lung cancer deaths are related to smoking.

Other risk factors include:

• Exposure to secondhand smoke.

• Exposure to harmful substances such as air pollution, radon, asbestos, uranium, diesel exhaust, silica, coal products and others.

• Previous radiation therapy to the breast (for example, for breast cancer or lymphoma).

• Having a family history of lung cancer.

For more science news, visit our New Discoveries section at The bright side of the news.

Note: Materials provided by Cedars-Sinai Medical Center above. Content can be edited for style and length.

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