Nationwide Problem: Serious Lung Infections Caused by Soil Fungi

Air Pollution Is Deadlier Than You Think

Air pollution is responsible for 8 million deaths a year globally, which is as many as tobacco. And air pollution isn't just causing lung cancer, it may cause other cancers too—including neck cancer and mesothelioma—and diseases such as cardiovascular disease, strokes, heart attacks, type 2 diabetes, and neurodegenerative disease. We urgently need public health measures to lower pollution levels.

In the lab, we've been studying how air pollution causes lung cancer. Recently, we've shown a close association between rising air pollution levels—specifically 2.5 micrometers particles (known as PM 2.5) from diesel exhaust and coal-fired power stations—and increasing incidence of lung cancer in patients who've never smoked. We were interested in understanding what the underlying mechanism is for this process. It's become apparent that it's very different from the way we normally understood how carcinogens—chemicals in the environment that cause cancer—usually act. Traditionally, we thought that chemicals in the environment caused cancer by mutating DNA. It turns out the air pollution doesn't mutate DNA. Instead, it creates an inflammatory response in a white cell called a macrophage. This cell releases an inflammatory mediator that can turn certain cells (those with a particular cancer-causing mutation) in the breathing apparatus of the lung into a cancer stem cell. In other words, the cancer-causing mutation and the air pollution work together in the right cell at the wrong time to initiate a cancer.

How does air pollution cause so many different clinical diseases? We don't yet know the answer to that. What we do know is that the macrophage takes up air pollutants. These particular particles are so large that they can't be digested by the cell. Instead, they remain in the cell until it dies. Because of this, throughout its life, the cell releases a sort of SOS signal—inflammatory mediators that communicate with other cells. This causes chronic long-term inflammation, which we speculate may be the central cause for the underlying pathologies associated with pollution, leading to damage to the pancreas, for example, or type-two diabetes, or damage to blood vessels, which results in strokes and heart attacks.

In London, authorities are increasing stringent mechanisms to control and curb air pollution—the yellow Ultra Low Emissions Zone, for example, is being extended. There's also an increasing move toward electric cars. That in itself won't eliminate the problem, however, because the air pollution doesn't just come from diesel and petrol exhausts. It also comes from car tires and brake dust. For instance, the levels of PM 2.5 particulates on the London Underground, which runs on electric trains, are particularly high. Also, in the winter, wood burners contribute to much higher levels of PM 2.5 particulates.

It's estimated that over 90 percent of the world's population lives in areas where the concentrations of PM 2.5 air pollutants are higher than the WHO recommended level of 5 micrograms per meter cubed. We need to make sure that individuals are aware of the risks to them by being exposed to high levels of pollution in urban areas. We need to walk more and we need to cycle more. And we need to redouble our efforts to try to control air pollution, limit exhaust fumes, and find cleaner fuels.

This article appears in the July/August 2023 edition of WIRED UK magazine.

What Causes A Spot On The Lung (or A Pulmonary Nodule)?

Persistent cough and spots on your lungs after a chest X-ray or CT scan may be signs of noncancerous pulmonary nodules. In some cases, though, more tests might be required to ensure the nodules are noncancerous.

A spot on the lungs usually refers to a pulmonary nodule. This is a small, round growth on the lungs that shows up as a white spot on image scans. Typically, these nodules are smaller than three 3 centimeters (cm) in diameter.

If your doctor sees a pulmonary nodule on a chest X-ray or CT scan, don't panic. Pulmonary nodules are common, and most are benign or noncancerous.

Nodules are found on up to half of all lung CT scans. When a pulmonary nodule is cancerous, the spot or growth is usually larger than 3 cm or has other characteristics like an irregular shape.

Noncancerous pulmonary nodules can develop from conditions that cause inflammation or scar tissue on the lungs. Possible causes include:

lung infections, such as pulmonary tuberculosis, which is caused by Mycobacterium tuberculosis

granulomas, which are small clumps of cells that grow because of inflammation

noninfectious diseases that cause noncancerous nodules, such as sarcoidosis and rheumatoid arthritis

fungal infections, such as valley fever or histoplasmosis, from inhalation of spores

neoplasms, which are abnormal growths that can be benign or cancerous

cancerous tumors, such as lung cancer, lymphoma, or sarcoma

metastatic tumors that spread from other parts of the body

The risk for cancer increases when:

Pulmonary nodules don't cause symptoms. You may have a nodule on your lungs for years and never know it.

If a spot on your lungs is cancerous, you may have symptoms related to the specific type of cancer. For example, growths caused by lung cancer may cause a persistent cough or breathing difficulties.

If your doctor believes a pulmonary nodule is cancerous, they may order more tests. Diagnostic testing used to confirm or rule out cancer includes:

Positron emission tomography (PET) scan: These imaging tests use radioactive glucose molecules to determine if the cells that make up the nodule are dividing rapidly.

Biopsy: Your doctor may order a biopsy, especially if the results of the PET scan are inconclusive. During this procedure, a tissue sample is removed from the nodule. It's then examined for cancer cells using a microscope.

Sometimes this is done by a needle biopsy that's inserted near the edge of your lung through the chest wall. Another option is a bronchoscopy where your doctor inserts a scope through the mouth or nose and passes it through your large airways to collect cells.

A pulmonary nodule may be first detected on a chest X-ray. After that, you may need further testing to better characterize the nodule to help determine if it's benign or cancerous.

Your doctor may request your medical history and your history of smoking. Additionally, your doctor needs to know if you've been exposed to secondhand smoke or environmental chemicals.

The first step of the process is examining the size and shape of the nodule. The bigger the nodule, and the more irregular the shape, the greater the risk of it being cancerous.

A CT scan can provide a clear image of the nodule and give more information about the shape, size, and location. If the results from a CT scan reveal that a nodule is small and smooth, your doctor may monitor the nodule over time to see if it changes in size or shape.

You'll have to repeat the CT scan a few times at regular intervals. If the nodule doesn't grow larger or change over a 2-year period, it's unlikely to be cancer.

In addition to a CT scan, your doctor may order a tuberculin skin test or more commonly an interferon gamma release assay (IGRA) to check for latent tuberculosis.

They may also request that your blood be drawn for additional tests to rule out other causes such as local fungal infections. These may include coccidioidomycosis (commonly known as valley fever) in the southwestern states like California and Arizona or histoplasmosis in the central and eastern states, especially in areas around the Ohio and Mississippi river valleys.

If a pulmonary nodule is cancerous, your doctor will determine the best course of treatment based on the stage and type of cancer.

Treatment options can include radiation or chemotherapy to kill and prevent the spread of cancer cells. Treatment may also include surgery to remove the tumor.

In most cases, pulmonary nodules can't be prevented. However, quitting smoking is the best way to help prevent cancerous pulmonary nodules. Early screening may help for those who are at high risk for lung cancer. If the nodules are detected early, then it's more likely to be treated successfully. Low-dose computer tomography scans can help find these nodules before people have cancer symptoms.

In most cases, your doctor can safely say that the nodule isn't cancer if it doesn't increase in size or develop points, lobes, or other irregularities over a period of 2 to 5 years. At that point, if you are not at high risk for lung cancer, there's no need for further testing.

If the nodule is cancerous, and there's only one, it's likely still in the early stages when treatment offers the best chance of a cure.

In some cases, a cancerous pulmonary nodule represents a metastasis from a cancer that began in another part of the body. If that's the case, treatment will depend on the original cancer.

Other causes of lung nodules are infections, inflammatory conditions, and benign tumors or cysts. If you have any of these underlying conditions, your doctor may recommend treatment that will depend on the underlying condition.

Breakdown Of 'protective Mechanisms' Can Drive Lung Cancer Development

Loss of two key "protector" proteins initiates epigenetic changes that transform healthy lung cells into cancerous ones, according to new research from Van Andel Institute scientists.

The findings, published in Cancer Research, are among the first to demonstrate a wholly epigenetic origin for cancer cells and may have implications for future cancer treatment and prevention strategies.

"Our findings shed new light on the importance of epigenetics in cancer development," said Gerd Pfeifer, Ph.D., a VAI professor and senior study author. "In theory, it is easier to target epigenetics than genetics in cancer treatment, which opens new possibilities for therapeutic development."

Cancers largely arise from mutations to the DNA sequence, which disrupts the genetic instructions required for normal function. The resulting errors allow malignant cells to flourish and spread, crowding out healthy cells and causing illness.

Since the 1980s, however, scientists have recognized the role of another critical regulatory system in cancer development: epigenetics.

Epigenetic mechanisms govern whether genes are "on" or "off" by adding or removing chemical tags called methyl groups. Inappropriate methylation wreaks havoc by activating or silencing genes at the wrong time; for example, a gene that regulates cell death may be erroneously switched off, allowing cancerous cells to replicate unchecked.

Although epigenetic mechanisms are now recognized as central players in cancer, exactly how these processes work has remained unclear.

To find answers, Pfeifer and his colleagues focused on two proteins that protect more than 4,000 genes from inappropriate methylation: TET and RYBP.

Their research, which was conducted in lab models of lung cancer, revealed that loss of either TET or RYBP on their own has only minimal to moderate impact. Loss of both, however, leads to widespread aberrant methylation—and, subsequently, cancer.

Their findings suggest the combination of RYBP and TET is crucial to preserving normal function. RYBP helps maintain a massive protein complex called PRC1, which shields thousands of genes from methylation. TET proteins protect the genome by removing methylation when it is not appropriate. When these protective mechanisms break down in tandem, methylation spins out of control.

Going forward, Pfeifer plans to explore this process in other cancer types to investigate whether it's a phenomenon restricted to lung cells or if it has wider applicability. If the combined loss of RYBP and TET in other cell types has the same result, it could have broad implications for our understanding of cancer and development of new therapies.

More information: Wei Cui et al, Deficiency of the Polycomb protein RYBP and TET methylcytosine oxidases promotes extensive CpG island hypermethylation and malignant transformation, Cancer Research (2023). DOI: 10.1158/0008-5472.CAN-23-0269

Citation: Breakdown of 'protective mechanisms' can drive lung cancer development (2023, June 22) retrieved 30 June 2023 from https://medicalxpress.Com/news/2023-06-breakdown-mechanisms-lung-cancer.Html

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