Tag Archives: Lung

Y Chromosome Loss: A Possible Factor in Lung Cancer Progression and Outcomes

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Insights into the impact of Y chromosome loss on lung cancer treatment outcomes may guide therapeutic choices.

Dakuku/Getty Images

Research indicates that men diagnosed with the predominant type of lung cancer are more likely to lose the Y chromosome in their cells. This phenomenon has both pros and cons; while it can prevent the immune system from combating tumors, it also enhances the effectiveness of standard anti-cancer therapies.

As men grow older, their cells frequently undergo mutations, leading to the loss of the Y chromosome. In immune cells, this loss is believed to correlate with heart disease and decreased life expectancy. Additionally, there is growing evidence that cancer cells that lose the Y chromosome may influence symptom progression, with bladder cancer being the most thoroughly researched case.

The loss of the Y chromosome is a binary occurrence—it either happens or it doesn’t. However, the health implications seem to depend significantly on the proportion of specific cells that lack the Y chromosome.

The recent study initiated by Dawn DeMeo and her team at Brigham and Women’s Hospital in Boston, Massachusetts, investigated how Y-chromosome genes are expressed in a publicly available dataset of lung adenocarcinoma samples. Lung adenocarcinoma, the most common form of lung cancer, originates from the mucus-producing cells lining the airways. Enhanced understanding of the relationship between Y loss and various health issues has motivated researchers to delve deeper into gene expression studies, according to DeMeo.

The team discovered that cancer cells, in contrast to healthy lung and immune cells, often lack the Y chromosome. This occurrence is independent of whether the tissue donor is a smoker—despite smoking being linked to lung cancer and Y chromosome loss.

The loss of Y chromosomes appears to accumulate over time. “Certain groups demonstrate a higher rate of Y chromosome loss across a greater number of cells, and we observe significant Y chromosome loss in a large fraction of tumors,” stated John Quackenbush from Harvard University.

To comprehend the reasons behind this accumulation, researchers examined other genetic alterations in Y-negative cells. They found that the loss of a common set of antigens produced by cancer cells correlates with diminished expression levels. These antigens usually notify immune T cells that cancer cells are abnormal and should be targeted. The decreased expression allows Y-negative cancer cells to proliferate unchecked.

“This implies that as tumor cells lose their Y chromosome, they become increasingly adept at evading immune surveillance, suggesting a selection of tumor cells that escape immune detection,” Quackenbush explained. T cell counts were consistently lower in samples with Y loss compared to those retaining the Y chromosome.

Positive findings emerged when researchers analyzed data from 832 lung adenocarcinoma patients treated with the immune checkpoint inhibitor pembrolizumab, a medication designed to restore the body’s immune response against tumors by reversing T-cell suppression. The analysis confirmed that Y chromosome loss was linked to improved treatment outcomes.

“Patients experiencing LOY [loss of Y] are more responsive to checkpoint inhibitors,” noted Dan Theodorescu from the University of Arizona, who found similar results in bladder cancer, establishing validation against an entirely different dataset.

However, while loss of the Y chromosome is linked to shorter life expectancies for men compared to women, existing data suggests it does not impact survival in patients with lung adenocarcinoma. Further research is needed to explore how the effects of such mutations influence survival across different cancer types, according to Theodorescu. As our understanding advances, he believes that loss of Y could eventually serve as a biomarker for clinical decision-making.

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Source: www.newscientist.com

Lung Inflammation May Increase Memory Retention of Traumatic Events

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Airway inflammation can arise from smoking or air pollution exposure

Lysenko Andrii/Shutterstock

Severe airway inflammation hampers the ability of mice to discern when dangerous situations are no longer a threat, indicating that lung conditions may influence emotions and behaviors. This connection between lung health and brain function could clarify why a small number of individuals who undergo trauma develop post-traumatic stress disorder (PTSD).

“While many people encounter trauma, only 5-10% ultimately develop PTSD,” explains Renu Sah from the University of Cincinnati in Ohio. Prior research has indicated that lung inflammation might be a contributing factor. For instance, individuals with PTSD are approximately eight times more likely to have asthma.

Sah and her team delved deeper into the correlation by observing eight mice exhibiting severe asthma-like symptoms. Their lungs were exposed to mites, inducing an allergic response and subsequent inflammation. Three days afterward, the mice were placed in cages and subjected to three mild electric shocks.

Over the subsequent six days, researchers returned the mice to the cage for five minutes daily, monitoring the duration they stood frozen in fear. On average, these mice were immobilized for about 40% of the final session, which was twice as long compared to another group of 11 mice without lung inflammation who faced the same electrocution.

The two groups did not exhibit differences in fear response the day after the shocks. However, the first group’s prolonged fear response after several days suggests that significant airway inflammation hampers the brain’s ability to recognize when a threat has subsided. “In PTSD patients, this process is dysfunctional, leading to persistent fear memories,” Sah elucidates.

The experiment was replicated with another set of mice experiencing severe lung inflammation, but this time, a medication inhibiting an inflammatory molecule called interleukin-17a was administered. During their final session in the previously shocked cage, these mice displayed about half the freezing response of those that did not receive the medication.

Further analysis revealed that immune cells in brain regions known as subcutaneous organs have receptors for this inflammatory molecule. Unlike most brain areas, subcutaneous organs lack a blood-brain barrier, a protective layer that limits substance exchange between blood and neurons. Consequently, it serves as a “window to the brain,” allowing it to monitor bodily changes and respond accordingly, according to Sah.

The team discovered that immune cells in this region sense inflammatory signals from the lungs, activating adjacent neurons that relay information to the cerebral cortex, a brain region associated with threat recognition.

Using a specialized compound known as chemogenetics, researchers inhibited this signaling pathway in mice with severe lung inflammation, resulting in a notable decrease in their freezing behavior post-shock.

“In essence, severe lung inflammation can impact higher cognitive functions and the ability to navigate traumatic experiences,” asserts Sah. She posits that similar pathways likely exist in humans, as the brain circuits regulating fear are comparable across species.

Other studies suggest that chronic psychological stress diminishes immune responses. Sah speculates that a heightened immune response, in turn, impairs cognitive functions such as the recognition of a threat’s resolution, possibly due to the body reallocating resources from the brain to combat lung issues.

“This research is crucial for understanding the connection between the body and mind,” states Douglas Vanderbilt from Los Angeles Children’s Hospital. He further discusses how his research indicated that children with severe asthma exhibit more pronounced PTSD symptoms. “What we’re uncovering suggests that these brain-body interactions are intricate, so this is likely not the only pathway,” he notes, pointing out that psychological stress from asthma attacks could also influence PTSD risk.

Sah emphasizes that this pathway might vary in women, as only male mice were utilized in her study, suggesting potential differences across genders that warrant additional investigation.

Ultimately, these discoveries may enhance our ability to identify individuals more susceptible to PTSD. For instance, medical professionals might consider screening children with severe asthma for mental health issues, as proposed by Vanderbilt. He further suggests that this line of research could lead to innovative PTSD treatments, such as immunotherapy aimed at reducing inflammation.

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Source: www.newscientist.com

COVID-19 and Flu Could Reactivate Dormant Lung Cancer Cells

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Lung tissue samples from mice, depicting cells (blue), cancerous cells (green), and proliferation markers (magenta)

Bryan Johnson

Respiratory viruses are capable of triggering the growth of dormant cancer cells that have metastasized to the lungs from other body areas. Infectious diseases, such as influenza, can instigate an inflammatory response that aids the immune system in combating pathogens, yet they may also adversely influence cancer progression.

Cancer fatalities frequently result from tumor cells migrating from their primary sites. These cells may remain dormant in new locations for extended periods—potentially years or decades—before forming detectable tumors.

While it is uncertain if these cells will eventually proliferate, previous studies have suggested that once cancer cells infiltrate the lungs, inflammation induced by respiratory virus infections might play a significant role. “Nevertheless, no comprehensive research has been conducted to establish a clear cause-and-effect relationship,” notes James DeGregori from the University of Colorado.

To address this research gap, DeGregori and his team employed genetically modified mice to develop tumors in their mammary glands. By two months of age, each mouse had developed a mammary tumor and fewer than ten dormant cancer cells in their lungs.

Subsequently, the researchers infected half of the mice with the H1N1 influenza strain, commonly referred to as swine flu, causing illness for approximately two weeks. During the nine days following the infection, the number of lung cancer cells surged by 100-fold, whereas uninfected mice exhibited minimal changes.

In complementary experiments, the team discovered that the SARS-CoV-2 virus, responsible for COVID-19, led to a tenfold increase in cancer cell numbers in the mice’s lungs, again with no significant alterations in uninfected counterparts.

The researchers hypothesized that this expansion occurred due to viral infections elevating the levels of inflammatory molecules known as IL-6.

To investigate this hypothesis, they conducted further experiments with genetically modified mice deficient in IL-6 and found significantly fewer lung cancer cells compared to typical mice with normal IL-6 levels.

Another experiment suggested that IL-6 seemed to rejuvenate dormant cancer cells that had already migrated to the lungs instead of promoting the dissemination of these cells from the breasts.

However, IL-6 levels wane when the infection subsides. At this juncture, the researchers observed that cancer cells in the mouse lungs had ceased to proliferate but had acquired alterations in gene expression typically associated with tumor metastasis, according to DeGregori.

These findings suggest a potential impact on individuals with undetected levels of cancer cells in the lungs who are believed to be in remission, as stated by Anne Zeuner at the National Institutes of Health in Rome, Italy.

To determine the relevance of these findings to humans, researchers analyzed health records from 36,800 women in the U.S. diagnosed with breast cancer before the COVID-19 pandemic, who were thought to be non-metastatic.

Women who tested positive during the initial three years of the outbreak were significantly more likely to receive a diagnosis of secondary lung cancer in that timeframe. However, some women may have avoided testing due to asymptomatic infections, while others might not have sought tests, thereby complicating the validation of this finding, notes DeGregori.

Further research is necessary to corroborate these findings and explore the interactions between various respiratory viruses and cancer types, according to Zeuner. “Individual factors are likely to significantly influence the relationship between respiratory infections and cancer recurrence,” she adds.

The research focused solely on swine flu and SARS-CoV-2, but DeGregori expresses hope that a spectrum of viruses will exhibit similar behaviors, as many are known to elevate IL-6 levels. He also underscores the importance of vaccination, stating, “As a cancer survivor, I would ensure I am protected against common respiratory viruses like influenza and COVID-19,” remarks DeGregori.

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Source: www.newscientist.com

New Study Shows Common Kitchen Worktop Material Can Lead to Irreversible Lung Disease

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Doctors are calling for a ban on artificial stone, a popular material used for kitchen worktops, following the confirmation of eight cases of artificial stone silicosis in the UK for the first time.

Also known as engineered or reconstituted stone, artificial stone has gained popularity for its aesthetics and durability over the last two decades. However, a new report published in the British Journal of Construction highlights the serious health risks posed by its high silica content, which exceeds 90% compared to 3% in marble and 30% in granite.

“Silicosis is a progressive lung disease caused by inhaling crystalline silica dust,” said Dr. Patrick Howlett, a spokesperson for BBC Science Focus. “The risk of developing silicosis is significantly higher for workers in the artificial stone industry compared to those with chronic respiratory conditions.”

“Various industries expose individuals to silicosis, including mining, pottery, cement work, and now artificial stone fabrication. Prolonged exposure to low levels of silica dust can lead to the development of silicosis over time,” added Dr. Howlett.

All eight affected individuals were male, with an average age of 34, and most worked for small businesses with fewer than 10 employees. Poor safety practices, such as inadequate respiratory protection and ventilation systems, were reported by workers during cutting and grinding operations.

The report’s authors emphasized the need for national guidelines and better enforcement to protect workers from artificial stone silicosis. They highlighted the urgent need for early detection of cases and preventative measures to avoid a potential epidemic.

Since 2010, cases of artificial stone silicosis have been reported worldwide, but the UK confirmed its first cases in mid-2023. California has identified nearly 100 cases of silicosis among countertop workers, prompting the adoption of new regulations to safeguard workers.

Australia has already banned the use of artificial stone as of July 2024, aiming to eliminate the health risks associated with its production and installation.

In related editorials, Dr. Christopher Barber and researchers from Sheffield Teaching Hospitals NHS Foundation Trust drew parallels between artificial stone silicosis and historical occupational health crises, urging stricter regulations and enforcement to protect workers.

Experts are currently reviewing exposure limits for crystalline silica dust in the UK, with a focus on mitigating the risks associated with artificial stone worktops. Silicosis remains a significant concern for clinicians and researchers in the occupational health field.

About our experts

Patrick Howlett: An MRC Clinical Research Fellow at the National Heart and Lung Institute, Imperial College London, focusing on silicosis and tuberculosis among small-scale miners in Tanzania.

Christopher Barber: A leading expert in occupational and environmental lung disease, serving as a medical advisor to the UK Health and Safety Executive and conducting extensive research in the field.

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Source: www.sciencefocus.com

Lung Association finds that 131 million Americans live in areas with unhealthy pollution levels

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Nearly 40% of Americans live in areas with unhealthy levels of air pollution, and the U.S. is set to regress in air-cleaning progress as the effects of climate change intensify, according to a new report from the American Lung Association. It’s coming. The group’s report, its 25th annual analysis of the nation’s “state of the air,” estimates that between 2020 and 2022, 131 million people will live in areas with unhealthy levels of air pollution. It turned out that it was. This number is an increase of nearly 12 million people from the previous survey a year ago. The report also found that people in the United States are experiencing the most “very unhealthy” or “hazardous” air quality day in the study’s history. Katherine Pruitt, national senior director of clean air policy at the American Lung Association, said the process has been in place for decades through the Clean Air Act, a federal law passed in 1963 to regulate air pollution and set air quality standards. He said that the cleanup efforts that have been made are gradually being undermined by climate change.

“Climate change, including heat, drought and especially wildfires, is starting to undo some of the progress we’ve made,” Pruitt said. “It’s sad to know that so many people live with air quality that threatens their health.” Wildfires are a rapidly growing source of pollution that policymakers are struggling to address. Climate scientists predict that wildfire smoke will increase in the future as greenhouse gas emissions raise temperatures. The Lung Association’s analysis reached the same conclusion as a peer-reviewed study published last year in Nature. The study’s author, Marshall Burke, suggested that wildfire smoke has undone about 25% of the Clean Air Act’s progress.

“If you take a step back and think about what the root cause is, it’s the burning of fossil fuels,” says Dr. Lisa Patel, a pediatrician and clinical associate professor at Stanford Medicine Children’s Health. “We don’t have to be in this situation. We have the technology and the federal investment to harness renewable energy. What we need now is the political will.”

Each year, the “State of the Air” report analyzes air quality data from the past three years. This analysis focuses on ozone exposure and short-term and annual exposure to particulate pollution. The report issues a rating for each measure and summarizes the number of areas that passed or failed for each rating. According to the report, nearly 44 million people currently live in areas that do not meet all three criteria.Small particles are a serious concern because they can enter a person’s lungs, circulate in the bloodstream, and affect other organs. Although these particles are only a fraction of the size of a human hair, they have been shown to increase the risk of asthma, lung cancer, chronic lung disease, premature birth, and miscarriage. Patel, who is also executive director of the Medical Societies Consortium on Climate and Health, has noticed an increase in preterm births during wildfire seasons and is educating parents about how heat and smoke are risk factors during pregnancy. He said he has started giving advice.

“After several weeks of poor air quality, more people will become pregnant and give birth before 37 weeks,” Patel said, adding that parents may wonder whether their actions led to premature birth. He added that he often thinks about this. “When people ask me about the risk of premature birth, I say climate change. Heat and wildfires are both risk factors. They are not within your control.” Additionally, Patel said she has noticed that when wildfire smoke incidents occur in California, patients at her pediatric clinic often complain of nasal infections, eye irritation, and asthma exacerbations, among other ailments. Pruitt said concerns about particle pollution used to be concentrated in the industrial Midwest and Northeast. But in this report, for the first time, all 25 cities with the highest daily particle pollution are in the West. Most were in California.

“Early in our history, we had a lot of particulate pollution coming from coal-fired power plants, transportation sources, and industrial processes,” Pruitt said. “Particle pollution problems in the eastern United States are less severe because the Clean Air Act has cleaned up these sources. But Western countries, of course, have similar access to regulation and cleanup; We are also affected by climate change and wildfires.” Daniel Mendoza, an assistant professor of atmospheric science at the University of Utah, said many communities in Western states are dealing with acute, short-term pollution episodes rather than long-term chronic exposure. Scientists are still trying to figure out how much damage wildfire outbreaks cause compared to long-term exposure from industrial sources. “Not all bad air pollution is created equal,” Mendoza said. Pollution from traffic and industrial sources could continue to decline if the Environmental Protection Agency’s proposed stricter standards could be implemented.

Last year, the EPA proposed a rule that would require nearly all coal and large gas plants in the country to reduce or capture about 90% of their carbon emissions by 2038. In March this year, the agency introduced stricter rules to reduce tailpipe emissions from passenger cars. Another EPA policy aimed at curbing nitrogen oxide pollution that spreads across states was challenged in the U.S. Supreme Court. In 2022, the Supreme Court limited the government’s ability to use the Clean Air Act to reduce greenhouse gas emissions. There is one bright spot in this report. That means ozone pollution continues to improve dramatically. Compared to last year, about 2.4 million fewer people live in areas with unhealthy ozone pollution. Since this analysis was completed, wildfire smoke has gotten even worse.

Americans in 2023 inhaled more wildfire smoke than in any other year on record, Stanford University researchers found last year.

Source: www.nbcnews.com

Using Inhalable Nanoparticles to Treat COPD, a Chronic Lung Disease

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Chronic obstructive pulmonary disease affects the lungs

Sebastian Kauricki/Science Photo Library

Using inhalable nanoparticles to deliver drugs to the lungs could help treat chronic obstructive pulmonary disease (COPD). In mice with signs of the condition, treatment improved lung function and reduced inflammation.

COPD causes the airways in the lungs to gradually narrow and stiffen, blocking airflow and blocking mucus drainage. As a result, mucus builds up in the lungs, attracting bacterial pathogens that further worsen the disease.

This thick layer of mucus also traps drugs, making it difficult to treat infections. So, Zhu Junliang Researchers at China's Dongzhou University have developed inhalable nanoparticles that can penetrate mucus and deliver drugs deep into the lungs.

The researchers constructed hollow nanoparticles from porous silica and loaded them with an antibiotic called ceftazidime. A shell of negatively charged compounds surrounding the nanoparticles blocked the pores and prevented the antibiotic from leaking. This negative charge also helps the nanoparticles penetrate mucus. The slight acidity of the mucus then changes the charge on the shell from negative to positive, opening the pores and releasing the drug.

Researchers used an inhalation spray containing nanoparticles to treat bacterial lung infections in six mice with signs of COPD. A similar number of animals received antibiotics only.

On average, mice treated with nanoparticles had about 98 percent fewer pathogenic bacteria in their lungs compared to mice given antibiotics alone. They also had fewer inflammatory molecules in their lungs and less carbon dioxide in their blood, indicating better lung function.

These findings suggest that nanoparticles could improve drug delivery to people with COPD and other lung diseases such as cystic fibrosis, where thick mucus makes infections difficult to treat. It has said. vincent rotello from the University of Massachusetts Amherst was not involved in the study. However, it is unclear whether these nanoparticles are cleared from the lungs. “If you have a delivery system that accumulates over time, that's a problem,” he says.

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Source: www.newscientist.com