The research team focused on the distal lung because it is both the site of gas exchange and the most vulnerable part of the respiratory system. Working with human lung epithelial and endothelial cells, as well as precision-cut human lung tissue, the investigators exposed these samples to e-cigarette vapor alone and, in separate experiments, exposed them to vapor followed by infection with a respiratory virus. Within just 24 hours of vapor exposure, the researchers observed damage to the protective barrier of the distal lung, the layer of cells that keeps the airspaces sealed and selectively controls what passes between the air and the blood.

The early cellular response was broad. Vapor exposure triggered cellular stress, impaired autophagy, the internal recycling process cells use to clear damaged components, slowed cell growth and repair, and increased cell death. Each of these processes is central to maintaining the integrity of the alveolar-capillary barrier. When barrier function is compromised, fluid and immune cells can leak into the airspaces, and the lung becomes less able to perform its essential task of transferring oxygen while keeping airborne threats out of the circulation.

Perhaps the most striking result was the persistence of injury. Signs of lung stress remained detectable 10 days after a five-day exposure period had ended. The team documented lasting changes in barrier function, tissue remodeling, and Th1 immunity, a branch of the adaptive immune system that is critical for mounting effective responses against viral infections. Tissue remodeling in the distal lung is a particular concern because, if sustained, it can interfere with the fine architecture of the alveoli and contribute to chronic scarring and reduced lung capacity.

The antiviral consequences were equally significant. In the preclinical models, prior vaping exposure increased the viral burden of SARS-CoV-2 following infection and suppressed several antiviral genes. These genes encode proteins that detect viral genetic material, interfere with viral replication, and recruit immune cells to infected tissue. Their suppression means that when a virus arrives, the lung’s early-warning and containment systems are blunted, potentially allowing the pathogen to replicate to higher levels before an effective immune response can be organized.

Senior author Irina Petrache, MD, a pulmonologist and chief of the Division of Pulmonary, Critical Care and Sleep Medicine at National Jewish Health, summarized the implications of the work. Our findings suggest that even short-term vaping exposure can initiate injury in the deepest and most delicate regions of the lung, she said. Importantly, some effects persisted after exposure ended and altered the immune response to a subsequent viral infection. That combination, acute injury followed by lingering immune alteration, is what distinguishes the current findings from earlier work that focused mainly on the immediate effects of vapor exposure.

The study helps explain, at a mechanistic level, why epidemiological and clinical observations have repeatedly linked vaping to lung injury and to greater susceptibility to respiratory infections. Rather than a single toxic event, the research points to a sequence: vapor exposure damages the barrier and stresses the cells, the cells’ repair machinery is slowed, and the immune programming of the tissue shifts in ways that reduce antiviral readiness. Repeated cycles of exposure, the researchers noted, could potentially contribute to chronic lung disease by sustaining cellular injury and disrupting normal repair processes over time.

Technically, the use of precision-cut human lung tissue is an important strength of the study. Unlike isolated cell lines, precision-cut slices preserve the three-dimensional structure of the distal lung, including the relationships between epithelial cells, endothelial cells, and the extracellular matrix that supports them. This means the observed barrier disruption and remodeling reflect interactions among multiple cell types rather than the response of a single cell population. The parallel use of epithelial and endothelial cultures allowed the team to separate contributions from the airside and bloodside linings of the barrier, both of which showed evidence of stress and dysfunction after vapor exposure.

The authors emphasize that the findings will need to be confirmed in future studies in people. Preclinical models, even those built from human cells and tissue, cannot fully capture the complexity of vaping in real-world users, who differ in the devices they use, the e-liquids they inhale, the frequency and depth of their puffing, and their baseline health. Human exposure histories are also far more variable than a controlled five-day exposure regimen. Nonetheless, the demonstration that a brief exposure window can produce measurable and persistent changes in human distal lung tissue provides a biological rationale for concern that complements the population-level associations reported in prior research.

For public health, the message is that risk is not confined to long-term, heavy vaping. If days of exposure can alter barrier integrity, autophagy, repair capacity, and Th1 antiviral immunity in human distal lung tissue, then occasional or new users may not be as protected as commonly assumed, particularly during respiratory virus season. The study also offers researchers concrete mechanistic targets, including barrier repair pathways, autophagy regulation, and antiviral gene expression, that could guide future investigations into which components of e-cigarette vapor drive injury and whether the effects are reversible once exposure stops. As e-cigarette use continues to evolve, work of this kind provides the cellular-level evidence needed to assess its consequences for lung health with greater precision.

Subject of Research: Effects of brief e-cigarette vapor exposure on human distal lung tissue and antiviral immune defenses

Article Title: Even brief e-cigarette use can cause lasting lung damage and weaken defenses against respiratory viruses, study finds

Article References: Even brief e-cigarette use can cause lasting lung damage and weaken defenses against respiratory viruses, study finds. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: e-cigarettes, vaping, lung injury, distal lung, epithelial barrier, autophagy, Th1 immunity, SARS-CoV-2, antiviral genes, JCI Insight, National Jewish Health, respiratory infection

Every cell in a man’s body normally carries one X chromosome and one Y chromosome. The phenomenon known as loss of Y, sometimes called mosaic loss of the Y chromosome, occurs when individual cells drop their Y chromosome as they divide over the course of a lifetime. Previous studies established that this change is widespread in men as they age and that when it occurs in immune cells circulating in the blood it is associated with elevated risk of a range of diseases. What remained unknown was whether the same process was happening in solid organs, and if so, whether it had any relationship to the development of cancer in those organs.

The new study set out to answer that question systematically. Rather than looking at a single tissue type, the research team profiled Y chromosome loss across normal, precancerous and malignant tissue drawn from 11 major human organs. The scale of the effort was considerable. The investigators analyzed 1,000 tissue samples from 405 men and used an automated fluorescent imaging system to inspect more than 4.3 million individual cell nuclei. By measuring the ratio of Y to X chromosomes in each nucleus, they could quantify precisely how much of the chromosome had been lost in every region of tissue they examined.

The most striking findings came from a portion of the study focused on bladder tissue removed during cancer surgery. The researchers built detailed maps of these surgical specimens, charting exactly where Y chromosome loss appeared across each sample. The maps revealed a clear spatial pattern. Y chromosome loss increased progressively as the tissue moved from visibly normal bladder lining, through early abnormal cells, and finally into full-blown cancer. The change behaved like a slope that grows steadily steeper, rising in intensity with every step toward malignancy.

That gradient extended beyond the bladder. When the team compared normal-appearing tissue adjacent to tumors across different organs, they found the highest levels of Y chromosome loss in tissue surrounding cancers of the colon, rectum, esophagus, pancreas and lung. In other words, the chromosome was disappearing most aggressively in the healthy-looking neighborhoods immediately surrounding tumors, even though those regions contained no cancer cells themselves. The observation points to what cancer biologists call a pre-neoplastic field effect, a hidden zone of genetic vulnerability within apparently normal tissue that provides fertile ground for a tumor to develop.

We were able to show that the loss of the Y chromosome is found in normal appearing tissues adjacent to a tumor, said Theodorescu, the paper’s senior author and holder of the Nancy C. and Craig M. Berge endowed chair for the director of the Cancer Center. That finding is what makes this discovery so exciting. It suggests we may be looking at one of the earliest signposts of cancer forming. The statement captures why the result has generated attention well beyond the field of cancer genetics: if Y chromosome loss marks tissue before tumors appear, it could serve as an early warning signal visible in ordinary biopsy material.

Theodorescu, who is also a professor at the University of Arizona College of Medicine in Tucson, described the pattern with a landscape metaphor. We are now thinking of this as a gradient, similar to a hillside that slowly gets steeper, he said. The closer the tissue is to a cancer, the more Y chromosome loss we see. That gradient could one day help doctors suspect trouble in biopsies that miss a smaller cancer. The clinical implication is significant. Pathologists currently assess biopsy samples for visible abnormalities, but a cancer can be missed if the needle or instrument samples only normal-appearing tissue. A measurable molecular signal, present even in that normal tissue, could alert clinicians that something malignant lies nearby.

The new findings also build on Theodorescu’s earlier work on the biology of Y chromosome loss inside tumors themselves. His previous research showed that when cancer cells lose their Y chromosome, they gain the ability to evade the immune system, an effect that helps explain why loss of the chromosome has been linked in earlier studies to increased mortality from carcinomas. Taken together, the two lines of research sketch a coherent arc. Loss of Y may first render normal tissue more permissive to malignant transformation, and then, once cancer has taken hold, help the tumor hide from the immune defenses that would otherwise destroy it. The chromosome, in this view, is not a passive passenger but a participant at multiple stages of the disease.

How exactly the loss of a single chromosome produces these effects remains an open question. The Y chromosome carries genes involved in immune signaling and cellular regulation, and its disappearance from cells in blood has been linked in prior research to inflammatory and age-related conditions. In solid tissue, the progressive gradient observed in this study suggests that the loss is not random noise but something tied to the local biology of a forming tumor, whether as a cause, a consequence, or both. Disentangling those possibilities is the next challenge for the field, and the pan-organ mapping approach used here provides a framework for pursuing it at scale.

The study was a collaborative effort involving first authors Arkadiusz Gertych and Dr. Huihui Ye, along with collaborators from Cedars-Sinai Medical Center, Fred Hutchinson Cancer Center, the University of Washington and the University of California San Francisco. The work was funded in part by the National Cancer Institute, a division of the National Institutes of Health, under award No. R35CA294022 to Theodorescu. The research was published in JCI Insight on September 8, 2026, under the title Human Y chromosome pan-organ mapping reveals progressive mosaic loss from normal to cancer, and the authors declared no conflicts of interest. For millions of aging men, the finding reframes a familiar genetic change as a potential early alarm, one that could eventually be read from a routine biopsy long before a tumor announces itself.

Subject of Research: Mosaic loss of the Y chromosome in normal tissue as an early indicator of cancer development in men.

Article Title: Loss of Y chromosome in men could be early warning sign of cancer

Article References: Loss of Y chromosome in men could be early warning sign of cancer. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: Y chromosome loss, cancer, mosaic loss of Y, bladder cancer, pre-neoplastic field effect, JCI Insight, University of Arizona Cancer Center, fluorescent imaging, aging genetics, tumor microenvironment, immune evasion, pan-organ mapping