Evolution of pulmonary hypertension in interstitial lung disease: a journey through past, present, and future

Climate Change And Its Negative Effects On Lung Health

A session at the recent American Thoracic Society (ATS) annual meeting focused on the effect that the environment has on lung health. It included a presentation from Gregory P. Downey, MD, executive vice president of academic affairs at National Jewish Health in Denver, on the consequences of a warming climate for patients with airway diseases such as asthma and chronic obstructive pulmonary disease.

In this exclusive MedPage Today video, Downey, who is also the immediate past president of ATS, goes over a few of the points he made in his presentation.

Following is a transcript of his remarks:

So there's some obvious things. As the temperature increases we get these temperature extremes. People don't tolerate extremes of temperature. And if you saw the news in the last few days, Phoenix was going to reach 115°F. I think some of the Middle Eastern countries, going to Celsius, now it's up to 50°C.

And when people are exposed to those environments, they have a difficult time temperature regulating. You can't sweat enough to make up for that heat. And the body temperature's 37°C. And if it's 50°C outside, your body starts to warm up. That dries out the respiratory secretions and causes many other changes -- heat stroke, etc.

In addition, the warming temperatures have increased the amount of pollen that is produced by trees and also the duration of the pollen season. And this has been mapped pretty carefully. And if you plot carbon dioxide and surface temperature versus pollen levels, it's a pretty linear relationship. And the problem is that we are all now faced with these increasing pollen concentrations and duration. And this is one of the triggers for allergic diseases -- so sinusitis, asthma -- and this has led to a significant increase in the incidence of asthma around the world.

Looking into the future, although it's still, I'd say, not completely settled, people who have chronic poorly controlled asthma are predisposed to getting chronic obstructive lung disease as they age. And we are now seeing an increased incidence of chronic obstructive pulmonary disease in patients who've never smoked a day in their lives, and have not been exposed to at least abnormally high concentrations of secondhand cigarette smoke. So the thought is that this is a consequence of other exposures. So this first example of how climate change is driving respiratory health problems relates to the increased pollen, the allergic diseases, and in the future, chronic obstructive pulmonary disease.

The other thing is that as the temperature increases and the conversion of oxygen in the atmosphere to ozone is increased. And so this is another interaction -- a complex interaction between the warming temperatures and then another pollutant, ozone, which again then interacts with the particulate matter and the allergens to increase the severity of lung disease.

People have looked at the consequences of exposure to particulate matter and other byproducts of combustion, nitrogen oxides, and ozone. And it is very clear that exposure, even before birth, can affect the developing fetal lungs, and that in the first few years of life where the lungs of humans are still developing, increased exposures also have been shown to cause abnormalities of development of the lung. And one of the thoughts right now is that given the totality of these exposures, many infants and young children will never retain their full pulmonary function.

So normally, after birth, we achieve our full lung capacity somewhere between 18 and 20 years. But if there are high levels of exposure to pollutants, many of those people will never attain their full lung function, and therefore they start off at a disadvantage in adulthood and with other exposures, with infections, they are much more susceptible to getting severe consequences of what normally could be dealt with by a normal adult with a normal lung.

Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams. Follow

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Research Explores Reversing Memory Loss With Existing Drugs

The loss of social memories caused by sleep deprivation could potentially be reversed using currently available drugs, according to a study in mice presented today (Friday) at the Federation of European Neuroscience Societies (FENS) Forum 2024.

Lack of sleep is known to affect the brain, including memory, in mice and in humans, but research is beginning to show that these memories are not lost, they are just 'hidden' in the brain and difficult to retrieve.

The new research shows that access to these otherwise hidden social memories can be restored in mice with a drug currently used to treat asthma and chronic obstructive pulmonary disease. The team of researchers have also shown that another drug currently used to treat erectile dysfunction can restore access to spatial memories. Researchers say these spatial memories in mice are akin to humans remembering where they put their keys the night before, whereas the social memories could be compared with remembering a new person you met.

The research was presented by Dr Robbert Havekes from the University of Groningen in the Netherlands. He said: "Ever since starting as a PhD student, many years ago, I have been intrigued by the observation that even a single period of sleep deprivation can have a major impact on memory processes and the brain as a whole. The early work published years ago helped us identify some of the molecular mechanisms that mediate amnesia.

By manipulating these pathways specifically in the hippocampus, we have been able to make memory processes resilient to the negative impact of sleep deprivation. In our new studies, we have examined whether we could reverse amnesia even days after the initial learning event and period of sleep deprivation."

Dr Robbert Havekes, University of Groningen

The new studies, presented at the FENS Forum and funded by the Air Force Office of Scientific Research (AFOSR), were conducted by Dr Havekes' PhD students Adithya Sarma and Camilla Paraciani, who will also be presenting their work as poster presentations.

To study social memories in the lab, the researchers gave mice the opportunity to choose between interacting with a mouse they have never encountered before or a sibling from their own cage. Under normal circumstances, the mice prefer interacting with the new mouse over their litter-mate that they already know. Given the same choice the next day, mice will interact to a similar extent with both their litter-mate and the mouse they met the day before as both mice are now considered familiar.

However, if the mice are sleep-deprived after their first encounter then the next day they still prefer to interact with the new mouse as if they never met it before. These findings suggest that they simply cannot recall their previous encounter.

The team found they were able to permanently restore these hidden social memories, first using a technique called optogenetic engram technology. This technique allows them to identify neurons in the brain that together form a memory (known as a memory engram) for a specific experience and alter those neurons so they can be reactivated by light. Researchers can then use light to reactivate this specific group of neurons resulting in the recall of the specific experience (in this case a social memory).

They were also able to restore the mice's social memories by treating them with roflumilast, a type of anti-inflammatory drug, approved by the US Food and Drug Administration, that is used to treat chronic obstructive pulmonary disease. Dr Havekes says this finding is particularly interesting as it provides a stepping stone towards studies of sleep deprivation and memory in humans, and he is now collaborating with another research group that is embarking on human studies.

In parallel, the same researchers have investigated the loss of spatial memory caused by sleep deprivation by studying mice's abilities to learn and remember the location of individual objects. A brief period of sleep deprivation following training meant the mice could not recall the original locations of the object and so they did not notice when an object was moved to a new location during a test.

As with the social memories, access to these spatial memories could be restored by treating the mice with another drug, vardenafil, that is currently used to treat erectile dysfunction. This is a second drug that is approved by the US Food and Drug Administration that the researchers have successfully used to reverse amnesia in mice.

Dr Havekes said: "We have been able to show that sleep deprivation leads to amnesia in the case of specific spatial and social recognition memories. This amnesia can be reversed days later after the initial learning experience and sleep deprivation episode using drugs already approved for human consumption. We now want to focus on understanding what processes are at the core of these accessible and inaccessible memories. In the long term, we hope that these fundamental studies will help pave the way for studies in humans aimed at reversing forgetfulness by restoring access to otherwise inaccessible information in the brain."

Professor Richard Roche is chair of the FENS Forum communication committee and Deputy Head of the Department of Psychology at Maynooth University, Maynooth, County Kildare, Ireland, and was not involved in the research. He said: "This research shows that social and spatial memories seemingly lost through sleep-deprivation can be recovered. Although these studies were carried out in mice, they suggest that it may be possible to recover people's lost social and spatial memories using certain drug treatments that are already approved for human use. There are many situations where people cannot get the amount of sleep they need, so this area of research has obvious potential. However, it will take time and a lot more work to move this research from mice into humans."

New COPD Treatment Widens Airways And Fights Inflammation

People with the lung disease COPD (chronic obstructive pulmonary disease) have a new treatment option: a multitasking medication called Ohtuvayre (ensifentrine) that was just approved by the U.S. Food and Drug Administration (FDA) as a maintenance therapy.

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COPD involves persistent inflammation in the airways that blocks airflow from the lungs and causes breathing problems and symptoms like coughing, wheezing, and shortness of breath. For decades, standard COPD medications have included options such as inhaled bronchodilators to relax muscles around the airways, steroids to reduce airway inflammation, and anticholinergics to encourage clearing of mucus from the lungs.

Ensifentrine is a new type of COPD drug that's designed to do several things at once: It serves as a bronchodilator, an anti-inflammatory, and a mucus-removal aid. Ensifentrine accomplishes this by acting on two enzymes in the lungs — phosphodiesterase 3 and phosphodiesterase 4 — that play a role in managing airway inflammation and muscle movements in the lungs.

The medication is delivered directly to the lungs through a standard jet nebulizer.

"We believe its bronchodilator and nonsteroidal anti-inflammatory activity has the potential to change the treatment paradigm," said David Zaccardelli, PharmD, the president and chief executive of ensifentrine's developer, Verona Pharma, in a statement. The drug, he added, is "the first novel mechanism available for the maintenance treatment of COPD in more than 10 years."

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How Does Ensifentrine Work?

In two clinical trials reviewed by the FDA prior to drug approval, researchers randomly assigned about 1,500 adults with moderate to severe COPD symptoms to take either ensifentrine or a placebo twice daily for 24 weeks.

Compared with the placebo, ensifentrine significantly improved what's known as forced expiratory volume (FEV1), or how much air somebody can exhale during a one-second breath. People taking ensifentrine were also 36 to 43 percent less likely to experience severe COPD exacerbations, according to results of the two trials published in the American Journal of Respiratory and Critical Care Medicine.

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Slightly more than one-third of patients taking ensifentrine experienced side effects related to treatment, similar to the proportion in the placebo group, the trials found. Roughly 6 to 10 percent of people on both ensifentrine and placebo stopped treatment due to side effects. Some common side effects included colds, elevated blood pressure, and back pain.

Another COPD Drug Approval Is on the Horizon As another potential new option for COPD, the FDA is currently reviewing data and considering whether to okay Dupixent (dupilumab), a drug the agency has already approved for conditions including asthma and atopic dermatitis (commonly referred to as eczema). A decision is expected in September, according to a statement from the drug's developers, Sanofi and Regeneron.

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In clinical trials, dupilumab reduced the annual odds of moderate to severe acute COPD exacerbations by up to 34 percent, according to the statement.

Pulmonologists Are Excited to Have More Treatment Options

Both dupilumab and ensifentrine represent promising new therapies for COPD that appear to be both safe and highly effective, says Antonio Anzueto, MD, a professor and specialist in pulmonology and critical care medicine at the University of Texas Health Science Center at San Antonio.

"I am very excited about these medications," Dr. Anzueto says. "Both will provide important additional treatment options to our patients."

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