Pulmonx to commence US study of emphysema therapy

The US Food and Drug Administration (FDA) has given pulmonary medical device manufacturers Pulmonx permission to initiate an investigational device exemption (IDE) pivotal clinical study for its Zephyr endobronchial valve therapy, designed to treat emphysema.

The multi-centre trial is designed to study the safety and efficacy of Zephyr in reducing volume in the diseased portion of the lungs, thereby improving the ability of the healthier portions of the lungs to function.

The trial will incorporate the use of the Pulmonx Chartis system to plan valve treatment, according to the company.

A recent multi-centre European study of Zephyr, using Chartis, demonstrated a statistically significant improvement in target lobe volume reduction and FEV1 at 30 days compared to those who were predicted not to respond.

The patients also showed a mean percentage increase in FEV1 of 16% and a mean improvement in quality of life as scored by the St. George's Respiratory Questionnaire (SGRQ), a clinically validated quality-of-life measure.

Temple University School of Medicine pulmonary and critical care medicine chief and Zephyr trial co-principal investigator Dr Gerard J Criner said a recently published trial in Europe highlighted the benefits of Chartis technology in planning endobronchial valve treatments.
"If we can confirm these benefits in this pivotal trial, Pulmonx's Zephyr EBV therapy could represent an important breakthrough in the treatment of emphysema in the US," Criner said.

The company intends to use the IDE study data to support a premarket approval application (PMA) to the FDA for the approval of Zephyr.

 new medical device for emphysema therapy

gene profiling in emphysema, looking for a cure

How gene profiling in emphysema is helping to find a cure


Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States and is thought to affect almost three million people in the UK. New research published in BioMed Central's open access journal Genome Medicine has identified genes whose activity is altered with increasing lung damage and, using a database of drug effects on gene activity (the Connectivity Map), finds that the compound Gly-His-Lys (GHK) affects the activity of these genes. When tested on human cells from lungs damaged by emphysema, GHK was able to restore normal gene activity and repair cell function.


The strongest cause of COPD is smoking, and at least 25% of smokers will develop this disease. Tobacco smoke and other irritants cause oxidative stress and chronic inflammation, which over time results in emphysema, the destruction of lung alveolar cells. Without these cells, the lungs are not able to efficiently exchange oxygen for carbon dioxide, leaving the patient continuously short of breath and with low levels of oxygen in their blood.

In a ground breaking, multi-centre, study funded by the National Institute of Health (NIH), researchers used cells taken from lungs donated by patients undergoing double lung transplant, whose own lungs were irrevocably damaged by COPD. Profiling of these samples showed that 127 genes had changes in activity that was associated with worsening disease severity within the lung. As would be expected from the nature of the disease, several genes associated with inflammation, such as the genes involved in signalling to B-cells (the immune system cells which make antibodies), showed increased activity.

In contrast genes involved in maintaining cellular structure and normal cellular function, along with the growth factors TGFβ and VEGF, were down-regulated and showed decreased activity. This included genes which control the ability of the cells to stick together (cell adhesion), produce the protein matrix which normally surrounds the cells, and which promote the normal association between lung cells and blood vessels.
Dr Avrum Spira and Dr Marc Lenburg, who co-led this study from the Boston University School of Medicine, explained, "When we searched the Connectivity Map database, which is essentially a compendium of experiments that measure the effect of therapeutic compounds on every gene in the genome, we found that how genes were affected by the compound GHK, a drug known since the 1970s, was the complete opposite of what we had seen in the cells damaged by emphysema."

Dr Joshua Campbell explained, "What got us especially excited was that previous studies had shown that GHK could accelerate wound repair when applied to the skin. This made us think that GHK could have potential drug's as a therapy for COPD."
Prof James Hogg, from the University of British Columbia continued, "When we tested GHK on cells from the damaged lungs of smokers with COPD, we saw an improvement in the structure of their actin cytoskeleton and in cell adhesion, especially to collagen. GHK also restored the ability of cells to reorganise themselves to repair wounds and construct the contractile filaments essential for alveolar function."
GHK is a natural peptide found in human plasma, but the amount present decreases with age. While more testing needs to be done on its effects in COPD, these early results are very promising. Therapeutic studies with GHK in animal models of COPD are now underway with the ultimate goal of moving this compound into clinical trials.

As more gene activity signatures are discovered, this method of matching drug to disease may provide a rapid method for discovering potential uses for existing drugs and compounds.

Temple testing lung foam for emphysema

Temple testing lung foam for emphysema

PHILADELPHIA - August 14, 2012 (WPVI) -- An innovative new treatment for emphysema is being tested in the Philadelphia area.



Dr. Gerard Criner of Temple University Hospital, is studying a foam tended to help those with the lung disease breathe easier.

Science & Tech newsIn emphysema, parts of the lungs become less elastic, so air gets trapped in them.

"If you could do something to lessen the air in the chest, then the lungs that remain and the breathing muscles in the chest wall work more normally," says Dr. Criner.

Surgery can do that, but it has risks, and emphysema patients are often too weak to go through it.

Instead, a bronchoscope and a thin catheter put a liquid into diseased areas.
It turns to foam, sealing them off.

In earlier tests here & overseas, the Aeriseal lung foam worked well.

"They had about a 30% improvement in lung function, their ability to walk during 6 minutes, an improvement in quality of life, and reduction in breathlessness," notes Dr. Criner.
And the effects appear to be long-lasting.

"Up to a year that's been studied so far," he says.

In the Temple study, 3 patients will receive the treatment for every that aren't, but at the end of 1 year, those who don't get treated initially can get the treatment if they want, and if they still qualify.



For more information, call the temple lung center at 215-707-1359, or email to: breathe@temple.edu.

Study Gives First Evidence That Adult Human Lungs Can Regrow

Researchers speculate growth was stimulated, at least in part, by stretching caused by exercise

By Barbara Bronson Gray
HealthDay Reporter

WEDNESDAY, July 18 (HealthDay News) -- Researchers have uncovered the first evidence that the adult human lung is capable of growing back -- at least in part -- after being surgically removed.
In an observational study, researchers used MRIs with hyperpolarized helium-3 gas to show that existing alveoli -- the tiny, air-exchange units of the lung -- actually increased in number after a 33-year-old woman had her entire right lung removed due to cancer.

The study showed a 64 percent increase in the number of alveoli in the woman's lung 15 years after surgery. "The research clearly shows that some form of lung growth can occur in the adult human," said study author James Butler, an associate professor of medicine in the department of medicine at Harvard Medical School in Boston.

The new alveoli were all shaped similarly. "It's striking, the degree of homogeneity of the new alveoli, as if the lung was responding to something," Butler added. The cause of the new growth could be stretching of the tissue, perhaps by exercise, he suggested. "Could other bio-molecular growth be triggered by stretch? It's a wide-open question now."

About a year and a half after surgery, the woman began a daily exercise program including walking, cycling and yoga. Previous studies in adult dogs have suggested that lung growth after pneumonectomy (removal of the lung) in dogs was possible, typically after periods of lung stress or strain.
Over a period of 15 years, data measuring lung size and capacity were collected, using common respiratory tests (called FEV and FVC) measuring how much air can be taken in and blown out with deep breaths. In the early months after surgery, the lung responded as researchers would expect. The total lung volume increased and the lung density fell below normal. But, the lung tissue volume gradually started to increase and the density returned to a level normally seen when a deep breath is taken, suggesting the growth of new tissue.


The ability of the lung to regenerate, potentially triggered by exercise, makes sense, said Dr. Norman Edelman, a professor of medicine at Stony Brook University and chief medical officer of the American Lung Association. "When the lung develops in utero [when the fetus is developing], the pulling force of the diaphragm is an important stimulation for the lung to grow," he said. "But, of course, the practical application of the research is a long way off."
Butler said the next step is to do a study involving more people over time. "If we can discover the underlying bio-molecular mechanisms, they would suggest potential therapeutic options," he explained.

 see the original article here

Lung Regeneration Closer to Reality after New Discovery

Researchers from Weill Cornell Medical College say they have taken an important step forward in their quest to "turn on" lung regeneration - a discovery that could lead to treatment for millions of people suffering from respiratory disorders.

In the journal Cell, the research team claims that they have discovered the biochemical signals in mice that initiate the regeneration of new lung alveoli: the tiny, numerous sacs within the lung where oxygen exchange occurs. Specifically, they found that regenerative signals originate from the specialized endothelial cells that line the interior of blood vessels in the lung.

Though it has been long known that mice can regenerate and expand the capacity of one lung if the other is missing, this study now pinpoints the molecular triggers that initiate this process, and the researchers believe these findings hold relevance for humans.

According to lead author, Dr. Shahin Rafii, "Several adult human organs have the potential upon injury to regenerate to a degree, and while we can readily monitor the pathways involved in the regeneration of liver and bone marrow, it is much more cumbersome to study the regeneration of other adult organs, such as the lung and heart.”

For the study, Dr. Bi-Sen Ding, first author of this paper, removed the left lungs of mice and studied the biochemical process of subsequent regeneration of the remaining right lung. Prior research has shown that when the left lung of mice is removed, the right lung regenerates by 80 percent, effectively replacing most of the lost alveoli.

htclick for the complete article on lungs




The researchers found that removal of the left lung triggers receptors on lung endothelial cells that respond to vascular endothelial growth factor and basic fibroblast growth factor. Activating these receptors promotes the creation of another protein known as MMP14. The researchers discovered that MMP14, by releasing epidermal growth factors, sparks the generation of new lung tissue.

The next step for researchers will be to determine in MMP14 and other unrecognized angiocrine factors are responsible for lung regeneration in humans as well as mice. According to Dr. Ding, "We believe the same process goes on in humans, although we have no direct evidence yet.” The study’s authors theorize that patients with COPD have so much damage to their lung endothelial cells that they no longer produce the proper inductive signals, thus impairing lung regeneration.

Co-author of the study, Dr. Zev Rosenwaks theorizes that, “"Perhaps replacement of angiocrine factors, or transplantation of normal lung endothelial cells derived from pluripotent stem cells, could restore lung regeneration. Currently, we are generating pluripotent stem cells derived from patients with genetic pulmonary disorders to identify potential pathways, which may ultimately enhance our understanding of how lung endothelial cells may improve lung function in these patients."

IV Oxygen Foam Could Buy Breathing Time

 Every time you inhale, oxygen passes from your windpipe to your lungs and on into your bloodstream. But what if your windpipe was blocked? Getting the gas straight to your blood could save your life. Wait, put down that syringe—a large air bubble in a blood vessel can kill you. But what if the bubbles were only a few millionths of a meter in diameter?

Researchers coated tiny amounts of oxygen gas with fatty molecules to create microparticles. Suspended in solution, the microparticles formed a foam containing 50 to 90 percent oxygen. In a beaker of blood, the foam was able to quickly transfer its oxygen to the cells.

Then the researchers tested it in animals. Normally, a blocked windpipe cuts off the blood’s supply of oxygen, leading to brain damage and death. But when rabbits with blocked windpipes received injections of the microparticles, their blood oxygen levels and heart rates remained stable. The work is in the journal Science Translational Medicine. [John N. Kheir et al, Oxygen Gas–Filled Microparticles Provide Intravenous Oxygen Delivery]

The foam may someday buy time for human patients. So that even someone with a closed airway can breathe easy.

—Sophie Bushwick


click to read the orginal iv oxygen foam article

Lung stents for Emphysema

click for the video om stents for Emphysema

Jennifer Mathews: For Barbara Greenfield, the simplest chores are taxing. An oxygen tank and cord are now her lifeline. Barbara started smoking at age 15. By the time she reached 55, she was up to three packs a day and had early stage emphysema. 

 

Armin Ernst: If you think of the lung is something like a sponge, a bath sponge with all the little bubbles, it destroys the walls between those bubbles.Jennifer Mathews: The destroyed walls make it difficult for patients to exchange oxygen for carbon-dioxide.

 

Barbara Greenfield: It's like I am suffocating.Jennifer Mathews:

 

 Dr. Armin Ernst is studying a minimally invasive treatment that could help. During the procedure, doctors placed a bronchoscope through the mouth, then make six small openings, openings to help the patient breathe. Stents are then inserted to keep the holes from collapsing.

 

Armin Ernst: The stents are covered with a medication that's called Taxol that is designed to prevent this happening.Jennifer Mathews: 

 

Barbara's husband hopes the treatment will help her live more comfortably.Martin Greenfield: There's always the concern of how much it will do to her and ultimately limiting the length of our life together.

 

Jennifer Mathews: She hopes she'll be breathing a little easier.Barbara Greenfield: This is my only hope. It's not going to cure me, but it's going to perhaps make my life a little simpler.Jennifer Mathews: This is Jennifer Mathews reporting.