Tag Archives: asthma

Hallucinogenic molecules and the brain

Psychedelic drugs seems to be enjoying a ‘moment’. After decades of being vilified and  declared illegal (in many jurisdictions), psychedelic (or hallucinogenic) drugs are once again being tested for use in therapy. A Sept. 1, 2017 article by Diana Kwon for The Scientist describes some of the latest research (I’ve excerpted the section on molecules; Note: Links have been removed),

Mind-bending molecules

© SEAN MCCABE

All the classic psychedelic drugs—psilocybin, LSD, and N,N-dimethyltryptamine (DMT), the active component in ayahuasca—activate serotonin 2A (5-HT2A) receptors, which are distributed throughout the brain. In all likelihood, this receptor plays a key role in the drugs’ effects. Krähenmann [Rainer Krähenmann, a psychiatrist and researcher at the University of Zurich]] and his colleagues in Zurich have discovered that ketanserin, a 5-HT2A receptor antagonist, blocks LSD’s hallucinogenic properties and prevents individuals from entering a dreamlike state or attributing personal relevance to the experience.12,13

Other research groups have found that, in rodent brains, 2,5-dimethoxy-4-iodoamphetamine (DOI), a highly potent and selective 5-HT2A receptor agonist, can modify the expression of brain-derived neurotrophic factor (BDNF)—a protein that, among other things, regulates neuronal survival, differentiation, and synaptic plasticity. This has led some scientists to hypothesize that, through this pathway, psychedelics may enhance neuroplasticity, the ability to form new neuronal connections in the brain.14 “We’re still working on that and trying to figure out what is so special about the receptor and where it is involved,” says Katrin Preller, a postdoc studying psychedelics at the University of Zurich. “But it seems like this combination of serotonin 2A receptors and BDNF leads to a kind of different organizational state in the brain that leads to what people experience under the influence of psychedelics.”

This serotonin receptor isn’t limited to the central nervous system. Work by Charles Nichols, a pharmacology professor at Louisiana State University, has revealed that 5-HT2A receptor agonists can reduce inflammation throughout the body. Nichols and his former postdoc Bangning Yu stumbled upon this discovery by accident, while testing the effects of DOI on smooth muscle cells from rat aortas. When they added this drug to the rodent cells in culture, it blocked the effects of tumor necrosis factor-alpha (TNF-α), a key inflammatory cytokine.

“It was completely unexpected,” Nichols recalls. The effects were so bewildering, he says, that they repeated the experiment twice to convince themselves that the results were correct. Before publishing the findings in 2008,15 they tested a few other 5-HT2A receptor agonists, including LSD, and found consistent anti-inflammatory effects, though none of the drugs’ effects were as strong as DOI’s. “Most of the psychedelics I have tested are about as potent as a corticosteroid at their target, but there’s something very unique about DOI that makes it much more potent,” Nichols says. “That’s one of the mysteries I’m trying to solve.”

After seeing the effect these drugs could have in cells, Nichols and his team moved on to whole animals. When they treated mouse models of system-wide inflammation with DOI, they found potent anti-inflammatory effects throughout the rodents’ bodies, with the strongest effects in the small intestine and a section of the main cardiac artery known as the aortic arch.16 “I think that’s really when it felt that we were onto something big, when we saw it in the whole animal,” Nichols says.

The group is now focused on testing DOI as a potential therapeutic for inflammatory diseases. In a 2015 study, they reported that DOI could block the development of asthma in a mouse model of the condition,17 and last December, the team received a patent to use DOI for four indications: asthma, Crohn’s disease, rheumatoid arthritis, and irritable bowel syndrome. They are now working to move the treatment into clinical trials. The benefit of using DOI for these conditions, Nichols says, is that because of its potency, only small amounts will be required—far below the amounts required to produce hallucinogenic effects.

In addition to opening the door to a new class of diseases that could benefit from psychedelics-inspired therapy, Nichols’s work suggests “that there may be some enduring changes that are mediated through anti-inflammatory effects,” Griffiths [Roland Griffiths, a psychiatry professor at Johns Hopkins University] says. Recent studies suggest that inflammation may play a role in a number of psychological disorders, including depression18 and addiction.19

“If somebody has neuroinflammation and that’s causing depression, and something like psilocybin makes it better through the subjective experience but the brain is still inflamed, it’s going to fall back into the depressed rut,” Nichols says. But if psilocybin is also treating the inflammation, he adds, “it won’t have that rut to fall back into.”

If it turns out that psychedelics do have anti-inflammatory effects in the brain, the drugs’ therapeutic uses could be even broader than scientists now envision. “In terms of neurodegenerative disease, every one of these disorders is mediated by inflammatory cytokines,” says Juan Sanchez-Ramos, a neuroscientist at the University of South Florida who in 2013 reported that small doses of psilocybin could promote neurogenesis in the mouse hippocampus.20 “That’s why I think, with Alzheimer’s, for example, if you attenuate the inflammation, it could help slow the progression of the disease.”

For anyone who was never exposed to the anti-hallucinogenic drug campaigns, this turn of events is mindboggling. There was a great deal of concern especially with LSD in the 1960s and it was not entirely unfounded. In my own family, a distant cousin, while under the influence of the drug, jumped off a building believing he could fly.  So, Kwon’s story opening with a story about someone being treated successfully for depression with a psychedelic drug was surprising to me . Why these drugs are being used successfully for psychiatric conditions when so much damage was apparently done under the influence in decades past may have something to do with taking the drugs in a controlled environment and, possibly, smaller dosages.

A t-shirt that monitors your breathing in real time

This May 18, 2017 news item on Nanowerk features research at the Université Laval (Québec, Canada), Note: A link has been removed,

Researchers at Université Laval’s Faculty of Science and Engineering and its Center for Optics, Photonics, and Lasers have created a smart T-shirt that monitors the wearer’s respiratory rate in real time.

This innovation, the details of which are published in the latest edition of Sensors (“Wearable Contactless Respiration Sensor Based on Multi-Material Fibers Integrated into Textile”), paves the way for manufacturing clothing that could be used to diagnose respiratory illnesses or monitor people suffering from asthma, sleep apnea, or chronic obstructive pulmonary disease.

A May 18, 2017 Université Laval press release, which originated the news item, provides a little more detail about the work,

Unlike other methods of measuring respiratory rate, the smart T-shirt works without any wires, electrodes, or sensors attached to the user’s body, explains Younès Messaddeq, the professor who led the team that developed the technology. “The T-shirt is really comfortable and doesn’t inhibit the subject’s natural movements. Our tests show that the data captured by the shirt is reliable, whether the user is lying down, sitting, standing, or moving around.”

The key to the smart T-shirt is an antenna sewn in at chest level that’s made of a hollow optical fiber coated with a thin layer of silver on its inner surface. The fiber’s exterior surface is covered in a polymer that protects it against the environment. “The antenna does double?duty, sensing and transmitting the signals created by respiratory movements,” adds Professor Messaddeq, who also holds the Canada Excellence Research Chair in Photonic Innovations. “The data can be sent to the user’s smartphone or a nearby computer.”

As the wearer breathes in, the smart fiber senses the increase in both thorax circumference and the volume of air in the lungs, explains Messaddeq. “These changes modify some of the resonant frequency of the antenna. That’s why the T-shirt doesn’t need to be tight or in direct contact with the wearer’s skin. The oscillations that occur with each breath are enough for the fiber to sense the user’s respiratory rate.”

To assess the durability of their invention, the researchers put a T-shirt equipped with an antenna through the wash—literally. “After 20 washes, the antenna had withstood the water and detergent and was still in good working condition,” says Messaddeq.

Protoype of the spiral antenna integrated into a cotton shirt. Inset: SEM images of the multi-material fiber structure. (© MDPI) (click on image to enlarge) Courtesy: Université Laval

Here’s a link to and a citation for the paper,

Wearable Contactless Respiration Sensor Based on Multi-Material Fibers Integrated into Textile by Philippe Guay, Stepan Gorgutsa, Sophie LaRochelle, and Younes Messaddeq. Sensors 2017, 17(5), 1050; doi:10.3390/s17051050 (This article belongs to the Special Issue Biomedical Sensors and Systems 2017) Published: 6 May 2017

This article is open access.

Soy and cellulose come together for a bionano air filter

A Jan. 18, 2017 news item on Nanowerk describes research into an environmentally friendly air filter from Washington State University,

Washington State University researchers have developed a soy-based air filter that can capture toxic chemicals, such as carbon monoxide and formaldehyde, which current air filters can’t.

The research could lead to better air purifiers, particularly in regions of the world that suffer from very poor air quality. …

Working with researchers from the University of Science and Technology Beijing, the WSU team, including Weihong (Katie) Zhong, professor in the School of Mechanical and Materials Engineering, and graduate student Hamid Souzandeh, used a pure soy protein along with bacterial cellulose for an all-natural, biodegradable, inexpensive air filter.

Here’s an image the researchers have made available,

Bionano air filter before and after filtration. Courtesy: Washington State University

A Jan. 12, 2017 Washington State University news release by Tilda Hilding, which originated the news item, expands on the theme,

Poor air quality causes health problems worldwide and is a factor in diseases such as asthma, heart disease and lung cancer. Commercial air purifiers aim for removing the small particles that are present in soot, smoke or car exhaust because these damaging particles are inhaled directly into the lungs.

With many sources of pollution in some parts of the world, however, air pollution also can contain a mix of hazardous gaseous molecules, such as carbon monoxide, formaldehyde, sulfur dioxide and other volatile organic compounds.

Typical air filters, which are usually made of micron-sized fibers of synthetic plastics, physically filter the small particles but aren’t able to chemically capture gaseous molecules. Furthermore, they’re most often made of glass and petroleum products, which leads to secondary pollution, Zhong said.

Soy captures nearly all pollutants

The WSU and Chinese team developed a new kind of air filtering material that uses natural, purified soy protein and bacterial cellulose – an organic compound produced by bacteria. The soy protein and cellulose are cost effective and already used in numerous applications, such as adhesives, plastic products, tissue regeneration materials and wound dressings.

Soy contains a large number of functional chemical groups – it includes 18 types of amino groups. Each of the chemical groups has the potential to capture passing pollution at the molecular level. The researchers used an acrylic acid treatment to disentangle the very rigid soy protein, so that the chemical groups can be more exposed to the pollutants.

The resulting filter was able to remove nearly all of the small particles as well as chemical pollutants, said Zhong.

Filters are economical, biodegradable

Especially in very polluted environments, people might be breathing an unknown mix of pollutants that could prove challenging to purify. But, with its large number of functional groups, the soy protein is able to attract a wide variety of polluting molecules.

“We can take advantage from those chemical groups to grab the toxics in the air,” Zhong said.

The materials are also cost-effective and biodegradable. Soybeans are among the most abundant plants in the world, she added.

Zhong occasionally visits her native China and has personally experienced the heavy pollution in Beijing as sunny skies turn to gray smog within a few days.

“Air pollution is a very serious health issue,” she said. “If we can improve indoor air quality, it would help a lot of people.”

Patents filed on filters, paper towels

In addition to the soy-based filters, the researchers have also developed gelatin- and cellulose-based air filters. They are also applying the filter material on top of low-cost and disposable paper towel to reinforce it and to improve its performance. They have filed patents on the technology and are interested in commercialization opportunities.

Here’s a link to and a citation for the paper,

Soy protein isolate/bacterial cellulose composite membranes for high efficiency particulate air filtration by Xiaobing Liu, Hamid Souzandeh, Yudong Zheng, Yajie Xie, Wei-Hong Zhong, Cai Wang. Composites Science and Technology Volume 138, 18 January 2017, Pages 124–133         http://dx.doi.org/10.1016/j.compscitech.2016.11.022

This paper is behind a paywall.

Trojan horse nanoparticle for asthma

A brand new technique for dealing with asthma is being proposed by researchers at Northwestern University (US), according to an April 18, 2016 news item on ScienceDaily,

In an entirely new approach to treating asthma and allergies, a biodegradable nanoparticle acts like a Trojan horse, hiding an allergen in a friendly shell, to convince the immune system not to attack it, according to new Northwestern Medicine research. As a result, the allergic reaction in the airways is shut down long- term and an asthma attack prevented.

The technology can be applied to food allergies as well. The nanoparticle is currently being tested in a mouse model of peanut allergy, similar to food allergy in humans.

“The findings represent a novel, safe and effective long-term way to treat and potentially ‘cure’ patients with life-threatening respiratory and food allergies,” said senior author Stephen Miller, the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. “This may eliminate the need for life-long use of medications to treat lung allergy.”

An April 18, 2016 Northwestern University news release (also on EurekAlert) by Marla Paul, which originated the news item, expands on the theme,

It’s the first time this method for creating tolerance in the immune system has been used in allergic diseases. The approach has been used in autoimmune diseases including multiple sclerosis and celiac disease in previous preclinical Northwestern research.

The asthma allergy study was in mice, but the technology is progressing to clinical trials in autoimmune disease. The nanoparticle technology is being developed commercially by Cour Pharmaceuticals Development Co., which is working with Miller to bring this new approach to patients. A clinical trial using the nanoparticles to treat celiac disease is in development.

“It’s a universal treatment,” Miller said. “Depending on what allergy you want to eliminate, you can load up the nanoparticle with ragweed pollen or a peanut protein.”

The nanoparticles are composed of an FDA-approved biopolymer called PLGA that includes lactic acid and glycolic acid.

Also a senior author is Lonnie Shea, adjunct professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and of obstetrics and gynecology at Feinberg, and chair of biomedical engineering at the University of Michigan.

When the allergen-loaded nanoparticle is injected into the bloodstream of mice, the immune system isn’t concerned with it because it sees the particle as innocuous debris. Then the nanoparticle and its hidden cargo are consumed by a macrophage, essentially a vacuum-cleaner cell.

“The vacuum-cleaner cell presents the allergen or antigen to the immune system in a way that says, ‘No worries, this belongs here,’” Miller said. The immune system then shuts down its attack on the allergen, and the immune system is reset to normal.

The allergen, in this case egg protein, was administered into the lungs of mice who have been pretreated to be allergic to the protein and already had antibodies in their blood against it. So when they were re-exposed to it, they responded with an allergic response like asthma. After being treated with the nanoparticle, they no longer had an allergic response to the allergen.

The approach also has a second benefit. It creates a more normal, balanced immune system by increasing the number of regulatory T cells, immune cells important for recognizing the airway allergens as normal. This method turns off the dangerous Th2 T cell that causes the allergy and expands the good, calming regulatory T cells.

If I understand this rightly, they’re rebalancing the immune system so it doesn’t treat innocuous material (dust, mould, etc.) as an allergen.

Here’s a link to and a citation for the paper,

Biodegradable antigen-associated PLG nanoparticles tolerize Th2-mediated allergic airway inflammation pre- and postsensitization by Charles B. Smarr, Woon Teck Yap, Tobias P. Neef, Ryan M. Pearson, Zoe N. Hunter, Igal Ifergan, Daniel R. Getts, Paul J. Bryce, Lonnie D. Shea, and Stephen D. Miller. PNAS 2016 doi: 10.1073/pnas.1505782113 Published ahead of print April 18, 2016,

This paper is behind a paywall.

Inadvertent carbon nanotube production from your car

It’s disconcerting to find out that cars inadvertently produce carbon nanotubes which are then spilled into the air we breathe. Researchers at Rice University (US) and Paris-Saclay University (France) have examined matter from car exhausts and dust in various parts of Paris finding carbon nanotubes (CNTs). Further, they also studied the lungs of Parisian children who have asthma and found CNTs there too.

The scientists have carefully stated that CNTs have been observed in lung cells but they are not claiming causality (i.e., they don’t claim the children’s asthma was caused by CNTs).

An Oct. 20, 2015 news item on Nanotechnology Now introduces the research,

Cars appear to produce carbon nanotubes, and some of the evidence has been found in human lungs.

Rice University scientists working with colleagues in France have detected the presence of man-made carbon nanotubes in cells extracted from the airways of Parisian children under routine treatment for asthma. Further investigation found similar nanotubes in samples from the exhaust pipes of Paris vehicles and in dust gathered from various places around the city.

The researchers reported in the journal EBioMedicine this month that these samples align with what has been found elsewhere, including Rice’s home city of Houston, in spider webs in India and in ice cores.

An Oct. 19, 2015 Rice University news release (also on EurekAlert), which originated the news item, painstakingly describes the work and initial conclusions,

The research in no way ascribes the children’s conditions to the nanotubes, said Rice chemist Lon Wilson, a corresponding author of the new paper. But the nanotubes’ apparent ubiquity should be the focus of further investigation, he said.

“We know that carbon nanoparticles are found in nature,” Wilson said, noting that round fullerene molecules like those discovered at Rice are commonly produced by volcanoes, forest fires and other combustion of carbon materials. “All you need is a little catalysis to make carbon nanotubes instead of fullerenes.”

A car’s catalytic converter, which turns toxic carbon monoxide into safer emissions, bears at least a passing resemblance to the Rice-invented high-pressure carbon monoxide, or HiPco, process to make carbon nanotubes, he said. “So it is not a big surprise, when you think about it,” Wilson said.

The team led by Wilson, Fathi Moussa of Paris-Saclay University and lead author Jelena Kolosnjaj-Tabi, a graduate student at Paris-Saclay, analyzed particulate matter found in the alveolar macrophage cells (also known as dust cells) that help stop foreign materials like particles and bacteria from entering the lungs.

The researchers wrote that their results “suggest humans are routinely exposed” to carbon nanotubes. They also suggested previous studies that link the carbon content of airway macrophages and the decline of lung function should be reconsidered in light of the new findings. Moussa confirmed his lab will continue to study the impact of man-made nanotubes on health.

The cells were taken from 69 randomly selected asthma patients aged 2 to 17 who underwent routine fiber-optic bronchoscopies as part of their treatment. For ethical reasons, no cells from healthy patients were analyzed, but because nanotubes were found in all of the samples, the study led the researchers to conclude that carbon nanotubes are likely to be found in everybody.

The study notes but does not make definitive conclusions about the controversial proposition that carbon nanotube fibers may act like asbestos, a proven carcinogen. But the authors reminded that “long carbon nanotubes and large aggregates of short ones can induce a granulomatous (inflammation) reaction.”

The study partially answers the question of what makes up the black material inside alveolar macrophages, the original focus of the study. The researchers found single-walled and multiwalled carbon nanotubes and amorphous carbon among the cells, as well as in samples swabbed from the tailpipes of cars in Paris and dust from various buildings in and around the city.

The news release goes on to detail how the research was conducted,

“The concentrations of nanotubes are so low in these samples that it’s hard to believe they would cause asthma, but you never know,” Wilson said. “What surprised me the most was that carbon nanotubes were the major component of the carbonaceous pollution we found in the samples.”

The nanotube aggregates in the cells ranged in size from 10 to 60 nanometers in diameter and up to several hundred nanometers in length, small enough that optical microscopes would not have been able to identify them in samples from former patients. The new study used more sophisticated tools, including high-resolution transmission electron microscopy, X-ray spectroscopy, Raman spectroscopy and near-infrared fluorescence microscopy to definitively identify them in the cells and in the environmental samples.

“We collected samples from the exhaust pipes of cars in Paris as well as from busy and non-busy intersections there and found the same type of structures as in the human samples,” Wilson said.

“It’s kind of ironic. In our laboratory, working with carbon nanotubes, we wear facemasks to prevent exactly what we’re seeing in these samples, yet everyone walking around out there in the world probably has at least a small concentration of carbon nanotubes in their lungs,” he said.

The researchers also suggested that the large surface areas of nanotubes and their ability to adhere to substances may make them effective carriers for other pollutants.

The study followed one released by Rice and Baylor College of Medicine earlier this month with the similar goal of analyzing the black substance found in the lungs of smokers who died of emphysema. That study found carbon black nanoparticles that were the product of the incomplete combustion of such organic material as tobacco.

Here’s an image of a sample,

 Caption: Carbon nanotubes (the long rods) and nanoparticles (the black clumps) appear in vehicle exhaust taken from the tailpipes of cars in Paris. The image is part of a study by scientists in Paris and at Rice University to analyze carbonaceous material in the lungs of asthma patients. They found that cars are a likely source of nanotubes found in the patients. Credit: Courtesy of Fathi Moussa/Paris-Saclay University

Caption: Carbon nanotubes (the long rods) and nanoparticles (the black clumps) appear in vehicle exhaust taken from the tailpipes of cars in Paris. The image is part of a study by scientists in Paris and at Rice University to analyze carbonaceous material in the lungs of asthma patients. They found that cars are a likely source of nanotubes found in the patients.
Credit: Courtesy of Fathi Moussa/Paris-Saclay University

Here’s a link to and a citation for the paper,

Anthropogenic Carbon Nanotubes Found in the Airways of Parisian Children by Jelena Kolosnjaj-Tabi, Jocelyne Just, Keith B. Hartman, Yacine Laoudi, Sabah Boudjemaa, Damien Alloyeau, Henri Szwarc, Lon J. Wilson, & Fathi Moussa. EBioMedicine doi:10.1016/j.ebiom.2015.10.012 Available online 9 October 2015

This paper is open access.

ETA Oct. 26, 2015: Dexter Johnson, along with Dr. Andrew Maynard, provides an object lesson on how to read science research in an Oct. 23, 2015 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers]),

“From past studies, the conditions in combustion engines seem to favor the production of at least some CNTs (especially where there are trace metals in lubricants that can act as catalysts for CNT growth),” explained Andrew Maynard Director, Risk Innovation Lab and Professor, School for the Future of Innovation in Society at Arizona State University, in an e-mail interview. Says Maynard:

What, to my knowledge, is still not known, is the relative concentrations of CNT in ambient air that may be inhaled, the precise nature of these CNT in terms of physical and chemical structure, and the range of sources that may lead to ambient CNT. This is important, as the potential for fibrous particles to cause lung damage depends on characteristics such as their length—and many of the fibers shown in the paper appear too short to raise substantial concerns.”

Nonetheless, Maynard praises the research for establishing that these carbon nanotube-like fibers are part of the urban aerosol and therefore end up in the lungs of anyone who breathes it in. However, he cautions that the findings don’t provide information on the potential health risks associated with these exposures.

It’s a good read not only for the information but the mild snarkiness (assuming you find that kind of thing amusing) that spices up the piece.

Acoustofluidics and lab-on-a-chip for asthma and tuberculosis diagnostics

This is my first exposure to acoustofluidics (although it’s been around for a few years) and it concerns lab-on-a-chip diagnostics for asthma and tuberculosis. From an Aug. 3, 2015 news item on Azonano,

A device to mix liquids utilizing ultrasonics is the first and most difficult component in a miniaturized system for low-cost analysis of sputum from patients with pulmonary diseases such as tuberculosis and asthma.

The device, developed by engineers at Penn State in collaboration with researchers at the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, and the Washington University School of Medicine, will benefit patients in the U.S., where 12 percent of the population, or around 19 million people, have asthma, and in undeveloped regions where TB is still a widespread and often deadly contagion.

“To develop more accurate diagnosis and treatment approaches for patients with pulmonary diseases, we have to analyze sample cells directly from the lungs rather than by drawing blood,” said Tony Jun Huang, professor of engineering science and mechanics at Penn State and the inventor, with his group, of this and other acoustofluidic devices based on ultrasonic waves. “For instance, different drugs are used to treat different types of asthma patients. If you know what a person’s immunophenotype is, you can provide personalized medicine for their particular disease.

A July 29, 2015 Pennsylvania State University news release, which originated the news item, describes the disadvantages of the current sputum analyses techniques and explains how this new technique in an improvement,

There are several issues with the current standard method for sputum analysis. The first is that human specimens can be contagious, and sputum analysis requires handling of specimens in several discrete machines. With a lab on a chip device, all biospecimens are safely contained in a single disposable component.

Another issue is the sample size required for analysis in the current system, which is often larger than a person can easily produce. The acoustofluidic sputum liquefier created by Huang’s group requires 100 times less sample while still providing accuracy equivalent to the standard system.

A further issue is that current systems are difficult to use and require trained operators. With the lab on a chip system, a nurse can operate the device with a touch of a few buttons and get a read out, or the patient could even operate the device at home. In addition, the disposable portion of the device should cost less than a dollar to manufacture.

Po-Hsun Huang, a graduate student in the Huang group and the first author on the recent paper describing the device in the Royal Society of Chemistry journal Lab on a Chip, said “This will offer quick analysis of samples without having to send them out to a centralized lab. While I have been working on the liquefaction component of the device, my lab mates are working on the flow cytometry analysis component, which should be ready soon. This is the first on-chip sputum liquefier anyone has developed.”

Stewart J. Levine, a Senior Investigator and Chief of the Laboratory of Asthma and Lung Inflammation in the Division of Intramural Research at NHLBI, said “This on-chip sputum liquefier is a significant advance regarding our goal of developing a point-of-care diagnostic device that will determine the type of inflammation present in the lungs of asthmatics. This will allow health care providers to individualize asthma treatments for each patient and advance the goal of bringing precision medicine into clinical practice.”

Here’s a link to and a citation for the paper,

An acoustofluidic sputum liquefier by Po-Hsun Huang, Liqiang Ren, Nitesh Nama, Sixing Li, Peng Li, Xianglan Yao, Rosemarie A. Cuento, Cheng-Hsin Wei, Yuchao Chen, Yuliang Xie, Ahmad Ahsan Nawaz, Yael G. Alevy, Michael J. Holtzman, J. Philip McCoy, Stewart J. Levine, and  Tony Jun Huang. Lab Chip, 2015,15, 3125-3131 DOI: 10.1039/C5LC00539F

First published online 17 Jun 2015

This is an open access paper but you do need to register for a free (British) Royal Society of Chemistry publishing personal account.

Asthma on a chip

Harvard University’s Wyss Institute for Biologically Inspired Engineering has found a way to mimic the lung’s muscle action when an asthma attack is being experienced according to a Sept. 23, 2014 news item on Nanowerk,

The majority of drugs used to treat asthma today are the same ones that were used 50 years ago. New drugs are urgently needed to treat this chronic respiratory disease, which causes nearly 25 million people in the United States alone to wheeze, cough, and find it difficult at best to take a deep breath.

But finding new treatments is tough: asthma is a patient-specific disease, so what works for one person doesn’t necessarily work for another, and the animal models traditionally used to test new drug candidates often fail to mimic human responses–costing tremendous money and time.

Hope for healthier airways may be on the horizon thanks to a Harvard University team that has developed a human airway muscle-on-a-chip that could be used to test new drugs because it accurately mimics the way smooth muscle contracts in the human airway, under normal circumstances and when exposed to asthma triggers. [emphasis mine]

A Sept. 23, 2014 Wyss Institute news release (also on EurekAlert*), which originated the news item, provides more details about the technology and its advantages,

The chip, a soft polymer well that is mounted on a glass substrate, contains a planar array of microscale, engineered human airway muscles, designed to mimic the laminar structure of the muscular layers of the human airway.

To mimic a typical allergic asthma response, the team first introduced interleukin-13 (IL-13) to the chip. IL-13 is a natural protein often found in the airway of asthmatic patients that mediates the response of smooth muscle to an allergen.

Then they introduced acetylcholine, a neurotransmitter that causes smooth muscle to contract. Sure enough, the airway muscle on the chip hypercontracted – and the soft chip curled up – in response to higher doses of the neurotransmitter.

They achieved the reverse effect as well and triggered the muscle to relax using drugs called β-agonists, which are used in inhalers.

Significantly, they were able to measure the contractile stress of the muscle tissue as it responded to varying doses of the drugs, said lead author Alexander Peyton Nesmith, a Ph.D./M.D. student at Harvard SEAS and the University of Alabama at Birmingham. “Our chip offers a simple, reliable and direct way to measure human responses to an asthma trigger,” he said.

The team then investigated what happened on a cellular level in response to the IL-13 and confirmed, for example, that the smooth muscle cells grew larger in the presence of IL-13 over time – a structural hallmark of the airways in asthma patients as well. They also documented an increased alignment of actin fibers within smooth muscle cells, which is consistent with the muscle in the airway of asthma patients. Actin fibers are super-thin cellular components involved in muscle contraction.

Next they observed how IL-13 changes the expression of contractile proteins called RhoA proteins, which have been implicated in the asthmatic response, although the details of their activation and signaling have remained elusive. To do this they introduced a drug called HA1077, which is not currently used to treat asthmatic patients – but targets the RhoA pathway. It turns out that the drug made the asthmatic tissue on the chip less sensitive to the asthma trigger – and preliminary tests indicated that using a combined therapy of HA1077 plus a currently approved asthma drug worked better than the single drug alone.

“Asthma is one of the top reasons for trips to the emergency room – particularly for children, and a large segment of the asthmatic population doesn’t respond to currently available treatments,” said Wyss Institute Founding Director Don Ingber, M.D., Ph.D. “The airway muscle-on-a-chip provides an important and exciting new tool for discovering new therapeutic agents.”

The scientists have provided an illustration of healthy and asthmatic airways,

Schematic comparing a healthy airway (few immune cells, normal airway diameter) to an asthmatic airway (many immune cells, constricted airway). Credit: Harvard's Wyss Institute and Harvard SEAS [School of Engineering and Applied Sciences]

Schematic comparing a healthy airway (few immune cells, normal airway diameter) to an asthmatic airway (many immune cells, constricted airway). Credit: Harvard’s Wyss Institute and Harvard SEAS [School of Engineering and Applied Sciences]

Here’s link to and a citation for the paper,

Human airway musculature on a chip: an in vitro model of allergic asthmatic bronchoconstriction and bronchodilation by Alexander Peyton Nesmith, Ashutosh Agarwal, Megan Laura McCain and Kevin Kit Parker.Lab Chip, 2014,14, 3925-3936 DOI: 10.1039/C4LC00688G First published online 05 Aug 2014

This paper is open access provided you have registered yourself for free at the site.

* EurekAlert link added Sept. 24, 2014.