Tag: 5/7/22

Urine Metabolites Yield Clues on Severe Asthma

Asthma inhaler
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A study published in the European Respiratory Journal found severe asthmatics have a distinct metabolite profile detectable in their urine, compared to healthy individuals and those with milder asthma.

Researchers analysed urine samples from more than 600 participants as part of the U-BIOPRED study, a Europe-wide initiative to identify and better understand different sub-types of severe asthma.

The research team discovered a specific type of metabolite, called carnitines, decreased in severe asthmatics. Carnitines play an important role in cellular energy generation and immune responses. Further analyses found carnitine metabolism was lower in severe asthmatics.

These new findings will help enable researchers work towards new, more effective therapies for asthmatics.

Study leader Dr Stacey Reinke said it is vital that asthma treatment is improved.

“To identify and develop new treatment options, we first need to better understand the underlying mechanisms of the disease,” she said.

Examining the body’s chemical profile, or ‘metabolome’, provides a snapshot of a person’s current physiological state and gives useful insight into disease processes.

“In this case, we were able to use the urinary metabolome of asthmatics to identify fundamental differences in energy metabolism that may represent a target for new interventions in asthma control,” Dr Reinke said.

Dr Reinke said it can be difficult and invasive to investigate the lungs directly – but fortunately they contain a lot of blood vessels.

“Therefore, any biochemical changes in the lungs can enter the blood stream, and then be excreted through the urine,” she said.

“These are preliminary results, but we will continue to investigate carnitine metabolism to evaluate its potential as a new asthma treatment target.”

‘Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study’ was published in the .

Source: Edith Cowan University

The Mental Health Benefits of Going on Holiday

Photo by Daniel Eledut on Unsplash

For better mental health, music and other forms of relaxation have been shown to have positive benefits. Now, researchers have identified a previously overlooked way to improve mental health – going on holiday, a luxury many have abandoned since COVID.

In a new cross-disciplinary paper, researchers from Edith Cowan University (ECU) propose that we view tourism, as not just as a recreational experience but as an industry that can provide real health benefits.

The interdisciplinary collaboration found that many aspects of going on holiday could have a positive impact on those with mental health issues or conditions.

Led by researcher Dr Jun Wen, a diverse team of tourism, public health and marketing experts investigated how tourism could benefit those living with dementia.

“Medical experts can recommend dementia treatments such as music therapy, exercise, cognitive stimulation, reminiscence therapy, sensory stimulation and adaptations to a patient’s mealtimes and environment,” Dr Wen said.

“These are all also often found when on holidays. This research is among the first to conceptually discuss how these tourism experiences could potentially work as dementia interventions.”

According to Dr Wen, the varied nature of tourism meant there were many opportunities to incorporate treatments for conditions such as dementia. Being in new environments and having new experiences could provide cognitive and sensory stimulation, for example.

“Exercise has been linked to mental wellbeing and travelling often involves enhanced physical activity, such as more walking,” Dr Wen said.

“Mealtimes are often different on holiday: they’re usually more social affairs with multiple people and family-style meals have been found to positively influence dementia patients’ eating behaviour.

“And then there’s the basics like fresh air and sunshine increasing vitamin D and serotonin levels. Everything that comes together to represent a holistic tourism experience, makes it easy to see how patients with dementia may benefit from tourism as an intervention.”

Dr Wen said COVID’s impact on travel in recent years had raised questions about tourism’s value beyond lifestyle and economic factors.

“Tourism has been found to boost physical and psychological wellbeing,” he said. So, after COVID, it’s a good time to identify tourism’s place in public health — and not just for healthy tourists, but vulnerable groups.”

Dr Wen said he hoped that new research could begin to examine how tourism can enhance the lives of people with various conditions.

“We’re trying to do something new in bridging tourism and health science,” he said. “There will have to be more empirical research and evidence to see if tourism can become one of the medical interventions for different diseases like dementia or depression.

“So, tourism is not just about travelling and having fun; we need to rethink the role tourism plays in modern society.”

The article ‘Tourism as a dementia treatment based on positive psychology’ was published in Tourism Management.

Source: Edith Cowan University

Slight Safety Edge for Ringer’s Lactate over Standard Saline

Intravenous IV drip
Source: Marcelo Leal on Unsplash

A new US study has found that Ringer’s lactate may be a better and safer treatment option for emergency department and hospital patients than saline solution, especially in sepsis.

According to the study of nearly 150 000 hospital patients, which was published in JAMA Network Open, Intermountain Healthcare researchers found that patients who received Ringer’s lactate solution instead of normal saline for IV fluids had a lower risk of kidney injury and death than when they were given saline.

Saline solution has long been the standard for IV solution with more than 200 million litres administered to hospital patients annually in the US.

Intermountain researchers found that patients who were given Ringer’s lactate as an alternative to saline solution had a 2.2% reduced risk of kidney injury and death.

Joseph Bledsoe MD, principal investigator of the study, said: “That might not sound like a big difference but considering how many patients receive IV fluids every day, it could lead to a major improvement in health outcomes. For our health system alone, that’s 3000 people every year who may avoid complications from normal saline, at no additional cost.”

For this large-scale, study researchers encouraged clinicians, through education and electronic order entry alerts, to use Ringer’s lactate solution rather than saline solution for IV fluid treatment.

Saline solution is a combination of sodium chloride and water at a concentration of 9g of salt per litre (0.9%) which are levels higher than blood, commonly called normal saline.

Mounting evidence points to intravenous normal saline solution increasing the risk of metabolic acidosis, acute kidney injury, and death. This could be due to normal saline having higher levels of chloride and being slightly more acidic than fluids in the human body.

Though they have different ingredients, both Ringer’s lactate and normal saline are used for replacing fluids and electrolytes in hospital patients who have low blood volume or low blood pressure.

Ringer’s lactate contains electrolytes more similar to blood plasma than saline solution. Ringer’s lactate, which is a type of balanced crystalloid, is also much closer to human fluid pH and did not show the same related risk of kidney injury, in line with previous smaller studies.

The study included 148 423 adult patients admitted to the emergency department or inpatient units at 22 Intermountain Healthcare hospitals in Utah and Idaho between November 1, 2018, and February 29, 2020.

At 30 days post treatment, researchers found a 2.2% reduction in major adverse kidney events, including persistent kidney dysfunction, new initiation of dialysis, and death in patients who were given Ringer’s lactate rather than normal saline solution during their emergency department or hospital treatment course.

The impact was even greater on patients with sepsis and on patients who received more fluids as part of their treatment. Not all patients benefit from Ringer’s lactate – patients with brain injury may still benefit from normal saline, but further studies are needed.

Researchers determined that before the study, approximately 25% of patients received Ringer’s lactate, and 75% received normal saline solution. Afterward, the percentages flipped to 25% receiving normal saline and 75% Ringer’s lactate.

Researchers found that nudges in the Intermountain electronic order system were more effective in changing clinician habits than relying on education.

“Given the success of nudges in making this change, our success could be replicated in other health systems and allows for sustained improvement,” said Dr. Bledsoe. “Given the scope of this study, and its success in addition to previous studies, hospitals around the country should consider what they use for IV fluids, too.”

In an editorial about these findings published in the same issue of JAMA Network Open, Matthew W. Semler, MD, MSc, assistant professor of medicine at Vanderbilt University Medical Center, wrote that the study “raises important questions about the choice between Ringer’s lactate solution and saline and, more broadly, how we should make evidence-based choices between widely available, commonly used treatment alternatives in acute care.”

Source: News-Medical.Net

New Universal Flu Vaccine Offers Broad Protection, Study Finds

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By focusing on key parts which remain stable over time, scientists have created a universal flu vaccine that offers broad cross protection against different strains and subtypes of influenza A viruses in both young and old populations, according to a new study reported in npj Vaccines.

The researchers developed the universal flu vaccine by genetically linking two highly conserved portions of the virus: the extracellular domain of matrix 2 (M2e) and the stalk protein found in influenza A H3N2 viruses. The findings show that vaccinating against M2e-stalk protein induced broad protection against different influenza virus strains and subtypes by universal vaccine-mediated immunity in adult and aged mice.

Developing effective influenza vaccines has been a challenge because the head portion of the influenza virus is constantly mutating. When comparing the H1N1 and H3N2 influenza A viruses, particular challenges exist in H3N2 subtypes because of stalk mutations in circulating strains and the unstable structure of stalk proteins for H3N2 viruses. These drawbacks have been difficult to overcome in developing effective H3 stalk-based vaccines.

In the past decade, vaccine effectiveness against H3N2 hovered around 33%, and during the 2014–2015 flu season, it dropped to 6%. New mutations of H3N2 variants emerged with increased virulence. Also, the outbreak of H7N9, another influenza A subtype, caused concern for potential pandemics. Therefore, developing an effective vaccine to protect against these viruses is a high priority.

“The M2e-stalk protein, for the first time, could be easily produced in bacterial cell cultures at high yields and was found to confer protection against heterologous and heterosubtypic cross-group subtype viruses (H1N1, H5N1, H9N2, H3N2 and H7N9) at similar levels in adult and aged mice,” said Dr Sang-Moo Kang, senior author of the study and a professor in the Institute for Biomedical Sciences at Georgia State. “These results provide evidence that M2e-stalk genetic fusion proteins can be produced in a large scale at low cost and developed as a universal influenza A virus vaccine candidate for young and aged populations.”

The study found this novel M2e-stalk protein vaccine induced M2e and stalk-specific Immunoglobulin G (IgG) antibodies that recognised antigenically diverse influenza viral antigens on virus particles and on the infected cell surface. The vaccine also stimulated protective cellular T cell immunity and effective lung influenza viral clearance in mice.

Source: Georgia State University

Airway Immune Risks of Fourth Generation e-Cigarettes

Photo by Nery Zarat on Unsplash

Fourth-generation e-cigarettes, such as Juul devices, are associated with unique changes in markers of immune responses inside our airways, according to a new peer-reviewed paper in the American Journal of Respiratory and Critical Care Medicine.

Third-generation e-cigarettes include vape pens and box mods. Fourth generation include nicotine-salt-containing e-cigarettes, such as Juul products, and disposable e-cigarettes, which have become increasingly popular, especially after the recent FDA ban on the sale of Juul products.

Researchers in the lab of Professor Ilona Jaspers at the UNC School of Medicine found that users of fourth-generation nicotine-salt-containing devices display a unique mix of cellular biomarkers indicative of immune suppression.

“Our work demonstrates the importance of considering device type in future clinical, epidemiological, and mechanistic studies on the health effects of e-cigarettes,” said Prof Jasper, who led the study. “We also think this research can help regulators determine which products cause the most severe types of biological changes in airway cells important for maintaining proper health.”

E-cigarettes have become popular in the last decade. Some started used them to quit smoking, believing vaping was a safer alternative, both in the short-term and long-term. Also, because electronic cigarettes don’t contain tar, consumers assumed vaping decreased their risk of cancer down the road.

“It’s impossible to know if vaping decreases cancer risk or many other long-term conditions,” Prof Jaspers said. “It took 60 years of research to show that smoking causes cancer.” In contrast, e-cigarettes have only been around for about 15 years. “Still, the research from our lab and many others has shown many of the same acute biological effects in the airways that we have documented in smokers,” she said. “And we’ve seen some changes to cells and immune defences in people who vape that, frankly, we’ve never seen before, which is very concerning.”

A major concern for researchers, doctors, and public health officials is the fact that teenagers who would not have otherwise tried cigarettes began using e-cigarettes, which contain nicotine – with its attendant health implications – and thousands of chemicals, many of which are FDA-approved for eating but not inhaling.

Several studies have documented that inhaling chemical-laden nicotine aerosols suppresses the immune responses in the respiratory tracts of smokers and e-cigarette users. Some studies, including some at UNC, have detailed how different chemicals in various e-cigarettes, including chemicals that make up thousands of different flavours, have adverse effects on airway cells. The Jaspers lab, which has been at the forefront of such research, set out to study the effects of different varieties of e-cigarette devices. For this study, her team collected central airway (sputum) samples from non-smokers, smokers, and users of both third-generation and fourth-generation e-cigarette devices.

They found that users of fourth-generation e-cigarettes had significantly more bronchial epithelial cells in their sputum, suggestive of airway injury because normally, bronchial epithelial cells make up an intact barrier in the airways and are not found in sputum samples. Levels of two proteins, sICAM1 and sVCAM1, were significantly lower in fourth-generation e-cigarette users compared to all other groups. These proteins are important in fighting infections and other disease.

In addition, proteins are important for overall immune defence were significantly lower in fourth versus third generation e-cigarette users. Lower of these proteins – CRP, IFN-g, MCP-1, uteroglobin, MMP-2, and VEGF – indications immune system depression. “Another key finding of the study was that, when examining the mixture of immune markers overall rather than one by one, fourth generation e-cigarette users had the most distinguishable changes out of all of the groups, indicating a shift away from immune homeostasis,” said the study’s lead author, Elise Hickman, PhD.

The study did not demonstrate that e-cigarettes cause cancer, emphysema, COPD, or other long-term diseases associated with long-term cigarette smoking. But researchers think that altering immune responses in the respiratory tract over the course of many years, especially for teens, could play a major role in the development of long-term health conditions and in susceptibility to inhaled pathogens.

Source: University of North Carolina