A 16-week course of dupilumab, a medication that targets a key immune pathway in allergies, resulted in more than half the children having at least a 75% reduction in signs of eczema and highly significant reductions in itch with improved sleep.

This is the first large-scale, randomized, placebo-controlled trial of a monoclonal antibody in any skin disease, including eczema, in children as young as 6 months. The study, which included 31 sites in Europe and North America, will be published Sept. 15 in The Lancet.

"Preschoolers who are constantly scratching, awake multiple times a night with their parents, irritable and markedly curtailed in their ability to do what other children their ages can do improved to the extent that they sleep through the night, change their personalities and have a normal life -- as babies and children should," said lead study author Dr. Amy Paller, chair of dermatology at Northwestern University Feinberg School of Medicine and an attending physician at Ann & Robert H. Lurie Children's Hospital of Chicago.

Eczema, also known as atopic dermatitis, is a chronic inflammatory skin disorder characterized by red, dry, often oozing skin and itch that can profoundly affect the lives of affected patients and their families.

An estimated 19% or more of all children under 6 years of age have eczema and 85 to 90% of individuals affected overall with eczema have the onset of disease during the first five years of life.

The children's debilitating itch leads to sleep disturbance, poor neurocognitive development and, on average, a full night of sleep lost per week.

"The ability to take this drug will significantly improve the quality of life for infants and young children who suffer tremendously with this disease," Paller said. "Atopic dermatitis or eczema is so much more than just itchy skin. It is a devastating disease. The quality of life of severe eczema -- not only for the child but also parents -- is equivalent to many life-threatening diseases."

As a result of this study, this medication is now available to infants and preschoolers as young as 6 months of age. It has "an outstanding safety profile" and does not even require any laboratory tests before starting the medication, Paller said.

Although one-half to two-thirds of young children with eczema have mild symptoms, which can be handled with steroid ointment and moisturizers, the other one-third or more have moderate-to-severe disease and require more aggressive management.

"Up to now, all we have had to treat more severe eczema is immune-suppressing medications, such as oral steroids, which we try to avoid in children, because they are associated with so many side effects and thus are not a preferred treatment for a chronic skin disease," Paller said. "The potential long-term impact on the development of the immune system in young children is also of concern with these immunosuppressants."

During the past few years, a new medication has become available called dupilumab, which is the first "biologic" drug to treat eczema in a targeted manner, meaning a narrow attack on just what scientists have found is causing the manifestations of the disease in skin. This medication was found to be effective and safe in studies with adults, then adolescents, then other school-aged children.

"But the group in whom we worry the most about safety -- those under 5 -- had not been tested and were unable to get this medication," Paller said.

The parent or a health care provider gives the child a monthly shot to administer the medication.

"The effect for most of these younger children is dramatic and at least as good as we've seen with the risky immunosuppressant medications," Paller said.

Potential added benefit by treating associated allergies

This medication has also been shown to be effective for treating asthma, gastrointestinal manifestations of allergy and other allergy-mediated problems but is not yet approved for these indications in infants and young children.

In fact, 66% of children in this trial had developed their eczema during the first six months of life and, by the time of initiating the dupilumab, more than 80% had already developed at least one allergic disorder, such as asthma or food allergy.

"By treating more aggressively to calm the immune system activation in these young children with early, severe eczema, we may also reduce the risk of their developing a range of allergic problems, changing their life beyond improving eczema," Paller said. "These associated allergic issues most often begin after the eczema starts."

Children were randomized to receive either a placebo injection or the dupilumab (weight-based dosing) every four weeks for 16 weeks. Only children who were not responding adequately to topical medications were allowed to enroll, and they had to be of a high severity, even with the topical medications.

As a result of the study, Paller said, scientists and physicians can start to better understand the relationships between eczema and a variety of allergic disorders and can consider the possibility of using this medication for other disorders that affect these very young children.

The trial was sponsored by Regeneron Pharmaceuticals, Inc. and Sanofi, who jointly developed dupilumab.

While a remedy for this severe disease has remained elusive, a recent study in the New England Journal of Medicine (Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease/Kanter et. al.), if proven applicable, may be a possible cure.

In an editorial in this week's New England Journal of Medicine, Martin Steinberg, MD, professor of medicine at Boston University School of Medicine, comments on the results of the study which was the first successful gene therapy for sickle cell disease that adds a gene to patient blood stem cells that prevents complications of sickle cell disease. "Gene therapy with autologous stem cells extends the possibility of a cure to all patients without the need for immunosuppression," explains Steinberg who also is hematologist at Boston Medical Center.

While patients in the study no longer had symptoms of sickle cell disease, Steinberg points out that most continued to have a shorter than normal lifespan of their red blood cells which he thinks could be associated with some complications in the longer-term.

Steinberg believes that for patients to accept this difficult and very expensive treatment it must be curative or nearly curative and last a lifetime. "At this point we do not yet know the sustainability of the results but based on this study the prospects seem good," he says.

Steinberg acknowledges that any highly effective gene therapy will not improve the health of most people with sickle cell disease throughout the world. "Most patients with this disease live in Africa and India where access to highly technological health care is limited. What is needed are more drugs that can be taken orally and increase fetal hemoglobin levels. This will have a higher likelihood of benefiting populations suffering the most from this disease."

The researchers, led by Krista Varady, UIC professor of nutrition, followed a group of pre- and post-menopausal obese women for a period of eight weeks on the "warrior diet" method of intermittent fasting.

The warrior diet prescribes a time-restricted feeding window of four hours per day, during which dieters can eat without counting calories before resuming a water fast until the next day.

They measured the differences in hormone levels, obtained by analyzing blood sample data, in groups of dieters who stuck to four- and six-hour feeding windows against a control group that followed no diet restrictions.

Varady and her team found that levels of sex-binding globulin hormone, a protein that carries reproductive hormones throughout the body, was unchanged in the dieters after eight weeks. The same held true for both testosterone and androstenedione, a steroid hormone that the body uses to produce both testosterone and estrogen.

However, dehydroepiandrosterone or DHEA, a hormone that fertility clinics prescribe to improve ovarian function and egg quality, was significantly lower in both pre-menopausal and post-menopausal women at the end of the trial, dropping by about 14%.

While the drop in DHEA levels was the most significant finding of the study, in both pre- and post-menopausal women, DHEA levels remained within the normal range by the end of the eight-week period.

"This suggests that in pre-menopausal women, the minor drop in DHEA levels has to be weighed against the proven fertility benefits of lower body mass," Varady said. "The drop in DHEA levels in post-menopausal women could be concerning because menopause already causes a dramatic drop in estrogen, and DHEA is a primary component of estrogen. However, a survey of the participants reported no negative side effects associated with low estrogen post-menopause, such as sexual dysfunction or skin changes."

As an added benefit, since high DHEA has been linked to breast cancer risk, Varady said a moderate drop in levels might be helpful in reducing that risk for both pre- and post-menopausal women.

The study measured levels of estradiol, estrone and progesterone -- all hormones vital to pregnancy -- as well, but only in post-menopausal women, due to the changing levels of these hormones throughout pre-menopausal women's menstrual cycles. Among post-menopausal women, there was no change in these hormones at the end of eight weeks.

Women in both the four-hour and six-hour dieting groups experienced weight loss of 3% to 4% of their baseline weight throughout the course of the study, compared with the control group, which had almost no weight loss. The dieters also saw a drop in insulin resistance and in biomarkers of oxidative stress.

Perimenopausal women, who are typically in their 40s, were excluded from the study.

Still, Varady said, "I think this is a great first step. We've observed thousands of pre- and post-menopausal women through different alternate-day fasting and time-restricted eating strategies. All it's doing is making people eat less. By shortening that eating window, you're just naturally cutting calories. Much of the negative information on intermittent fasting reported has come from studies on mice or rats. We need more studies to look at the effects of intermittent fasting on humans."

Story Source:

Materials provided by Boston University. Original written by Jessica Colarossi. Note: Content may be edited for style and length.

"It's possible that tomatoes impart benefits through their modulation of the gut microbiome," said senior author Jessica Cooperstone, assistant professor of horticulture and crop science and food science and technology at The Ohio State University.

"Overall dietary patterns have been associated with differences in microbiome composition, but food-specific effects haven't been studied very much," Cooperstone said. "Ultimately we'd like to identify in humans what the role is of these particular microorganisms and how they might be contributing to potential health outcomes."

The research is published in the journal Microbiology Spectrum.

The tomatoes used in the study were developed by Ohio State plant breeder, tomato geneticist and co-author David Francis, and are the type typically found in canned tomato products.

Ten recently weaned control pigs were fed a standard diet and 10 pigs were fed the standard diet fine-tuned so that 10% of the food consisted of a freeze-dried powder made from the tomatoes.

Fiber, sugar, protein, fat and calories were identical for both diets. The control and study pig populations lived separately, and researchers running the study minimized their time spent with the pigs -- a series of precautions designed to ensure that any microbiome changes seen with the study diet could be attributed to chemical compounds in the tomatoes.

Microbial communities in the pigs' guts were detected in fecal samples taken before the study began and then seven and 14 days after the diet was introduced.

The team used a technique called shotgun metagenomics to sequence all microbial DNA present in the samples. Results showed two main changes in the microbiomes of pigs fed the tomato-heavy diet -- the diversity of microbe species in their guts increased, and the concentrations of two types of bacteria common in the mammal microbiome shifted to a more favorable profile.

This higher ratio of the phyla Bacteroidota (formerly known as Bacteriodetes) compared to Bacillota (formerly known as Firmicutes) present in the microbiome has been found to be linked with positive health outcomes, while other studies have linked this ratio in reverse, of higher Bacillota compared to Bacteroidota, to obesity.

Tomatoes account for about 22% of vegetable intake in Western diets, and previous research has associated consumption of tomatoes with reduced risk for the development of various conditions that include cardiovascular disease and some cancers.

But tomatoes' impact on the gut microbiome is still a mystery, and Cooperstone said these findings in pigs -- whose gastrointestinal tract is more similar than rodents' to the human GI system -- suggest it's an avenue worth exploring.

"This was our first investigation as to how tomato consumption might affect the microbiome, and we've characterized which microbes are present, and how their relative abundance has changed with this tomato intervention," she said.

"To really understand the mechanisms, we need to do more of this kind of work in the long term in humans. We also want to understand the complex interplay -- how does consuming these foods change the composition of what microbes are present, and functionally, what does that do?

"A better understanding could lead to more evidence-based dietary recommendations for long-term health."

This work was supported by the U.S. Department of Agriculture, the Ohio Agricultural Research and Development Center and the Foods for Health initiative at Ohio State.

The study was led by Mallory Goggans, who received her master's degree in food science and technology from Ohio State in 2020.Additional co-authors include Emma Bilbrey, Cristian Quiroz-Moreno and Sheila Jacobi of Ohio State, and Jasna Kovac of Penn State University.

Story Source:

Materials provided by Ohio State University. Original written by Emily Caldwell. Note: Content may be edited for style and length.

According to Corkey, all of these purported explanations assume an environmental cause that is detrimental to the organism involved, (humans). "However, if we use the principle of symbiosis and Darwin's theory of evolution, perhaps we can understand obesity prevalence as an interim stage in the evolution of man reacting to his environment in order to gain long-term survival and ultimate longevity," says corresponding author Corkey, professor emeritus of medicine and biochemistry at Boston University Chobanian & Avedisian School of Medicine.

Humans have developed a method to feed the billions of people on the planet, by developing processed foods with preservatives and other chemicals that can make food last longer and can be made cheaply to increase calorie density in small packages. Corkey points out that those who develop obesity store body fat in response to excess calories. "Therefore the cause of obesity has as much to do as the human reaction to overfeeding as it does the production of foods that are being overfed," she states.

Corkey notes that key developments in the obesity/diabetes field include bariatric surgery as well as multiple agents (drugs) with different mechanisms of action to treat obesity and prevent weight regain. "Novel drug combinations are beginning to close the gap with bariatric surgery and appear to be very powerful new tools to treat obesity as a disease."

Corkey believes recognition of obesity as a disease and earlier diagnosis of diabetes and other consequences of obesity will support early and more effective treatment and prevention. "Importantly, disease recognition will help to support insurance coverage of effective obesity treatments," she adds.

Lastly, Corkey examines culinary medicine as an emerging evidence-based field that brings together nutrition and culinary knowledge and skills to assist patients in maintaining health and preventing and treating food-related disease by choosing high-quality, healthy food in conjunction with appropriate medical care. "Culinary medicine has the advantage of being an intervention that can be implemented at the earliest time point in the development of obesity with no negative side effects," says Corkey.

Story Source:Materials provided by Boston University School of Medicine. Note: Content may be edited for style and length.

The research, published June 13 in the Proceedings of the National Academy of Sciences (PNAS), could help explain disparities in age-related health, including the unequal toll of the pandemic, and identify possible points for intervention.

"As the world's population of older adults increases, understanding disparities in age-related health is essential. Age-related changes in the immune system play a critical role in declining health," said lead study author Eric Klopack, a postdoctoral scholar in the USC Leonard Davis School of Gerontology. "This study helps clarify mechanisms involved in accelerated immune aging."

As people age, the immune system naturally begins a dramatic downgrade, a condition called immunosenescence. With advanced age, a person's immune profile weakens, and includes too many worn-out white blood cells circulating and too few fresh, "naive" white blood cells ready to take on new invaders.

Immune aging is associated not only with cancer, but with cardiovascular disease, increased risk of pneumonia, reduced efficacy of vaccines and organ system aging.

But what accounts for drastic health differences in same-age adults? USC researchers decided to see if they could tease out a connection between lifetime exposure to stress -- a known contributor to poor health -- and declining vigor in the immune system.

They queried and cross-referenced enormous data sets from University of Michigan's Health and Retirement Study, a national longitudinal study of the economic, health, marital, family status, and public and private support systems of older Americans.

To calculate exposure to various forms of social stress, the researchers analyzed responses from a national sample of 5,744 adults over the age of 50. They answered a questionnaire designed to assess respondents' experiences with social stress, including stressful life events, chronic stress, everyday discrimination and lifetime discrimination.

Blood samples from the participants were then analyzed through flow cytometry, a lab technique that counts and classifies blood cells as they pass one-by-one in a narrow stream in front of a laser.

As expected, people with higher stress scores had older-seeming immune profiles, with lower percentages of fresh disease fighters and higher percentages of worn-out white blood cells. The association between stressful life events and fewer ready to respond, or naive, T cells remained strong even after controlling for education, smoking, drinking, BMI and race or ethnicity.

Some sources of stress may be impossible to control, but the researchers say there may be a workaround.

T-cells -- a critical component of immunity -- mature in a gland called the thymus, which sits just in front of and above the heart. As people age, the tissue in their thymus shrinks and is replaced by fatty tissue, resulting in reduced production of immune cells. Past research suggests that this process is accelerated by lifestyle factors like poor diet and low exercise, which are both associated with social stress.

"In this study, after statistically controlling for poor diet and low exercise, the connection between stress and accelerated immune aging wasn't as strong," said Klopack. "What this means is people who experience more stress tend to have poorer diet and exercise habits, partly explaining why they have more accelerated immune aging."

Improving diet and exercise behaviors in older adults may help offset the immune aging associated with stress.

Additionally, cytomegalovirus (CMV) may be a target for intervention. CMV is a common, usually asymptomatic virus in humans and is known to have a strong effect accelerating immune aging. Like shingles or cold sores, CMV is dormant most of the time but can flare up, especially when a person is experiencing high stress.

In this study, statistically controlling for CMV positivity also reduced the connection between stress and accelerated immune aging. Therefore, widespread CMV vaccination could be a relatively simple and potentially powerful intervention that could reduce the immune aging effects of stress, the researchers said.

In addition to Klopack, other authors include Eileen Crimmins, a University Professor and the AARP Chair in Gerontology at the USC Leonard Davis School; and Steve Cole and Teresa Seeman of UCLA.

The study was supported by grants from the National Institute on Aging (P30AG017265, U01AG009740).

Story Source:Materials provided by University of Southern California. Original written by Leigh Hopper. Note: Content may be edited for style and length.