Specialized T cells may trigger severe asthma attacks

Scientists have uncovered a group of immune cells that may drive severe asthma. These cells gather in the lungs and appear to cause the most harm in men who develop asthma in later life. The new research suggests asthma patients with these cells in their lungs may be more likely to have hard-to-treat, and potentially fatal, asthma attacks. Normally a doctor would give an asthma patient a general therapy to dampen their immune response, but these cells do not respond to treatment. The scientists uncovered these T cells, called 'cytotoxic CD4+ tissue-resident memory T cells'. It follows hundreds of asthma patients of different ages, sexes, and disease severities. By following patients over many years, and analysing their immune cell populations, researchers are making new connections between asthma symptoms and immune cell activity. Scientists now hope to learn more about these cells and their role in asthma development in order to develop personalised therapies for asthma patients. The T cells are called "memory" cells because they react to molecules that the body has previously fought off. They help protect the body from viruses and bacteria, but the same T cell memory is a big problem for asthma patients. Their misguided T cells see harmless molecules, such as pollen, and produce a dangerous inflammatory response. Men who developed asthma later in life had an overwhelming number of these potentially harmful T cells. Their lungs should have been home to a diverse bunch of CD4+ T cell types but, in this group, more than 65 percent of their cells were cytotoxic CD4+ tissue-resident memory T cells. Single-cell RNA sequencing by LJI scientists provides a 'biomarker' to help detect cytotoxic CD4+ tissue-resident memory T cells in more patients going forward. Before now, scientists and clinicians separated asthma patients into just two groups: 'T2 high' and T2 low'. In a study published earlier this year, the research team showed the importance of drilling down to identify many more asthma patient subgroups; their analysis reveals that 93 percent of WATCH subjects with severe asthma were in the T2 high category. The researchers now want to use sequencing tools and other techniques to discover additional biomarkers and asthma patient subtypes.

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                                      Hormones have the potential to treat liver fibrosis

Researchers have discovered previously unknown changes in a specific type of liver cells, potentially opening avenues for a new treatment for liver fibrosis, a potentially life-threatening condition. Liver fibrosis may occur as a result of liver diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), and currently, there is no medical treatment to cure liver fibrosis. Doctors often try to address the underlying causes of the diseases, such as obesity and diabetes, and these treatments may lead to improved liver function over several years but they do not eliminate fibrosis. The processes that initiate the formation of scar tissue in the liver, i.e., fibrosis, are cellular. Scientists report that they have found previously unknown changes in the cell types responsible for fibrosis formation. These are the liver's so-called stellate cells, named for their star-like appearance. Scientists have found a way to inactivate these cells and thus halt the fibrogenic process. This may offer a real opportunity for halting the formation of scar tissue. The liver's stellate cells, in particular, have a high expression of specific VIP receptors on their surface. VIP stimulates the liver's blood supply but also appears to keep the stellate cells inactive. The researchers believe that their work could provide the basis for the treatment of liver fibrosis. This could result in new ways to treat patients. For example, one could develop synthetic hormones designed to target the receptors on specific cells. Research on liver fibrosis is ongoing worldwide, with many efforts focused on developing effective drugs. Unfortunately, these often come with serious side effects and for this reason, they are not approved. Scientists target these drugs more towards the cell changes have discovered. The results of the research team were initially seen in mice that for a year were fed what the scientist refers to as "a pretty bad western diet"; high in fat and sugar. The researchers will now continue studying stellate cells and their surface receptors in patient samples.

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                               Reducing SBP to less than 120 mmHg reduced cardiovascular risk

An intensive three-year intervention to lower the top blood pressure number to less than 120 mm Hg was more effective at preventing death, heart attack, stroke and other cardiovascular events in adults at high risk for cardiovascular disease, compared to the standard treatment target of under 140 mm Hg, according to new research. The study provides evidence to support targeting systolic blood pressure to less than 120 mm Hg in hypertensive patients with high cardiovascular risk and normal or mild-reduced kidney function, regardless of their diabetes status (Type 1, Type 2 or none) or history of stroke. The researchers conducted a multi-center, randomized controlled trial to evaluate the effects of an intensive blood pressure-lowering strategy on the incidence of major cardiovascular events, including heart attack, stroke, cardiovascular death, revascularization, or hospitalization or emergency room visit for heart failure, in participants with increased cardiovascular risk. Participants in the ESPRIT trial were randomized to receive intensive blood pressure treatment with a systolic blood pressure target of less than 120 mm Hg or standard treatment, with a target measurement of under 140 mm Hg over a three-year period. Antihypertensive medication was prescribed to lower blood pressure in both groups. Patients in the intensive treatment group received multiple classes of hypertensive medications and higher doses of antihypertensive medications in comparison to the usual-treatment group. Safety was assessed between treatment groups by comparing serious adverse events among participants. The researchers found that after two years, participants in the intensive treatment group had significantly better outcomes than those receiving standard care. There was no significant difference in serious adverse events of low blood pressure, electrolyte abnormality, fall resulting in an injury, acute kidney injury or renal failure. Syncope, or fainting, was one of the serious adverse events used to evaluate safety. Syncope occurred at a rate of 0.4% per year in the intensive group and 0.1% in the standard group. This means that for every 1000 patients receiving the intensive treatment for 3 years, 3 patients would experience a serious adverse event of syncope, while 14 major vascular events and 8 deaths would be further prevented, researcher noted. These results provide evidence that intensive hypertension treatment focused on achieving systolic blood pressure of less than 120 mm Hg is beneficial and safe for individuals with high blood pressure and increased cardiovascular risk factors. Implementing this intensive treatment strategy for high-risk adults has the potential to save more lives and reduce the public health burden of heart disease worldwide. Study limitations included that the cardiovascular benefits of the intensive intervention emerged after two years, while the intervention only lasted three years, meaning the relatively short study period may underestimate the benefits, Li said. In addition, the study was conducted in China and therefore, the results may not be generalizable to people in other racial and ethnic groups or living in other countries.

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              A blood test shows Multiple Sclerosis worsening 1 to 2 years before it happens

The study is the first to quantify the timeframe preceding disability worsening in which injury to the central nervous system takes place. Almost 1 million Americans suffer from MS. In advanced cases, patients may have limited mobility and experience spasticity, weakness, poor coordination and incontinence. However, recent advances suggest that more severe symptoms can be substantially delayed or even averted. In the study, the researchers looked at the incidence of disability worsening, defined as six months or more of increased impairment reflected in a higher score on the Expanded Disability Status Scale. They distinguished between disability worsening with relapse, which involves residual symptoms or the return of old ones following relapse, and gradual progression of symptoms without relapse. The researchers tracked data spanning a 10-year period from approximately 4,000 patient. Together, the two studies included almost 1,900 patients. Among those, 570 patients were identified with disability that continued to worsen, of which the majority were independent of relapses. Elevated NfL levels were associated with up to a 91% higher risk of worsening disability with relapse approximately a year later, and up to a 49% higher risk of worsening disability without relapse nearly two years later, the researchers found. Researchers that NfL elevation occurs earlier in disability worsening without relapse. This different pattern may indicate "a more prolonged process that decreases in intensity in advance of increased impairment. This aligns with recognition that death of nerve cells is a slow process that builds toward permanent disability and means that interventions to protect nerve cells might have time to also stop disability. In addition to the groundbreaking findings on the temporal relationship between NfL increases and gradual disease progression in MS. Monitoring NfL levels might be able to detect disease activity with higher sensitivity than clinical exam or conventional imaging. Future investigation will look into therapies that can stop progression during this period of elevated NfL.

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                                  Mindfulness Program Equals Antidepressants in Easing Anxiety Disorders

A new study harnesses the power of mindfulness to help overanxious people calm themselves and the benefit may equal the use of an antidepressant, according to researchers. All were offered either the SSRI antidepressant escitalopram or eight weeks of Mindfulness Based Stress Reduction (MBSR). The mindfulness classes were given weekly and lasted 2.5 hours. People using MBSR were also sent on a weekend mindfulness retreat at about week 5 or 6 of the program. They were also asked to do daily 45-minute practices at home. Participants' anxiety levels were assessed prior to enrollment in the study and then again at completion (eight weeks later). They got follow-up assessments 12 and 24 weeks later, as well. Professionals who conducted the assessments were not told whether the person had undergone the MBSR program or had simply taken the antidepressant. Participants' anxiety was graded on a standard 7-point scale, with 7 representing severe anxiety levels. The people enrolled in the study had an average anxiety score of 4.5, the research team said. Both methods of anxiety reduction seemed to help. Folks who took the antidepressant saw their anxiety scores drop by an average of 1.46 points, while those taking MBSR got an average 1.35-point reduction, which the researchers say is a statistically equivalent benefit. The point drop equals about a 30% decline in anxiety scores. The researcher noted that a big advantage of mindfulness meditation is that it doesn't require a clinical degree to train someone to become a mindfulness facilitator, and additionally, sessions can be done outside of a medical setting, such as at a school or community center. While antidepressants can be effective in easing excess worry, they can sometimes be tough for patients to access or they may come with side effects ranging from sexual dysfunction, nausea or drowsiness. The effectiveness of virtual delivery of MBSR for anxiety disorders is now being studied by the same group of researchers.

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