Category: Respiratory Diseases

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Mortality Risk is Six Times Higher in Hospital Patients with Dyspnoea

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The risk of dying is six times higher among patients who become short of breath after being admitted to hospital, according to research published on Monday in ERJ Open Research. Patients who were in pain were not more likely to die.

The study of nearly 10 000 people suggests that asking patients if they are feeling short of breath could help doctors and nurses to focus care on those who need it most.

The study is the first of its kind and was led by Associate Professor Robert Banzett from Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA. He said: “In hospital, nurses routinely ask patients to rate any pain they are experiencing, but this is not the case for dyspnoea. In the past, our research has shown that most people are good at judging and reporting this symptom, yet there is very little evidence on whether it’s linked to how ill hospital patients are.”

Working with nurses at Beth Israel Deaconess Medical Center, who documented patient-reported dyspnoea twice per day, the researchers found that it was feasible to ask hospital patients to rate their dyspnoea from 0 to 10, in the same way they are asked to rate their pain. Asking the question and recording the answer only took 45 seconds per patient.

Researchers analysed patient-rated shortness of breath and pain for 9 785 adults admitted to the hospital between March 2014 and September 2016. They compared this with data on outcomes, including deaths, in the following two years.

This showed that patients who developed shortness of breath in hospital were six times more likely to die in hospital than patients who were not feeling short of breath. The higher patients rated their shortness of breath the higher their risk of dying. Patients with dyspnoea were also more likely to need care from a rapid response team and to be transferred to intensive care.

Twenty-five per cent of patients who were feeling short of breath at rest when they were discharged from hospital died within six months, compared to seven per cent mortality among those who felt no dyspnoea during their time in hospital.

Conversely, researchers found no clear link between pain and risk of dying.

Professor Banzett said: “It is important to note that dyspnoea is not a death sentence – even in the highest risk groups, 94% of patients survive hospitalisation, and 70% survive at least two years following hospitalisation. But knowing which patients are at risk with a simple, fast, and inexpensive assessment should allow better individualised care. We believe that routinely asking patients to rate their shortness of breath will lead to better management of this often-frightening symptom.

“The sensation of dyspnoea is an alert that the body is not getting enough oxygen in and carbon dioxide out. Failure of this system is an existential threat. Sensors throughout the body, in the lungs, heart and other tissues, have evolved to report on the status of the system at all times, and provide early warning of impending failure accompanied by a strong emotional response.

“Pain is also a useful warning system, but it does not usually warn of an existential threat. If you hit your thumb with a hammer, you will probably rate your pain 11 on a scale of 0-10, but there is no threat to your life. It is possible that specific kinds of pain, for instance pain in internal organs, may predict mortality, but this distinction is not made in the clinical record of pain ratings.”

The researchers say their findings should be confirmed in other types of hospital elsewhere in the world, and that research is needed to show whether asking patients to rate their shortness of breath leads to better treatments and outcomes.

Professor Hilary Pinnock is Chair of the European Respiratory Society’s Education Council, based at the University of Edinburgh and was not involved in the research. She said: “Historically, the monitoring of vital signs in hospitalised patients includes respiratory rate along with temperature and pulse rate. In a digital age, some have questioned the value of this workforce-intensive routine, so it is interesting to read about the association of subjective breathlessness with mortality and other adverse outcomes.

“Breathlessness was assessed on a 0-10 scale which took less than a minute to administer. These noteworthy findings should trigger more research to understand the mechanisms underpinning this association and how this ‘powerful alarm’ can be harnessed to improve patient care.”

Source: EurekAlert!

Categories : Respiratory DiseasesTags :

Study Reveals How a Stubborn Lung Infection Evolves Inside Patients over Years

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Researchers wanted to know what allows the infection to hang on or come back, and whether it develops new tricks or resistances while living inside the lungs.

Photo by Anna Shvets

Researchers at Trinity Translational Medicine Institute (TTMI) and the Irish Mycobacterial Reference Laboratory at St James’s Hospital have uncovered how the bacterium Mycobacterium avium – a leading cause of difficult-to-treat chronic lung infections – changes and adapts inside patients over many years of illness. Their findings, published in Genome Medicine, could help doctors understand why M. avium infections come back and why antibiotics sometimes fail.

The team undertook this research to understand how M. avium manages to survive for years in people’s lungs, even during long courses of antibiotics. This bacterium causes a type of chronic lung infection that’s becoming more common around the world. By looking closely at its genetic code, the team hoped to see how it changes inside the body and why it can be so difficult to clear.

Treating M. avium lung disease is difficult – patients often need 12 months or more of several antibiotics, and treatment still fails in up to half of cases. Many patients get sick again even after therapy.

The team used whole-genome sequencing to analyse nearly 300 bacterial samples from patients in Ireland, the UK and Germany, including 20 Irish patients treated at St James’s Hospital. By reading the DNA of these bacteria over time, the scientists tracked how M. avium evolves, swaps strains and develops resistance while living in the human lung.

They found that infection is often not caused by one single long-term strain, but by repeated reinfection with new ones, sometimes closely related to strains seen in other European countries—hinting at shared environmental sources. The bacterium acquires roughly one new genetic change per year, and most importantly, the team found that thirteen specific genes showed signs of adaptation to antibiotics, immune attack and low-oxygen stress.

Lead author Dr Aaron Walsh, researcher in the Trinity Translational Medicine Institute said:

 “Our study shows that M. avium can evolve in real time inside the lung. Understanding which genes help it survive may point us towards new treatment targets for this increasingly common and stubborn infection.”

This is the first study to use whole-genome sequencing to follow M. avium infections inside patients over many years, revealing how the germ evolves within the lungs.

Key findings from study

  1. Reinfection is common: Many patients picked up new strains over time, suggesting they were reinfected from the environment rather than suffering relapse of the same infection.
  2. International connections: Some Irish strains were genetically almost the same as ones from UK and Germany.
  3. Thirteen key genes changed under pressure: These genes help the bacterium cope with antibiotics, low oxygen, or attack by the immune system.
  4. Resistance can appear during treatment: We saw changes in a gene linked to rifampicin resistance in two patients receiving that drug.

Uniquely, in this study researchers found that thirteen genes under “positive selection” was new for M. avium.

Dr Emma Roycroft, Specialist Medical Scientist in the Irish Mycobacterial Reference Laboratory. “Some of those genes weren’t previously linked to survival of M. avium inside the body. For example, one involved in handling oxidative stress and another in forming biofilms. This has highlighted important pathways that could be targeted with new treatments. It was also striking that Irish, British and German samples were so closely related, even though the patients had never met.”

The team’s next steps are:

  • Test in the lab how those thirteen genes help the bacterium survive.
  • Use long-read sequencing to see genetic changes that short-read methods miss.
  • Study environmental samples to find where reinfections come from.
  • Expand their research to other patient groups to see if the same patterns occur.

Source: Trinity College Dublin

Categories : Paediatrics Respiratory DiseasesTags :

Combination Inhaler Cuts Asthma Attacks in Children by Nearly Half

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Findings from a trial comparing the real-world effectiveness of asthma inhalers could reshape how children with asthma are treated.

In the first randomised controlled trial to investigate the use of a 2-in-1 inhaler as the sole reliever therapy for children aged 5 to 15, an international team found the combined treatment to be more effective than salbutamol, the current standard for asthma symptom relief in children, with no additional safety concerns.

The results show that using a single 2-in-1 anti-inflammatory reliever inhaler – which combines the inhaled corticosteroid (ICS) budesonide and the fast-acting bronchodilator formoterol – reduced children’s asthma attacks by an average of 45%, compared to the widely-used salbutamol inhaler.

Asthma attacks in children may be life-threatening and reducing their frequency and severity is a public health priority.

The 2-in-1 budesonide-formoterol inhaler is widely recommended as the preferred reliever treatment for adults, but children are still usually prescribed salbutamol.

Researchers say the findings, published in The Lancet, provide the evidence needed to bring children’s global asthma guidelines into line with adults’, which could benefit millions of children around the world with mild-to-moderate asthma.

The CARE study (Children’s Anti-inflammatory REliever) was designed and led by the Medical Research Institute of New Zealand (MRINZ), in collaboration with Imperial College London, University of Otago Wellington, Starship Children’s Hospital, and the University of Auckland. It recruited 360 children across New Zealand who were then randomly assigned to receive either budesonide-formoterol or salbutamol for on-demand symptom relief.

The trial lasted a year and the budesonide-formoterol reliever resulted in a lower rate of asthma attacks than salbutamol reliever, with rates of 0.23 versus 0.41 per participant per year. This means that for every 100 children with mild asthma who are switched from salbutamol to a 2-in-1 budesonide-formoterol inhaler, there would be 18 fewer asthma attacks per year. Importantly, the study also confirmed the safety of the combined-inhaler approach, with no significant differences in children’s growth, lung function, or asthma control between the two groups.

Dr Lee Hatter, lead author of the study and Senior Clinical Research Fellow at the MRINZ, said: “This is a key step in addressing the evidence gap that exists between asthma management in adults and children. For the first time, we have demonstrated that the budesonide-formoterol 2-in-1 inhaler, used as needed for symptom relief, can significantly reduce asthma attacks in children with mild asthma. This evidence-based treatment could lead to improved asthma outcomes for children worldwide.”

Professor Richard Beasley, Director of MRINZ and senior author of the study, said: “Implementing these findings could be transformative for asthma management on a global scale. The evidence that budesonide-formoterol is more effective than salbutamol in preventing asthma attacks in children with mild asthma has the potential to redefine the global standard of asthma management.”

The burden of asthma in the estimated 113 million children and adolescents with asthma worldwide is substantial. The latest study builds on previous studies in adults led by MRINZ researchers which shaped international asthma treatment guidelines. These findings contributed to the recommended use of the 2-in-1 ICS–formoterol reliever inhaler as the preferred reliever treatment for adults with asthma around the world.

The incorporation of findings from the CARE study into global asthma treatment strategies could help reduce disparities in care and ensure that more children access effective, evidence-based treatments.

The researchers say that global health organisations have long advocated for child-targeted asthma interventions, and their findings provide crucial evidence to support those efforts.

However, the authors acknowledge some limitations of the clinical trial. It was undertaken during the COVID-19 pandemic, during which stringent public health measures and fewer circulating respiratory viruses contributed to the lower than predicted rate of severe asthma attacks. The authors also acknowledge the challenges with the identification of asthma attacks in children, and the potential bias with the lack of blinding of the randomised treatments. They say though that the study’s findings are generalisable to clinical practice due to its pragmatic, real-world design.

Professor Andrew Bush, from Imperial College London, senior respiratory paediatrician and co-author of the CARE study, said: “Having an asthma attack can be very scary for children and their parents. I’m so pleased that we’ve been able to prove that an inhaler that significantly reduces attacks – already a game-changer for adults – is safe for children with mild asthma too. We believe this will transform asthma care worldwide and are excited to be building on this work with the CARE UK study.”

Professor Helen Reddel, Chair of the Science Committee of the Global Initiative for Asthma (GINA), commented on the global significance of the study, saying that it fills a critically important gap for asthma management globally. Professor Reddel said: “Asthma attacks have a profound impact on children’s physical, social and emotional development and their prevention is a high priority for asthma care. It is in childhood, too, that lifelong habits are established, particularly reliance on traditional medications like salbutamol that only relieve symptoms and don’t prevent asthma attacks.”

Professor Bob Hancox, Medical Director of the New Zealand Asthma and Respiratory Foundation, said: “This is a very important study for children with mild asthma. We have known for some time that 2-in-1 budesonide/formoterol inhalers are better than the traditional reliever treatment in adults, but this had not been tested in children. This research shows that this 2-in-1 inhaler is effective and safe for children as young as 5. This information will help to reduce the burden of asthma for many children, and both they and their families will breathe easier because of it.”

Source: Imperial College London

Categories : Respiratory DiseasesTags :

First Drug Treatment for Sleep Apnoea Succeeds in Clinical Trial

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The drug sulthiame reduces the number of breathing pauses and improves sleep quality in patients with obstructive sleep apnoea, according to a European clinical study in which the University of Gothenburg played a significant role. The findings offer hope for a drug-based treatment for people who cannot tolerate CPAP breathing masks.

The study, published in The Lancet, included 298 patients with moderate to severe sleep apnoea. One quarter received a placebo, while the remaining participants were given sulthiame in different doses. The double-blind clinical trial was conducted in four European countries.

A possible breakthrough

The study found that patients receiving the higher doses of the drug had up to 47% fewer breathing interruptions and better oxygenation compared with those given placebo. Sulthiame works by stabilizing the body’s breathing control and increasing respiratory drive, thereby reducing the risk of the upper airway collapsing during sleep. Most side effects were mild and transient.

Jan Hedner, senior professor of pulmonary medicine at the Sahlgrenska Academy, University of Gothenburg, has played a leading role in the study. 

“We have been working on this treatment strategy for a long time, and the results show that sleep apnoea can indeed be influenced pharmacologically. It feels like a breakthrough, and we now look forward to larger and longer studies to determine whether the effect is sustained over time and whether the treatment is safe for broader patient groups,” says Jan Hedner.

Many struggle with CPAP

Sleep apnoea occurs when the upper airways collapse during sleep, causing repeated breathing pauses, oxygen deprivation, and disrupted sleep. Over time, untreated sleep apnoea increases the risk of high blood pressure, cardiovascular disease, stroke, and type 2 diabetes.

Although the condition is common, there is still no drug that treats the underlying cause. The standard treatment – continuous positive airway pressure (CPAP) – is highly effective but difficult for many to tolerate. Up to half of all patients discontinue CPAP within a year, as the mask can feel uncomfortable or disturb sleep.

Sulthiame is an existing medication previously approved for treating a form of childhood epilepsy, and is now being evaluated for sleep apnoea.

Source: University of Gothenburg

Categories : Antibiotics Respiratory DiseasesTags :

Targeted Steroid Use Might Offer a Universal Complementary Treatment for TB

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Tuberculosis bacteria. Credit: CDC

While steroids like dexamethasone are used in certain tuberculosis cases (eg, TB meningitis), their impact on immune cells is not well understood. Given the renewed interest in the steroid dexamethasone, as a host-directed treatment during the COVID-19 pandemic, a Trinity College Dublin team provides evidence that treating patients with steroids may enhance the function of their macrophages to kill the mycobacteria, while diminishing pathways of inflammatory damage. The study is published now in the journal Scientific Reports.

The team’s goal was to determine whether dexamethasone impacts the macrophage’s ability to fight TB. Although glucocorticoids can reactivate TB, they are paradoxically the only adjunctive host-directed therapies that are recommended by the World Health Organization for TB. Steroids are given to patients alongside antimicrobials in certain circumstances, however, scientists don’t fully understand the effect of these drugs on the immune system, especially innate immune cells such as macrophages.

The researchers studied immune cells called macrophages derived from the blood of healthy volunteers or isolated from lung fluid donated by patients undergoing routine bronchoscopies. By treating and infecting these macrophages in the lab with Mycobacterium tuberculosis (Mtb), the scientists could examine and understand how dexamethasone affects the immune response that protects the lungs during infection.

Key findings from the study

  • Dexamethasone a potent glucocorticoid reduces glycolysis in human lung and blood derived macrophages. This reduces the amount of energy available in the cell.
  • Dexamethasone reduced the production of both pro and anti-inflammatory cytokines measured in the study, IL-1β, TNF, IL-6, IL-8 and IL-10. Although helpful for immunity, limiting the production can also limit damage from excessive inflammation.
  • Mtb-infected macrophages have increased survival when they were treated with dexamethasone. This suggests that dexamethasone may protect macrophages from dying due to the harmful effects of infection or detrimental immune responses to infection.
  • Dexamethasone reduces bacterial burden in infected macrophages, and we have identified that this is at least partly mediated by autophagy and phagosomal acidification. Dexamethasone can enhance the macrophages’ ability to degrade and clear bacteria helping to overcome infection with Mtb.

This study identifies that macrophages from different sources have differential responses to glucocorticoids. This highlights that tissue origin can influence how macrophages react to drugs, which may be important for targeting treatment strategies. This is one of the first studies to show that dexamethasone can reduce inflammation while preserving or enhancing antimicrobial function in primary human lung macrophages infected with Mtb.

How could this research change a patient’s life?

The findings support the use of steroids as an extra therapy in conjunction with existing antimicrobial therapies in TB treatment, especially in cases with excessive inflammation. Steroids might also be useful with antimicrobials in TB preventative therapy, to reduce progression from latent TB infection to active TB disease. This study opens avenues for macrophage-targeted steroid therapies that balance inflammation control with antimicrobial defence.

For now, researchers hope this study will hasten the recovery of TB patients who experience debilitating symptoms, often for months into existing therapy.

Dr Donal Cox, Senior Research Fellow, Clinical Medicine, Trinity College Dublin said:

“Our study shows that dexamethasone, which is known to dampen inflammation, can also help macrophages fight tuberculosis more effectively. This challenges the assumption that steroids always suppress immunity and opens the door to smarter, targeted adjunctive therapies that balance inflammation control with antimicrobial defence.”

Prof Joseph Keane, Professor of Medicine, Trinity College Dublin and Consultant Respiratory Physician, St James Hospital said:

“In clinical practice, steroids are the most under-used adjunctive therapy for TB. We often rely on steroids to manage inflammation in tuberculosis, particularly in severe forms like TB meningitis. What’s reassuring from this study, is that dexamethasone not only tempers inflammation but also appears to support the macrophage’s ability to control infection. This study provides new evidence to help us redefine steroid use in TB care—targeting inflammation without compromising antimicrobial defence.”

Next steps for this research

Developing steroid therapies that can be specifically targeted to lung macrophages via mechanisms such as inhaled nanoparticles might be an option to translating this into better therapy. The team also wants to identify how steroids altered different metabolic pathways in human lung macrophages and not in blood derived macrophages so they can exploit this to make steroid therapies better in the future.

Source: Trinity College Dublin

Categories : Lab Tests and Imaging Respiratory DiseasesTags :

Researchers Pioneer New Breathing Test to Detect Lung Disease Earlier

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Credit: Scientific Animations CC4.0

A new project led by Oxford University aims to develop a novel breathing test that could detect asthma and COPD earlier, more accurately, and closer to home – reducing pressure on the NHS and improving outcomes for patients.

This work is included in a portfolio of research funded by the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation, to make diagnostic testing more accessible by designing simple, affordable tools that can be used in everyday settings. The project, called ACCESS (A Community-based diagnostiC for early airwayS disease), focuses on airway diseases, and will receive £1.3 million over three years.

Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) affect more than half a billion people worldwide and cause over four million deaths every year. In the UK, these conditions hit disadvantaged communities hardest, with people in areas of socioeconomic deprivation facing particular challenges in accessing hospital-based diagnostic care.

A volunteer undertaking a computed cardiopulmonography based breath test. (The volunteer is Dr Nick Smith, a member of the research team developing the CCP technology). Credit: Department of Chemistry, University of Oxford.

Currently, asthma and COPD diagnosis relies on a test called spirometry. This measures how much air a person can forcefully breathe out, but it is difficult for many patients to perform and often fails to detect disease in its earliest stages. By the time spirometry picks up abnormalities, damage to the lungs is usually irreversible, resulting in late diagnoses, missed chances for early treatment, and poorer outcomes.

The project is enabled by the strong ethos for collaborative and innovative research in this University and will be delivered by a multi-disciplinary team, working across university departments and the NHS.

Project lead Professor Grant Ritchie

To address these issues, Oxford researchers have developed a new test, known as computed cardiopulmonography (CCP), that could transform the way lung diseases are diagnosed. CCP is performed while a patient breathes normally for 12 minutes through a mouthpiece linked to a highly accurate gas analyser. Using cutting-edge laser technology and advanced mathematical modelling, the test captures a detailed picture of how evenly air flows through the lungs. This “fingerprint” of lung function changes early in the course of disease, making CCP a powerful tool for spotting subtle problems that spirometry can miss.

Early studies in people with asthma, COPD, and even in otherwise healthy smokers suggest CCP is a highly sensitive marker of small airways damage. But while the results are promising, the test currently takes too long and requires specialist gas supplies, restricting its use to hospitals and research labs.

The goal of the ACCESS project is to adapt CCP for community use, for instance in GP surgeries, pharmacies, and community diagnostic hubs. Specifically, the research team will work to reduce the time duration and volume of gas needed for each test, and speed up the data analysis so that results can be shared with the patient during the same appointment. Towards the end of the project, CCP will be trialled in a community diagnostic centre to gather feedback from patients and healthcare professionals.

The long-term goal is to support earlier diagnosis and treatment, helping reduce hospital visits and tackle health inequalities. By enabling earlier intervention and delivering care closer to home, CCP has the potential to improve outcomes for millions of people living with lung disease.

Source: Oxford University

Categories : Respiratory Diseases Substance UseTags :

Inhaling Cannabis May Greatly Increase Risk of Lung Disease

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For those looking to reduce their chances of developing lung disease, say experts at UC San Francisco, then it may be smart to avoid inhaling cannabis.

A new study in the Journal of General Internal Medicine found that inhaling marijuana every day is associated with a 44% increased chance of developing asthma. It also increases the odds of developing a common set of lung diseases known as chronic obstructive pulmonary disease (COPD) by 27%.

The risk of COPD, which includes emphysema and chronic bronchitis, may be understated. The disease takes decades to develop, and the researchers did not have detailed information on how long people in the study had been using cannabis.

Researchers defined “inhaling” as smoking, vaping, and so-called “dabbing,” which involves breathing in the vapors of concentrated marijuana. The study found an association between elevated risks to a person’s lungs and doing any of those things with cannabis even for those who had never smoked cigarettes.

For those who never smoked cigarettes, inhaling marijuana every day was linked to a 51% increased likelihood of developing asthma. The association with COPD was also elevated, but it was not statistically significant.

The study is the largest yet to examine the association between inhaling cannabis and risks to respiratory health among people who have not smoked cigarettes. Of the 380 000 adult participants, nearly 222 000 had never smoked tobacco. The data comes from the Behavioral Risk Factor Surveillance System, a national survey by the Centers for Disease Control and Prevention (CDC).

Experts say the broad legalization of marijuana across much of the country and the perception that it is healthier than tobacco has led people to minimize the risks.

“The message about smoking tobacco being bad for you has gotten out there, but for cannabis, it’s much less clear,” said Alison Rustagi, MD, PhD, assistant professor at UCSF and first author of the paper.

“If people are looking to reduce their likelihood of developing a chronic lung disease, they should not start using cannabis,” she said. “And if they already smoke cannabis, they should do it less often.”

Source: University of California – San Francisco

Categories : Paediatrics Respiratory DiseasesTags :

Study Finds that Even Healthy Children Are Vulnerable to RSV

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Photo by William Fortunato

It is not only premature babies and children with underlying diseases who suffer from serious respiratory syncytial virus (RSV) infections. Even healthy, full-term babies are at significant risk of intensive care or prolonged hospitalisation – especially during the first three months of life. This is according to a comprehensive registry study from Karolinska Institutet published in The Lancet Regional Health – Europe.

RSV is a common cause of respiratory infections in young children and accounts for around 245,000 hospital admissions annually in Europe. Researchers have now analysed data from over 2.3 million children born in Sweden between 2001 and 2022 to find out who is at greatest risk of suffering serious complications or dying from an RSV infection.

Preventive treatment available

It is well-known that premature babies and children with chronic diseases are at increased risk of developing severe illness when infected with RSV. It is also known that children under three months of age are particularly vulnerable, but it has not been entirely clear how common severe disease is among previously healthy children. The study shows that the largest group among the children who needed intensive care or were hospitalised for a long period of time were under three months of age, previously healthy and born at full term.

“When shaping treatment strategies, it is important to take into account that even healthy infants can be severely affected by RSV,” says the study’s first author, Giulia Dallagiacoma, a physician and doctoral student at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “The good news is that there is now preventive treatment that can be given to newborns, and a vaccine that can be given to pregnant women.”

Starting September 10, 2025, all newborns in Sweden are being offered preventive treatment with antibodies during the RSV season. The drug works much like a vaccine and protects against severe RSV infection for about six months.

Several risk factors identified

A total of 1.7 per cent of the children in the study were diagnosed with RSV infection. Among those, just under 12 per cent (4,621 children) had a severe course of illness. The median age of children who needed intensive care was just under two months, and the majority of them had no underlying disease.

The researchers identified several factors that were linked to an increased risk of needing intensive care or dying. Children who were born in the winter, or had siblings aged 0–3 years or a twin, had approximately a threefold increased risk, while children who were small at birth had an almost fourfold increased risk. Children with underlying medical conditions had more than a fourfold increased risk of severe illness or death.

“We know that several underlying diseases increase the risk of severe RSV infection, and it is these children who have so far been targeted for protection with the preventive treatment that has been available,” says the study’s last author, Samuel Rhedin, resident physician at Sachs’ Children and Youth Hospital and associate professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “However, the study highlights that a large proportion of children who require intensive care due to their RSV infection were previously healthy. Now that better preventive medicines are available, it is therefore positive that the definition of risk groups is being broadened to offer protection during the RSV season to previously healthy infants as well.”

Source: Karolinska Institutet

Publication

“Risk factors for severe outcomes of respiratory syncytial virus infection in children: a nationwide cohort study in Sweden”, Giulia Dallagiacoma, Cecilia Lundholm, Awad I Smew, Emma Caffrey Osvald, Pekka Vartiainen, Santtu Heinonen, Tobias Alfvén, Catarina Almqvist, Samuel Rhedin, The Lancet Regional Health – Europe, online 10 September 2025, doi: 10.1016/j.lanepe.2025.101447.

Categories : Respiratory DiseasesTags :

Researchers Identify Promising New Compound to Treat Tuberculosis

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As part of the ongoing fight against tuberculosis, scientists within Texas A&M AgriLife Research and Calibr-Skaggs have developed a promising new compound targeting a key bacterial enzyme on M. tuberculosis. The compound, using a novel mechanism, proved effective against even drug-resistant strains of tuberculosis in early studies. (Inna Krieger/Texas A&M AgriLife)

Scientists have developed a new compound that could offer a breakthrough in the global fight against tuberculosis, history’s deadliest infectious disease.

A study recently published in Nature describes the treatment potential of the novel compound known as CMX410. The drug uniquely targets a crucial enzyme in Mycobacterium tuberculosis, the bacterium responsible for tuberculosis. Importantly, this compound even proved effective against drug-resistant infections, which are common globally and pose a significant challenge for controlling the disease’s spread and progression.

The study was led by James Sacchettini, PhD, the Rodger J. Wolfe-Welch Foundation Chair in Science, Texas A&M AgriLife Research scientist and professor in the Texas A&M College of Agriculture and Life Sciences Department of Biochemistry and Biophysics and College of Arts and Sciences Department of Chemistry. He was joined by Case McNamara, PhD, senior director of infectious disease at Calibr-Skaggs Institute for Innovative Medicines, the nonprofit drug development division of Scripps Research dedicated to accelerating next-generation medicines.

The discovery was made possible through collaborations formed by the TB Drug Accelerator program, an initiative funded by The Gates Foundation to support research focused on developing the most promising tuberculosis treatments.

“A lot of people think of tuberculosis as a disease of the past,” Sacchettini said. “But in reality, it remains a major public health issue requiring significant attention, collaboration and innovation to overcome.”

A smarter way to fight back

The new compound identified by AgriLife Research and Calibr-Skaggs works by blocking a crucial enzyme, polyketide synthase 13 or Pks13, that M. tuberculosis needs to build its protective cell wall. Without the functionality of this protein, the bacteria can’t survive to cause infection.

For over a decade, scientists have recognised this protein as a high-value target in the fight against tuberculosis. Yet, despite its potential, drug development efforts have repeatedly fallen short – largely because compounds must clear a high bar for both safety and therapeutic performance.

The unique mechanism of CMX410 makes it highly specific for its target, which translates to a favourable safety profile. By incorporating a reactive chemical group that forms an irreversible bond with a critical site on Pks13, the researchers enhanced the compound’s selectivity, minimising potentially negative off-target effects. This modification also reduces the likelihood of resistance emerging.

The addition of this key chemical group was accomplished with click chemistry, a method that snaps molecules together like puzzle pieces. Click chemistry was developed by co-author Barry Sharpless, Ph.D., W.M. Keck Professor of Chemistry at Scripps Research and two-time Nobel Laureate, and it has led to the development of extensive libraries of chemical compounds.

“This technique represents a new tool for drug design,” said McNamara. “We expect to see its uses expand in the coming years to help address public health concerns with a critical need, including tuberculosis.”

Early results prove safe and effective

The team began by investigating a library of compounds shared by the Sharpless lab to identify molecules that could inhibit bacterial growth of M. tuberculosis.

After intensive optimization to improve compound potency and other pharmacological properties led by Calibr-Skaggs tuberculosis team members and co-first authors Baiyuan Yang, Ph.D., associate director of medicinal chemistry, and Paridhi Sukheja, Ph.D., investigator of infectious diseases, CMX410 was identified as a strong contender.

Yang, who led the chemistry optimisation, said the team explored more than 300 analogues to identify a compound with the right balance of potency, selectivity and safety. The team ultimately tested CMX410 against 66 strains of M. tuberculosis and found that it worked on both laboratory and multidrug-resistant strains collected from real patients.

“Identifying this novel target was an exciting moment,” said Sukheja, who led many early studies showing CMX410 could target a previously unexplored gene. “It opened up a completely new path forward, especially against strains that have learned to evade existing treatments.”

In other early experiments, the researchers determined that CMX410 could be safely combined with other tuberculosis antibiotics. This was an especially important factor for this disease, as treatment regimens require multiple drugs to be taken together for months at a time.

Researchers found no adverse effects in their initial tests in animal models even at the maximum dose level. And because CMX410 is highly specific to its target protein, they see it as unlikely to disrupt other beneficial bacteria or cause broader microbiome imbalances, a common side effect of conventional antibiotics.

Progress toward better treatments

The addition of a specialised chemical group that allows CMX410 to irreversibly bind to its target makes the compound extremely selective. These types of inhibitors remain an exciting and underexplored class of drugs, and further research will be needed to confirm their safety for humans.

Nonetheless, the precision, unique mechanism, good safety profile and other key features all make CMX410 a promising candidate for treating tuberculosis.

“These early results are very encouraging,” said Inna Krieger, Ph.D., senior research scientist in Sacchettini’s lab and co-first author of the study. “Cell wall-targeting antibiotics have long been a cornerstone of tuberculosis treatment. However, after decades of widespread use, their effectiveness is waning due to the rise of drug-resistant strains.

“We are working to discover new drugs that disrupt essential biological processes and identify optimal combinations with existing drugs to enable shorter, safer and more effective treatment regimens. Through these efforts, we hope to help move the world closer to a future free from tuberculosis.”

Source: Scripps Research

Categories : COVID Respiratory DiseasesTags :

COVID Infection Linked to Increased Risk of Asthma – Vaccination Offers Protection

On By ModernMedia
Respiratory tract. Credit: Scientific Animations CC4.0

People who have had COVID are at increased risk of developing certain inflammatory diseases of the airways, such as asthma, hay fever and chronic sinusitis. However, vaccination against the SARS-CoV-2 virus appears to reduce the risk, according to a comprehensive epidemiological study led by researchers at Karolinska Institutet.

The international research team used an electronic health database in the United States, TriNetX, to investigate the link between COVID and so-called type-2 inflammatory diseases, a group of chronic conditions in which the immune system overreacts to allergens or infections.

The researchers compared 973 794 people who had had COVID with 691 270 people who had been vaccinated against the SARS-CoV-2 virus and 4 388 409 healthy controls with no documented infection or vaccination.

Inflammation in the airways

The results are presented in The Journal of Allergy and Clinical Immunology. People who had had COVID had a 66% higher risk of developing asthma, a 74% higher risk of chronic sinusitis and a 27% higher risk of hay fever compared with healthy controls. However, no increased risk was seen for the skin disease atopic eczema or for eosinophilic oesophagitis, an inflammation of the oesophagus.

“Our results suggest that COVID-19 can trigger type-2 inflammation in the airways, but not in other organs,” says Philip Curman, a physician and researcher at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet, Sweden, who led the research.

Vaccination against the virus had the opposite effect. The risk of asthma was 32% lower among vaccinated individuals compared with healthy unvaccinated individuals. The risk of sinusitis and hay fever was also slightly lower.

More than twice the risk

When people who had had COVID were compared with vaccinated individuals, an even clearer effect was seen. Infected individuals had more than twice the risk of developing asthma or chronic sinusitis and a 40% higher risk of developing hay fever compared with those who had been vaccinated.

“It is interesting to see that vaccination not only protects against the infection itself, but also appears to provide good protection against certain respiratory complications,” says Philip Curman.

The study is retrospective, i.e. based on data that has already been collected. This means that the researchers cannot draw any firm conclusions about causal links. Another limitation is that some infections may have gone undiagnosed, especially if they were detected through self-testing.

The research was conducted in close collaboration with the University of Lübeck and the Lübeck Institute of Experimental Dermatology in Germany, the Technical University of Madrid in Spain and Bar-Ilan University in Israel. It was mainly funded by the German Research Foundation (Deutsche Forschungsgemeinschaft), Region Stockholm and Karolinska Institutet. Two researchers received travel grants from TriNetX, which provides the database used in the study, and one of the authors is employed by the company.

Source: Karolinska Institutet