The study analyzed data from almost 500 patients hospitalized with COVID-19 across six countries. Patients who inhaled heparin were half as likely to require ventilation and had a significantly lower risk of dying compared with those receiving standard care.

Heparin, a drug traditionally injected to treat blood clots, was tested in this study in an inhaled form, targeting the lungs directly. As well as acting as an anticoagulant, heparin has anti-inflammatory and pan-antiviral properties. Earlier research results showed breathing and oxygen levels improved in COVID-19 patients after they inhaled a course of heparin.

The researchers believe the drug could also be useful in fighting other serious respiratory infections such as pneumonia.

Professor Clive Page, Emeritus Professor of Pharmacology at King's who co-led the international study with ANU's Professor van Haren, said: "Inhaled heparin is anti-viral, anti-inflammatory and anti-coagulant. There's no other drug that has that unique combination. We know it's only a matter of time until the next pandemic, and there are still COVID-19 patients who get very sick. This is a great weapon to have up our sleeve."

While the findings highlight the potential of inhaled heparin, further development is required before the treatment can be routinely adopted. The researchers believe the drug could also be useful in fighting other serious respiratory infections such as pneumonia, which can be caused by a range of viruses and bacteria.

According to Professor van Haren, the drug would also be helpful for those with a compromised immune system, such as cancer patients, when they experience a respiratory infection.

Professor Frank van Haren, lead author, ANU and Director of the Intensive Care Unit at the St George Hospital in Sydney, said: "It doesn't matter what kind of respiratory infection the patient is dealing with, the drug -- when inhaled -- will stop it from infecting the patient and from damaging the lungs. We're aiming to conduct another trial in Europe to confirm its effectiveness in fighting other common respiratory infections such as influenza and RSV. And because it's inexpensive, it's much more accessible for those from low-income countries"

The researchers are now also developing an improved formulation of heparin, specifically designed to be given by inhalation.

The research is published in eClinicalMedicine and simultaneously presented of at the European Respiratory Society (ERS) International Congress in Amsterdam on Sunday, September 28, the leading annual gathering for respiratory research.

The study was presented by Pimpika Kaewsri, a PhD student from the Centre for Environmental Health and Sustainability at the University of Leicester, UK.

She explains: "Over 90% of the global population is exposed to air pollution levels that exceed WHO guidelines, and ample research shows that exposure to higher air pollution levels is associated with reduced lung function.

"Separately, a healthy diet -- particularly one high in fruits and vegetables -- has been linked to better lung function. We wanted to explore whether a healthy diet or specific food groups could modify or partly mitigate the known adverse effects of air pollution on lung function."

Using UK Biobank data from around 200,000 participants, Kaewsri compared people's dietary patterns -- including their fruit, vegetable and whole grains intake -- with their lung function (FEV₁ - the amount of air exhaled in one second) and their exposure to air pollution in the form of fine particulate matter (PM_2.5). PM_2.5 concentration is the amount of very tiny particles, 2.5 micrometers or smaller, released into the air, for example by vehicle exhausts and industrial processes. The team also accounted for other factors such as age, height, and socioeconomic status.

For every increase in exposure to PM_2.5 of five micrograms per cubic meter of air, the team observed a 78.1ml reduction in FEV₁ in the low fruit intake group, compared to only a 57.5ml reduction in the high fruit intake group in women.

Kaewsri explains: "Our study confirmed that a healthy diet is linked to better lung function in both men and women regardless of air pollution exposure. And that women who consumed four portions of fruit per day or more appeared to have smaller reductions in lung function associated with air pollution, compared to those who consumed less fruit.

"This may be partly explained by the antioxidant and anti-inflammation compounds naturally present in fruit. These compounds could help mitigate oxidative stress and inflammation caused by fine particles, potentially offsetting some of the harmful effects of air pollution on lung function."

Kaewsri also noted that, in the study population, men generally reported lower fruit intake than women. "This difference in dietary patterns may help explain why the potential protective effect of fruit against air pollution was only observed in women," she adds.

Kaewsri plans to extend the research by exploring whether diet can influence changes in lung function over time.

Professor Sara De Matteis, Chair of the European Respiratory Society's expert group on occupational and environmental health, based at the University of Turin, Italy, who was not involved in the research said: "This study confirms the potential respiratory health benefits of a healthy diet, especially rich in fresh fruit intake.

"However, access to a healthy diet is not equally distributed in the population and, even if the authors adjusted for socioeconomic status, some residual confounding cannot be ruled out.

"A healthy plant-rich diet should be promoted in the population starting from primary school, not only for preventing chronic diseases, but also to reduce the carbon-footprint of meat-rich diets.

"This does not exempt governments from continuing with environmental policies to reduce air pollution to as low as possible, given there are no safe exposure levels, and it does not transfer their accountability to individuals whose diet choices are often constrained by economic needs."

In the first randomized 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 on Sept. 27 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 (see detail in Notes, below) 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 organizations 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 randomized treatments. They say though that the study's findings are generalizable to clinical practice due to its pragmatic, real-world design.

Professor Andrew Bush, from Imperial College London, senior respiratory pediatrician 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."

Study key points:

1. The CARE study is the first randomized controlled trial comparing ICS-formoterol anti-inflammatory reliever inhaler treatment with salbutamol reliever inhaler treatment, in children aged five to 15 years with asthma.
2. Budesonide-formoterol demonstrated a significant reduction in asthma attacks, with a 45% decrease in the rate of attacks compared to salbutamol (0.23 vs 0.41 attacks per participant per year; relative rate 0.55, 95% CI 0.35-0.86, p=0.01).
3. These findings are consistent with established benefits seen in adults, where ICS-formoterol has become the preferred reliever treatment for asthma management.
4. The study found no safety concerns regarding the use of a combined inhaled steroid treatment in children, with no adverse effects on growth or lung function.
5. This study provides compelling evidence that switching from a salbutamol reliever inhaler to a budesonide-formoterol reliever inhaler can help prevent asthma attacks in children with mild asthma as young as five, which could lead to a potential shift in asthma treatment globally

The study was made possible by the generous support of the Health Research Council of New Zealand, Cure Kids (New Zealand), and the Barbara Basham Medical Charitable Trust managed by Perpetual Guardian. Symbicort Rapihalers for the trial were provided by AstraZeneca.