By Debbie Bunch
November 3, 2025
Rethinking the Cause of Asthma
Asthma is driven by inflammation in the lungs that causes airway constriction, thus making it hard to breathe. Leukotrienes, chemicals released by white blood cells in response to an irritant, play a significant role in this process. Asthma medications aim to block the molecular cascade initiated by these chemicals.
End of story, right?
According to researchers from Case Western Reserve University, the University of Toledo, and the Cleveland Clinic Children’s Hospital, maybe not. In a laboratory study, they discovered that a different group of chemicals, which they have dubbed “pseudo leukotrienes,” may really be to blame.
The study was built on years of prior research on lipid oxidation. The authors note that while leukotrienes are formed under the control of enzymes that transform lipids, pseudo leukotrienes are formed by adding oxygen to lipids via molecules called “free radicals.”
People with asthma may lack enzymes and antioxidant molecules that keep free radicals in check, thus allowing the production of more pseudo leukotrienes.
After discovering the existence of these chemicals, the researchers developed methods to detect them in urine samples from patients with mild or severe asthma. These samples were then compared to urine from people without asthma.
Pseudo leukotrienes were found in the urine of the asthma patients, and the amount of the chemicals was directly correlated to disease severity. However, whether the asthma was severe or mild, asthma patients still had four to five times more pseudo leukotrienes than the healthy controls.
The researchers believe pseudo leukotrienes could be a new biomarker for clinicians to use when testing for asthma severity and monitoring the effectiveness of therapies. The discovery could lead to new treatments as well.
“We’ve found molecules that are alike in structure but generated through a completely different chemical pathway in the body,” said lead researcher Robert Salomon, PhD, from Case Western Reserve. “The real importance of this discovery is the possibility of treating these diseases with drugs that prevent the free radical process or moderate it rather than drugs that block the receptor.”
Next steps will also involve studies aimed at seeing whether pseudo leukotrienes are involved in other respiratory diseases, such as RSV, bronchiolitis, and COPD. The study was published in the Journal of Allergy and Clinical Immunology.
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New Guideline for Pediatric Tracheostomies
The American Thoracic Society has published a new clinical practice guideline to help clinicians and family caregivers decide whether a tracheostomy is needed in a child. Published in the American Journal of Respiratory and Critical Care Medicine, the guideline recommends:
- Applying ethical principles to guide shared decision-making about tracheostomy placement (strong recommendation).
- A standardized discharge process involving comprehensive family caregiver training for safe transitions from hospital to home (conditional recommendation).
- A continuously awake, trained caregiver to manage emergencies for high-risk patients (strong recommendation).
- Tracheal aspirate cultures during acute respiratory episodes to guide antibiotic therapy, but not for routine surveillance (conditional recommendation).
- Bronchoscopy for thorough airway examination before tracheostomy decannulation (strong recommendation).
- Polysomnography before decannulation to ensure respiratory stability (conditional recommendation).
An expert panel developed the recommendations using the evidence-based Grading of Recommendations, Assessment, Development and Evaluation framework. The panel included leading physicians and other clinicians from the U.S., Canada, and Australia, as well as family caregivers. It was led by Christopher Baker, MD, director of the Ventilator Care Program at Children’s Hospital Colorado, and Reshma Amin, MD, director of the Sleep Medicine and Long-Term Ventilation Programs at The Hospital for Sick Children.
“Whether or not to get a tracheostomy can be a difficult decision for family caregivers to make for their child,” said Dr. Baker. “We wrote these guidelines to help clinicians and family caregivers provide the best care possible, but ultimately it is up to each provider-caregiver partnership to decide what is best.”
Crystal Costante, one of the family members included on the panel, shared her perspective on the new guidance.
“The new guidance for clinicians gives me a sense of hope and relief as a parent of a ventilator-dependent child with a tracheostomy,” she said. “Clear and consistent guidance means that clinicians across different settings will have a shared understanding of what high-quality, family-centered tracheostomy care looks like. For caregivers like me, this helps build trust, improves communication, and makes it easier to take part in shared decision making.”
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On/Off Switch Offers Hope for Regenerative Medicine in Lung Disease
A recent study from the Mayo Clinic may hold the key to better therapies for chronic lung conditions such as COPD and pulmonary fibrosis.
The research centers around alveolar type 2 (AT2) cells, which are known for two major functions. First, they fight infections by secreting surfactant proteins that keep alveoli open, and second, they act as reserve stem cells by regenerating alveolar type 1 (AT1) cells that line the surface of the lung and enable the exchange of oxygen, considered essential for lung injury repair.
Unfortunately, they can’t do both at the same time.
The Mayo Clinic investigators decided to track the life history of AT2 cells to see why. Using single-cell sequencing, advanced imaging, and preclinical models of lung injury, they found that these cells retain their stem cell-like flexibility for only about 2 weeks after birth before specializing in one or the other of their key functions.
At that point, any transition between the two is governed by three key regulators, one of which, C/EBPα, acts as a clamp that prevents cells from behaving like stem cells. Adult AT2 cells cannot regenerate after injury unless this clamp is released, and in the face of diseases like COPD, pulmonary fibrosis, and severe COVID-19, it often is not.
The team believes fine-tuning this process could open the door to new possibilities for regenerative medicine in lung disease, enabling the rebuilding of lung tissue and reducing scarring.
“Taken together, these observations suggest that C/EBPα might suppress a larger program that alternates between two states — one regenerative and the other defensive,” they wrote. “If true, said program would represent a more robust response to pathogen-mediated injury than previously appreciated, as alternating between regenerative and defense states could ensure enough AT2s are available at a given time to both promote clearance of the pathogen as well as repair damaged alveoli.”
Nature Communications published the study.
