Tag: gadolinium

Limiting the Damage from an Asthma Attack could Halt the Disease

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Scientists at King’s College London have discovered that the features of asthma attacks, a disease usually treated as being inflammatory, in fact stem from constriction of airways, making breathing difficult. The new study, published in Science, shows for the first time that many features of an asthma attack – inflammation, mucus secretion, and damage to the airway barrier that prevents infections – result from this mechanical constriction in a mouse model.

The findings suggest that blocking a process that normally causes epithelial cell death could prevent the damage, inflammation, and mucus that result from an asthma attack.

Professor Jody Rosenblatt from King’s College London said: “Our discovery is the culmination of more than ten years work. As cell biologists who watch processes, we could see that the physical constriction of an asthma attack causes widespread destruction of the airway barrier. Without this barrier, asthma sufferers are far more likely to get long-term inflammation, wound healing, and infections that cause more attacks. By understanding this fundamental mechanism, we are now in a better position to prevent all these events.”

Asthma symptoms include wheezing, coughing, feeling breathlessness and a tight chest. Triggers such as pollen or dust can make asthma symptoms worse and can lead to a life-threatening asthma attack.

Despite the disease commonality, the causes of asthma are still not understood. Current medications treat the consequences of an asthma attack by opening the airways, calming inflammation, and breaking up the sticky mucus which clogs the airway, which help control asthma, but do not prevent it.

The answer to stopping asthma symptoms may lie in cell extrusion, a process the researchers discovered that drives most epithelial cell death. Scientists used mouse lung models and human airway tissue to discover that when the airways contract, known as bronchoconstriction, the epithelial cells that line the airway get squeezed out to later die.

Because bronchoconstriction causes so many cell extrusions, it damages the airway barrier which causes inflammation and excess mucus.

In previous studies, the scientists found that the chemical compound gadolinium can block extrusion. In this study, they found it could work in mice to prevent the excess extrusion that causes damage and inflammation after an asthma attack. The authors note that gadolinium has not been tested in humans and has not been deemed to be safe or efficacious.

Professor Rosenblatt said: “This constriction and destruction of the airways causes the post-attack inflammation and excess mucus secretion that makes it difficult for people with asthma to breathe.

“Current therapies do not prevent this destruction – an inhaler such as Albuterol opens the airways, which is critical to breathing but, dishearteningly, we found it does not prevent the damage and the symptoms that follow an attack. Fortunately, we found that we can use an inexpensive compound, gadolinium which is frequently used for MRI imaging, to stop the airway damage in mice models as well as the ensuing inflammation and mucus secretion. Preventing this damage could then prevent the build-up of musculature that cause future attacks.”

Professor Chris Brightling from the University of Leicester and one of the co-authors of the study said: “In the last decade there has been tremendous progress in therapies for asthma particularly directed towards airway inflammation. However, there remains ongoing symptoms and attacks in many people with asthma. This study identifies a new process known as epithelial extrusion whereby damage to the lining of the airway occurs as a consequence of mechanical constriction and can drive many of the key features of asthma. Better understanding of this process is likely to lead to new therapies for asthma.”

The discovery of the mechanics behind cell extrusion could underlie other inflammatory diseases that also feature constriction such as cramping of the gut and inflammatory bowel disease.

Source: King’s College London

Hypersensitivity Link Between MRI and X-Ray Contrast Agents

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People with a history of hypersensitivity to iodine-based contrast agents for X-ray based scans, are also susceptible to similar reactions from commonly used MRI contrast agents, according to a large, eight-year cohort study. The study, published in the journal Radiology, also found that premedication or switching to a different MRI contrast agent may reduce risk in patients who have had previous contrast agent reactions.

For a long time, gadolinium-based contrast agents (GBCA) have been used to enhance visualisation of organs, tissues and blood vessels on MRI and provide a more accurate depiction of disease. Though GBCA are relatively safe, recent studies have reported several adverse reactions related to their use, including allergic-like hypersensitivity reactions, such as rash and flushing.

These reactions are increasing in incidence with the widespread use of GBCA, prompting an urgent need for research into risk factors, according to the study’s senior author Hye-Ryun Kang, MD, PhD.

Analysing more than 330 000 cases of GBCA exposure in 154 539 patients over an eight-year period, the researchers found 1304 cases of allergic-like hypersensitivity reactions, for a rate of 0.4%. In patients who had a previous GBCE reaction, the average recurrence rate was 15%.

Acute allergic-like hypersensitivity reactions, or those that occur within one hour of contrast administration, accounted for 1178 cases, while a far smaller number of 126 cases were delayed allergic-like hypersensitivity reactions, or those that occur beyond the first hour and mostly within one week after exposure.

The risk of allergic-like hypersensitivity reactions to GBCAs was higher in those with a history of similar reactions to iodinated contrast media. Normally, having a history of iodinated contrast media hypersensitivity was not thought to be a risk factor for hypersensitivity to GBCAs and vice versa, because of their structural and compositional differences.

“The results of our study challenge this idea,” Dr Kang said.

An underlying predisposition to drug allergies in susceptible patients could be the cause, Dr Kang said, as opposed to any cross-reactivity associated with structural similarities between iodinated contrast media and GBCA. In fact, the risk of hypersensitivity reactions to iodinated contrast media was also higher in those who previously experienced a similar reaction to GBCA.

“Thus, physicians should be aware that patients with a history of hypersensitivity to one of iodinated contrast media or GBCA are at greater risk of developing hypersensitivity reactions to the other,” she said.

Analysis of the data showed that premedication, typically with steroids and antihistamines, and changing the GBCA showed preventive effects in patients with a history of acute allergic-like hypersensitivity reactions. Patients who received premedication and before MRI or were switched to a different GBCA showed the lowest rate of recurrence. Only premedication significantly reduced the incidence of reactions in patients with a history of delayed reactions.

“As the most important preventive measure is avoidance of the culprit agent, a precise record of previously used GBCA should be kept for all patients,” Dr. Kang said. “Physicians should discuss appropriate premedication strategies with their patients prior to MRI procedures.”

Dr Kang nevertheless stressed that contrast-enhanced MRI examinations are invaluable in the diagnosis and follow-up of various diseases, and the overall risk remains low.

“As most of these reactions are mild, we believe the benefits of MRI outweigh the potential risks associated with GBCA use,” she said.

Dr Kang recommended that in all patients receiving an MRI with GBCA exposure, a detailed history of previous hypersensitivity allergic reactions be conducted, and when necessary, appropriate prevention measures should be implemented, such as using premedication and switching to different GBCA types.

Future work would be to perform studies with larger populations to identify possible risk factors and effective preventive strategies for delayed hypersensitivity reactions to GBCA.

Source: Radiological Society of North America