Fixed Airway Obstruction Found in 33% of Severe Asthma Cases

SEVERE asthma (SA) is a heterogeneous condition, and a key factor influencing patient outcomes is whether airway obstruction is fixed or reversible. Recent analysis from the Severe Asthma Network in Italy (SANI) registry has provided new insights into the prevalence and characteristics of fixed airway obstruction (FAO) among severe asthma patients.

Fixed Airway Obstruction Versus Bronchodilator Responsiveness

Among 354 patients enrolled in the registry, 190 (53.7%) had airway obstruction, of whom 116 (60.1%) were classified as having FAO. This represents an overall FAO rate of 32.8%. Patients with FAO displayed significantly better asthma control than those with bronchodilator responsiveness (BDR), with 34.5% achieving well-controlled asthma compared with 20.3% in the BDR group. FAO patients also had higher asthma control test (ACT) scores (17.4 vs 15.2) and asthma quality of life questionnaire (AQLQ) scores (4.6 vs 3.8).

Hospitalisations and emergency visits were less frequent in FAO patients than in BDR patients, although overall exacerbation rates were similar. Interestingly, fractional exhaled nitric oxide (FeNO) levels were lower in FAO patients (29.5 ppb) than BDR patients (46.0 ppb), suggesting airway calibre rather than type 2 inflammation contributed to differences in biomarker expression.

Potential Reversibility of FAO

The study also highlighted that FAO is not necessarily permanent. Transition from FAO to BDR or normal lung function was observed, particularly in patients with late-onset severe asthma (ages 30–39) and lower inhaled corticosteroid use. The Global Initiative for Asthma classification influenced this shift, with step 4 versus step 5 patients showing higher rates of improvement.

Implications for Clinical Practice

These findings emphasise the importance of phenotyping severe asthma patients. Identifying FAO can guide personalised management strategies, including monitoring for potential reversibility and optimising therapy based on airway obstruction type. This approach may improve patient outcomes and reduce unnecessary hospitalisations.

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Which Medical Tests Are Useless? Find Out Here.

Usually, when we go to the doctor or the hospital for treatment or testing, we do what the doctor tells us without questioning their decisions. This is not necessarily the correct approach, because, contrary to what many think, doctors don’t actually provide us with treatments tailored to us personally, since the complaints we come to them with are usually not so different to other patient’s complaints except for small changes that they think are negligible. 

 

In recent years, an international initiative, Choosing Wisely, has begun to promote the quality and safety of treatments we receive by avoiding unnecessary ones. We invite you to familiarize yourself with the 21 treatments and tests for which the doctors received special instructions. Now you’ll also be able to know how to preserve your safety and health better, especially if you encounter an instruction that isn’t compatible with one you’ve received from your doctor.

What is the Choosing Wisely project?  

This blessed project began in the United States as an educational campaign for physicians by ABIM, whose goal is to improve the relationship between doctors and patients, to encourage patient care that focuses on the patient’s welfare, and to inform doctors and patients of unnecessary treatment and testing that may even be harmful. The project began in 2013, and since then, each year discussions have been held between senior medical personnel, during which treatments and tests are raised that the practitioners have become accustomed to using without giving them much thought. Various countries, such as Canada, Britain, and Australia, have also adopted the project. The following are some of the most important things you should know. 

 

21 treatments and tests that you don’t have to undergo 

The following information is important for both physicians and patients, and it is recommended that you know and remember it for the next time you need to undergo a test or treatment that’s on this list: 

 

1. Chemotherapy can be provided to cancer patients as long as they reduce the symptoms of the disease, but treatments should be reduced if they are painful to the patients, as the pain may cause greater distress to the process of coping with the disease. 

 

2. A person who has suffered minimal head injury does not have to undergo X-ray scanning, as it probably won’t be useful at all.

3. An X-ray won’t help you learn more about the medical condition of a person with lower back pain as long as he or she does not have any other pain.

4. A routine x-ray scan for cancer patients should be given only after a treatment that has helped them - otherwise, it won’t reveal any new or useful information. 

 

5. In the event that a person arrives for intensive care, physical examinations must be done only to answer questions that arise from their condition, and not routinely. 

 

6. People who undergo artificial respiration don’t have to be completely anesthetized. If possible, daily tests should be performed to verify how much anesthetic dosage can be reduced. 

 

7. Children with flat head syndrome don’t have to be treated with a corrective helmet. 

 

8. For children who suffer from chronic constipation, consider changes in diet to reduce symptoms before administering medication. 

 

9. People who are supposed to have surgery don’t have to get to the hospital the day before, as long as they have already been evaluated and prepared before the operation, and in cases of minor surgery, pre-op preparation may not even be necessary.

10. For children with acute or normal bronchitis, a bronchodilator should not be used for treatment unless there is a situation that unquestionably requires this treatment. 

 

11. Children who suffer from a small wrist fracture don’t need a cast on their whole hand. A stint that can be easily removed will work as efficiently. 

 

12. People who have dislocated their hip or shoulder can get sedatives before starting treatment instead of general anesthesia. 

 

13. Do not give a woman aspirin or progesterone to stabilize a pregnancy if she has undergone repeated or unexplained miscarriages in the past. 

 

14. Pregnant women should not be given aspirin to contract their blood vessels. 

 

15. A prostate-specific antigen test (PSA) will not help a person who is not at risk for prostate cancer due to family or ethnic history.

16. Do not use an ultrasound to determine whether the baby is larger than normal at a certain stage of pregnancy if the mother has diabetes. 

 

17. People should have a calcium test only if they have symptoms that may indicate kidney inflammation, bone disease, or nerve-related disorders. In addition, it is not necessary to conduct another test sooner than 3 months after the previous one, except in severe cases, before surgery or if the patient suffers from a chronic illness. In any case, there is no need to repeat this test until 48 hours have passed since the previous test. 

 

18. If an antidepressant that a patient has received hasn’t made a significant change in their condition after two months, consider changing medications. 

 

19. A person diagnosed with psychosis should not undergo CT or MRI unless there are symptoms that may indicate a neurological problem. 

 

20. For women over the age of 45, there is no need for a blood test to diagnose menopause. 

 

21. Use of blood pressure medications to prevent heart disease or stroke should be considered only if the patient's blood pressure is above 140-159 / 90-99, and as long as there is another risk factor.

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Drug discovery study identifies promising new compound to open constricted airways

Despite the progress made in managing asthma and chronic obstructive pulmonary disease (COPD), poorly controlled symptoms for both respiratory diseases can lead to severe shortness of breath, hospitalizations or even death.

"Only about 50 percent of asthmatics, and an even lower percentage of people with COPD, achieve adequate control of lung inflammation and airway constriction with currently available medications," said Stephen Liggett, MD, vice dean for research at the University of South Florida Morsani College of Medicine and a USF Health professor of medicine, molecular pharmacology and physiology, and biomedical engineering. "So, we're clearly missing something from our drug armamentarium to help all these patients."

Dr. Liggett's laboratory has discovered several subtypes of bitter taste receptors (TAS2Rs)—G protein-coupled receptors expressed on human smooth airway muscle cells deep inside the lungs. In asthma and COPD, tightening of smooth muscles surrounding bronchial tubes narrows the airway and reduces air flow, and Dr. Liggett's lab found that these taste receptors open the airway when activated. They are now looking for new drugs to treat asthma and other obstructive lung diseases by targeting smooth muscle TAS2Rs to open constricted airways.

A promising bronchodilator agonist rises to the top

In a preclinical study published Nov. 5 in ACS Pharmacology and Translational Science, Dr. Liggett and colleagues identified and characterized 18 new compounds (agonists) that activate bitter taste receptor subtype TAS2R5 to promote relaxation (dilation) of human airway smooth muscle cells. The cross-disciplinary team found 1,10 phenanthroline-5,6-dione (T5-8 for short) to be the most promising of several lead compounds (drug candidates). T5-8 was 1,000 times more potent than some of the other compounds tested, and it demonstrated marked effectiveness in human airway smooth muscle cells grown in the laboratory.

For this drug discovery project, Dr. Liggett's laboratory collaborated with Jim Leahy, Ph.D., professor and chair of chemistry at the USF College of Arts and Sciences, and Steven An, Ph.D., professor of pharmacology at the Rutgers Robert Wood Johnson Medical School.

In an extensive screening conducted previously, another research group identified only one compound that would bind to and specifically activate the TASR5 bitter taste receptor—although apparently with limited effectiveness. Using this particular agonist (called T5-1 in the paper) as a starting point, the team relied on their collective disciplines to devise new activators, aiming for a much better drug profile for administration to humans.

"The two key questions we asked were: 'Is it possible to find a more potent agonist that activates this receptor?' and 'Is it feasible to deliver by inhalation given the potencies that we find?'" said Dr. Liggett, the paper's senior author. "T5-8 was the bronchodilator agonist that worked best. There were a few others that were very good as well, so we now have multiple potential new drugs to carry out the next steps."

The researchers developed screening techniques to determine just how potent and effective the 18 compounds were. A biochemical test assessed how well these new agonists activated TAS2R5 in airway smooth muscle cells isolated from non-asthmatic human donor lungs. Then, the researchers validated the effect on airway smooth muscle relaxation using a technique known as magnetic twisting cytometry, pioneered by Dr. An.

'Team science' solves a structural problem

"The biggest challenge we faced was not having a 3-D crystal structure of TAS2R5, so we had no idea exactly how agonist T5-1 fit into this mysterious bitter taste receptor," Dr. Liggett said. "By merging our strength in receptors, pharmacology, physiology, and drug development, our team was able to make the breakthrough."

T5-8 was superior to all the other bronchodilator agonists screened, exhibiting a maximum relaxation response (50%) substantially greater than that of albuterol (27%). Albuterol belongs to the only class of direct bronchodilators (beta-2 agonists) available to treat wheezing and shortness of breath caused by asthma and COPD. However, this drug or its derivatives, often prescribed as a rescue inhaler, does not work for all patients and overuse has been linked to increased hospitalizations, Dr. Liggett said. "Having two distinct classes of drugs that work in different ways to open the airways would be an important step to help patients optimally control their symptoms."

The ACS Pharmacology paper highlights the importance of translational research in bridging the gap between laboratory discoveries and new therapies to improve human health, he added. "This study yielded a drug discovery that successfully meets most of the criteria needed to advance the compound toward its first trial as a potential first-in-class bronchodilator targeting airway receptor TAS2R5."

This is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.     

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