Tag: COPD

Autistic Adults Have Higher Risks of Injury and Disease

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A large-scale registry study found that older autistic adults have a significantly higher risk of injury, especially self-inflicted, and physical conditions such as type 2 diabetes, anaemia, heart failure and COPD. The findings were published in The Lancet Healthy Longevity.

“We found an increased disease burden in middle-aged and older autistic adults, both men and women, irrespective of the presence of intellectual disability,” says Shengxin Liu, doctoral student at Karolinska Institutet. “Our findings point up the need to improve the support and care of older autistic adults.”

In the population-based study, the KI researchers linked different national registers and compared the risk for five types of injury and 39 age-related physical conditions in people over the age of 45. Of the four million-plus people born between 1932 and 1967, 1930 women and 3361 men had an autism diagnosis. For each physical condition, they evaluated the 25-year cumulative incidence and the relative risk in autistic people compared with non-autistic people of the same sex and age.

Seven-fold risk of self-harm

Autistic people had a higher risk of four of five studied injures, for which self-harm accounted for the greatest risk increase, followed by poisoning, falls and other physical injuries.

“The risk of self-harm was worryingly high, a full seven times higher than in non-autistic people,” says Liu. “Reasons behind this remain largely unknown. One possible contributing factor could be mental health conditions that commonly co-occur with autism, such as anxiety and depression.”

The researchers also found a risk increase for 15 physical conditions. For example, autistic people had three times the risk of anaemia and glucose dysregulation and almost double the risk of heart failure, type 2 diabetes, and COPD (chronic obstructive pulmonary disease).

Multiple contributory factors

“We now need to find out the cause of these associations and how they are affected by factors such as biology, age when diagnosed with autism, psychotropic treatment and psychosocial environment,” says the study’s last author Mark Taylor, senior researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “But most importantly, researchers, health services and policymakers need to cooperate to make sure that older autistic adults have a better quality of life.”

Since this was an observational study, no causal relationships can be ascertained, and the researchers were not able to take into account variables such as socioeconomic status. Furthermore, given that the study used Swedish registers, it is difficult to make generalisations to other countries.

Source: Karolinska Institutet

New Compounds Could Activate the Bitter Taste Receptors in Lung Airways

Anatomical model of lungs
Photo by Robina Weermeijer on Unsplash

A surprising fact is that bitter taste receptors are found not just in the mouth, but elsewhere including the airways. Activating those receptors dilates up lung passageways, making them a potential target for treating asthma or chronic obstructive pulmonary disease (COPD). Now, researchers report in the Journal of Medicinal Chemistry that they have designed a potent and selective compound that could lead the way to such therapies.

Among the 25 different types of bitter taste receptors, the TAS2R14 subtype is one of the most widely distributed in tissues outside the mouth. Scientists are uncertain about the structure of the receptor, and they haven’t identified the particular compound or “ligand” in the body that activates it. However, a few synthetic compounds, such as the nonsteroidal anti-inflammatory drug (NSAID) flufenamic acid, are known to bind to and activate TAS2R14s. But these compounds aren’t very potent, and they don’t have similar structural features. These difficulties make it challenging to create a better ligand. Nevertheless, Masha Niv, Peter Gmeiner and colleagues used flufenamic acid as a starting point to design and synthesise analogues with improved properties. Next, the team wanted to extend that work to develop a set of even better TAS2R14 ligands.

Building on these earlier findings, the researchers made several new variations. They tested these compounds in a cell-based assay that measures receptor activation. This approach revealed that replacing a phenyl ring with a 2-aminopyrimidine and substituting a tetrazole for a carboxylic acid group was a promising strategy. One of the new ligands was six times more potent than flufenamic acid, meaning less of the compound was needed to produce a similar response as the NSAID. This ligand was also highly selective for TAS2R14 compared to non-bitter taste receptors, which could potentially minimise side effects. The researchers speculate that new compounds will help shed light on the structure, mechanism and physiological function of bitter taste receptors and guide development of drug candidates to target them.

Source: American Chemical Society

A Simple Device to Help COPD Sufferers Breathe Easier

Tired woman after exercise
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Chronic obstructive pulmonary disease (COPD) affects one in 10 adults, reducing quality of life and making physical activity challenging as they struggle to get enough air. Research around a new breathing device developed by pulmonologists at the University of Cincinnati offers promise for improving their lives. The research was published in the journal Respiratory Care.

The device, called PEP Buddy, was created by Muhammad Ahsan Zafar, MD, and Ralph Panos, MD. “Dr Panos and I both see patients with COPD, and it’s a huge population,” says Zafar. “Their life really changes when they have COPD. They were active individuals but now they’re debilitated and limited, so we wanted to come up with something easy that helps improve their life.”

For people with COPD, it takes longer to get inhaled air out of their lungs with each breath due to tighter air tubes. Therefore, when they breathe fast, like during physical activities, air is retained in the lungs. This air stacking or “dynamic hyperinflation” is the main reason for breathlessness and also leads to lower oxygen levels. As the breathing gets difficult during physical activity, people become less and less active and more isolated.

Panos and Zafar developed a hands-free device that is the size of a whistle. Zafar said he looked at positive-expiratory pressure (PEP) breathing devices on the market and they were handheld, big and bulky, so they tried to come up with something that is very simple, lightweight and easy to use. The device is designed to be worn around the neck with a lanyard for day-to-day use and inserted into the mouth when needed, during or after exertion.

In the study, they examined people with COPD who were short of breath and gave them two tasks. “We conducted a six-minute walk test with and without the device,” says Zafar. “They were given the device to take home and use in their daily routines. In two weeks, there was a follow-up to see how PEP Buddy use impacted their shortness of breath and quality-of-life scores.”

The study found 72% of the participants had a significant impact in reducing their shortness of breath and improving their quality of life. Among those who would drop their oxygen levels during walking, 36% of them did not drop oxygen levels when using PEP Buddy. This is the first mechanical device to show such an impact on oxygen levels in people with COPD.

Maja Flannery, a PEP Buddy user with chronic lung disease and airflow obstruction, says the device has changed her day-to-day living.

“I am so happy that I was lucky enough to be part of the study and able to use this great little device to breathe better,” Flannery says. “I use it when I get up in the morning. It helps with the air requirement when changing position from laying down to standing and exercises my lungs to get them more prepared for the day. I find it helpful in getting the trapped air out as I am active, so I can play longer points during tennis, and also recover between points more quickly. My friends at tennis laugh that it is my ‘magic whistle.'”

UC’s Zafar says the next step in this research is to conduct a long-term study to see the impact on the use of rescue inhalers, emergency department visits and long-term symptoms and functional capacity in people with COPD. PEP Buddy may also be a promising addition to pulmonary rehabilitation programs for faster improvement and sustaining better outcomes. They are also exploring other uses of PEP Buddy in health care.

“As a physician I feel gratified that we are providing something new that can actually improve people’s lives,” says Zafar. “That’s where my passion is. These people are really debilitated with not many tools in their hand to improve their symptoms right now. PEP Buddy will be one such tool.”

Source: University of Cincinnati

Bronchodilators Don’t Ease Smoking-related Respiratory Symptoms in non-COPD Patients

Anatomical model of lungs
Photo by Robina Weermeijer on Unsplash

A study published in the New England Journal of Medicine have found that dual bronchodilators do little to help people who do not have chronic obstructive pulmonary disease (COPD), but who do have respiratory symptoms and a history of smoking.

Millions of people who smoke or used to smoke and have some symptoms of COPD have been prescribed bronchodilators.

“We’ve assumed these medications worked in patients who don’t meet lung function criteria for COPD, but we never checked,” said MeiLan K. Han, MD, a principal investigator and first author of the study. “We now know these existing medications don’t work for these patients.”

According to scientists, the implications are significant. First, they show the importance of diagnosing lung conditions through spirometry, a lung function test Dr Han noted is underutilised in clinical practice. Second, they show the need for new, effective therapies for patients without COPD.

Inhalers have long been the primary go-to treatment for these patients, she explained, because doctors either assume a patient has COPD, or else that their smoking-related symptoms could be helped by the inhalers. But while tobacco smoking causes a large spectrum of lung damage, the study showed bronchodilator therapy only helps patients with enough lung damage that would result in abnormal spirometry readings.

In the 12-week, randomised, double-blinded study, which was part of the Redefining Therapy in Early COPD for the Pulmonary Trials Cooperative (RETHINC), researchers enrolled 535 adults with symptoms of COPD, ages 40–80. Participants used an inhaler twice daily that contained either medication or a placebo.

By the end of the trial, some adults in the medication and placebo groups saw slight respiratory improvements, eg coughed less, produced less phlegm, or felt less winded, which was assessed through the St. George’s Respiratory Questionnaire. However, the researchers found no significant differences between those receiving medication or placebo. They reported 56% (128 of 227) of participants who received the medication saw respiratory symptom improvements, compared to 59% (144 of 244) of those who took the placebo.

According to Dr Han, these data underscore the need to change the standard practice, which is not doing spirometry and just treating patients with the same COPD medications and expecting to see improvement.

Antonello Punturieri, MD, PhD, program director of NHLBI’s Chronic Obstructive Pulmonary Disease/Environment Program, said spirometry testing should be used for any patient who shows signs of COPD, airflow obstruction, or who has a history of cigarette smoking. Though spirometry readings are used during about one-third of medical visits related to COPD, roughly half of patients who would meet criteria for COPD go undiagnosed.

Promoting smoking cessation a primary way to prevent COPD or COPD-like symptoms, the study noted. About one in four current or former smokers without COPD have reported having shortness of breath. In addition to encouraging smoking cessation, doctors can help patients who do not meet lung-function criteria of COPD by working with them to address any other underlying issues, such as overweight and obesity, heart failure, or other lung issues.

“In the meantime, research should be focused on finding new treatments for them,” Dr Han explained. “The next question is, can we develop more targeted therapies for these patients who are on the milder end of the spectrum?”

“Because cough and mucus production show up prominently among these patients, we believe therapies that target mucus production in the airways may be effective,” said Prescott G. Woodruff, MD, a principal investigator and senior author of the study.

Some of these therapies are already in development, and data from other studies may offer insight into the biological causes of excessive airway mucus, which could help point to additional therapies.

Source: NIH/National Heart, Lung and Blood Institute

Simple COPD Screening Could Benefit Millions

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The global burden of Chronic Obstructive Pulmonary Disease (COPD) could be significantly reduced with a simple health assessment available in low- and middle-income countries (LMICs), according to a large-scale international study.

The greatest burden on COPD is in LMICs, which account for around 90% of COPD related deaths. 

In high-income countries, COPD is typically caused by tobacco smoking and is diagnosed using a spirometer, the straightforward ‘gold standard’ diagnosis, and symptoms can be effectively treated.

However, in LMICs the primary cause of COPD is more varied and includes household air pollution in the form of biomass smoke for cooking and heating; other causes include impaired lung growth, chronic asthma and post-tuberculosis lung damage. Spirometry is often unavailable in LMICs. These reasons, combined with a shortage of clinicians, means COPD is commonly undiagnosed in LMICs.

In the new study, published in JAMA, researchers found that people with a high risk of COPD could be identified in 7 to 8 minutes using either a questionnaire on its own or a questionnaire combined with a Peak Expiratory Flow (PEF) assessment.

Explaining the study, lead researcher Professor John Hurst said: “Chronic Obstructive Pulmonary Disease is one of the world’s major public health issues, causing both individual and economic harm: there is a clear and pressing need to find better ways to identify people early, in all manner of settings.

“Screening tools for COPD have been shown to have reasonable diagnostic accuracy in high-income countries, but due to better population health and treatment in these settings, this has tended to identify milder disease, not requiring much intervention.

“Up until now the performance of these screening tools has not been adequately studied in LMICs; we aimed to test both the diagnostic accuracy and feasibility of simple screening tools.”

Researchers assessed three COPD screening tools (a combination of PEF and/or questionnaires) on populations in three distinct settings: semiurban Bhaktapur, Nepal, urban Lima, Peru and rural Nakaseke, Uganda.

To establish diagnostic accuracy of the tools, all participants were also given a spirometry test.    

In total 10709 adults aged 40 years or older from the three communities took part.

Study findings:

  • Prevalence of COPD varied by site, from 3% in Lima (Peru) to 7% in Nakaseke (Uganda) and 18% in Bhaktapur (Nepal).
  • 49% of COPD cases were clinically significant as defined by symptoms and or exacerbation burden, and 16% had severe or very-severe disease measured on spirometry. 95% of cases were previously undiagnosed.
  • The screening instruments performed similarly within each population setting and were feasible to deliver using trained research staff, taking an average of 7 to 8 minutes.

Commenting Professor Hurst said: “Our findings support the accuracy and feasibility of using simple screening tools to identify people affected by COPD living in diverse low- and middle-income settings.

“It is alarming that a high percentage of screen-identified COPD cases were clinically important, had severe or very severe changes in lung function, and that most were unaware of their diagnosis despite the high prevalence of symptoms and lower quality of life.

“In addition, only a minority of people had a history of smoking, further highlighting the poor conditions, exacerbated by biomass smoke, that people in low- and middle-income countries are living.”

Professor Hurst added: “Action is needed: the global health community has neglected the burden of chronic respiratory diseases for too long.  It is now time for people with chronic respiratory diseases such as COPD to be promptly identified, informed about their condition and treated – wherever they live in the world.”

Researchers say more work is needed to assess whether COPD screening can be implemented in routine LMIC healthcare settings; if screening for COPD is of benefit to those testing positive, and it is cost-effective, for a given population, to implement COPD screening in LMIC settings.  

Source: University College London

Small RNA Molecule Holds COPD Treatment Potential

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Researchers have identified a small RNA molecule called microRNA-21 as a therapeutic target and its inhibition as a potential treatment for chronic obstructive pulmonary disease (COPD). An inflammatory lung disease that makes it hard to breathe, COPD is the third most common cause of death in the world. It is often caused by smoking tobacco products or inhaling air pollution.

In the pre-clinical study which was published in Science Translational Medicine, the researchers found elevated levels of microRNA-21 in mouse models of COPD. MicroRNA-21 inhibitor (antagomir-21) as a therapeutic treatment reduced inflammation and improved lung capacity and function in these models.

The researchers said antagomir-21 both reduced microRNA-21 expression and also suppressed the influx of inflammatory cells – macrophages, neutrophils and lymphocytes – into the airways and lungs. Lung cytokine production, that amplifies inflammatory responses, was also inhibited through use of antagomir-21.

The paper’s senior author, Professor Phil Hansbro, said that their findings offered up a completely new understanding of COPD.

“MicroRNA-21 is a common molecule that is expressed in most cells in the human body and regulates many critical biological processes. Our findings demonstrate, however, that microRNA-21 levels increase when it comes to COPD,” said Professor Hansbro.

“We believe that the development of new drugs that inhibit microRNA-21 may offer up an entirely new therapeutic approach when it comes to COPD treatment.”

Professor Hansbro said that the findings may address the limited effectiveness that current therapies have in controlling COPD or halting its progression.

“The development of effective COPD treatments has been hampered by a lack of understanding of the disease’s underlying mechanisms. Our data defines microRNA-21 as a novel therapeutic target and its inhibitors as a potential new treatment for this major, currently intractable lung disease.”

Source: News-Medical.Net