Disease pathways lead to possible new treatment for severe asthma

Here’s a sobering thought: Nearly half of Americans with severe asthma do not respond to conventional drugs, leaving them with few ways to minimize the often-debilitating symptoms of the chronic disease. But researchers at NHLBI have developed a new treatment that has the potential to dramatically change that: A synthetic peptide that mimics the work of a protein, called apolipoprotein, that appears to reduce inflammation in the lungs and improve their ability to function normally.

The researchers made the discovery by studying the pathways of asthma, leading them to conclude that, despite the similarity in patient’s symptoms, the severe form of the disease could have several genetic root causes, each resulting in different responses to treatment.

Microscopic images of the lungs of mice.

Effect of the 5A apoA-I mimetic peptide on the lungs and the airway hyperreactivity in mice with asthma.

About 25 million people in the United States suffer from asthma, which is marked by inflammation and narrowing of the airways and causes wheezing, coughing, chest tightness and shortness of breath. It affects people of all ages, but it most often starts during childhood—seven million children have the disease—and it disproportionately affects minorities and families living at or below the poverty line. The condition can greatly reduce a person’s quality of life and is a major contributing factor to absences at school and work. Severe asthma attacks may require emergency room visits and hospitalizations, and they can be fatal.

In an effort to understand why some people respond to some asthma medications and others do not, researchers started with the basics. “By studying the pathways of the disease, we identified a new biological mechanism that leads to asthma,” explained Stewart J. Levine, M.D., Chief of the NHLBI Laboratory of Asthma and Lung Inflammation.

About half asthmatics have type 2-high asthma, while the others have type 2-low asthma. Type 2-high asthma is caused by an increase in the lungs and blood of inflammatory cells called eosinophils, Levine explained. But people with type 2-low asthma do not have these increased levels of eosinophils. This suggests, he said, that their asthma develops through other pathways—for instance, neutrophils, another type of inflammatory cell.

These differences, it turns out, have profound implications for treatment. For some patients with severe type 2-high asthma, standard medications,...

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UCSF Research Finds Medicaid Could Save $2.6 Billion Within a Year if Just 1 Percent of Recipients Quit Smoking

The Median State Would Save an Estimated $25 Million in Medicaid Expenditures, Says UCSF Research

Reducing smoking, and its associated health effects, among Medicaid recipients in each state by just 1 percent would result in $2.6 billion in total smoking Medicaid savings the following year, according to new research by UC San Francisco.

The median state would save $25 million, ranging from $630.2 million in California (if the smoking rate dropped from 15.5 percent to 14.5 percent) to $2.5 million in South Dakota (if the rate dropped from 41.3 to 40.3 percent), the research found.

The study, by Stanton A. Glantz, PhD, director of the UCSF Center for Tobacco Control Research and Education, is published April 12, 2019 in JAMA Network Open

“While 14 percent of all adults in the U.S. smoke cigarettes, 24.5 percent of adult Medicaid recipients smoke,” said Glantz. “This suggests that an investment in reducing smoking in this population could be associated with a reduction in Medicaid costs in the short run.”

Total Medicaid costs in 2017 were $577 billion.

“There is no question that reducing smoking is associated with reduced health costs, but it’s commonly assumed that it takes years to see these savings, which has discouraged many states from prioritizing helping smokers quit,” said Glantz.

“While this is true for some diseases, such as cancer, other health risks such as heart attacks, lung disease and pregnancy complications respond quickly to changes in smoking behavior. So reducing the prevalence of smoking would be an excellent short-term investment in the physical health of smokers and the fiscal health of the Medicaid system,” he said.

Glantz derived state-by-state percentages of Medicaid recipients who smoke based on data from the 2017 Behavioral Risk Factors Surveillance System, which provides the percentage of smokers among the population of each state, and the 2017 National Health Interview Survey, which identifies Medicaid recipients in four major regions in the United States (Northeast, Midwest, South and West).

He then estimated potential Medicaid savings based on a previous research finding which showed that a 1 percent relative reduction in smoking prevalence is associated with a reduction of 0.118 percent in per capita health care spending.

Glantz noted that the study looked only at the potential savings from reducing the total number of Medicaid recipients who smoke. But even if each smoker...

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Circassia’s Duaklir Approved by FDA for Maintenance Treatment of COPD

Circassia announced that the U.S. Food and Drug Administration (FDA) approved its medication Duaklir for the maintenance treatment of chronic obstructive pulmonary disease (COPD). The company plans to launch the therapy in the United States in the second half of 2019.

Duaklir is a combination of two long-acting bronchodilators: aclidinium bromide (400 mcg) and formoterol fumarate (12 mcg). It is administered twice daily, via the Pressair inhaler, a plastic device which automatically delivers the medication upon inhalation.

The two bronchodilators increase the caliber of the airways by relaxing smooth muscle tone.

Smooth muscle is a type of muscle that surrounds the airways, and that is not under voluntary control. It is regulated by sympathetic and parasympathetic nerves — parasympathetic nerves, acting through muscarinic receptors, constrict it, whereas sympathetic nerves, acting through beta-adrenergic receptors, relax it.

Aclidinium bromide is a long-acting muscarinic antagonist (LAMA); it blocks muscarinic receptors, thereby preventing airway constriction. Formoterol fumarate is a long-acting beta agonist (LABA); it activates beta-adrenergic receptors, thereby promoting airway relaxation.

The FDA approval was based on positive results from three Phase 3 studies — ACLIFORM (NCT01462942), AUGMENT (NCT01437397), and AMPLIFY (NCT02796677) — and on the phase 4 ASCENT study (NCT01966107), which specifically showed that the therapy was effective at reducing COPD exacerbations.

“With guidelines recommending combined LAMA and LABA therapy for a number of COPD patient groups, we believe Duaklir will make an important contribution to the treatment of this debilitating disease,” Michael Asmus, Circassia’s vice president, U.S. medical affairs, said in a press release.

“Duaklir’s approval is based on a broad clinical database, including data demonstrating a reduction in the risk of COPD exacerbations driven by its aclidinium component, and we look forward to making this new therapeutic option available to patients across the United States,” Asmus said.

According to Circassia, Duaklir will be the only twice-daily LAMA/LABA medication in the U.S. with COPD exacerbation data included in its prescribing information.

Steve Harris, chief executive of Circassia, said: “We are delighted with the FDA approval of Duaklir, which we believe will provide a valuable treatment option for the significant number of patients with...

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Vitamin D may protect against pollution-associated asthma symptoms in obese children

Over 6 million American children have the lung condition.

A new study finds vitamin D may be protective among asthmatic obese children living in urban environments with high indoor air pollution. The study out of Johns Hopkins University School of Medicine, funded by the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, was published in The Journal of Allergy and Clinical Immunology: In Practice.

“The research team has identified many factors that make children susceptible to health problems from air pollution throughout Baltimore’s inner city,” said Kimberly Gray, Ph.D., administrator for the Children’s Environmental Health Research Centers program at NIEHS.

According to the Centers for Disease Control and Prevention, one in 12 children in the U.S. have asthma, which totals 6.1 million children nationally. Additionally, asthma disproportionately impacts urban minority populations, such as black children. Higher indoor air pollution, from sources such as cigarette smoke, cooking, burning of candles, and incense, is linked to greater respiratory problems, including worsening of asthma symptoms and more hospital visits.

“Asthma is an immune-mediated disease,” said Sonali Bose, M.D., lead author of the study and assistant professor of medicine, pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai, and adjunct faculty at Johns Hopkins. “From previous scientific studies, we knew that vitamin D was a molecule that may influence asthma by impacting antioxidant or immune-related pathways.”

Bose explained that at the time the study was being conceived, researchers were seeing vitamin D deficiencies across the U.S. “It became very clear that African-Americans were at higher risk for vitamin D deficiency, particularly black children,” she said. “We were also noticing a heavy burden of asthma in inner city minority children. It seemed as though vitamin D deficiency and asthma were coincident and interacting in some way.”

The study tested three factors – air pollution levels in homes, blood vitamin D levels, and asthma symptoms – in 120 school-aged children with preexisting asthma in the Baltimore area. One-third of the study participants were also obese. The children were evaluated at the start of the study and three times over the next nine months.

Overall, they found that having low blood vitamin D levels was related to...

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Quitting Smoking Reduces Risk for Rheumatoid Arthritis

Sustained smoking cessation decreases the risk for seropositive rheumatoid arthritis (RA), according to a new study published in Arthritis Care & Research. Seropositive RA is the most common form of RA and is generally accompanied by more severe symptoms and deformities than seronegative RA.

Previous research has demonstrated that smoking increases the risk for RA. Whether quitting smoking has the opposite effect had remained unclear.

Investigators at Brigham and Women’s Hospital studied the impact of smoking cessation on the development of seropositive RA and seronegative RA. The researchers analyzed 38 years of data from the Nurses’ Health Study and the Nurses’ Health Study II, which investigate risk factors for chronic disease in women. Among 230,732 women, the researchers identified 1528 who had developed RA. Twice as many (63.4%) women had developed seropositive RA (63.4%) as seronegative RA (36.6%).

Smokers were 47% more likely to develop all types of RA than nonsmokers and 67% more likely to develop seropositive RA. Compared with women who had quit smoking within the previous 5 years, women who had quit smoking ≥30 years earlier were 37% less likely to develop seropositive RA. No link was found between seronegative RA and smoking.

The researchers concluded that, in addition to confirming smoking as a strong risk factor for seropositive RA, the results “demonstrate for the first time that a behavior change of sustained smoking cessation could delay or even prevent seropositive RA.”


Liu X, Tedeschi SK, Barbhaiya M, et al. Impact and timing of smoking cessation on reducing risk for rheumatoid arthritis among women in the Nurses’ Health Studies [published online February 21, 2019]. Arthritis Care Res. doi: 10.1002/acr.23837

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Study: COPD patients need more support when understanding new chest symptoms

People with Chronic Obstructive Pulmonary Disease (COPD) need more support when understanding and acting on new chest symptoms, a study in the journal Psycho-Oncology reports.

During this unique study, led by the University of Glasgow and University of Surrey, researchers investigated how the experience of COPD, influences how individuals understand new or changing chest symptoms and their decision to seek help from medical professionals.

COPD is the name for a group of lung conditions, including emphysema and chronic bronchitis, which cause breathing difficulties. Incidence of lung cancer is four-times higher in those with COPD compared to the general population and patients often confuse early signs of the devastating disease with a deterioration of their existing condition and do not seek medical advice.

Interviewing 40 participants with COPD, researchers discovered that none of the participants were aware that having the condition put them at increased risk of developing lung cancer. Due to a lack of knowledge and support, participants often attributed chest symptoms to external factors such as the weather or illness.

Researchers found that some participants did not seek medical advice following the development of symptoms as they were keen to 'not make a fuss' and believed that poor health was something to be accepted when diagnosed with the condition. A stigma associated with continued smoking was also identified by researchers, as participants were found to be reluctant in seeking help as they felt the doctor would blame their symptoms on smoking.

Participants also spoke about barriers in accessing care, which included scheduling appointments outside of usual working hours and difficulties in getting to the GP's surgery, when symptoms present themselves.

Early diagnosis of lung cancer is vital to improving survival. Figures from Cancer Research UK reveal that when diagnosed at its earliest stage, almost 6 in 10 people with lung cancer will survive their disease for five years or more, compared with almost 5 in 100 people when diagnosed at a later stage.

Dr. Katie Robb, Senior Lecturer at the University of Glasgow, said: "Healthcare professionals need to do more to educate those with COPD about their increased risk of developing lung cancer and be more vigilant when a patient with the illness presents changing symptoms."

Dr. Katriina Whitaker, Reader in Cancer Care at the University of Surrey, said: "Early diagnosis of...

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Study: E-cigarettes outperform patches and gums in quit-smoking study

New study says e-cigarettes are twice as effective as nicotine gum and patches — the strongest evidence yet that vaping can help smokers quit cigarettes.

A major new study provides the strongest evidence yet that vaping can help smokers quit cigarettes, with e-cigarettes proving nearly twice as effective as nicotine gums and patches.

The British research, published Wednesday in the New England Journal of Medicine, could influence what doctors tell their patients and shape the debate in the U.S., where the Food and Drug Administration has come under pressure to more tightly regulate the burgeoning industry amid a surge in teenage vaping.

“We know that patients are asking about e-cigarettes and many doctors haven’t been sure what to say,” said Dr. Nancy Rigotti, a tobacco treatment specialist at Harvard Medical School who was not involved in the study. “I think they now have more evidence to endorse e-cigarettes.”

At the same time, Rigotti and other experts cautioned that no vaping products have been approved in the U.S. to help smokers quit.

Smoking is the No. 1 cause of preventable death worldwide, blamed for nearly 6 million deaths a year. Quitting is notoriously difficult, even with decades-old nicotine aids and newer prescription drugs. More than 55 percent of U.S. smokers try to quit each year, and only about 7 percent succeed, according to government figures.

Electronic cigarettes, which have been available in the U.S. since about 2007 and have grown into a $6.6 billion-a-year industry, are battery-powered devices that typically heat a flavored nicotine solution into an inhalable vapor.

Most experts agree the vapor is less harmful than cigarette smoke since it doesn’t contain most of the cancer-causing byproducts of burning tobacco. But there is virtually no research on the long-term effects of the chemicals in the vapor, some of which are toxic.

At the same time, there have been conflicting studies on whether e-cigarettes actually help smokers kick the habit.

Last year, an influential panel of U.S. experts concluded there was only “limited evidence” of their effectiveness.
In the new study, researchers tracked nearly 900 middle-age smokers who were randomly assigned to receive either e-cigarettes or nicotine replacement products, including patches, gums and lozenges. After one year, 18 percent of e-cigarette users were smoke-free, versus 9.9 percent of those using the other products.


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Vaccination Cuts Risk of Severe Flu in Hospitalized Patients With COPD

Hospitalized patients with chronic obstructive pulmonary disease (COPD) who tested positive for the flu and were unvaccinated had worse death rates and more severe illness than those who were vaccinated, according to a recent study.

A large national study from Canada showed influenza vaccination is effective in reducing flu-related hospitalizations among patients with chronic obstructive pulmonary disease (COPD). Hospitalized patients who tested positive for the flu and had COPD and were unvaccinated had worse death rates and more severe illness than those who were vaccinated.

Despite recommendations to get flu shots, patients with COPD have a low uptake of the vaccination—about 50% to 60%. The researchers said initiatives to increase vaccination rates as well as early antiviral use among patients with COPD could reduce flu-related hospitalization, severe illness, and lower healthcare costs.

Previous research inferring poor outcomes in this population of patients with COPD comes from studies of elderly patients with a mix of chronic lung diseases, according to the study, which was published in the journal CHEST.

Forty-six hospitals across 5 Canadian provinces participated in this study. Patients with COPD, hospitalized with any acute respiratory illness or exacerbation, were studied between 2011 to 2015 and were included if their flu vaccination status was known. All patients received nasopharyngeal swabs with polymerase chain reaction (PCR) testing for influenza. The primary outcome was an influenza-related hospitalization.

Among 4755 hospitalized COPD patients, 4198 (88.3%) patients with known vaccination status were analyzed. The adjusted analysis demonstrated a 38% reduction in influenza-related hospitalizations in vaccinated versus unvaccinated individuals.

Compared with hospitalized patients without the flu, patients with influenza (1490/4198, 35.5%) were older (age >75 years; 50.8% vs 47.6%), more likely to be smoking (34.2% vs 26.9%), more likely to reside in long-term care (9.2% vs 7%), and less likely to be vaccinated during the season of hospitalization (58.9% vs 70.6%).

Influenza positive patients (n = 1833, 38.5%) experienced higher crude mortality (9.7% vs 7.9%, P = .047), and critical illness (17.2% vs 12.1%, P <.001) compared with influenza-negative patients. However, in the adjusted analysis, vaccination wasn’t associated with significant mortality reduction (odds ratio [OR], 0.9; 95% CI 0.6-1.4).


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