Category: Asthma Research and Studies

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Asthma and Gas Stoves

Gas Stove Emissions Worsen Asthma Symptoms

According to published reports bu the U.S. National Institute of Health, Johns Hopkins University scientists supported by NIEHS report that high levels of nitrogen dioxide gas from cooking and heating stoves in indoor environments aggravate asthma symptoms in inner-city children, especially pre-school aged children. Nitrogen dioxide gas is most prevalent in industrial settings, but it also found at high levels in many poor, inner-city homes that have unvented gas stoves. In a recent report published in Environmental Health Perspectives the Hopkins researchers report that asthma exacerbations were directly related to high concentrations of nitrogen dioxide in the inner-city homes they studied.

The research team compared the nitrogen dioxide levels in the homes of 150 inner-city Baltimore children aged 2-6 to the frequency and intensity of coughing, wheezing, shortness of breath, and chest tightness. Each 20-point increase in nitrogen dioxide levels led to 10 percent more days of coughing and 15 percent more days of limited speech due to wheezing. Eighty-three percent of the homes had gas cooking stoves and 72 percent were heated with natural gas. Forty-two percent of the households had annual incomes less than $25,000.

Asthma is the most common pediatric chronic disease affecting 6.2 million children in the United States alone. It is widely known that severe asthma is most prevalent in the inner-city environment. This is due in part to poor access to health care and environmental conditions such as the disproportionate exposure to indoor allergens, dust, cigarette smoke, and automobile exhaust. The authors conclude that physicians caring for children with asthma should ask about their home’s heating and cooking appliances and recommend using alternatives if possible or at least encourage the parents to have the stoves properly vented.

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Asthma Risk and Birth Weight Reported

Accelerated infant growth increases risk of future asthma symptoms in children says study from The Generation R Study Group at Erasmus Medical Center in the Netherlands.

According to the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine, accelerated growth in the first three months of life, but not fetal growth, is associated with an increased risk of asthma symptoms in young children. a

“We know that low birth weight is associated with an increased risk of asthma symptoms in children, but the effects of specific fetal and infant growth patterns on this risk had not been examined yet,” said researcher Liesbeth Duijts, MD, PhD. “In our study, weight gain acceleration in early infancy was associated with an increased risk of asthma symptoms in children of preschool age, independent of fetal growth patterns, suggesting that early infancy might be a critical period for the development of asthma.”

This study was embedded in the Generation R Study, a population-based prospective cohort study, and included 5,125 children who were followed from fetal life through the age of four. Information on asthma symptoms was obtained by questionnaires at the ages of 1, 2, 3, and 4.

No consistent relationships between fetal length and weight growth during different trimesters and the development of asthma symptoms were observed. Accelerated weight gain from birth to 3 months following normal fetal growth was associated with increased risks of asthma symptoms, including wheezing (overall odds ratio (OR) 1.44 (95% confidence interval (CI): 1.22, 1.70), shortness of breath: 1.32 (1.12, 1.56), dry cough: 1.16 (1.01, 1.34), and persistent phlegm: 1.30 (1.07, 1.58)). The associations between accelerated infant growth and risk of developing asthma symptoms were independent of other fetal growth patterns and tended to be stronger among children of atopic mothers.

“Our results suggest that the relationship between infant weight gain and asthma symptoms is not due to the accelerated growth of fetal growth-restricted infants only,” said Dr. Duijts. “While the mechanisms underlying this relationship are unclear, accelerated weight growth in early life might adversely affect lung growth and might be associated with adverse changes in the immune system.”

The study had a few limitations, including the possibility of measurement error in the estimation of fetal weight and the use of self-report for asthma symptoms.

“Further research is needed to replicate our findings and explore the mechanisms that contribute to the effects of growth acceleration in infancy on respiratory health,” concluded Dr. Duijts. “The effects of infant growth patterns on asthma phenotypes in later life should also be examined.”

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Asthma Risk and Children Born by C-Section Study

Published reports in the American Journal of Epidemiology reflect that children delivered by Cesarean section appear to be at a slight increased risk of developing asthma by age 3.

According to press reports, researchers analyzed data from more than 37,000 participants in the Norwegian Mother and Child Cohort Study in order to compare the health of children who were delivered by planned or emergency C-section with those who were born vaginally.

The results showed that children delivered by C-section had a slightly increased risk for asthma at age 3, but no increased risk for wheezing or frequent lower respiratory tract infections. The risk of asthma was highest among those whose mothers did not have allergies.

According to the Norwegian Institute of Public Health, “It is unlikely that a Cesarean delivery itself would cause an increased risk of asthma, rather that children delivered this way may have an underlying vulnerability,” study primary author Maria Magnus, a researcher at the department of chronic diseases.

Possible reasons for the increased risk of asthma among children delivered by C-section include an altered bacterial flora in their intestine that affects their immune system development, or the fact that these children are more likely to

While the study found an association between C-section birth and asthma, it did not demonstrate a cause and effect.

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Asthma Control and Biofeedback

Study Shows Promise Says U.S. National Jewish Study

Press reports reflect that researchers see great potential. They’re hoping asthma sufferers can eventually depend on biofeedback to breathe.

With sensors on each wrist to take his pulse and one monitoring his diaphragm, Kyle Laubenstein was all hooked up and ready to breathe.

“As you breathe in, feel your belly gently expanding. As you breathe out, feel it gently collapsing again,” a nurse told Laubenstein.

Laubenstein followed the instructions with his eyes on a screen, pacing him so he breathed easily and comfortably. That’s not always the case with Laubenstein because he struggles with asthma.

“Wheezing, coughing, shortness of breath after a vigorous exercise,” Laubenstein said.

Laubenstein has medication called albuterol to open his airways, but he’d like to do without it. That’s why he signed up to try biofeedback, controlling his heart rate.

Once a week Laubenstein goes to National Jewish Health to practice, and he practices at home.

“It’s somewhat like learning to ride your bike. Once you have it down you can keep doing it,” Dr. Fred Wamboldt said.

Wamboldt is leading the study evaluating biofeedback and how controlling heart rate or certain brain waves impacts the lungs.

“The techniques we’re using here we know work for a variety of conditions, and what we want to see is, do they work for asthma?” Wamboldt said.

Laubenstein is sold.

“It seems to be working very well. I haven’t had to use the albuterol for about a month and a half, 2 months,” Laubenstein said.

National Jewish needs study participants — non-smoking adults with persistent asthma who have not taken inhaled steroid medication in the last 30 days. Participants have to commit to weekly visits over 4 months. They will be reimbursed for their time. Visit the National Jewish Health website for more information.

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Safer Asthma Treatment Explored

Salk Institute for Biological Studies discovery may lead to safer treatments for asthma, allergies and arthritis


Scientists find link between biological clock and sugar metabolism Says Study

Scientists have discovered a missing link between the body’s biological clock and sugar metabolism system, a finding that may help avoid the serious side effects of drugs used for treating asthma, allergies and arthritis.

In a paper published last week in Nature, scientists at the Salk Institute for Biological Studies report finding that proteins that control the body’s biological rhythms, known as cryptochromes, also interact with metabolic switches that are targeted by certain anti-inflammatory drugs.

The finding suggests that side effects of current drugs might be avoided by considering patients’ biological rhythms when administering drugs, or by developing new drugs that target the cryptochromes.

“We knew that our sleep and wake cycle are tied to when our bodies process nutrients, but how this happened at the genetic and molecular level was a complete mystery,” says Ronald M. Evans, a professor in Salk’s Gene Expression Laboratory, who led the research team. “Now we’ve found the link between these two important systems, which could serve as a model for how other cellular processes are linked and could hold promise for better therapies.”

Glucocorticoids are steroid hormones that occur naturally in the body and help control the amount of sugar in a person’s blood, so that nutrient levels rise in the morning to fuel daily activities and fall again at night. They function in cells by interacting with glucocorticoid receptors, molecular switches on the outside of the nucleus, which Evans first discovered in 1985.

Glucocorticoids also play a role in regulating inflammation and are used as anti-inflammatory drugs for diseases caused by an overactive immune system, such as allergies, asthma and rheumatoid arthritis. They are also used to treat inflammation in cancer patients.

However, because of their role in sugar metabolism, the steroids can disrupt a person’s normal metabolism, resulting in dangerous side effects, including excessively high blood sugar levels, insulin resistance and diabetic complications.

The Salk researchers may have found a way around these side effects by discovering a new function for cryptochromes 1 and 2, proteins that were previously known for their function in the biological clock.

The cryptochromes serve as breaks to slow the clock’s activity, signaling our biological systems to wind down each evening. In the morning, they stop inhibiting the clock’s activity, helping our physiology ramp up for the coming day.

In their new study on mouse cells, Evans and his colleagues made the surprising discovery that cryptochromes also interact with glucocorticoid receptors, helping to regulate how the body stores and uses sugar.

“We found that not only are the crytopchromes essential to the functioning of the circadian clock, they regulate glucocorticoid action, and thus are central to how the clock interacts with our daily metabolism of nutrients,” says Katja A. Lamia, an assistant professor at The Scripps Research Institute and former post-doctoral researcher in Evan’s laboratory at Salk.

Mouse cells function much like human cells, so the findings could have important implications for treatment of autoimmune diseases and cancer. By taking into account the daily rise and fall of cryptochrome levels, the scientists say, doctors might be able to better time administration of glucocorticoid drugs to avoid certain side effects related to sugar metabolism.

The discovery also raises the possibility of developing new anti-inflammatory drugs that avoid some side effects by targeting cryptochromes instead of directly targeting the glucocorticoid switches.

More broadly, Evans says, the study may help explain the connection between sleep and nutrient metabolism in our bodies, including why people with jobs that require night work or erratic hours are at higher risk for obesity and diabetes.

“Disrupting the normal day-night cycle of activity may prevent a person’s biological clock from synchronizing correctly with their daily patterns of nutrient metabolism,” Evans says. “As a result, the body might not store and process sugar normally, leading to metabolic disease.”

The study was funded by the National Institutes of Health, the Glenn Foundation for Medical Research, the Leona M. and Harry B. Helmsley Charitable Trust and the Life Sciences Research Foundation.

Contact: Andy Hoang
Ahoang@salk.edu
619-861-5811
Salk Institute

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Asthma and Stem Cell Therapy

Stem Cell Therapy May Help Treat Patients with Severe Asthma Says Study

According to a study conducted by Dr Eva Mezey, of the National Institutes of Health in Maryland, mice that developed Asthma by being exposed to pollen were protected against attacks after the cells obtained from bone marrow were injected into them.

These particular stem cells are already used to suppress inflammatory response after bone marrow transplants in humans according to the report.

The researchers believe the bone marrow stem cells reduce inflammation in the airways, the immune system’s normal response to severe cases of asthma.

The researchers whose findings are published in Proceedings of the National Academy of Sciences say about 5,000 people a year die from asthma in the US alone with 100,000 fatalities throughout the world.

Treatments for severe cases are largely inadequate at resolving the sufferer’s conditions so new ones are needed for therapy-resistant ones.

They say the stem cells are already used to treat autoimmune diseases and the same approach could provide help treat asthma and other severe allergic conditions.

Lead researcher Dr Mezey and colleagues said: “These data suggest that allergic conditions — specifically therapy resistant asthma — might also be a likely target of the recently discovered cellular therapy approach using BMSCs.

“These data provide another example of the ability of BMSCs to ‘sense’ their immunological environment and respond accordingly.

“It is hard to imagine a drug or combination of drugs that could act this way and further work should be done to determine whether the cells could be used to treat patients with therapy-resistant asthma.”

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Asthma: Searching for a Cure; Are Antibiotics the Answer?

Asthma: Searching for a Cure;
Are Antibiotics the Answer?

By Tinka Davi

This is a story about one mans search for a cure for Asthma.

For more than seven years, Bill Cullifer of Folsom, CA has suffered from asthma. His conversation is punctuated by deep, uncontrollable coughs that occur frequently and without warning. His children can often locate him by his frequent coughs.

Asthma prevents him from strenuous physical activity. In fact, Cullifer’s energy is so regularly sapped, he finds it difficult to exercise at all.

First diagnosed with adult onset asthma in 2004 Cullifer sought treatment from his primary physician and has consulted with a variety of specialist ranging from allergist, ear nose and throat specialist and pulmonologist.

To treat his Asthma they’ve prescribed three different medications, Zymbicort, Sprivia and Prednisone,

Now Cullifer has added another med, an antibiotic, azithromycin to the mix. That medication is the result of his ceaseless pursuit of information about asthma, its causes, remedies and a possible cure.

To assist him in his research, Cullifer established an Asthma foundation, a news blog and a Facebook page to help him educate himself and others about Asthma and lung disease. It was there (https://worldasthmafoundation.org/asthma-and-chlamydia-pneumoniae.htm ) that he ran across a press release and a video presentation from the American Society of Microbiology annual conference that talked about the role of bacteria in severe asthma and the potential for antibiotic treatment. A study presented by Eduard Drizik, a microbiologist at the University of Massachusetts, Amherst, showed a significant link between Chlamydia pneumoniae (bacteria that causes severe asthma symptoms, not the sexually transmitted disease) and the severity of asthma.

“We know that asthma is a multifactorial disease and has many phenotypes.” Phenotypes are observable properties of an organism that are produced by the interaction of the genotype and the environment.

“We have found infectious phenotypes and based on the data and findings that have shown that there is one phenotype that can be curable with antibiotics,” said Drizik.

The article stated that “. . . patients who were treated on the basis of asthma severity with antibiotics had significant improvements in asthma symptoms and some even experienced a complete abolition of these symptoms.” Drizik recommended that physicians should further explore the involvement of microbes in difficult to treat asthma cases, since there might be a cure for some types of asthma.

The word “cure” definitely caught Cullifer’s attention.

He dug further and found a physician in Wisconsin, David L. Hahn, who has pioneered the research and has published a paper on the treatment of C. pneumoniae. Hahn, a family practitioner and Dean of the Medical Center and Clinical Professor at the University of Wisconsin School of Medicine and Public Health, began treating his asthma patients with antibiotics several years ago.
Cullifer called and interviewed Hahn. Their discussion is podcast on Facebook at http://facebook.com/asthmafoundation.

In the interview, Hahn said that the patients with new onset asthma who had documented C. pneumoniae infections and who received antibiotics improved. In fact, he said, their asthma disappeared after early treatment. However, those with longstanding persistent asthma didn’t respond well to traditional treatments and Hahn prescribed the antibiotic azithromycin.

Hahn said, “Azithromycin is unique . . . almost like a magic bullet for intracellular infections, because of all the macrolide antibiotics, which are effective against Chlamydia pneumoniae, it concentrates intracellularly and doesn’t get out of the cells very easily.” Because that’s where the bacteria live, that’s where the medicine should be.

Hahn credits Pfizer, Inc. developers of Zithromax (azithromycin) who showed an early interest in doing clinical trials on the effect of the drug and asthma. “They did help in very significant ways…but made a decision not to lodge major clinical trials in asthma,” Hahn said.

The doctor recommends long-term dosing of Zithromax/azithromycin, instead of the typical 10 days to two weeks of treatment. Cullifer is taking the medication for 14 weeks and is already feeling better. “I’m into my fourth week and I definitely have more energy,” he said.

There’s a downside to taking azithromycin long term. It’s what Hahn calls an antibiotic resistance on the part of physicians who have been trained not to prescribe antibiotics unnecessarily. Other physicians just don’t sign on to prescribing it, but Hahn and patients including Cullifer are hopeful that will change when the benefits are widely publicized and understood.

Hahn noted that many asthma patients who ask to be treated with azithromycin are being turned away because their physicians don’t know about the potential for treatment and it’s not in the guidelines. He’d like to see pressure on the part of the public to let physicians and practice know there is a real demand for this sort of treatment with antibiotics.

He’s writing a book that he hopes might broaden the public’s awareness of the issue. “This is creative gonzo marketing and may be the only way to go because I have tried all the traditional routes,” Hahn said.

Cullifer has had asthma episodes and been hospitalized more than once. “I could have died,” he said. That’s why he’s supporting physicians like Drizik and Hahn and their diligent efforts to find treatment for long term and severe asthma. Cullifer is continually providing resources and updates on the World Asthma Foundation blog and on Facebook. Like other asthma sufferers, he is campaigning for a cure.

About Asthma
The World Health Organization estimates that 235 million people suffer from asthma, a chronic disease characterized by recurrent attacks of breathlessness, coughing and wheezing. These attacks vary in severity and frequency from person to person. The disease is managed by controlling symptoms, which may occur several times in a day or week in affected individuals. For some people, symptoms become worse during physical activity or at night. Asthma is a strong risk factor for the development of Chronic Obstructive Lung Disease (COPD), one of the most chronic lung diseases that make it difficult to breathe. The recognition that asthma pathogenesis involves chronic inflammation has led to studies investigating the presence of various infectious organisms. There is no cure for asthma.

Tinka Davi, contributing writer and editor for the World Asthma Foundation, writes on a variety of health issues and lifestyle topics. She is based in Folsom, CA.

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Asthma and Childhood Obesity

Asthma and Children with Obesity have More Asthma Problems Says University of California Study

The study was conducted at the University of California San Diego and looked at over 32,000 children who had been diagnosed with asthma with half of them also suffering from excessive weight or obesity. Researchers found that the children who were overweight had numerous prescriptions for inhalers to provide them with albuterol, which opens the airways during an asthma attack, than those whose weights were normal.

Rates of inhaler use were close, at 2.8 inhalers for normal weight and 3.1 inhalers for those overweight, but still show an increased effect that weight could have on controlling the symptoms. They also noted that the heavier children used more steroid based inhalers as well which are used to keep airway inflammation controlled on a daily basis.

“Preventing obesity, and stressing the importance of weight loss might improve asthma control and exacerbation risk in children and decrease the incidence of asthma in adults,” wrote the researchers in the Journal of Allergy and Clinical Immunology. This is particularly relevant as they also showed that obesity had risen by 17% with asthma by 10% in the past decades.

Dr. Kenneth B. Quinto from the University of California, San Diego, and colleagues looked back at more than 32,000 kids who’d been diagnosed with asthma and were enrolled in a Kaiser Permanente health plan. Nearly half of the children were overweight or obese.

The researchers found that the heavier kids were more likely to have more than a handful of yearly prescriptions for rescue inhalers, which contain short-acting drugs such as albuterol that open up the airways when an asthma attack is coming on.

On average, normal-weight children used 2.8 rescue inhalers a year, whereas obese kids used 3.1.

The heavy youngsters also used more inhaled steroids, such as Pulmicort or Flovent, which are a mainstay treatment to keep airway inflammation under control on a daily basis in asthmatics.

And the results held up after Quinto and his colleagues accounted for alternative explanations of the differences, such as sex, race, diabetes and parents’ education levels.

The team speculates that the extra pounds might be weighing on the lungs, making obese kids feel like they need more medication. Scientists have also found that overweight people don’t respond as well as others to steroids, which might help explain the new findings.

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Asthma and Ozone

Does Ozone Matter?

According to Mount Sinai School of Medicine of New York, NY climate change may lead to more asthma-related health problems in children, resulting in more emergency room visits in the next decade.

Researchers found changing levels of ozone could lead to more than a seven percent increase in ER visits by children under 17.

The team used regional and atmospheric chemistry models to simulate ozone levels for June through August in the 2020s and compared them to 1990s levels.

Study authors say they plan to continue using these models to understand specific impacts of climate change. They conclude better measures to reduce carbon pollution need to be implemented to protect our health.

The abstract was presented on Sunday, May 3, 2009 at the Pediatric Academic Societies Annual Meeting in Baltimore, Maryland. The lead author of this research is Perry Elizabeth Sheffield, MD, Pediatric Environmental Health Fellow in the Department of Community and Preventive Medicine and the Department of Pediatrics at Mount Sinai School of Medicine. Mount Sinai worked with Natural Resources Defense Council and the Columbia University Mailman School of Public Health on this eye-opening research that finds a direct connection between air pollution and the health of children.Ozone has many known negative respiratory health effects to which children are particularly vulnerable.

An important projected consequence of climate change is the increase in ground-level ozone. Urban areas such as the New York City metropolitan area are at a higher risk of increasing temperature compared to rural areas. However, while more ozone is formed in higher temperatures, the downwind suburban areas are predicted in some of the models to experience higher ozone levels.

For this study, Dr. Sheffield and her colleagues created a model describing future projected rates of respiratory hospitalizations for children less than two years of age using baseline NYC metropolitan area hospitalization rates from publicly available corresponding state Department of Health databases.

These hospitalization rates were then compared to a previously developed dose-response relationship between ozone levels and pediatric respiratory hospitalizations, and the expected New York City eight-hour daily maximum ozone levels for the 2020s, as projected by a regional climate model created by the NY Climate and Health Project, supported by a grant from the US Environmental Protection Agency.

Two separate future scenarios were used. The two scenarios differed by the amount of projected ozone precursor emissions (chemicals that are converted to ozone by light and heat).

In both scenarios, ozone levels rise by 2020. The study found that by 2020, respiratory hospitalizations are projected to rise between four and seven percent for children under two years old because of projected air pollution (ozone) increases. The scenario with increased ozone precursors showed less of an overall increase in hospital admissions because of a paradoxical reduction in ozone due to the effects of air pollutant interactions, sometimes referred to as the scavenger molecule effect. These are likely conservative estimates because population was held constant, a single dose response function was used for the entire area, and most counties were not weighted by race and ethnicity. “These significant changes in children’s hospitalizations from respiratory illnesses would be a direct result of projected climate-change effects on ground-level ozone concentrations,” said Dr. Sheffield. “This research is important because it shows that we as a country need to implement policies that both improve air quality and also prevent climate change because this could improve health in the present and prevent worsening respiratory illness in the future.”

Our study supports the necessity of improving air pollution around the world. We need to begin to make these improvements through industry emission controls, traffic reduction policies, and increased enforcement of traffic regulations, said study co-author Dr. Philip Landrigan, Professor and Chair of Community and Preventive Medicine, and Director of the Children’s Environmental Health Center, at Mount Sinai School of Medicine.

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Can Pharma Improve Asthma and COPD Meds

Are Safer and more Effective Therapeutic Asthma and COPD Medications on the Horizon?

Companies to Watch

Apellis Pharmaceuticals in collaboration with leading U.S. universities believes that safer and more effective therapeutic Asthma and COPD medications are on the horizon and it aims to bring a new class of anti-inflammatory drugs to the market to address chronic inflammatory diseases in areas of significant unmet need such as asthma and chronic obstructive pulmonary disease (COPD).

Severe Asthma and COPD

According to the Apellis Pharmaceuticals website, Asthma affects 7% of the population of the United States and a total of 300 million people worldwide. In 2009 asthma represented a $12.7B market. The standard-of-care in asthma is dominated by corticosteroids, beta-agonists and to a lesser extent leukotriene inhibitors and anti-IgE antibodies. While these drugs control asthma in a majority of patients, there remains a significant unmet medical need for safer and more effective therapeutics. Especially in severe asthma there is a tendency to have poor control with corticosteroids. Due to the continued immune aggression on the lungs, patients with severe asthma account for ~50% of asthma-related healthcare costs and are at greater risks of complications, including the development of COPD and death.

COPD is the third-leading cause of death in the USA after heart disease and cancer. In spite of the large number of people affected (~14 million people have been diagnosed withGrade II-IV COPD) and its enormous cost (the NIH estimated the cost of COPD to the healthcare system to be $42.6B in 2007) there are no treatments that effectively treat COPD. The standard of care is almost exclusively symptomatic (suppressing inflammation and opening the airways) but no drug has been successful in slowing or halting the immune process that slowly destroys the airways (chronic bronchitis) and lung tissues (emphysema).

Apellis explores novel mechanisms to modify these diseases by inhibiting complement activation and has assembled an innovative and multi-faceted drug pipeline through a combination of selective in-licensing and internal research and development. As an important component of its long-term strategy, Apellis also engages in and catalyses the development of broad-ranging and complementary technologies such as drug delivery systems and diagnostic tools through collaborations and grant-funded programs.

If confirmed, the most important distinguishing feature of complement inhibition would be its exceptional ability to change the immunological micro-environment and thus resolve the immune process at work in these pulmonary diseases. APL-1 might thus halt or reverse anatomic remodeling of the lungs, the principle cause of irreversible loss of respiratory capacity, morbidity and mortality in severe asthma and COPD.