Visualizing Asthma-causing Immune Cells At Work

Immune cells known as eosinophils have a central role in causing asthma. Now, a team of researchers at Massachusetts General Hospital, Boston, has developed approaches to noninvasively visualize in real-time eosinophil responses in the lungs and airways of mice with a disease that mimics asthma (experimental allergic airway inflammation); they hope that these approaches might be developed to help assess the efficacy of treatments (both old and new) for the disease.

The team, led by Mikael Pittet and Ralph Weissleder, visualized eosinophils at single-cell resolution using various noninvasive real-time molecular imaging technologies (specifically, near-infrared fluorescence fiber optic bronchoscopy, intravital microscopy, and fluorescence-mediated tomography) following injection of an optical sensor that targets proteins produced by eosinophils known as MMPs.

Using a combination of the sensitive optical sensor and fluorescence-mediated tomography, it was observed that dexamethasone (a drug used to treat severe asthma) decreased the number of eosinophils in the lungs of mice with allergic airway inflammation.

As some of the imaging techniques have the potential to be developed for the clinic, the authors suggest that in combination with an appropriate optical sensor they might improve our ability to diagnose asthma and assess treatment efficacy.

Cells That Mediate Steroid-resistant Asthma Identified

Children's Hospital of Pittsburgh of UPMC researchers have identified cells that may play a key role in some forms of steroid-resistant asthma, a complication of the condition that makes treatment even more challenging.

The identification of a lineage of cells known as T Helper Type 17 (Th17) may help scientists in the development of new treatments that lead to better control of asthma, according to the study's senior author, Jay K. Kolls, MD, chief of the Division of Pediatric Pulmonary Medicine, Allergy and Immunology at Children's Hospital.

More than 22 million Americans (including 9 million children) are diagnosed with asthma, according to the U.S. Centers for Disease Control and Prevention (CDC). As many as 50 percent of them have asthma that can be resistant to steroids, which are intended to reduce lung inflammation during an asthma attack, Dr. Kolls said.

"Asthma is a challenging condition to treat. For many patients, if they take preventive medications regularly, the condition can be controlled and they can lead relatively normal lives," Dr. Kolls said. "Inhaled steroids are an important treatment for patients to prevent asthma attacks. Unfortunately, some patients have attacks despite the use of inhaled steroids, meaning they don't respond to steroids or they need such high doses that side effects are experienced."

In a study published in the September issue of the Journal of Immunology, Dr. Kolls and colleagues found that Th17 cells mediated steroid-resistant airway inflammation and hyper-responsiveness in animal models of asthma. Th17 cells are part of the immune system and are found where the body comes in contact with the external environment, such as the lungs and the lining of the gastrointestinal tract.

"Identifying Th17 cells as a potential mechanism by which steroid-resistant asthma gives us a potential new target for the development of drugs that focus on these cells and lead to better overall control of asthma," said Dr. Kolls, the Niels K. Jerne Professor of Pediatrics and Immunology at the University of Pittsburgh School of Medicine.

Asthma is characterized by repeated wheezing, breathlessness, chest tightness, and nighttime or early morning coughing. Every year, more than half of all Americans diagnosed with asthma suffer at least one acute attack, according to the CDC. These flare-ups lead to approximately 2 million emergency room visits, 10 million outpatient visits and 100 million days of restricted activity every year.

Visualizing Asthma-causing Immune Cells At Work

Immune cells known as eosinophils have a central role in causing asthma. Now, a team of researchers at Massachusetts General Hospital, Boston, has developed approaches to noninvasively visualize in real-time eosinophil responses in the lungs and airways of mice with a disease that mimics asthma (experimental allergic airway inflammation); they hope that these approaches might be developed to help assess the efficacy of treatments (both old and new) for the disease.

The team, led by Mikael Pittet and Ralph Weissleder, visualized eosinophils at single-cell resolution using various noninvasive real-time molecular imaging technologies (specifically, near-infrared fluorescence fiber optic bronchoscopy, intravital microscopy, and fluorescence-mediated tomography) following injection of an optical sensor that targets proteins produced by eosinophils known as MMPs.

Using a combination of the sensitive optical sensor and fluorescence-mediated tomography, it was observed that dexamethasone (a drug used to treat severe asthma) decreased the number of eosinophils in the lungs of mice with allergic airway inflammation.

As some of the imaging techniques have the potential to be developed for the clinic, the authors suggest that in combination with an appropriate optical sensor they might improve our ability to diagnose asthma and assess treatment efficacy.

Cells That Mediate Steroid-resistant Asthma Identified

Children's Hospital of Pittsburgh of UPMC researchers have identified cells that may play a key role in some forms of steroid-resistant asthma, a complication of the condition that makes treatment even more challenging.

The identification of a lineage of cells known as T Helper Type 17 (Th17) may help scientists in the development of new treatments that lead to better control of asthma, according to the study's senior author, Jay K. Kolls, MD, chief of the Division of Pediatric Pulmonary Medicine, Allergy and Immunology at Children's Hospital.

More than 22 million Americans (including 9 million children) are diagnosed with asthma, according to the U.S. Centers for Disease Control and Prevention (CDC). As many as 50 percent of them have asthma that can be resistant to steroids, which are intended to reduce lung inflammation during an asthma attack, Dr. Kolls said.

"Asthma is a challenging condition to treat. For many patients, if they take preventive medications regularly, the condition can be controlled and they can lead relatively normal lives," Dr. Kolls said. "Inhaled steroids are an important treatment for patients to prevent asthma attacks. Unfortunately, some patients have attacks despite the use of inhaled steroids, meaning they don't respond to steroids or they need such high doses that side effects are experienced."

In a study published in the September issue of the Journal of Immunology, Dr. Kolls and colleagues found that Th17 cells mediated steroid-resistant airway inflammation and hyper-responsiveness in animal models of asthma. Th17 cells are part of the immune system and are found where the body comes in contact with the external environment, such as the lungs and the lining of the gastrointestinal tract.

"Identifying Th17 cells as a potential mechanism by which steroid-resistant asthma gives us a potential new target for the development of drugs that focus on these cells and lead to better overall control of asthma," said Dr. Kolls, the Niels K. Jerne Professor of Pediatrics and Immunology at the University of Pittsburgh School of Medicine.

Asthma is characterized by repeated wheezing, breathlessness, chest tightness, and nighttime or early morning coughing. Every year, more than half of all Americans diagnosed with asthma suffer at least one acute attack, according to the CDC. These flare-ups lead to approximately 2 million emergency room visits, 10 million outpatient visits and 100 million days of restricted activity every year.

Low-sodium Advice For Asthmatics Should Be Taken With A Grain Of Salt

Following a low-sodium diet does not appear to have any appreciable impact on asthma control, according to new research.

Contrary to past studies — which have suggested a link between low-sodium diets and improved asthma control — a new study by researchers at The University of Nottingham found no evidence that cutting back on salt helps patients with their symptoms.

Dr Zara Pogson, clinical research fellow at The University of Nottingham, said: “Despite the clear benefit of a low-sodium diet on cardiovascular risk factors, there is no therapeutic benefit in the use of a low-sodium diet…on asthma control in our study population.”

Nearly 200 subjects completed the study which compared the effect of changes in bronchial reactivity — a measure of asthma activity — on asthma patients who followed a strict low-sodium diet. Each subject either received sodium supplements to approximate normal sodium intake of 80 millimoles per litre (mmol) a day, or placebo tablets, for six weeks.

Dr Pogson and colleagues hypothesized that the subjects on the low sodium intake would show improved clinical control of asthma symptoms based on a test of asthma activity, measures of lung function, asthma symptoms and use of asthma medication. Contrary to their hypothesis, however, they detected no differences in any measures of asthma between the groups.

“We observed no difference in the outcome measures related to asthma activity in adults with asthma and bronchial reactivity who adopted a low-sodium diet for six weeks compared with those who did not, despite a final difference in daily sodium excretion of 50 mmol,” wrote Dr Pogson.

While past studies have suggested a link between low-sodium diets and improved asthma control, none were as large or tightly controlled as this study, suggesting that their findings may have been artifacts of study design rather than reflective of a true therapeutic benefit.

“We were disappointed that a simple measure, such as a decrease in sodium intake, does not result in improvements in asthma control,” said Dr Pogson. “We therefore cannot advise people with asthma to alter their sodium intake to improve control of their asthma, despite the fact that a low-sodium diet improves cardiovascular risk factors. This study suggests that further dietary research in asthma should be directed to factors other than sodium.”

According to Asthma UK, 5.2 million people in the UK have asthma — and 50 per cent of these people have severe asthma symptoms that have a major impact on their daily lives.

The results of the randomised, double-blind, placebo-controlled trial were published in the second issue for July of the American Journal of Respiratory and Critical Care Medicine by the American Thoracic Society.

Low-sodium Advice For Asthmatics Should Be Taken With A Grain Of Salt

Following a low-sodium diet does not appear to have any appreciable impact on asthma control, according to new research.

Contrary to past studies — which have suggested a link between low-sodium diets and improved asthma control — a new study by researchers at The University of Nottingham found no evidence that cutting back on salt helps patients with their symptoms.

Dr Zara Pogson, clinical research fellow at The University of Nottingham, said: “Despite the clear benefit of a low-sodium diet on cardiovascular risk factors, there is no therapeutic benefit in the use of a low-sodium diet…on asthma control in our study population.”

Nearly 200 subjects completed the study which compared the effect of changes in bronchial reactivity — a measure of asthma activity — on asthma patients who followed a strict low-sodium diet. Each subject either received sodium supplements to approximate normal sodium intake of 80 millimoles per litre (mmol) a day, or placebo tablets, for six weeks.

Dr Pogson and colleagues hypothesized that the subjects on the low sodium intake would show improved clinical control of asthma symptoms based on a test of asthma activity, measures of lung function, asthma symptoms and use of asthma medication. Contrary to their hypothesis, however, they detected no differences in any measures of asthma between the groups.

“We observed no difference in the outcome measures related to asthma activity in adults with asthma and bronchial reactivity who adopted a low-sodium diet for six weeks compared with those who did not, despite a final difference in daily sodium excretion of 50 mmol,” wrote Dr Pogson.

While past studies have suggested a link between low-sodium diets and improved asthma control, none were as large or tightly controlled as this study, suggesting that their findings may have been artifacts of study design rather than reflective of a true therapeutic benefit.

“We were disappointed that a simple measure, such as a decrease in sodium intake, does not result in improvements in asthma control,” said Dr Pogson. “We therefore cannot advise people with asthma to alter their sodium intake to improve control of their asthma, despite the fact that a low-sodium diet improves cardiovascular risk factors. This study suggests that further dietary research in asthma should be directed to factors other than sodium.”

According to Asthma UK, 5.2 million people in the UK have asthma — and 50 per cent of these people have severe asthma symptoms that have a major impact on their daily lives.

The results of the randomised, double-blind, placebo-controlled trial were published in the second issue for July of the American Journal of Respiratory and Critical Care Medicine by the American Thoracic Society.

Ear Infections In Children Linked To Passive Smoking

A new report from Perth's Telethon Institute for Child Health Research has found a strong link between childhood ear infections and exposure to tobacco smoke.

The families of 100 Aboriginal children and 180 non-Aboriginal children participated in the Kalgoorlie Otitis Media Research Project, allowing the collection of social, demographic, environmental and biological data to investigate the causes of otitis media (middle ear infections). The children had regular ear examinations from birth until 2 years of age.

Chief Investigator Dr Deborah Lehmann, who heads the Institute's infectious diseases research, said ear infections were the most common reason that young children see a doctor and can cause life-long problems.

"Up to 20 per cent of children have more than three ear infections between 1 and 2 years of age. If their hearing is damaged, it can seriously affect their educational outcomes and social circumstances in adulthood," Dr Lehmann said.

"In Aboriginal children, these ear infections typically start at a younger age, are much more common and more likely to result in hearing loss."

Key findings from the project include:

• Otitis media was diagnosed at least once in 74% of Aboriginal children and 45% of non-Aboriginal children.
• 64% of Aboriginal children and 40% of non-Aboriginal children were exposed to environmental tobacco smoke.
• If we eliminated exposure to tobacco smoke we estimate that we could reduce ear infections by 27% in Aboriginal children and 16% in non-Aboriginal children
• The impact of passive smoking in the home on ear infections was reduced if the children also attended day care.

Dr Lehmann said there is evidence that passive smoking can increase the adherence of bacteria in the respiratory passages and depress the immune system.

"These results highlight the importance of reducing children's exposure to passive smoking, and this is particularly important for Aboriginal people where the rates of both smoking and otitis media are high," she said.

"Few Aboriginal children have access to formal childcare despite studies showing that it is an effective way to improve early development and educational outcomes for disadvantaged children. The fact that it could also reduce the burden of ear infections in Aboriginal children adds weight to calls for appropriate childcare facilities to be provided."

The results are published in the latest edition of the Medical Journal of Australia.

Ear Infections In Children Linked To Passive Smoking

A new report from Perth's Telethon Institute for Child Health Research has found a strong link between childhood ear infections and exposure to tobacco smoke.

The families of 100 Aboriginal children and 180 non-Aboriginal children participated in the Kalgoorlie Otitis Media Research Project, allowing the collection of social, demographic, environmental and biological data to investigate the causes of otitis media (middle ear infections). The children had regular ear examinations from birth until 2 years of age.

Chief Investigator Dr Deborah Lehmann, who heads the Institute's infectious diseases research, said ear infections were the most common reason that young children see a doctor and can cause life-long problems.

"Up to 20 per cent of children have more than three ear infections between 1 and 2 years of age. If their hearing is damaged, it can seriously affect their educational outcomes and social circumstances in adulthood," Dr Lehmann said.

"In Aboriginal children, these ear infections typically start at a younger age, are much more common and more likely to result in hearing loss."

Key findings from the project include:

• Otitis media was diagnosed at least once in 74% of Aboriginal children and 45% of non-Aboriginal children.
• 64% of Aboriginal children and 40% of non-Aboriginal children were exposed to environmental tobacco smoke.
• If we eliminated exposure to tobacco smoke we estimate that we could reduce ear infections by 27% in Aboriginal children and 16% in non-Aboriginal children
• The impact of passive smoking in the home on ear infections was reduced if the children also attended day care.

Dr Lehmann said there is evidence that passive smoking can increase the adherence of bacteria in the respiratory passages and depress the immune system.

"These results highlight the importance of reducing children's exposure to passive smoking, and this is particularly important for Aboriginal people where the rates of both smoking and otitis media are high," she said.

"Few Aboriginal children have access to formal childcare despite studies showing that it is an effective way to improve early development and educational outcomes for disadvantaged children. The fact that it could also reduce the burden of ear infections in Aboriginal children adds weight to calls for appropriate childcare facilities to be provided."

The results are published in the latest edition of the Medical Journal of Australia.

Common Cold Linked To Ear Infections, Researchers Confirm

A new five-year study at the University of Texas Medical Branch at Galveston confirms the suspected close link between the two most common diseases of young children: colds and ear infections.

The study, which appears in the March 15 issue of Clinical Infectious Disease, confirmed the suspected close link between the two most common diseases of young children, viral colds and ear infections. It also identified the viruses associated with higher rates of ear infections.

"Understanding how viruses and ear infections are linked will definitely help us find new ways to prevent ear infections," said Dr. Tasnee Chronmaitree, a pediatric infectious disease specialist who is the study's principal investigator. "To break the link you must first understand it."

Ear infections are the driving force behind antibiotic resistance, a troubling medical issue, as physicians often administer antibiotics for the painful, persistent ailment.

Chonmaitree has studied otitis media (ear infection) for more than two decades. She said parents could best protect their children by avoiding exposure to sick children and to have their children vaccinated against influenza. She suggested that children in day care might face reduced exposure to viruses if they are enrolled in smaller day care facilities with fewer children.

Funded by the National Institutes of Health, Chonmaitree and colleagues followed 294 children ages 6 months to 3 years for up to one year each. Researchers documented about 1,300 cold episodes and a 61 percent rate of ear infection complication including asymptomatic fluid in the middle ear, which can cause hearing problems. Researchers also identified the types of cold viruses -- adenovirus, respiratory syncytial virus and coronavirus -- that most often resulted in ear infection.

"Because we now know that the common cold is the precursor to an ear infection, it is important for parents to make extra efforts to prevent their children from catching colds," Chonmaitree said. "It's important to avoid exposure to sick children or adults, to avoid day care attendance, if possible, and if that's not an option, to choose a smaller group day care."

Chonmaitree also recommended the use of influenza vaccine, the only vaccine available to prevent respiratory viral infection, which is now available for children older than 6 months. The antiviral drug has also been shown to prevent ear infections associated with influenza, she said.

Chonmaitree and colleagues will continue to study the role of viruses in ear infection aiming to find a way to prevent the disease. Continued funding from the NIH will allow them to study children born with genetic variations who are prone to having ear infections and at the interactions between genes and the environment.

Common Cold Linked To Ear Infections, Researchers Confirm

A new five-year study at the University of Texas Medical Branch at Galveston confirms the suspected close link between the two most common diseases of young children: colds and ear infections.

The study, which appears in the March 15 issue of Clinical Infectious Disease, confirmed the suspected close link between the two most common diseases of young children, viral colds and ear infections. It also identified the viruses associated with higher rates of ear infections.

"Understanding how viruses and ear infections are linked will definitely help us find new ways to prevent ear infections," said Dr. Tasnee Chronmaitree, a pediatric infectious disease specialist who is the study's principal investigator. "To break the link you must first understand it."

Ear infections are the driving force behind antibiotic resistance, a troubling medical issue, as physicians often administer antibiotics for the painful, persistent ailment.

Chonmaitree has studied otitis media (ear infection) for more than two decades. She said parents could best protect their children by avoiding exposure to sick children and to have their children vaccinated against influenza. She suggested that children in day care might face reduced exposure to viruses if they are enrolled in smaller day care facilities with fewer children.

Funded by the National Institutes of Health, Chonmaitree and colleagues followed 294 children ages 6 months to 3 years for up to one year each. Researchers documented about 1,300 cold episodes and a 61 percent rate of ear infection complication including asymptomatic fluid in the middle ear, which can cause hearing problems. Researchers also identified the types of cold viruses -- adenovirus, respiratory syncytial virus and coronavirus -- that most often resulted in ear infection.

"Because we now know that the common cold is the precursor to an ear infection, it is important for parents to make extra efforts to prevent their children from catching colds," Chonmaitree said. "It's important to avoid exposure to sick children or adults, to avoid day care attendance, if possible, and if that's not an option, to choose a smaller group day care."

Chonmaitree also recommended the use of influenza vaccine, the only vaccine available to prevent respiratory viral infection, which is now available for children older than 6 months. The antiviral drug has also been shown to prevent ear infections associated with influenza, she said.

Chonmaitree and colleagues will continue to study the role of viruses in ear infection aiming to find a way to prevent the disease. Continued funding from the NIH will allow them to study children born with genetic variations who are prone to having ear infections and at the interactions between genes and the environment.

Childhood Respiratory Disease Boosts Illness And Death Risks In Adulthood, Study Suggests

Respiratory disease, particularly bronchitis, in early childhood boosts the risks of illness and premature death in adulthood, indicates research published ahead of print in Thorax.

The researchers base their findings on around 10,000 male graduates who went to Glasgow University between 1948 and 1968 and agreed to be part of a long term study to track their health. No women were included because fewer went to university at that time than do now.

As students they were examined by a doctor and supplied details of childhood illness, including bronchitis, asthma, and pneumonia, as well as their weight, height, and blood pressure.

Between 1998 and 2002, efforts were made to trace and survey those who were still alive. In all, 4044 out of 8410 responded.

Those who had had bronchitis, pneumonia, or asthma in early childhood were 57% more likely to die of respiratory disease than those who had not had these illnesses as children.

And they were more than twice as likely to die of chronic obstructive pulmonary disease or COPD, the umbrella term for progressive respiratory diseases, such as emphysema and bronchitis.

Students who had had bronchitis were also 38% more likely to die of cardiovascular disease.

Respiratory illness during childhood was also associated with a higher risk of assorted respiratory problems in adulthood, ranging from the relatively minor to the severe. These findings also held true among those who had never smoked.

Journal reference: Association between early life history of respiratory disease and morbidity and mortality in adulthood Online First Thorax 2008; doi 10.1136/thx.2007.086744

Childhood Respiratory Disease Boosts Illness And Death Risks In Adulthood, Study Suggests

Respiratory disease, particularly bronchitis, in early childhood boosts the risks of illness and premature death in adulthood, indicates research published ahead of print in Thorax.

The researchers base their findings on around 10,000 male graduates who went to Glasgow University between 1948 and 1968 and agreed to be part of a long term study to track their health. No women were included because fewer went to university at that time than do now.

As students they were examined by a doctor and supplied details of childhood illness, including bronchitis, asthma, and pneumonia, as well as their weight, height, and blood pressure.

Between 1998 and 2002, efforts were made to trace and survey those who were still alive. In all, 4044 out of 8410 responded.

Those who had had bronchitis, pneumonia, or asthma in early childhood were 57% more likely to die of respiratory disease than those who had not had these illnesses as children.

And they were more than twice as likely to die of chronic obstructive pulmonary disease or COPD, the umbrella term for progressive respiratory diseases, such as emphysema and bronchitis.

Students who had had bronchitis were also 38% more likely to die of cardiovascular disease.

Respiratory illness during childhood was also associated with a higher risk of assorted respiratory problems in adulthood, ranging from the relatively minor to the severe. These findings also held true among those who had never smoked.

Journal reference: Association between early life history of respiratory disease and morbidity and mortality in adulthood Online First Thorax 2008; doi 10.1136/thx.2007.086744

Study Of 'Big Eaters' Could Lead To Better Asthma Treatments

A new study into the role of a particular immune cell in the lungs could lead to better treatments for the 5 million people in the UK affected by asthma.

Scientists from the University of Southampton's School of Medicine will study the role of macrophages (literally 'big-eaters' in Greek) in the lungs of people with asthma and examine how they affect the airway narrowing that can worsen asthma symptoms.

Macrophages are the predominant type of white cells found in the lungs and their function is to clear any particulate matter, bacteria or damaged cells that may be present in the airway.

Asthma is characterised by damage to the cells lining the airway and the act of removing these particular damaged cells can cause the macrophages to switch to working in a negative rather than a positive way. They start releasing chemicals that recruit and activate other inflammatory cells to the lung, which can cause further damage to the airway.

At the same time, the macrophages also release growth factors that can re-model the airways leading to narrowing and increased twitchiness. What is not understood is why macrophages from the lungs of people with asthma release these inflammatory and growth factors, while macrophages from those without asthma do not.

Dr Karl Staples and Professor Ratko Djukanovic, from the University's School of Medicine, will study macrophages isolated from the lungs of people both with and without asthma, to discover what inflammatory and growth factors are released from these cells when they 'eat' damaged cells. They will also be looking at the ways in which the alternative activation status of macrophages in asthma may be inhibited.

The research, funded by the charity Asthma UK, may uncover new signalling mechanisms that can be targeted using drug therapy, leading to better treatments for asthma.

Dr Staples comments: "Current asthma therapies provide symptom relief and disease control and are not cures. As a result, asthmatics are on constant medication which can impact on their lifestyle. However, these treatments do not seem to be effective in those patients with more severe disease."

Professor Djukanovic adds: "By focusing the spotlight on these important inflammatory cells, which despite being the major immune cell present in the lungs, have long been neglected in the study of asthma, we hope to clarify novel drug targets that could lead to more effective treatments."

According to Asthma UK 5.2m people in the UK are currently receiving treatment for asthma, including 1.1m children, and there is a person with asthma in one in five households in the UK.

Study Of 'Big Eaters' Could Lead To Better Asthma Treatments

A new study into the role of a particular immune cell in the lungs could lead to better treatments for the 5 million people in the UK affected by asthma.

Scientists from the University of Southampton's School of Medicine will study the role of macrophages (literally 'big-eaters' in Greek) in the lungs of people with asthma and examine how they affect the airway narrowing that can worsen asthma symptoms.

Macrophages are the predominant type of white cells found in the lungs and their function is to clear any particulate matter, bacteria or damaged cells that may be present in the airway.

Asthma is characterised by damage to the cells lining the airway and the act of removing these particular damaged cells can cause the macrophages to switch to working in a negative rather than a positive way. They start releasing chemicals that recruit and activate other inflammatory cells to the lung, which can cause further damage to the airway.

At the same time, the macrophages also release growth factors that can re-model the airways leading to narrowing and increased twitchiness. What is not understood is why macrophages from the lungs of people with asthma release these inflammatory and growth factors, while macrophages from those without asthma do not.

Dr Karl Staples and Professor Ratko Djukanovic, from the University's School of Medicine, will study macrophages isolated from the lungs of people both with and without asthma, to discover what inflammatory and growth factors are released from these cells when they 'eat' damaged cells. They will also be looking at the ways in which the alternative activation status of macrophages in asthma may be inhibited.

The research, funded by the charity Asthma UK, may uncover new signalling mechanisms that can be targeted using drug therapy, leading to better treatments for asthma.

Dr Staples comments: "Current asthma therapies provide symptom relief and disease control and are not cures. As a result, asthmatics are on constant medication which can impact on their lifestyle. However, these treatments do not seem to be effective in those patients with more severe disease."

Professor Djukanovic adds: "By focusing the spotlight on these important inflammatory cells, which despite being the major immune cell present in the lungs, have long been neglected in the study of asthma, we hope to clarify novel drug targets that could lead to more effective treatments."

According to Asthma UK 5.2m people in the UK are currently receiving treatment for asthma, including 1.1m children, and there is a person with asthma in one in five households in the UK.

Bronchial Thermoplasty Offers Asthma Treatment

McMaster physicians have proven that a routine medical procedure can provide an improvement in asthma control.

The study by co-principal investigators Dr. Gerard Cox and Dr. John Miller on bronchial thermoplasty as the first non-drug treatment for asthma has been published in the New England Journal of Medicine (NEJM).

The publication entitled, Asthma Control during the Year after Bronchial Thermoplasty, showed that patients treated with bronchial thermoplasty, compared to another group that did not receive the procedure, showed significant positive changes such as decreases in asthma attacks, increases in days with no asthma symptoms, improvement in quality of life, reduction in using medication, and an improvement in asthma control at one year following the procedure. Asthma affects more than 2 million Canadians.

"These findings are very encouraging and are consistent with earlier trial results on bronchial thermoplasty," explains Cox. "These results make us hopeful that bronchial thermoplasty may be a new option for asthma patients who have asthma symptoms despite use of current drug therapies."

Bronchial thermoplasty is a minimally invasive procedure that reduces the amount of airway smooth muscle that is responsible for the constriction of airways in asthma patients.

Using a flexible bronchoscope through the nose or the mouth, a routine procedure, physicians treat small to medium sized airways with bronchial thermoplasty (BT). The BT device generates radio frequency/thermal energy and reduces areas of underlying smooth muscle in the airways.

The procedure is completed in three treatment sessions, each lasting less than one hour, and spaced apart by about three weeks. The procedure, like many other flexible endoscopy procedures, is done under light anesthesia, and the patient returns home the same day.

The objective of the Asthma Intervention Research (AIR) Trial, led by Cox and Miller as part of a global clinical trial, was to examine the effectiveness and safety of bronchial thermoplasty as a treatment for patients with moderate or severe asthma. The randomized controlled trial included 112 patients between the ages of 18 and 65 at 11 centers in four countries, and followed these patients for one year after treatment.

Miller began limited bronchial thermoplasty procedures several years ago in patients who were scheduled to have lung surgery.

"We saw that this particular way of treating the airway had a profound effect on the smooth muscle and not much else," Miller said. "The amount of smooth muscle is significantly reduced by thermoplasty and we recognized that this procedure might therefore be an appropriate treatment for people with asthma."

"I'm quite pleased to say that our experience suggests that the bronchial thermoplasty procedure is quite well-tolerated, and it holds considerable promise for patients with asthma."

Cox is a professor of medicine and a respirologist at the Firestone Institute for Respiratory Health. Miller is an associate professor of surgery and head of thoracic surgery at St. Joseph's Healthcare Hamilton.

Asthma is a common disease in which the airways in the lung become inflamed, excess airway mucus is produced, and airways narrow when muscles within the airway walls contract. During an asthmatic attack, in response to an asthma trigger such as an allergen or irritant, the airway smooth muscle may contract leading to airway narrowing and breathing difficulties.

Bronchial Thermoplasty Offers Asthma Treatment

McMaster physicians have proven that a routine medical procedure can provide an improvement in asthma control.

The study by co-principal investigators Dr. Gerard Cox and Dr. John Miller on bronchial thermoplasty as the first non-drug treatment for asthma has been published in the New England Journal of Medicine (NEJM).

The publication entitled, Asthma Control during the Year after Bronchial Thermoplasty, showed that patients treated with bronchial thermoplasty, compared to another group that did not receive the procedure, showed significant positive changes such as decreases in asthma attacks, increases in days with no asthma symptoms, improvement in quality of life, reduction in using medication, and an improvement in asthma control at one year following the procedure. Asthma affects more than 2 million Canadians.

"These findings are very encouraging and are consistent with earlier trial results on bronchial thermoplasty," explains Cox. "These results make us hopeful that bronchial thermoplasty may be a new option for asthma patients who have asthma symptoms despite use of current drug therapies."

Bronchial thermoplasty is a minimally invasive procedure that reduces the amount of airway smooth muscle that is responsible for the constriction of airways in asthma patients.

Using a flexible bronchoscope through the nose or the mouth, a routine procedure, physicians treat small to medium sized airways with bronchial thermoplasty (BT). The BT device generates radio frequency/thermal energy and reduces areas of underlying smooth muscle in the airways.

The procedure is completed in three treatment sessions, each lasting less than one hour, and spaced apart by about three weeks. The procedure, like many other flexible endoscopy procedures, is done under light anesthesia, and the patient returns home the same day.

The objective of the Asthma Intervention Research (AIR) Trial, led by Cox and Miller as part of a global clinical trial, was to examine the effectiveness and safety of bronchial thermoplasty as a treatment for patients with moderate or severe asthma. The randomized controlled trial included 112 patients between the ages of 18 and 65 at 11 centers in four countries, and followed these patients for one year after treatment.

Miller began limited bronchial thermoplasty procedures several years ago in patients who were scheduled to have lung surgery.

"We saw that this particular way of treating the airway had a profound effect on the smooth muscle and not much else," Miller said. "The amount of smooth muscle is significantly reduced by thermoplasty and we recognized that this procedure might therefore be an appropriate treatment for people with asthma."

"I'm quite pleased to say that our experience suggests that the bronchial thermoplasty procedure is quite well-tolerated, and it holds considerable promise for patients with asthma."

Cox is a professor of medicine and a respirologist at the Firestone Institute for Respiratory Health. Miller is an associate professor of surgery and head of thoracic surgery at St. Joseph's Healthcare Hamilton.

Asthma is a common disease in which the airways in the lung become inflamed, excess airway mucus is produced, and airways narrow when muscles within the airway walls contract. During an asthmatic attack, in response to an asthma trigger such as an allergen or irritant, the airway smooth muscle may contract leading to airway narrowing and breathing difficulties.

MRI Technique To ID Microstructural Changes In Asthma

Chengbo Wang, Ph.D., assistant professor of Radiology has developed a novel magnetic resonance imaging (MRI) technique that – for the first time ever –identified microscopic structural damages deep in the lungs of patients with asthma.

Wang says he and his research team used a special type of magnetic resonance imaging to detect microstructural changes in the lungs. “We found structural alterations in asthmatics, which were not expected. These findings contribute to a new understanding of the pathophysiology of asthma.”

Wang’s study, which will be published in the upcoming July issue of Journal of Magnetic Resonance Imaging, involved 14 healthy volunteers and 14 patients with difficult-to-treat asthma.

The research team polarized helium-3 to make it visible for MR imaging. Then the research subjects inhaled the polarized helium-3 gas, and MR images of the lung were obtained. These images measured how far the helium atoms could move in the lung.

Researchers found that the helium-3 atoms moved a greater distance in the lungs of patients with asthma than in healthy subjects, indicating that there are subtle lung structural differences between asthmatics and healthy volunteers. Wang previously used similar MRI techniques last year to show the first evidence of structural lung damage from secondhand cigarette smoke.

“We had expected to see the opposite effect in asthma due to narrowing of airways. Our unexpected results, however, may reflect alterations at the level of the alveoli or smallest bronchi,” says Wang. Although these findings require more study, he says, they may be the reason why some asthmatics are difficult to treat, and they may be related to “remodeling” in asthma – permanent alterations in lung tissue caused by the disease.

“This study raises new questions about our understanding of asthma,” says Wang. “We hope our further research can help resolve some of these questions and help us better understand and manage this sometimes puzzling disease.”

Wang has received the W.S. Moore Young Investigator Award for Clinical Science from the International Society for Magnetic Resonance in Medicine for this work.

MRI Technique To ID Microstructural Changes In Asthma

Chengbo Wang, Ph.D., assistant professor of Radiology has developed a novel magnetic resonance imaging (MRI) technique that – for the first time ever –identified microscopic structural damages deep in the lungs of patients with asthma.

Wang says he and his research team used a special type of magnetic resonance imaging to detect microstructural changes in the lungs. “We found structural alterations in asthmatics, which were not expected. These findings contribute to a new understanding of the pathophysiology of asthma.”

Wang’s study, which will be published in the upcoming July issue of Journal of Magnetic Resonance Imaging, involved 14 healthy volunteers and 14 patients with difficult-to-treat asthma.

The research team polarized helium-3 to make it visible for MR imaging. Then the research subjects inhaled the polarized helium-3 gas, and MR images of the lung were obtained. These images measured how far the helium atoms could move in the lung.

Researchers found that the helium-3 atoms moved a greater distance in the lungs of patients with asthma than in healthy subjects, indicating that there are subtle lung structural differences between asthmatics and healthy volunteers. Wang previously used similar MRI techniques last year to show the first evidence of structural lung damage from secondhand cigarette smoke.

“We had expected to see the opposite effect in asthma due to narrowing of airways. Our unexpected results, however, may reflect alterations at the level of the alveoli or smallest bronchi,” says Wang. Although these findings require more study, he says, they may be the reason why some asthmatics are difficult to treat, and they may be related to “remodeling” in asthma – permanent alterations in lung tissue caused by the disease.

“This study raises new questions about our understanding of asthma,” says Wang. “We hope our further research can help resolve some of these questions and help us better understand and manage this sometimes puzzling disease.”

Wang has received the W.S. Moore Young Investigator Award for Clinical Science from the International Society for Magnetic Resonance in Medicine for this work.

Hot Drinks Help Fight Cold And Flu

A hot drink may help reduce the symptoms of common colds and flu, according to new research by Cardiff University's Common Cold Centre.

New research at the Centre has found that a simple hot drink of fruit cordial can provide immediate and sustained relief from symptoms of runny nose, cough, sneezing, sore throat, chilliness and tiredness.

Published in the December 2008 edition of the clinical journal Rhinology, the research compared the effects of a commercially produced cordial apple and blackcurrant drink either 'hot' or at room temperature in 30 volunteers with common cold symptoms.

The Centre's Director, Professor Ron Eccles, is urging people suffering from colds or flu to have a hot drink to help reduce their symptoms.

Professor Eccles said: "It is surprising that this is the first scientific research on the benefit of a hot drink for treating cold and flu symptoms.

"With temperatures falling and Christmas just round the corner, cold viruses love this time of year. Having a bottle of fruit cordial in the cupboard and making a hot drink could help fight off the symptoms of festive cold and flu. The big advantage of this type of treatment is that it is cheap as well as safe and effective."

The Common Cold Centre is the world's only centre dedicated to researching and testing new medicines for treatment of the symptoms of flu and the common cold. It is based in Cardiff University's School of Biosciences.

Hot Drinks Help Fight Cold And Flu

A hot drink may help reduce the symptoms of common colds and flu, according to new research by Cardiff University's Common Cold Centre.

New research at the Centre has found that a simple hot drink of fruit cordial can provide immediate and sustained relief from symptoms of runny nose, cough, sneezing, sore throat, chilliness and tiredness.

Published in the December 2008 edition of the clinical journal Rhinology, the research compared the effects of a commercially produced cordial apple and blackcurrant drink either 'hot' or at room temperature in 30 volunteers with common cold symptoms.

The Centre's Director, Professor Ron Eccles, is urging people suffering from colds or flu to have a hot drink to help reduce their symptoms.

Professor Eccles said: "It is surprising that this is the first scientific research on the benefit of a hot drink for treating cold and flu symptoms.

"With temperatures falling and Christmas just round the corner, cold viruses love this time of year. Having a bottle of fruit cordial in the cupboard and making a hot drink could help fight off the symptoms of festive cold and flu. The big advantage of this type of treatment is that it is cheap as well as safe and effective."

The Common Cold Centre is the world's only centre dedicated to researching and testing new medicines for treatment of the symptoms of flu and the common cold. It is based in Cardiff University's School of Biosciences.

Common Cold May Send Some Young Children To The Hospital; Those With Asthma Most At Risk

New evidence supports the link between a cause of the common cold and more severe respiratory infections such as pneumonia and acute bronchitis. The study is published in the March 15 issue of The Journal of Infectious Diseases, now available online.

Rhinoviruses are among the most common viral infections, and are responsible for at least 50 percent of all common colds. Although the association between rhinoviruses and other acute respiratory illnesses in children is increasingly accepted and has been shown in previous reports, the new study is the first to determine age-specific rates of hospitalization across the entire population of two counties. This study shows that the link between rhinoviruses and hospitalizations is especially strong when children have a history of wheezing or asthma.

The study, conducted by E. Kathryn Miller, MD, MPH, and colleagues at Vanderbilt University, the Centers for Disease Control and Prevention, and the University of Rochester, surveyed children under the age of 5 years admitted with fever and respiratory symptoms in Davidson County, Tenn. (which includes Nashville) and Monroe County, N.Y. (which includes Rochester) over a one-year period.

Their results showed that of the 592 children involved in the study, 26 percent tested positive for rhinovirus, representing almost 5 rhinovirus-associated hospitalizations per 1000 children. The study detected more rhinoviruses (26 percent) than respiratory syncytial viruses (20 percent), which have been considered the major cause of respiratory infections in infants and children.

These findings are particularly important given the age-specific rates of hospitalization observed. Among children 0-5 months, there were 17.6 hospitalizations per thousand; among those age 6-23 months, 6.0 per thousand; and among those 24-59 months, 2.0 hospitalizations per thousand. Miller remarked, "This study shows that rhinoviruses are associated with hospitalizations for fever and respiratory illnesses, even in young infants."

Children with a history of wheezing or asthma had more than eight times as many rhinovirus-associated hospitalizations than those without such a history. Asthma was the only significant factor that distinguished children hospitalized with rhinoviruses from those with other viruses or no viruses. Of those hospitalized with a history of asthma or wheezing, rhinoviruses were found in 36 percent of children aged 0-2 years and in 48 percent of children aged 2-5 years. According to Miller, the finding that asthma was the only risk factor significantly associated with rhinovirus hospitalizations should indicate that "patients with asthma might be particularly good candidates for prevention and treatment strategies for rhinovirus infection."

As a next step to their study, Miller suggested, "additional studies over multiple years in multiple geographic regions are needed to more completely understand the role of rhinoviruses in hospitalizations in children. As discussed in our study, rhinoviruses are sometimes found in healthy children; thus, further studies are required to determine the actual rate of 'carriage' in healthy children as opposed to those who are sick or have had recent symptoms of illness. There should also be further investigation into the question, 'Why are children with asthma disproportionately burdened by the "common cold" virus?'"

In an accompanying editorial, Ronald B. Turner, MD of the University of Virginia School of Medicine, noted the value of studies on rhinoviruses because of their frequency and huge cost to society. Turner echoed Miller's sentiment, remarking that the study should stimulate future research into the medical implications of rhinoviruses.

Fast Facts

• Rhinoviruses cause at least half of all common colds.
• The study found 26 percent of the hospitalized children had rhinovirus infections--more than were infected with a virus previously thought to be the main cause of serious respiratory illness.
• Children with a history of wheezing or asthma had more than eight times as many rhinovirus-associated hospitalizations than those without.

Cold Virus Found To Manipulate Genes

Sneezing, runny nose and chills? You might blame the human rhinovirus (HRV), which causes 30 to 50 percent of common colds. But in reality, it's not the virus itself but HRV's ability to manipulate your genes that is the true cause of some of the most annoying cold symptoms.

For the first time, researchers have shown that HRV hijacks many of your genes and causes an overblown immune response that ends up with your nose being overblown.

The research is the first study to comprehensively review gene changes caused by HRV.

"The study's findings are a major step toward more targeted cold prevention and treatment strategies while also serving as a valuable roadmap for the broader respiratory science community," said David Proud, PhD, a professor in the Department of Physiology and Biophysics at the University of Calgary, and lead author of the study. The study was done in collaboration with scientists at the University of Virginia and the Procter & Gamble Company.

Proud added that while colds are usually considered to be minor infections of the nose and throat, they can have much more serious health repercussions. "Rhinovirus is the major cause of the common cold, but it is also an important pathogen in more serious conditions, such as asthma and chronic obstructive pulmonary disease (COPD)," he said.

"Advances in our understanding of the biology of the common cold may eventually lead to improvements in treatment or methods for prevention of colds," said Dr. Ron Turner, of the University of Virginia, one of the study's authors.

The researchers recruited volunteers who were inoculated with either HRV or a sham inoculation and obtained cell scrapings from the nasal passages 8 and 48 hours after inoculation and assessed the genetic changes by microarray, also know as gene chip technology.

After 8 hours, there were virtually no differences between the control and the HRV-inoculated group, but by the 48-hour mark, more than 6500 genes has been significantly up- or down-regulated in the HRV subjects—many of the more highly up-regulated genes fell into two major categories: genes making antiviral proteins, including viperin; or genes making pro-inflammatory cytokines.

"This is the first comprehensive picture to identify several groups of genes that are likely to contribute to the pro-inflammatory and antiviral response," said Dr. Proud.

The researchers also found that viral titer more than doubled in cells that had had the viperin-producing gene "knocked down," showing that HRV replication was hampered by viperin. "This had never been examined during rhinovirus infections," said Dr. Proud. "Some evidence existed that this protein (only discovered a few years ago) had effects on influenza, but nothing was known about its role in rhinovirus infections. So it was a bit unexpected."

"Overall these data provide new insights into the host response to HRV infection and identify several novel candidate genes that require further study to clarify their role in disease pathogenesis," said Dr. Proud. "This may identify proinflammatory, or host defense pathways that could be targeted for drug development, not only as treatments for colds but also for viral exacerbations of asthma and COPD.

The fact that genes associated with structural 'remodeling' or the airways were also altered, supports further study of the role of rhinovirus infections in airway remodeling in asthma."

Common Cold May Send Some Young Children To The Hospital; Those With Asthma Most At Risk

New evidence supports the link between a cause of the common cold and more severe respiratory infections such as pneumonia and acute bronchitis. The study is published in the March 15 issue of The Journal of Infectious Diseases, now available online.

Rhinoviruses are among the most common viral infections, and are responsible for at least 50 percent of all common colds. Although the association between rhinoviruses and other acute respiratory illnesses in children is increasingly accepted and has been shown in previous reports, the new study is the first to determine age-specific rates of hospitalization across the entire population of two counties. This study shows that the link between rhinoviruses and hospitalizations is especially strong when children have a history of wheezing or asthma.

The study, conducted by E. Kathryn Miller, MD, MPH, and colleagues at Vanderbilt University, the Centers for Disease Control and Prevention, and the University of Rochester, surveyed children under the age of 5 years admitted with fever and respiratory symptoms in Davidson County, Tenn. (which includes Nashville) and Monroe County, N.Y. (which includes Rochester) over a one-year period.

Their results showed that of the 592 children involved in the study, 26 percent tested positive for rhinovirus, representing almost 5 rhinovirus-associated hospitalizations per 1000 children. The study detected more rhinoviruses (26 percent) than respiratory syncytial viruses (20 percent), which have been considered the major cause of respiratory infections in infants and children.

These findings are particularly important given the age-specific rates of hospitalization observed. Among children 0-5 months, there were 17.6 hospitalizations per thousand; among those age 6-23 months, 6.0 per thousand; and among those 24-59 months, 2.0 hospitalizations per thousand. Miller remarked, "This study shows that rhinoviruses are associated with hospitalizations for fever and respiratory illnesses, even in young infants."

Children with a history of wheezing or asthma had more than eight times as many rhinovirus-associated hospitalizations than those without such a history. Asthma was the only significant factor that distinguished children hospitalized with rhinoviruses from those with other viruses or no viruses. Of those hospitalized with a history of asthma or wheezing, rhinoviruses were found in 36 percent of children aged 0-2 years and in 48 percent of children aged 2-5 years. According to Miller, the finding that asthma was the only risk factor significantly associated with rhinovirus hospitalizations should indicate that "patients with asthma might be particularly good candidates for prevention and treatment strategies for rhinovirus infection."

As a next step to their study, Miller suggested, "additional studies over multiple years in multiple geographic regions are needed to more completely understand the role of rhinoviruses in hospitalizations in children. As discussed in our study, rhinoviruses are sometimes found in healthy children; thus, further studies are required to determine the actual rate of 'carriage' in healthy children as opposed to those who are sick or have had recent symptoms of illness. There should also be further investigation into the question, 'Why are children with asthma disproportionately burdened by the "common cold" virus?'"

In an accompanying editorial, Ronald B. Turner, MD of the University of Virginia School of Medicine, noted the value of studies on rhinoviruses because of their frequency and huge cost to society. Turner echoed Miller's sentiment, remarking that the study should stimulate future research into the medical implications of rhinoviruses.

Fast Facts

• Rhinoviruses cause at least half of all common colds.
• The study found 26 percent of the hospitalized children had rhinovirus infections--more than were infected with a virus previously thought to be the main cause of serious respiratory illness.
• Children with a history of wheezing or asthma had more than eight times as many rhinovirus-associated hospitalizations than those without.

Cold Virus Found To Manipulate Genes

Sneezing, runny nose and chills? You might blame the human rhinovirus (HRV), which causes 30 to 50 percent of common colds. But in reality, it's not the virus itself but HRV's ability to manipulate your genes that is the true cause of some of the most annoying cold symptoms.

For the first time, researchers have shown that HRV hijacks many of your genes and causes an overblown immune response that ends up with your nose being overblown.

The research is the first study to comprehensively review gene changes caused by HRV.

"The study's findings are a major step toward more targeted cold prevention and treatment strategies while also serving as a valuable roadmap for the broader respiratory science community," said David Proud, PhD, a professor in the Department of Physiology and Biophysics at the University of Calgary, and lead author of the study. The study was done in collaboration with scientists at the University of Virginia and the Procter & Gamble Company.

Proud added that while colds are usually considered to be minor infections of the nose and throat, they can have much more serious health repercussions. "Rhinovirus is the major cause of the common cold, but it is also an important pathogen in more serious conditions, such as asthma and chronic obstructive pulmonary disease (COPD)," he said.

"Advances in our understanding of the biology of the common cold may eventually lead to improvements in treatment or methods for prevention of colds," said Dr. Ron Turner, of the University of Virginia, one of the study's authors.

The researchers recruited volunteers who were inoculated with either HRV or a sham inoculation and obtained cell scrapings from the nasal passages 8 and 48 hours after inoculation and assessed the genetic changes by microarray, also know as gene chip technology.

After 8 hours, there were virtually no differences between the control and the HRV-inoculated group, but by the 48-hour mark, more than 6500 genes has been significantly up- or down-regulated in the HRV subjects—many of the more highly up-regulated genes fell into two major categories: genes making antiviral proteins, including viperin; or genes making pro-inflammatory cytokines.

"This is the first comprehensive picture to identify several groups of genes that are likely to contribute to the pro-inflammatory and antiviral response," said Dr. Proud.

The researchers also found that viral titer more than doubled in cells that had had the viperin-producing gene "knocked down," showing that HRV replication was hampered by viperin. "This had never been examined during rhinovirus infections," said Dr. Proud. "Some evidence existed that this protein (only discovered a few years ago) had effects on influenza, but nothing was known about its role in rhinovirus infections. So it was a bit unexpected."

"Overall these data provide new insights into the host response to HRV infection and identify several novel candidate genes that require further study to clarify their role in disease pathogenesis," said Dr. Proud. "This may identify proinflammatory, or host defense pathways that could be targeted for drug development, not only as treatments for colds but also for viral exacerbations of asthma and COPD.

The fact that genes associated with structural 'remodeling' or the airways were also altered, supports further study of the role of rhinovirus infections in airway remodeling in asthma."

Common Cold Symptoms Caused By Immune System -- Not The Cold Virus

A University of Calgary scientist confirms that it is how our immune system responds, not the rhinovirus itself, that causes cold symptoms. Of more than 100 different viruses that can cause the common cold, human rhinoviruses are the major cause.

The research, published in the American Journal of Respiratory and Critical Care Medicine, is the first study to comprehensively review gene changes in rhinovirus. “The study’s findings are a major step toward more targeted cold prevention and treatment strategies while also serving as a valuable roadmap for the broader respiratory science community,” says David Proud, PhD, a professor in the Department of Physiology and Biophysics at the Faculty of Medicine, and lead author of the study.

Proud adds that while colds are usually considered to be minor infections of the nose and throat, they can have much more serious health repercussions. “Rhinovirus is the major cause of the common cold, but it is also an important pathogen in more serious conditions, such as asthma and chronic obstructive pulmonary disease (COPD),” Proud says.

For example, children who get recurrent rhinovirus-induced wheezing in early life are 10 times more likely to develop asthma. Rhinovirus infections are also a major cause of acute attacks of asthma and COPD and, therefore, exert a huge impact on health care costs.

The study was done in collaboration with scientists at the University of Virginia and the Procter & Gamble Company. Dr. Ron Turner, of the University of Virginia, is one of the study’s authors. He says, “Advances in our understanding of the biology of the common cold may eventually lead to improvements in treatment or methods for prevention of colds.”

In the past, researchers have measured specific compounds made by the body that may protect against a cold or may be triggered by a cold virus. This is the first time anyone has conducted a comprehensive assessment of what happens when a rhinovirus infects a person. This is also the first time researchers have established that a recently discovered antiviral protein called viperin plays a role in our body’s defense against rhinovirus. That discovery will lead scientists to targeted study and treatments against the common cold.

This assessment of gene changes was conducted using gene chip technology, performed by scientists at Proctor & Gamble. With this technology scientists can see every gene in the human genome, and see how genes respond to a stimulus, in this case a cold virus.

The results of this study will open new lines of investigation into how rhinovirus impacts asthma and COPD. A new Experimental Lung Research Suite at the University of Calgary will be integral to developing new research strategies to aid patients with asthma and COPD.

David Proud is a member of the Calvin, Phoebe and Joan Snyder Institute of Infection, Immunity and Inflammation He is a Canada Research Chair in Inflammatory Airway Diseases. His research is supported by the Canadian Institutes of Health Research (CIHR).

Common Cold Symptoms Caused By Immune System -- Not The Cold Virus

A University of Calgary scientist confirms that it is how our immune system responds, not the rhinovirus itself, that causes cold symptoms. Of more than 100 different viruses that can cause the common cold, human rhinoviruses are the major cause.

The research, published in the American Journal of Respiratory and Critical Care Medicine, is the first study to comprehensively review gene changes in rhinovirus. “The study’s findings are a major step toward more targeted cold prevention and treatment strategies while also serving as a valuable roadmap for the broader respiratory science community,” says David Proud, PhD, a professor in the Department of Physiology and Biophysics at the Faculty of Medicine, and lead author of the study.

Proud adds that while colds are usually considered to be minor infections of the nose and throat, they can have much more serious health repercussions. “Rhinovirus is the major cause of the common cold, but it is also an important pathogen in more serious conditions, such as asthma and chronic obstructive pulmonary disease (COPD),” Proud says.

For example, children who get recurrent rhinovirus-induced wheezing in early life are 10 times more likely to develop asthma. Rhinovirus infections are also a major cause of acute attacks of asthma and COPD and, therefore, exert a huge impact on health care costs.

The study was done in collaboration with scientists at the University of Virginia and the Procter & Gamble Company. Dr. Ron Turner, of the University of Virginia, is one of the study’s authors. He says, “Advances in our understanding of the biology of the common cold may eventually lead to improvements in treatment or methods for prevention of colds.”

In the past, researchers have measured specific compounds made by the body that may protect against a cold or may be triggered by a cold virus. This is the first time anyone has conducted a comprehensive assessment of what happens when a rhinovirus infects a person. This is also the first time researchers have established that a recently discovered antiviral protein called viperin plays a role in our body’s defense against rhinovirus. That discovery will lead scientists to targeted study and treatments against the common cold.

This assessment of gene changes was conducted using gene chip technology, performed by scientists at Proctor & Gamble. With this technology scientists can see every gene in the human genome, and see how genes respond to a stimulus, in this case a cold virus.

The results of this study will open new lines of investigation into how rhinovirus impacts asthma and COPD. A new Experimental Lung Research Suite at the University of Calgary will be integral to developing new research strategies to aid patients with asthma and COPD.

David Proud is a member of the Calvin, Phoebe and Joan Snyder Institute of Infection, Immunity and Inflammation He is a Canada Research Chair in Inflammatory Airway Diseases. His research is supported by the Canadian Institutes of Health Research (CIHR).

Giving Mice A Cold Virus Offers Hope Of New Asthma Treatments

Scientists have been able to recreate rhinovirus infection, which is behind most common colds, in a small animal for the first time. For fifty years since they were discovered, it had been thought that rhinoviruses could only infect humans and chimpanzees. But now a team of scientists led by Professor Sebastian Johnston at the MRC/Asthma UK Centre in Allergic Mechanisms of Asthma at Imperial College London, has been able to infect mice with rhinoviruses.

Rhinoviruses are an unwelcome inconvenience for the majority of the population as they cause around three quarters of common colds. However they can also have serious consequences. In susceptible people, they can be fatal. They can lead to the hospitalisation of infants, pneumonia in people with weakened immune systems and they trigger most asthma attacks. They are also the major cause of acute attacks of COPD (chronic bronchitis and emphysema), and are thus the major killer in these diseases.

Professor Johnston said: “Until now it has not been possible to study rhinovirus infection in small animals. This has been a major obstacle to developing new treatments and there is currently no effective treatment for rhinovirus infection.”

It had been thought that mice and other small animals were resistant to rhinoviruses. Of the 100 known strains of rhinovirus, 90 per cent use a binding molecule, called ICAM-1 that is found on the surface of human cells, as their receptor. But the viruses are unable to bind to the mouse version of this receptor.

Professor Johnston explained: "We previously found that once inside the mouse cell a rhinovirus reproduces itself as well as it does in human cells. But the virus couldn’t infect the mouse cell because the receptor (acting like a door key) couldn’t get into the cell.

“Now we’ve modified the mouse receptor so it is more like a human one. This means the virus can infect the cells of these modified mice.”

Professor Johnston added: "We found that mice with the modified receptor were susceptible to infection with a rhinovirus. If combined with an allergen (ovalbumin which is found in egg white) that could cause an allergic reaction in the lungs, the virus could make the response worse and lead to an 'asthma attack'."

The team was able to observe that when the virus was combined with an allergic reaction, the mouse responded similarly to humans. This means it provides a good model for the study of severe asthma attacks.

"These mouse models should provide a major boost to research efforts to develop new treatments for the common cold, as well as for more potentially fatal illnesses such as acute attacks of asthma and of COPD."

The chief executive of the Medical Research Council, Sir Leszek Borysiewicz said: “This important and fundamental discovery will enable us to understand the effects rhinoviruses and common colds have on our health. It will open up new paths to finding treatments which have been delayed for many years and provides us with the opportunities for further breakthroughs in the future.”

Leanne Male, Assistant Director of Research at Asthma UK commented: "Ninety per cent of people with asthma tell us that colds and flu triggers their asthma symptoms but as yet there is no specific treatment for virally induced asthma attacks and steroid treatments are only partially effective against them. We welcome this latest advancement as it will lead to a greater understanding of viral infections and their link with asthma and may help the development of a suitable treatment for virus-induced asthma attacks, thus greatly improving the lives of the 5.2 million people with the condition in the UK."

Journal article: Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Published online in Nature Medicine.

The research was funded by the Medical Research Council, Asthma UK and GlaxoSmithKline.

Giving Mice A Cold Virus Offers Hope Of New Asthma Treatments

Scientists have been able to recreate rhinovirus infection, which is behind most common colds, in a small animal for the first time. For fifty years since they were discovered, it had been thought that rhinoviruses could only infect humans and chimpanzees. But now a team of scientists led by Professor Sebastian Johnston at the MRC/Asthma UK Centre in Allergic Mechanisms of Asthma at Imperial College London, has been able to infect mice with rhinoviruses.

Rhinoviruses are an unwelcome inconvenience for the majority of the population as they cause around three quarters of common colds. However they can also have serious consequences. In susceptible people, they can be fatal. They can lead to the hospitalisation of infants, pneumonia in people with weakened immune systems and they trigger most asthma attacks. They are also the major cause of acute attacks of COPD (chronic bronchitis and emphysema), and are thus the major killer in these diseases.

Professor Johnston said: “Until now it has not been possible to study rhinovirus infection in small animals. This has been a major obstacle to developing new treatments and there is currently no effective treatment for rhinovirus infection.”

It had been thought that mice and other small animals were resistant to rhinoviruses. Of the 100 known strains of rhinovirus, 90 per cent use a binding molecule, called ICAM-1 that is found on the surface of human cells, as their receptor. But the viruses are unable to bind to the mouse version of this receptor.

Professor Johnston explained: "We previously found that once inside the mouse cell a rhinovirus reproduces itself as well as it does in human cells. But the virus couldn’t infect the mouse cell because the receptor (acting like a door key) couldn’t get into the cell.

“Now we’ve modified the mouse receptor so it is more like a human one. This means the virus can infect the cells of these modified mice.”

Professor Johnston added: "We found that mice with the modified receptor were susceptible to infection with a rhinovirus. If combined with an allergen (ovalbumin which is found in egg white) that could cause an allergic reaction in the lungs, the virus could make the response worse and lead to an 'asthma attack'."

The team was able to observe that when the virus was combined with an allergic reaction, the mouse responded similarly to humans. This means it provides a good model for the study of severe asthma attacks.

"These mouse models should provide a major boost to research efforts to develop new treatments for the common cold, as well as for more potentially fatal illnesses such as acute attacks of asthma and of COPD."

The chief executive of the Medical Research Council, Sir Leszek Borysiewicz said: “This important and fundamental discovery will enable us to understand the effects rhinoviruses and common colds have on our health. It will open up new paths to finding treatments which have been delayed for many years and provides us with the opportunities for further breakthroughs in the future.”

Leanne Male, Assistant Director of Research at Asthma UK commented: "Ninety per cent of people with asthma tell us that colds and flu triggers their asthma symptoms but as yet there is no specific treatment for virally induced asthma attacks and steroid treatments are only partially effective against them. We welcome this latest advancement as it will lead to a greater understanding of viral infections and their link with asthma and may help the development of a suitable treatment for virus-induced asthma attacks, thus greatly improving the lives of the 5.2 million people with the condition in the UK."

Journal article: Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Published online in Nature Medicine.

The research was funded by the Medical Research Council, Asthma UK and GlaxoSmithKline.

Vitamin D Deficiency Common In Patients With IBD, Chronic Liver Disease

New research presented at the 73rd Annual Scientific Meeting of the American College of Gastroenterology in Orlando found patients with inflammatory bowel disease or chronic liver disease were at increased risk of developing Vitamin D deficiencies. Two separate studies highlight the importance of regular Vitamin D checkups in the evaluation of patients with certain digestive diseases.

For IBD Patients, Vitamin D Deficiency Associated with Lower Quality of Life and Higher Disease Activity

Researchers at the Medical College of Wisconsin investigated whether Vitamin D deficiency in patients with IBD is associated with a lower quality of life or higher disease activity independent of other known risk factors and medication use.

Disease activity and quality of life were assessed using validated questionnaires, which were administered at every clinic visit. The researchers also looked at the prevalence and seasonality of Vitamin D deficiency in this inflammatory bowel disease population, as well as its association with IBD-related hospitalizations, surgeries and medication use.

This retrospective cohort study conducted by Dr. Alex Ulitsky and his colleagues analyzed vitamin D levels of 504 inflammatory bowel disease patients. They recorded the patients' lowest Vitamin D measurements and date when each low measurement was taken.

Dr. Ulitsky and his team found almost 50 percent of the patients were Vitamin D deficient at some point, with 11 percent being severely deficient. Vitamin D deficiency was not significantly associated with being hospitalized for IBD or having IBD-related surgeries. However, in both Crohn's disease (CD) and ulcerative colitis (UC) patients, vitamin D deficiency was independently associated with having increased disease activity scores compared to those with normal levels of Vitamin D. Vitamin D deficient CD patients, but not UC patients, had worse quality of life when compared to patients who were not Vitamin D deficient.

According to Dr. Ulitsky, "All IBD patients, irrespective of their disease, disease location or nature should have their Vitamin D levels checked regularly and corrected aggressively when insufficiency is found."

Vitamin D Deficiency Prevalent in Patients with Chronic Liver Disease

Researchers from the University of Tennessee in Memphis measured the vitamin D levels of 118 chronic liver disease patients. Researchers found 92.4 percent of chronic liver patients had some degree of vitamin D deficiency and at least one third were severely deficient. Severe vitamin D deficiency was more common among cirrhotics.

"Since deficiency is common among these patients, Vitamin D replacement may hopefully prevent osteoporosis and other bone complications related to end stage liver disease," said lead researcher Dr. Satheesh P. Nair.

The study included 43 hepatitis C patients with cirrhosis; 57 hepatitis C patients without cirrhosis; 18 cirrhosis patients without hepatitis C. The severity of vitamin D deficiency was divided into three groups: mild (between 20-32 ng/ml), moderate (between 7-20 ng/ml), and severe (less than 7 ng/ml).

Importance of Vitamin D and Bone Health

Vitamin D, a fat-soluble vitamin, helps the body absorb calcium and plays a crucial role in the growth and maintenance of strong, healthy bones. A lack of vitamin D causes calcium-depleted bone, which can weaken the bones and increase the risk of fractures resulting from osteoporosis.

A diet rich in vitamin D, such as fish, eggs, fortified milk, and cod liver oil, is essential to maintaining good bone health.

Vitamin D Deficiency Common In Patients With IBD, Chronic Liver Disease

New research presented at the 73rd Annual Scientific Meeting of the American College of Gastroenterology in Orlando found patients with inflammatory bowel disease or chronic liver disease were at increased risk of developing Vitamin D deficiencies. Two separate studies highlight the importance of regular Vitamin D checkups in the evaluation of patients with certain digestive diseases.

For IBD Patients, Vitamin D Deficiency Associated with Lower Quality of Life and Higher Disease Activity

Researchers at the Medical College of Wisconsin investigated whether Vitamin D deficiency in patients with IBD is associated with a lower quality of life or higher disease activity independent of other known risk factors and medication use.

Disease activity and quality of life were assessed using validated questionnaires, which were administered at every clinic visit. The researchers also looked at the prevalence and seasonality of Vitamin D deficiency in this inflammatory bowel disease population, as well as its association with IBD-related hospitalizations, surgeries and medication use.

This retrospective cohort study conducted by Dr. Alex Ulitsky and his colleagues analyzed vitamin D levels of 504 inflammatory bowel disease patients. They recorded the patients' lowest Vitamin D measurements and date when each low measurement was taken.

Dr. Ulitsky and his team found almost 50 percent of the patients were Vitamin D deficient at some point, with 11 percent being severely deficient. Vitamin D deficiency was not significantly associated with being hospitalized for IBD or having IBD-related surgeries. However, in both Crohn's disease (CD) and ulcerative colitis (UC) patients, vitamin D deficiency was independently associated with having increased disease activity scores compared to those with normal levels of Vitamin D. Vitamin D deficient CD patients, but not UC patients, had worse quality of life when compared to patients who were not Vitamin D deficient.

According to Dr. Ulitsky, "All IBD patients, irrespective of their disease, disease location or nature should have their Vitamin D levels checked regularly and corrected aggressively when insufficiency is found."

Vitamin D Deficiency Prevalent in Patients with Chronic Liver Disease

Researchers from the University of Tennessee in Memphis measured the vitamin D levels of 118 chronic liver disease patients. Researchers found 92.4 percent of chronic liver patients had some degree of vitamin D deficiency and at least one third were severely deficient. Severe vitamin D deficiency was more common among cirrhotics.

"Since deficiency is common among these patients, Vitamin D replacement may hopefully prevent osteoporosis and other bone complications related to end stage liver disease," said lead researcher Dr. Satheesh P. Nair.

The study included 43 hepatitis C patients with cirrhosis; 57 hepatitis C patients without cirrhosis; 18 cirrhosis patients without hepatitis C. The severity of vitamin D deficiency was divided into three groups: mild (between 20-32 ng/ml), moderate (between 7-20 ng/ml), and severe (less than 7 ng/ml).

Importance of Vitamin D and Bone Health

Vitamin D, a fat-soluble vitamin, helps the body absorb calcium and plays a crucial role in the growth and maintenance of strong, healthy bones. A lack of vitamin D causes calcium-depleted bone, which can weaken the bones and increase the risk of fractures resulting from osteoporosis.

A diet rich in vitamin D, such as fish, eggs, fortified milk, and cod liver oil, is essential to maintaining good bone health.

Low Vitamin D Levels Appear Common In Healthy Children

Many healthy infants and toddlers may have low levels of vitamin D, and about one-third of those appear to have some evidence of reduced bone mineral content on X-rays, according to a new report.

Reports of a resurgence of vitamin D deficiency and rickets, the resulting bone-weakening disease, have emerged in several states, according to background information in the article. Vitamin D deficiency also appears to be high in other countries, including Greece, China, Canada and England.

Catherine M. Gordon, M.D., M.Sc., and colleagues at Children's Hospital Boston, studied 380 healthy children ages 8 months to 24 months who visited a primary care center for a physical examination between 2005 and 2007. Parents filled out a questionnaire regarding their nutritional intake and that of their children, and also reported on the use of vitamin D and other supplements, time spent outdoors, socioeconomic status and education level.

Among the 365 children for whom blood samples were available, 12.1 percent (44) had vitamin D deficiency, defined as 20 nanograms per milliliter of blood or less, and 40 percent (146) had levels below the accepted optimal level of 30 nanograms per milliliter. Breastfed infants who did not receive vitamin D and toddlers who drank less milk were at higher risk of deficiency (for each cup of milk toddlers drank per day, blood vitamin D level increased by 2.9 nanograms per milliliter).

Forty children of the 44 with vitamin D deficiency underwent X-rays of the wrist and knee. Thirteen (32.5 percent) had evidence of bone mineral loss, and three (7.5 percent) exhibited changes to their bones suggestive of rickets.

"Only one child had signs of rickets on physical examination," the authors write. "Thus, these infants and toddlers had a sub-clinical deficiency that could make detection of this issue particularly problematic in routine clinical practice, as a child's vitamin D status is not typically evaluated as part of routine care."

The data suggest that infants should receive vitamin D supplements while breastfeeding and raise the question of whether some children, including those with established risk factors for vitamin D deficiency, should receive regular measurements of blood vitamin D levels. "Given the potential benefits of vitamin D on bone and other tissues, and growing data supporting its immunomodulatory and antiproliferative effects, the current findings support recommendations advocating for vitamin D supplementation for all young children," they conclude.

This study was supported by grants from the Allen Foundation Inc. and the McCarthy Family Foundation; a grant from the National Center for Research Resources; and a project of the Maternal and Child Health Bureau, U.S. Health Resources and Services Administration.

Editorial: Additional Information Needed About Risks of Low Vitamin D Levels

"The results of this study suggest that a vitamin D level is not a good screening test for rickets in asymptomatic children; 92.5 percent of those with hypovitaminosis [low levels of] D, as defined by Gordon et al, had no evidence of rickets on radiograph [X-ray]," writes James A. Taylor, M.D., of the University of Washington, Seattle, in an accompanying editorial.

"Future research is needed to determine whether infants and toddlers with vitamin D levels of 20 nanograms per milliliter or lower are at significant short- or long-term risk for other bone disease or different conditions," Dr. Taylor writes. "Pending this research, the recommendations by Gordon et al that all young children should receive vitamin D supplementation and that children with risk factors should have periodic vitamin D levels obtained may be premature."

Low Vitamin D Levels Appear Common In Healthy Children

Many healthy infants and toddlers may have low levels of vitamin D, and about one-third of those appear to have some evidence of reduced bone mineral content on X-rays, according to a new report.

Reports of a resurgence of vitamin D deficiency and rickets, the resulting bone-weakening disease, have emerged in several states, according to background information in the article. Vitamin D deficiency also appears to be high in other countries, including Greece, China, Canada and England.

Catherine M. Gordon, M.D., M.Sc., and colleagues at Children's Hospital Boston, studied 380 healthy children ages 8 months to 24 months who visited a primary care center for a physical examination between 2005 and 2007. Parents filled out a questionnaire regarding their nutritional intake and that of their children, and also reported on the use of vitamin D and other supplements, time spent outdoors, socioeconomic status and education level.

Among the 365 children for whom blood samples were available, 12.1 percent (44) had vitamin D deficiency, defined as 20 nanograms per milliliter of blood or less, and 40 percent (146) had levels below the accepted optimal level of 30 nanograms per milliliter. Breastfed infants who did not receive vitamin D and toddlers who drank less milk were at higher risk of deficiency (for each cup of milk toddlers drank per day, blood vitamin D level increased by 2.9 nanograms per milliliter).

Forty children of the 44 with vitamin D deficiency underwent X-rays of the wrist and knee. Thirteen (32.5 percent) had evidence of bone mineral loss, and three (7.5 percent) exhibited changes to their bones suggestive of rickets.

"Only one child had signs of rickets on physical examination," the authors write. "Thus, these infants and toddlers had a sub-clinical deficiency that could make detection of this issue particularly problematic in routine clinical practice, as a child's vitamin D status is not typically evaluated as part of routine care."

The data suggest that infants should receive vitamin D supplements while breastfeeding and raise the question of whether some children, including those with established risk factors for vitamin D deficiency, should receive regular measurements of blood vitamin D levels. "Given the potential benefits of vitamin D on bone and other tissues, and growing data supporting its immunomodulatory and antiproliferative effects, the current findings support recommendations advocating for vitamin D supplementation for all young children," they conclude.

This study was supported by grants from the Allen Foundation Inc. and the McCarthy Family Foundation; a grant from the National Center for Research Resources; and a project of the Maternal and Child Health Bureau, U.S. Health Resources and Services Administration.

Editorial: Additional Information Needed About Risks of Low Vitamin D Levels

"The results of this study suggest that a vitamin D level is not a good screening test for rickets in asymptomatic children; 92.5 percent of those with hypovitaminosis [low levels of] D, as defined by Gordon et al, had no evidence of rickets on radiograph [X-ray]," writes James A. Taylor, M.D., of the University of Washington, Seattle, in an accompanying editorial.

"Future research is needed to determine whether infants and toddlers with vitamin D levels of 20 nanograms per milliliter or lower are at significant short- or long-term risk for other bone disease or different conditions," Dr. Taylor writes. "Pending this research, the recommendations by Gordon et al that all young children should receive vitamin D supplementation and that children with risk factors should have periodic vitamin D levels obtained may be premature."

New Guidelines Double Amount Of Recommended Vitamin D For Young

The American Academy of Pediatrics (AAP) is doubling the amount of vitamin D it recommends for infants, children and adolescents. The new clinical report, "Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents," recommends all children receive 400 IU a day of vitamin D, beginning in the first few days of life.

The previous recommendation, issued in 2003, called for 200 IU per day beginning in the first two months of life.

The change in recommendation comes after reviewing new clinical trials on vitamin D and the historical precedence of safely giving 400 IU per day to the pediatric population. Clinical data show that 400 units of vitamin D a day will not only prevent rickets, but treat it. This bone-softening disease is preventable with adequate vitamin D, but dietary sources of vitamin D are limited, and it is difficult to determine a safe amount of sunlight exposure to synthesize vitamin D in a given individual. Rickets continues to be reported in the United States in infants and adolescents. The greatest risk for rickets is in exclusively breastfed infants who are not supplemented with 400 IU of vitamin D a day.

Adequate vitamin D throughout childhood may reduce the risk of osteoporosis. In adults, new evidence suggests that vitamin D plays a role in the immune system and may help prevent infections, autoimmune diseases, cancer and diabetes.

"We are doubling the recommended amount of vitamin D children need each day because evidence has shown this could have life-long health benefits," said Frank Greer, MD, FAAP, chair of the AAP Committee on Nutrition and co-author of the report. “Supplementation is important because most children will not get enough vitamin D through diet alone.”

"Breastfeeding is the best source of nutrition for infants. However, because of vitamin D deficiencies in the maternal diet, which affect the vitamin D in a mother’s milk, it is important that breastfed infants receive supplements of vitamin D,” said Carol Wagner, MD, FAAP, member of the AAP Section on Breastfeeding Executive Committee and co-author of the report. “Until it is determined what the vitamin D requirements of the lactating mother-infant dyad are, we must ensure that the breastfeeding infant receives an adequate supply of vitamin D through a supplement of 400 IU per day.”

The new recommendations include:

• Breastfed and partially breastfed infants should be supplemented with 400 IU a day of vitamin D beginning in the first few days of life.
• All non-breastfed infants, as well as older children, who are consuming less than one quart per day of vitamin D-fortified formula or milk, should receive a vitamin D supplement of 400 IU a day.
• Adolescents who do not obtain 400 IU of vitamin D per day through foods should receive a supplement containing that amount.
• Children with increased risk of vitamin D deficiency, such as those taking certain medications, may need higher doses of vitamin D.

Given the growing evidence that adequate vitamin D status during pregnancy is important for fetal development, the AAP also recommends that providers who care for pregnant women consider measuring vitamin D levels in this population.