Treatment with the calcium-sensitizing drug levosimendan may be effective in improving muscle function in patients with respiratory muscle weakness, which often accompanies chronic diseases such as chronic obstructive pulmonary disease (COPD) and congestive heart failure, according to researchers in the Netherlands, who studied the effects of the drug on healthy volunteers. The drug, which is normally prescribed in patients with acute heart failure,increases the sensitivity of muscle tissue to calcium, improving the muscle’sability to contract.

The findings were published online ahead of the print edition of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

“We found that the calcium sensitizer levosimendan improves the mechanical efficiency ofthe human diaphragm, suggesting a new, therapeutic approach to improve respiratory muscle function in patients with respiratory failure,” said Leo Heunks, M.D. PhD, who is a pulmonary and critical care physician at Radboud University Nijmegen Medical Centre inNijmegen, the Netherlands.

“Respiratory muscle weakness frequently occurs in patients with chronic diseases, and also in critically ill patients on the ventilator, making breathing more difficult and causing more severe illness and even death,” Dr. Heunks added. “To date, there is no specific drug treatment available to improve respiratory muscle function in patients with respiratory muscle failure.”

Calcium is a necessary element in muscle contraction, and calcium sensitizers like levosimendan improve muscle tissue’s ability to contract by making them especially sensitive to the effects of calcium. In vitro studies have demonstrated calcium sensitizers improve the function of the respiratory muscles, and results of animal studies have shown calcium sensitivity is reduced in specific chronic illness settings. A recent in vitro study of diaphragm muscle tissue taken from COPD patients showed levosimendan enhanced the ability of those tissues to contract.

Based on the results of those studies, the researchers in this study hoped to determine whether levosimendan would improve the ability of the diaphragm muscle to contract in healthy volunteers, Dr. Heunks explained.

The researchers enrolled 30 healthy volunteers and randomized them to receive either levosimendan or placebo. Each volunteer performed two identical breathing exercises, one before receiving levosimendan or placebo and one afterward. During each exercise, the researchers used a specialized catheter to measure the nervous system’s stimulation of the respiratory muscles and the amount of force those muscles used in forced exhalation. Magnetic nerve stimulation was used to evaluate the movements of the diaphragm before and after the exercise period, and heart rate, blood pressure, exhaled carbon dioxide and blood oxygen levels were continuously measured.

At the end of their study, the researchers found subjects in the placebo group had a 9-percent loss of muscle contraction following the exercises, while those in the levosimendan group had no loss of contraction. In addition, the mechanical efficiency of the diaphragm during the exercises improved by 21 percent in the levosimendan group compared to the placebo group, meaning subjects treated with levosimendan needed less effort than those treated with placebo to achieve the same amount of muscle force in the diaphragm.

“On average, the breathing exercises in subjects receiving placebo resulted in significant reductions in diaphragm muscle contractions, while the group receiving levosimendan had no significant decrease in contractions,” Dr. Heunks said. “Essentially, levosimendan prevents the development of muscle fatigue of the respiratory muscles.”

Dr. Heunks noted that while these results indicate calcium sensitizers like levosimendan may provide an effective therapeutic option for chronically ill patients with respiratory muscle weakness or patients using mechanical ventilation, larger studies are necessary to confirm these results and determine the optimal dose.

“The dose of levosimendan used in this current study was derived from earlier studies in healthy subjects, demonstrating limited side effects,” he said. “Future studies should evaluate the effects of lower doses of levosimendan on respiratory muscle function in humans, to ensure patients can be effectively treated with as little risk for side effects or complications as possible.”

A drug used to treat cancer may also be effective in diseases that cause scarring of the internal organs or skin, such as pulmonary fibrosis or scleroderma.

The drug, with the generic name bortezomib, stopped the production of fibrotic proteins in human cells and the development of fibrous scarring in a mouse model of fibrotic disease, according to a new Northwestern Medicine study published in the journal Thorax.

“This drug appears to put the brakes on abnormal development of scar tissue in the lungs and skin and may also work in other organs,” said lead author Manu Jain, M.D., associate professor of medicine and of pediatrics at Northwestern University Feinberg School of Medicine and a physician at Northwestern Memorial Hospital and Children’s Memorial Hospital. “These diseases have a high fatality rate, and there is no truly effective treatment for them right now.”

Scleroderma is an autoimmune disease that causes progressive thickening and tightening of the skin and can lead to serious internal organ damage and, in some cases, death. Scleroderma affects an estimated 300,000 people in the United States, most frequently young to middle-aged women.

Idiopathic pulmonary fibrosis is a scarring or thickening of the lungs without any known cause that makes it increasingly difficult to breathe. It may affect up to 200,000 people in the U.S. between 50 and 70 years old.

Jain said the drug appears to inhibit a protein called transforming growth factor beta, which is essential for the growth of the scar tissue. Patients with fibrosis have increased levels and activity of the growth factor. Bortezomib is currently used to treat multiple myeloma and lymphoma.

In the study, when researchers gave bortezomib to mice, it prevented the development of a fibrotic-like disease. “The mice that normally get this disease didn’t get it,” Jain said.

Researchers also took fibroblast cells from scleroderma and pulmonary fibrosis patients and incubated those cells with the drug. Fibroblast cells are believed to be important in the development of scarring in humans. The drug prevented the expression of proteins that are necessary for scarring.

Opioids – a class of medicines commonly given for pain – were associated with a higher risk of pneumonia in a study of 3,061 adults, aged 65 to 94, e-published in advance of publication in the Journal of the American Geriatrics Society. The study from researchers at Group Health Research Institute and the University of Washington (UW) also found that benzodiazepines, which are drugs generally given for insomnia and anxiety, did not affect pneumonia risk.

“Pneumonia is a common infection that can have serious consequences in older adults,” said study leader Sascha Dublin, MD, Ph.D, a Group Health Research Institute assistant investigator and Group Health primary care physician.

“Opioids and benzodiazepines work in different ways, but both can decrease the breathing rate. Both are also sedatives, which can increase the risk of aspiration.” Aspiration is inhaling material (including saliva or food particles) from the mouth into the lungs, which can lead to pneumonia.

A 2009 study estimated that two million Americans age 65 and older received long-term opioid treatment for non-cancer pain. Prescription opioid use has been on the rise in the United States. In earlier Group Health research, the use of chronic opioid therapy for chronic non-cancer pain doubled in the prior decade. And a 1998 report found that one in 10 older Americans used benzodiazepines.

“In animal studies, some opioids – including morphine, codeine, and fentanyl – harm the immune system, which also might contribute to pneumonia,” said Dr. Dublin. She and her research team hypothesized that risk of pneumonia would be higher in people using opioids or benzodiazepines than in people not using these medications, and would be highest for opioids that suppress the immune system. Study subjects were members of Group Health Cooperative, a nonprofit health care system with extensive computerized pharmacy, laboratory, and medical records that were used in the analysis.

Dublin and colleagues conducted a “case-control study,” matching patients who had pneumonia during the study period of 2000 to 2003 (“cases”) with similar patients who did not have pneumonia (“controls”). All were living in the community, not hospitalized or in nursing homes, and the researchers excluded people whose immune systems were suppressed.

The researchers measured whether people with pneumonia were more likely than controls to have taken opioids or benzodiazepines before the start of their illness. Among pneumonia cases, 13.9 percent were using opioids and 8.4 percent were using benzodiazepines. In subjects without pneumonia, 8.0 percent were using opioids and 4.6 percent were using benzodiazepines.

Statistical analysis by the researchers showed that:
Patients taking long-acting opioids such as sustained-release morphine were more than three times as likely to get pneumonia as were those not taking opioids.
Recently starting use was a risk factor: During their first 14 days of use, patients who took opioids were more than three times as likely to get pneumonia as were those not taking opioids.
Patients using immunosuppressing opioids were nearly 1.9 times as likely to get pneumonia as were those not using opioids.
Use of opioids for a longer time period, defined as three months or more before getting pneumonia, was not associated with infection.
Taking benzodiazepines did not affect the risk of getting pneumonia.

This was the first large epidemiological study to look at how opioid use affects the risk of getting pneumonia in a general population. It lays the foundation for research on additional questions about the safety of opioid drugs in older Americans.

“Benzodiazepines don’t seem to be associated with increased risk of pneumonia,” said Dr. Dublin. “But our results mean that it is crucial to look more closely at opioid prescriptions and infections.”

Dr. Dublin was funded by a Paul Beeson Career Development Award from the National Institute on Aging, by the Branta Foundation, and by Group Health Research Institute internal funds. The Beeson award is also supported by the Hartford and Starr Foundations and Atlantic Philanthropies. The work was also funded in part by the National Institute on Drug Abuse.

Treatment with the calcium-sensitizing drug levosimendan may be effective in improving muscle function in patients with respiratory muscle weakness, which often accompanies chronic diseases such as chronic obstructive pulmonary disease (COPD) and congestive heart failure, according to researchers in the Netherlands, who studied the effects of the drug on healthy volunteers. The drug, which is normally prescribed in patients with acute heart failure, increases the sensitivity of muscle tissue to calcium, improving the muscle’s ability to contract.

The findings were published online ahead of the print edition of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

“We found that the calcium sensitizer levosimendan improves the mechanical efficiency of the human diaphragm, suggesting a new, therapeutic approach to improve respiratory muscle function in patients with respiratory failure,” said Leo Heunks, M.D. PhD, who is a pulmonary and critical care physician at Radboud University Nijmegen Medical Centre in Nijmegen, the Netherlands.

“Respiratory muscle weakness frequently occurs in patients with chronic diseases, and also in critically ill patients on ventilators, making breathing more difficult and causing more severe illness and even death,” Dr. Heunks added. “To date, there is no specific drug treatment available to improve respiratory muscle function in patients with respiratory muscle failure.”

Calcium is a necessary element in muscle contraction, and calcium sensitizers like levosimendan improve muscle tissue’s ability to contract by making them especially sensitive to the effects of calcium. In vitro studies have demonstrated calcium sensitizers improve the function of the respiratory muscles, and results of animal studies have shown calcium sensitivity is reduced in specific chronic illness settings. A recent in vitro study of diaphragm muscle tissue taken from COPD patients showed levosimendan enhanced the ability of those tissues to contract.

Based on the results of those studies, the researchers in this study hoped to determine whether levosimendan would improve the ability of the diaphragm muscle to contract in healthy volunteers, Dr. Heunks explained.

The researchers enrolled 30 healthy volunteers and randomized them to receive either levosimendan or placebo. Each volunteer performed two identical breathing exercises, one before receiving levosimendan or placebo and one afterward. During each exercise, the researchers used a specialized catheter to measure the nervous system’s stimulation of the respiratory muscles and the amount of force those muscles used in forced exhalation. Magnetic nerve stimulation was used to evaluate the movements of the diaphragm before and after the exercise period, and heart rate, blood pressure, exhaled carbon dioxide and blood oxygen levels were continuously measured.

At the end of their study, the researchers found subjects in the placebo group had a 9-percent loss of muscle contraction following the exercises, while those in the levosimendan group had no loss of contraction. In addition, the mechanical efficiency of the diaphragm during the exercises improved by 21 percent in the levosimendan group compared to the placebo group, meaning subjects treated with levosimendan needed less effort than those treated with placebo to achieve the same amount of muscle force in the diaphragm.

“On average, the breathing exercises in subjects receiving placebo resulted in significant reductions in diaphragm muscle contractions, while the group receiving levosimendan had no significant decrease in contractions,” Dr. Heunks said. “Essentially, levosimendan prevents the development of muscle fatigue of the respiratory muscles.”

Dr. Heunks noted that while these results indicate calcium sensitizers like levosimendan may provide an effective therapeutic option for chronically ill patients with respiratory muscle weakness or patients using mechanical ventilation, larger studies are necessary to confirm these results and determine the optimal dose.

“The dose of levosimendan used in this current study was derived from earlier studies in healthy subjects, demonstrating limited side effects,” he said. “Future studies should evaluate the effects of lower doses of levosimendan on respiratory muscle function in humans, to ensure patients can be effectively treated with as little risk for side effects or complications as possible.”

Drinking alcohol in moderate quantities can reduce the risk of asthma, according to Danish researchers.

The study, which was presented at the European Respiratory Society’s Annual Congress in Amsterdam, found that drinking 1-6 units of alcohol a week could reduce the risk of developing the condition.

The research examined 19,349 twins between the ages of 12 and 41 yrs of age. All participants completed a questionnaire at the start and end of the study to compare alcohol intake with the risk of developing asthma over 8 yrs.

The results showed that the lowest risk of asthma was seen in the group which had a moderate intake of alcohol, as less than 4% of those who drank 1-6 units per week developed asthma.

The highest risk of asthma was observed in people who drunk rarely or never, as they were 1.4-times more likely to develop the condition. Heavy drinkers also had an increased risk of asthma development and were 1.2-times more likely to develop asthma.

The results also suggested that a preference for beer drinking was associated with an increased risk of asthma when compared with no preference.

Previous studies have found a link between excessive intake of alcohol and asthma attacks; however, this is the first study of its kind to show a link between alcohol intake and the onset of asthma for adults over a long period of time.

Sofie Lieberoth, from the Bispebjerg Hospital in Denmark, said: “Whilst excessive alcohol intake can cause health problems, the findings of our study suggest that a moderate intake of 1-6 units can reduce the risk of developing asthma. By examining all the factors linked with the development of asthma, we can understand more about what causes the condition and how to prevent it.”

People who cycle through London and other major cities have higher levels of black carbon in their airway cells, experts from the UK have shown.

The research, which was presented at the European Respiratory Society’s Annual Congress in Amsterdam, suggests that cyclists inhale more black carbon than pedestrians, which may cause damage to the lungs.

The combustion of fossil fuels results in the generation of large numbers of inhalable particles of soot (black carbon). There is increasing evidence that inhalation of black carbon particles is associated with a wide range of health effects – including heart attacks and reduced lung function.

The researchers, led by Professor Jonathan Grigg from Barts and the London School of Medicine, aimed to identify whether the way healthy adults commute to work affects their exposure to black carbon. Specifically, they tested the hypothesis that cyclists have higher personal exposure to black carbon.

To test this theory the study compared the lung dose of black carbon in cyclists and pedestrians. To measure lung dose the researchers sampled a lower airway cell called the airway macrophage – a specialised cell that sits on the airway surface and ingests foreign material.

The researchers collected sputum samples from five adults who regularly cycled to work in London and five pedestrians and analysed the amount of black carbon found in their airway macrophages. All participants in the study were non-smoking healthy urban commuters aged between 18 and 40 yrs.

The results showed that in this small sample, cyclists have 2.3-times more black carbon in their lungs when compared with pedestrians. The probability that this difference occurred by chance is less than 1 in 100.

Dr Chinedu Nwokoro, one of the researchers of the study and an active cyclist, said: “The results of this study have shown that cycling in a large European city increases exposure to black carbon. This could be due to a number of factors including the fact that cyclists breathe more deeply and at a quicker rate than pedestrians while in closer proximity to exhaust fumes, which could increase the number of airborne particles penetrating the lungs. Our data strongly suggest that personal exposure to black carbon should be considered when planning cycling routes. Whether cycling by healthy individuals is in itself associated with adverse health effects is currently being assessed in a larger ongoing study.”

Belly fat, known clinically as central obesity, has been linked to the development of asthma in a new study.

The findings, which were presented at the European Respiratory Society’s Annual Congress in Amsterdam, have shown central obesity as a risk factor for the disease.

Excess abdominal fat has been linked with a number of health effects, such as diabetes and heart disease, but there has been little focus on its link with lung disease.

Previous studies have found a link between asthma and body mass index (BMI), which is a marker for overall obesity. This new study looked at waist circumference, which is a marker for central obesity, to see whether this form of obesity could also contribute to asthma risk. The research is one of the first prospective studies to investigate the individual and combined effect of central and overall obesity on incident asthma in adults.

Researchers followed 23,245 adults without asthma, aged 19-55 years from the second Norwegian Nord-Trondelag Health Study (HUNT), for 11 years. The participants had their BMI measured along with their waist circumference to test overall obesity and central obesity, respectively. They were also asked to report incidence of asthma.

The results showed that people who were centrally obese but not overall obese were 1.44-times more likely to develop asthma. Additionally, people who were both centrally obese and obese overall were 1.81-times more likely to develop asthma.

Ben Brumpton, from the Norwegian University of Science and Technology, said: “Asthma can affect people of all sizes, but our study has highlighted both the individual and combined effect of central obesity and overall obesity on asthma development. Both these measures have an individual impact on asthma and an additive effect when they are combined.

It is not yet clear why this association exists. Central obesity is closely associated with insulin resistance and metabolic syndrome. These factors may play important roles concerning central obesity-related asthma. We will evaluate the effects of these factors on the development of asthma in future studies.”

Commuters who regularly cycle through major cities like London every day inhale more carbon than pedestrians, and this
may cause damage to their lungs, according to new research from the UK that was presented on Sunday at the European
Respiratory Society’s Annual Congress in Amsterdam. The researchers say planners should think about this when devising city cycling routes.

Because of fossil fuel combustion, there are large amounts of black carbon particles (soot) in the air, which can end up in people’s
lungs when they breathe it in.

More and more studies are showing that inhaling black carbon particles can affect health and lead to heart attacks and reduced
lung function.

Professor Jonathan Grigg from Barts and the London School of Medicine and colleagues wanted to test the idea that the way a
person commutes to work in a large city affects their exposure to black carbon; more specifically that a cyclist has a higher
personal exposure than a pedestrian.

To test their hypothesis, they compared the lung dose of black carbon in healthy volunteers by sampling their airway
macrophages – immune system cells that sit on the surfaces of the lower airways and ingest foreign substances.

The volunteers, all regular urban commuters, were five healthy cyclists that regularly used their bikes to get to work in London
and five healthy pedestrians. None of them were smokers, and their ages ranged from 18 to 40 years.

They gave sputum samples from which the researchers were able to test the amount of black carbon in their airway
macrophages.

Although only a small sample, the results showed that the cyclists had 2.3 times more black carbon in their lungs than the
pedestrians. The results were statistically significant (the probability that this finding would occur by chance was less than 1 in
100).

One of Grigg’s colleagues on the study, Dr Chinedu Nwokoro, an active cyclist who also works in London, said:

“The results of this study have shown that cycling in a large European city increases exposure to black carbon.”

Nwokoro said this could be due a number of reasons, such as cyclists breathe faster and more deeply than pedestrians and do this
while being much closer to the exhaust fumes of cars and other road vehicles.

“Our data strongly suggest that personal exposure to black carbon should be considered when planning cycling routes,” said
Nwokoro, who also pointed out:

“Whether cycling by healthy individuals is in itself associated with adverse health effects is currently being assessed in a larger
ongoing study.”

Catharine Paddock PhD

According to a new investigation, individuals who suffer with chronic obstructive pulmonary disease (COPD) or those with reduced lung function have a serious risk of developing cardiovascular disease.

Presented at the European Respiratory Society’s Annual Congress in Amsterdam, the discoveries indicate that because individuals with COPD and reduced lung function appear to be at a significantly higher risk of developing cardiovascular disease, they should be routinely screened for it.

For medical experts, the problem of co-morbidities, when a person is suffering from more than one condition at the same time, is an increasing concern, especially as the commonness of co-morbid conditions are due to increase as people live longer. Often individuals are treated by a specialist for one particular symptom, however, it will become crucial for all physicians to recognize other symptoms as the frequency of co-morbidities increases.

Despite it being common for individuals to have both COPD and cardiovascular disease, it usually goes unrecognized by physicians due to overlapping clinical manifestations. In individuals with heart disease, COPD diagnosis can remain unsuspected, however, having both of these conditions can lead to a considerably worse outlook for the patient.

Prior studies revealed very little epidemiological evidence connecting the two conditions. This investigation is the first to discover that nasal symptoms and heart disease are common in individuals with COPD and this may link the two conditions.

They gathered data on nasal symptoms and heart disease from 993 individuals with COPD and 993 without the condition. Patients were then divided into two groups, those with normal lung function and those with restricted lung function. 50.1% of individuals with COPD had cardiovascular conditions, such as heart disease, stroke and hypertension, in comparison to individuals with normal function (41%).

Results revealed that nasal symptoms were common among individuals who had both COPD and heart disease (53%) compared to those with normal lung function and heart disease (35.8%).

Furthermore, 62.2% of individuals with both restricted lung function and cardiovascular disease had nasal symptoms, indicating that the symptoms could be used as an indicator for identifying increased risk of cardiovascular disease and COPD among those yet to be diagnosed with either condition.

Dr Anne Lindberg, from the Sunderby Hospital in Sweden, explained:

“Our findings are the first to shed light on the links between both nasal symptoms and cardiovascular condition, in relation to people with COPD and restrictive lung function. This has important implications for clinicians who need to understand the potential overlaps of these conditions when they are treating people with COPD. In addition to raising awareness of these co-morbidities, it will also be important to investigate these links further and look at the effect that co-morbid conditions have on exacerbations and disease progression. ”

Professor Marc Decramer, President of the European Respiratory Society, said:

“Clinicians often forget that people with one chronic condition usually have another illness at the same time. Many of the illnesses that are common alongside COPD, such as cardiovascular disease, may also share similar traits and it is vital that we build on research such as this study to identify new therapeutic targets in the future.

The European Respiratory Roadmap, which was launched last month, outlines the need for great coordination between medical specialists. As the population is aging, the presence of co-morbidities will increase. The roadmap suggests that clinicians need to improve their recognition of other conditions to improve patient care and look at how to manage COPD in conjunction with other health conditions.”

Grace Rattue

AfroAmerican and Hispanic* children seem to have a higher risk of developing asthma compared to Caucasian children; their outcomes are frequently worse, even within a comprehensive health insurance system, says a report published in Archives of Pediatrics & Adolescent Medicine, a JAMA/Archives journal.

* “Hispanic” in the USA tends to mean people of Latin American Amerindian ancestry, while in the UK the meaning includes all the Spanish-speaking world, including (mainly Caucasian) Spain. In this text, “Hispanic” means people of Latin American Amerindian ancestry.

The researchers wrote as background information that many factors contribute to well-documented racial and ethnic differences in children’s health and health care. Universal health care coverage is widely considered an essential component of strategies to reduce these disparities.

The authors wrote:

Because the Military Health System provides comprehensive health insurance to a racially and ethnically diverse population of beneficiaries, studying disparities in health care treatments and outcomes among this population could add significantly to our understanding of the potential effect of universal coverage on reducing disparities in health care.

Kate A. Stewart, Ph.D., of Mathematica Policy Research, Chicago, and team studied data from 822,900 children aged 2 to 17 who were continuously enrolled throughout 2007 in TRICARE Prime, a Department of Defense health maintenance organization-type plan. Asthma prevalence, treatment patterns and outcomes were assessed among children age 2 to 4, 5 to 10 and 11 to 17.

Racial and ethnic differences were evident in numerous measures and age groups. AfroAmerican and Hispanic children were more likely to be diagnosed with asthma at all ages. AfroAmerican children of all ages and Hispanic children age 5 to 10 were more likely to have potentially avoidable asthma-related hospitalizations or emergency department visits.

The researchers wrote:

Our findings with regard to treatment patterns were mixed. Black children, who at all ages were more likely to have a diagnosis of asthma and to have poorer outcomes than white children, were also more likely to receive recommended asthma medications, especially inhaled corticosteroids.

However, this could be related to the higher rates of emergency department visits and potentially avoidable hospitalizations among these children, as drugs could have been prescribed and filled during or after these visits.

Details revealed that AfroAmerican children were also less likely to receive care from a specialist, who may be more inclined to treat asthma according to guidelines, including appropriate use of controller medications.

The authors wrote:

Thus, even though AfroAmerican children filled more prescriptions for asthma medications, they may have been less likely than white children who visited specialists to control their asthma and use the medications appropriately.