Emphysema is a lung condition in which tiny air sacs in the lungs – alveoli – fill up with air. As the air continues to build up in these sacs, they expand, and may break or become damaged and form scar tissue. The patient becomes progressively short of breath. Emphysema is a type of COPD (chronic obstructive pulmonary disease). The main cause of emphysema is long-term regular smoking.

The alveoli turn into large, irregular pockets with holes in them. The surface area of the lungs is gradually reduced, resulting in less oxygen entering the bloodstream.

The small elastic fibers that hold open the small airways leading to the alveoli also become destroyed. When the patient breathes out they collapse, i.e. the patient has problems exhaling air.

Emphysema is not curable, the condition cannot be reversed. However, treatment may slow down its rate of progression and alleviate symptoms.

The alveoli are the grape-like sacs

According to Medilexicon’s medical dictionary, emphysema is:

1. Presence of air in the interstices of the connective tissue of a part.

2. A condition of the lung characterized by increase beyond the normal in the size of air spaces distal to the terminal bronchiole (those parts containing alveoli), with destructive changes in their walls and reduction in their number. Clinical manifestation is breathlessness on exertion, due to the combined effect (in varying degrees) of reduction of alveolar surface for gas exchange and collapse of smaller airways with trapping of alveolar gas in expiration; this causes the chest to be held in the position of inspiration (“barrel chest”), with prolonged expiration and increased residual volume. Symptoms of chronic bronchitis often, but not necessarily, coexist. Two structural varieties are panlobular (panacinar) emphysema and centrilobular (centriacinar) emphysema; paracicatricial, paraseptal, and bullous emphysema are also common.
What are the signs and symptoms of emphysema
A symptom is something the patient feels and describes, such as pain, while a sign is something everybody can detect, such as a rash.

A patient with emphysema may experience no symptoms for many years. Eventually, as the condition progresses, there is a shortness of breath (dyspnea), which starts off gradually. An individual with early stages of emphysema may avoid physical activity because it makes them pant too much. Eventually, the shortness of breath is present even when the person is resting.
What are the causes of emphysema?
The main cause of emphysema is long-term, regular tobacco smoking. It may also be caused by marijuana smoking (much less common), exposure to air pollutions, factory fumes, coal and silica dust.

In rare cases, a patient may have inherited a deficiency of Alpha-1 antitrypsin, a protein that protects the elastic tissue in the lungs.
What are the possible complications of emphysema?
Pneumothorax, also called collapsed lung. This can be fatal in patients with severe emphysema because the lungs have become so weak.

Cor pulmonale – a part of the heart expands and becomes weak. This happens when pressure in the arteries that connect the lungs and heart increases.

Giant bullae – empty spaces, called bullae develop in the lungs. Giant bullae are very large, sometimes half the size of the lung. Not only does the lung have a much smaller surface area, the bullae can become infected. Patients with giant bullae are more likely to develop pneumothorax.

Recurring infections – chest infections, pneumonia, influenza, cold and the common cold are like to occur more often in patients with emphysema.

Pulmonary hypertension – abnormally high blood pressure in the arteries of the lungs.
Diagnosing emphysema
The doctor will carry out a physical examination and ask some questions, such as:

smoking status and history
whether he/she suffers from shortness of breath and how long for
what makes shortness of breath worse
whether there is a cough and if that cough brings up sputum
the patient’s medical history
whether his/her family have a history of lung disease

The doctor may order some tests, which may include:

Chest X-ray – this can help the doctor determine whether the emphysema is advanced, and also exclude any other reasons for the dyspnea.
CT (computerized tomography) scan – this may be ordered to help the doctor decide whether lung surgery is required.
Blood test – blood may be taken from an artery to determine how well the lungs are transferring oxygen into the blood, and removing CO2.
Lung function tests – these tests tell the doctor how well the patient’s lungs inhale and exhale air, as well as showing how much air the lungs can hold. The doctor will also have a better idea of how efficiently the lungs are transferring oxygen into the bloodstream. The patient will probably be asked to blow into a spirometer. Spirometry can be done at the doctor’s office or a nearby hospital or clinic. The patient has to blow as hard as possible into a small tube that is attached to a machine. The machine measures the time taken to blow all the air out of the lungs. If the patients airways are blocked it will take longer.

A modern USB PC-based spirometer [image from Wikimedia]
What are the treatment options for emphysema?
Emphysema is incurable; there is no treatment to reverse the condition. However, symptoms can be relieved and its progression can be slowed down with proper treatment.

Stop smoking – smoking is the main cause of emphysema in the first place. Stopping smoking will considerably slow down its progress.

Bronchodilators – types of medications that relax airways that have become constricted, thus relieving shortness of breath, breathing problems, and coughing. These drugs are more effective for the treatment of chronic bronchitis or asthma, but can help emphysema patients to some degree.

Steroid aerosol sprays – these are inhaled. Corticosteroids are effective for shortness of breath. However, they must be used under the careful monitoring of a doctor because long-term usage can result in weakened bones, elevated blood pressure and cataracts. Long-term steroid use also significantly raises the risk of developing diabetes.

Antibiotics – patients with emphysema generally get more infections, such as pneumonia or acute bronchitis than other people. Such conditions require antibiotic treatment.

Rehabilitation techniques – the patient can be taught certain breathing exercises that may help reduce shortness of breath and improve his/her ability to do exercise. Patients may undergo weight changes, which need to be addressed.

Oxygen – those with severe symptoms may require supplemental oxygen, which is usually administered through the nostril via a narrow tubing.

Surgery – a surgeon may surgically remove some of the damaged tissue, which helps the remaining lung tissue work better, this may help the patient breath better.

Lung transplant – when other options have not worked and symptoms are very severe, the doctor may recommend lung transplant

Original article date: 01 Jun 2004
Article updated: 22 Sept 2011

The US Food and Drug Administration (FDA) confirmed that the Decemember 31st 2011 ban on Chlorofluorocarbon (CFC) based asthma inhalers will go into force. The ban is part of the Montreal Protocol on substances that deplete the Ozone Layer., which dates back to international agreements made in the late 1980s. Since the protocol went into force in 1989 many products that use large amounts of CFC, such as refrigerators and deodorants have gone out of production.

Badrul Chowdhury, M.D., director of the Division of Pulmonary, Allergy and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research. Confirmed :

“If you rely on an over-the-counter inhaler to relieve your asthma symptoms, it is important that you contact a health care professional to talk about switching to a different medicine to treat your asthma.”

More importantly the ban will affect over the counter Epinephrine based inhaler marketed by Armstrong Pharmaceutical Inc. called Primatene Mist. This OTC product allows those with only mild asthma to treat themselves as and when they see fit. However it is the only FDA approved OTC product available on the market for asthma, leaving those who have been relying on it, needing to seek a doctor’s prescription for an alternative product.

Public discussions have been in progress since 2006, in regards to the CFC epinephrine inhalers and while most manufacturers have switched to the new hydrofluoroalkane (HFA) as an aerosol propellant in asthma inhalers, there is no product with HFA to replace the CFC based Primatene Mist.

The FDA has encouraged Armstrong Pharmaceutical Inc. to inform its consumers and Primatene Mist now carries alerts to warn consumers that it will be discontinued at year end. However as the deadline approaches it is obviously important to make sure the transition occurs without incident, as Asthma suffers that have been relying on the product will now need prescriptions. Doctors should be careful to alert patients to the changes.

More information is available on these links :

Phase Out of Epinephrine CFC Metered-Dose Inhalers

Epinephrine CFC Metered-dose Inhalers – Questions and Answers

Consumer Update: Primatene Mist with Chlorofluorocarbons No Longer Available After Dec. 31, 2011

Rupert Shepherd BSc.

Children with severe therapy-resistant asthma (STRA) may have poorer lung function and worse symptoms compared to children with moderate asthma, due to lower levels of vitamin D in their blood, according to researchers in London. Lower levels of vitamin D may cause structural changes in the airway muscles of children with STRA, making breathing more difficult. The study provides important new evidence for possible treatments for the condition.

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

“This study clearly demonstrates that low levels of vitamin D are associated with poorer lung function, increased use of medication, worse symptoms and an increase in the mass of airway smooth muscle in children with STRA,” said Atul Gupta, MRCPCH, M.D., a researcher from Royal Brompton Hospital and the National Heart and Lung Institute (NHLI) at Imperial College and King’s College London. “It is therefore plausible that the link between airway smooth muscle mass and lung function in severe asthma may be partly explained by low levels of vitamin D.”

While most children with asthma can be successfully treated with low doses of corticosteroids, about 5 to 10 percent of asthmatic children do not respond to standard treatment. These children have severe therapy-resistant asthma, or STRA, experience more asthma episodes and asthma-related illnesses, and require more healthcare services, than their treatment-receptive peers.

Although previous studies of children with asthma have linked increases in airway smooth muscle mass with poorer lung function and in vitro studies have established a connection between levels of vitamin D and the proliferation of airway smooth muscle, this is the first study to evaluate the relationship between vitamin D and the pathophysiology of children with STRA.

“Little is known about vitamin D status and its effect on asthma pathophysiology in these patients,” Dr. Gupta noted. “For our study, we hypothesized that children with STRA would have lower levels of vitamin D than moderate asthmatics, and that lower levels of vitamin D would be associated with worse lung function and changes in the airway muscle tissue.”

The researchers enrolled 86 children in the study, including 36 children with STRA, 26 with moderate asthma and 24 non-asthmatic controls, and measured the relationships between vitamin D levels and lung function, medication usage and symptom exacerbations.The researchers also examined tissue samples from the airways of the STRA group to evaluate structural changes in the airway’s smooth muscle.

At the conclusion of the study the researchers found children with STRA had significantly lower levels of vitamin D, as well as greater numbers of exacerbations, increased use of asthma medications and poorer lung function compared to children with moderate asthma and non-asthmatic children. Airway muscle tissue mass was also increased in the STRA group.

“The results of this study suggest that lower levels of vitamin D in children with STRA contribute to an increase in airway smooth muscle mass, which could make breathing more difficult and cause a worsening of asthma symptoms,” Dr. Gupta said.

The findings suggest new treatment strategies for children suffering from difficult-to-treat asthma, he added.

“Our results suggest that detecting vitamin D deficiency in children with STRA, and then treating that deficiency, may help prevent or reduce the structural changes that occur in the airway smooth muscle, which in turn may help reduce asthma-related symptoms and improve overall lung function,” Dr. Gupta said.

Before any widespread treatment recommendations can be made, however, larger studies will need to be conducted to confirm the results, he added.

“The determination of the exact mechanism between low vitamin D and airway changes that occur in STRA will require intervention studies,” Dr. Gupta said. “Hopefully, the results of this and future studies will help determine a new course of therapy that will be effective in treating these children.”

Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered how a novel type of antibody works against pneumococcal bacteria. The findings, which could improve vaccines against pneumonia, appear in the September/October issue of mBio, the online journal of the American Society for Microbiology.

Until recently, scientists thought that antibodies work against pneumococcal bacteria by killing them with the help of immune cells. However, several years ago, Einstein researchers discovered antibodies that were very effective against experimental pneumococcal disease in mice even though they were not able to induce bacterial killing by immune cells. In the current study, the researchers examined how these antibodies interact with pneumococcal bacteria and found that they cause the bacteria to clump together, enhancing a phenomenon called quorum sensing.

“Quorum sensing is a way that bacteria communicate with one another,” explained senior author Liise-anne Pirofski, M.D., professor of medicine and of microbiology & immunology, chief of infectious diseases at Einstein and Montefiore Medical Center, the University Hospital for Einstein, and the Selma and Dr. Jacques Mitrani Professor in Biomedical Research at Einstein. “Here, the ability of antibodies to enhance quorum sensing causes the bacteria to express genes that could kill some of their siblings, something called fratricide, and weaken the defense mechanisms that enable bacteria to survive and grow in a hostile environment.”

The National Foundation for Infectious Diseases estimates that 175,000 people are hospitalized with pneumococcal pneumonia in the United States each year. In addition, pneumococcal bacteria cause 34,500 bloodstream infections and 2,200 cases of meningitis annually.

There are two pneumococcal vaccines: one for adults and one for infants and children. The pediatric pneumococcal conjugate vaccine has dramatically reduced the incidence of pneumococcal disease in children and adults by protecting vaccinated children and by reducing person-to-person transmission of the bacterium, (a phenomenon known as herd protection). However, the vaccine doesn’t cover all strains of disease-causing pneumococcus, and the vaccine currently used for adults does not prevent pneumonia. Fortifying current pneumococcal vaccines to stimulate antibodies that make pneumococcal bacteria less able to protect themselves or kill them directly could enhance their effectiveness.

The paper is titled “Antibodies to Streptococcus pneumoniae Capsular Polysaccharide Enhance Pneumococcal Quorum Sensing.” Co-authors include lead author Masahide Yano, Ph.D, Shruti Gohil, M.D., J. Robert Coleman, Ph.D., and Ph.D. candidate Catherine Manix, all of Einstein. The research was supported by research and training grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

The University of Kentucky’s Dr. Susanne Arnold and colleagues were awarded a grant by the Department of Defense to study potential environmental reasons for the high lung cancer rates in Eastern Kentucky. The grant is for $1.43 million over three years and the study began on Sept. 15.

Kentucky has the highest lung cancer rates in the nation, but counties in the southeastern portion of the state those in the 5th Congressional District have an exceptionally high incidence of lung cancer. Data from the Kentucky Cancer Registry, a Surveillance, Epidemiology and End Result (SEER) site, revealed that the age-adjusted incidence rate for lung cancer in Appalachian Kentucky from 2003-2007 was 115.2 cases per 100,000 residents, compared to 61.6 cases per 100,000 residents nationally.

A “high” lung cancer rate is defined as more than 101.6 cases per 100,000 residents. By this definition, 83 percent of the counties in the 5th District have high rates, compared to 38 percent for the rest of Kentucky.

Tobacco use is the leading cause of lung cancer, and 25 percent of Kentuckians smoke, compared to the 21 percent of people nationally. But smoking on its own doesn’t explain the discrepancy between southeastern Kentucky and the rest of the nation, said Arnold.

“We know that tobacco is the number one cause of lung cancer, but that isn’t the only factor causing the high cancer burden for southeastern Kentucky,” Arnold says. “So we started to look for other possible reasons. Could environmental carcinogens play a role? That’s what this grant will allow us to investigate.”

Arnold says the idea for the lung cancer study came about because of preliminary data from a study of colon cancer patients in Appalachia. The study examined toenail clippings from patients to assess their exposure to trace elements. Appalachian colon cancer patients showed significantly higher amounts of arsenic, chromium and nickel than non-Appalachian patients, suggesting that they had been exposed to these trace elements more extensively.

Although trace amounts of metals (such as iron) are necessary for the body’s normal functions, prolonged exposure to trace elements including arsenic, beryllium, cadmium, cobalt, chromium, nickel and vanadium has been linked to several types of cancer including lung cancer. These trace elements are known to promote carcinogenesis by increasing oxidative stress, inflammation and DNA damage, and reduced DNA repair efficiency.

There are several potential sources for trace element exposure in southeastern Kentucky. Residents could be exposed through their water source, their soil, the local food sources they eat, or in other unknown ways.

Arnold says her study will define age- and gender-matched cancerous and non-cancerous residents. Each participant will be asked to fill out a questionnaire about his or her smoking habits. Researchers will determine the amount of exposure to trace elements by taking samples of residents’ toenails, hair, urine and blood. To determine the source of the exposure, they’ll also collect samples of water and soil from the home. The biological and environmental samples generated from this study will also be made available to other researchers to use for other studies on health in Appalachia.

This project is also partnering with Kentucky Homeplace, an advocacy organization known and trusted throughout southeastern Kentucky. The organization provides access to medical, social, and environmental services for the citizens of the Commonwealth.

“We are extremely lucky to have this outstanding organization helping with this important initiative,” Arnold said. “They will play a crucial role in helping us collect our data.”

Arnold also spearheads the Marty Driesler 5th District Cancer Project, a rural health care initiative dedicated to increasing the survival rates for people with deadly cancers through out Kentucky’s 5th Congressional District. The project encourages partnerships of the Markey Cancer Center and community health care providers and facilities to establish a community program for early detection, prevention, and treatment of lung, liver and esophageal cancer.

“As an eighth-generation Kentuckian, this work is really personal for me,” Arnold said. “I was raised by a doctor who committed his life to research in Kentucky because he really believed it was important for us to help solve Kentucky’s problems. And now I am a doctor that takes care of lung cancer in Kentucky. I feel like it’s our job to be a champion for the people of Appalachia. I hope this study will help us to understand the epidemic that is ravaging southeastern Kentucky and begin to find solutions to this devastating problem.”

Researchers in the Netherlands conducted a study, which revealed that people suffering from respiratory muscle weakness, which often accompanies chronic diseases, such as chronic obstructive pulmonary disease (COPD) might benefit from levosimendan, a calcium-sensitizing drug that could improve muscle function. Levosimendan is usually prescribed for patients with acute heart failure as it increases muscle tissue’s sensitivity to calcium and therefore enhances 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.

Leo Heunks, M.D. PhD, who is a pulmonary and critical care physician at Radboud University Nijmegen Medical Centre in Nijmegen, the Netherlands, said:

“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. 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. To date, there is no specific drug treatment available to improve respiratory muscle function in patients with respiratory muscle failure.”

Calcium is a vital element for the contraction of muscles. By enhancing the muscle tissue sensitivity to Calcium, drugs like levosimendan improve the tissue’s ability to contract. In vitro studies have proven that calcium sensitizers improve respiratory muscle function, while findings of animal studies have demonstrated that calcium sensitivity is reduced in specific chronic illness settings. A recent in vitro study that took diaphragm muscle tissue from COPD patients confirmed levosimendan’s ability to enhance muscle tissue contraction.

Based on the results of those studies, Dr. Heunk and his team decided to examine whether levosimendan would improve the ability of the diaphragm muscle to contract in healthy volunteers. They conducted a study involving 30 healthy volunteers who were randomized to receive either levosimendan or placebo.

Both groups performed two identical breathing exercises, one prior to receiving levosimendan or placebo and one afterward.

To measure the nervous system’s stimulation of the respiratory muscles and the amount of force those muscles used in forced exhalation during each exercise the researchers used a specialized catheter. Heart rate, blood pressure, exhaled carbon dioxide and blood oxygen levels were continuously measured in all volunteers and diaphragm movements before and after the exercise period were assessed by magnetic nerve stimulation.

At the end of the study findings revealed that after the exercises, volunteers in the placebo group had a 9-percent loss of muscle contraction, while those in the levosimendan group showed no loss of contraction. Researchers also discovered that the diaphragm’s mechanical efficiency improved by 21 % in the levosimendan group during the exercises compared with the placebo group. This means that volunteers in the levosimendan group required less effort to achieve the same amount of muscle force in the diaphragm than those treated with placebo.

Dr. Heunks explained:

“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. Essentially, levosimendan prevents the development of muscle fatigue of the respiratory muscles.”

He pointed out that to confirm these results and determine the optimal dose, larger studies are required even though these findings indicate calcium sensitizers like levosimendan may provide an effective therapeutic option for chronically ill patients with respiratory muscle weakness or those using mechanical ventilation.

In a concluding statement Heunks said:

“The dose of levosimendan used in this current study was derived from earlier studies in healthy subjects, demonstrating limited side effects. 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.”

Petra Rattue

The children of mothers who reported being abused by their partner appear to have a higher risk of becoming obese by the time they are 5 years old, says a report in the June issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

The authors wrote that approximately 3 to 10 million children witness intimate partner violence – sexual, physical or psychological abuse by a former or current spouse or partner – each year.

Exposure to intimate partner violence in childhood is associated with altered neuroendocrine system profiles, impaired socioemotional development, cognitive functioning, attachment to caregivers and emotional regulation, and poorer physical and mental health the authors explained.

RenГ©e Boynton-Jarrett, M.D., Sc.D., Boston University School of Medicine, USA, and team studied 1,595 children born between 1998 and 2000. Their mothers were interviewed when the children were born, and then again after 12, 36 and 60 months; children’s height and weight were measured at 3 and 5 years.

49.4% of mothers reported some type of intimate partner violence, and 16.5% of children were obese when they were 5 years old. Children who were exposed to intimate partner violence were more likely to be obese at age 5 than those who had not been exposed. The link was stronger in girls than boys, and also among children whose mothers said they lived in less safe neighborhoods.

The findings persisted even when many proposed intermediary and potentially confounding factors – including obesity at age 3, television watching, depression among mothers, smoking during pregnancy and child birth weight – were considered in the analyses, the authors observed.

The researchers suggest that the link could work through several pathways:

First, if intimate partner violence influences maternal responsiveness to the socioemotional needs of the child, then feeding practices may be influenced. Second, witnessing family violence may be associated with emotional distress and emotion-focused coping using food to self-soothe and address negative emotions.

In addition, the disruption of the neuroendocrine system in early childhood could increase the risk for disordered eating and changes in fat storage and distribution.

The researchers concluded:

Medical and public health practitioners must consider the impact of family violence on obesity risk when designing and implementing primary obesity prevention interventions. Interventions to prevent intimate partner violence, particularly those aimed at educating adolescents about healthy relationships prior to childbearing, may play a crucial role in prevention of early childhood obesity. Moreover, interventions aimed at improving neighborhood safety may have a benefit on reducing childhood obesity risk, even among those exposed to family violence.

“Association Between Maternal Intimate Partner Violence and Incident Obesity in Preschool-Aged Children – Results From the Fragile Families and Child Well-being Study”
RenГ©e Boynton-Jarrett, MD, ScD; Jessica Fargnoli, MPH; Shakira Franco Suglia, MS, ScD; Barry Zuckerman, MD; Rosalind J. Wright, MD, MPH
Arch Pediatr Adolesc Med. 2010;164(6):540-546.

The research will be presented tomorrow (25 September 2011) at the European Respiratory Society’s (ERS) Annual Congress in Amsterdam. The ERS Congress will officially open today (24 September 2011).

In the first study of its kind, researchers from the UK aimed to assess the impact of weather, pollution and geography on the symptoms of people with chronic obstructive pulmonary disease (COPD). This is the first evidence to find a link between increased respiratory symptoms and lower altitude areas of river valleys.

River valleys are typically damp areas in which cool layers of air get trapped below layers of warmer air. Known as a temperature inversion, this leads to mists and fogs which keep suspended droplets of water in the air, causing humid conditions.

Over the course of a year, daily respiratory symptoms of 52 people with COPD were monitored. The frequency of symptom exacerbation was then compared with the altitude and how close the subjects lived to the river, as well as with selected weather and pollution variables. These variables included humidity, temperature and dew point, which is the temperature below which water droplets begin to condense and dew can form.

To measure the impact of these factors, the researchers compared their data with the average number of exacerbations and the usual symptoms experienced by all participants.

The results demonstrated that there were a number of links between the weather conditions in a river valley and an exacerbation of COPD symptoms. The findings revealed that patients experienced a higher frequency of COPD exacerbations the lower the altitude they lived at, and symptoms were also exacerbated by high humidity and low dew point.

The authors conclude that lung problems can be heightened due to the unique climate in a river valley. The suspended droplets of water in the air retain particles and pollutants, leading to adverse symptoms.

Prof Richard Lewis, one of the lead authors from the Worcestershire Acute Hospitals NHS Trust, said: “Our study is the first to assess the impact that living in a river valley has on the symptoms of COPD patients. As a result of this unique combination of weather and climate, toxic particles and pollutants which would otherwise be small enough to be inhaled but subsequently exhaled become attached to droplets and are then retained within the lung causing exacerbation of symptoms.”

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.