Patients May Suffer Dangerous Blood Ammonia Levels After Lung Transplantation

According to a collaborative study by researchers at the Hospital of the University of Pennsylvania and The Children’s Hospital of Philadelphia, a small percentage of patients who undergo lung transplantation develop a deadly increase of blood ammonia levels. A report on the findings appeared in the February 15 issue of the Annals of Internal Medicine.
   The researchers studied 145 consecutive adult patients who received lung transplantation over a 5-year period at the University of Pennsylvania Medical Center. Six of the 145 patients (4% ) developed high levels of blood ammonia, called hyperammonemia. Of those six patients, four (67%) died within 30 days of the surgery, compared to deaths in 24 (17%) of the 139 patients with normal levels of blood ammonia. A fifth patient with hyperammonemia died 34 days after the surgery. In all five cases, death was preceded by coma and increased pressure in the brain.
   The only lung transplant patient with hyperammonemia who survived had her condition recognized early and received hemodialysis and medications to lower her blood ammonia level. “This one case does not prove that this therapy will benefit all patients with this post-transplant complication, but it does suggest a useful area for further study,” says Gerard T. Berry, MD, an endocrinologist and geneticist at The Children’s Hospital of Philadelphia and senior author of the study.
   The number of lung transplantations nationwide increased rapidly during the 1990s, for conditions such as emphysema, cystic fibrosis, and other pulmonary diseases. Among the lung transplant recipients in the study sample who developed hyperammonemia, the researchers identified certain risk factors: major gastrointestinal complications (such as intestinal bleeding, intestinal perforation, or infection), the need for feeding through an intravenous line (total parenteral nutrition), and high pressure in the arteries leading to the lungs (primary pulmonary hypertension). Another possible risk factor is deficiency in a liver enzyme called glutamine synthetase, which plays a role in ammonia metabolism.
   “Further studies are needed to characterize the causes and possible treatments of hyperammonemia after lung transplantation,” says Gary R. Lichtenstein, MD, a member of the Gastroenterology Division of the Department of Medicine and director of the Inflammatory Bowel Disease Center at the Hospital of the University of Pennsylvania, and lead author of the paper. “In the meantime, physicians need to be aware of this potential complication of lung transplantation.”

IL-4 Receptor Is Effective in Persistent Asthma
Soluble interleukin-4 receptor (IL-4R) was found to be a safe and effective way to manage moderate persistent asthma, according to a study released at the recent American Academy of Allergy, Asthma and Immunology Annual Meeting in San Diego. Larry Borish, MD, FAAAAI, of the University of Virginia, Charlottesville, and colleagues from the National Jewish Medical and Research Center, Denver, study sites and the University of Wisconsin-Madison reported the findings.

The study assessed the safety of inhaled IL-4R following the discontinuation of inhaled corticosteroids. IL-4R inhibits IL-4, a naturally occurring protein that regulates a variety of immune system functions and is the initiator and perpetrator of the asthma cascade. Investigators compared three doses of IL-4R to a placebo and administered each treatment by inhalation once a week for up to 12 weeks. Overall, treatment with IL-4R was well tolerated and there were no serious adverse events related to the drug. Patients receiving the highest dose of IL-4R experienced the best asthma control compared to those receiving the placebo.

Prior to the study, all patients were dependent on inhaled corticosteroids. Following discontinuation of inhaled corticosteroid use, patients in the 3-mg IL-4R group experienced continued asthma control over the treatment period with maintained FEV1 (forced expiratory volume in 1 second), compared to a decline in FEV1 in the placebo group.

IL-4R represents the next generation of treatments for controlling asthma. The use of soluble receptors as therapeutics is an approach that has proven both safe and effective in other disease areas such as rheumatoid arthritis. Unlike current therapies, IL-4R is taken once a week by inhalation, which will improve patient compliance, one of the greatest challenges to the effective treatment of asthma. IL-4R holds the potential for safe, effective control of asthma without the use of steroids.

AARD Logo.jpg (8920 bytes)AARC Announces International Fellowship Program
The American Associaton for Respiratory Care (AARC) offers a program bringing health care professionals from other countries to the United States to observe respiratory care practice. The program is called International Fellowships in Respiratory Care and each participant will visit two cities in the United States for 1 week. The hosts in these cities will introduce the participants to the concepts and practice of cardiopulmonary care. The program also includes their attendance at the 46th International Respiratory Congress in Cincinnati, which is scheduled for October 7-10, 2000. The International Fellowships have been sponsored by the AARC since 1990. Since its inception, 74 professionals from more than 34 countries have been chosen to participate in the program. The AARC is seeking City Hosts for this year’s program. Respiratory therapists in cities and metropolitan areas within a 60-mile radius of a major city may apply by contacting the AARC at (972) 243-2272; fax: (972) 484-2720; [email protected].

Body Mass Index Predicts Asthma in Men
Researchers have released findings that link a higher body mass index (BMI) in men to asthma. The study was presented at the recent American Academy of Allergy, Asthma and Immunology Annual Meeting in San Diego. This is the first study to show BMI as an asthma predictor in men, although previous studies have linked asthma to obesity in women and children.
   Kathryn Held from the University of Oklahoma analyzed questionnaire data on nearly 12,000 men from a 1988 to 1994 national health survey. After the men were sectioned into quartiles, obesity was found to correlate strongly with asthma prevalence. According to Held, “Inactivity may be a big risk factor for asthma. There may also be hormonal differences in fatter people that affect lung health.” From the thinnest to the heaviest subjects, 5.30%, 8.09%, 8.93%, and 17.31%, respectively, had asthma.
   Researchers conclude that BMI is a strong predictor of asthma in men, especially those without a hereditary predisposition to the condition.

ALA Logo.jpg (8115 bytes)ALA Proposes Tobacco-Control Treaty
The American Lung Association (ALA), Washington, DC, is working with the World Health Organization to develop a Framework Convention on Tobacco Control to propose to members of the United States delegation. A Framework Convention is a type of multilateral treaty that allows states to proceed incrementally by establishing a general framework followed by specifics that supplement, clarify, amend, or qualify the general agreement. The two organizations are working toward coordinating international response to one of the most deadly epidemics of our time. Public health advocates are concerned that large transnational companies are using their political influence to weaken the treaty.

“It is high time for us to apply the principles that govern the international trade in narcotics to an even more hazardous product—tobacco,” says Alfred Munzer, MD, former president of the American Lung Association. “We urge our US delegates to stand up to Big Tobacco and make certain the treaty is strong, enforceable, and binding, and will truly hold the tobacco companies accountable for the harm they do,” he continues.

The ALA believes the tobacco industry should not be allowed to be an official or unofficial party to the negotiations. “An industry whose products cause 3.5 million deaths per year worldwide does not deserve a place at the table. Just as we would not allow US policy against narcotics to be dictated by the Medellin drug cartels, we must not condone tobacco industry participation,” Munzer says. “The treaty will be only as effective as its enforcement provisions. It should not be a negotiation with tobacco companies. This is a tremendous opportunity. Let’s not squander it,” he concludes.

Genetic Variation May Be Responsible for Serum IgE Levels
A study conducted by American and German researchers published in the March 2000 issue of the Journal of Allergy and Clinical Immunology concluded that a variation, or polymorphism, on the interleukin-13 (IL-13) gene was found to be correlated with total serum immunoglobulin-E (IgE) levels in a large group of children in Arizona and Germany. Researchers studied the DNA of 1,399 children in three populations living in divergent social and geographical conditions. They identified seven genetic polymorphisms present in the gene for IL-13. IL-13 and IL-14 are the only known cytokine signals that can initiate IgE production. IgE is a class of antibodies normally present in low levels in humans but found in larger quantities in people with allergic disease. It is the primary antibody responsible for initiating allergic and asthmatic reactions. Carriers of these seven genetic variants had significantly higher levels of IgE than subjects without the same polymorphisms. The authors concluded that these genetic variants in the IL-13 gene may be very important determinants of total serum levels of IgE.

CpG-ODN Reduces Allergic Asthma in Mice
Researchers at the recent American Academy of Allergy, Asthma and Immunology Annual Meeting in San Diego reported that CpG oligodeoxynucleotides (CpG-ODN) reduced allergic asthma in mice and may be useful in the treatment of allergic asthma in humans. Allergic asthma is triggered by allergens such as pollens, molds, animal dander, dust mites, and cockroaches. CpG-ODN helps facilitate Th1-like responses.
   Previous research has demonstrated that CpG-ODN inhibits antigen-induced sensitization, airway inflammation, and airway hyperreactivity in experimental animal models. This study sought to explore the possible therapeutic effect of CpG-ODN on allergic airway responses. Ariel Teper, MD, and colleagues from Mount Sinai School of Medicine, New York City, and Johns Hopkins University School of Public Health, Baltimore, found that CpG-ODN reduced inflammation, airway hyperreactivity, mucus-containing cells, and IgE levels in mice. (800) 822-2762;

HEALTHSOUTH NERH Opens Outpatient Program
HEALTHSOUTH New England Rehabilitation Hospital (NERH), Woburn, Mass, announces the opening of its outpatient pulmonary rehabilitation program, which was created to promote optimal physiologic improvement and improved quality of life for patients with chronic pulmonary disease. With its existing inpatient pulmonary rehabilitation program, NERH becomes the first New England facility offering a fully integrated pulmonary rehab program.
   Like all programs at NERH, an interdisciplinary approach is taken in the new outpatient pulmonary program, which includes professionals from pulmonology and psychiatry, nursing, physical and respiratory therapy, case management, and dietary counseling. More specifically, the program is composed of various tests (pulmonary function testing, blood gas analysis, oximetry testing), treatment (oxygen therapy, relaxation/stress management techniques), education (proper usage of medical equipment and medications, bronchial hygiene), and exercise (individualized and monitored).
   With more than 14.2 million Americans suffering from chronic obstructive pulmonary disease (COPD), the new outpatient pulmonary rehabilitation program at NERH clearly addresses a medical condition that is more widespread than the general public understands. The overall concept of pulmonary rehabilitation is a sound one: research shows that there is a decrease in the total number of hospitalizations required for a patient with COPD following completion of a comprehensive pulmonary rehabilitation program compared to the years immediately preceding rehabilitation. For more information, call (781) 935-5050.

Book 1.jpg (10805 bytes)Books Featuring Hyperbaric Medicine
Best Publishing, Flagstaff, Ariz, introduces two new books titled Hyperbaric Medicine Practice, edited by Eric P. Kindwall and Harry T. Whelan, and Hyperbaric Facility Safety: A Practical Guide, edited by W.T. Workman. The new second edition to the best-selling Hyperbaric Medicine Practice solidifies its position as the standard work in the field of clinical hyperbaric oxygen therapy. Written by a large team of accomplished specialists, the second edition retains the clinical and therapeutic orientation and comprehensive approach that practitioners have come to appreciate. At the same time, it is extensively updated on every aspect of the field of hyperbaric medicine. With new developments in the field, four new chapters have been added to the book. Book No. D479, $128 plus shipping.

Hyperbaric Facility Safety covers a complex issue with an extremely broad range of topics, including safe engineering design practices, regulatory guidance, training, staffing, maintenance, and operational procedures. Tragic accidents in the international hyperbaric medicine community have focused attention on the need for more comprehensive information on this multifactorial topic. Hyperbaric Facility Safety was written with the objective of creating a comprehensive source document to assist established hyperbaric programs, serve as a safety primer for those developing programs throughout the world, and help cultivate the mind-set so vital to maintaining a safe environment for staff and patients alike. The information contained in this publication applies to both operational and clinical hyperbaric facilities. Book No. B0997, $128 plus shipping. For more information for both books, contact Best Publishing Company (800) 468-1055; (520) 527-1055; fax: (520) 526-0370; email: [email protected].

Alcoholic Drinks May Trigger Asthma
According to a recent study by Australian researchers, published in the March 2000 issue of the Journal of Allergy and Clinical Immunology, alcoholic beverages are linked to asthmatic reactions. Researchers surveyed 366 asthmatics with a self-administered food allergy questionnaire that assessed alcoholic drink-induced asthma in detail. Asthmatic reactions were generally rapid in onset and moderate in severity. Results showed that 156 (42.6%) respondents reported allergic or allergic-like reactions to alcoholic drinks, including cough, blocked nose, itching, facial swelling, and hives; 121 (33.1%) respondents reported asthmatic responses to alcoholic beverages, with 97 indicating that asthma was the main adverse symptom experienced. Wine was the most frequent cause of asthmatic reactions, with 139 (37.7%) people experiencing reactions to it; 109 (29.8%) respondents reported reactions to red wine, 95 (26%) to white wine, and 46 (12.6%) to champagne. Fortified wines caused reactions in 42 (11.5%) individuals, beer in 46 (12.6%), and spirits such as brandy, whisky, and vodka in 21 (5.7%) individuals. No significant difference was found between alcoholic drink-sensitive asthmatic subjects and those not sensitive to these drinks with respect to age, sex, race, asthma severity, oral corticosteroid use, or prior positive allergy skin test reactivity.

The last issue of RT Magazine had two errors. In the introduction to the Pulse Oximeter Product Showcase, the third paragraph should have read, “In addition to the above conditions, add ambient light effects—issues of skin tone, tattoos, and nail polish—as well as low peripheral perfusion due to trauma, being in shock, and hypothermia.” The author, Paul Mathews, PhD, RRT, FCCM, FCCP, says, “While ‘wearing a sock’ [as the text reported] and trying to perform pulse oximetry on toes of the encased foot will certainly interfere with accurate pulse oximetry, ‘being in shock’ is more likely to be a source of accuracy problems.”
   The second error occurred in reference to the Case Report, “Hypoxic Drive Theory Revisited.” The correct Web site is

Houston Anderson, past president of the American Association for Respiratory Care and long-time director of Respiratory Care Services at Duke University Medical Center, Durham, NC, passed away on March 12 after a long battle with cancer.

At the time of his death, Houston and his wife, Ouida, were living in Purvis, Miss. Houston had retired and moved to Mississippi to be closer to his wife’s family.

Men With Chronic Lung Disease Five Times More Likely To Get Osteoporosis
Men with chronic lung disease are more than five times as likely to develop osteoporosis than those without chronic lung disease. If they are receiving chronic glucocorticoid therapy, a common asthma treatment, they are nine times more likely to develop osteoporosis.
   These are the key findings in a new study appearing in the December issue of Chest. Appearing in the same issue is a literature review on the association between glucocorticoid therapy and osteoporosis in which the authors state that specialists and generalists alike fail to recognize asymptomatic bone loss in high-risk lung patients and miss the opportunity to prevent, slow, or reverse bone loss progress.
   Previous studies have suggested an association between chronic obstructive lung disease (COPD) and osteoporosis in men as well as glucocorticoid-induced osteoporosis. But, according to researchers at Emory University and the Veterans’ Administration Medical Center in Atlanta, the relative contributions of chronic lung disease, drug therapy, and other factors contributing toward bone loss in men had not been established. They conducted a cross-sectional medical survey among 171 patients between the ages of 23 and 90. Medical charts were reviewed and additional information was obtained from an electronic database of laboratory values and pharmacy records. Patients also underwent bone density measurement of the spine and left hip.
   Patients were assigned to one of four groups: those with chronic lung disease being treated with oral glucocorticoid therapy, or inhaled glucocorticoid therapy, or not receiving treatment with glucocorticoids; and a control group that did not have chronic lung disease and were not on glucocorticoid therapy.
   Mark S. Nanes, MD, and colleagues reported that bone density measurement did not show any difference in mean density between those with COPD and asthma so both types of patients were pooled into one group. He also noted that COPD patients being prescribed inhalation glucocorticoid therapy had an overall bone loss that was indistinguishable from bone loss in those who were receiving oral therapy. Other studies have found the connection with osteoporosis to be less strong with inhaled glucocorticoids than with oral glucocorticoids.
   COPD patients without any glucocorticoid therapy had five times the likelihood of developing osteoporosis as compared to the control group. Chronic lung patients on glucocorticoid therapy had a ninefold chance of developing osteoporosis compared with the control group.
   The investigators said, “Patients with COPD comprise a high-risk group for osteoporosis. In comparison to postmenopausal women for whom the prevalence of osteoporosis is as much as 30%, men with COPD have an almost identical burden of disease.” They added that recent prospective data suggest that the relationship between bone mass density and fracture incidence is the same for men and women. “Thus, it would be prudent to consider men with COPD for bone density screening even if they are not treated with glucocorticoid therapy,” they concluded.

LVRS Offers End-Stage Emphysema Patients Clinical Improvement
Seven of 26 elderly patients with emphysema who faced almost certain death from respiratory failure were alive with much improved lung function 4 years after undergoing lung volume reduction surgery (LVRS), according to a study published in the December issue of Chest.
   The 26 study patients, who averaged age 67, suffered from end-stage emphysema. They were able to walk less than 100 yards, and 18 required full or part-time oxygen supplementation. All suffered markedly from very difficult, labored breathing. Each patient had exhausted all medical therapy for their disease, including antibiotics, aerosol and systemic bronchodilators and corticosteroids, plus repeated attempts at physical conditioning, according to the researchers.
   “The results indicate significant clinical and physiologic improvement in nine patients at 3 years and seven at 4 years following LVRS,” says Arthur F. Gelb, MD, FCCP, of the Pulmonary Division, Department of Medicine, Lakewood Regional Medical Center, University of California at Los Angeles, who, with five associates, performed the study.
   Emphysema is a disease in which the tiny air sacs at the end of very small air passages in the lungs become damaged, usually from cigarette smoking. The damaged alveoli can cause severe shortness of breath. Serious cases lead to respiratory and heart failure. An estimated 2 million adults in the United States suffer from the problem. Along with other forms of chronic pulmonary disease, it accounts for 90,000 deaths annually.
   LVRS, reintroduced in 1992, is based on the premise that patients with severe emphysema have lungs that have become too large for their chests. Removing lung tissue reduces the volume of the hyperinflated lung, leading to improvement in function. Surgery is usually carried out on both lungs. In this study, approximately 20% to 30% of both lungs were removed.
   The average survival time for the 16 non-long-term responders was almost 30 months. One patient died shortly after surgery.
   Vital capacity, used to determine the status of lung tissue, is a test designed to determine the maximum amount of air that can be exhaled after maximum inhalation.

Asthma and Child Care: A Crisis in America
It is not easy for parents to find child care. Coordinating a good match between the child and the care facility can be time-consuming and expensive, and if the child has asthma, it can be nearly impossible.
   Asthma is the leading chronic illness among children in the United States. It is approaching epidemic proportions, and more parents than ever are working away from home. However, expertise at managing asthma is often not a priority at child-care facilities. A study recently published in Working Mother, titled “Cost, Quality & Outcomes Study,” reported that the majority of child-care centers provide mediocre care in important areas such as health and safety. For children with asthma, the quality of care can mean the difference between life and death.
   Many child-care facilities are not prepared to handle the special requirements of children with asthma. The staff often lack the necessary training that would enable them to recognize the warning signs of asthma, administer medications, and properly manage asthma emergencies. Even though allergies are the primary trigger of asthma attacks in children, child-care facilities do not necessarily take steps to reduce the presence of such common allergens as dust mites, molds, and pollen.
Concerned about their inability to care for children with asthma, child-care providers may choose not to accept a child with this disease, or may ask for higher payment to cover the costs of extra staff. Left with few options, desperate parents may turn to less-qualified child-care providers. Worse, they may keep their child’s illness a secret.
   To address this need, the Asthma and Allergy Foundation of America is preparing for the national rollout of a child-care program, “Asthma and Allergy Essentials for Child-care Providers,” currently being piloted by its Maryland chapter. The program instructs child-care providers in how to manage asthma in children.
   Children with asthma would benefit greatly if states raised health standards at child-care centers to make them safe for those with asthma and allergies. States should also look for a solution to the financial impact that increased fees have on families with asthmatic children. Across the country, employers need to develop better child-care options for working parents—especially those who have children with chronic illnesses.

Ventilatory Support Reduces Chance of Death
Through a simple, noninvasive procedure for ventilatory support, German clinical investigators successfully restored systemic oxygen levels. The restoration significantly reduced the chance of death in postsurgical patients who had gone into acute respiratory failure following removal from mechanical ventilation. The research appears in the April issue of Chest, the journal of the American College of Chest Physicians.

New Office Spirometry Urged to Detect Treatable Lung Disease in Smokers
A recently released consensus statement calls for more widespread use of a new form of office spirometry to detect more chronic obstructive pulmonary disease (COPD) in its most treatable stage, particularly in smokers over 45. The statement released by the National Lung Health Education Program calls for the widespread use of new office spirometers, which differ in specifications somewhat from the more traditional spirometers used for diagnosis. Traditional diagnostic spirometers cost about $2,000 and about $10 of time per test is spent in testing and disposable supplies. Office spirometers will cost less than $800 and require less testing time than diagnostic spirometers.
   The consensus statement was based on conferences sponsored by the American College of Chest Physicians and the National Heart, Lung, and Blood Institute of the National Institutes of Health.

Improper COPD Reevaluation May Be Costing Millions
A recent study reveals that improper reevaluation of chronic obstructive pulmonary disease (COPD) patients may be costing Americans $153 million per year in unnecessary continuous oxygen therapy (COT) treatment. The study shows that many COPD patients (primarily smokers over 45) remain on COT unnecessarily either because they are not reevaluated in a timely manner or because of inaccurate reevaluation.
   The study report refers to the Third Oxygen Consensus Conference, which recommended that patients receiving COT be reevaluated 1-3 months after therapy is initiated when the patient is medically unstable. The Medicare system currently allows a full year to pass before reevaluation.
   The full study, “Reevaluation of Continuous Oxygen Therapy After Initial Prescription in Patients with Chronic Obstructive Pulmonary Disease,” appears in the April issue of the American Association for Respiratory Care’s Respiratory Care journal.

Lung Association Calls for Withdrawal of Nicotine Delivery Device
The American Lung Association (ALA) has called on RJ Reynolds Tobacco Company to withdraw its Eclipse nicotine delivery device from the market. The Food and Drug Administration (FDA) has not tested this drug delivery device for sale in the United States. The Eclipse device is not a cigarette but a high-tech nicotine delivery device that RJ Reynolds is touting as a less hazardous alternative to its highly addictive cigarettes. According to John R. Garrison, CEO of the ALA, consumers should not be misled by the tobacco company’s statements that this product is “safe.” The ALA fears that RJ Reynolds’ claims that this device is “safe” or “safer than cigarettes” may discourage smokers from quitting. The ALA reminds all Americans that there is no “safe” cigarette. The Eclipse device is not a “safe” alternative to cigarettes, Garrison says. Research in the 1990s raised serious health concerns about the device. RJ Reynolds research on the Eclipse has not been independently reviewed by any federal regulatory agency. Garrison notes, “Nicotine patches and gum had to undergo rigorous review and approval by the FDA prior to their introduction into commerce. The Eclipse device should too. The fact that the Eclipse device is similar in appearance to a cigarette and is manufactured by a tobacco company does not excuse this device from regulatory oversight. In fact, the health claims being made by RJ Reynolds demand immediate regulatory action.”