By John Easton

Few people realize the important role that math plays in organ transplants. Complex formulas convert medical information about each patient, including diagnosis, age, and test results, into a single “allocation score” that determines who has priority when an organ becomes available. One factor not included in these calculators is proximity of the organ to a patient. More than a decade ago, the U.S. Department of Health and Human Services issued the “Final Rule,” intended to ensure that organs were allocated “based on medical criteria, not accidents of geography.” However, new data show that where a transplant candidate lives continues to influence access to donated lungs.

The current system for allocating donated lungs based on proximity and not on need appears to decrease the potential benefits of lung transplantation and increase the number of patients who die waiting, researchers said at an annual meeting of thoracic surgeons in Fort Lauderdale. Using data provided by the United Network for Organ Sharing (UNOS), Mark Russo and colleagues at the University of Chicago Medicine and Columbia University found that donor lungs were routinely allocated to less urgent, local candidates even when there were patients within the region but outside the local donor service who were in much greater need.

One unfortunate but not unusual example was a 27-year-old man with cystic fibrosis who was in an intensive care unit awaiting a lung transplant. He had a lung allocation score of 91 out of 100, one of the highest of such scores in the U.S. at the time. He was expected to die within a week without a transplant. An appropriately matched lung donor did became available less than 20 miles from the hospital where this man was waiting, but because the candidate was just outside of the donor’s local service area, two candidates from within the service area, each with an LAS in the 40s, took priority. One of these candidates received the organs. Five days later the 27-year-old patient died.

Such circumstances are not uncommon, said Russo, assistant professor of surgery at the University of Chicago Medicine.

“Ideally, a suitable donor organ would be available for every person who could benefit from transplantation,” he said. “Unfortunately, there remains a critical scarcity of donor organs. More efficient allocation of this scarce and precious resource could dramatically increase the overall benefit from lung transplantation.”

Among the 580 locally allocated double-lung transplants performed in 2009, 480 less needy candidates, or 83 percent of all double-lung transplants, received the organs even though a well-matched candidate in greater need existed in the region.

Twenty-four percent of such cases involved skipping over regional candidates with lung allocation scores — which range from 1 to 100, based on need and likely benefit — more than 10 points higher than the local recipient. More than 7 percent of the events involved a regional candidate with a lung allocation score (LAS) more than 25 points higher than the local recipient. Overall, 185 of the bypassed regional candidates ultimately died on the waitlist.

“We found that too often, and to many patients’ detriment, organs are allocated according to geography rather than urgency,” Russo said. When lungs go to less needy candidates within the local Donor Service Area and never become available to sicker candidates at the regional or national level, “this decreases the overall benefits of a transplant,” he said.

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Since the Roe v. Wade decision of 1973, abortion has been a woman’s legal right (with ever-changing state-specific restrictions) in the United States. But one factor often trumps the legal status of abortion: access. Though abortion training is required for medical residents studying to become obstetrician-gynecologists, physicians are not required to perform the procedure or even to refer a patient to a ob-gyn who will. That voluntary basis can create pockets of the country where access to an abortion provider is a larger obstacle than any legislation.

As a window into these access issues, a team led by Debra Stulberg, assistant professor of family medicine, conducted a survey of more than 1,000 Ob-Gyn physicians on their experience regarding abortion requests and providing the procedure. Their answers, published in Obstetrics & Gynecology, reflected how commonly ob-gyns are approached for the procedure - 97% of respondents said they had encountered patients seeking abortions. However, only 1 in 7 (14.4%) of those surveyed said that they had provided abortions themselves.

The data collected from other question on the survey allowed Stulberg and her colleagues to paint a picture of who was more or less likely to provide an abortion. Some of the results were unsurprising: female ob-gyns were more like to perform the procedure than men, those with strong religious beliefs were less likely to provide abortions, and those who worked at Catholic hospitals were very unlikely to provide the option to their patients. Geographically, ob-gyns from the Northeastern, Western, and urban regions of the United States were more likely to have performed an abortion, while those from the South, Midwest, and rural areas were less likely. That could contribute to large areas of the country where there are limited options for women seeking abortion - regions that happen to be where abortion providers commonly experience harassment, the authors note.

Breaking down the responses by age also reveals an interesting U-shaped curve. The most likely age group to provide abortions was ob-gyns 35 years or younger. But the second most likely were those aged 56-65 years old - the generation that was in medical school around the time of the Roe v. Wade decision. As that age group heads toward retirement, the number of abortion providers could drop even lower, the authors speculate, should the younger generation not pick up the slack. For responses to this data from both sides of this always polarized issue, see U.S. News & World Report. More coverage can be found at the Los Angeles Times, NPR, and the State Column.

Our New Facebook Home

Thanks to the hard work of our colleague Matt Wood, the Medical Center has a new Facebook page! The page will be updated daily with articles and videos about Medical Center care and research, including the occasional article from this here blog. If you are so inclined, please visit the page and click the all-important Like button.

Elsewhere…

It sounds counter-intuitive: burning the smooth muscle of the lung to improve symptoms for people suffering from severe asthma. But bronchial thermoplasty is a promising new procedure, and has worked for patients like swimmer Stephanie Manikas, featured in this CBS Early Show piece from Thursday. Manikas’ physician, the Medical Center’s Kyle Hogarth, has previously explained the procedure as part of ScienceLife’s Dr. FAQ series.

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Cancer used to be a black box, a disease that physicians could only monitor through surgical biopsies and indirect measures. But for the last thirty years, the use of computed tomography imaging, better known as CT scans, has allowed oncologists and cancer researchers to keep close watch on the growth or shrinkage of a tumor for many different types of cancer. A patient with a lung tumor, for example, can be scanned every few months in order to see whether their therapy is working - and if it’s not, doctors may choose to switch treatments. Clinical trials of new therapies for cancer also make use of CT scans, using the increase or decreased size of the tumor as a primary data point.

But for all the benefits of scans over surgeries to monitor tumor size, flaws remain for CT scans. A new study published this week in the Journal of Clinical Oncology shines a harsh light on one of the primary problems - the technology’s variability. Patients usually are given CT scans months apart, and trained radiologists measure the tumors to see whether they are growing or receding. But how much of those changes can be attributed to random error from the imperfect resolution of the scan or the breathing of the patient?

To test this baseline error, researchers from Memorial Sloan-Kettering Cancer Center got a little tricky. Instead of taking two scans from a patient months apart, they took two scans in quick succession, within 15 minutes. The scans were then handed off to experienced radiologists, who were told to measure the change in tumor size without knowing how much time had elapsed between the images. The results were sobering - despite the tumor being biologically identical between the two near-simultaneous scans, the radiologists found changes in size of 1mm or more in more than half of the samples and a 10 percent error range in either direction overall. Although the criteria for tumor progression is an increase in size of 20 percent or more, that 10 percent error could considerably distort the data when clinical and research decisions are made using normally-spaced scans.

The result doesn’t render CT scans obsolete, but offers new caution about the method’s shortcomings.

“It’s the sense of, ‘Really? Is this first happening now?’” Michael Maitland, assistant professor of medicine at the Medical Center, commented to Reuters Health about the study findings. “This is telling us scientifically how much noise is naturally there without any treatment or the cancer getting worse. It’s an important thing to do whenever you are going to use any kind of marker for a disease.”

In an accompanying editorial in the Journal of Clinical Oncology, Maitland went further, writing with his co-authors that it was time for oncologists to rely less upon CT scans alone and move toward integrating those images with other measures to create more precise monitoring technologies. As cancer edges toward more personalized treatment strategies, developing better diagnostic tools will become even more important, they argued.

“It is time to cast away familiar conventions and turn to better methods of evaluating malignant disease therapeutics,” they wrote. “It is time to replace these systems with more innovative, quantitative approaches that have the potential to define relationships between solid tumors, disease progression, and therapeutic outcomes in patients.”

Elsewhere…

It might have come out a few days late for the 4th of July, but Travis Carter’s study of the effects of seeing the American flag on political beliefs is still timely. If the Booth Business School researcher is right, we’ll all be slightly more Republican for at least the next 8 months. Ed Yong at Not Exactly Rocket Science did a great writeup that was featured on the Colbert Report this week (and also wrote up our own Neil Shubin’s study on the origin of limb genetic programs this week as well).

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A Magic 8-Ball for Cardiac Arrest

Cardiac arrest is one of the most common ways that people die, and hospitals need to be constantly vigilant about the threat of heart stoppage in their patients. So physicians have long sought to develop a way of predicting who is most at risk for cardiac arrest when checked into the hospital, such that extra care and surveillance can be taken. At the 2011 international meeting of the American Thoracic Society, held this past week in Denver, two Medical Center fellows presented research refining these early warning systems to make them a more effective hospital tool.

In the first study, pulmonary and critical care fellow Gordon E. Carr connected cardiac arrest with another frequent sight on the hospital ward: pneumonia. Carr’s study found that patients admitted with pneumonia are at elevated risk of cardiac arrest over the next three days after admission, and that almost 40 percent of these cardiac arrests occurred while the patient was outside of the intensive care unit. “We found a compelling signal that some patients with pneumonia may develop cardiac arrest outside of the ICU, without apparent shock or respiratory failure,” Carr said in a press release. “If this is true, then we need to improve how we assess risk in pneumonia.”

Adding extra caution about cardiac arrest to the care of patients with pneumonia is a specific way to improve surveillance. But to apply to more patients, a broader scale is needed, one that can be easily assembled from the vital signs that are already routinely measured in the wards. One such scale, called the Modified Early Warning Score or MEWS was tested by pulmonary and critical care fellow Matthew Churpek as a predictor of cardiac arrest, who found it to be better at predicting a cardiac arrest in the next 48 hours than any individual vital sign. But MEWS was designed for general risk of death, not specifically for cardiac arrest, and Churpek suggested a more specialized risk score could be calculated for use by hospitals. The benefits of such a measure, he said in a press release, would be immense.

“Rapid response teams are a complex and resource-intensive intervention, so providing evidence-based criteria for their activation is crucial,” Churpek said. “Our patients will do better if we can detect who is at high risk early enough to intervene and prevent a cardiac arrest.”

Doctors Against Ronald McDonald

Childhood obesity is a growing problem in the United States, and doctors point the finger of blame directly at increased consumption of junk food and fast food. Chains such as McDonalds have made noise about making their food healthier, especially for children, by posting calorie counts on menus and offering snacks such as apples and carrots instead of fries. But according to an open letter signed by over 500 health care professionals and placed in newspapers around the country this week, they have not done enough.

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Cooking indoors over firewood and dung is a tough habit to break for billions of poor people around the world. But Sola Olopade, MD, professor of medicine and family medicine, found a way. He wanted to stop women from hunching for hours over open fires inside their houses, cooking with babies strapped to their backs. The air in such houses quickly becomes filled with toxins, and the women and children have a host of bad health consequences.

“It’s the most unclean combustion you can get,” Olopade said in his seminar earlier this month at the MacLean Center for Clinical Medical Ethics. “The women and children have coughs, headaches, runny noses, chest tightness.”

Those are just the health problems he could measure. “I wonder what kind of cognitive dysfunction people develop in spaces where the carbon monoxide is so high.”

Unfortunately, the billions of poor people who cook their daily meals over firewood and dung have few other options. Without electricity, Olopade said, “energy poverty drives people to use whatever they can get their hands on.” But Olopade was determined to see whether education and a little technology could make it less dangerous for people to breathe inside their houses.

Olopade, who is clinical director of the University of Chicago Global Health Initiative, went to two small villages in his native Nigeria, ready to distribute energy-efficient ceramic stoves. He believed the simple stoves could make an enormous improvement in the community’s health. His team measured the air quality inside 100 homes, and found heavy metals, carbon monoxide, and particulate matter more than twenty times the World Health Organization acceptable standards. The researchers also educated the community about the dangers of exposure to smoke from using firewood to cook indoors and the benefit of using the new stoves, handing out brochures about cooking in their native dialect.

“I told them without medical jargon that this was killing people,” Olopade said.

Three months after giving the stoves to the families in the villages, Olopade returned. He took the same air quality measurements, repeated the survey of symptoms and saw a remarkable improvement. Carbon monoxide and particulate matter levels were dramatically lower, much closer to the WHO standards.

“People were very happy with the stoves. They’re very simple. They’re lined with ceramic which retains a lot of heat and promotes more complete combustion of the firewood or biomass fuel,” Olopade explained.

The women were burning the same fuel - cow dung, agricultural waste, and firewood - but the stoves had kept most of the pollutants from pouring into the homes. With this small change, “you can really improve the indoor environment,” Olopade said.

The health benefits were drastic. Before the intervention, many of the children and most of the mothers suffered from dry cough, runny noses, burning eyes, breathing difficulties, chest tightness, headaches and dizziness. All of these health problems plummeted after they started cooking on the clean stoves.

“Just by engaging the community in partnership, educating them on the dangers of exposure to toxic fumes and giving people efficient stoves, without changing their lives much, the change in symptoms is dramatic,” Olopade concluded.

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ScienceLife ran 219 posts in 2010, and choosing the best of them is as hard as picking a favorite gene.  So here’s a month-by-month scan of a busy year at the University of Chicago Medical Center, full of exciting discoveries in the laboratory and the clinic. The impact of some of this research is already being felt by patients receiving improved, evidence-based medical care. For other studies, the clinical benefit may be years in the future, and may take unpredictable forms. As a closing message for 2010, we’ll re-quote the recently departed Eugene Goldwasser, whose laboratory research isolating and purifying the hormone erythropoietin has helped millions of people worldwide.

“It is a particularly impressive example of how basic research can pay a dividend that could not be anticipated at the start,” Goldwasser wrote about his life’s work, “and it is a pity that the lesson still has not been learned by those who control public funding of science.”

January: Tong Chuan-He looked at how cancer may result from cells who don’t want to grow up. Scientists studied how sleep affects the language learning skills of starlings (with painstakingly acquired video of the experiment!). Richard Jones combined two laboratory staples - Western blots and DNA micro-arrays - to develop a new method for studying protein networks. While physicians such as Tammy Utset treat patients with lupus, UChicago scientists are looking for the genetic origins of the autoimmune disorder.

February: Many Medical Center employees returned from volunteering with relief efforts in Haiti, and we filmed video interviews with Rex Haydon, Tiffany Cupp, Richard Cook, and Dima Awad on their experiences. Most of the human genome is “junk” between protein-encoding regions, but Marcelo Nobrega developed a way to find important regulatory elements in that genetic sea. Like birds, human learning can be affected by sleep, and Leila Kheirandish-Gozal reported on the impact of obstructive sleep apnea upon learning in children. Can a single protein in the brain create behaviors associated with drug addiction in rats?

March: Everyone knows air travel is stressful, but did you know that eastbound flights cause stronger cortisol changes than westbound trips? The laboratory of Milan Mrksich found a way to direct stem cells to form fat or bone by shaping them into stars or flowers, a brilliant example of bioengineering. Computational neuroscientists discovered how touch is like vision in the brain, knowledge that could be used to someday re-engineer Luke Skywalker’s robot hand. Dartmouth president and Partners in Health co-founder Jim Yong Kim visited to talk about a new, needed area of research: health care delivery.

April: Researchers at the Field Museum and the University of Chicago teamed up for the Emerging Pathogens Project, an effort to find new viruses in animals before they jump to humans. Cardiologist Martin Burke tested out a new type of internal defibrillator device that can go under the skin, instead of into the heart (the clinical trial, reported in May, was a success). In a lecture to the MacLean Center of Clinical Medical Ethics, transplant surgeon J. Michael Millis described his efforts to bring American organ transplant practices to China.

May: A trial testing the erectile dysfunction drug Viagra for a rare, untreatable lung disease failed, but pulmonologist Imre Noth found a silver lining. Lauren Sallan and Michael Coates uncovered evidence of a previously unappreciated mass extinction event 360 million years ago that changed the path of life on Earth. Researchers from the University of Chicago and around the world presented science at the frontier of biotechnology at the annual BIO conference.

June: In a study that is literally the size of an entire country, epidemiologist Habibul Ahsan measured the toll of a tragic, accidental exposure of millions to arsenic in Bangladesh. Putting a gene from fireflies into the pancreas of mice isn’t mad science, it’s an imaging tool that will help study cures for diabetes. Epigenetics, the modifications that turn genes on and off, took off in 2010, and cardiologists Stephen Archer and Jalees Rehman linked one epigenetic factor to pulmonary artery hypertension.

July: Scientists don’t often get to see the fruits of their research in the flesh, but the Celebrating the Miracles gathering of diabetic children weaned off injected insulin thanks to genetic research was a moving exception (video of the event can also be viewed). Another hot topic in science and medicine this year was the use of computational analysis to sift through rapidly accumulating data, topics explored by Gary An and Andrey Rzhetsky. Or you can build a computer model of a brain network to study the dynamics of epilepsy, like neurologist Wim van Drongelen.

August: Air pollution is a problem indoors as well as outdoors in developing countries where dung and firewood are used to cook food - a problem being tackled in a project led by Sola Olopade. A study of the hormonal changes induced by a stressful test revealed a surprising protective effect of marriage and long relationships. Microbiologist Olaf Schneewind’s laboratory developed two new strategies against MRSA, the most-wanted cause of hospital-acquired infections.

September: To study multiple sclerosis, neurologist Brian Popko’ s laboratory developed a new mouse model that can replicate the disease, then spontaneously recover. Meanwhile, a new drug to treat MS, originally isolated from fungus found in wasps, was approved by the FDA and is being studied for broader uses at the Medical Center. The micro-organisms that live in humans were analyzed as part of a “microbiome” study looking at the protective effects of breast-feeding against a intestinal disease.

October: Common wisdom on quitting smoking says to stay away from cigarette-associated cues, but research from psychiatrist Harriet de Wit’s laboratory revealed that abstinence could make craving even worse. A study of how getting a good night’s rest affects dieting results suggested that “sleeping off the pounds” isn’t merely a fantasy. Graduate student Daniel Matute solved a 100-year-old riddle about how quickly new species become reproductively incompatible with each other.

November: In perhaps our favorite study of the year, geneticist George Perry found a way to acquire the genomic information of endangered species from…poop. The evolutionary biologist Leigh Van Valen passed away, but his Lewis Caroll-inspired Red Queen Hypothesis lives on. Sometimes statistics don’t tell the whole truth, as in the curious case of the aspirin paradox - why the cardio-protective drug may actually predict worse outcomes after heart attack.

December: Evolution textbooks may need a rewrite after geneticist Manyuan Long’s laboratory discovered that new genes can be just as essential as old genes. A study by neurobiologist Nicholas Hatsopoulos proved that the only thing better than a thought-controlled device is a thought-controlled device equipped with a robot arm. Ripped from the headlines: microbiologist Jack Miller weighed in on the hype over arsenic-based bacteria, and ethicist/physician/friar Daniel Sulmasy discussed the Presidential Bioethics Commission’s report on synthetic biology.

All told, it was a great year of science and medicine. Let’s do it again in 2011! Regular posting will resume Jan. 3rd. Happy Holidays.

Endoscopy and colonoscopy are well-known tools of the physician, minimally invasive devices that navigate the channels of the digestive system to spot cancers, ulcers, and other defects once difficult to spot without major surgery. In the shadow of these procedures lies bronchoscopy, which uses similar technology to explore the labyrinth of the lungs. With the flexible tube of the bronchoscope, a pulmonologist can detect potentially cancerous lesions, take samples for pathological testing, help remove dangerous nodules, and apply heat or install valves to help treat asthma and emphysema. We discussed this exciting new world of bronchoscopy with D. Kyle Hogarth, assistant professor of medicine at the University of Chicago Medical Center and an expert on the field. Hogarth discusses the basic warning signs and risk factors for lung disease, talks about the innovative new bronchial thermoplasty treatment for severe asthma, and gives an overview of how bronchoscopes help physicians locate and remove lung cancers.

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Chronic Fatigue Syndrome (CFS) is known as a “diagnosis of exclusion,” a disease with non-specific symptoms that can only be considered when all other reasonable diseases have been ruled out. Because there are no known proven causes of CFS, it’s impossible to design a test for the disease, and there is no defined treatment strategy. And yet, the CDC estimates that more than one million Americans have CFS, and patient groups are desperate for research into the origins of the disease.

Medical desperation begets controversy, and that’s what kicked up again this week with the publication Tuesday of a second report linking CFS to a mouse retrovirus. The research - which found DNA from the murine leukemia virus (MLV) family in more than 86 percent of CFS patients vs. only 7 percent of controls - would be interesting in and of itself. But the paper is the latest salvo in a scientific battle that has raged in the last year over the connection between CFS and viruses, exposing the modern balance between the slow crawl of research and the urgent desire of patients for information in the Internet age.

The first paper to link CFS with a mouse retrovirus was published last year in Science, creating a stir in the media and hope for CFS patients hungry for an explanation and a cure. But several subsequent studies failed to replicate the original finding, leading many to question whether the original experiments had been contaminated by mouse DNA or were simply not conducted properly. The controversy moved beyond the battlefield of scientific journals when the study’s senior author, Judy Mikovits, began to aggressively push the link between the retrovirus and CFS and other diseases - a saga recapped in an article earlier this summer by our friend Trine Tsouderos at the Chicago Tribune.

The new article, published by scientists from the FDA, NIH, and Harvard, gives conditional support to Mikovits’ original findings, detecting similar (but not identical) viral DNA in blood samples from CFS patients. The new study’s methods, which included extreme measures to ensure that no mouse DNA contamination could occur, were praised by many in the field. But the stench of controversy remained, as the paper only came out after being delayed two months while the authors reassessed their findings in light of yet another paper that failed to detect virus. CFS patient groups, who had received leaked word of the positive findings, cried foul over the delay.

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The link between sports-related concussions and severe brain injury has been percolating in the press for several years now, due mostly to the tireless reporting of Alan Schwarz at the New York Times. But until this week, the research was lacking a prominent face, with most of those found to have suffered from early dementia and even death after multiple concussions unknown to all but the biggest football fans. That changed Wednesday with an article by Schwarz with an impossible to ignore hook: what if Lou Gehrig didn’t have Lou Gehrig’s Disease? In the ensuing days, the story has gained traction around the world, but also generated some justifiable skepticism.

That speculation (based on particularly circumstantial evidence) was an extension of an article published this week by researchers with the Center for Study of Traumatic Encephalopathy, which has led the way on the link between concussion and brain disorders in athletes. Previously, the group had found that deceased football players who had suffered multiple concussions during their careers, such as Lou Creekmur and Mike Borich, had several physical markers of Alzheimer’s disease despite dying at a young age. The new study shifts the focus to ALS, or amyotrophic lateral sclerosis, which was diagnosed in Lou Gehrig, prompting one of the most famous speeches in sports history.

In three athletes diagnosed with chronic tramuatic encephalopathy (CTE), the Alzheimer’s-like condition reported earlier, the researchers also found symptoms that resembled ALS: muscle weakness, atrophy, and spasticity. Autopsies on the athletes also found extensive death of motor neurons - the cause of ALS - but test showed that the damage resembled the brain damage seen in CTE rather than typical ALS damage. That suggests that brain traumas suffered during athletic competition can produce damage that simulates not one, but two of the most frightening neurological disorders. With exquisite timing, Carl Zimmer had a story at Discover the same day on just how such traumas could irreversibly damage neurons by stretching and contorting their string-like axons.

But while the science is interesting (and frightening), the link to Gehrig is shakier. Though the baseball player does not appear in the scientific article, the authors use Gehrig as a prominent example in the New York Times article, and cite newspaper records of the famous Ironman suffering head injuries in games but returning to play again the next day. But since his remains were cremated and his medical records remain confidential, there’s no way to tell whether Gehrig truly had ALS or the CTE-related faux-ALS described in the new article. That’s one of many criticisms Gary Schwitzer raises in his critique of the NYT article, alongside a neurologist urging caution regarding a journal publication based on a mere three case studies.

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Since the middle of the 20th century, fighting air pollution has been a primary goal of the growing environmental movement in the United States and around the world. Encounters with smog and toxic gases inspired waves of public anger and protest that led to Clean Air Acts being passed in several countries and a steady progression toward tighter standards. But most of these efforts have concentrated on pollutants in the air outside the home produced by factories, automobiles, and other industrial sources. Meanwhile, another source of air pollution closer to home has gone unnoticed, even as it causes potentially millions of death in the developing world.

The main cause of indoor air pollution, explains Sola Olopade, professor of medicine at the University of Chicago Medical Center, is the burning of biomass for cooking food. In impoverished areas without access to electricity, people resort to using firewood, agricultural residue, and even cow dung as fuel for their kitchen stoves. In structures with poor ventilation, the burning of these items can create a high concentration of toxic fumes with serious health effects for those exposed.

“The problem is when you use firewood to cook, the smoke from it contains a lot of polluted dust that is carcinogenic and can also lead to airway damage and infection,” said Olopade, who is also clinical director of the University of Chicago Global Health Initiative. “When you look at it globally, there are about 3 billion people, mostly women and children, who are exposed to indoor pollution from using firewood to cook.”

The World Health Organization estimates that indoor air pollution is responsible for roughly 1.6 million deaths each year, from acute lower respiratory infections, chronic obstructive pulmonary disease, lung cancer, and other diseases. Half of those deaths are children, and nearly a third are children under the age of five, Olopade said.

“To put it in the right context, indoor pollution from biomass contributes to about 2.6 percent of the global burden of disease, actually kills more people every year than HIV and maybe even malaria, and yet nobody knows about it,” Olopade said. “So if we can accomplish bringing sensitivity or attention to this problem, and use it to influence policy and help people who are poor and would otherwise have no opportunity to have more efficient stoves, I think we will be very delighted.”

Just such an effort is currently underway thanks to a grant awarded to Olopade by the CHEST Foundation, an organization of American pulmonologists. Olopade has traveled back to his birth country of Nigeria to launch an effort against indoor air pollution in three rural communities named Eruwa, Igo-Ora, and Abanla. While doing a previous study on asthma in Nigeria, Olopade said he found that an overwhelming number of asthmatic children experienced high concentrations of toxic fumes at home.

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In 2008, a twenty-year-old environmental treaty had a dramatic impact upon the care of asthma in the United States. Due to the 1987 ban on chlorofluorocarbons (CFCs), the ozone-depleting propellents once found in hair spray and other aerosol-can products, the inhalers used by millions of asthmatics underwent a mandatory switch to a CFC-free version. Unfortunately, patient education about the switch was scarce, leaving many unaware that they would be receiving the new inhalers. Even more concerning, many physicians were equally uninformed about the switch and how to counsel their patients on use of the new devices, called HFA inhalers.

That impending storm of confusion, as highlighted by a May 2008 New York Times article, inspired a group of University of Chicago Medical Center residents and faculty to launch the Chicago Breathe Project. Modeled upon the Medical Center’s community-based Neighborhood Health Exchange, an effort to raise health literacy on diet, nutrition and heart health in underserved communities, the project focused on asthma education - for patients and medical residents alike. Their two-pronged educational effort was described this month in the Journal of the National Medical Association.

“Reports were saying that patients and physicians are completely unprepared for this transition,” said Valerie Press, instructor in the section of hospital medicine and one of the Chicago Breathe Project founders. “We found that a large majority of the residents really didn’t know much about these HFAs, and also didn’t know a ton about how to teach patients about inhalers in general.”

Community health clinics and respiratory health organizations also reported a need for patient education on the new inhalers, Press said. Minority populations in Chicago suffer at least twice the national hospitalization rate and mortality rate for asthma. More recently, a litany of complaints and questions related to the new inhalers - that the spray was too cold, tasted different, wasn’t working, was working too strongly, or was too expensive - had come in from patients, the organizations reported.

So the Chicago Breathe Project set about educating both groups, and like the Neighborhood Health Exchanges, a team of residents led the educational efforts. With a grant from the American College of Physicians Foundation, the team was able to go to four other Chicago medical centers and teach a workshop to their residency programs, with the added allure of free lunch. Residents learned about the inhaler switch, how to best instruct a patient on inhaler use, and discussed case studies of patients having trouble with the devices. Those surveyed 6 months after the workshops said that they were more likely to assess a patient’s inhaler technique and were more comfortable discussing proper use with their patients.

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In the New Yorker last month, Malcolm Gladwell wrote elegantly about the euphoria and frustration of cancer drug discovery. Tracing in parallel the path of a modern biotechnology company and a team of doctors in the 1950’s, Gladwell illustrated the unexpected twists and turns that mark every new drug’s journey from laboratory to clinic, in a game where the stakes are literally life and death. The dramatic scene that Gladwell chose to open his piece? The American Society of Clinical Oncology meeting, a huge gathering of cancer researchers where the highly-anticipated results of clinical trials for the next wave of promising anti-cancer agents are presented in a flourish of success or a sigh of failure.

The ASCO meeting this year is being held in Chicago, whose McCormick Place is one of the few convention centers gargantuan enough to hold tens of thousands of researchers from around the world. Throughout the Escher-like hallways of that building, echoes of Gladwell’s opening scene were taking place, with Kaplan-Meier curves - the graph that shows differences between the drug-treated group of patients and the control group - delivering their positive and negative verdicts. Over the weekend, two success stories featured University of Chicago involvement; both were exciting small steps in the battle of science against different types of cancer.

One of the most difficult to treat cancers is also one of the most common: lung cancer, which is newly diagnosed in more than 200,000 people a year in the United States. Lung cancer researchers, including Ravi Salgia of the University of Chicago Medical Center, have been looking for proteins that are behaving badly inside lung cancer cells and that may represent promising targets for cancer therapy. One such target, the enzyme anaplastic lymphoma kinase or ALK, is overactive in a small percentage of lung cancer patients due to a chromosomal translocation - a break in the DNA that produces a dangerous Frankenstein protein called EML4-ALK.

While only 4 percent of patients with lung cancer are positive for EML4-ALK, the mechanism suggests that an inhibitor of the protein may be effective in attacking cancer in that population. Sunday, researchers (including Salgia) presented evidence of that strategy working - an inhibitor of ALK called crizotinib successfully controlled lung cancer in 90 percent of patients enrolled in a small trial. In 57 percent of the patients, tumors actually shrank - an incredible advance in a cancer that is nearly always untreatable. The authors said that a larger, Phase 3 trial is already underway to verify the findings in a larger population.

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Please welcome Ankur Thakkar, who works in our Publications Department, with this fine post on the controversy over paid compensation for organ donation.

The economic crisis over the last three years caused many Americans to change their lifestyles to make ends meet. They turned to second jobs, second mortgages and tighter budgets. They sold the possessions they could live without. What else could they part with to make money? What if they could sell their organs?

Organ selling has polarized physicians and bioethicists since the beginning of clinical transplantation, but year after year it gains steam. This makes sense when there are 80,000 people in the United States waiting for a kidney and more than 5,000 of them will die this year, according to the Organ Procurement and Transplantation Network. Most people who need organs have to wait for donors they’ve never met to pass away, with the chances for a successful outcome deteriorating the longer they have to wait. There aren’t enough kidneys to go around.

“One reason for this is that modern medicine can now keep people alive long enough for their kidneys to fail,” said medical ethicist Lainie Ross, MD, PhD, associate director of the MacLean Center for Clinical Medical Ethics. “This means the waiting list for organs grows, while the number of usable organs from deceased donors is reduced.”

A 2010 study by researchers from the University of Pennsylvania and the Pennsylvania Veterans Affairs Medical Center found that when people were offered money for their organs, it made them more willing to donate. The researchers concluded that creating a financial incentive would increase the national supply of organs, resulting in saved lives.

Ross isn’t convinced. An outspoken opponent of opening the organ market, she believes it is socially irresponsible to allow people to make money from their organs. Far too many donors will assume that selling their organs will lift them out of poverty, without understanding the risks to their health.

The Pennsylvania study, conducted on Philadelphia commuters, found the opposite. The participants rated their willingness to donate their organs with and without payment. The responses were similar despite the participants’ incomes, suggesting that offering money for organs did not disproportionately change the minds of poorer people.

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A critical step in the design of any clinical trial is picking the right primary endpoint, the result that will usually make or break the study. That’s more difficult than it sounds - one’s hope is to cure a disease or relieve a patient’s symptoms, but choosing the best specific measure for those goals is something of a guessing game. Further, the process can be made even more difficult for diseases that do not have a long history of clinical research and thus no established endpoints.

Idiopathic pulmonary fibrosis, an unexplained and very serious scarring of the lung tissue, is one such disease. Because of the extremely poor prognosis for patients with IPF, where most patients die within five years of symptoms first appearing, no large-scale clinical trials were tried until 1999, said Imre Noth, Associate Professor of Medicine at the University of Chicago Medical Center. Even today, some groups of IPF patients are still left out of clinical trials.

“The area that has been neglected by far and away are the severe patients,” Noth said. “The rationale beyond most biologics that have been looked at is you need to start early to make an impact.”

But the results of a promising clinical trial of a new treatment for severe IPF patients was published last week in the New England Journal of Medicine. The bad news? The primary outcome chosen for the study - improvement in a patient’s walking distance during a 6-minute test - failed to improve in the group treated with drug. Nevertheless, the trial was greeted with an optimism unusual for the IPF field, Noth said, thanks to a silver lining of secondary successes and promising near-misses.

“This has been a very frustrating disease for pulmonologists,” said Noth, a member of the Idiopathic Pulmonary Fibrosis Clinical Research Network, which designed and administered the trial. “The sense is, ‘Finally something we can give to our patients,’ because at least you can make them feel better, which is a great first step.”

The drug itself is an interesting story. Called sildenafil, it has already been marketed by Pfizer under the name Revatio as a treatment for pulmonary arterial hypertension. But most readers probably know sildenafil by its other commercial name: Viagra. The drug’s more famous use was actually an unintentional side effect, as it was originally developed to be a hypertension treatment. Trying sildenafil for IPF is going back to those primary intentions, capitalizing upon the drug’s ability to improve blood supply to the lungs.

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