The Science of Medicine

InterMune, Inc. (Nasdaq: ITMN) announced that the results of a comprehensive review of safety data from four clinical studies were presented at the 2009 European Respiratory Society Annual Congress in Vienna, Austria by Dr. Ulrich Costabel of the Ruhrlandklinik, Essen, Germany.

In order to assess the risk-benefit profile of pirfenidone in IPF patients, a comprehensive review of safety was conducted involving two Phase 3 trials (CAPACITY 1 and CAPACITY 2) and two open-label studies (RECAP and PIPF-002). RECAP is an on-going open-label extension study that enrolled 603 patients who completed CAPACITY. PIPF-002 is an on-going long-term, open-label study in 83 IPF patients.

The summary and conclusions from the safety analysis as presented at ERS were:

– A comprehensive review of safety data from four clinical studies showed that treatment with pirfenidone was safe and generally well tolerated

– In the CAPACITY studies:

– The majority of adverse events (AE) were mild to moderate in nature and relatively few patients discontinued treatment due to adverse events.

– A similar incidence of serious adverse events (SAE) was observed in the pirfenidone group relative to the placebo group

– Fewer deaths were observed in the pirfenidone group relative to the placebo group and this difference was driven by a reduction in IPF-related deaths

– GI and skin AE were more common in pirfenidone-treated patients and were generally mild to moderate, transient, and rarely led to treatment discontinuation

– Transaminase (liver enzyme) elevations were slightly more common in the pirfenidone group, generally low-grade and without clinical sequelae (or secondary effect)

– Results from the two open label studies also suggest that long-term pirfenidone therapy is safe and generally well-tolerated

Dr. Costabel commented on the results, “Based on this comprehensive analysis of safety, pirfenidone appears to be safe and generally well tolerated in patients with IPF and for treatment periods longer than 72 weeks. These safety results, coupled with the evidence of a clinically meaningful pirfenidone treatment effect reported in three Phase 3 clinical trials and taken in the context of the urgent unmet medical need for new medicines for IPF patients, suggest that pirfenidone provides a reasonable risk-benefit profile for patients suffering from IPF. The new analysis presented today on the incidence of IPF-related deaths provides further support for the potential role of pirfenidone in the treatment of patients with this devastating disease.”

In this analysis of safety, fewer treatment emergent deaths (those occurring after the first dose and within 28 days of the last dose of study treatment) were observed in the pirfenidone group relative to the placebo group, and this difference was driven by a reduction in IPF-related deaths. In this exploratory analysis of pooled results of the two CAPACITY trials, the incidence of IPF-related deaths was 3.5% in the high-dose pirfenidone arm, compared to 7.2% in the placebo arm (p=0.031; Hazard Ratio = 0.48), indicating that patients treated with pirfenidone had a 52% lower risk of IPF-related death than those treated with placebo. The incidence of treatment emergent death from any cause was 5.5% in the 2403 mg/day pirfenidone arm compared to 8.4% in the placebo arm (p=0.141; Hazard Ratio = 0.65) indicating that patients treated with pirfenidone had a 35% lower risk of death from any cause than those treated with placebo.

A similar incidence of SAEs was observed in the pirfenidone group relative to the placebo group. In the CAPACITY trials, 32.8% of patients in the 2403 mg/day dose pirfenidone arm experienced a treatment related SAE, compared to 31.4% of patients in the placebo arm.

As observed in previous studies, gastrointestinal and skin adverse events, such as rash and photosensitivity, were more common in pirfenidone-treated patients, were generally mild to moderate in severity, transient, and rarely led to treatment discontinuation.

Liver enzyme (transaminase) elevations were slightly more common in the pirfenidone group than in the placebo group (4.1% and 0.6%, respectively), were generally low grade, rarely led to treatment discontinuation (0.3% of pirfenidone patients discontinued treatment for liver enzyme elevations versus 0.6% of placebo patients) and were without clinical sequelae.

“IPF is a progressive and uniformly fatal lung disease affecting 250,000 Americans and Europeans and for which there is no approved medicine in the United States or Europe,” said Dan Welch, Chairman, Chief Executive Officer and President of InterMune. “The comprehensive and generally favorable safety data for pirfenidone presented today, combined with the evidence of a consistent and meaningful treatment effect of pirfenidone observed in three multi-center, randomized, placebo-controlled Phase 3 studies in IPF suggest that if approved for marketing, pirfenidone could play a meaningful role in the treatment of this devastating disease.”

Report at ERS of New Data from the Pirfenidone Phase 3 Study in Japan

Poster P666 entitled “Enhanced effects of pirfenidone on the early phase of idiopathic pulmonary fibrosis (IPF),” was presented on Sunday, September 13 by M. Ebina et al. The authors reported that an analysis of the previously reported Phase 3 study sponsored by Shionogi suggested enhanced effects of pirfenidone in the early phase of IPF.

InterMune is preparing a New Drug Application (NDA) for pirfenidone for the treatment of IPF which it expects to submit in the fourth quarter of 2009, to be followed by a Marketing Authorization Application (MAA), which is expected to be submitted to the European Medicines Agency (EMEA) during the first quarter of 2010.

About CAPACITY and RECAP

The CAPACITY program consisted of two multinational, randomized, double-blind, placebo-controlled Phase 3 trials, named CAPACITY 1 and CAPACITY 2, designed to evaluate the safety and efficacy of pirfenidone in IPF patients with mild to moderate impairment in lung function. The primary endpoint of both trials was change in percent predicted Forced Vital Capacity (FVC) after 72 weeks of treatment evaluated with a nonparametric rank ANCOVA analysis. Both trials enrolled patients in North America, Europe and Australia with roughly 75% of the total 779 patients enrolled in North America.

CAPACITY 1 enrolled a total of 344 patients. Patients were randomized 1:1 to receive a total daily dose of 2403 mg pirfenidone, or placebo. CAPACITY 2 enrolled a total of 435 patients, and patients were randomized 2:2:1 to receive a total daily dose of 2403 mg pirfenidone, or placebo, or a total daily dose of 1197 mg pirfenidone, respectively, administered in three divided doses. The lower dose of pirfenidone in CAPACITY 2 provided safety and tolerability data. The pre-specified statistical analysis plan did not call for this low-dose group to be used in comparative analyses of efficacy. The pooled analyses of the primary and secondary efficacy outcome measures were based on a combined analysis of the 2403 mg group compared with the placebo group across both CAPACITY studies and were considered exploratory.

Enrollment of both trials was completed in less than 13 months following randomization of the first patient into the program in late April 2006. Ninety-seven percent (97%) of all patients in the two CAPACITY studies who were living and had not received a lung transplant, completed their Week 72 study visit.

Regarding RECAP, 603 patients who completed CAPACITY were enrolled in this on-going open-label study. The objective of RECAP is to provide further data on the long-term safety of pirfenidone in patients with IPF.

About Pirfenidone

Preclinical and in-vitro evidence had shown that pirfenidone inhibits collagen synthesis, down-regulates profibrotic cytokines and decreases fibroblast proliferation. Prior to the current results, data were presented from one Phase 3 study and four Phase 2 clinical trials in more than 400 patients which suggested that pirfenidone may positively affect lung function and disease progression in patients with IPF. In those clinical studies, pirfenidone was generally safe and well tolerated with the most frequent side effects reported being photosensitivity rash and gastrointestinal symptoms. In October of 2008, pirfenidone was approved for use in IPF patients in Japan and is marketed as Pirespa(R) by Shionogi in that country.

About IPF

Idiopathic pulmonary fibrosis (IPF) is a disabling and ultimately fatal disease that affects approximately 250,000 patients in the United States and Europe combined, with approximately 30,000 new cases reported per year in each of the United States and Europe.

IPF is characterized by inflammation and scarring (fibrosis) in the lungs, hindering the ability to process oxygen and causing shortness of breath (dyspnea) and cough and is a progressive disease, meaning that over time, lung scarring and symptoms increase in severity. The median survival time from diagnosis is two to five years, with a five-year survival rate of approximately 20%. Patients diagnosed with IPF are usually between the ages of 40 and 70, with a median age of 63 years and the disease tends to affect slightly more men than women. There are no medicines approved in the U.S. or Europe for IPF; pirfenidone was approved in Japan in October of 2008.

About InterMune

InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has an R&D portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes pirfenidone for which a Phase 3 program in patients with IPF (CAPACITY) has been completed and the compound is currently in the pre-registration stage. The company also has a research program focused on a pirfenidone analog named ITMN-520. The hepatology portfolio includes the HCV protease inhibitor compound ITMN-191 (referred to as RG7227 at Roche) that entered Phase 2b in August of 2009 and a second-generation HCV protease inhibitor research program.

Forward-Looking Statements

This news release contains forward-looking statements within the meaning of section 21E of the Securities Exchange Act of 1934, as amended, that reflect InterMune’s judgment and involve risks and uncertainties as of the date of this release, including without limitation the statements related to anticipated product development timelines, the interpretation of the CAPACITY clinical data, including certain exploratory analyses conducted by the Company with respect to such data and the likelihood of regulatory success. All forward-looking statements and other information included in this press release are based on information available to InterMune as of the date hereof, and InterMune assumes no obligation to update any such forward-looking statements or information. InterMune’s actual results could differ materially from those described in InterMune’s forward-looking statements. Pirfenidone failed to achieve statistical significance on the primary endpoint in one of its two pivotal clinical trials and there can be no assurance that the regulatory authorities in either the United States or Europe will grant regulatory approval based upon these data, in combination with the other efficacy analyses and safety results the company currently intends to submit in support of its NDA and MAA filings. Further analyses of the CAPACITY results will be conducted in the future and additional observations may be made which may lead to material change in the company’s current regulatory strategy for pirfenidone, including a decision by the company not to proceed with either or both of its regulatory submissions in the United States and Europe. These analyses and observations will be included in one or more scientific publications. Factors that could cause or contribute to such differences include, but are not limited to, those discussed in detail under the heading “Risk Factors” in InterMune’s most recent annual report on Form 10-K filed with the SEC on March 16, 2009 (the “Form 10-K”) and other periodic reports filed with the SEC, including the following: (i) risks related to the long, expensive and uncertain clinical development and regulatory process, including having no unexpected safety, toxicology, clinical or other issues or delays in anticipated timing of the regulatory approval process; (ii) risks related to failure to achieve the clinical trial results required to commercialize our product candidates; and (iii) risks related to timely patient enrollment and retention in clinical trials.

Source: InterMune, Inc

Scientists have identified the main genetic switch that causes excessive mucus in the lungs, a discovery that one day could ease suffering for people with chronic lung diseases like asthma and cystic fibrosis, or just those fighting the common cold.

The discovery was reported in a study posted online Sept. 14 by the Journal of Clinical Investigation. The new research sheds light on what has been a medical mystery – the precise biological reasons that the lungs in people with asthma, cystic fibrosis and other respiratory ailments clog with thick mucus.

Identifying the genetic circuits that cause mucous hyper-production gives researchers potential targets for new therapies to moderate or stop it, said Jeffrey Whitsett, M.D., the head of Neonatology, Perinatal and Pulmonary Biology at Cincinnati Children’s Hospital Medical Center and the study’s senior investigator.

“Everyone has had a stuffed up nose and cough after two or three weeks of a bad cold and most over-the-counter cold medications deal with mucus,” Whitsett explained. “We still don’t have effective therapies for removing excess mucous, whether it’s someone with a cold or chronic lung disease. That’s why we still tap on the chests of kids with cystic fibrosis to try and clear it.”

The current study provides an entirely new understanding of how certain cells promote chronic lung infection and excess mucus production. Scientists previously thought that, after airways were attacked by an allergic response or inflammation, mucus cells (known as goblet cells) divided and proliferated at a very fast rate – a process known as hyperplasia. Instead, the Cincinnati Children’s team discovered that beneficial lung cells, called Clara cells, instead change their cell type to become goblet/mucous cells in a process called metaplasia.

Dr. Whitsett and his colleagues also found the metaplasia process in this instance to be reversible. Goblet cells can change back to Clara cells if the detrimental genetic influence is blocked, highlighting a possible pathway for new treatments, according to Dr. Whitsett, who also is executive director of the Perinatal Institute at Cincinnati Children’s.

The study identifies a transcription factor, SPDEF, as the master gene that regulates a chain of dozens of downstream genes involved in mucus production. SPDEF is an active player in other organ systems that need to produce mucus for normal function, such as the digestive system. In healthy lungs, however, the researchers report the gene is mostly quiet, as healthy lungs don’t produce significant amounts of mucus.

Using an egg white protein called ovalbumin to induce an allergic reaction and inflammation in the lungs of mice, the researchers observed a dramatic elevation in the expression of SPDEF in the lung tissues of the affected animals. The animals also experienced hyper-production of thick mucus in their lungs. In mice where the SPDEF gene was switched off, inflammation and excessive mucus production did not occur, demonstrating the gene’s potential as therapeutic or diagnostic target. Mice lacking SPDEF were unable to increase mucus production or develop goblet cells.

In mice where respiratory inflammation and excessive mucus production were present, the researchers report that SPDEF turned off genes involved in biological processes that help protect lung tissues from infection and damage. Conversely, SPDEF activated genes that promote inflammation and excessive mucus – in particular FOXA3, AGR2 and mucins.

By composition, mucus is a sugar-coated collection of large proteins that, in healthy conditions, help the body defend itself by collecting and then clearing out contaminants. In the case of AGR2 for example, the gene helps assemble mucus proteins by folding together different molecules. When SPDEF is over-expressed, it results in increased production of AGR2, which in turn promotes an over-abundance of protein folding and mucus production.

Dr. Whitsett cautioned it will be several years before the research results in a specific therapeutic approach that can be tested in people. In the meantime, his team has received several significant grants to conduct more extensive studies into the various genetic and molecular influences that control, or are controlled by, SPDEF and involved in excess mucus production.

The first author on the current study was Gang Chen, a graduate student in Dr. Whitsett’s laboratory. The laboratory’s research is supported by funding from the National Institutes of Health and the Cystic Fibrosis Foundation. The study was done in collaboration with the Netherlands Institute of Developmental Biology, with the research there being led by Dr. Hans Clevers.

About Cincinnati Children’s

Cincinnati Children’s Hospital Medical Center is one of 10 children’s hospitals in the United States to make the Honor Roll in U.S. News and World Reports 2009-10 America’s Best Children’s Hospitals issue. It is #1 ranked for digestive disorders and is also highly ranked for its expertise in respiratory diseases, cancer, neonatal care, heart care, neurosurgery, diabetes, orthopedics, kidney disorders and urology. One of the three largest children’s hospitals in the U.S., Cincinnati Children’s is affiliated with the University of Cincinnati College of Medicine and is one of the top two recipients of pediatric research grants from the National Institutes of Health.

President Barack Obama in June 2009 cited Cincinnati Children’s as an “island of excellence” in health care. For its achievements in transforming health care, Cincinnati Children’s is one of six U.S. hospitals since 2002 to be awarded the American Hospital Association-McKesson Quest for Quality Prize for leadership and innovation in quality, safety and commitment to patient care. The hospital is a national and international referral center for complex cases.

Source: Cincinnati Children’s Hospital Medical Center

An Alaska ballot initiative that would require parental notification for minors seeking abortion services should be removed from the ballot because its proponents used inaccurate summary language when collecting signatures in support of their petition, a lawyer for Planned Parenthood of the Great Northwest argued Thursday at a state Supreme Court hearing, the AP/Anchorage Daily News reports. In the case, PPGNW is appealing Superior Court Judge Frank Pfiffner’s decision to allow the initiative on the August primary ballot. Pfiffner also ordered state officials to write an accurate summary.

PPGNW attorney Jeff Feldman said the more than 36,000 voters who signed the petition were not given crucial facts, including that physicians who failed to properly notify a parent could be charged with a felony. Signature collection serves an essential screening purpose in Alaska’s initiative process that should not be circumvented by simply promising a correction, he added.

Feldman said the summary used for signature gathering should list any rights that would be abolished or created by the initiative’s passage. Although the summary gave detailed information about how a minor could be excused from school to have an abortion or attend a court hearing to request a waiver of parental notification, Feldman said it left out several “absurd” and “onerous” requirements for physicians. For example, physicians would be required to call parents as many as five times in two-hour increments during a 24-hour period, and they would have to verify guardians’ identities with two forms of identification, Feldman said. Physicians convicted of violating the law would face penalties of up to five years in prison.

Attorneys for the state and the initiative’s sponsors argued that the errors in the ballot summary were minor and could be fixed. Kevin Clarkson — an attorney representing the sponsors, including former Lt. Gov. Loren Leman; Kim Hummer-Minnery, spouse of the president of the antiabortion-rights group Alaska Family Council; and Mia Costello, a Republican candidate for the state House — said the sponsors were being penalized for an initiative summary that the lieutenant governor’s office wrote. Clarkson also said that summaries are not intended to include all details of an initiative’s effects and that there is no evidence voters were misled.

Assistant Attorney General Joanne Grace, representing the lieutenant governor’s office, said voters who signed the petition had sufficient information to know that they wanted to support the measure. The initiative summary language could be corrected through ballot language, Grace said, adding that media coverage and public discussion could also help inform voters. Throwing out the measure could undermine public faith in the initiative process, she argued (Joling, AP/Anchorage Daily News, 5/21).

Reprinted with kind permission from nationalpartnership. You can view the entire Daily Women’s Health Policy Report, search the archives, or sign up for email delivery here. The Daily Women’s Health Policy Report is a free service of the National Partnership for Women & Families.

© 2010 National Partnership for Women & Families. All rights reserved.

European Respiratory Society Congress 2009, Vienna, Austria, 15 September 2009: Symbicort® (budesonide/formoterol) Turbuhaler® Maintenance and Reliever Therapy (Symbicort SMART®) provides effective symptom control and reduces the risk of severe exacerbations in symptomatic asthma patients on inhaled corticosteroids (ICS) or combination therapy of ICS and long-acting beta agonists (LABAs) over six months according to today’s results from EUROSMART, a large pan-European study of more than 8,000 patients.1

Professor Michel Aubier of HГґpital Bichat, Paris, France, a study investigator said: “EUROSMART shows that budesonide/formoterol maintenance and reliever therapy is highly effective for improving patient outcomes, by controlling symptoms and reducing the risk of asthma attacks. In simple terms, it helps patients to get on with their everyday lives and know that they are also benefitting from a reduced risk of future exacerbations.”

The study examined the efficacy and safety of a lower and the highest recommended maintenance doses. Patients in the study took either one or two inhalations of Symbicort Turbuhaler 160/4.5Вµg twice daily as maintenance therapy, with additional reliever inhalations as needed. The primary endpoint was measured as time to first severe exacerbation and was prolonged with two inhalations of Symbicort 160/4.5Вµg twice daily as maintenance therapy (hazard ratio 0.82; p=0.03) compared to those patients on one inhalation.

In addition, secondary endpoints included severe exacerbation rate and asthma daily control, as measured by the Asthma Control Questionnaire 5 item version (ACQ-5). ACQ scores improved from 1.85 to 1.09 for patients in the higher maintenance dose inhalation group and from 1.85 to 1.18 for patients in the lower maintenance inhalation group. In addition, the number of uncontrolled patients (ACQ>1.5) was significantly reduced from 60% to 27% in the patients taking two maintenance inhalations twice daily and from 60% to 30% in patients taking one maintenance inhalation twice daily.1

Further results from the EUROSMART study showed that some more severe asthma patients treated in the higher inhalation group may be offered improved efficacy compared to the lower maintenance dose. Lung function as a measure of asthma severity was found to be a significant predictor of improved response to the highest recommended maintenance dose of Symbicort Turbuhaler therapy.2 Patients taking two 160/4.5Вµg maintenance inhalations twice-daily plus reliever inhalations as needed who had a baseline peak expiratory flow (PEF) of less than 80% predicted normal (PN) reduced their risk of exacerbation by 31% (p=0.02) compared to those taking one 160/4.5Вµg maintenance inhalation twice-daily plus reliever inhalations as needed.2 In patients with a PEF of above 80% PN, there was a non-significant reduction in the risk of exacerbation by 14% (p=0.2).2

Professor Michel Aubier continued: “Whereas most patients are well-controlled on a maintenance dose of one 160/4.5Вµg inhalation twice-daily, there are certain patients with more severe asthma who require additional treatment. These patients can benefit from the higher maintenance dose of two 160/4.5Вµg inhalations twice-daily, and a simple lung function test that can be conducted in a primary care setting can help identify these patients.”

EUROSMART also highlighted that patients lacking in asthma control may have lung function values within the normal range, indicating that measures of asthma control in addition to lung function are useful in managing asthma in the clinical setting.3

Additional retrospective analyses derived from five pivotal Symbicort SMART studies were also presented in three abstracts during the ERS Congress. As set out by the GINA guidelines, the goal of asthma management is to achieve daily control and minimise future risk including prevention of exacerbations. Overall Asthma Control (OAC) is the composite of both of these aspects and was demonstrated by the analysis, which showed that Symbicort SMART provided similar or better daily asthma control, as measured by ACQ-5, but with a reduced risk of exacerbations, compared to other common treatment regimens.4

Symbicort SMART was compared to: higher dose ICS, same dose ICS/LABA (long-acting beta agonist) and higher dose ICS/LABA plus SABA (short-acting beta agonist) to assess the percentage of patients with GINA-based controlled asthma and the probability of a change in control status over time.5

The percentage of patients whose asthma was controlled/partly controlled was at least similar with Symbicort SMART compared with higher dose ICS (wk 52: 56% vs 45%), same-dose ICS/LABA (wk 52: 56% vs 53%) and higher dose ICS/LABA plus SABA (wk 25: 54% vs 54%), and also improved over time. The study also showed that across all treatment groups the current level of asthma control in any week predicts stability in the next. Patients who were partly controlled or uncontrolled in any week had significantly lower risk of having an exacerbation the following week when treated with Symbicort SMART compared to all comparators.5

Professor O’Byrne, McMaster University, Hamilton, Canada, an investigator in the analysis, said: “The ability of budesonide/formoterol maintenance and reliever therapy to effectively control asthma daily, as well as reduce the risk of exacerbations compared to other treatment regimens, is extremely important. The incidence of asthma in Europe has doubled to almost 30 million in the past decade and it is still a significant cause of morbidity and mortality.6 It is important that we look at optimising an individual’s treatment regime to be able to give them the day-to-day control they need.”

Further results from the study confirmed that the similarity between GINA and GOAL definitions of asthma control, with both GINA controlled and partly controlled and GOAL totally and well controlled asthma being similar to ACQ-5

A popular stomach-acid reducer used to prevent stress ulcers in critically ill patients needing breathing machine support increases the risk of those patients contracting pneumonia threefold, according to researchers at Wake Forest University School of Medicine.

Hospital-acquired pneumonia is the leading cause of infection-related deaths in critically ill patients. It increases hospital stays by an average of seven to nine days, cost of care, and the risk of other complications.

“As best we can tell, patients who develop hospital-acquired pneumonia or ventilator-acquired pneumonia have about a 20 to 30 percent chance of dying from that pneumonia,” said senior study author David L. Bowton, M.D., professor and head of the Section on Critical Care in the Department of Anesthesiology. “It’s a significant event.”

The study, published in a recent issue of CHEST, compared treatment with two drugs that decrease stomach acid: ranitidine, marketed under the name ZantacTM, and pantoprazole, marketed under the name ProtonixTM or PrilosecTM.

Both drugs decrease stomach acid, but the newer pantoprazole is considered more powerful and has become the drug of choice in many hospitals.

However, in the analysis of 834 patient charts, the researchers found that hospitalized cardiothoracic surgery patients treated with pantoprazole were three times more likely to develop pneumonia.

“We conducted this study, in part, because we thought we were seeing more pneumonias than we were used to having,” said study co-author Marc G. Reichert, Pharm.D., pharmacy coordinator for surgery at Wake Forest University Baptist Medical Center.

Both acid-reducing drugs can make the stomach a more hospitable place for bacteria to colonize. Patients on breathing machines sometimes develop pneumonia when stomach secretions reflux into the lungs.

Current treatment guidelines to prevent pneumonia recommend raising the head of the bed for patients on breathing machines, which reduces the risk of stomach secretions getting into the lungs.

But the study’s findings suggest some other steps could keep critically ill patients from developing ventilator-associated pneumonia.

Doctors should consider whether an acid reducer is needed at all, Bowton said. The occurrence of stress ulcer bleeding has gone down in recent years, perhaps because patients with breathing tubes are fed earlier, and food in the stomach may neutralize or reduce the effects of stomach acid.

Bowton added that in cases where an acid reducer is needed, ranitidine is recommended, given the apparent decreased risk in developing pneumonia.

Doctors should stop using the drug as soon as the risk of bleeding passes – once the patient is off the breathing machine and eating, either on his/her own or through a feeding tube.

“Stopping the drugs earlier appears to be the best thing for patients,” Reichert said.

Todd A. Miano, Pharm.D., formerly of Wake Forest University Baptist Medical Center and now with the Hospital of the University of Pennsylvania, is the study’s lead author. Co-authors, all from Wake Forest University School of Medicine, are Timothy T. Houle, Ph.D., and Drew A. MacGregor, M.D., of the Department of Anesthesiology; and Edward H. Kincaid, M.D., of the Department of Cardiothoracic Surgery.

Source:
Shannon Koontz

Wake Forest University Baptist Medical Center

View drug information on Ranitidine Capsules.

Chlorine is effective at killing pathogens in swimming pools, but it also irritates the skin, eyes and upper respiratory tract of swimmers. Recent research has found swimming in outdoor or indoor chlorinated pools can increase asthma risks. The study, “Impact of Chlorinated Swimming Pool Attendance on the Respiratory Health of Adolescents” found that children who swam in chlorinated pools had a higher risk of asthma, as well as other allergic diseases such as hay fever and allergic rhinitis.

Researchers in Belgium compared the health of adolescents who swam in chlorinated pools to adolescents who swam in pools sanitized with a concentration of copper and silver. In children with allergic sensitivities (atopy), exposure to chlorinated pools significantly increased the prevalence of asthma and respiratory allergies. Study authors suggest the chlorine-based oxidants in the water or just above the water cause changes in the airway and promote the development of allergic diseases. The findings reinforce the need for further research and to enforce regulations on the level of these chemicals in the water and air of swimming pools.

Source
American Academy of Pediatrics

An article on the epidemiology, cause and risk factors of asthma is the first in a special report on asthma in CMAJ (Canadian Medical Association Journal) designed for clinical practitioners. This review looks at risk factors for persistent asthma at different ages, including prenatal, infancy, childhood and adulthood.

Genetics, environment and host characteristics are risk factors for asthma. The significant increases in the incidence of asthma and geographic variation in prevalence rates support the idea that the environment plays a large role in the current asthma epidemic. As well, environmental triggers may affect asthma differently during various life stages and risk factors may change over time.

The report comes from the researchers conducting the Canadian Healthy Infant Longitudinal Development (CHILD) Study, a multicentre Canadian study involving 5000 pregnant women with the aim of better understanding the development of allergy and asthma in children.

“While many cross-sectional studies confirm a true increase in incidence and prevalence of asthma over the last 2-3 decades, much remains unknown as to the fundamental immune, genetic and environmental mechanisms underlying its development, and its increased expression especially in the developed world,” write Dr. Malcolm Sears from McMaster University, Dr. Padmaja Subbarao, The Hospital for Sick Children (SickKids) and coauthors.

Reduction in risk of asthma, as well as true prevention, is a key but elusive goal of asthma management.

Source:
Kim Barnhardt

Canadian Medical Association Journal

While daily bathroom showers provide invigorating relief and a good cleansing for millions of Americans, they also can deliver a face full of potentially pathogenic bacteria, according to a surprising new University of Colorado at Boulder study.

The researchers used high-tech instruments and lab methods to analyze roughly 50 showerheads from nine cities in seven states that included New York City, Chicago and Denver. They concluded about 30 percent of the devices harbored significant levels of Mycobacterium avium, a pathogen linked to pulmonary disease that most often infects people with compromised immune systems but which can occasionally infect healthy people, said CU-Boulder Distinguished Professor Norman Pace, lead study author.

It’s not surprising to find pathogens in municipal waters, said Pace. But the CU-Boulder researchers found that some M. avium and related pathogens were clumped together in slimy “biofilms” that clung to the inside of showerheads at more than 100 times the “background” levels of municipal water. “If you are getting a face full of water when you first turn your shower on, that means you are probably getting a particularly high load of Mycobacterium avium, which may not be too healthy,” he said.

The study appeared in the Sept. 14 online edition of the Proceedings of the National Academy of Sciences. Co-authors of the study included CU-Boulder researchers Leah Feazel, Laura Baumgartner, Kristen Peterson and Daniel Frank and University Colorado Denver pediatrics department Associate Professor Kirk Harris. The study is part of a larger effort by Pace and his colleagues to assess the microbiology of indoor environments and was supported by the Alfred P. Sloan Foundation.

Research at National Jewish Hospital in Denver indicates that increases in pulmonary infections in the United States in recent decades from so-called “non-tuberculosis” mycobacteria species like M. avium may be linked to people taking more showers and fewer baths, said Pace. Water spurting from showerheads can distribute pathogen-filled droplets that suspend themselves in the air and can easily be inhaled into the deepest parts of the lungs, he said.

Symptoms of pulmonary disease caused by M. avium can include tiredness, a persistent, dry cough, shortness of breath, weakness and “generally feeling bad,” said Pace. Immune-compromised people like pregnant women, the elderly and those who are fighting off other diseases are more prone to experience such symptoms, said Pace, a professor in the molecular, cellular and developmental biology department.

The CU-Boulder researchers sampled showerheads in homes, apartment buildings and public places in New York, Illinois, Colorado, Tennessee and North Dakota.

Although scientists have tried cell culturing to test for showerhead pathogens, the technique is unable to detect 99.9 percent of bacteria species present in any given environment, said Pace. A molecular genetics technique developed by Pace in the 1990s allowed researchers to swab samples directly from the showerheads, isolate DNA, amplify it using the polymerase chain reaction, or PCR, and determine the sequences of genes present in order to pinpoint particular pathogen types.

“There have been some precedents for concern regarding pathogens and showerheads,” said Pace. “But until this study we did not know just how much concern.”

During the early stages of the study, the CU team tested showerheads from smaller towns and cities, many of which were using well water rather than municipal water. “We were starting to conclude that pathogen levels we detected in the showerheads were pretty boring,” said Feazel, first author on the study. “Then we worked up the New York data and saw a lot of M. avium. It completely reinvigorated the study.”

In addition to the showerhead swabbing technique, Feazel took several individual showerheads, broke them into tiny pieces, coated them with gold, used a fluorescent dye to stain the surfaces and used a scanning electron microscope to look at the surfaces in detail. “Once we started analyzing the big metropolitan data, it suddenly became a huge story to us,” said Feazel, who began working in Pace’s lab as an undergraduate.

In Denver, one showerhead in the study with high loads of the pathogen Mycobacterium gordonae was cleaned with a bleach solution in an attempt to eradicate it, said Pace. Tests on the showerhead several months later showed the bleach treatment ironically caused a three-fold increase in M. gordonae, indicating a general resistance of mycobacteria species to chlorine.

Previous studies by Pace and his group found massive enrichments of M. avium in “soap scum” commonly found on vinyl shower curtains and floating above the water surface of warm therapy pools. A 2006 therapy pool study led by Pace and CU-Boulder Professor Mark Hernandez showed high levels of M. avium in the indoor pool environment were linked to a pneumonia-like pulmonary condition in pool attendants known as “lifeguard lung,” leading the CU team into the showerhead study, said Pace.

Additional studies under way by Pace’s team include analyses of air in New York subways, hospital waiting rooms, office buildings and homeless shelters. Indoor air typically has about 1 million bacteria per cubic meter and municipal tap water has rough 10 million bacteria per cubic meter, said Pace.

So is it dangerous to take showers? “Probably not, if your immune system is not compromised in some way,” said Pace. “But it’s like anything else — there is a risk associated with it.” Pace said since plastic showerheads appear to “load up” with more pathogen-enriched biofilms, metal showerheads may be a good alternative.

“There are lessons to be learned here in terms of how we handle and monitor water,” said Pace. “Water monitoring in this country is frankly archaic. The tools now exist to monitor it far more accurately and far less expensively that what is routinely being done today.”

In 2001 the National Academy of Sciences awarded Pace the Selman Waxman Award — considered the nation’s highest award in microbiology — for pioneering the molecular genetic techniques he now uses to rapidly detect, identify and classify microbe species using nucleic acid technology without the need for lab cultivation. That same year he was awarded a MacArthur Foundation “genius grant” for his work.

Source:
Norman Pace

University of Colorado at Boulder

Most of us have a daily shower to keep us clean, not to infect our faces with potentially pathogenic bacteria. According to a study carried out by scientists at the University of Colorado at Boulder, USA, 30% of showerheads harbor significant levels of Mycobacterium avium (M avium), a bacterium associated with lung disease that can pose serious health risks for people with weakened immune systems, and can sometimes infect healthy people too.

The study, led by Professor Norman Pace, analyzed about 50 showerheads from nine US cities, including New York, Denver and Chicago. Pace said it is not surprising to find pathogens in municipal waters (a pathogen is an organism that can cause disease, such as a bacterium or virus). However, the scientists found that some M avium and other pathogens were accumulated in slimy biofilms that stuck to the inside of showerheads at over 100 times the background levels of municipal water. “If you are getting a face full of water when you first turn your shower on, that means you are probably getting a particularly high load of Mycobacterium avium, which may not be too healthy,” he said.

You can read about this study in Proceedings of the National Academy of Sciences. The study was part of a larger one which aimed to assess the microbiology of indoor environments and was supported by the Alfred P. Sloan Foundation.

According to research carried out at The National Jewish Hospital, Denver, Colorado, USA, the increase in lung infections (pulmonary infections) in the USA over the last twenty or so years from non-tuberculosis mycobacteria species, such as M avium may be linked to a rise in the number of showers people have been taking in comparison to baths, Pace said.

Water spraying out of showerheads can spread pathogen-filled droplets that float around in the air and are inhaled by humans into the deepest parts of the lungs.

Symptoms of pulmonary disease caused by M avium include:

Fatigue (tiredness)
Persistent, dry cough
Breathlessness (panting, shortness of breath)
Weakness
General feeling of malaise (feeling generally unwell)

People with weakened immune systems are more susceptible to develop these symptoms when exposed to M avium.

Pace added that although researchers have tried cell culturing to detect showerhead pathogens, the technique cannot detect 99.9% of bacteria species present in any given environment. A technique developed by Pace in the 1990s, using molecular genetics, allows scientists to swab samples directly from the showerheads, isolate DNA, amplify it using the polymerase chain reaction (PCR), and determine the sequences of genes present so as to identify specific pathogen types (types of disease-causing organisms).

Pace said “There have been some precedents for concern regarding pathogens and showerheads. But until this study we did not know just how much concern.”

Initially, this study tested showerheads in small cities and towns, where many showers were using well-water instead of municipal water. “We were starting to conclude that pathogen levels we detected in the showerheads were pretty boring. Then we worked up the New York data and saw a lot of M. avium. It completely reinvigorated the study.”

The scientists also broke several showerheads into tiny pieces, coated them with gold, used a fluorescent dye to stain the surfaces and used a scanning electron microscope to view the surfaces in detail. “Once we started analyzing the big metropolitan data, it suddenly became a huge story to us,” said team member Leah Feazel.

A showerhead from Denver with high loads of M gordonae, a pathogen, was cleaned with a bleach solution. Several months later tests showed the bleach solution had caused a three-fold increase in M gordonae – this indicates resistance to chlorine by M gordonae.

Studies that had been carried out previously by Pace and team found enormous enrichments of M avium in soap scum, which is commonly found on vinyl shower curtains and floating on the water surface of warm therapy pools. A therapy pool study carried out by Pace and team showed that significantly high levels of M avium in the indoor pool environment were associated with lifeguard lung – a pneumonia-like pulmonary condition in pool attendants. This study led Pace and team into the showerhead study.

Asked whether it is dangerous to take showers, Pace answered “Probably not, if your immune system is not compromised in some way. But it’s like anything else – there is a risk associated with it.”

Pace added that as metal showerheads to not “load up” with so many pathogen-enriched biofilms, compared to plastic ones, metal showerheads may be a good alternative.

“There are lessons to be learned here in terms of how we handle and monitor water. Water monitoring in this country is frankly archaic. The tools now exist to monitor it far more accurately and far less expensively that what is routinely being done today,” said Pace.

“Opportunistic pathogens enriched in showerhead biofilms”
Leah M. Feazel, Laura K. Baumgartner, Kristen L. Peterson, Daniel N. Frank, J. Kirk Harris and Norman R. Pace
Proceedings of the National Academy of Sciences, September 14, 2009, doi: 10.1073/pnas.0908446106

A new study published in the September 15, 2009, issue of PLoS ONE found that patients with cavitary pulmonary tuberculosis receiving anti-TB medications supplemented with nebulized interferon-gamma have fewer bacilli in the lungs and less inflammation, thereby reducing the transmissibility of tuberculosis in the early phase of treatment.

Tuberculosis, often called TB, is an infectious disease that usually attacks the lungs and infects one-third of the world’s population, resulting in 9.2 million active cases per year. TB is usually spread between family members, close friends and people who work or live together. With estimates that nearly 1 billion people will become newly infected between now and 2020, the World Health Organization has set the goal of halving the prevalence and mortality of the disease by 2015. The study shows that patients who inhale interferon through a nebulizer can reduce their disease’s transmissibility during the first few weeks of treatment.

“Our findings create an opportunity to combat TB bacilli in the lungs and reduce inflammation in the early stages of the disease when the tuberculosis is transmissible,” says William N. Rom, MD, MPH, the Judith and Sol Bergstein Professor of Medicine and Environmental Medicine, director of the Bellevue Chest Service, and director of the Division of Pulmonary and Critical Care Medicine at NYU Langone Medical Center. “Nebulized interferon doesn’t replace medications used to fight tuberculosis, but it shortens the time when the disease is spread – which could be critical for control of the spread of the disease.”

In the study, researchers recruited 89 eligible patients with active tuberculosis in Cape Town, South Africa, and performed a randomized, controlled clinical trial. One group of the patients took anti-TB medications supplemented with nebulized interferon-gamma over a four-month period, and another took TB mediations alone. Dr. Rom and his colleagues found that those patients that inhaled interferon had a significant decrease in the amount of tubercle bacilli from the sputum smear at four weeks and fewer symptoms of cough, night sweats, fever and wheezing. Scientists also found that this group also had fewer inflammatory cytokines in lung cells recovered by bronchoalveolar lavage after four months.

This study was performed, in part, at Bellevue Hospital Center, affiliated with NYU School of Medicine. The co-authors of the study include Rany Condos, MD, of the Department of Medicine at NYU Langone Medical Center and Dr. Rod Dawson, MBChB, of the Department of Medicine at the University of Cape Town in South Africa. The research was funded by the National Heart, Lung and Blood Institute of the National Institutes of Health in Bethesda, Maryland.

Source
NYU Langone Medical Center