COPD & asthma linked to poor anaphylaxis outcomes

Researchers have found that patients with chronic lung diseases, including asthma and chronic obstructive pulmonary disease (COPD), are significantly more likely to have poor outcomes when hospitalized for anaphylaxis and other allergic conditions compared with other patients.

Zuber Mulla, MSPH, PhD, Associate Professor and Director of Epidemiologic Research at the University of Texas School of Public Health and Estelle Simons, MD, FRCP from the University of Manitoba, Winnipeg, Canada identified 30,390 patients who were hospitalized in Texas for allergic conditions between 2004 and 2007. Of these, 2,410 had a primary or secondary diagnosis of anaphylaxis at discharge.

The 2,772 (9.1%) patients in the overall cohort who had asthma were 67% more likely to receive mechanical ventilation than patients without asthma, while the 1,818 (6.0%) patients with COPD were 35% more likely to be admitted to the intensive care unit (ICU), 41% more likely to experience a prolonged stay in hospital (over 3 days), and 98% more likely to receive mechanical ventilation than those without the condition.

In the sub-cohort of patients with anaphylaxis, patients with asthma (n=334; 13.9%) did not have an increased risk for mortality compared with other patients, but they were over two-times more likely to be mechanically ventilated than patients without asthma).

Meanwhile, COPD patients with anaphylaxis (n=149; 6.2%) were 86% more likely to experience a prolonged hospital stay and 61% more likely to receive mechanical ventilation than patients without COPD.

Other lung conditions associated with poor outcomes included pulmonary eosinophilia, which increased the odds for ICU admission in patients with allergic conditions, while chronic bronchitis, emphysema, and interstitial lung diseases were linked to an increased risk for hospital mortality.

In particular, in the sub-cohort of patients with anaphylaxis, interstitial lung disease was linked to an 8.71-fold increased odds for mortality and a 5.16-fold increased odds for mechanical ventilation.

Writing in BMJ Open, Mulla and Simons say that their “unique exploratory analysis of a large database offers new insight into the effects of chronic pulmonary disease on anaphylaxis, an area for which there has previously been a dearth of information.”

Asthma drug helps shed pounds

According to new research, a drug commonly used to treat asthma and COPD may also burn fat.

When taken in pill form, the drug formoterol boosted fat burning while preserving protein metabolism, and muscle mass.

“Fat burning was increased up to 25%,” says researcher Paul Lee, MD, PhD, of the Garvan Institute of Medical Research and an endocrinologist at St. Vincent’s Hospital in Sydney, Australia.

Formoterol is used as an inhaled medication for asthma and chronic obstructive pulmonary disease (COPD) and is one of the ingredients in Symbicort and Dulera.

In this study, Lee used it in pill form, and gave it to 8 men at a dose of 160 micrograms a day for one week. Before and after the study, he measured the men’s energy rates, fat oxidation, and whole body protein metabolism.  Each time, the measurements were taken after the men drank a standardized, high-carbohydrate liquid meal.

Comparing their before and after rate, their overall energy rate increased by more than 10% and their fat burning by 25%.

Theoretically, an average person weighing 155 pounds could burn an extra 200 calories a day with the pill. Over time, that could translate to noticeable fat loss and maintained or gained muscle.

The inhaled form of the drug can cause tachycardia – an abnormally fast heartbeat, but Lee did not see this side effect in the patients who took the pill form. “Some had insomnia, but it was mild,” he says. It was also temporary. “Some reported loss of appetite.”

In addition to burning fat, the drug might prevent or treat muscle wasting that can accompany age. “It may potentially reverse or prevent this process and treat frailty,” Lee says.

”The report is certainly intriguing,” says Bruce Wolfe, MD, President of the American Society for Metabolic and Bariatric Surgery and Professor of Surgery at Oregon Health and Science University, Portland.  However, he cautions that the increase in fat burning is modest. Eating a couple of cookies, or drinking a small glass of wine could undo the benefit. Nevertheless, over time, taking the formoterol could make a noticeable difference.

SRxA’s Word on Health eagerly awaits the results of further studies.

The changing co-morbidities of COPD

It seems that people suffering from chronic obstructive pulmonary disease (COPD) who are on long-term oxygen therapy (LTOT) have more to worry about than breathing difficulties.

According to a new study from Sweden, COPD patients on LTOT face an increased risk of death from cardiovascular disease and other non-respiratory ailments. The findings were published in the online version of the American Journal of Respiratory and Critical Care Medicine.

“In recent decades the demography of patients starting LTOT for COPD has changed markedly,” said principal researcher Magnus P. Ekström.

The mean age of patients starting LTOT increased from approximately 66 to 73 years between 1987 and 2000.  In parallel there has also been a significant increase in the proportion of women receiving LTOT for COPD.

The researchers enrolled 7,628 adult patients who started LTOT for COPD between January 1987 and December 2004. Patients remained in the study until LTOT was suspended or until death. Study participants were followed for a median of 1.7 years.

5,497 patients died during the course of the study. Although the risk of death decreased annually for both respiratory disease (2.7%) and lung cancer (3.4%), it increased for circulatory disease (2.8%) and digestive organ disease (7.8%). The overall risk of death increased by 1.6% per year during the study period.

In total, the risk of death for cardiovascular disease increased by 61.5% between 1987 and 2004, the authors noted.  According to the authors, the shift in mortality is partly attributable to an increase in the age of patients starting LTOT, which in turn may be related to decreases in tobacco use.

“In our view, the mechanism that underlies the increases in both overall mortality and mortality due to non-respiratory causes is that the patients have a progressively higher burden of coexisting diseases and conditions, and become more vulnerable with increasing age,” Dr. Ekström said. “Physicians who treat COPD with LTOT need to be aware of these shifts and to monitor for other conditions that may influence the risk of death in these patients.”

SRxA’s Pulmonology and Health Outcomes Advisors can help pharmaceutical companies develop programs to educate physicians about COPD. To find out more, contact us today.

New Sun Rising

 

Sunovion Pharmaceuticals Inc. formerly known as Sepracor, Inc. announced its new name this week.  The name change and updated branding follows Sepracor’s acquisition by Dainippon Sumitomo Pharma Co., Ltd last year.

“This is an exciting time for Sunovion Pharmaceuticals Inc. and we are poised to deliver on our vision to become a leading global pharmaceutical company known for scientifically-advanced products that improve the lives of patients,” said Mark Iwicki, President and Chief Operating Officer of Sunovion. “The meaning of Sunovion combines the strength of the sun with innovation and, for us, represents the start of a great new company. Launching our new corporate identity is a meaningful next step for our employees and partners who have contributed to our past success. We remain focused on our goal to grow our current brands and advance our pipeline candidates.”

Sunovion will continue its sales and marketing efforts offering brands including ALVESCO®,  BROVANA®, OMNARIS®, XOPENEX®, XOPENEX HFA®.

We at Word on Health applaud Sunovion’s continued dedication to improving patients’ respiratory health.

To Give or Not to Give? – That is the question!

Few people in the respiratory community will have missed the study published last week in the New England Journal of Medicine (NEJM) that demonstrated Spiriva is comparable to Serevent in adults with uncontrolled asthma.

For those of you who did, SRxA’s Word on Health is pleased to provide you with a quick recap:

210 people with uncontrolled asthma were enrolled in a three-way, double-blind, triple dummy study.

All patients were treated with a beclamethasone inhaler (Qvar) to which was added Spiriva (tiotropium bromide), Serevent (salmeterol xinafoate) or a double dose of Qvar.

Results showed that Boehringer Ingelheim’s Spiriva, which is not currently FDA approved for asthma,  worked better than doubling the dosage of Teva’s Qvar and was just as effective as GlaxoSmithKline’s Serevent.

Interesting stuff, but in our opinion that was not the real news!

In an accompanying editorial, editors of the NEJM, chastised GSK for failing to provide free study drug to investigators from the National Heart, Lung, and Blood Institute. Apparently manufacturers were approached to supply both active drug and placebo inhalers, and while Boehringer Ingelheim (the manufacturer of tiotropium) and Teva (the manufacturer of Qvar) agreed to provide the materials, GlaxoSmithKline (the manufacturer of Salmeterol) refused.

The net result of this, say the editors was that investigators had to spend $900,000 from the National Institutes of Health (NIH) – and therefore they say, from taxpayers – to repackage the active drug and to create a visually identical placebo for use in the trial.

In a passionate conclusion to the editorial, Curfman, Morrissey and Drazen say:

“The most precious commodity that drug manufacturers possess is the trust of their research subjects, and to maintain this trust they need to be willing to put their products at risk. When they refuse to provide their drugs to legitimate investigators, the researchers will get their studies done without company help. It will take more time and cost more money, but in the end, the research will be done and the company will be perceived as having acted in its own self-interest rather than having worked to enhance the health of the community.”

This story was picked up by various news media who continued the vilification of GSK.

Here at Word on Health we’re not so sure that this criticism is justified.

First, pharmaceutical companies are not required to donate products for third party studies.

Second, Serevent is already licensed for the treatment of asthma. The company has previously performed numerous trials to demonstrate its efficacy and safety, including four studies on its effects in patients with asthma on concomitant inhaled corticosteroids.  In other words GSK did not need this study.

Boehringer, on the other hand did.

Two years ago, safety concerns were raised with Spiriva inhalers. Although the FDA has since said that recent data do not show a connection between the inhaler and previously reported risks of stroke, heart attack and death, doubts continued to linger in the market.  Additionally, as Spririva is not yet approved for use in asthma, any data that could show efficacy in this indication would potentially be an important step in gaining an additional licensed indication.

It is also worth noting that the total cost of the study was > $5.3 million. Tax payers money was being spent regardless.

And finally, it’s not as if Glaxo don’t pay their dues.  They are a member of the Partnership for Quality Medical Donations (PQMD), an alliance of pharmaceutical companies and humanitarian agencies that works to encourage the donation and timely delivery of appropriate medicines to people in need. They were one of the biggest donors of drugs and emergency medical relief following the monsoon floods that hit Pakistan in August; they have provided in excess of $1 million dollars of drugs to Haiti since the earthquake, more than $2 million to South East Asia. They also helped out following floods in El Salvador, wild fires in California, cyclones in Myanmar and the 2009 earthquake in China.

Should companies be forced to donate product to studies that are of no interest to themselves, or should they be free to spend the money and donate their product where they wish?

Should highly respected medical journals be allowed to single out companies for exercising their right to chose how they allocate their product?

Word on Health would love to know what you think.

In the interests of full disclosure we’d like to point out that none of the companies mentioned in this story are current clients of SRxA.

COPD – E

Word on Health was interested to note that regular use of vitamin E in women over 45 may help decrease the risk of chronic obstructive pulmonary disease (COPD), according to researchers at Cornell University and Brigham and Women’s Hospital. Long-term, the risk falls by approximately 10% in both smokers and non-smokers.

“As lung disease develops, damage occurs to sensitive tissues through several proposed processes, including inflammation and damage from free radicals,” commented Anne Hermetet Agler, of  Cornell University’s Division of Nutritional Sciences. “Vitamin E may protect the lung against such damage.”

Previous research had found that higher intake of vitamin E was associated with a lower risk of COPD, but this is the first time it has been shown that increasing vitamin E intake can prevent COPD.

In this study, nearly 40,000 women aged 45 years and older were randomized to receive either 600 mg of vitamin E or a placebo every other day.  Although fewer women taking vitamin E developed COPD, the supplement appeared to have no effect on asthma.

If results of this study are borne out by further research, clinicians may recommend that women take vitamin E supplements to prevent COPD.

While this may be good news for some, Word on Health reminds its readers that vitamin E supplements are known to have detrimental effects in some people. For example it can cause increased risk of congestive heart failure in cardiovascular disease patients. As such, any future recommendations would need to balance both benefits and risks.

Do you have COPD, or tips for those who are living with the disease?  If so, SRxA’s Word on Health is waiting to hear from you.

Oral Corticosteroids as Effective as Intravenous Dosing in COPD

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States.  It affects more than 6 percent of adults in the US, and accounts for $32 billion in direct health care costs. Each year there are approximately 600,000 hospital admissions for acute exacerbation COPD, making this 1 of the 10 leading causes of hospitalization nationwide.

Systemic corticosteroids are known to be beneficial for patients hospitalized with acute exacerbation of COPD; however, their optimal dose and route of administration has, until now, been uncertain.

According to a new study published in JAMA , despite guidelines recommending use of the low-dose oral route, a higher-dose intravenous route was used in 92% of patients admitted to over 400 U.S. hospitals.

Researchers compared the outcomes of those initially treated with low doses of steroids administered orally to those initially administered high dose intravenous steroids during the first 2 hospital days.

The primary outcome analyzed was a composite measure of treatment failure, defined as the initiation of mechanical ventilation, in-patient mortality, or readmission for acute exacerbation of COPD within 30 days of discharge.

After results were adjusted for various factors including patient, hospital, and physician characteristics, the risk of treatment failure among patients given low doses of steroids orally was not significantly different from those treated with high-dose steroids intravenously. Also, pa­tients treated with low doses of steroids administered orally had shorter lengths of hospital stay and lower costs.

The authors concluded that the use of high dose intravenous steroids does not appear to be associated with any measurable clinical benefit and at the same time exposes patients to the risks and inconvenience of an intravenous line, potentially unnecessarily high doses of steroids, greater hospital costs, and longer lengths of stay.

An editorial in the same journal added that the results “are sufficient to take action to change practice now.”

Or as we frequently say here at Word on Health – less is sometimes more!

Breathing Easy

SRxA is pleased to report that it has been a week of good news for two of the top players in the pharmaceutical industry.

First, GlaxoSmithKline announced that they see little threat of generic competition for their asthma and COPD drug Advair^® (fluticasone propionate and salmeterol inhalation powder) when it comes off patent in the US in 2011.  Noting that “it is very difficult to make a generic version of Advair,” GSK’s CEO, Andrew Witty, told the audience of a JP Morgan healthcare conference that “we are working on the basis of substantial Advair business for the foreseeable future.”

Shortly thereafter, in a separate announcement, the FDA noted that it completed the safety review of Pfizer and Boehringer Ingelheim‘s once daily COPD drug, Spiriva^® (tiotropium bromide inhalation powder) and came to the conclusion that “available data do not support an association” between use of the drug and increased risk of stroke, heart attack or death due to cardiovascular causes.  The safety review was initiated in 2008 after data from a meta-analysis suggested a small excess risk of stroke compared with placebo.

Word on Health hopes that the new year will continue to bring good news for pharma.