Link

Just curious why there is a new substance that Dr. Sears looks into now after mercury… aluminum.  Anyone have any insight into why the FDA puts a restriction yet many vaccine contain aluminum?

Is Aluminum the New Thimerosal?
By Robert W. Sears
Issue 146, January/February 2008

Vaccines have become the most controversial parenting topic of the decade. When parents are considering whether or not to vaccinate their children, one of the things that must be considered is aluminum toxicity.

Aluminum is added to a number of vaccines to help them work better. Normally, one wouldn’t consider aluminum to be a problem. It’s a naturally occurring element that is present everywhere in our environment—in food, water, air, and soil. It’s also a main ingredient in over-the-counter antacids. And because the body doesn’t absorb aluminum, it’s harmless when swallowed.

I didn’t think much about aluminum when, 13 years ago, I began researching vaccines. In fact, the early seminars on vaccine education that I offered to parents included a brief statement that aluminum was nothing to worry about. But as I read each product insert and saw the number of micrograms (mcg) of aluminum contained in several vaccines, I wondered, “Has anyone determined what a safe level of injected aluminum actually is?” I didn’t have to wonder for long, because the answer is easy to find; go to www.fda.gov, search on “aluminum toxicity,” and you’ll find several documents about aluminum.

The first document I came across discusses the labeling of aluminum content in injected dextrose solutions (the sugar solutions added to intravenous fluids in hospitals): “Aluminum may reach toxic levels with prolonged parenteral administration [i.e., injected into the body] if kidney function is impaired. Research indicates that patients with impaired kidney function, including premature neonates [i.e., babies], who received parenteral levels of aluminum at greater than 4 to 5 micrograms per kilogram of body weight per day, accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading [i.e., toxic buildup in certain body tissues] may occur at even lower rates of administration.”¹ For a tiny newborn, this toxic dose would be 10 to 20 mcg; for an adult, it would be about 350 mcg.

The second document discusses aluminum content in IV feeding solutions, or Total Parenteral Nutrition (TPN) solutions. The FDA requires these solutions to contain no more than 25 mcg of aluminum per liter of solution. A typical adult in the hospital would get around 1 liter of TPN each day, thus about 25 mcg of aluminum. The FDA document also states, “Aluminum content in parenteral drug products could result in a toxic accumulation of aluminum in individuals receiving TPN therapy. Research indicates that neonates and patient populations with impaired kidney function may be at high risk of exposure to unsafe amounts of aluminum. Studies show that aluminum may accumulate in the bone, urine, and plasma of infants receiving TPN. Many drug products used routinely in parenteral therapy may contain levels of aluminum sufficiently high to cause clinical manifestations [i.e., symptoms]. . . Aluminum toxicity is difficult to identify in infants because few reliable techniques are available to evaluate bone metabolism in premature infants. . . Although aluminum toxicity is not commonly detected clinically, it can be serious in selected patient populations, such as neonates, and may be more common than is recognized.”²

Elsewhere, I found a relevant 2004 statement by the American Society for Parenteral and Enteral Nutrition (ASPEN), a group that monitors oral and injectable nutritional products for safety and side effects. It reiterated the cited FDA warnings to the letter, and recommended that doctors purchase IV products with the lowest aluminum content possible, “and should monitor changes in the pharmaceutical market that may affect aluminum concentrations.”³

The source of the daily limit of 4 to 5 mcg of aluminum per kilogram of body weight quoted by the ASPEN statement seems to be a study that compared the neurologic development of about 100 premature babies who were fed a standard IV solution that contained aluminum, with the development of 100 premature babies who were fed the same solution with almost all aluminum filtered out. The study was prompted by a number of established facts: that injected aluminum can build up to toxic levels in the bloodstream, bones, and brain; that preemies have decreased kidney function and thus a higher risk of toxicity; that an autopsy performed on one preemie whose sudden death was otherwise unexplained revealed high aluminum concentrations in the brain; and that aluminum toxicity can cause progressive dementia. The infants who were given IV solutions containing aluminum showed impaired neurologic and mental development at 18 months, compared to the babies who were fed much lower amounts of aluminum. Those who got aluminum received an average of 500 mcg of the metal over a period of 10 days, or about 50 mcg per day. The other group received only about 10 mcg of aluminum daily—4 to 5 mcg per kilogram of body weight per day.⁴ This seems to be the source of this safety level.

However, none of these documents or studies mentions vaccines; they look only at IV solutions and injectable medications. Nor does the FDA require labels on vaccines warning about the dangers of aluminum toxicity, although such labels are required for all other injectable medications.

All of these studies and label warnings seem to apply mainly to premature babies and kidney patients. What about larger, full-term babies with healthy kidneys? Using the 5 mcg/kg/day criterion from the first document as a minimum amount we know a healthy baby could handle, a 12-pound, two-month-old baby could safely receive at least 30 mcg of aluminum per day. A 22-pound one-year-old could receive at least 50 mcg safely. Babies with healthy kidneys could probably handle much more than this, but we at least know that they can handle this much. However, these documents don’t tell us what the maximum safe dose would be for a healthy baby or child, and I can’t find such information anywhere. This is probably why the ASPEN group suggests, and the FDA requires, that all injectable solutions be limited to 25 mcg; we at least know that that level is safe.

Calculating Aluminum in Vaccines
Here are the current levels of aluminum per shot of the following vaccines, as listed on each vaccine’s packaging:

• DTaP (for Diphtheria, Tetanus, and Pertussis): 170-��625 mcg, depending on manufacturer
• Hepatitis A: 250 mcg
• Hepatitis B: 250 mcg
• HIB (for meningitis; PedVaxHib brand only): 225 mcg
• HPV: 225 mcg
• Pediarix (DTaP-��Hepatitis B-��Polio combination): 850 mcg
• Pentacel (DTaP-��HIB-��Polio combination): 330 mcg
• Pneumococcus: 125 mcg

In other words, a newborn who gets a Hepatitis B injection on day one of life would receive 250 mcg of aluminum. This would be repeated at one month with the next Hep B shot. When, at two months, a baby gets its first big round of shots, the total dose of aluminum could vary from 295 mcg (if a non-aluminum HIB and the lowest-aluminum brand of DTaP are used) to a whopping 1225 mcg (if the Hep B vaccine is given along with the brands with the highest aluminum contents). These doses are repeated at four and six months. With most subsequent rounds of shots, a child would continue to get some aluminum throughout the first two years. But the FDA recommends that premature babies, and anyone with impaired kidney function, receive no more than 10 to 25 mcg of injected aluminum at any one time.

As a medical doctor, my first instinct was to worry that these aluminum levels far exceed what may be safe for babies. My second instinct was to assume that the issue had been properly researched, and that studies had been done on healthy infants to determine their ability to rapidly excrete aluminum. My third instinct was to search for these studies. So far, I have found none. It’s likely the FDA thinks that the kidneys of healthy infants work well enough to excrete aluminum before it can circulate through the body, accumulate in the brain, and cause toxic effects. However, I can find no references in FDA documents that show that using aluminum in vaccines has been tested and found to be safe.

So I did what any pediatrician would do. I turned to the American Academy of Pediatrics (AAP), who in 1996 published a policy statement, “Aluminum Toxicity in Infants and Children,” that made the following points:

• Aluminum can cause neurologic harm.
• A study from 30 years ago showed that human adults increase their urine excretion of aluminum when exposed to higher levels of the metal, which suggests that adults can clear out excess aluminum.
• Adults taking aluminum-containing antacids don’t build up high levels of aluminum in their bodies.
• Reports of infants with healthy kidneys show elevated blood levels of aluminum from taking antacids.
• People with kidney disease who build up bloodstream levels of aluminum greater than 100 mcg per liter are at risk of toxicity.
• The toxic threshold of aluminum in the bloodstream may be lower than 100 mcg per liter.
• The buildup of aluminum in tissues has been seen even in patients with healthy kidneys who receive IV solutions containing aluminum over extended periods.⁵

However, nowhere in this paper was there any mention of aluminum in vaccines.

To put this in perspective: Because the body of the average adult contains about 5 liters of blood, receiving more than 500 mcg of aluminum in the bloodstream all at once will be toxic if the kidneys aren’t working well. (Toxicity has also been seen in patients with healthy kidneys.) Because a newborn’s body contains about a liter (300 milliliters) of blood, more than 30 mcg of aluminum floating around in the bloodstream could be toxic if the baby’s kidneys aren’t working well. The body of a toddler or preschool-age child contains about 1 liter of blood, so more than 100 mcg in his system could be toxic—and, as we’ve seen, babies can receive more than 1000 mcg of injected aluminum all at one time. Fortunately, this amount doesn’t all go into the blood at once, but is slowly diffused into the bloodstream over a period of time from the muscle or skin where it was injected.

But that is the main point of this article. No one has measured the levels of aluminum absorption by the bloodstream when it is injected into the skin and muscle of infants, or the levels of excretion from the body via urination. All of the FDA and AAP documents that I’ve read state that aluminum might be a problem, but that they haven’t studied it yet, so we should limit the amount of aluminum included in injectable solutions. But, again, no one is talking about the levels of aluminum in vaccines.

What I think may have happened is that because aluminum used to be found in only one vaccine—DTP, an older version of the current DTaP vaccine—no one thought much about it. Then, in the 1980s, the PedVaxHib brand of HIB meningitis vaccine was released, which also included aluminum; but other brands of HIB vaccine did not, so again, no one thought much about it. In the 1990s, the Hepatitis B vaccine began to be widely used; in the 2000s, the Pneumococcus vaccine; and, more recently, the Hepatitis A vaccine. Administering one aluminum-containing vaccine at a time involves only a small amount of the metal; administering four such vaccines simultaneously is a different story. It seems this issue has simply escaped everyone’s attention. Or has it?

Limited Studies limit thinking
Several years ago, some suspected cases of aluminum toxicity resulted in various neurologic and degenerative problems. The Cochrane Collaboration, a group that studies health-care issues around the world, wanted to look at a very large study group to see if there was a real correlation between neurologic problems and the aluminum in vaccines. They investigated all the reported side effects of one aluminum-containing vaccine, DTP (no longer used), and looked for any evidence that such vaccines caused more side effects than non-aluminum vaccines. Other than more redness, swelling, and pain at the injection site, they found no indication that an aluminum-containing vaccine caused any more problems, and concluded that no further research should be undertaken on this topic.⁶ That is a very bold statement. Most researchers will draw conclusions from the findings of their own research; it’s unusual to say that no one else should do any more research into the matter.

This is especially surprising because of the limitations of the Cochrane Collaboration’s study. They looked at the effects of only one standard aluminum-containing vaccine, rather than the effects of all four being administered at once. They didn’t study aluminum metabolism itself. They didn’t test aluminum levels in children after vaccination, nor did they explore whether or not the amount of aluminum in vaccines builds up in the brain or bone tissues. They looked only for evidence of external symptoms of aluminum toxicity, not internal effects. Nor did they do their own research; instead, they reviewed all available studies conducted by other investigators. Despite all this, the Cochrane Collaboration study essentially closed the book on investigating aluminum toxicity from vaccines, without really having opened it in the first place.

The most obvious way to study this matter would be to inject various amounts of aluminum into children and see what happens to them internally. We know from the FDA documents that aluminum toxicity does occur from other types of injectable treatments; that it accumulates in the brain and bones in toxic amounts; that this may occur more commonly than is recognized; and that aluminum toxicity is hard to detect by looking for external symptoms. The question remains: What happens when these amounts of aluminum are injected via vaccines? Vaccine manufacturers may have begun to wonder about the same thing; I found some interesting research in the product insert of the new HPV vaccine, Gardasil. In researching the safety of Gardasil, Merck & Co., Inc., the vaccine’s developer and manufacturer, added a step to their testing procedure by injecting aluminum into a separate group of test subjects used as a safety control group. They then compared the side effects of the Gardasil vaccine with a saline placebo that contained neither Gardasil nor aluminum, as well as with the placebo containing no Gardasil but the same amount of aluminum as the vaccine. They found that the placebo containing aluminum was much more painful than the saline placebo, and about as painful as the full HPV shot. The aluminum placebo also caused much more redness, swelling, and itching than the saline placebo, though not quite as much as the full HPV shot.

Unfortunately, Merck looked only at the effects of aluminum at the injection site. Nor did they state in the Gardasil product insert what role the aluminum placebo played in all the other standard side effects, such as fever and flu-like symptoms. Nor did they study the body’s internal metabolism of aluminum. However, their research did show how irritating aluminum can be when injected into the muscles. It was a good first step. If aluminum can be toxic, why not just remove it from vaccines, as is being done with the preservative thimerosal, which contains the neurotoxin mercury? It’s not that simple. Aluminum is an adjuvant; in other words, it helps vaccines work more effectively. When the metal is mixed with a vaccine, the body’s immune system more easily recognizes the vaccine and creates antibodies against the disease. Thimerosal was easy to omit, because it has nothing to do with the efficacy of the vaccine itself. But the pharmaceutical companies would need good evidence that aluminum is harmful before they would invest in coming up with new, aluminum-free vaccines. (The Cochrane Collaboration report pointed out that removing aluminum from vaccines would then require extensive trials of the reformulated vaccines.⁷)

What, exactly, does a toxic level of aluminum do to the brain? While no one has studied healthy babies to see how much, if any, aluminum builds up in the brain from the amounts of aluminum used in vaccines, the study on IV feeding solutions in premature babies mentioned above revealed that aluminum impaired their neurologic and mental development.⁸ But that was in premature babies, not healthy, full-term infants. I found several animal studies involving aluminum and/or aluminum-containing vaccines that did show neurologic harm. Not only did aluminum build up in the brain and cause damage, but some of the damage looked similar to what is seen in the brains of Alzheimer’s patients.^9-1314 However, it’s hard to draw conclusions about aluminum’s effects on humans from studies of animals. What we need are more studies of human infants.

A Call for Better Research
There is good evidence that large amounts of aluminum are harmful to humans. Because no meaningful research has specifically been done on aluminum in vaccines, there is no existing evidence that the amount in vaccines is harmful to infants and children. However, no one has actually studied aluminum levels in healthy human infants after vaccination to make sure it is safe. Should we now stop and research this matter? Or should we just go on, continuing to hope that it is safe to use aluminum as an adjuvant in vaccines?

Vaccine policy makers and advocates may read this article, review my perspective, and initiate research studies to explore the risks of aluminum. I would hope that those researchers do not conduct a retrospective review of all the old vaccine safety studies and journal articles to look for the side effects of aluminum. As the FDA, AAP, and others have stated, aluminum toxicity can’t be detected by external observation alone. It would be a waste of time, and a grave disservice to the health of America’s children, to have several such reports show up in the medical literature. The only way the issue of aluminum safety can be put to rest is to conduct real-time studies on thousands of infants and measure aluminum levels after vaccination.

In such a study, the researchers should look not only at blood levels. They should also find out whether or not aluminum accumulates in the body, where it accumulates, how the body eliminates it, and at what rate. Once I see such research, and have determined to my satisfaction that aluminum has been proven safe, I will post an update on www.thevaccinebook.com, and revise future editions of the book accordingly. If such research finds that aluminum may not be safe, then I would expect a new vaccine schedule to be adopted in which the administering of vaccines is spread out to minimize the amount of aluminum a child receives at any given time. I would also expect vaccine manufacturers to begin finding ways to reduce or remove aluminum from vaccines without compromising their effectiveness. We need to know the answers to many questions: Why does one brand of HIB vaccine require aluminum to make it work while another brand does not? Why does one brand of DTaP vaccine contain four times as much aluminum as another?

Learning from the Past
I worry that aluminum may end up being another thimerosal. I am relieved that, as of 2002, the mercury-containing preservative had been removed from most vaccines. But according to an article in the Los Angeles Times, Merck & Co., the makers of several vaccines, knew in 1991 that the cumulative amount of mercury in vaccines given to infants by six months of age was about 87 times the level then thought to be safe.14 The article includes a copy of an internal memo, written by one of Merck’s research doctors and sent to the president of Merck’s vaccine division, clearly stating the doctor’s worry about mercury overload. What was done with that information back in 1991? We’ll never know. What we do know is that vaccine manufacturers knew that we were overdosing babies, but that the mercury wasn’t removed from vaccines until 10 years later. This was because few paid attention to the potential problems with mercury. When we did find out, we hoped it wasn’t harmful, we did extensive research to try to show that it wasn’t, and we slowly removed it from most vaccines.

The issue of mercury toxicity from vaccines is moot for infants receiving vaccines today, as long as doctors and parents choose a flu shot without mercury, know which brands of vaccines still contain barely detectable traces of mercury, and are aware that some plain Tetanus and Diphtheria-Tetanus vaccines still contain mercury (though these last vaccines are not parts of the routine vaccine schedule). [For a current list of vaccines and their thimerosal contents, go to www.vaccine safety.edu/thi-table.htm.—Ed.]

What isn’t moot is the question of aluminum toxicity. As doctors, we can choose certain vaccine brands that contain less or no aluminum. We can be careful about giving only one aluminum-containing vaccine at a time. And we can talk about it instead of sweeping the issue under the rug. I pray that my fears about aluminum are unfounded, and that objective studies performed by completely independent groups with no ties to vaccine manufacturers or political organizations show that it is safe. If not, I would hope that manufacturers would start to reduce or eliminate the aluminum content of their vaccines as soon as possible. I know this won’t be an easy task, but our children are worth it.

Excerpted from The Vaccine Book � 2007 by Robert Sears, MD. Reprinted by permission of Little, Brown and Company. New York, NY. All rights reserved. For more information, see www.thevaccinebook.com. For the notes to this article, see www.mothering.com/ articles/growing_child/vaccines/aluminum-new-thimerosal-notes.html.

And only revisited because Blonde Pharmacist is now a new mother.  Wow is all I can say.  Thus the reason I haven’t been on in awhile.  I ended up having a wonderful labor and delivery - requested an epidural at 8 cm and then immediately after was 10 cm…  this is the way to do it ladies…  though 6 and 7 cm contractions are intense.  Unfortunately the baby was whisked off to the NICU where he was given surfactant and put on a cpap and a week of oxygen, etc…  He’s fine now and at home.  I wonder how much pharmacy knowledge I’ll lose during this time.

Wish me luck!

Now I have to actually worry about vaccines and wonder if there are any effects on little man.  I opted out of the engerix (hepatitis B) vaccine since he’s not having sex, shooting up drugs, or has a mother with it.  Any thoughts from the medical community (blogging community) on what to do at the first round of vaccines at the 8 week appointment?

Without getting too personal about my own life, I have had the opportunity to be involved with a family member staying in the hospital for a week.  During this time I have found the general perception of pharmacists, especially hospital, to be against the nurses.  When one of the nurses (a newly graduated one in fact) made a joke about “being on hold for the pharmacist in the in-patient pharmacy because she hadn’t received her IVs ordered” another nurse told her to go check a box that was received.  She was on hold for the pharmacist and then just abruptly hung up.  Yep, the pharmacists had sent it in fact, and I smiled on the inside.  Not that pharmacists forget or don’t follow through sometimes… it’s just that the general perception is that we do all the time… nahhhh…

Another thing that I have watched is that nurses really can make a difference in patient care more than any other discipline.  Not only are they touching the patient, assuring them, etc…  They can go the extra mile.  I had one nurse who was wonderful, another who was not and wanted to blame someone else… and I’m an easy patient.  Just think about all the things you don’t even have to explain to me.  I won’t ask many questions though I want to read the chart all the time…  it’s hard to talk them into that.

Apparently I’m flagged though because they all know I work for the same company that owns the hospital.  That has helped!  I will return!

Merck back on the hot seat with possible connection between Singulair and the risk of suicide. 

Impaired Sense of Smell May Be A First Indicator of Parkinson’s Disease

Superbug MRSA Spreading

Disposing of Medications in an Environmentally Friendly Way

My mouth just dropped open.  It’s obvious to me that physicians do NOT read medication reconcilliation forms for home meds at all.  The ones that do, kudos, but the ones that don’t make my job more interesting and at times really get to me.

Case-in-point:  50-something presenting to the hospital with lower GI bleed.

The doctor signed off to CONTINUE HER HOME MED OF PHENTERMINE FOR WEIGHT LOSS.  Are you kidding me? 

I guess the nurse could have written “Purina Dog Chow - take one cup by mouth daily” and the physician would have signed off on it.

Way to go Joint Commission on putting in a requirement with no means of adhering to any sort of THINKING for anyone involved.

 Except for the pharmacist of course to wade through the BS and find what is really needed.

Well I had a pingback in my email this morning from The Angriest Pharmacist.  Somehow he views my post as “another enemy” and “cheap shot.” 

Gosh, not hardly.  My post, if you read it is what you would label as satirical sarcasm…. in other words, how deep does this rivalry go?  Apparently deep at the reaction I received from him.  Yes, I rank low (sorry guys and gals, I don’t blog for anyone but myself really, and I know I know… that’s a bad blogger, you should really think of your audience when blogging ;)).  Yes I post things that are boring to most of you… but there’s are a few of us that keep up with FDA stuff…  No, I’m not quite as witty and angry.  I don’t have customers or patients yelling in my face.  I’m not in a rivalry with The Red Pharmacist, The Brunette Pharmacist, or heck even the other female pharmacists out there.  Who has the time really?  Dakota Fanning is cute

But anyway, suffice it to say the Angry, Angriest, Anger, and so forth runs deep in the pharmacy blogosphere.  LOL  You can’t really drag the Blonde into it.  Because really insults and rankings don’t really bother this one.  In fact, it just made me smile this morning on a long ten hour day… of course, I’m kicked back in my PJs, reading the paper, eating some Cocoa Puffs, and getting ready to log into some hospitals to do my job for the next ten hours sans any sort of crap from patients demanding a 3 minute turnaround on their xanax refill.

Really Angriest, I’m a fan, not an enemy… I actually read your blog!  I need to come up with the kind of post you COULD interpret as enemy and picking a fight material so that the next time you’ll be able to take off your angry colored glasses and see that in reality this is what you call “jest,” “facetious,” etc…  And the rankings? I graduated from high school many years ago… I really don’t get very motivated by popularity contests, unfortunately. Maybe I WOULD have a better blog if I did!

Oh and just in case my reply to him does not get published:

Blonde Pharmacist says March 26th, 2008 at 7:14 am
Your comment is awaiting moderation.
You are really hilarious. My post is tongue-in-cheek… an enemy? I hardly think so! I think if your readers read my post, they’ll see it’s what you would call facetious, no hardly enemy material… I really don’t mind if there are other bloggers with Blonde in the name… As far as popularity on the net goes? That is yet another thing that doesn’t matter to me. I don’t scour the internet trying to find where I rank, but thanks for letting me know. LOL

What is really funny here is your reaction to a post in jest. I find it funny and ironic that there was even a fight between two bloggers that use different forms of the word angry! It cracks me up actually…

Considering I am not angry enough to really elaborate on a short post noticing the two of you… wondering who came first, the chicken or the egg… I find it even MORE amusing that you inserted your own anger into my post to interpret it as a FIGHT?

A fight? No, sweetie… Blonde Pharmacist isn’t picking a fight. I’m just noticing something that made me chuckle awhile back and thought I’d post about it (for myself) - and then later see who is still left standing in the end. Not that it matters, but more for my own innate curiosity.

Yours truly, Dakota Fanning

I don’t know… is it just me… or maybe it’s the “semi-jacking” of the name that makes me think that perhaps either the attention was GOOD for their ratings (if ratings DO matter) OR is it that a creative, witty, ORIGINAL name (not claiming I have that either) would be more apropos?

Yes, MySpace move over… there’s now an online site for patients with the same afflictions.  Interesting!

There’s nothing worse that grates under my skin as a pharmacist than to drive to a retail pharmacy and find a pharmacist digging in the trenches with a sourpuss expression and basically giving us ALL a bad name.  We’re not ALL miserable.

Here’s a post about waking a retail pharmacist up only to find out she had the wrong drug.

Not that we cannot make mistakes… but please.

U.S. health officials have identified a contaminant in batches of the blood thinner heparin associated with 19 deaths and are trying to determine how the chemical got into the drug.

The lots of heparin, whose key ingredient was imported from China, were recalled Feb. 28, and Food and Drug Administration officials said Wednesday that no new deaths have been reported since that time.

Dr. Janet Woodcock, head of the FDA’s Center for Drug Evaluation and Research, said the contaminant is oversulfated chondroitin sulfate, a chemical that does not occur naturally.

Chondroitin sulfate is a natural compound that occurs widely and is used as a dietary supplement but the oversulfated version has not been widely studied.

”We cannot rule in or out whether this was accidentally or deliberately introduced into the product,” Woodcock said, ”We are investigating how it got in.”

Boehringer Ingelheim and FDA notified healthcare professionals that ongoing safety monitoring has identified a possible increased risk of stroke in patients who take Spiriva. This product contains tiotropium bromide and is used to treat bronchospasm associated with chronic obstructive pulmonary disease. Boehringer Ingelheim reported to the FDA that it has conducted an analysis of the safety data from 29 placebo controlled clinical studies (“pooled analysis”). Based on data from these studies, the preliminary estimates of the risk of stroke are 8 patients per 1000 patients treated for one year with Spiriva, and 6 patients per 1000 patients treated for one year with placebo. This means that the estimated excess risk of any type of stroke due to Spiriva is 2 patients for each 1000 patients using Spiriva over a one year period.