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Teleconference Update on Southwest Asia Pneumonia Review

Presenters: William Winkenwerder, Jr., ASD (Health Affairs)
September 09, 2003

(Participating was Dr. Winkenwerder, assistant secretary of defense for health affairs; Dr. Steve Ostroff, CDC; Col. Bob DeFraites, Army Surgeon General's Preventive Medicine Officer; and Col. John Grabenstein, Deputy Director of the Military Vaccine Office.)

 

            Staff:  Okay.

 

            Dr. Winkenwerder is with us.  Just a few ground rules if I might and that is we will be on the record this afternoon the topic is pneumonia.  We will be recording the conversation and we'll post it to the DefenseLink press site later on this afternoon so for everyone's convenience.  I would ask that as you speak if you would identify yourself so that we know who it is that's asking a question or who it is that's speaking.  With that I would like to turn it over to Dr. William Winkenwerder who is the Assistant Secretary of Defense for Health Affairs.

 

            Sir.

 

            Winkenwerder:  Good afternoon ladies and gentlemen.  We have a number of representatives on the phone call today and I thank you for taking the time to join the call.  Joining us also just came on the line I believe is Dr. Steve Ostroff whose the Deputy Director of the National Center for Infectious Diseases at the CDC - Centers for Disease Control and Prevention in Atlanta.  With me here around the table is Col. Bob DeFraites and let me spell that for you it's capital D-E and then capital D then E then capital FRAITES Col. Bob DeFraites who is the Army Surgeon General's Preventive Medicine Officer and Bob is the individual whose spearheading and leading our investigation.

 

            We also have Col. John Grabenstein that's GRABENSTEIN who is the Deputy Director of the Military Vaccine office and as Marianne Coates has noted, Jim Turner from Public Affairs, Marianne Coates and Perry Bishop and Lynn Kukral from the Army Surgeon General's office.

 

            We promised when we last updated the media on this matter to keep you informed of our progress in this investigation and that's our intent today.  It's my hope that through this dissemination of information and what we talk about we can offer you and the public an accurate assessment of what we know and a somewhat improved understanding of what we dealing with and where we hope to go with our investigation.

 

            Before we get into some of the details let me just cover some very important points from the top.  The first is that we do not have an epidemic.  The rates of pneumonia among personnel deployed to Southwest Asia in the past six months are consistent with what we would have expected and we have data that strongly supports that.  We've had approximately 100 cases and Col. DeFraites will go into this out of several hundred thousands of service members who've been deployed to that area of the world since March - between March 1 and the end of August.

 

            The second point is there's no evidence of SARS involvement in any of these cases.  The third is that those points noted, we do have cluster of 19 cases of severe pneumonia and we have learned something about these cases that we find interesting and it's a leading point of our investigation.

 

            The first point is, is that four cases can be explained by known agents and known causes in a couple of cases, usual cases, and in a couple cases less common and I'll have Bob DeFraites talk about that.  And then there are 10 of the 19 cases that are associated with eosinophilia and for the non-clinical people in the audience here let me spell that.  It's eosinophilia - eosinophilia, which is an elevation of a blood component.  It's one of the components in everyone's blood like white blood cells or red blood cells or so forth.  But it's a blood component that associated with when it is elevated with allergies sometimes with parasites and sometimes with certain other exposures but generally not bacteria or viruses.

 

            The final point and Bob will go into more detail on this.  There appears to be an association with an onset - a recent onset of smoking.  The fourth point in all of this is that we're working closely with the CDC and I'll ask Steve to talk about that relationship.  They've been very helpful in supporting our investigation and reviewing our findings.

 

            And then finally we believe although we don't have all the answers we would like to have at this point that we're making good progress with this investigation, certainly able to better characterize what we're dealing with than we were two or three weeks ago.

 

            So with that let me - let me stop and turn over to Col. DeFraites to really get into some of the more detail here.

 

            Bob.

 

            DeFraites:  Yes.  Thank you everyone.  This Col. Bob DeFraites.  As Dr. Winkenwerder already mentioned the study of this pneumonia problem or issue in the CENTCOM area started around the first of July and now we're well advanced in our understanding of what this phenomenon represents.

 

            As he mentioned we're up to 19 cases of what we have termed more severe pneumonia and what that means is that the patient has a pneumonia which is a, you know, a diagnosis that a doctor makes based on examination of the patient and x-ray findings.  And this pneumonia in our cases is - involves both of the lungs and so it's both sides and also it's severe enough to require that the patient be required ventilator support so he needs to have a respirator or a ventilator to support his breathing.

 

            And since March 1, we've had 19 of these cases that have been identified throughout the area that we call the central command area of operations, so that's most of Southwest Asia, horn of Africa and South Central Asia.  The cases have been - of the 19, 17 have been treated and recovered and two have died.  The last admission of a case was on the 20th of August, and that patient has recovered and has been discharged from the hospital, so currently we don't have any patients with the severe pneumonia in any of our hospitals at present.

 

            There are 18 men and 1 women, there are 17 soldiers, one sailor - so one Navy person - and then one Marine.  Thirteen of the cases were in Iraq at the time they became ill and the other six were in other areas of the - of other countries in the CENTCOM area, Kuwait, Qatar, Uzbekistan and Djibouti.  There was only one patient each admitted from Qatar, Uzbekistan and Djibouti and there were three from Kuwait.

 

            There's no evidence of any spread of this illness from one person to the other.  These 19 cases were spread out over the six months from March through the end of August and spread throughout the countries of that broad area, the world as I mentioned.

 

            As Dr. Winkenwerder already mentioned you know one of our focuses of our study has been on looking for causes and we found infectious causes because, pneumonia can be caused by infectious disease agents such bacteria, viruses, fungi, parasite and it also can be non-infectious.  And we found so far in our study - we've found the cause what we believe to be infectious cause in four other cases.  Two of them were infected with a very common cause of pneumonia around the world called streptococcus pneumonia or otherwise known as the pneumococcus.

 

            One other soldier became ill with what's called Q fever that's caused by a bacteria called coxiella burnetti otherwise known as Q fever and one other soldier was infected with what's call - a bacteria called acinetobacter baumannii for those who are interested in that.

 

            Again I think one of the interesting things about these cases is the sporadic nature of their occurrence.  Previously I think we had mentioned before how no two of these soldiers that were ill were from the same unit, well since these additional cases that have occurred in August, a second soldier from a unit from which a soldier earlier had come was found.  So we've had just two cases that have come from the same battalion but those where two cases occurred about four months apart.  So again, it lends credence to our earlier conclusion that there was no evidence for person-to-person transmission or spread of this pneumonia because of the sporadic nature of it.

 

            Aside from the four cases that we have infectious cause identified or at least presumably infectious cause identified.  The other interesting finding has been the finding of this eosinophilia that Dr. Winkenwerder already spelled for you found in ten of our 19 cases.  The eosinophilia sometimes was found in some of these 10 cases in the circulating blood on a blood test.  The eosinophils, which are normally found in very small numbers in everyone were found in higher numbers than one would expect - you know in a usual course of an illness.  In some cases, a limited number of cases, we recovered the eosinophils from fluid that was actually extracted from the lung in a procedure called a lavage, sort of lung lavage, so a patient - because they were intubated or on the ventilator there was access to their lungs and these eosinophils were found in their lungs.

 

            The other interesting association with the eosinophilia and again there's a long list of potential conditions that can cause the eosinophilia and we haven't worked through all of those potential causes.  The very interesting association that we're found and then at least eight of these 10 severe pneumonias that have had the eosinophilia there's been the soldier or military person reports recent onset of cigarette smoking since the deployment.

 

            And that finding is something that we're investigating further.

 

            Are we still on?

 

            Voice:  Yeah there's some interference.

 

            DeFraites:  Shall I continue?

 

              Now as we had mentioned some of the activities that we'd launched in response to this phenomenon we've had two epidemiology consultation teams working - one in Iraq and one in Germany - along with certainly a lot of support back here, gathering this data and looking at the background information, collected a lot of data.  The work is coming to a conclusion in Iraq and most of the focus on additional data analysis and work is going to back here in the United States following up the patients that have already become ill.

 

            We will be looking at following up, calling back in all the patients who have become ill with this severe pneumonia to be reevaluated - in other words, checked again by physicians and some more work being done with those patients.  In addition we are going to be initiating what's called a case control study to study further this association of cigarette smoking and the eosinophilia with the severe pneumonia.

 

            I think I'll stop there and I can get into more details about other things as I respond to questions.

 

            Winkenwerder:  Steve maybe I should to turn to you at this point and just ask you to comment on the CDC's involvement and any perspectives you'd like to share.

 

            Ostroff:  Thank you very much.

 

            Let me just start by thanking Dr. Winkenwerder and the folks from Health Affairs for giving the opportunity to participate in this discussion and I'll keep my comments quite brief so there's ample time for those on the phone to have their questions addressed and answered.

 

            I know last month that there were questions that arouse about why there was not more involvement on the part of the Centers for Disease Control and  Prevention in the investigation of this cluster of cases and I think it's important to point out that we've been engaged in discussions with Health Affairs and with the services on issues related to this investigation even before those types of questions arouse.  I actually wear two different hats in this particular situation both in my role as the Deputy Director of the National Center for Infectious Diseases here at CDC but also as the President of the DoD Advisory Board on Public Health and Medical Issues, which is the Armed Forces epidemiology board.  And as a result even in early July we were engaged in discussions with those that were looking into the circumstances of these cases as to what they may possibly be and how to go about conducting a systematic investigation of the circumstances of these cases and what the possible causes may be.

 

            Our involvement has been multifaceted, it includes having extensive groups of discussions here amongst personnel and both the Infectious Disease components of CDC as well as the non-infectious or the environmental components of the agency where groups of individuals have been discussing what could be a very long differential diagnosis for a pneumonitis or a pneumonia of unknown cause.  And in addition to that there's been a subgroup of the AFEB - the Armed Forces Epidemiologic Board that has been having weekly discussion with our counterparts that are conducting the investigations not only in Washington but also in those in Germany that actually looking at the case records and going into more depth and detail in terms of the laboratory diagnostics.  In terms of the laboratory diagnostics, in addition to that we've actually had an individual from our Environmental Health Center assigned to Walter Reed to work with the group that's actually coordinating the investigation for the last several weeks and he's been serving as a conduit to those that are here that are thinking about and helping to guide the investigations that are being done by DoD personnel.

 

            In addition to that we have also received specimens from a number of the individuals that are part of this cluster.  We have looked at these specimens in both infectious laboratories as well as in the toxicology laboratories looking for potential etiologic diagnosis and we've also been working on thinking through the investigations that Col. DeFraites mentioned both in terms of the types of questions that are being asked, the types of analysis that will be done and the follow up of the ill individuals.  And I have a high degree of confidence in the depth of investigation that is being done to get to the bottom of this particular circumstance and see if we can come up with some answers as to what might be causing this cluster of illnesses and hopefully be able to prevent additional cases from occurring.

 

            What I can say is that there is a high degree of cooperation and collaboration not only here at CDC but also I think with other outside consultants and experts to see if we can get the best science and to discerning exactly what may be the cause of these circumstances.  And I think with that I'll close and turn it back over to Dr. Winkenwerder.

 

            Winkenwerder:  Okay thank you so much Steve.

 

            Maybe we'll just turn it over for questions at this point if people have questions that we can try to address at this time.

 

            Falco:  I've got a question, Mariam Falco from CNN.

 

            Winkenwerder:  Okay.

 

            Falco:  Actually I have a couple.  I always have a couple.

 

            Number one.  You've explained what you think four patients have had and 10 others  - that leaves out five more.  What do you know or what don't you know about those?  And you made a point about the smoking.  Are you talking about that the lungs are weakened because of the smoking or is there something in the cigarettes.  Why is that so significant?  And of those folks you said no body is hospitalized anymore who have survived.  Are they back on the job in the theatre?

 

            That's it.

 

            Staff:  That sounds like three questions.

 

            The first was the gap between the sort of the explained or associated - the four infectious cases, the 10 eosinophilia and what's the difference.

 

            DeFraites:  Right.  I think I got it.

 

            This is Col. DeFraites again.

 

            As I mentioned we have a known infectious - well at least a presumptive infectious cause for four of the cases, then 10 of them we have a - this eosinophilia connection.  The others fit into the category of just a - what I would consider a more severe pneumonia that for whatever reason we have yet to find a known infectious cause.  I would like to caution though in general, it's not uncommon for a cause - infectious cause especially or a known cause not to be found, so it's not all that surprising even at the end of the day which we're not finished yet but even at the end I wouldn't be a bit surprised if we weren't able to really come down with a definite cause and affect relationship for each one of these cases.  That would be - that would exceed my wildest expectations.  I hope we can but I wouldn't be a bit surprised if we ran a little short of that.  And that would not be totally unexpected either because you know pneumonia is a very common condition in the United States.  If you look at the rates of pneumonia in the general U.S. population that we looked at it sort of correspond to the same age groups as the active duty force so those people between the age of 15 and 45 in the year 2000, which is the last year that we had data we were able to look at for the U.S. population about - is about 10 patients out of every 10,000 citizens that are admitted for pneumonia every year.  And most of these never have a none cause and affect - a known cause for their pneumonia.  For the most part physicians when faced with a patient with pneumonia presumptively treat that patient as if they had the condition for which they have a good treatment which is antibiotics for a bacteria pneumonia and for the most part, thank goodness, the patient responds and recovers whether they had a bacterial infection or not that's the usual standard of care, a mode of practice.  And that's sort of been our approach with these patients to as we give them the best of care and now we're looking back to see if we can identify a cause so it's going a few extra steps for these 19 cases and we're not finished yet, we're still going to look as hard as we can to come up with that diagnosis but we may not come up with a specific cause for each one of the cases.  I'd love to have one.

 

            Winkenwerder:  I think the other question related to smoking.  What about the smoking?

 

            DeFraites:  What we're thinking - our current thinking about smoking in terms of what  - the interesting connection and I think I may have misspoke before, I think I said at least eight of 10 of these eosinophilia cases were recent-onset smokers.  The real number is nine, so its yeah there's at least eight but the actual number is nine of 10.

 

            And what we think the significance of that is, is that cigarettes, tobacco it is a known lung irritant and we think what's going on here is that it's playing a role in at least sensitizing the lungs and maybe making them more susceptible to pneumonia.  You know why, and that's why it may be a combination of the dessert deployment with the heat, the dust and everything else in conjunction but again like I said, it's just an interesting - it's not a coincidence, it's an association of this recent smoking history with this eosinophilic pneumonitis.  So we don't think it's by chance alone that this is happening and our explanation right now is that there's something - it's a known irritant of course cigarette smoke is a known irritant for lungs and a known risk factor for pneumonia in general.  So it's not that surprising and we think that to some affect it sort of sensitizing the lungs for the pneumonia which then progresses in these cases to be more severe.

 

            And what other question did you have?

 

            Falco:  The other one was, are all those who've recovered have left the hospital are they back on the job in the region?

 

            DeFraites:  Well I know of one case - one of our earlier cases that actually is redeployed back into theatre again but again the rest of them are either on convalescent leave - especially the more recent cases or are back on the job but generally they didn't deploy back into theatre again, just that one I know of.

 

            Winkenwerder:  Other questions?

 

            Kelly:  Yes this Matt Kelly with the Associated Press I have a couple of question too.  Number one could you give us a better lay person's explanation of what these eosinophils are they like white blood cells or are they immune system cells are they substances, what are they?  Number two, with the history of recent smoking among these troops, is there any indication whether they were smoking American cigarettes or Iraqi or local cigarettes, is there a connection there?  And third, on the cases that were definitely infectious, where do the two fatalities fall into there, we're they ones that were definitely infectious?  Were they ones that were undetermined?  Where do they fit in?

 

            Winkenwerder:  Okay, I'm going to turn to Bob on this.  Eosinophils first.

 

            Bob:  Eosinophils are one of the types of white blood cells along with nutrifils, basophils, leukocytes, I mean lymphocytes.  So there one of the classes of white blood cells and they're found in small numbers in everybody and they're elevated in certain conditions, so when I say elevated I mean you find them in higher numbers in the blood with certain conditions so they're one of the white blood cells.

 

            Was there anything else about eosinophils?

 

            Ostroff:  Yes this is Dr. Ostroff I would sort of all so emphasis that you know in terms of Marilyn's question that the eosinophils are not a cause but they are a potential signal as to what the cause of the illnesses may be and in that as Col. DeFraites said that they're one of the types of components of the immune response that tends to be evaluated in certain types of conditions whether they're non-infectious conditions such as allergies or whether they're hypersensitivity types of reactions or in certain types of infections and so the differential in terms of what may cause in excess in the number of the eosinophils is quite a broad differential diagnosis and part of the investigations are to try to winnow through all those various diagnosis and see if one of them fits with this particular situation.

 

            Winkenwerder:   Okay, other questions?

 

            I think there was question about the tobacco smoke or the tobacco - the cigarettes themselves, American or other?

 

            DeFraites:  Oh yes, early on we had some indications that soldiers were and it seems to be a practice of buying locally available cigarettes in Iraq.  It turns out that for these cases we have here for the most part that doesn't seem to be that big of an issue, these smokers are all smoking for the most part American brand procured cigarettes.  A couple of them also and I don't know what the exact number is also locally procured.  It turns out that it's sort of misleading to think of them as quote Iraqi cigarettes unquote because I guess internally tobacco products are repackaged, and packaged in many different you know - under many different brand names so it's difficult to know right off the bat what the origin of the cigarettes.  To call it an Iraqi cigarette would probably not be correct  It's probably better to call it locally purchased or locally procured cigarettes.  But that doesn't seem to be explained majority - that's not the majority of these ten eosinophil cases for the most part they're smoking American cigarettes.

 

            The other thing I think the other question you had was about the fatal cases.  And those two tragic soldiers who died with their pneumonia both of them had features of eosinophilia.  But I'll tell you we haven't completed the study of those two cases yet in terms of really looking at what other factors might have been playing a role in their deaths.  So that's still not quite completed yet.

 

            Winkenwerder:  Other questions?

 

            Altman:  Yeah, this is Larry Altman.  I have several questions.  The first is, there was an outbreak of eosinophilia several years ago in New Mexico and tied into L-tryptophan.  Is there any type of link raised in this one?  Second, I have a further question on those cigarettes, even if they're American cigarettes is there any link to a particular brand or any law that the military gets it's cigarettes that may be different than some where else.  Is there anyway you can track that down?  The third is, do you have any information on the rate of new smokers in the military?  And how high - the fourth one is how high were the eosinophilic counts.  And lastly, has there been any attempt to link it to vaccines in terms of the anthrax vaccine in timing or has there been any link to adenoviruses viruses in terms of virological studies?

 

            Winkenwerder:  The L-tryptophan, Bob?

 

            The L-tryptophan I guess phenomenon with over the counter drugs or supplements several years ago that was also considered - maybe Dr. Ostroff.

 

            Ostroff:  Let me just comment very briefly on that.  Some of you may recall back in the late 1980's there was outbreak of disease that was referred to as eosinophilia myalgia syndrome that was a - for want of a better term a rheumatological condition that turned out to be highly correlated with the use of L-tryptophan dietary supplements.  And we have actually had engaged here in a number of the discussions that we had with DoD, some of the individuals that were involved, not only with that investigation but also with some of our other environmental investigations in which eosinophilia has been somewhat prominent.  The other one that comes to mind is an outbreak in Spain in the 1970's and the 1980's which was due to toxic oil.  And I can pretty well assure you that they're convinced that the constellation of signs and symptoms here particularly the pneumonitis and the pneumonia are so distinctly different than what was seen with the eosinophilia myalgia syndrome and with toxic oil that we're probably not looking at something that's linked and certainly there are questions being asked in the case control studies that Col. DeFraites mentioned that will explore whether or not there's anything else that might be playing a role in terms of dietary supplements and other types of food.  But there seems to be no similarity here to what we've seen with eosinophilia myalgia.

 

            Winkerwerder:  Cigarettes, particular brand, U.S.

 

            DeFraites:  I don't have any information on any particular brands.

 

            Winkerwerder:  Will you be looking at that?

 

            DeFraites:  The information we probably already have it yeah, I'm just not aware of it.  I think we will be looking at that.

 

            Winkerwerder:  Rate of new smokers.

 

            DeFraites:  I don't have the information right off hand.  We're doing a study in a brief survey in theatre to see the incidents of smoking on this deployment since that seems to be the sort of issue.  Certainly in the DoD we're aware that persons when they join the military may take up smoking as part of their growing process, if you will and or culturation into the military, take up smoking either temporarily or unfortunately permanently.  But I don't have those statistics right at hand of what our rate of new smokers may be.  You asked a question about the level or the degree of eosinophilia.  I'll just say normally when we count eosinophils in the blood it's less than 600 cells per micro liter of blood, that's the normal, less than 600.  And these eight patients, now I mentioned 10 patients had some eosinophilia and I also said that it could have been found in the blood or could have been found in the lungs so of the 10, eight of the patients with the eosinophilia had a high eosinophil count in their blood and of those eight the maximum that each one exhibited was between 2,000 and 6,600 compared to a normal of less than 600.

 

            Winkenwerder:  And for the vaccine linkage question we've our folks that evaluate vaccine adverse events and particular the - well, anthrax or smallpox vaccine to look at some data.  And let me turn to John Grabenstein for that.

 

            Grabenstein:  Good afternoon.  Anthrax vaccines in inactivate vaccine, small pox vaccine is a live vaccine that gets at the likelihood of them causing various adverse events.  With anthrax vaccine we've had five years experience in giving the vaccine to over half a million people.  We knew it before hand that the rate of pneumonia in anthrax vaccined people and in anthrax unvaccinated people were essentially the same so our starting point was that this was unlikely.  We then subsequently looked just very recently at the anthrax vaccinees and compared to historic rates and statistically the pneumonia rate is the same.  Similarly for smallpox vaccine historically there's been no association to pneumonia, and we looked again to our recent experience in smallpox vaccines and statistically the rates of pneumonia in the smallpox vaccines is the same as what our expected levels are.  If it was elevated we did of course expect it to be higher.  We also looked at people who got both and they also have statistically the same level of pneumonia occurring so that leaves to conclusion that vaccinations are unrelated.  We then went further and said maybe there - we should look at the time post-vaccination to see if there is any clustering of cases after vaccination and in fact there is not, it is statistically a flat line so all of this boiled together leads us to a conclusion that vaccinations - we have evidence that there is no association between vaccination and pneumonia.

 

            And then the final question of Dr. Altman I believe was regarding adenovirus.

 

            DeFraites:  We don't have all - we haven't tested all of the cases serologically for adenovirus but of those we have some results.  The adenovirus titers have been negative so we really haven't - it hasn't been a lead so far but again we've got some more testing to do but adenovirus doesn't seem to be playing a role here.

 

            Winkenwerder:  Other questions?

 

            Bor:  Yes this Jonathan Bor from the Baltimore Sun, I have well it's really one question.  You had indicated before that the eosinophilic cases can have - just generally speaking can have an infectious or a non-infectious cause but you are assuming that in all of these eosinophilic cases the cause is non-infectious?

 

            Winkenwerder:  The infectious - I'll ask Bob to comment.  The infectious most common thing that, at least the general clinician, clinician I used to be - not the infectious disease specialist that looks for the oddballs but would be a parasitic infection but there might be others, again Bob do you want to comment?

 

            DeFraites:  Yeah in terms of looking for - I guess to answer your first question the way I thought you had asked it first of all is that, yeah, in general we're leaning in these eosinophilia cases to more non-infectious causes.  We had considered parasitic infection for sure but the level of eosinophilia in these cases and also the pattern on x-ray of this sort of bio-lateral (inaudible) - the appearance on x-ray is not what you find in the way that parasites that can cause lung problems in patients who are infected with them, the pattern just does not fit.  And so we really weren't encouraged to pursue that line of investigation much further based on those types of indications.

 

            So, in terms of the eosinophilic connection we're tending to lean more toward non-infectious causes - I guess.

 

            Bor:  And for those of us who are laymen can you give us sort of a general picture as to how non-infectious agents can give rise to pneumonia - just what the process is?

 

            DeFraites:  Right, generally what the sequence of events is, is that there is some kind of irritation or sensitivity where the lung - the air sacks in the lung where oxygen is exchanged become inflamed and so you can - in cases of like a vapor or a chemical or some type of toxin that would sensitize.  Now what would follow then is part of the immune response or the bodies normal response to that is - fluids starts becoming secreted within the lung.  These inflammatory cells like eosinophils or other inflammatory cells start migrating to the lungs to sort of fight this inflammation or causing the inflammation that this toxin sort of incites.  What we're thinking in terms of if you go back to sort of the analogy with smoking and again like I said, this is one of the associations that right now has jumped out at us, it's not the only thing but it's probably the one that's worth talking about is what we're looking at.  And the sequence is, something in the cigarette smoke, and there's a lot compounds, a lot of chemicals in the cigarette smoke that could be blamed for inciting this response in people.  And again the interesting thing to us is the fact that it's happening here in a deployed force so, maybe it's that the soldiers are already set up by the stress of being in a hot environment with some dehydration that makes them more susceptible to the inflammation coming form the cigarette smoke than his body then attempt to respond to this toxin sort of generates this response and maybe goes overboard and causes this problem which the fluid collects in the lungs, when you look at an x-ray when there's fluid defused throughout the lungs, you get this picture on x-ray that we've seen with these cases.  Oxygen becomes harder for the lungs to exchange between the air and the body and the patient becomes, it become harder and harder for them to breathe, they need assistance, they go on the ventilator and that's sort of the.  Now the interesting thing is after treatment, after treatment starts again for the most part that the response is fairly dramatic and fairly soon with support of treatment on the ventilator, with treatment for antibiotics for whatever reason, maybe there's a infection playing back in the background somewhere.  But other treatment that it seems to resolve fairly quickly a matter of just several days.

 

            Unfortunately, very unfortunately tragically for the two who died that didn't happen and that's what were looking at those closer why did that result in a fatal outcome but fortunately for the others the other eosinophilia case they seem to turn around, resolve under treatment fairly quickly.

 

            Ostroff:  This is Dr. Ostroff just one other think that I'd like to mention is that while we've all been all focusing on the eosinophils potentially telling us something about a potential cause for these cases, there are those who continue to remind us that it may not necessarily be that this is telling us about cause but it may be related to some treatment or some therapy that was used to treat these people once they actually became ill because obviously one can have an allergy to a particular type of medication or a particular type of therapy and that is certainly a line of investigation that we can't entirely exclude.  Although I think some of the preliminary data that's been collected from the team that's in the field in Iraq as well as the investigators in Germany suggest that that's probably a less likely cause in that there doesn't seem to be any particular unifying type of treatment that was given to these individuals which might so uniformly result in this type of eosinophilia but I think it's important to emphasis that the investigation certainly remains on-going and we all keep a very open mind to any and all possibilities as to what maybe going on here and I think the other point that mitigates against this being a result rather than having some causal relationship is this as was pointed out this striking relationship to recent onset of smoking.

 

            Winkenwerder:  I think we're - unless there's any other burning question I think we're at about the end our time here.  Bob had one other comment.

 

            DeFraites:  This is Col. DeFraites again, I think we might have mentioned before that we have found some precedent for this situation.  We are aware of two case reports of soldiers who had deployed to the national training center that's in you know Southern California who developed a similar, very, very, almost identical picture with this eosinophilic pneumonia you know back in 1997.  In addition in the medical literature especially from Japan there have been studies that have been published that indicate the connection with the cigarette smoking so that's what we're kind of basing some of our lines of investigation are kind of based on this precedent that's been set before so I just wanted to remind you I think we may have mentioned this before but.

 

            Falco:  Mariam Falco from CNN I have one quick question because although this is a phenomenon from March until the end of August of this year.  We had soldiers in theatre, in that general theatre for a while who presumably have been smoking cigarettes as well.  Do we have any data prior to this that indicates how many cases of pneumonia from various sources may have occurred?  And is this something that might be the soldiers and the one Marine and the one sailor was in a location that was extremely uninhabitable.  You wouldn't normally find Iraqis there or wherever?  I mean I'm trying to find more than just the precedent you just listed from 1997, which I hadn't heard about?

 

            Winkenwerder:  I think the answer to the last question is no.  These people were not in places that other people were not either Iraqis or American soldiers, lots of people were in these areas.  Bob, do you want to comment?

 

            DeFraites:  Yeah that's a very good question about what is our past history with this phenomenon.  We have information on at least the rates, you know we look back at our information from Dessert Storm and Dessert Shield again it's a slightly different season because you were talking about Saudi Arabia from August through - for Dessert Shield, August through January or February and then Dessert Storm February through maybe July.  Slightly different area but the rate of pneumonia overall rate is remarkably - I think the figures we saw - I know what the figures were 8.6 cases per 10,000 soldiers per year.  And as I mentioned our reference rate in the Army is 9 case per 10,000 per year so it's very similar to what we're seeing.  Overall pneumonia -what we're not able to extract is whether or not is this whole question of eosinophilia -we just don't have the data and that level of detail where we can go back and extract, did they have a blood count done and did it have a high eosinophil account.  Right now the level of information that we have on those cases treated that way, we just don't have that level of detail.  We're still looking to see if we can find more information.  I'll tell you we've had a lot of help from people writing in and calling who have had similar situations you know from all over the country since this we first talked about this last month.  Yet I have not heard from anyone whose served medically in Dessert Shield, Dessert Storm that's talked about a similar eosinophil pneumonitis in their experience.  I didn't have the benefit of deploying as a doctor to Dessert Storm but I have not heard from any that did.  So the one thing that we have certainly here and it really is one of the factors that called this situation to our attention in the first place aside from the two tragic fatalities was the fact that all of these cases were going through Landstuhl Regional Medical Center in Germany and having a few patients in the intensive care unit with the same condition at the same time brought it somewhat  - to helped to bring it to our attention and that may not have been - certainly there were a lot more hospitals deployed in the theatre for Dessert Shield than we had now so it may have been disbursed but yet know one has come back and said that they had a similar situation.  Is it something to do with the - certainly most of the eosinophilia cases and most of the cases we've had just to look back at the few months we had two in March, two in April, only one in May and then we had six in June, four in July and four in August so certainly in  most of these eosinophilia cases occurred in the summer it may well be - yeah it gets hot in Saudi Arabia but the fact that the majority of the troops in Saudi Arabia for Dessert Shield and Dessert Storm were not there for the full season, the full heat of the season may have a lot to do with it, the fact that they showed the troops.  The troops started showing up in August of 1990 and most were gone before the next summer. 

 

            Winkenwerder:  We'll learn something as this continues.  Let me just close because I think at the end of our time.

 

            Bor:  I had one question.  I'll be real quick.  You had referred early to the severe cases as a cluster so by that do you mean that the rate as it were it was higher than average or what you would expect.  In a similar population elsewhere but that there's no apparent you know common links to these cases?

 

            Winkenwerder:  The overall rate of pneumonias that we've seen is consistent with what we've would have expected for overall pneumonias but the cluster I'm referring to is in these 19 cases that all required ventilator support that were more severe, two of which died and the other 17 or the whole group of which Bob has characterized. 

 

            Let me just close by making a couple of comments.

 

            Again this investigation is very important to us and I have directed Bob and those associated with this team and John and others to exert all efforts to find the answers.  We're committed to finding the answers.  We believe we've made some important progress and that's what we've shared with you today.   We believe we've been able to say pretty definitively a number of things about what this is not and begin to put our arms around what we think this might be.

 

            But as all have said, more work needs to be done.

 

            We appreciate your interest in this and your desire to get this information out.  Obviously for family members and for others who have family and loved ones in that part of the world serving, I think it's important to be able to characterize this as accurately as we can and you can certainly help in that regard.

 

            So thank you very much and we appreciate you being part of the call.

 

            Altman:  Is there anyway we can get the references to those previous cases that you referred to or can you fax the papers?

 

            Winkenwerder: Yeah we can give you the references.

 

            Altman:  Well it would be hard to look them up if you can fax the actual paper it would be a lot easier.

 

            Staff:  Who is that speaking?

 

            Altman:  Larry Altman

 

            DeFraites:  Yeah I think we can get those to you.

 

            Altman:  If you call back I'll give you a fax number.

 

            Winkenwerder:  Okay great.

 

            Thank you.

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