I have had severe asthma since infancy, but the past 1.5 years it has gotten much worse. I am on every asthma medication available, including at least 40 mg of prednisone a day, xolair, and ivig.
my docs are now suggesting trying more aggresive treatments, as my pft's are slowly drifting down and begining to become irreversible.
they are suggesting cellcept, and antirejection drug, or even methotrexate, a type of chemotherapy.
has anyone heard of this type of treatment, and whether or not its very effective? had any side effect of it?
i've read a lot of clinical studies, but they just talk abouit the results, not what they patients felt or went through during treatment.
Methotrexate is used in the UK for severe asthma that is unresponsive to Steroids. (Cyclosporin is also used) People have varying success with it but it also has its own side effects too plus you need regular blood tests. I haven't had it but there are some people here who do use it so they may be able to help more.
Also If you search the archives on these message boards there is some info there.
I am brittle asthmatic, steroid dependent at the mo (grrrr!) and use a subcutaneous infusion of Ventolin (Salbutamol) to help control my symptoms - I don't know if this is used in the US? I haven't had Xolair as my IgE levels are normal so it wouldn't work in me anyway.
Take care
Kate
I have read several case stuides on methotrexate and cyclosporin... they same to have mixed results. I was hoping, as you say, to find someone who had gone through the treatment to see what their side effects were.
They don't use Injectible ventoline - never heard of that - but I will ask my doc.
Thanks for your reply!
Mia
I have had methotrexate and azathioprine and am waiting to start cyclosporin. Over here the first one is methotrexate then some hosp try cyclosporin 2nd then azathioprine but mine do it the other way around!!
When i was on methotrexate once on the effective dose as you have to start with the lowest and build up, her we start on 5 and build up to 15mgs max if its not working by then its unlikely too. As for me as ann add on it worked quite well stabilising me and it did get my steroids down from 30mgs to 17.5mgs but then my kliver dicided enough was enough so it had to be stopped. As for side effects, its a weekly drug and all i noticed was some hair loss, mnot major that you could tell i could tell when washing and brushing etc, and the day after taking i felt generally a bit off like when you hav a cold brewing but the following day was fine again. There are post on here before about it and alot of people were quite frightened by the side effects listed but they are so rare and the more severe ones will probably be caught early as your more aware and your blood is checked regularly.
As Kate said we over here use sub cut terbutaline and salbutamol? maybe worth asking your doc about them, they are iv or sub cut use of our two broncodilators? ( relivers ).
jope this helps
Love Andrea xxx
Hi, My 11 yr old son has been taking ciclosporin as part of asthma meds for 6 months. He has needed bloods taken weekly then fortnightly but results have always been normal but his levelsof drug in blood have dropped at times randomly. The only side effect he has shown is very hairy arms,otherwise ok. On a negative I dont think ciclosporin has done what we were hoping it would, he still needing very high dose oral steriods and has been very unwell for last 3 mth. We are due to see chest consultant on friday and I know he will ask if my son should remain on this drug as it was a six mth trail at first to see results, I really dont know what to decide as I will wonder wether another couple months will help even though i suspect not. My son is also on sub cut bricanyl which to be honest is the only drug (apart from ventolin nebs) that i am convinced works for him.
Good luck in making your decision.
julie x
Hi Mia,
I can understand your concern with these scary-sounding drugs, as a lot of the side effects do sound worrying, but most of them are not as bad as they sound, and the side effects of pred are not exactly easy to cope with!
Methotrexate is being used primarily in this case as an immunosupressive agent, not a chemotherapy drug, although it is a cytotoxic agent too. The two most studied immunosuppressives used as steroid sparing agents are, as Kate says, methotrexate and ciclosporin, and there is a little evidence that they can be effective in some people. Azathioprine is also used although there is less evidence for this. I've never heard of mycophenylate (Cellcept) being used in asthma, although there are a couple of lab based in vitro studies (done on cells) to suggest that it might be useful.
I have steroid dependent Type I brittle asthma, and have been on methotrexate twice, once in 1998 - 99 for about ten months, and more recently from May to September of this year. I didn't notice any side effects except a slight feeling of nausea and loss of appetite the day after taking it (it's usually taken weekly), although I obviously had to be closely monitored whilst on it because of the potential side effects of liver dysfunction and so on. I didn't find it particularly helpful, however, in lowering my steroid dose, although I know that some people do find it useful. In September I had my second episode of Ventilator Associated Pneumonia in 3 months, and at that point my methotrexate was stopped by my consultant in case it was contributing to that - I personally don't think that it did contribute to me getting pneumonia, but I was happy to stop it on the grounds that the risks outweighed the benefits, as I wasn't really getting my pred dose down much anyway. I'm still on a high dose of pred, and having problems with steroid-induced diabetes and high blood pressure, so I'm now considering trying azathioprine (I can't have ciclosporin because of the high blood pressure).
I know there are others on here who have tried both methotrexate and other immunosuppressive drugs, and if you do a search with the word 'methotrexate' etc, you will find some previous threads describing other people's experiences with it. Although methotrexate didn't work for me, I know there are other people who have had better experiences with it.
I don't have any personal experience of continuous subcutaneous salbutamol or terbutaline (although am considering that too at the moment) although if your doctors are not familiar with it I can point you in the direction of some papers that discuss it - most of them deal with terbutaline (another beta 2 agonist like salbutamol (abuterol in the US) - terbutaline is marketed as Bricanyl in the UK, not sure about the US) as terbutaline is most commonly used subcut here.
You don't mention who looks after your asthma - I'm not totally familiar with the way the system works in the US but have you been seen by anyone with an interest in severe asthma? In the UK most people on the level of treatment that you're on would have been referred to a centre with an interest in managing difficult asthma patients, such as Heartlands in Birmingham or the Brompton in London. The only equivalent I know of in the States is the National Jewish in Denver - their website describes their asthma programme here: nationaljewish.org/disease-...
(paste it into your address bar and then delete any spaces that the AUK website has inserted into it).
Have you also been properly assessed for other conditions that might be co-existing with and contributing to your asthma? I'm thinking of things like gastro-oesophageal reflux, vocal cord dysfunction, bronchiectasis and so on. Again a specialist centre would test for and treat these things, as well as doing absorption tests for some of the drugs you're on, particularly the steroids and theophylline/aminophylline.
Sorry this is a bit long but I hope some of it helped! Do stick around here if you'd like, there are a lot of us who are in the same or a very similar boat to you with difficult/brittle/severe/chronic/whatever-you-want-to-call-it asthma (we've had 'extreme' and 'chaotic', both of which I like!). I wish you all the best in your quest for solutions, do let us know if you find the magic bullet!
Take care,
Em H
PS - incidentally, Kate, Xolair can be effective in people with normal IgE levels - the original studies that showed benefit were done in people with levels of 30 - 700 IU/ml (normal range is upto 90 IU/ml), although different PCTs have different levels at which they will consider treatment. NICE are due to give their proclaimation on who should have it on 31st Jan 2007, so it's still a postcode lottery at the moment.
The Brompton have strongly recommended to me that I try Xolair despite the fact that my IgE is only 36 IU/ml. My PCT will fund it automatically for anyone with an IgE of 70 - 400 who has been in ICU - I'm going to have to apply for special funding, but they have granted it to my friend here in these parts who has brittle asthma and has an IgE of 0.2 IU/ml (!) and she has had some benefit from it! Apparently the thinking is that your blood IgE levels and lung IgE levels can be vastly different, and in fact a low blood IgE level *may* imply a high lung level. Ironically the people with sky high IgE (it can be in the tens of thousands) who you would think might benefit the most, can't have it in an appropriate dose because the dose required to bind all that IgE would be toxic.
THANKS TO EVERYONE
Thanks to everyone for your replies. That really helped a lot. I am going to ask my doc about the azathioprin, and sub cat therbutaline/salbutamol. I wrote everything down and will discuss it with him tomorrow during a phone conference. Thank you all for your suggestions.
I know this treatment can cause sdie effects, but frankly the prednisone is tearing my body apart. I already have cataracts and osteoporosis - at 22!
MY PFT's are constantly down, and meds are becoming less efffective - more steroids, in other words!
I am willing at this point to try anything.
So, thanks all for the suggestions, and I will keep you updated.
Mia
I know this is not quite answering the question you asked, but let me say that I'm really sad to hear about your condition, especially at 22. I'm 24 and I cannot even imagine how much of a struggle your daily life is - I used to be a moderate asthmatic, and that was absolutely awful.
Since this thread is about unconventional treatment, I should maybe put my thoughts in. As everyone here knows, (but is unlikely to want to admit), your pharmaceutical treatment of asthma will only ever increase or stay constant. It is very very rare for people's asthma to significantly improve, or cut down their medication dramatically. There is certainly no cure, no magic pill or drug in existance that will cure your asthma. Equally, there is no such wonder-drug in development, not even in ten or twenty years will we see a drug that can _treat_ asthma (like antibiotics treat infection) rather than maintain it (like insulin for diabetics).
I seem to be mentioning this in every thread I post in and getting flamed for it, but Buteyko really worked for me. It is essentially a complementary series of breathing exercises - so as long as you don't stop taking your prescribed medication, it is completely safe.
You are at a stage where you are considering taking unknown, untested, or even cancer drugs. If that isn't a desperate move, i don't know what is! Try Buteyko, and I promise you will learn at least something that will help you. At this point, what have you got to lose?
I appreciate your comment. I am on day 4 of Buteyko. I feel grateful for the possibility to one day reduce my meds, in particular steroids. I am taking an online course with Patrick McKeown. Can you tell me how long you have been doing it and how it helped?
Thanks,
Lillian
The treatments discussed are NOT unknown or untested but a furture treatment for this severity of a life thretening illness. They are used in cancer but to a much higher level, they are safely used for other conditions, please dont dismiss without medical knowledge and reason. Lewis as said manty times on here just because buteko worked for you its ahsnt been proven and is shown in some studies to do more harm in the severe scale of asthma of which we are? Thats why you have been shot down as you say before. So please if anyone is considering it dont do so without medical advice.
Andrea xx
Andrea,
Sorry, but I'd like to see your evidence for when Buteyko has done more harm than good. A huge part of Buteyko focuses on relaxation, lifestyle changes, simple and safe breathing exercises. In that sense, Buteyko is like physiotherapy or osteopathy. I agree that severe asthmatics are constantly on a knife-edge, but Buteyko provides valuable advice that you may not know. As a severe asthmatic you may think you are an expert on asthma (and able to judge Buteyko) but I assure you, you aren't.
As far as i have found, there is ONLY positive clinical evidence for Buteyko. Take a look at this study from Dec 2003 Study in New Zealand: nzma.org.nz/journal/116-118...
or check out thorax.bmj.com/ and type ""Buteyko"" as a search keyword. Theres plenty to read.
I have never said and never intended the impression that i am an expert on severe asthma and quite frankly begrudge you saying i do!! i am going of what i have been told be two experts is the severe asthma field. All i wanted to get across was it isnt too be undertaken without medical advise.
I must say i am deeply upset by your comments!!
Andrea
Hi there,
I just want to step in here quickly. Bukeyto is a method that can help some people. I do not know enough about it to say one way or another wether it works so wont. We need to rememeber here that there are different varients of asthma to different levels, different people have diffferent triggers, such as infection, allergies, hot to cold, etc. If Bukeyto works for you then fantastic, and if it didn't, then you can only say you tried. I understand it has made some people on here more poorly, but has also helped some people. Like sub/cut, helps some people and gives them a new lease of life, but for some it caused more problems and is dangerous. People come on here to give opinions and get advice. PLease remember that people are not doctors, are only talking from experiance and so if something works for them it may not work for you. What people are saying on here is aproach things with some caution and get doctors advice before trying anything and under doctors or medical supervision.
I am sorry if this post has offended anyone, it was not meant to.
Miaraw, i hope the advice here has helped and you get some answers from your doctor.
Hi guys,
As some of you will know, I have a keen (enquirying) interest in allergy, immunology and cell-mediated mechanisms.
In light of current discussions I would be grateful if someone could provide me with a link to some published research material that confirms that methotrexate and/or ciclosporin is used sucessfully to treat asthma and/or allergy patients. I can find plently of links to support the use in other conditions like organ transplant and autoimmune disease but not asthma or allergy.
Take care,
Derek
I have no links to papers but was told by rbh that ciclosporin acts as a steriod sparing agent and the reason that it given sometimes to asthmatics is it acts in similar way to steriods which is helpful for people like my son who have become steroid resistant. I did read a study last year on 10 severe steriod dependant kids started on ciclosporin, half managed to lower oral steriod doses. I presume there must be some evidence to suggest this drug could help as why would leading chest cons prescribe if there wasnt? As with any drug we were warned of all side effects and uncertain success but there were no other options open to us at the time. I think medication and treatments are a very individual decision, what suits one person may not suit another.
julie
I am no expert but I do have an expert team that includes drs, nurses, physios and OT's at what is acknoledged to be a world specialist hospital and when I mentioned butekeyo I was told in no incertain terms not to attempt it. As part of pulmonary rehab at the Bromptom you do relaxation and breathing techniques but they are not butekeyo. It is not a cure all and in severe asthmatics can also alter the way they breath and this means their gasses can be messed up anyway without randomly doing breathing exercises that might alter those for the worse.
If it works for you fine but no-one should try it especially the more extreme mouth taping without medical supervision by your asthma team.
Bex
Can I just say? ENOUGH already we've had enough flaming lately. We all have our thoughts and opinions on Butekyo, from what I understand about it, if you are a hyperventilating (over breathing) asthmatic you probably would benefit from it but not without proper medical instruction first. Alot of asthmatics do hyperventilate because asthma is a scary condition but some, that suffer from carbon dioxide retention don't hyperventilate so Butekyo may cause them more harm than good through trying to force air through already narrow airways possibly making them even more narrow and causing even more carbon dioxide retention. From what I understand Butekyo is no more of a cure than any of the drugs mentioned on this thread, it can treat hyperventilation that can cause asthma but not actually cure asthma itself. If you don't suffer from hyperventilation the chances are butekyo won't help you.
Tks xxx
Lewis, I would just like to confirm these drugs or not unknown,untested or cancer drugs. Both methotrexate and ciclosporin are used in much much lower doses for asthma. Ciclosporin is also used for severe psariosis (sorry cant spell it ).
In response to the comment to wheezyab about her not being an expert on asthmatic, I think it was unfair and upsetting comment to make as she was only trying to help and make suggestion to another member of boards. Just because she didnt agree with your staements on buteyko doesnt make her way wrong either'
Everyone is entitled to their own opinion and if breathing excercises work for you thats fantastic but I have to say I have 100% faith in my sons chest doc (who is a respiratory prof) and if he thought this would benefit my son instead of loads of drugs i'm sure he would have reccomeneded it. You are a believer in buteyko the same way i am a believer in s/c bricanyl We are at rbh on friday so i will ask for their advice on this method..
Julie
Hi everyone,
Deek - I have lots of papers concerning methotrexate and azathioprine if you would like the references.
Methotrexate: there are around 70 papers suggesting benefit, many of them providing level 1 evidence, ie double-blind, randomised, placebo controlled trials. For example:
Comet R, et al, 'Benefits of low weekly doses of methotrexate in steroid-dependent asthmatic patients. A double-blind, randomised, placebo controlled trial. Respiratory Medicine. 100(3): 411-9, 2006 Mar
Aaron AD et al, 'Management of steroid-dependent asthma with methotrexate: a meta-anaylsis of randomized clinical trials' Respiratory Medicine. 92(8): 1059-65, 1998 Aug.
Hedman J et al, 'Controlled trial of methotrexate in patients with severe chronic asthma' European Journal of Clinical Pharmacology. 49(5): 347-9, 1996.
....and many others.
Ciclosporin: there is slightly less evidence but still around 50 papers; a lot of them are case reports or in vitro cell line studies and animal studies, but there are still a few randomised controlled trials, for example:
Lock SH et al, 'Double blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma.' American Journal of Respiratory and Critcal Care Medicine. 153(2): 509-14, 1996 Feb
Matusiewicz, R. Urbankowska, B, 'Effects of cyclosporin A on the clinical state and spirometric parameters in patients with steroid-dependent bronchial asthma' Pneumonologia i Alergologia Polska. 60(11-12): 53-7, 1992.
Azathioprine: less evidence, no trials but quite a few case reports and some reasonably convincing animal and in vitro evidence.
Other immunosuppressants, eg mycophenylate (Cellcept), gold: the odd case report but mostly in vitro studies.
Of course individual consultants will also have their preferences and experience to go on... the bottom line is that with asthma at the severe end of the spectrum there are never going to be huge studies to provide really robust evidence because of the small number of patients involved, but there is some evidence that these drugs can be helpful.
I've quoted the studies above as examples of some fairly good studies, but I have a lot more examples - if anyone would like the references just PM me and I'll let you have them.
Xephos - I'm sorry you are feeling got at but I don't think anyone is flaming you. In my book flaming is making a personal attack on someone, and I don't believe anyone is attacking you personally. You have to understand our caution - you have started posting on here relatively recently and you have mentioned Buteko in almost every post you have made. In the past people who have come onto the boards who fit that profile have turned out to have a vested interest, ie to be salesmen for various Buteyko courses. I'm NOT saying that you are too, and I can totally understand why you would be evangelical about a treatment that has worked so well for you. You can see, though, why we are cautious.
I'm not going to get into the whole Buteyko debate (although if anyone wants references, both good and bad, PM me) but I think it is perfectly reasonable for us to suggest that all treatment changes including trying Buteyko should be discussed with your doctor prior to trying them. Some of us are so much 'on a knife edge' as you rightly describe it that ANY change can tip us over into an attack. To use the examples you gave, I would not have physiotherapy or osteopathy without consulting my doctor either! (and incidentally both of those can be dangerous in the wrong hands!)
Most people, by the time they get to the stage of considering steroid-sparing agents, are pretty desperate to find something that works, and when people are desperate, feelings run high. A critisism of a drug which someone is considering as their 'last hope' of some kind of normality is bound to be taken very much to heart. But we have to remember that different things work for different people and that one person's bad experience can be another person's life saving drug.
And on that note, I personally believe that it makes a lot of sense to try several of these immunosuppressive steroid sparing therapies if the first doesn't have an effect (I'm thinking of Sean, here, Julie, but equally of others in similar situations). Since we don't know the exact immune system problem in any individual asthmatic, and all these drugs affect the different components of the immune system in different ways, it makes sense that one drug may not work and another may be successful. It also explains why response varies so widely between different people! So I would recommend that if one agent hasn't been useful, you should talk to your doctor about trying a different one. PLEASE NOTE: this recommendation is not based on any of my medical experience or on any research, it's just my own little pet theory!
Anyway once again I seem to be competing for the title of 'Poster of the longest posts' so I'll finish.
Take care all
Em H
TKS - u are spot on on the issue of the harm it can do if u dont overbreathe! I tried Buteyko under supervision - one lesson and I landed in ITU as I dont overbreathe and it messed up my gaseous exchange so much so I went into respiratory arrest!
Xephos u personal experience is it helps u -- my experience is it almost killed me!
I am being considered for azaithioprine as a steroid sparing medication - these drugs are not new, unknown or untested!
They are rare yes and lept as a last resort for uncontrollable asthamatics or steroid tablet dependent asthmatics!
Xephos, I assume you didn't mean for remarks to come across as they did.
I would add a comment to yours regarding ""experts"" on asthma; a lot of the asthmatics on this board, by virtue of their experiences, severity and chronicity of illness, will know more about asthma than the average doctor. And they are certainly experts on their own asthma.
It's not rare for people's asthma to improve and for medication to decrease. I see it on a reasonably frequent basis, both professionally and personally. Your remarks would certainly probably be true for the severe chronic end of the asthma spectrum - most of the guys on this board will testify to this.
Now can we please leave the Buteyko debate and go back to what the thread was originally about, i.e. steroid sparing agents such as azathioprine, methotrexate and cyclosporin for asthma.
Regards,
Cathy (Moderator)
My apologies
My sincere apologies for any offence caused.
I was just deeply saddened and angered by the plight of our original poster. She is my age and I could not even start to comprehend the seriousness of her condition. Cataracts and osteoporosis at 22 years old? And the drugs we are talking about in this thread weren't even developed FOR asthma - as you have admitted they are the last resort, desperate measures, and the side-effects are far from minor.
The thing is: if I hadn't found Buteyko the person posting this thread could have been me! Thats what scares me the most. I have had asthma since birth, hospitalised several times before I was four years old. I swear that all the steroids I took when I was younger stunted my growth (i'm 5""7 and thin as a rake, my brother and father are well over 6"" each). As a teenager I had terrible problems with asthma and the steroids, tablets and nebulisers only seemed to increase and increase. On the first day of school I remember that we had to introduce ourselves and say one interesting fact about ourselves. Mine was 'I have asthma'.
I know my viewpoint is skewed to support Buteyko, but I believe in it and more importantly, i believe that every asthmatic should know that it exists. It is a serious complementary (i.e. hand-in-hand with pharmaceutical) therapy and if by posting on this forum I can help just ONE person - I believe it is worth it.
Lewis
Wow!
Geez - I did not expect my little ole question to cause such contreversy!
I am sorry that feelings have been hurt - as was said, when you are in a DESPERATE situation, feelings run high.
For the sake of the post on breathing exercises - I haven't tried that particular type, but have tried other types of breathing/relaxation exercises. They can help me keep calmer and more relaxed (ie to keep my VCD from also triggering) but I have found that they do not help my overall lung function improve. Again - That is my experience PERSONALLY.
As far as methotrexate being untested - I have read many articles about the use of this drug in SEVERE asthmatic cases (as stated - ""last hope"" situations) since about 1985. That's two decades worth of treatment on patients - pediatric and adult. So, I would not consider than untested.
As far as the other drugs, like cyclosporine, I haven't read much about that.
CellCept was recommended to me by a Doc at National Jewish Respiratory Research Center, one of the top respiratory hospitals in the nation. So --> I don't think they would recommend something that is ""experimental.""
I guess the bottome line for me is this - as everyone suggested, you shouldn't change any treatment without serious consideration with your doc. Also --> ALWAYS weight the risks with benefits. ie; no use fixing your lungs if you ruin your liver in the meantime, right?
I thannk everyone for their suggestions, comments, and experiences. I will take all of this into consideration when I next talk to me doc, and will also let you know what I've decided and update all on how the treatment goes.
Thanks!
Thanks Xephos. You are quite right in that sometimes we do lose the sight of the wood for the trees - i.e. what a terribly difficult position to be in at such a young age.
Mia, you do sound like a very confident and outgoing individual so I'm sure you will bounce back and overcome your problems. I hope you have the best of luck with your treatments and I also hope you continue posting updates here with your progress to let us know how you are getting better
Lewis
Hi EmH,
Thanks for the methotrexate/ciclosporin info, very interesting. Yes if don’t mind providing some links this would help me get my wig around this subject. I am sure you can appreciate that I am not in any way challenging the validity of your comments or the use of methotexate/ciclosporin.
Apologies for the enquiring mind. Its just that I am struggling to grasp the concept that taking immunosuppressants improve the health of asthmatics as this appears to contradict standard allergy teaching which suggests that all immunosuppresors should be avoided. To add fuel to this train of thought – it is my understanding that one of the serious side effects of taking steroids is in fact their immunosuppressive properties. Reading these boards provides anecdotal evidence of this as some asthmatics are refused the flu jab due to the window of vulnerability caused by taking a long term course of pred.
I thought that pred is prescribed for its anti-inflammatory properties not because its an immunosuppressant. I find difficulty accepting that methotrexate is a replacement medication as it is my understanding that methotrexate is purely an immunosuppressant and does not have any (direct) anti-inflammatory properties. This being the case, methotrexate will not provide (direct) anti-inflammatory relief. It will of course dampen down all immunological responses providing indirect anti-inflammatory relief/masking of symptoms but this may well leave the patient seriously immunocompromised. What happens if the status of the immune system needs to be reinstated to provide protection against a serious contracted infection? I wonder if this would be possible and at what price would the patient have to pay, asthma wise.
I read recently in a research paper that a significant difference between asthmatics and patients with COPD is that COPD patients have a predominantly higher level of CD8 (suppressor T-cells) cells than asthmatic patients. My interpretation of this is that lowering immunity (by suppressing the immune system) may in time lead to irreversible lung disease.
Derek
Deek
How I was explained it was that they supress the cells that cause the inflamation - bad cells!
But obviously they supress some good cells too!
Hi Derek,
It’s alright, I know your intention is not to challenge the info I have given but just to find out a little more about it! Don’t apologise for that.
I’ll e-mail you my complete list of references concerning steroid-agents when I get a chance.
To try and answer some of your questions (warning, this will be long!):
I don’t believe it’s entirely true to say that standard allergy teaching suggests that all immunosuppressors should be avoided. Allergy is at its most simplistic level due to an overactivity of certain parts of the immune system, or if you prefer, an aberrant immune regulation. Although immunosuppression is not usually used for the more benign manifestations of allergic disease, such as allergic rhinitis, it has been used for allergic asthma and severe eczema since the 1970s, as you can see from the references I will send you. Indeed, two of the drugs most recently developed specifically for allergic asthma, Xolair and the leukotriene antagonists, are themselves immunosuppressors in a sense, albeit that they suppress one very specific part of the immune response.
You are right to say that pred is prescribed largely for its anti-inflammatory properties – however, whilst many of these effects are direct, there is also an indirect effect on inflammation via its effects on the immune system, as the majority of the chemicals and cells involved in the inflammatory response are immune system components. Inflammation is part of the immune response and as such it is often very difficult to ‘un-pick’ the effects of these drugs and separate out the two effects.
It is not true to say that methotrexate and the other drugs are purely immunosuppressants and do not have any direct anti-inflammatory properties – most of the drugs concerned have been shown to have direct anti-inflammatory properties as well, and indeed at the doses normally used in asthma it would be fair to say that the anti-inflammatory effects predominate. (See these papers on methotrexate - ard.bmj.com/cgi/content/ful... and rheumatology.oxfordjournals... - I do have many other references which I can let you have but most of them do not have open access to free full text on-line.)
You are right of course that these drugs also provide indirect anti-inflammatory action by their effect on the immune system, and this is a double edged sword. Whilst they do treat the underlying disease to a variable extent (I don’t think it’s accurate to describe them as ‘masking the symptoms’ as they are treating the underlying pathology, unlike, say, beta 2 agonists) they can, of course, in some cases cause significant and dangerous levels of immunosuppression, and this is one reason why bloods are monitored frequently whilst on these drugs.
To answer your question about management of immunosuppression in the event of a severe infection, it would very much depend on the specific type of immunodeficiency that had manifested in that patient. The drug is of course stopped. IF there is a low neutrophil count (which can occur with methotrexate among others) a drug can be given to stimulate the bone marrow to release more neutrophils. If circulating levels of antibodies are low, infusions of antibodies can be given. Neither of these would be expected to produce a worsening of asthma symptoms, since the specific parts of the immune system they are stimulating are not usually implicated in the pathogenesis of asthma. Other forms of immunosuppression cannot usually be treated directly, but in most cases all that is needed is to withdraw the drug and treat the patient aggressively with antibiotics.
I had not read that COPD patients have higher levels of CD8 cells, that is interesting. I do not believe, though, that this necessarily implies that suppressing the immune system may lead to irreversible lung disease. COPD is a very different disease to asthma in general, with a much less strong component of immune overactivity. The higher levels of CD8 cells may merely reflect this. Equally, it is impossible to tell if the CD8 levels are a cause of the disease or a compensatory reaction. Also remember that the vast majority of COPD patients are current or ex-smokers, which is in itself immunomodulatory in ways that are not fully understood.
I think we have to bear in mind that asthma is a very complex and heterogeneous condition, which is far from fully understood. Abnormalities in expression of many of the components of the immune system and inflammatory response have been implicated in asthma, from cells such as eosinophils, neutrophils and mast cells to chemical mediators such as leukotrienes and some of the interleukins, among many others, and antibodies such as IgE and possibly some forms of IgG. Other cells and chemical mediators of the immune system are involved in trying to damp down the abnormal immune response. If we see a high level of a particular cell or chemical, it’s often impossible to know whether this is a component of the pathogenesis of the disease or a compensatory response. Of course, in an ideal world any immunotherapy for asthma would be aimed at suppressing the disease causing components whilst boosting the activity of the body’s own suppressing elements, but at the moment we have neither enough information about which is which nor the sort of high tech drugs which can achieve that. To further complicate things, the chemicals and so on responsible for the disease are likely to differ from person to person, a fact borne out by the inconsistent study results when these factors are studied, and the fact that immunomodulatory drugs such as Xolair and the leukotriene antagonists tend to work extremely well in some and not at all in others. I think the most we can hope for in the ‘sledgehammer’ immunomodulatory drugs that we have at present is that it knock out most of the ‘bad’ elements and leave most of the ‘good’ elements intact, and whether it is having that effect is often only discernable by clinical trial, whether that be a large randomised controlled trial or a therapeutic trial in an individual patient. Arguably, some of the immunosuppressant drugs we are talking about may in fact be ‘better’ (ie more specifically targeted) than prednisolone, which affects many different components of the immune system.
Immunosuppressive treatment is clearly not for everyone, and obviously has to be approached with caution in anyone with a history of recurrent infections or colonization with a particular bacteria. It can be a valuable tool though when many of the other weapons in the asthma armoury have proven ineffective or are not tolerated. Prednisolone is often seen as a more benign drug, as so many people are prescribed short courses, but taken long term it is far from benign, and many of these drugs offer a way to reduce or even stop the pred with fewer side effects. Clearly it must be carefully monitored to try and achieve the best possible balance in keeping the disease controlled without paying too high a price in terms of immunosuppression. To use an analogy, many forms of cancer chemotherapy are profoundly immunosuppressive and can cause life threatening infections, but they are clearly an essential part of the management of the disease and very few people would suggest that they should not be used. Immunosuppression in asthma can be equally life-saving in some cases. Sometimes weighing up the risks and benefits of a treatment is not easy!
I look forward to the day when every asthmatic patient has their exact defect in immunoregulation characterised and then precisely treated; until we have these tools available, we have to make the best of the blunt ones we do have!
Sorry this is so long but it does provide me with a welcome chance to use my brain, which has atrophied somewhat in the last few months!
Take care,
Em (who surely now officially wins the title of 'Poster of the Longest Post Ever'!
Well EmH, your award winning wee post has certainly suppressed my enquiring mind, …for the moment – LOL.
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