Tagged: 

  • CF is more than just lungs

    Posted by tim-blowfield on March 9, 2022 at 7:01 pm

    Today the CFTrust launched its CFTruths campaign once more concentrating on the pulmonary effects of CF. While the effects of thick mucous in the lungs is the most serious issue in most with CF limiting the discussion to just that seriously short changes most. Bowell and pancreatic problems are well recognised and attributed to the viscous mucous but is that all. Many pwCf have a plethora of Co-morbidities and renal and hepatic failure are all too common. Obstruction of airways and ducts does not explain failure of the endocrine glands such as the Islets of Langerhans in the Pancreas (causing Diabetes), nor Adrenal dysfunction causing Hypokalaemia and Addisons Disease. Hyperparathyroidism too occurs despite the Parathyroid Gland having no goblet cells secreting mucous. Heart failure was reported as long ago as 1980.

    Many of these so called Co-morbidities cause considerable distress and disability in pwCF, are often overlooked by the superb Respiratory Physicians leading CF Teams. Unfortunately too, specialists in other fields rarely understand the role of the faulty CF gene in their cause.

    The thick mucous is well ascribed to the failure of the Chloride transport from the cell caused by the faulty CFTR channel and gene.  If the Chloride (an anion) is not being pumped out then the levels within the cells must be high and must be balanced with cations esp Potassium (K) and Calcium (Ca). High K within the Adrenal cells will surely make the cells ‘think’ K is too high and increase Aldosterone secretion, causing hypokalaemia. Similarly high Ca within the Parathyroid cells will affect PTH and the Ca metabolism balance.  K & Ca are also involved in the function of muscle cells (incl Heart Muscle), neurons   and to some extent every cell of the body. No wonder pwCF are so complex!

    We do need the CFF to lead research into these co-morbidities.  Cardiologists, Endocrinologists and other Specialists need to understand the effect of the faulty CFTR channel and gene is having in the organ they specialize in. To date, they usually don’t. Cardiologists do not understand why pwCF and heart failure often have severe problems with many heart drugs. ACI’s, ARB’s & Ca Channel blockers often increase blood pressure rather than decrease it.

     

    tim-blowfield replied 3 weeks, 5 days ago 6 Members · 31 Replies
  • 31 Replies
  • paul-met-debbie

    Member
    March 16, 2022 at 8:41 am

    Very true indeed Tim. CF is working all over the body in many systems in ways many of which are not yet known.CF care is currently organised in little islands of expertise, that are scattered and incomplete. Often they do not work together very well either. There needs to be an interdisciplinary approach both in treatment and in research. The focus on only the lungs and digestion, however understandable from an historic point of view, must vanish. Perhaps we need a real super cf specialist, who is proficient in all the systems of the body that can be affected by cf. This could be a specialisation within internal medicine, the cf-internist. And under her suoervision, the normal specialists would work together in a team to optimise treatmemt for each individual pwcf in the clinic.

  • tim-blowfield

    Member
    March 17, 2022 at 7:05 pm

    On Wed had a consult with Reva’s cardiologist. Once more he showed that he has no understanding of CF – no understanding that in pwCF heart disease does occur. With all Reva’s co-morbidities I find it impossible to believe that they are all unrelated in causality including the Heart. My theory is about intracellular electrolyte inbalance (high  Cl, K  & Ca in particular)  is causing intracellular fluid retention and cellular dysfunction. But he is unwilling to listen and consider possibilities beyond the textbook protocols. He is a good technician, less so a good doctor. We have not found a cardiologist that is willing to “think beyond the box”.

    • jenny-livingston

      Member
      March 21, 2022 at 10:16 am

      Tim, this can be so frustrating! As you mentioned, there is real cause to believe these things are related. I’m sorry you’ve yet to find a cardiologist who is willing to entertain and investigate your theory. My life has been quite literally been saved by doctors who’ve been willing to listen and act on my concerns and ideas. I hope that Reva will be able to find a physician willing to do the same.

  • paul-met-debbie

    Member
    March 18, 2022 at 2:48 am

    That is exactly the problem.
    Tim, are there any specific tests or examinations or treatments or strategy you can think of yourself that you would like your cardiologist to look into or to perform? Your theory sounds almost self evident to me, but perhaps is too much for your doctor to accept. When you present it as small practical steps he might be more inclined to look into it. Often when doctors feel helpless, they hide behind textbook knowledge. What would you have been willing to do as a vet in a situation like this, when a dog owner presents his pet to you with strange comorbidities and a theory of his own, that is not in your textbook or education? How would he have been able to make you overcome your position and go along to assess whether or not his theory holds ground? Try to find out this for yourself and then apply it on your cardiologist, try to break through his passivity, try to evoke his curiosity, give him something to look into in a way he is familiar with. I gather you will not be satisfied with him to only acknowledge your theory, you want him to do things. So bypass the convincing, the theory, and think of something to make him do things you deem useful anyway.

    • tim-blowfield

      Member
      March 28, 2022 at 5:48 pm

      Thanks Paul for your encouragement. Last Monday week our cardiologist threw a spacko because our Endocrinologist had not put Reva on a SGLT2 inhibitor. The result is the Endo has acted and Reva has now started on dapagliflozin with promising results. Dapagliflozin is has been in use in diabetes for some years and has been shown to be beneficial in heart failure especially in HFrEF. Recently it has been registered for such and also for weight loss.

      It does have some issues that must be watched for: 1. can cause Ketosis  but that is rare and 2: can predispose to thrush (quite common).

       

      • paul-met-debbie

        Member
        March 29, 2022 at 2:53 am

        Wow, that is indeed important Tim. Since 2019 (DAPA-HF study by McMurray et al.)  it is known that added  SGLT2 inhibitors (10 mg dapaglifonzine daily) have good results in case of heartfailure with HFrEF (LVEF <40%) indeed. Recently this is also deemed useful in case HFmEF (LVEF between 40 and 50%).  The DAPA study was a large one, 4744 patients were included of which half were on placebo and half on dapaglifozine and the results had a medium GRADE value and a relatively low NNT of 20. It seems a good thing to try and watch, indeed there are some unwanted effects to be monitored, especially in patients with diabetes.

        We sincerely hope for the both of you that Reva’s health and well being will improve from this!

  • tim-blowfield

    Member
    March 28, 2022 at 5:31 pm

    Hi all,

    The good news from Australia this week is that TRIKAFTA IS TO BE AVAILABLE FOR ALL over 12 years with one copy of F508del. on the PBS from Friday

    The sad news is that it is not available for those who have one of the rare mutations (eg R75Q) but not F508. These may be few such that I call them the “Forgotten 10”. Most with these rare mutations (there are about 100 in Aussie) will be compound heterozygous with F508 on their other chromosome but about 10 in Australia do not. They will miss out despite VERTEX having shown that pwCF with about 120 mutations should benefit.  They will miss out as a result of the bureaucracy and red tape of the Australian registration system.

    • paul-met-debbie

      Member
      March 29, 2022 at 2:55 am

      Great news indeed! Let’s hope the missing 10 will get access some how too, albeit by way of trial and error.

    • jenny-livingston

      Member
      March 29, 2022 at 11:25 am

      Tim, this is indeed great news! I had read a bit about that and was excited to discuss it here on the forum. Now, as you mentioned, there is work to be done in order to get this drug or something as effective to ALL!

    • kay

      Member
      March 12, 2024 at 4:37 pm

      Tim – Just wondering if you are in the 100 Australians?

  • paul-met-debbie

    Member
    March 29, 2022 at 4:35 am

    To Throw a Spacko! Thanks for this expression Tim, I didn’t know it and couldn’t even find it on the net. Does it have something to do with being “spastic” from anger/amazement? aka to throw a fit, flip one’s lid, blow up, hit the roof, hit the ceiling, have kittens (! nice one for you), combust, blow one’s stack, fly of the handle, flip one’s wig, blow a fuse, go ballistic?

    Anyway, I would think both the cardiologist and the endocrinologist are equally at fault here and they should throw a stone at themselves.

    This is typical for what happens because of the fragmentation of specialist healthcare in general, and in CF care in particular. A medicine that is commonly used for diabetes (and hence prescribed by the endo) turns out to be effective for heart failure (and hence is on the field of the cardio). And neither of them picks it up for three years, perhaps thinking that the collegue will do it and/or afraid to ask about it and overstep some imaginary borders of competence. This stresses my appeal for a CF super specialist who coordinates the care and medication. The current system of CF teams does not work sufficiently at all.

  • tim-blowfield

    Member
    March 29, 2022 at 5:36 am

    Yes. To throw  a spacko is precisely as you suspected. Australian jargon. We have some wonderful terms. Australians are the only people in the world that can call a dark horse a fair cow and get away with it! ‘fair cow’ = a very badly behaved animal.

    We still have much work to get our CF teams headed by Drs with broad understanding of CF – indeed, as you say, a CF super specialist .

    Keep peddling!

  • tim-blowfield

    Member
    March 29, 2022 at 5:46 am

    Maybe that shouldn’t thrown stones at each other – just learn & learn to work together.

    While in Kenya some 50 years ago there were 2 waring tribes. One invaded the other and carried off the Chief’s throne. The victors installed it in their Chief’s hut (It was much more grand than their own). Then they had to find somewhere to store the old throne – could not throw it out as after all it was their Chief’s. They stored it in the rafters of the Chief’s hut. After a while, after the white ants took one too many bites, there was a loud crack and the old throne came crashing down on the Chief, killing him stone dead!

    The moral is: People who live in grass houses shouldn’t stow thrones!

    • paul-met-debbie

      Member
      March 30, 2022 at 2:17 am

      We threw a laughing fit reading this great story! Thanks, Tim.

  • tim-blowfield

    Member
    March 31, 2022 at 1:42 am

    Then there was the American Indian Chief who had 3 wives. His favourite was huge. He went to  Africa on a hunting trip and shot an hippopotamus and 2 gazelles,  the hides of which he took back home, one for each wife.

    The squaw on the hippopotamus was equal to the sum of the squaws on the other two hides.

  • tim-blowfield

    Member
    November 2, 2023 at 2:27 am

    An update:

    3 Months ago Reva was admitted ’cause she had splenic infarcts causing severe pain and caused by clots been thrown off from the left atrium. Was in hospital for 7 weeks. She now has a device blocking off the left Atrial Appendage which should reduce clots being formed by 90%. The Alfred Hospital which has the CF Unit just wanted to treat her palliatively so she transferred to Cabrini where the LAA was blocked off and she gradually recovered. But throughout her ordeal we had to be very vigilant and assertive to ensure her multiple co-morbidities of CF were not neglected.

    It is amazing how usual it is that doctors treat the problem in their field and refuse to consider other co-morbidities and the CF that underlies it all.

    We need

    1: a better understanding of CF in our wider medical fraternity

    2: CF Physicians that see CF as being a problem that affects more than just the lungs.

    There are some wonderful reports of the benefits of Trikafta on the lungs and respiratory tracts but in all the research effects on other organ systems are unreported at best reported as ‘side effects’ to be avoided. Are we seeing benefits in Adrenal function? Cardiac & Muscle function and strength? Diabetes? Vascular health?

    What is happening in Mental health? Headaches have been reported when pwCF start TK and is a reason many stop. But is it a result of intracellular electrolyte changes caused by improved Chloride transport?

    A recent report <b style=”background-color: var(–bb-content-background-color); font-family: inherit; font-size: inherit; color: var(–bb-body-text-color);”>Trikafta leads to clinical gains for 2 adults with rare M1101K mutation<font color=”rgba(0, 0, 0, 0)” face=”inherit”> while wonderful is an example reporting on the lungs but nothing as to whether improvements had </font>occurred<font color=”rgba(0, 0, 0, 0)” face=”inherit”> in other organ systems. </font>

    <font color=”rgba(0, 0, 0, 0)” face=”inherit”>We need pwCF being assessed as whole persons not just a pair of lungs!</font>

    • kay

      Member
      March 12, 2024 at 4:39 pm

      <div>Are you in a clinic in Australia? Would love to DM you if you are…</div>

  • tim-blowfield

    Member
    November 2, 2023 at 5:03 pm

    The last section of my post yesterday was was rendered somewhat incomprehensible by formatting instructions. I commented on the report received yesterday:

    “”Trikafta leads to clinical gains for 2 adults with rare M1101K mutation”

    I commented that while wonderful, it was an example reporting on the lungs but nothing as to whether improvements had occurred in other organ systems.

    We need pwCF being assessed as whole persons – not just a pair of lungs!”

  • William

    Moderator
    November 9, 2023 at 12:42 pm

    It’s true that CFTR’s have had innumerable affects on the body outside of the respiratory area, both good and bad, but a lot of people would argue that the benefits to their lungs have made life worth living. To another point you made, CF does need to be made more aware to those who do not often treat it within the medical field.

  • tim-blowfield

    Member
    November 16, 2023 at 4:40 pm

    Yes the benefits to the lungs is amazing and MUST not be sidelined. But in assessing Lumacaftor, Trikafta & other therapies for pwCF the co-morbidities also should not be ignored. Too often the effects on other body systems are reported as adverse and undesirable side effects without any attempts of trying to understand why they are occurring. Often they are just ignored in the reporting.

    I postulate that many of the ‘side effects’ are the drugs correcting (lowering) the Chloride levels within cells to levels similar to that of a ‘normal’ person thus lowering balancing cation levels esp Calcium & Potassium. These lower cation levels should be expected to beneficially affect not just Adrenal and Parathyroid gland functions but also muscle and neurological function. WE may even find Diabetes improves with these electrolyte improvements.

    In assessing treatments a wholistic approach is needed assessing not just lung function but the effects on the function of all other body systems.

  • jeanne

    Member
    February 9, 2024 at 2:46 pm

    Hi. I’ve been off the forum for some time – but popped in today. Great read, this thread. Clear to me that you, Tim, and many others, understand CF far more than I do. As my lungs are not greatly impacted by CF (or so it seems), I have focused my light medical studies on the sarcoidosis that I have (pulmonary). Currently dealing with a non-healing wound from a skin cancer surgery on my leg… _getting anyone to consider that sarcoidosis should be checked out_, I am still frustrated by this 6 months after the cancer MOHS surgery.

    For an update, I also had a lousy lung CT in December, but not feeling as bad (sarcoid-wise) as a year ago… my clinic letting that go until May, then another CT (& hopes to get the wound cleared up, as prednisone or methotrexate and a wound are “not pals”).

    Enjoyed the turns of jargon (LOL) & indigenous people history stories. Thx. Most importantly, wishing the best for Reva!!!

    • tim-blowfield

      Member
      February 13, 2024 at 3:02 pm

      One may question the cause of your sarcoidosis. little is known about it in ‘normal’ people though like Sjogren’s it is thought to be autoimmune. In CF both these conditions appear to be inflammatory reactions in the damaged lungs. Could be a sign of the presence of Mycobacteria, a bacteria not uncommonly seen in pwCF.

  • tim-blowfield

    Member
    February 13, 2024 at 2:52 pm

    One may question the cause of your sarcoidosis. little is known about it in ‘normal’ people though like Sjogren’s it is thought to be autoimmune. In CF both these conditions appear to be inflammatory reactions in the damaged lungs. Could be a sign of the presence of Mycobacteria, a bacteria not uncommonly seen in pwCF.

  • tim-blowfield

    Member
    February 13, 2024 at 3:01 pm

    The latest news from Aus:

    1. Ivacaftor has been recommended by the PBAC (The Pharmaceutical Benefits Advisory Committee – a Gov Committee) that it should be available to any pwCF who has a mutation where there is evidence it should help. This will make it available for about 10 persons in Aus. that can’t get it now, incl Reva. Just have to wait for the Health Minister/Gov to act!

    2. Trikafta is being considered in March for kids aged 2 to 6 years by the same committee .

  • jeanne

    Member
    March 10, 2024 at 1:02 am

    Jumping back to Feb 13 – hi william, tim, all. An update and bit of history. History: “MAC” was the first thought by the specialist who read my first CT scan in March 2022. But then the F508 showed up in bloodwork… let’s skip a lot and jump to my CF diagnosis, trial of Trikafta (resulting in badly elevated liver enzymes), and then off Trikafta… in Nov 2022, they did an exhaustive bronchoscopy with what seemed a zillion biopsies in my lungs and lymph nodes. No micobacteria and no common “bad” CF bacteria. Lots and lots of granulomas all over the place. Only a little bit of bronchiecstasis.

    Update: (1) my sarcoid team put decision on hold wrt going on methotrexate and or a combo with prednisone. Unsure if the decision might have to do with the “now-healing non-healing” wound I’ve been dealing with since an August skin cancer surgery on my tibia. Anyway, will do a new lung CT mid-May, then in early June they/we will re-address treatment of the sarcoid. (2) my non-healing wound is now healing – I changed wound care teams. Different treatment is working. Healing is slow, though. (3) I’m experiencing increasing shortness of breath and fatigue these days, but it comes and goes (going partly away). Still not as bad as spring/summer 2022. I am also, again, a bit anemic – but also, not as bad as 2022. And my FEV is over 100… I feel like I shouldn’t complain. I still often feel “misplaced” in these forums… but often wonder if my extreme spinal arthritis might be related to CF.

    Tim – really glad to have read some good news about Reva. Any more news?

    All of you ‘guyz’ leave me in the dust wrt your medical/bilogical knowledge. It’s impressive. At least it offers me some exposure to the terminology (thank you). -jeanne-

  • tim-blowfield

    Member
    March 11, 2024 at 4:29 pm

    Are they going to try you on a lower dose of Trikafta, Orkambi or on Lumacaftor (an earlier drug)? That often reduces the liver damage. It appears your sarcoidosis is an inflammatory response to past infections.

  • tim-blowfield

    Member
    March 13, 2024 at 3:27 am

    Hi Kay. No I am not in a CF Clinic just a humble husband of a wife who does have CF and has done so for nearly 82 years but only diagnosed 15 years ago. She has one of the 100 or so mutations, R75Q; of which just 9 are recorded in the Australian CF Registry and is probably the only person in Australia with that variant and not F508del on her other chromosome.

    As a retired Vet who has had to nut out some curly problems in my patients over a 50 year career I am not averse to posing curly questions. With CF I see that there is much unknown especially as to why pwCF have so many co-morbidities. Abnormal intracellular chloride and other electrolytes seem to be a reasonable explanation. I fear that just treating the lungs is shortchanging pwCF.

    CF Physicians, while needing to be experts in the lungs, need to be expert general physicians!

    • kay

      Member
      March 14, 2024 at 6:37 pm

      Hi Tim,

      Does your wife attend a CF clinic? Does the mutations she have – are they normally tested for in the full screening? What was her sweat test result? What was the trigger for the diagnosis?

      The reason I ask is…. I was diagnosed at 54yrs. I have one common mutation 5T and the other one is in the great unknown. They said it was “not worth checking as it wouldn’t change my treatment”. My treatment is pretty much nothing. Trialing pulmozyme now and have already experienced the terror of hemoptysis which I suspect is because I was sick combined with the pulmozyme being just too drying out of my lungs.

      My trigger for the diagnosis was advanced pulmonary NTM (4 cavities) and all the drama that followed afterwards. A very deep, dark rabbit hole of drama indeed.. Yes, I was presenting at GPs with symptoms but misdiagnosed again and again and …. I was really let down by what I can only say was a “team effort by the medical profession”.

  • tim-blowfield

    Member
    March 14, 2024 at 6:19 pm

    Unfortunately, it seems that still far to many of our CF Experts are experts in lungs only, appearing to be in denial that any other organs than mucous membranes are affected by the faulty CFTR protein and Chloride channel. Except they do recognize that sweat glands are affected. Even the registries fail to record the extent of CF co-morbidities, most of which do appear to be CF caused. And Vertex; ……….. enough said.

    And researchers concentrating on replacing the faulty gene in the airways only I fear will leave pwCF short changed – in other words up the creek without a paddle! We are also seeing this in pwCf who have had lung transplants. They haven’t been cured of their co-morbidities though some may have their Adrenal failure improves by the anti-rejection drugs given post-transplant.

  • tim-blowfield

    Member
    March 19, 2024 at 6:03 pm

    Hi Kay,

    my wife attends the CF Clinic in the Alfred Hospital in Melbourne. She was found to have G542X and R75Q when her gene was sequenced by the Canterbury, NZ lab in 2009. Her sweat test was equivocal but her list of symptoms were 20 of 25 for CF. I would reply to your Dr who said it is not worth finding your other mutation “Bulldust! It might be rare BUT it could be one of the 180 variants that Vertex has shown should respond to Ivacaftor, Trikafta etc. ” If it is then being on TK may be the best treatment for you. You may have some unpleasant symptoms at first as your body adjusts but in most those symptoms peter out. Go fot it!

Log in to reply.