Thursday, May 22, 2014

"Should I take NAC for my pulmonary fibrosis?"

This has been an exciting week in the world of Pulmonary Fibrosis. The results of three well-designed clinical trials were published online and were presented at the American Thoracic Society meeting in San Diego. I reported on the results of two of these trials in a previous post. In this post, I am going to talk to you about the results of the PANTHER-IPF trial, which studied N-acetylcysteine (or "NAC") for idiopathic pulmonary fibrosis (or IPF).

NAC is an anti-oxidant used to treat a wide variety of medical conditions, including TylenolⓇ overdose and chronic obstructive pulmonary disease. NAC has also been used in the past to treat IPF for two reasons: (1) there is evidence that oxidative stress (the bad thing that anti-oxidants help treat) may contribute to the development of IPF, and (2) there was a clinical trial published in The New England Journal of Medicine in 2005 (called the IFIGENIA trial) that found that NAC slowed the progression of IPF. Everyone in the IFIGENIA trial was also taking prednisone and azathioprine (also known as ImuranⓇ), two drugs that weaken the immune system. At the time that the IFIGENIA results were published, there was excitement about the possibility that NAC might help treat IPF, but there was also some well-deserved concern that NAC might only be helping to treat some of the side effects of prednisone and azathioprine. 

Based on these concerns, the National Institutes of Health (or NIH) funded the PANTHER-IPF clinical trial to try to finally answer the question of whether or not NAC helps treat IPF. The PANTHER study was designed in an interesting way. Instead of comparing one treatment to a placebo, the PANTHER study compared two different treatments to a placebo. Each person who enrolled in the PANTHER-IPF study was randomly assigned one of three different treatment options (doctors use the word "arm" to refer to each of these options -- so there are 3 "arms" to the study):

Option 1 was called the "triple therapy arm": Prednisone, azathioprine, and NAC (just like the IFIGENIA trial)

Option 2: NAC alone

Option 3: Placebo 

This was a smart way of designing the study because it would answer two important questions instead of one:

1. Does triple therapy help treat IPF?
 
2. Does NAC help treat IPF?

After the study was well underway, something unexpected happened. In 2011, during a routine safety analysis about half way through the study, it was found that the people in the "triple therapy arm" were doing very poorly. People assigned to the triple therapy arm were more likely to die, more likely to end up in the hospital, and more likely to have a sudden worsening of their disease (called an "acute exacerbation"). Here is a graphic showing the results of the study:


The red bars represent the outcomes of people with IPF who took prednisone, azathioprine, and NAC ("triple therapy"). The blue bars are the outcomes of those who took placebo. These data come from the PANTHER-IPF clinical trial results published in The New England Journal of Medicine in 2012 which you can access here.


It is clear that triple therapy is harmful for people with IPF. Based on these results, the team running the PANTHER-IPF study did exactly what you would expect. Patients enrolled in the triple-therapy arm were told to stop taking their study medications, and as new patients were enrolled into the study, they were not permitted to enroll in the triple therapy arm. New patients entering the study could only enroll in the NAC or placebo arms.

This brings us to this week. The results of the NAC alone arm were published online and presented in San Diego. NAC had no meaningful effect on the risk of death, disease progression, lung function tests, or breathlessness. NAC did seem to prevent worsening of mental well being, but it isn't clear exactly why that is or even what this means for people with IPF.  I wonder if perhaps NAC is helping "mental well being" by perhaps treating cough (which was not specifically measured in the PANTHER-IPF study).

My interpretation of this study is that NAC does not seem to have a meaningful effect on many of the things that matter to people suffering from IPF. But, please don't stop taking NAC without talking to your doctor first. NAC may still be appropriate for some people. 

I am interested in hearing your thoughts about NAC. If you have been taking it, do you feel that it had helped you?

27 comments :

  1. I have taken NAC for nearly 2 years, as suggested by my primary pulmonologist. MN Mayo doctor said "it won't hurt you" 1 year ago. I have cHP (DXed by VATS BX July 2012). I do not have/have never had a cough, I have never had an exacerbation and my disease has remained unchanged since the first symptoms appeared in 2010.
    I have to say my empirical evidence is that NAC probably doesn't do anything for me personally. I have a supply on hand that I will use up, and not purchase any more.
    I am reluctant to take any RX/OTC, as I have a deep in my soul feeling that my cHP is in fact the result of my having taken the RX hydrochlorothiazide. I coincidentally stopped taking this medication 1 month before I was DXed.
    I usually want loads of information whenever I am prescribed anything.

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  2. Dr. Lederer,
    My hepatologist told me to take NAC 500mg/bid since, around 2 years ago. (Tylenol was my favorite pain killer).
    He told me NAC is an antidote for acetaminophen poisoning in the liver. He added Glutathione is a powerful antioxidant that helps the body defend against toxicity, and it is most needed by those living with chronic liver disease. Because I'm living with a liver disease,plus Pulmonary Fibrosis, with a little COPD... I'll continue with NAC.
    When I have a cold, I need to take tylenol (for fever). I need NAC to help my liver to detoxify. Both, liver fibrosis and lung fibrosis are not progressing. (Praise the Lord!)
    BTW, I'll let him know about this study on October/2014 when I have to see him again.
    Anyway,thanks David for all the information.
    The Lord be with you!
    Pam Huff.

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    1. Sounds like a good reason to stay on NAC, Pam. Thanks for sharing

      Dave Lederer

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  3. Quite frankly, I don't believe that NAC really is helping me. I have been taking 600 mg, three times per day, for three years. It didn't really seem to help my cough, nor decrease mucus production. I have gone a week, or more, at times, without it, and didn't notice a difference.

    I have not other major illnesses, and I am currently still taking the NAC.

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  4. Hi Dr. Lederer
    I have been taking NAC for about a year now same as many 600mg 3x a day. I do not know if it's helping me or not and probably won't know unless I go off it completely. With nothing out there to help those of us with IPF and since it's probably not hurting me I plan to stay on it for now unless the doctors tell me otherwise.
    My question to you, how many people were enrolled in the NAC only part of the study?
    Thanks for taking time out of your very busy schedule to do these blogs
    Laura

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    1. Hi Laura,

      There were about 130 people with IPF in the NAC only part of the study. There were also about 130 people with IPF in the placebo part of the study.

      Dave Lederer

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  5. I started taking NAC in December, 2005, immediately after the IFIGENIA trial was published. From the beginning, I have only taken pharmaceutical grade 20% solution, which requires a prescription. July, 2014 will be ten years since diagnosis, and almost nine years on NAC. I have been stable all of that time at about 50% FVC. My "recovery" from a low point, where I was very sick, required a period of more than two years, and it was very gradual. NAC is the only treatment I have taken for IPF. Although I don't have a lot of physical strength, I don't even feel sick, and I am fairly active. In August, 2014, I will be 79. I have no intention of giiving up NAC or trying anything else. If you (IPF patients) are taking NAC, give it plenty of time--it is not a quick fix. Your progress will be measured in months, not days or weeks.

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  6. i started taking NAC mid 2006 just as i was diagnosed. after vats in sept showed uip, consultant wanted me to start pred and imuran. i resisted both but in jan 07 started imuran. i have continued to take NAC and imuran ever since. my tlco was 23 in 2006 and is now about 19. my consultant told me earlier this year that the expectation was that someone like me would lose 50litres of lung function a year and i had only lost 30. i am currently awaiting transplant evaluation here in uk. for me NAC made my life worth living. previous to taking it i coughed all day long (had to give up work in 06) and was in distress. i believe it has helped ameliorate the toxicity of the imuran, given me an anti oxident boost and thinned my mucous to enable less coughing. i havent had a chest infection. i have been on o2 24/7 since 2009. my consultants now want to me stop imuran and change to cytoxan which i am not keen on at all.

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  7. I started taking NAC a few years ago and it has helped me by making it easier to cough. I haven't seen any other benefits. But during that time my TLCO dropped from 40 to 25. I am now taking Pirfenidone as well but having already survived 8 years I feel that I am one of the lucky ones. My biggest concern with all of these trials is that they are trying to find a cure for IPF but how can they be sure that all of us with IPF symptoms have the same illness?

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    1. Hi Malcolm,

      "...how can they be sure that all of us with IPF symptoms have the same illness?"

      That is truly a great question! There is a lot of research going on trying to figure out if "IPF" is actually more than one single disease. Eventually, we will sort this out and be able to target specific treatments to those most likely to benefit based on their own specific disease. I often tell my patients that everyone has their own kind of pulmonary fibrosis. Same idea you have here.

      All the best.

      Dave Lederer

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    2. First, I want to express my gratitude for the updated information included here and for the web site, Patients Like Me; it has given me a calmness about my IPF I had been seeking unknowingly, to communicate with others with the common rare illness.I was diagnosed in Dec 2011 coincidentally on a CT scan when looking for another problem, I had had a dry cough for a year, my O2 remains good to date. I took prednisone for about a year and asked if I could stop it because of long term side effects and did, could feel no difference. I took NAC 600 twice a day for about 2.5 years and felt no difference. My cough is worse with cold weather and I started taking Mucinex when it was so bad. I developed a sensitivity to fragrances, chemicals, etc to include some foods cooking which triggers terrible coughing spurts. I wear a mask in public frequently. I had my first exacerbation in May 2015 which lasted for about five weeks, I thought it was the beginning of the end at the time. I did go thru pulmonary rehab and high recommend it for every IPF patient. Again, thank you for the great information. Shirley Singleton

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  8. I have a question for Anonymous of Sept 22,2015. I was diagnosed with IPF over a year ago and was told there is no treatment, nothing works and I would get oxygen at the end. I was told to lose weight and exercise more so that my lungs would have less body weight to support. Because there is no hope or help for this disease, I decided not to go back for further tests. Why bother, I'm going to die anyways. I was not told about pulmonary rehab. What does that consist of? I am aware it will not be a cure. Thank you. Elizabeth

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    1. Hi Elizabeth. I know you directed your post to Anonymous of Sept 22, 2015 -- I hope you don't mind if I also comment. There is a lot that can be done to help people living with IPF:

      1. If you smoke, quit smoking
      2. Get tested for the need for supplemental oxygen -- it is one of only 3 treatments that helps improve breathlessness and your quality-of-life
      3. Enroll in pulmonary rehabilitation -- also improves breathlessness and quality-of-life
      4. Make sure your vaccines are up to date (particularly influenza and pneumococcal vaccinations)
      5. Talk to your doctor about lung transplantation - also improves breathlessness and quality-of-life for many
      6. Talk to your doctor about pirfenidone and nintedanib -- two drugs available in many parts of the world to treat IPF. They each cut the rate of progression of IPF in half.
      7. Participate in an ILD/PF support group.
      8. Learn more at pulmonaryfibrosis.org

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  9. I have PF PAH tachycardia and a bit of COPD. Worse almost I have long standing nerve pain in my thigh post shingles years ago.I have almost finished a pulmonary rehab course. It has made a simply huge difference to me. More the exercise component rather than the lectures as I was well informed. The exercise component is partially aerobic and partly strength training. It is not as demanding as a regular circuit class but otherwise similar. Many participants are doing the course with their oxygen bottles as company. After a few weeks my recovery after aerobic exercise is very quick and I can go back to 95-99 blood oxygen in a couple of minutes post exercise. During exercise I drop to about 90. I love being stronger it is very empowering. I can, for a while anyway, now walk at the same speed as normal people; though I have problems talking at the same time. Before my walking speed was pathetic. I am 74. F Go for it Elizabeth it will change your life.

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  10. Hi, Dr.

    I'mean an anesthesia resident at an Institute in México.
    My dad has pulmonary fibrosis because of silicosis and a neumologist recommended him NAC, about PANTHER-IPF, I have wonder why they didn't measure more outcomes and I have my doubts about the number of patients in the study.

    Specific question: what do you think about NAC in pulmonary fibrosis of other etiologies than idiopathic.

    Great article by the way, my best wishes from Mexico

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    1. Hi Iván. I am sorry to hear about your dad. I hope he isn't suffering. I generally do not use NAC for my patients with pulmonary fibrosis, and the ATS/ERS/JRS/ALAT guidelines do NOT recommend its widespread use in idiopathic pulmonary fibrosis, although the guidelines do recognize that NAC might be appropriate for some people with IPF. The PANTER-IPF study suggests that NAC does not influence the progression of IPF. The decision to take NAC should be made after a detailed conversation of the risks and benefits between your dad, his doctor, and you. I can't make any medical recommendations for your dad.

      best wishes and thanks for your kinds words

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  11. I have been on Ofev for almost a year after being diagnosed with IPF 09/15. I seem to be unchanged and of course the only way to know is to be tested again. My question is if it would be unwise to use NAC with Ofev. I understand there is little research and I don't want to make things worse. So far I have SOB with exertion but otherwise have a decent quality of life. Thank you for the above information - greatly appreciated.

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    1. Hi Ace. As you might suspect, I cannot give you specific medical advice or recommendations, but I can give you medical information. Currently, the highest quality evidence we have (from a randomized trial) is that NAC does not slow the progression of IPF. In addition, current guidelines recommend against the use of NAC to treat IPF. in the end, any decision to start NAC should be individualized -- only you and your doctor can decide that. I am sorry that I can't give you an individualized recommendation myself. All the best.

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    2. Thank you for your reply. This has been very helpful. I don't see a reason to use NAC at this point.

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  12. Hi Doc thank you for your publication.Am an oral surgeon 59 years old.Ive been diagnosed IPF after CT since last year scan and mild breathlessness on exertion.I was advised to take steroids and Azoran but i resisted because i was not feeling so sick and at the same time knowing the side effects .After 1 year ive done another CT and there is a little progression.I have done tests to exclude autoimmune diseases not yet got the results.Anothr doctor wants to put me on Pirfenidone.But am very scared of side effects like rash photosensitivity and somnolence.Right now am living a normal life and working normally. If taking drugs will worsenconsiderably my quality of life and unable to work then ill not go for it.On the other hand my dad had respiratory problems but died fromCVA. two of my sisters have breathlessness on exertion but still living a normal life . they are 72 and 65 y.old. and both are on steroids azoran since long.Me i want to try serrapeptase, H2o2 and NAC and other natural remedies first, then ill see. And if one day i have to embark on heavy drugs then i would prefer cortisone and Azoran which have been usedfor more than 70 years. The new drugs are so expensive, also lot of side effects, with unknown mechanism of action and needs more studies. Finally i am scared that the published efficacy of the new drugs may be commercially driven because the papers blacklists all former treatment options. I would like to have your humble opinion while knnowing that everyone may have his own one and may differ. Thank David. Fred

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    1. Hi Fred. Thank you not only for sharing your story here, but also for reminding me -- and hopefully other readers -- that we are each allowed to have our own opinions. About anything and everything. I completely respect your opinion to decide not to take a drug to slow the progression of scarring. It sounds like you have educated yourself about it -- and certainly any decision you make should be preceded by a discussion with your doctor (i hope this has already happened. if not, please please please do discuss it with your doctor before making any decisions). Some treatments are right for some people, and no treatment is right for all people. My only substantial comment is that there are strong data that indicate that treatment with steroids (prednisone) and azathioprine (Azoran) increase the risk of dying if you have IPF: http://www.nejm.org/doi/full/10.1056/NEJMoa1113354#t=abstract.

      My patients with IPF will tell you that I recommend that most of them take one of the new drugs to slow progression of fibrosis. I would rather try to slow the progression rather than waiting for progression to occur. Perhaps something you can talk to your doctor about.

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  13. I've been taking NAC for reactive airway dz for about a year. If I miss more than a couple days of dosing, I become extremely wheezy to the point of requiring duonebs bid. I know that it has made a huge difference for me.

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  14. Im Simone Bever i was diagnosed of Pulmonary Fibrosis for 4 years, i have tried several doctors with different types of medications with no help, i was browsing the net and i came across Standard Herbs Home i decided to give a try and i purchased their herbal remedy and i used it for 3 weeks and i am totally cure of Pulmonary fibrosis. Thanks to you Standard Herbs Home. Will advice you to have a contact with them if you have any similar problem or any type of disease through website: www.standardherbshome.com or info@standardherbshome.com

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