Study discovers biomarkers to predict the progression of idiopathic pulmonary fibrosis

Article via;   http://www.medicalnewstoday.com

A new blood test developed by experts at Royal Brompton Hospital could give patients with idiopathic pulmonary fibrosis (IPF) a better idea of their prognosis and whether or not treatments that can slow down the progression of the disease are working. 

The condition - thought to affect up to 20,000 people in the UK - causes progressive scarring of the lungs and is often fatal. 

The Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE) study, the largest and most detailed observational IPF study of its kind, recruited 214 patients, who were identified by Royal Brompton Hospital and the University of Nottingham. The findings have been published online in the Lancet Respiratory Medicine this week in a paper written by IPF experts, including Dr Toby Maher, consultant respiratory physician at Royal Brompton and head of the Fibrosis Research Group at Imperial College London, Anne-Marie Russell, senior research nurse at Royal Brompton and Dr Gisli Jenkins at the University of Nottingham. 

The study, conducted at the National Institute for Health Research (NIHR) Royal Brompton Respiratory Biomedical Research Unit (BRU), took samples of blood and analysed the concentrations of several neoepitopes, which are types of proteins. These were measured at baseline and then at regular intervals throughout the following six months. Physiological measurements, including the amount of air which could be forcibly exhaled from the lungs and how much oxygen travels from air sacs (alveoli) in the lungs to the bloodstream, were also taken to detect how the condition was progressing. 

The research, which is the largest and most detailed observational IPF study of its kind, showed that the concentration of neoepitopes were higher in people with the condition compared with healthy controls. Some of the biomarkers were associated with worsening disease and outcomes and changes in their concentrations after three months appeared to predict the progression of IPF earlier than the physiological measurements. 

The results suggest that biomarkers could also be useful in the early stages of clinical trials for new treatments, as the measurements could indicate when the patient is responding to them.

Measurement of the neoepitopes may also be of use to clinicians when it comes to deciding what treatment to give patients, as it could potentially inform them if medication is working and thus help with the management of the disease. 

This could now have particular use because there are two antifibrotic drugs, pirfenidone and nintedanib, which have been approved for use in the UK within the last two years and both have been shown to slow disease progression. 

Commenting on the research, Dr Maher said: 
"These biomarkers have the potential to improve the treatment of IPF by enabling doctors to determine whether treatments are working or not at an early stage and before permanent lung damage has developed. Furthermore, the biomarkers may enable clinical trials in IPF to be much shorter, something which should speed up the process of making new treatments available for this devastating disease." 

Dr Maher and Dr Jenkins are involved in continued research which aims to make these blood tests available in specialist clinics. Further research, to search for other biomarkers of IPF and potential new ways of treating the disease, is ongoing.

 It is not known why IPF occurs, but it appears to affect cells that line the alveoli in the lungs, causing them to become damaged and die. In response, the body tries to repair the damage by releasing fibroblast cells, but the over-production of these cells leads to scarring and hardening (fibrosis) of lung tissue. The scarring means the lungs cannot work properly and patients are often short of breath and have a persistent dry cough, fatigue and gastric reflux. Patients with the condition have an average life expectancy of three years and the number of cases in the UK is increasing by around five per cent a year. 

Dr Maher said:
 "Although newly available treatments may help, this ongoing research is required to ensure better outcomes for patients with IPF." 

The research was funded by GlaxoSmithKline and the Medical Research Council and sponsored by Royal Brompton & Harefield NHS Foundation Trust and the University of Nottingham. Royal Brompton has the only unit in the UK solely dedicated to the management of patients with interstitial lung disease (ILD), the term used for more than 200 lung diseases that affect the tissue and space around the air sacs in the lung, including IPF. Experts at the hospital care for the largest number of IPF patients in the UK and receive around 1,000 new referrals every year. 

Longitudinal change in collagen degradation biomarkers in idiopathic pulmonary fibrosis: an analysis from the prospective, multicentre PROFILE study, R Gisli Jenkins, PhD, Juliet K Simpson, PhD, Gauri Saini, MD, Jane H Bentley, PhD, Anne-Marie Russell, MSc, Rebecca Braybrooke, RGN, Philip L Molyneaux, MD, Tricia M McKeever, PhD, Athol U Wells, MD, Aiden Flynn, PhD, Prof Richard B Hubbard, MD, Diana J Leeming, PhD, Richard P Marshall, PhD, Morten A Karsdal, PhD, Pauline T Lukey, PhD, Dr Toby M Maher, PhD, Lancet Respiratory Medicine, doi: 10.1016/S2213-2600(15)00048-X, published online 11 March 2015.
Source: Royal Brompton & Harefield NHS Foundation Trust

Rapid Progressors Speed to End Stage Pulmonary Fibrosis

Article Via; http://www.medpagetoday.com/pulmonology/smokingcopd/5805

Published: May 31, 2007

Download Complimentary Source PDF 

By  Crystal Phend , Staff Writer, MedPage Today

Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine

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Action Points

• Explain to interested patients that the study suggests that idiopathic pulmonary fibrosis may affect patients differently depending on gene expression and environmental factors, such as smoking.
• Caution patients that the study was preliminary and further study will be needed before physicians can prospectively determine which patients could experience rapid disease progression.

MEXICO CITY, May 31 -- A difference in genetic patterns may explain why some idiopathic pulmonary fibrosis patients, especially men who smoke, die more quickly after diagnosis than others do.

These rapid progressors were 6.5-fold more likely to be men and seven-fold more likely to have been smokers than slow progressors, found Moisés Selman, M.D., of the Instituto Nacional de Enfermedades Respiratorias here, and colleagues.

In the retrospective study, gene expression patterns differed between fast and slow progressors, implying biologically-distinct phenotypes of the disease, they wrote online in the journal Public Library of Science ONE.

The findings suggest that physicians should pay more attention to the time of onset of symptoms to identify these patients who are at greater risk, they said.

Most idiopathic pulmonary fibrosis patients have symptoms long before diagnosis, then slowly progress, with death coming within five years of diagnosis, they noted.

But, they said, distinct patterns of disease progression have become increasingly clear clinically.

To characterize these patterns, the researchers reviewed the charts of 167 consecutive patients with the disease who were evaluated at a single center between 1995 and 2004. Seven healthy volunteers as well as lung samples from autopsies were also studied as controls for immunohistochemistry, cellular and genetic profiling.

Rapid progressors were defined as those with no more than six months of symptoms before seeking medical attention.

From symptom onset, these 26 patients had a median follow-up of 13.5 months and median survival of 27 months. From diagnosis, median follow-up was 10 months and survival was 25 months.

Slow progressors were defined as those with at least 24 months of symptoms before presentation.

From symptom onset, these 88 patients had a median follow-up of 60.5 months and median survival of 93 months. From diagnosis, median follow-up was 17 months and median survival was 32 months.

In a multivariate analysis, significant factors in survival among the overall cohort included time from symptom onset to first consult, smoking, male gender, and lung function as measured by forced vital capacity.

Among the 80% to 85% of patients with known vital status, rapid progressors had significantly lower survival rates than slow progressors (hazard ratio 9.0, 95% confidence interval 4.48 to 18.3, P<0.001) or intermediate progressors (P=0.045).

Mortality determined from the time of diagnosis also tended to be higher in the rapid progressors (HR 1.5, 95% CI 0.81 to 2.87, P=0.18).

Among rapid progressors, significantly more patients were:

• Male (odds ratio 6.5, 95% CI 1.4 to 29.5, P=0.006).
• Ever smokers (OR 3.04, 95% CI 1.1 to 8.3, P=0.04).
• Current smokers (OR 7.1, 95% CI 1.2 to 40.9, P=0.02)

These rapid progressors, though, were not simply patients presenting at a different stage of disease or an acute exacerbation, the researchers said. Their physiologic, radiologic, and histopathologic parameters were similar to those of slow progressors.

Socioeconomic and educational background -- which can influence when patients seek treatment -- as well as initial treatment were similar between groups, they said. And there were no differences between rapid and slow progressors in pack-years smoked.

Nor were there baseline differences in age, lung function alterations, oxygen saturation, extent of changes seen on high resolution computed tomography, or bronchoalveolar lavage cellular profile, the researchers noted.

Lung biopsies done on 31% of patients showed no differences in baseline morphology for interstitial inflammation, pulmonary hypertension changes, smooth muscle hyperplasia, type 2 cell hyperplasia, or extent of fibrosis or honeycombing.

However, Dr. Selman wrote, there were important differences showing that "rapid progressors appear to represent a distinct biological phenotype among patients with idiopathic pulmonary fibrosis."

In a global gene expression analysis in a subset of patients, the researchers found that 437 genes were expressed differently between groups.

Rapid progressors overexpressed genes involved in morphogenesis, oxidative stress, migration and proliferation, and fibroblast and smooth muscle cell function.

This upregulation was seen on immunohistochemistry for the adenosine-2B receptor, which is involved in a key process of fibrotic remodeling, and prominin-1/CD133, which is found in hematopoietic stem cells and embryonic epithelium.

Furthermore, bronchoalveolar lavage showed that rapid progressors had more than a twofold increase in active matrix metalloproteinase-9, which may contribute to abnormal tissue repair and remodeling, compared with slow progressors.

Rapid progressors also had higher fibroblast migration than slow progressors (238% versus 123%, P<0.05) or controls (238% versus 30%, P<0.01).

While these subgroup studies were of limited size, "the relatively stringent selection of genes, the protein verification by immunohistochemistry on additional samples, and the biological relevance of the genes suggest that our results are biologically meaningful," the investigators wrote.

They also noted, however, that their study was preliminary and limited by retrospective data collection and dependence on patient recall of symptom duration.

However, "taken together with reports of the impact of acute exacerbations of idiopathic pulmonary fibrosis on morbidity and mortality, our results further highlight the variability in the progression and outcome of [the disease]," they concluded.

"These findings may explain, in part, the difficulty in obtaining significant and reproducible results in studies of therapeutic interventions in patients with idiopathic pulmonary fibrosis," they added.

The study was partially supported by a grant from the Universidad Nacional Autónoma de México. One of the researchers was supported by grants from the National Institutes of Health and by a donation from the Simmons family. The researchers reported no conflicts of interest.

Pulmonary Function Test (PFT)

Many people diagnosed with lung restricted diseases are referred to take a Pulmonary Function Test (PFT). National Jewish Health gives an over-all description of what the test will entail.

Routine Pulmonary Function Test

Here is also a link that will help you understand the results of your PFT:

http://www2.nau.edu/~daa/lecture/pft.htm

Idiopathic Pulmonary Fibrosis via; The Canadian Pulmonary Fibrosis Foundation

Every Breath Counts~ Idiopathic Pulmonary Fibrosis- Discovery Channel- June 21st- 8:00 am ET/PT

I can't tell you how excited I am to see this documentary, Every Breath Counts~ Idiopathic Pulmonary Fibrosis on the Discovery Channel- June 21st- 8:00 am ET/PT. 

Finally, an opportunity for others to learn about this disease.  Despite the many lives it affects, it is still relatively unknown.  People who suffer from this disease, as well as their family members, desperately want to live.  Many also want awareness and general understanding of what they have to go through. In this documentary is a little piece of all of our stories. 

I lost my beautiful husband to this disease and as I watched the trailer to this film, for a brief moment, I felt as though I am watching something that is affecting someone else.  It wasn't us- this wasn't our family....  But, it was us.  This was our family's story.  My family lost a father and husband to this disease and I can never hold his hand in mine again.   

When I think about the tremendous impact of this experience being multiplied by all the others who are still being diagnosed, I know that every bit of awareness is necessary.  Even if you have never heard of IPF, do try to watch this and discuss it with a friend. You never know how that one action might help to find a cure.  

With Love,

 ~Breathing

To watch a preview, Click:  http://everybreathcountsfilm.com/

Since you have been gone~ 2 years, 4 months

It is Spring once more, Babe.  This year I have been much better about pulling my head out from the covers and enjoying going outside.  It still was a struggle to see that a new season has come upon us and you are not here, physically to share it with.  Sometimes, I think it was because you passed away in December, two-weeks before Christmas, and I tend to stay in that space too long.  -The space in which it is cold outside and the shortness of the day descends upon me like a shadowy cloak.  I feel invisible during that season.  The feeling is familiar and reassuring, but then, like a surprise, a new season gradually comes upon stretching sunlight into my world. Rather than hide reluctantly from it, as my previous tendency has been, I realize that it will still come and that time will move forward.   

Not a day goes by that I do not speak to you (as you know) and most of the time I hope you can hear me. The rest of the time, I am not so sure because you know I can be long winded and sometimes tend to ramble.  I think you might even know when I am going to do that before I do.  I see the signs you send me, especially all the birds, and I also feel the way you still support me and there are times I really do sense a larger, overall feeling of glowing love with the intensity that can only be from you.  I also think about the year-long period that you were sick.  The heart-breaking moments when you struggled and there was nothing I could do.  

I think about the moments that I used to step out onto the balcony and look at the stars and think that this could not be happening and I would wish with all my might that something might turn around the progression of Pulmonary Fibrosis within your body.  At that time, I also had a sense that what I was praying for was bigger than you and I, almost like I wanted to re-write the stars themselves.  

I stay involved with the Pulmonary Fibrosis community and I have to say, since you have been gone, there have been so many new names and each person has such an individual story that at times I wonder if our individual story has made any kind of a difference at all.  But then, I realize all of our stories, collectively, create's one large entity of its own.  Still, there is not a cure for the disease, although it seems as though there is more conversation regarding a variety of treatments as well as possible links as to why this disease occurs in some people.  I know you always wondered what caused it for you. 

 It even scared your best friend and co-worker enough that he, himself, went and had a CT scan while you were ill. He was afraid it was something environmental that he may have been exposed to as well.  He showed no signs of it.  Of course, he never told you that, but he let me know about the ways your illness affected him, shortly after your funeral.  Speaking of friends, I have to say that there are so many wonderful people who, unfortunately, have become familiar with Pulmonary Fibrosis, either by having it themselves, or through losing a family member to it.  I feel honored to know some of these people and am truly amazed at the support we feel for one another.  

Home is going well.  I planted 4 lilac bushes along our west fence-line and 10 more are due to arrive, soon. It was one of your favorite plants and I won't forget that one time we were sitting at our favorite hamburger shop and you were talking about the Lilac because there were a whole bunch outside.  You were saying how much you enjoyed the smell of them during spring and as you were talking, a really large gust of wind started up outside the window and the Lilacs started to lose petals from their bloom.  It looked like it was snowing Lilac.  That was right about when you wanted to discuss getting married at that exact hamburger shop!  That makes me giggle.  I still go there, but I am glad we found our own perfect spot for our wedding. 

 I think a lot about our wedding, too.  That was a perfect day ~always.  I see your face, the way it looked when I was walking down the aisle toward you.  I know the bride is supposed to be glowing, but you really had a light emulating from you and it made me want to run up the aisle to join you!  I had to pace myself.  I also remember how you got Strawberry Lace cake on the top of my wedding dress because you tried to shove the wedding cake into my face.  Not cool!

Speaking of Strawberries, I planted a whole strawberry patch!  All I could think about the whole time is how much you would have loved if I did that years ago.  We now have six, good sized rows.  I really do feel you guiding me.  It was amazing because about 3 weeks back I kept posting pictures of strawberry stuff on Breathing's Face Book page and that same week at my orthodontist appointment, the assistant and I started talking gardening and she mentioned that she is going to thin out her strawberry patch.  I said, "I'll take them!!!"  and Viola! We have baby strawberries!  

It has really been a Godsend.  Because of the strawberries, and the preparation thereof, I have been wearing my gardening hat at 8:am in the morning.  It feels good.  It feels good on the outside and on the inside.  To be out there, not caring what anyone thinks, and why should I?  I am doing what you and I loved doing together.  Boy, after losing you, I had the hardest time carrying on working in the yard because you and I spent most of our free time together doing it together.  We found it so beautiful and it almost hurt to do it without you.  The same goes for traveling.  Everywhere I went, I remembered everything we ever saw together.  And, we put on a lot of miles with each other.  When I do these things now, I feel it is when I am closest to you.  

Thank Goodness for Spring.  It literally has come to save me.  I love you so much!  ~And I will see you tomorrow in the garden.  

~Breathing

We Should All Have This Discussion ~Malcolm Weallans

It seems that being semi-retired is a misnomer, or at least it is in my case. I seem to have less time now than I used to. Besides helping NICE to train other Guideline Development Group members I also seem to have got involved with the Patient Voices part of NHS England. I think it was because of this that I heard of a conference that I attended today. The subject of the conference "The Leadership Alliance for the Care of Dying People" engagement.

This conference was one of a series of 12 being run in 12 different locations in England. The basic concept is that they are looking at how to replace the Liverpool Care Pathway and are looking for the views of patients, care-givers, care workers, and professionals as to what next. The conferences are being facilitated by a number of organizations including MacMillan, Marie Curie, help the hospices, and most of the locations are hospices so obviously they weren't expecting a large turnout.

But the subject is of great importance to all patients with a terminal condition. They really want to know what patients feel about these plans but as yet they don't know how to get patients to attend. I was appalled by the document that I received telling me about the events and I couldn't forward that to this group as I felt it gave a wrong impression. The thing I found most difficult was the title which referred to "for people at the end of life" and accompanied this by pictures of geriatrics. As we know from this group end of life is not confined to geriatrics.

But I still decided that this was worth me spending a few hours at showing people that there are significant other groups of people who should be considered in this context. I know that many of the group members will need to think about these issues and would want to make sure that they and/or their loved ones would be getting the best possible care at end of life.

The afternoon centered on discussing a document that has been produced by the Leadership Alliance for the care of Dying People. This was in response to the report produced by Julia Neuberger into what was wrong with the Liverpool Care Pathway. Basically they have decided to throw away the Liverpool Care Pathway and replace it with something else and they want to know what else. They have produced a discussion document which can be downloaded from 
www.england.nhs.uk/ourwork/qual-clin-lead/lac/
and you can also comment on this. The discussions from the 12 conferences will be discussed to make sure that whatever happens there will be no repeat of the Liverpool Care Pathway debacle.

What I found most surprising this afternoon was that there were only 3 or 4 patients and there were 30-40 others. These others were representatives from hospices and care organizations, many of whom have been trained as nurses but have chosen to give up their vocation in favor of an office job. How significant is that? The other thing that I found surprising was that they all talked about how many of the proposals in the document were covered by advance care directives and the fact that this plan does not really cover what as wrong with the LCP. As they all seemed to agree the Liverpool Care pathway was not a bad idea, it had just been misused by a number of medics who seemed to forget that there is a need for compassion towards the patient and the family and instead concentrated on making sure that they ticked all the boxes so that they would not be penalized financially.  But there was also a group who had read the document and felt that this was merely another way of explaining Advanced care Directives/Plans. I don't know about you but I have never been asked about my preferences for end of life care, and that is despite having a long term terminal condition, and having spent 5 days in a coronary care unit. And I don't recall many people mentioning such directives or plans. Surely we should all have this discussion. 

Please take some time to get involved in this process and make your views heard. It is very important that patients and carers should make their feelings known.

Written By:  Malcolm Weallans

For further information: http://www.england.nhs.uk/ourwork/qual-clin-lead/lac/

**Thank You Malcolm for sharing this fantastic information! This particular link is for those in the United Kingdom, although the concept is sound, no matter where we live. ~Breathing

Sounds of IPF Mini-mentary

Soul SAT's

Oxygen Saturation (SAT): 

Oxygen is vital for human survival. All the cells in our body need a certain amount of oxygen to carry out their duties. Oxygen saturation is the amount of oxygen that red blood cells carry, which attach to hemoglobin molecules. Normal saturation levels are 95 to 99 percent. Typically, a person will only reach 100 percent when supplemental oxygen is used. It's when saturation levels fall below 90 percent that the body begins to suffer adverse effects.  (via eHow.com)

 

The above photo is of an Oxygen Saturation journal that I kept while caring for my husband.  We usually took his SAT measurements when he was resting, then right after activity, such as a bath.  We documented how far his SAT levels dropped and how long they took to recover.  It was helpful for my husband and I to see how we could adjust his Oxygen intake according to his needs. 

 

As the description above indicates, that Oxygen is vital for human survival.  If the saturation level drops below certain levels then it can affect the rest of the body.  When my husbands SAT's dropped, he became tired and listless.

 

This has me wondering if the Soul or Spirit within us needs its own nourishment, just as our body does.  After my husband passed away, I spent a great deal of time in shock.  I dealt with this loss by realizing all the things that needed to be done around me and I busied myself with this.  As I wrote previously, I created a list of goals to achieve and set about achieving them all. 

 

Now, I seem to be taking a time out.  Wondering to myself what list of goals I should create next.  I sat down and started writing all of my goals, whether planting a garden or painting the house.  I know these are positive things.  But, I just sit and look at the list.  Stumped as to where to start.  My heart does not seem to be in it.  I have realized that may be because my soul needs nourishment so that it can breathe and grow.  To listen to my soul, my spirit.  To give it nourishment, feed it new oxygen.  I want to put that at the top of my list.

Reconciling the Two of You

"You know, a year is a long time to be sick" a person once told me in regard to my husband.

I really didn't think it was.  To be terminally ill within a period of a year, seemed like a pretty fast course of events in my eyes.  After all, it is not as though my husband was immediately incapacitated the moment he was diagnosed with Pulmonary Fibrosis.  As a matter of fact, he only went into the doctor's office thinking he had developed allergies...

The illness occurred in stages, as well as his acceptance of what was happening.  He had always been a very active man.  He took care of everything.  To everyone who knew him, and even to himself, he was strong.  I can tell you, I have never felt so safe and secure with anyone else.  Being that he was a bit of a traditional person, this worked out nicely.  He was my protector.  His physical strength led to the belief that he was emotionally the same way.  Dependable and strong.  Which was true as well.  At least, he worked very hard to be so.  I think he tried to give me the best of himself. 

These things do not immediately change when diagnosed with a disease.  The disease itself did not truly begin to reveal itself until a good six-months later.  That was when everything he did began to take a great deal of effort.  He was gallant in his will to hold onto his strength.  But, in stages and degrees, his strength began to slip away from him.  Within each degree, he suffered greatly emotionally.  It was so hard for him to believe that this was happening.  It was hard for me to believe it, too.

By October, I knew he had become a different person than he was before.  He needed me.  He always had needed me, although now he needed me to help him through the rest of his life.  I took a leave from work.  I didn't want to do this because it meant he would not have much more time, and how could I possibly accept this?  The logical side of me knew it was time, but my heart denied it all the way.  All the way up until the day he passed away, in December.  

Now, when my heart and mind goes to him, I think about all the things we did in our years together.  We are active.  Moving.  Always moving.  Now and then, my mind and heart jumps to the other spectrum -his last days.  All the things I blocked out as they were happening, come back so fresh it fills my eyes with tears.  Him, carried into the bathtub for his last bath.  The few steps he was able to take before resigning himself to bed, for good.   

I know this is hard to hear.  Especially if you are reading this and have Pulmonary Fibrosis.  The interesting thing is that it affects each person differently and many have found ways to live a flourishing life and go much further than my hubby and I did.  This is hard for me to say, too.  But, I have to be honest to my experience.  What I am currently struggling with, is how this disease could have changed my husband so quickly?  I was there with him, but still can't seem to believe what has happened.  My heart can't seem to reconcile the vast differences in memories I have about one person.

Kinky

Every morning, after my husband wakes up, we take some time to build up his SATs and work the stiffness  out of his body.  After all, his body is primarily in one position for most of the time and it is good to work the kinks out.  Off goes the covers and the morning air hits his body, then we begin to do our version of "yoga".  


Our "yoga" consists of myself, bending and lifting his legs into all sorts of positions.  Bringing them up close to his chest and turning his hips from side to side.  To this, he moans while joints pop and creak.  Ahhhh, it does feel good, though.  At least that is how I imagine it, living vicariously through him. 

"This is what happens when you get old."  He says this morning.

"But, Honey, you're not old!"   I respond.

To this he replies, "I know!  That is what I've been saying.  Someone sure got this wrong."

He is right, you know. 
There is never the "right" person that this should happen to.

Pulmonary Fibrosis affects many people of all ages and gender. 

I don't like it. 

I don't like any of this one bit.