Thursday, March 24, 2016

To be or not to be (Musings on IPF and Esbriet)

Updated: 25 March 2016
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Another blog on my spouse having idiopathic pulmonary fibrosis (IPF) and its treatment with pirfenidone (Esbriet®). See Further Reading for additional resources.

The theme is how do patients with an incurable disease make decisions when the treatment has adverse side effects that make life miserable. Who helps them?

In brief, idiopathic pulmonary fibrosis (IPF) is an incurable, chronic progressive disease typically affecting people over 65, in which the lung's normal connective tissue is replaced by scar tissue. Scar tissue forms when the body has an injury anywhere, but in IPF, for unknown reasons, the scarring (fibrosis) does not stop as it normally does. 

IPF's cause is unknown but the disease causes the lungs to become stiff and impairs their ability to function, i.e., move oxygen into the bloodstream and body tissues.

IPF has a median survival of 2-4 years from diagnosis. Most patients die within 3-5 years but some patients live much longer. See a simplified diagram of ways IPF typically progresses.


Until pirfenidone (Esbriet®)) no effective treatment existed for IPF. In clinical trials Esbriet® was shown to decrease scarring (fibrosis formation) and the incidence of death from all causes and from IPF alone. See below for more details.

Cost: Esbriet® was funded in the UK and elsewhere before in Canada but it now is, In Canada Esbriet® costs provincial governments ~$43,000 CDN per patient per year.

Esbriet® gives IPF patients hope for a longer life but, to some, that comes at an incredible cost to quality of life due to side effects.

The good stuff 
Although not a cure, Esbriet® offers the hope of maintaining lung function as measured by FVC (forced vital capacity - how much air a person can exhale during a forced breath). In IPF, FVC is a key measure of disease progression. Esbriet® doesn't improve FCV but does slow its decline.

Esbriet® has also has been shown to offer patients better life expectancy. For example, after one year:
  • 3.5% of patients on Esbriet® (n=22 of 278) died from all causes, versus 6.7% on placebo (n=42 of 277), a reduction of ~48%. 
  • 1.1% (7 of 278) died from IPF related causes versus 3.5% (22 of 277), a reduction of ~68%.
Of course, given the type of IPF disease a patient has makes such statistics iffy at best. No one knows how an individual's IPF will progress.

The bad stuff 
Unfortunately, Esbriet® has many side effects, also known as adverse events/reactions. It's important to recall that all drugs have side effects, ranging from harmless to severe reactions that require drug cessation.  

Also, with any drug's side effects, an individual may experience none, some, or all. A given side effect may show up immediately or only after being on the drug for awhile. Plus some side effects occur more commonly, others are rare. 

A complicating factor with side effects is that identifying them as directly related to the implicated drug can be difficult. The side effect may be due to drug interactions, a symptom of a co-existing disease, etc. 

Identification is easier if a side effect is well documented as commonly occurring and stops when the drug is stopped, even temporarily. This applies to sun sensitivity and Esbriet® (see below).
Adverse events related to Esbriet® include:
  • abdominal pain
  • bloating
  • gas
  • nausea
  • constipation
  • diarrhea
  • vomiting
  • decreased appetite
  • taste changes
  • difficulty sleeping
  • hot flushes
  • headache
  • indigestion, heartburn, or acid reflux
  • itchy, dry, or red skin
  • sun sensitivity (e.g., sunburn, skin rash, blistering or peeling skin)
  • sweating
  • tiredness
  • weight loss
  • muscle or joint aches or pains
  • Cough or hoarseness
  • sore throat
  • sneezing
  • ear congestion
  • dizziness
From my spouse's experience: 
  • Suppose you cannot get proper sleep, night after night (insomnia), so you always wake up tired.
  • Even when sleeping reasonably well, you're exhausted during the day.
  • You have no appetite and what you eat tastes different (awful).
  • You lose ~5 lbs every 10-14 days because you must force yourself to eat.
  • After eating anything, you're always bloated, have a stomach pain, suffer indigestion, and feel nauseous, often gagging during meals. 
  • After eating (and taking Esbriet®), you feel dizzy for a short time.
  • You alternate between diarrhea and constipation, the latter sometimes requiring extreme measures.
  • Your throat is always sore and you think you're coming down with a cold but it doesn't happen. 
  • You spend 1 hour in the sun and develop a sunburn and measles-like rash on exposed skin which lasts for weeks and requires stopping Esbriet® for a month, then going back on in increasing doses until the optimum dosage is reached.
    • The rash also means in future wearing long sleeves and a wide-brimmed hat (even in summer with temperature 30oC+) and lathering exposed skin with 50+ SPF lotion to walk outside and enjoy a sunny day.
  • You regularly suffer severe headaches. 
With these side effects eventually life becomes miserable. Do you 
  • Stay on Esbriet® because it extends your life?
  • Stop taking Esbriet® and opt for a better of quality of life though it may be shorter than if on the drug?
In general, respirologists/pulmonologists review lung function tests, and, if they see lab measures like FCV haven't decreased, assume you will stay on the drug because it's helping. Indeed, they want you to stay on the drug, because opting for life is paramount in their world.

Severe side effects seem to mean almost nil to physicians, presumably because they've never experienced such hell. Also, as physicians, naturally they want to believe they can do some good, even if a disease is devastating and incurable. 

What doesn't happen is discussing the options and consequences (albeit uncertain), i.e., the reality of an incurable disease and what patients can expect, albeit based on population studies, which may or may nor apply to individual patients.

Often well meaning physicians assumes patients and their families want only hope and cannot deal with grim realities. Best to ignore them? 

To be fair, I'm unsure what physicians could say, given the uncertainties. As well, they know that some patients may grab onto something they say and it could come back to bite them. And some doctors may not want to unduly influence patients one way or the other. Mind you, in other circumstances, I've found that's often not true. And so it goes....

But physician reluctance to discuss realities gives patients precious little upon which to base life and death decisions, even if definitive outcomes  are unknown. Fortunately, I'm okay with reading the medical literature and research findings, but suspect many are not. 

Perhaps that's how it must be. As in life, after all is said and done, individuals are responsible for their own choices. But it would be nice to make informed choices based on a physician's knowledge and experience of your circumstances combined with what population studies show. 

How can patients with incurable diseases choose the best treatment option, even when one doesn't exist?  In our case, my spouse went off Esbriet®  for a month due to sun sensitivity adverse event (mandated by physician), then again later, due to other side effects that led to an unbearable quality of life. While off the drug, the symptoms lessened and many disappeared altogether.

He's back on Esbriet® now, opting for extending life and coping with drug's side effects. We'll see how it goes. Sadly, we have no real support nor wise advice when making decisions. We could join a support group and may do that in time. 

In closing, let me emphasize that there are far worse fates than developing IPF later in life. Overall, both I and my spouse feel pretty darn lucky, even with the latest side effects being a 'bummer', as we'd say in the 60s. Life is good, all things considered.

As always, comments are most welcome. Be aware that comments are moderated, but only to prevent spam.

Idiopathic pulmonary fibrosis: now a treatable disease and other highlights from the 2014 American Thoracic Society Annual Conference. CMAJ, May 27, 2014. 

Brett Ley B, Harold R. Collard HR, and Talmadge E. King, Jr TE. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011;183( 4): 431-40.

King TE Jr, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2083-92. Epub 2014 May 18.

My earlier blogs on IPF

Saturday, March 12, 2016

One love (Musings on Chelsea fans' blame game)

Updated 13 Mar. 2016
Chelsea FC exited the UEFA Champions League 9 March and among some fans the blame game is on, or rather, continues. Blame has been fan norm since Chelsea's play this year was shown to be far from the excellence it was in 2014-15 when we won the Premier League, indeed led from start to finish. 
Today (12 March) we exited the FA Cup and blame reached a fever pitch. I need to get this off my chest while fresh. Many, perhaps most, Chelsea fans will disagree but this is how I see it.

Please keep in mind that I grew to respect José Mourinho but eventually that eroded as I watched his poor decisions and eventual crass manipulation to preserve his reputation. 


    • He was widely trashed after José Mourinho was fired and Emanalo spoke of "palpable discord" between José and the players and referred to José as 'the individual'. Emenalo haters, often longtime Chelsea fans, like to mention he has zero qualifications, coached a girl's club, and imply he has the job only because he's pal of Roman Abramovich, Chelsea's billionaire Russian owner since 2003.
    • Emenalo is blamed for not recruiting wisely. 
    • Some 'fair and balanced' fans use the Twitter hashtag #EmenaloOUT. Check it out with a Twitter search. Slightly less hateful than #RafaOut
  • Chelsea's Board of Directors, who presumably want the club to be winners but who many fans currently diss as incompetent. Fans didn't say this in earlier years when Chelsea won PL titles, and the UCL. Miraculously in space of one year, BOD are sh*t. 
    • Did José have no input into signings? Was he just a poodle to Emenalo and the Board's decisions? Hard to believe.
  • Specific Chelsea players, who it is claimed would not play for José and 'betrayed' him (José's own word). José played the blame game to protect his image as a great manager.
    • Chief culprits are players whose form dropped dramatically compared to last year, including
    • Diego Costa (20 PL goals 2014-15; 11 PL goals to date)
    • Eden Hazard (14 PL goals 2014-15; 0 PL goals to date)
  • Chelsea players in general (with one exception*), because they are deemed to lack club loyalty. You know the drill, score a goal and pound the club crest on your jersey. Indicates you are loyal to and devoted to your club. Pretty phony, given most players today are hired guns who play for several big businesses (clubs) over their careers.
    • *Exception is John Terry - Chelsea's Captain, Leader, Legend, who's been with the club from a young age, indeed more than half his life. When he taps the CFC crest, you know it means something.
WHO'S NOT BLAMED - José  Mourinho
Few longtime fans blame Mourinho who took Chelsea from PL winner to bottom of Premier League in 8 months and was fired after the club lost 9 of 16 PL games. José is the 'teflon manager', in same category as Jesus Christ or an infallible Pope to adoring fans. José rightly has huge deposits in fan's goodwill bank for his 3 PL wins.

The case for why José played a role in Chelsea's decline
(1) José's management style exhausts players after 2-3 years. Sooner rather than later millionaire players will say enough, I don't need this cynical manipulation. Players play for intrinsic reasons like love of the game and personal pride. Suspect the brighter among them resent José's mind games, see them for what they are, and naturally rebel.  

Takes a big personality to maintain control, keep the respect of players, adopt to changing circumstances, and develop youth. José Mourinho is an Alex Ferguson wannabee but his record shows he  lacks whatever it takes to manage a club for more than a few years. For interest:

(2) José prefers defense to freewheeling offenseJosé's preferred style of play tends to stifle creative players, especially midfielders used to pressing forward on the hunt for goals. For example, José couldn't let Juan Mata  - Chelsea's 2 time POTY  - be Juan Mata. Most fans grieved Mata's sale to Man United, but few criticized José for the loss. The magic of Mata-Hazard-Oscar was lost forever.

(3) José did not give Chelsea's young players (long list) a chance to shine, prove their worth. Why? Likely because to validate his genius as the 'special one', he needed wins now. Always playing the first squad, barring injuries, was the result. Even then, 'kids' seldom got a chance to play, gain top flight experience, prove their worth.  

(4) José was out of control, stressed and fearful for his reputation if the club lost a game, as shown by his treatment of Eva Carneiro and Jon Fearn. Only Eva had guts to call him on it, demand an apology

José quote: "I wasn't happy with my medical staff because even if you are a medical doctor or secretary on the bench you have to understand the game." Apparently, 
José winning takes precedence over giving medical help to a player who is on the pitch and asking for it.

At his core, José is a skilled manipulator who excels at obscuring his role in creating problems. He's an expert at the blame game. His main schtick is to blame referees and encourage fans to see the entire world as against us. As if Chelsea is so important that the entire Premier League - referees, referee association, FA -  would conspire to keep us down. Really?

He's done this act for years and it's worked well until senior management cottons on that there's dissension in the ranks and is forced to jettison him for the good of the club.

WHAT'S NOT BLAMED - Circumstance/Chance
Few Chelsea fans blame circumstance and chance. But Chelsea had many key players injured this year, including Gary Cahill, Diego Costa, Radamel Falcao, Eden Hazard, Nemanja Matić, Oscar, Loïc Rémy, John Terry, and Kurt Zouma.

Besides losing those players, injuries meant  that healthy substitutes were tossed into games lacking experience (because José gave them none to little) and key players like Willian often played exhausted. 

Players often lose form from year to year. Just a few of many:

  • Papiss Cisse, Newcastle United
  • Radamel Falcao, Man United
  • Wayne Rooney, Man United
  • Roberta Soldado, Tottenham Hotspurs
  • Fernando Torres, Chelsea
  • Thomas Vermaelen, Arsenal
Were all these players dogging it, out to get the manager fired? Or just struggling with circumstances that meant they lost their magic?

WHAT'S NOT BLAMED - Top players shun Chelsea
Many top players have not opted for Chelsea in recent years. Maybe they are happy where they are but maybe some are not keen to join Chelsea, even under genius manager José. 

In sports, as in life, some people prefer the blame game as opposed to examining themselves and those dear to them. To some fans, if something goes wrong, someone must be identified and blamed. The reasoning is as follows:

  • Those who I support are never responsible else I will be diminished as a savvy fan who knows it all.
  • When folks play the blame game, they often engage in irrational thinking to justify blaming others. 
    • For example, why in hell's name would Chelsea players want to sabotage the club and their reputations and future earnings by choosing to become losers - to say nothing of lowering their own feelings of self worth - all to cost José his job? Does not compute. 
If that were true, then following José's exit, form would miraculously reappear. It hasn't.

Also, the blame game crowd aren't satisfied with 'what players did was wrong.' Instead, players become lesser beings, unworthy of respect. It's personal and they are demonized as cretins who destroyed both 
José  and the fans' dreams of eternal Chelsea glory under José. 

What gets me most is Chelsea fans who put it all, or mostly all, down to lazy, pampered rich players betraying Gawd Almight, José.

Mourinho is a multi-millionaire who frequents Victoria Secrets fashion shows and GQ awards. With this lifestyle, he's interested in protecting his brand and earning power and expertly practices the blame game to do so. Any footie manager's decisions and actions are NOT infallible. 

To me, the players did NOT deliberately sabotage Chelsea. Which is not to say that José did not p*ss some of them off with cynical mind games and manipulation. Plus he creates unrelenting stress to perform perfectly, always. But to blame Chelsea's 2015-16 season on player sabotage is nuts. Players too want to protect their pride, brand and earning power. 

Sometimes bad things happen for complex, interrelated causes, not simplistic reasons like 'the players did it because beloved José could never be responsible.' Sort of akin to 'the dog ate my homework' vs admitting I, and my hero José, are responsible. 

Seems José's responsible for nothing when a club loses but gets credit for everything when it wins. 

Folks like simple explanations but simple seldom conforms to reality. 

Football clubs are big businesses where players are mere commodities to be bought and sold. To think of players as loyal souls who play their hearts out for a big business that they have no history with, that they know will dump them sooner or later, is deluded. Today most, indeed almost all, play for several clubs over a career.

In my view, several factors played a role to a varying extent in Chelsea's unprecedented fall from PL champs to mid-table ordinary in 2015-16. In particular: 

1. José Mourinho's management style, his tendency to manipulate players (always) and blame them for losing (once losing becomes the norm - otherwise he plays the role of I'll take the heat for the odd loss), and his failure to develop Chelsea's young players by giving them adequate game time. 

    • Is José to blame? Not really. He did what was best for José and no doubt what he thought was best for Chelsea. Was he a factor in the rapid decline? Had to be a major factor. He was 'the boss' running the club day-to-day, preparing and motivating the players, developing tactics.
 2. Circumstance/chance - injuries, loss of form by key players. Yes, poop happens.

3. Emanalo, Board of Directors and José too (because he must have had some say) in failing to recruit top players for key positions. 
Many top players are happy where they are and a body at rest tends to stay at rest unless a significant outside force acts on it (Newton's First Law of Motion). Chelsea is not a significant outside force. Chelsea club history with Roman in charge reeks of instability. The number of managers is the canary in the coal mine. Top players shun Chelsea for good reason. 
For Fun
Having spent 6 months bumming around Jamaica, I'm a reggae and Bob Marley fan. This ditty expresses how I feel about Chelsea. And by implication, what I think about Chelsea fans who diss the club and its players and feel the need to play the blame game. How about feeling the 'one love' for our club and players? Okay to love 
José too, but he's not the 'one love', my fellow fans.