PATIENT STORIES:

> LAM - The disease that's killing young mums
> Dying to breathe
> Giving the gift of life
> Havi Carel: My 10-year death sentence

LAM - The disease that's killing young mums
Australian Woman's Weekly, September 2005

The first sign of trouble came when Shani Eldridge was pregnant with her first son. Her lung collapsed. No one knew what caused it. However, she went through her second pregnancy without a problem. Then, three years later, she started getting very short of breath.

“When I went to functions at my sons’ schools, I’d run out of breath walking up the hill to their classroom. I’d pretend to talk into my mobile so people wouldn’t notice something was wrong,” says Shani.

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Dying to breathe
University of Auckland News, April 2005

Why is one of the University’s leading heart researchers on a quest to find a cure for a rare lung disease?
Tess Redgrave investigates.

Ever heard of Lymphangioleiomyomatosis (LAM) – a rare lung disease that knocks young women down in their reproductive prime?

No? Well you’re in fi ne company then because fi ve years ago neither had Associate-Professor Mervyn Merrilees (Anatomy with Radiology). Yet now he is at the forefront of an international research effort urgently trying to understand and fi nd a cure for this devastating (and often fatal) condition, which spurns all familial links, choosing its victims at random.

As the News goes to print, Dr Merrilees is in Cincinnati, Ohio, at the 10th annual conference of the USA LAM Foundation, giving a platform presentation on the fi ndings of cutting edge research he and his postgraduate team have been undertaking. If the Auckland research is on the right track, it will add an important piece to the puzzle that is LAM, offering hope to thousands of women around the world and to 14 women in New Zealand, including one 37-year-old Auckland family lawyer.

The story of why one of the University’s foremost heart researchers is on a quest to understand LAM is irrevocably linked with Auckland woman Bronwyn Gray and her daughter, Lisa.

Let’s rewind here a moment back to February 1997: 29-year-old Lisa, after weeks of looking tired, wheezing, coughing and even spattering tissues with blood, is sent by her GP to Greenlane Hospital’s respiratory department. A few days later the results of a bronchoscopy and CT scan show that the exercise-induced asthma she thought she had suffered since her early 20s is in fact something far more insidious: LAM – a rare disease (caused by a defect in a gene called TSC2) which affects only women – usually between the onset of puberty and menopause – and is characterised by the growth of an unusual type of smooth muscle cell around lymph channels and blood vessels resulting in an increase in the amount of tissue in the lung and a loss of airspace.

“I went into a blind panic when I heard Lisa’s diagnosis,” remembers Bronwyn Gray, when we meet at her Freemans Bay villa. “In 1997 no one in New Zealand could tell us anything about LAM except that Lisa was unlikely to live to be an old lady.” (Early reviews of the disease, which affects about one or two per million, reported a dire prognosis: most patients died of progressive respiratory failure within 4-10 years of onset). Not a mother to lie down and watch her daughter slowly die, Bronwyn Gray, a former Auckland Girls’ Grammar English and history teacher – determined, articulate and focused – abandoned retirement plans to live half of each year in France, and set out to fi nd out as much as she could about LAM, garnering whatever help she could fi nd along the way to save her daughter’s life.

Her quest took her to London, Paris, America, Australia, back to New Zealand, and fi nally to a meeting on November 13, 2000, in the conference room on the fi fth fl oor of Auckland’s Medical and Health
Sciences Faculty. “I was invited to that meeting even though I’d never heard of LAM,” remembers Mervyn, “because at the time I was working on smooth muscle cells in blood vessels of the heart. It’s the change in the function of these vessel smooth muscle cells that leads to coronary artery disease.” There were six people at the November meeting but Bronwyn Gray “beamed in” on Mervyn. Eighteen months earlier she had set up the NZ LAM Charitable Trust and begun a mammoth fund-raising effort; now she was looking for someone in New Zealand to be part of an international research effort to fi nd a cure for LAM. Mervyn’s work on smooth muscle cells was the closest she’d come.

“I didn’t make any promises,” remembers Mervyn, “but I was interested so I went away and read up on LAM.”

Then early in 2001 Bronwyn, via the Trust, offered to pay for Mervyn’s flights to attend the 2001 USA LAM conference in Cincinnati.

“It was a real eye-opener,” he says. “The LAM conferences are driven by patient advocate groups so you’ve got clinicians, scientists and patients working together – a whole community working on LAM. You meet the patients and you see the urgency. They’re all women in the prime of life, some mothers, some of them very ill. Many sit at the conference connected to portable oxygen tanks….”

LAM had got under the skin of this quiet, unassuming Auckland academic. Back in New Zealand, just as Bronwyn had hoped, and with help from his technical officer Brent Beaumont and a masters student, Elyshia Hankin, he began a research project studying LAM lung tissue samples from six patients who had had transplants in America, and three in Australia.

Studying the cell structure of these under a microscope he came up with a radical new perspective on the disease: that smooth muscle cells may not be the only culprit in LAM! “We discovered that some of the normal cells, without the TSC2 gene defect, get stimulated to proliferate too, and actually take up much more space in the lung than the abnormal smooth muscle cells. Presumably the smooth muscle cells send out a message to the normal cells which makes them start proliferating – the end result is the lungs run out of airspace.”

Mervyn published this finding in the prestigious UK Journal of Pathology last year and it forms the basis of one of the papers he is now presenting at Cincinnati. But his research hasn't stopped there. In 2003, he again accompanied Bronwyn to the annual USA LAM conference and heard a presenter suggest that a drug called rapamycin (made from a soil fungus found on Rapa Nui, part of the Easter Island group, and originally used as immune suppressant to control rejection of transplanted tissue) might be able to stop the growth of smooth muscle cells.

In an interesting piece of serendipity, back in New Zealand, Mervyn discovered that of the two pharmaceutical companies in the world that manufacture Rapamycin, one is based in the USA, and the other, Industrial Research Limited (IRL), is in Wellington. Already interested in testing rapamycin on “normal” lung tissue, Bronwyn, on Mervyn’s behalf, approached IRL; the Lower Hutt-based company has since got in behind the Auckland research and donated two milligrams of rapamycin (it costs about $800 per milligram to import from the USA).

In 2004 Mervyn and his team began observing rapamycin’s impact on normal lung cells in culture imported from the US.

“We found the drug significantly decreased the growth of these cells and also decreased the matrix material which gets laid down outside the cell. It’s these matrix molecules [the same molecules that bind cholesterol in the blood vessel wall, and that the heart researcher had discovered also stop the formation of elastic fibres] that bind a lot of water and make the LAM tissue swollen and puffy, slowly smothering the lungs.”

While Mervyn has been beavering away in Auckland, researchers in the US have begun to trial rapamycin on LAM patients, with early results indicating the drug may indeed be beneficial.“

So rapamycin may well offer an opportunity and the best hope for LAM we’ve ever had,” he says. “Like some cancers, in which cells start to proliferate when a tumour suppressor gene is damaged, LAM seems to occur when TSC2, also a tumour suppressor gene, malfunctions, allowing cells to grow. So basically rapamycin reasserts control; its very effective at stopping cells growing.”

As a result of both the Auckland research and research in Australia and America, an international double blind rapamycin trial is likely to get underway later this year. Bronwyn Gray is playing a key role in organising the Australasian arm of the trial and is hopeful her daughter may be a candidate.

At the moment Lisa works in a family law chambers in Ponsonby (she is a Counsel for Child) but her lung function is “slowly but progressively decreasing.

“Every three months she has FEV1 (forced expiratory volume in one second) tests to measure how much breath she can get out in one second and every time it’s a little less,” says Bronwyn.

Lisa was not interviewed for this story (though happily photographed). “She just wants to get on with her life,” explains Bronwyn. “But she gets very irritated and angry with this disease, she’s so healthy, she doesn’t drink, she doesn’t smoke; she’s in the prime of her life; she wants to have a child but is worried about further deterioration [much of the anecdotal evidence indicates that the hormonal changes of pregnancy, in particular raised estrogen levels, are likely to heighten the symptoms of LAM: some women only find out they have the disease when they experience difficulty breathing during pregnancy]; she doesn’t know what the future holds.”

So while Lisa gets on with her life, her mother and greatest advocate works from her Freemans Bay home raising awareness about LAM, organising conferences, helping other New Zealand patients, collaborating on the international trial, and finding funds so Dr Merrilees can continue investigating his perspective on LAM.

“Mervyn is absolutely pivotal,” she stresses. “He and the team in his lab are the only people in New Zealand doing any work on LAM and I believe that after his presentation in Cincincatti [Bronwyn is going too] there will be quite a major response to what he is saying.“

Mervyn in turn has obviously been personally touched by Bronwyn Gray, her daughter Lisa, and LAM. “It’s always struck me that LAM patients are extraordinary women with enormous courage,” he says “There’s a sense of being closely involved with this disease – often as a researcher you don’t meet the recipients of your research, but with LAM, you meet the patients, you see the urgency – it focuses your mind.”

After Cincinnati Mervyn will continue to work on LAM in tandem with his heart research; he is currently making a three-dimensional model of the elastic fibres in LAM lungs using a pair donated from a New Zealand patient who recently had a lung transplant at Auckland hospital. “

The understanding of this disease has happened very quickly,” he says. “The US LAM foundation was only formed ten years ago and since then there have been huge strides in understanding but it’s a hard road to solve a disease, we have to be realistic…”

As the international quest to find a cure for lymphangioleiomymoma-tosis continues you can bet that Mervyn and the work he is doing at the University will be a part of the mix. LAM has left an indelible mark on this academic and he is not likely to let the puzzle of it go.

> View original PDF of story here

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Giving the Gift of Life

Southland Times, 14 October 2005
by Kate Buchanan

Lisa Wishart-Wyeth has no face to recall, no name to pay tribute to. But the teenage girl that fills her thoughts bestowed the Otatara woman with the ultimate gift - a set of healthy lungs that saved her life.

"Sometimes at night when I can't sleep, I lie there and can feel the rise and fall of my lungs and I think about her and wonder what she was like," Lisa Wishart-Wyeth said.

Mrs Wishart-Wyeth is one of just nine New Zealanders to undergo a lung transplant operation last year.

"It's my duty now to protect these lungs, not only for myself but for her and her wishes," she said.

Mrs Wishart-Wyeth, 38, was diagnosed 11 years ago with the rare and fatal lung disease lymphangioleiomyomatosis, or LAM.

Havi Carel: My 10-year death sentence

'The Independent' UK, 19 March 2007
http://news.independent.co.uk

As a philosopher, Havi Carel spends her days grappling with questions of mortality. But her theoretical notions on the meaning of life and death were turned upside down when she was diagnosed with a terminal illness - and told she had just 10 years to live

"So, how long have you got?" The first time I was asked this question, I was dumbstruck. The horror of it, and the casualness with which it was asked, was too incongruous for words. Was it simply curiosity? Ignorance? A clumsy attempt to "connect" with me? What else could motivate someone to ask such a horrific question? Yet, it's a question I have been asked again and again - by friends, acquaintances, even strangers who have seen me sitting in a café with an oxygen cylinder beside my feet.

Once you are ill, I realise, you become fair game. You slide down an implicit social ladder. Others begin to perceive you as weak and unimportant, an object of pity and fascination. In asking: "How long have you got," they compress all their horror, anxiety, pity, and relief that this is someone else's story. How else to explain how people find the obtuseness and cruelty to ask you - in so many words - "When are you going to die?"

I am not impressed. I feel like screaming like that old lady on The Catherine Tate Show: "What a fucking liberty!" To the people who really piss me off, I quote the figure from Wikipedia: five years. I watch them deflate, shoulders sagging, thinking: "How awful. Gosh, I'm glad it's not me."

To others, I provide the official figure: 10 years. I can see them doing the sum in their heads: "Wow, that's really young. I wonder what she feels like, poor thing." To the people I feel deserve more respect, I give a slightly more complex answer, explaining the possibility of medical advance and lung transplantation. To my loved ones, I say that everything is open, we don't know what the future holds, and anyway, no one knows when they are going to die.

Imagine the opposite situation: me approaching one of my colleagues smoking a fag at lunchtime and asking, amicably, in that faux-concerned tone, "So, how are you coping with your mortality? Do you often think about the fact that an average smoker your age has only another 10 years to go?" That wouldn't really cut it, would it.

But somehow, when you are my age (36) and ill with one of the rarest diseases known to mankind (lymphangioleiomyomatosis, or LAM), asking you the most intimate of questions becomes legitimate. The rules change when you are ill. You are, as Erving Goffman put it bluntly, stigmatised. You become an outsider to the world of the healthy, an offensive reminder of the ugly underbelly of life.

Having written as a philosopher on death, years before my diagnosis, I often think about the real meaning of the question. What those people seem to be asking me is: "What is it like to be acutely aware of your mortality? How do you prepare for death? What does helplessness feel like?" They ask because they know that I have, unusually, been given access to a terrible and unwanted vision of my future.

Something has happened to my temporal existence. My future has folded in on itself. It has exposed itself to me, contrary to both the laws of nature and of human nature. We are not meant to be able to see into our future. We are propelled into our future, thrown into our projects with no premonition, no peeking. Our life stories are meant to unravel as we go along, at a rate of one second per second. No slower, and certainly no faster. But I was given a crystal ball through which, with painful accuracy and nauseating detail, I can see my future: further decline, hopeless prospects, premature death.

The Greek philosopher Epicurus argued that the fear of death was irrational. "Where death is, I am no longer," he said, "and where I am, death is not." So long as you are alive, death is nothing to you. And once you are dead, you are no longer there to feel anything, fear included. Life and death are mutually exclusive. If you think about it carefully, Epicurus said, you realise that what you are really afraid of is not death but dying, the pain of illness and decay. There is nothing to fear in death itself, because death is a state of non-existence. It is incoherent to say that you fear not existing. Epicurus thought that those who fear death were confused and should use rational arguments, like the ones he provides, to overcome their fear.

Another philosopher, Martin Heidegger, thought differently. He argued that death is a constant presence in life, and renamed human existence "being towards death". What is human existence, he said, if not a limited stretch from birth to death? Human existence is marked by finitude and limitation, and those of us who ignore this fact are engaged in a futile pursuit, trying to escape the inescapable. So Heidegger rejects the Epicurean idea that death is irrelevant to our lives. To understand life fully, Heidegger argued, one must understand oneself as finite.

Which of these two views is more compelling? In some ways, Epicurus is right. If I do not believe in the persistence of my mind after the death of my body, what have I to fear? I am not afraid of non-existence. But on the other hand, there are other things to regret in death. Like the grief of others, missed opportunities and having to take a different course in life than the one I wanted.

I have always thought about death. In fact, only a month before my diagnosis, my first book was published: Life and Death in Freud and Heidegger. After my diagnosis, I was petrified by the coincidence. The futility of philosophical arguments was suddenly glaringly obvious to me in the face of the practical problems I was facing. Its intellectual approach seemed evasive; its explicit analysis of death, crass.

But after a while, I began to see what I have gained from thinking long and hard about death. It helped me to formulate the questions and, later, develop a view that addresses the issues that are so close to my heart, both professionally and personally. How can I make sense of a finite life? What is the role of finitude within human life? Can a limited life still be a good one? These were questions I had grappled with as a philosopher, long before I had any idea how my own life would turn out. But now, these abstract questions have a real urgency for me.

I need to face these questions in order to forge a way forward. I feel obliged to find a way to remain sane, to enjoy what little time and health I have, and to refuse bitterness and envy, the most tempting vice of all. Moreover, I want not just to be able to accept my illness - for I have no choice, really - but to make my life a good one, with all its limitations and truncated future. With Heidegger, I think that in order to understand my life I must understand it as finite. I see my actions and possibilities as limited and ultimately nested within a finite existence. Perhaps some people - the healthy - can live in accordance with Epicurus's ideas. But where I am, death is. It is a constant presence, a perpetual shadow.

I had been feeling breathless for a while, probably since 2004. But it was only in February 2006 that I went to the doctor. Why did I wait so long? The sad and surprising fact is that we can lose up to 50 per cent of our lung capacity without noticing much change. I felt a little breathless, especially going uphill and climbing stairs, but I thought that was normal.

I was living in Australia at the time, leading an active life, which probably masked my breathlessness, as my muscles were efficient and I wasn't overweight. But sometimes on walks I would see other people climbing hills effortlessly, while I was struggling to breathe. In my kick-boxing class I could do everything as well as the next person, but for the life of me I couldn't skip rope. I bought a skipping rope and practised at home, but nothing happened. I never improved.

By the time we were back in the UK, I could no longer deny that there was something wrong. I went to a specialist who said that it was "unusual asthma". She gave me inhalers and told me to plot my breathing. Over two months, it just got worse. I began to lose weight and got a nasty cold that stayed with me for two months. I'd never had a cold like that. When boxes arrived from Australia, one of them contained my scales. I weighed myself and my heart sank. I was a meagre 48kg, just under 8 stone. There I was, coughing up gack, unable to wear half my clothes, going to work in a taxi because I couldn't cycle, giving lectures sitting down, wrapped in my coat. Yes, I was ill. And yes, I was scared, but I didn't know what of.

In April, I went to visit my parents in Israel. When I arrived, my father, who works in a medical institute, said that he'd arranged a chest CT scan for me, just to make sure everything was OK. I had the scan and went on to see friends in Tel Aviv. I bought sunglasses that afternoon and sat in a café with an old schoolfriend. We talked about Michael Haneke's film Hidden. I wore a lavender jumper that my sister had just given me. Everything was normal.

My parents picked me up from the café. My father suggested that we swing by the medical centre to collect the test results. He parked and walked into the building, while my mum and I waited in the car. Ten, 15, then 20 minutes passed. He was not back. By then I understood something was wrong. I walked to the radiologist's office. The secretary tried to stop me, but I told her my father was in there and I needed to see him.

I entered a dimly lit room. The radiologist was showing my father something on a computer screen. My father was holding his head in his hands. The radiologist looked up, surprised and displeased to see me. "Oh, it's you," he said. "Do you know what's going on?"

"No," I answered. "What is it?" He smiled awkwardly and handed me a big book, a diagnostic manual. He pointed to a word I didn't know: lymphangioleiomyomatosis. "What's that?" I asked. He simply pointed to the text below and said: "Read about what you've got."

Words flashed before my eyes: bullae, pneumothorax, chylous effusion... I didn't understand any of them. I skimmed further down. "Prognosis: 10 years from onset of severe respiratory symptoms." That would make me 45, I thought.

I was suspended in mid-air with one thought only: my life will end in 10 years. I continued sitting there. All the while, the radiologist was speaking to my father and pointing to what I now understood were my lungs. The black balls on the screen were not meant to be there, they were cysts created by LAM cells. I stared at the screen. I stared at the radiologist. I stared at my father. No one looked at me. After what seemed like a very long time, I said the only thing I could think of: "Can someone get my mother?"

Illness changes everything. It changes not only my internal organs, but my relationship to my body, my relationship to others, their relation to me, to my body... In short, illness changes how one is in the world. Moreover, the world of the ill person changes; it transforms into a different landscape, filled with obstacles. Distances increase. It becomes uncanny. The world of the sick belongs to a different universe from that of the healthy, and the interaction between them is clunky, difficult, abrasive.

Stairs used to lead somewhere interesting or important. Now, stairs go nowhere. Offices and rooms on the fourth floor no longer exist for me. Slight inclines have become hills, hills have become mountains. I cycle a circuitous route to work, avoiding a hill. I think twice before going downstairs to collect the post. Groceries now come from the internet, books are no longer carried to and from work. The geography of my world is no longer a shared one. It belongs to me alone, and separates me from the people I walk with. The healthy ones who don't even notice they are healthy.

The future used to be something to look forward to. Now it is something to dread. I know the route my future will take. Nearly all LAM patients decline. I know of women dying in their sleep, going in and out of hospital with collapsed lungs, sitting at home for years waiting for a call from the transplant centre, a call that may never come. I also know of women dying of chronic rejection, weeks, months or years after their transplant. A great wave of helplessness envelops me when I think about the future. I face a dead end, a cul-de-sac, literally: the bottom of the bag.

A few months ago, I went to a conference in Durham. The porter took me to my room: the third floor, of course. He looked at me with a mix of curiosity and pity, a mix I now know well: a young woman with a big rucksack and an oxygen cylinder, looking so independent and yet so disabled. I had to ask him to move me to the ground floor.

It suddenly hit me that I have to tell people, in situations like this, that I am disabled. I still have to take a deep breath before saying this. Being able to engage in projects, to carry out actions, to act freely - we take all that for granted. Our actions define who we are, give us a sense of potency and agency. But being disabled means being unable to do the things you love. Unable to go on long walks, to run, to play with your dog. What kind of being is being disabled, being unable to be?

Illness breaks down the neutrality and transparency of our bodily existence. But it has also given me perspicuity. I observe my life and the lives of others and see them for what they are: brief, full of emotion and agony, activity and joy. I see people arguing over nothing, worrying about wrinkles and careers. Illness makes you immune to that. From the loneliness into which my illness forced me, I became able to see the world anew. My horizons and expectations shifted. I was made aware of the many healthy years I enjoyed. I cherish the things I can still do, like cycling along a canal in summer, the visceral joy of fresh smells and colours.

I learnt to pace myself and rejoice in small pleasures. I became generous towards myself and others; less worried about a looming deadline. I no longer cringe when children ask: "Mummy, what's wrong with that lady?" I am grateful for every moment that is not consumed by sorrow, pain or despair. I try not to think about the future.

I discovered that there can be health within illness, joy within difficult circumstances, and emotional freedom within the adversity of disability. I learnt to be less controlling and more accepting of my inability to do things, my inability to be. Within this inability, I found an ability to be unable, to face myself as unable and to embrace this unable self.

This is not to say that there is nothing that can be done. I have become a patient-activist, working for the LAM Treatment Alliance, trying to push forward research and drug trials. LAM is a disease that has few advocates because it is so rare. That is why I have become my own advocate, like many other women with LAM. We find it hard to accept that the world carries on as before, while we suffer from a terrible disease about which so little is known.

I continue to live as before. Despite the awkwardness and the stares, I still cycle, go to (non-smoking) pubs, do yoga. A pannier with an oxygen cylinder was followed by an electric bike. When people offer help, I no longer refuse it. This is not the life I wanted, but I refuse to indulge in "what if". The first rule I made for myself is never to ask "Why?" Never say, "if only". Never think that things could have been different.

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