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History of Lung Transplantation

Transplantation has become a well-recognized treatment option for people with organ failure. Three major factors have made transplantation a success:

• advances in surgical techniques
• the discovery of anti-rejection medications
• an increasing public awareness for organ donors

Prior to the 1980's, lung transplantation was relatively unheard of. Heart/lung transplantation evolved from pioneering work done on heart transplant surgery by a group of professionals at Stanford University. A group from Toronto, Ontario, was the first to perform single lung transplantation. In 1983, the first long-term survivor received a single lung transplant.

Double lung surgery was performed on individuals not suitable for single lung transplantation. In 1986, the first long-term survivor of double lung surgery was transplanted.

In 1989, the first single lung transplant was performed in B.C., and three heart-lung transplants were also performed that year. A year later, the first double lung transplant took place and since then, more than 100 lung transplants have been performed in BC

Surgical techniques and criteria for selecting lung recipients have been improved over time. The medication programs used to prevent rejection have also been modified, but researchers continue to try and identify better drugs for preventing rejection, and to improve the long-term success of lung transplant procedures.

Success for Lung Transplantation

Success with lung transplantation has continued to improve over the last two decades. Lung transplantation can offer an excellent quality of life to carefully selected patients with advanced lung disease.

Click here for patient and graft surival rates

How your Lung Works

In the same way that cars require fuel to run, your body required fuel or food to work. However, food cannot be "burned" unless your body has enough oxygen. When oxygen requirements are met, energy is produced, and carbon dioxide is the waste produce of this burning. These gases are exchanged in a continuous cycle in your lungs.

Your lungs are divided into lobes. The right lung is larger than the left lung. Your right lung has three lobes, and your left lung has two lobes. When breath is inhaled, your lungs expand and fresh air is sucked into your chest. Blood is pumped from the right side of your heart through your lungs, where the oxygen enters your blood stream. It is then transported throughout your body and organs to supply oxygen and remove carbon dioxide. The carbon dioxide is returned to your heart and exchanged though your lungs to be exhaled.

The lungs are normally pink, spongy, and soft. They are made of elastic material that allows them to stretch and recoil. Between the chest and the abdomen is a dome-shaped muscle called a diaphragm. The diaphragm is one of the muscles you use to breathe. When you take a breath, the diaphragm moves down, allowing the chest to lengthen. At the same time, the ribs move outward, while the enlarging cavity pulls the lungs out. When you breathe normally, these muscles work automatically, without conscious effort.

When your lungs need more oxygen-for example, during strenuous exercise-other muscles in your neck, shoulders, and back are also used. These muscles, called accessory muscles, allow your lungs to take in more oxygen to meet the increased demand. Respiratory muscles must work against the elasticity of the lungs and chest wall, which both want to spring back to their original shape, just as an elastic band would. These muscles must also overcome the resistance against the flow of air into and out of your airways.

Air enters your nose or mouth and flows through the trachea, or windpipe. Your windpipe divides into two main bronchial tubes, one going into each lung. The bronchial tubes divide into smaller and smaller tubes, like a tree with many branches. These airways warm, moisten, and clean the air you breathe, and are lined by a mucous blanket, which consists of special cells that secrete mucous. The mucous blanket traps any irritating particles that you breathe into your airways. Other cells have hair-like projections called cilia that move the mucous toward your mouth so that you can swallow it or cough it out. At the end of the smallest tubes are elastic air sacs called alveoli. In these sacs, inhaled oxygen is transferred into the blood, and carbon dioxide is removed from the blood and exhaled.

How Lung Failure Affects your Health

A healthy lung exchanges gases to meet the body's demands. A lung that is not functioning properly is not able to exchange gases adequately, causing shortness of breath. This interferes with the normal activities of daily living, and will likely strongly influence your quality of life.

To determine which type of transplant is most suitable for you, physicians must thoroughly investigate your case. They must understand what caused your lungs to fail, and also consider your overall medical condition.

You may be best suited for a single lung transplant if you do not have a chronic infective process in your lungs and if your heart is in good working condition. If you have a chronic infective process in your lungs, but have a good heart, you may be best suited for a double lung transplant. If your heart and lungs have been damaged as a result of congenital problems, separate disease processes, or increased pressure because one organ is not working properly, you may require heart/lung transplantation.

Transplant Assessment

Although transplantation is considered an established treatment for end-stage organ failure, it is not suitable for everyone. You will undergo a comprehensive assessment to make sure that a lung transplant is the right treatment option for you. Remember that a transplant is only done when there is no longer any other form of treatment available. Even then, not all people are suitable for a heart transplant. This will be discussed in detail when you visit the clinic.

The assessment phase starts when your specialist or family doctor refers you to the transplant team. The team consists of several professionals including: clinical coordinators, transplant surgeons, psychologists, social workers, and dietitians.

Once referred to the transplant team, you may need to undergo an extensive range of tests. Some of these tests may be familiar to you, such as:

• blood tests
• pulmonary function tests
• echocardiogram or "echo"
• chest x-ray

Some may not be as familiar for example:

• cardiac catherization
• lung scan
• bone density

You may not require all these tests or there may be other tests you need that are not mentioned here. This will be decided and discussed with you when you come to see the team. You may need to see other specialists to make sure the rest of your body is in the best condition for a possible transplant.

Another aspect of the assessment process is building a comprehensive profile of your personal, medical and family history. All of this is important to determine whether or not a lung transplant is suitable for you.

Waiting for a transplant

Once you and the transplant team have decided to proceed with a transplant, your name is placed on the active waiting list. How long you will wait for an organ once you are on the waiting list is difficult to predict. Some people are matched with a suitable organ in a few weeks, while others may wait well over a year. How long you will wait will depend on how you match with a donor, and the seriousness of your condition.

There is no order to the waiting list—it is not first come, first served. When an organ is available, the list is checked to find the best possible match. Some people may have to wait longer, because they are harder to match, due to their size or blood type.

All patients on the waiting list are treated equally and evaluated objectively.

Stress during the waiting period

For many, the waiting period is beginning to be recognized as the most stressful time for patients and family alike. The challenge at this time is being able to maintain hope, while at the same time coming to terms with always being sick

In spite of such challenges, we have faith that you can successfully cope with such difficulties. Individual and group counseling are available if you require additional assistance during any phase of the transplant process. We expect that you will have ups and downs while you wait. Rest assured, we don't view your asking for help as being a sign of weakness. The opposite is true, the team is here to help you through the entire transplant process.

A lung transplant support group meets on a regular basis. Please contact your clinical coordinator for more information.

Receiving a Lung Transplant

When a suitable organ has been found, arrangements are made for you to be admitted to the transplant ward and prepared for surgery. You will need to make your own arrangements to get to the hospital. It is a good idea to have a plan to follow for when the call comes. This plan will include arrangements for children, work, pets, and plants.

Sometimes the donor organ is found to be unsuitable and the transplant is cancelled. This can be very disappointing for everyone involved. This is commonly called a dry run, and occurs about 30% of the time.

If the transplant is cancelled, you will return to the transplant unit and discharged from the hospital. For this reason, tell your family or support person not to leave the hospital, or to stay close by, until they know the transplant is a go.

Transplant Surgery

The average length of time for an uncomplicated surgery is four hours for a single lung transplant, and six to eight hours for a double lung or heart-lung transplant. More details on the actual surgical procedure are available from your transplant team.

After the Operation

After the operation, you will be taken to the intensive care unit to recover. When you first wake up, you will hear voices, bubbling noises, and the sounds of medical equipment around you. For several hours you will be very drowsy. You will also notice a bandage on your chest, and various tubes and lines connected to you.

During the first day or two, you will not be able to eat or drink. You will gradually be given liquids, and then solid foods.

While you are in the intensive care unit, you will receive one-to-one nursing. You will be given medications for pain to ensure that you are as comfortable as possible.

The average stay in the intensive care unit is two to four days.

Recovery on the Transplant Unit

Recovery time varies from person to person. The length of time you remain in intensive care will depend on your progress. Once you have recovered sufficiently, usually within a few days, you will be moved to the transplant unit.

While on the Transplant Unit, the transplant team will continually monitor your progress and aid in your recovery. This will include physical exercise, breathing exercises, and diet.

How long you stay on the transplant unit will depend on how fast you are recovering. Most people are discharged within three weeks. The transplant team will keep you informed about your progress.

Living with a Lung Transplant

Anti-rejection drugs
Rejection episodes
Bronchoscopies and Biopsies
Infection
Medication and other costs

You must live in the lower mainland (close to Vancouver and VGH/SPH) for approximately three months following surgery so that you can be closely monitored. When you first leave the hospital, you will need to visit the clinic usually twice a week, and sometimes more frequently depending on the care you require. If you are from out of town, this is a major consideration and should be discussed prior to coming to Vancouver for transplant. For many, this involves both financial and emotional hardship. Discussion with your social worker prior to transplantation is key, and your social worker will work with you to establish a plan.

After six months, your clinic visits decrease to once a month, and eventually, to once every three to four months or less. The frequency of your follow-up visits to the clinic depends on your health and progress. This varies for each individual.

Anti-rejection drugs

Acute rejection is a common complication for transplant recipients. It occurs because your body's immune system recognizes your transplanted organ as "foreign" and tries to get rid of it. This process is called rejection. Your immune system is your body's defense against infection and disease. If nothing were done to stop the immune system, it would eventually damage or destroy your new organ.

Successful organ transplantation is now possible because of the use of anti-rejection drugs. To try to prevent your immune system from rejecting your new organ, you will be given immunosuppression or anti-rejection drugs (these two names are interchangeable). The doses of these drugs are carefully measured and monitored so that they prevent rejection, but still allow your immune system to recognize and fight rejection.

With the use of these drugs, your chance for a successful organ transplant is excellent. You will have to take the anti-rejection medications for as long as you have your transplanted organ.

Various immunosuppressive drugs are used in combination. When you first start taking anti-rejection drugs, the doses will be high. After the initial period (the first three to six months), as the risk of acute rejection decreases, the doses will be lowered. Usually by the end of your first year after transplant you are taking a considerably lower dose than in the initial period.

The most commonly used drugs are Cyclosporine or Tacrolimus, Azathioprine or Mycophenolate, and Prednisone. Each drug works in a slightly different way and has different side effects. By taking two or three drugs together, you can be on lower doses of each drug to minimize their side effects, while maintaining an effective defense against rejection and infection.

After you are transplanted, the nurses and the pharmacists on the ward will teach you about your medications, how and when to take them. Initially, nurses will give the medications. Gradually, before your discharge, you will have the responsibility for taking them yourself.

It is a good idea to record the daily doses of drugs taken, and to bring this record to each clinic visit. The dosage of the anti-rejection drugs are frequently changed in the early phase post-transplant, and many people find it easier to write down the changes to prevent any misunderstanding or medication error.

Commonly prescribed anti-rejection drugs

Cyclosporine or Neoral Cyclosporine
Tacrolimus (Prograf®)
Azathioprine (also known as Imuran®)
Mycophenolate (also known as CellCept®)
Prednisone

Cyclosporine (also known as Neoral®)

Cyclosporine revolutionized transplantation because it was the first drug found to be consistently effective for preventing rejection. This drug modifies certain white blood cells called lymphocytes, which are involved in rejection.

To be effective, the drug must stay at a certain level in your blood. If the level is too low, your transplanted organ may be rejected. If the level is too high, your kidneys or liver may be damaged. Usually, any damage is reversible once the drug returns to its proper level. The level of Cyclosporine is measured frequently with a blood test while you are in the hospital, and after discharge during visits to the clinic.

Cyclosporine is available in soft gelatin capsules. The capsules are available in 25 mg (grey), 50 mg (white), and 100 mg (grey). Each capsule is wrapped in foil, and should be kept in the foil until you need a dose. When you are ready to take a dose, remove the number of capsules you need to make up the dose. Swallow the capsules whole. You may take Cyclosporine with any drink except grapefruit juice (as grapefruit juice will alter the absorption of Cyclosporine) unless your physician instructs you otherwise. It is very important that you take Cyclosporine with the same drink every time.

The most common side effects of Cyclosporine are listed below. Remember that everyone responds differently to medications, so you may experience only some of the side effects or none at all.

Possible side effects of Cyclosporine:

•	high blood pressure, and headaches
•	increased risk of infection
•	mild hand tremors
•	fine hair growth on the upper body
•	gum tenderness (to prevent problems with your gums, brush and floss your teeth daily, and visit your dentist regularly)
•	sensitivity to hot and cold, flushing
•	runny nose
•	vivid dreams

If you notice any of these side effects, tell a member of your transplant team. They will assess whether you are suffering from side effects of the drug or something else.

Tacrolimus (also known as Prograf® or FK-506)

Tacrolimus is another anti-rejection drug that acts in much the same way as cyclosporine. Tacrolimus is used in some transplant patients in place of Cyclosporine (Tacrolimus and Cyclosporine should not be taken together). Tacrolimus, like cyclosporine, is used with steroids and Azathioprine (Imuran®) or MMF (Mycophenolate Mofetil) to prevent or treat rejection of the transplant organ.

Tacrolimus is available in 1 mg and 5 mg capsules. The 1 mg capsules are white and oblong with "1 mg" written on the top. The 5 mg capsules are grayish-red and oblong with "5 mg" written on the top.

Like other medications, Tacrolimus may cause side effects in some people. If you think you are experiencing side effects, talk to your doctor right away. Do not stop taking tacrolimus on your own.

Possible side effects of Tacrolimus (Prograf®):

• headaches
• tremor
• tingling in your hands or feet
• nausea and vomiting
• diarrhea or constipation
• difficulty sleeping
• changes in moods or emotions

Like other anti-rejection medications, try to take your dose at the same time every day. Make sure your doctor, dentist, and pharmacist are aware of all medications you are taking, including anything you buy off the shelf, such as over-the-counter drugs and herbal or home remedies. Taking antacids at the same time as Tacrolimus, for example, may affect the way Tacrolimus works for you, so these drugs should not be taken together.

Some patients may experience side effects not listed above. If any side effect becomes bothersome or won't go away, contact your doctor, transplant clinic, or pharmacist.

Azathioprine (also known as Imuran®)

Azathioprine is also used to prevent rejection. The use of Imuran has changed recently, to be incorporated into your transplant medication regime in the 2nd year of your transplanted kidney. Mycophenolate (described in the next paragraph, has been proven to be more effective for the first year). This drug suppresses the production of certain white blood cells, which are active in the process of rejection. The drug also suppresses the production of cells that are important in fighting infection. A complete count of blood cells (by a blood test) is done daily while you are in the hospital, and regularly at the clinic once you are discharged. The dosage of Azathioprine is adjusted to keep the blood counts within safe limits.

Azathioprine is very well tolerated and most people are not really aware of any problem while on this medication. However, like any drug, side effects are always possible. The most common side effects of Azathioprine are listed below. Remember that everyone responds differently to medications, so you may experience only some of these side effects or none at all.

Possible side effects of Azathioprine:

• nausea and vomiting
• loss of appetite
• skin rash
• muscle/joint pain
• infection

If you notice any of these side effects, tell a member of your transplant team. They will make sure the problem is a side effect of the drug, and not a sign of rejection of your transplant, or another medical problem.

Azathioprine is available in both intravenous solution and oral tablet form. It comes in 50 mg tablets, which can be broken for smaller doses.

Mycophenolate (also known as CellCept®)

Mycophenolate is an anti-rejection drug that works in much the same way as Azathioprine (Imuran®). Recently, Mycophenolate has been incorporated into the kidney transplant medication regime for use in the first year of your transplanted graft. It has been proven to be very effective in preventing acute rejection during this first year. Some transplant patients take Mycophenolate instead of Azathioprine. Mycophenolate is used with either Cyclosporine or Tacrolimus, and steroids to prevent or treat rejection of the transplanted organ.

Mycophenolate is available in blue/brown gelatin capsules with "CellCept 250" printed in black ink on the blue cap and "ROCHE" on the brown body. Each capsule contains 250 mg of Mycophenolate Mofetil.

It is important to leave the capsules in the blister pack until you need a dose. When you are ready to take a dose, remove the number of capsules you need to make up the dose. Mycophenolate should be taken on an empty stomach. Swallow the capsules whole.

Like other anti-rejection medication, try to take your dose at the same time every day. Make sure your doctor, dentist, and pharmacist are aware of all medications you are taking, including anything you buy off the shelf, such as over-the-counter drugs and herbal or home remedies. Taking antacids at the same time as Mycophenolate, for example, may affect the way Mycophenolate works for you, so these drugs should not be taken together.

Like other medications, Mycophenolate may cause side effects in some people. If you think you are experiencing side effects, talk to your doctor right away. Do not stop taking Mycophenolate on your own.

Possible side effects of Mycophenolate:

• nausea and vomiting
• diarrhea
• loss of appetite
• weakness
• swelling of legs and hands
• infection
• headaches

Some patients may experience side effects not listed above. If any side effect becomes bothersome or won't go away, contact your doctor, transplant clinic, or pharmacist.

Prednisone

Prednisone is a steroid, similar to one that your body produces normally. It decreases tissue swelling and suppresses rejection. The initial high dose of Prednisone is gradually reduced until a low maintenance dose is established. Higher doses of steroids, called "pulse therapy", are used to treat acute rejection.

The most common side effects of Prednisone are listed below. Again, remember that everyone responds differently to medications, so you may experience only some of these side effects or none at all.

Possible side effects of Prednisone:

• stomach upset (should always be taken with food)
• weight gain and fluid retention
• bone thinning
• fullness of the face
• acne/rash
• easy bruising
• joint pain
• mood swings
• medication induced diabetes (high blood sugars)
• infection

If you notice any of these side effects, tell a member of the transplant team. The team will make sure the problem is a side effect of the drug, and not a sign of rejection or another medical problem.

Taking Anti-rejection Drugs

It is important to take your medications at the same time each day so that you maintain adequate levels of medication in your blood. To ensure that the drugs work properly, you must take them exactly as prescribed.

If you miss your dose and it is less than half the time before your next dose is due, then take the missed dose. If it is more than half the time to your next dose, then skip the missed dose and wait for your next dose. Do not double your dose.

For example, if you were scheduled to take your medication every 12-hours and you remember to take your medication within 6-hours of the time it was due, then you can take the missed dose. If you have any questions regarding the schedule of your medications or taking missed doses, then make a note of the time and date of the missed dose and inform the transplant team as soon as possible. If you vomit within one hour of taking your medication, repeat the dose.

*Never change the dose of your drugs or stop taking them unless directed by the transplant team.

*Remember to always inform your doctor and dentist of the medications you are taking.

Rejection Episodes

It is likely that at some time you will experience an episode of rejection. It is referred to as an episode of rejection because it is usually a temporary, reversible event. It is most likely to occur in the first six months of having your new organ, but it can happen at any time as long as you have the organ.

Rejection may occur even if you have been taking your medications faithfully. While you may find this thought unsettling, it is a common occurrence. In most cases, with early detection and treatment, the transplant team should have no problem reversing the rejection completely.

The best way to fight rejection is to stop it before it starts, and to recognize it and treat it early. You can work at preventing rejection by taking your medications faithfully. For early detection learn to identify the signs and symptoms of rejection and report them immediately to the transplant clinic nurse.

Signs of Rejection

Early identification and reporting of symptoms are important in successfully treating and reversing rejection. Most rejection episodes are mild. It is common in fact to have no symptoms with rejection. Your doctors may only be aware that rejection is occurring because it was detected with a biopsy. On the hand, some individuals may feel symptoms of the rejection episode. To ensure that the rejection is treated quickly, watch for any of the following warning symptoms:

• reduction of your FEV1 by 10% below its baseline (baseline lung function varies during the first few weeks; your clinic physician will determine your baseline FEV1 and the level it should not go below)
• decreased energy level
• weight gain of one kilogram (2.2 pounds) per day, or more, sometimes with swelling of the ankles
• increased temperature/fever
• tenderness over transplant site
• shortness of breath while doing normal activities
• decreased blood pressure

If you experience any of these symptoms, report it to your transplant team immediately.

Treatment of Rejection

When rejection is detected, it must be treated immediately. Most people are admitted to the hospital for about three days for their first episode. Treatment usually involves high doses of a steroid, which can be taken either intravenously (through a vein), or by an increase in prednisone tablets taken orally. In most cases, this will reverse the rejection.

If high doses of steroids are not effective, OKT3 is most often given. OKT3 is a medication which blocks the function of the immune cells that are responsible for rejecting the organ. It is given intravenously for up to 10 days. OKT3 can cause sever flu-like symptoms during the initial two or three doses. You will be admitted to hospital for the initial doses and given medication to help minimize the symptoms. If you have any unusual discomfort or symptoms, report them to your doctor or nurse. You may also be switched to tacrolimus.

Approximately six weeks after the treatment for the rejection episode, you will have a bronchoscopy and biopsy as a check. Such biopsies will be repeated at six-week intervals until there are two normal biopsy results.

Chronic Rejection

Chronic rejection of the lungs usually occurs over a long period of time. Physicians usually refer to it as bronchiolitis obliterans (OB). This form of rejection involves inflammation of the small airways, possibly causing scarring. Scarring will cause the airways to narrow and the lung to function less effectively.

Bronchoscopies and Biopsies

Any time there is a significant drop in your lung function, or signs of rejection or infection, your physicians will do a bronchoscopy and biopsy. During a bronchoscopy, the major air passages to the lungs are examined. The physician looks at your windpipe (trachea) and other major bronchial tubes.

You will usually be asked not to eat or drink anything for several hours before the procedure. You will be given medication to make you drowsy and to ensure that you will not remember the procedure. Your nasal passage or throat will be anaesthetized ("frozen") to diminish your normal gag reflex. Once the medication has taken effect, a small tube (bronchoscope) is passed down either your nose or your mouth. The physician is able to see your major lung passages and take small biopsy specimens through this tube.

After the procedure, your mouth and throat will remain numb from the anaesthesia, which usually takes several hours to wear off. You will be asked not to eat or drink anything until your gag reflex returns so that food or drink does not accidentally go down your windpipe into your lungs.

Since the bronchoscopy is passed through your vocal cords, you may experience some hoarseness to your voice.

Bronchoscopy is a safe diagnostic procedure that carries very little risk. Complications that can occur include collapsed lungs (pneumothorax) and bleeding from the biopsy site. These are very rare.

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Infection

A possible side effect of anti-rejection drugs is an increase in infections. While suppression of the immune system is necessary to prevent organ rejection, it weakens the body's ability to fight off infections. Fortunately, there are ways of reducing the risk of infection while still maintaining adequate defenses against rejection.

The risk of contracting an infection is higher during the first few months following a transplant when your doses of anti-rejection drugs are high. As the doses fall, the risk of infection falls. As with rejection, the key to fighting an infection is to prevent it, identify it early, and treat it quickly.

Preventing Infection

The best way to prevent an infection is by avoiding close contact with people who may be ill. Most viruses, bacteria, and fungi are passed from person to person in tiny water droplets and may be transferred simply by shaking hands. Someone sneezing or coughing is sending out droplets, which you might breathe in, or transfer to your mouth or other mucous membrane (such as your eyes) with your hands.

During the first few months following your transplant, you must be diligent in avoiding infections. This may mean having to avoid normal close contact with family members or your spouse if they are sick.

You may not be able to prevent all infections, but you can certainly reduce the risk by washing your hands regularly and avoid putting your fingers in your mouth or touching your eyes. Family and friends with infections should also wash their hands before touching you.

Also avoid:

• people with colds or infections
• crowded, poorly ventilated, smoke-filled rooms
• public transportation, especially at rush hours
• public whirlpools
• activities that may cause breaks in the skin (when gardening, for example, wear gloves)
• changing cat and bird litter

It also helps to alert your co-workers to the fact that you are on immunosuppressants. You will find that people are remarkably considerate when they know the situation. After the transplant, you may be taking medications as a preventative measure against commonly occurring infections.

Medication and other costs

The three anti-rejection drugs you will be prescribed are available free of charge from the Transplant Outpatient Pharmacy located in the Transplant Clinic. Other non-immunosuppressive drugs must be purchased by you at your local pharmacy. Keep your receipts so you can apply for reimbursement of a portion of these costs through BC's Pharmacare Plan. Application forms are available from your pharmacy. For more information, talk to your pharmacist.

During the first three to six months, you may also be taking drugs to prevent infections, treat high blood pressure, or help with acid reflux, so the total cost of your medications will be quite high. Once you stop taking some of these drugs, the cost will come down significantly. Talk to your transplant team and other recipients about the best and cheapest places to buy your drugs.

Besides medications, there are other expenses that you may incur after your transplant, including:

• Accommodation in Vancouver before you can return to your community
• travel to and from the Transplant Clinic
• health monitoring equipment and supplies, such as blood pressure device, weight scale, and thermometer
• medic alert bracelet or necklace
• other supplies if required (gauze, tape, cleaning solutions)