Robert Sandhaus, MD, PhD

If a child has been identified as an Alpha, when should he/she begin seeing a pulmonologist? For example, should there be a baseline done on lung function?

It is usually not necessary to see a pulmonologist until a child with Alpha-1 is in their teens, unless there are other pulmonary problems that prompt such a visit.  Pulmonary function testing is not very accurate until that time and the appearance of pulmonary disease in children or even younger adults is extremely rare.

What are the current recommendations for target oxygen saturation levels with COPD?   Is 88% still the current Medicare guideline for coverage through Medicare?  Is more oxygen better than less when above 90% or is it still considered that giving too much oxygen will lessen the drive to breathe.  What is current research recommending?

There has been no change in these recommendations because there have been no new studies advising us otherwise since the initial studies done several decades ago.  Once your oxygen saturation is in the low 90s, little is gained by getting higher saturations.  The concern regarding too much oxygen turning off the drive to breathe is only true in people with the most severe COPD – those who are retaining carbon dioxide CO2 as measured on a blood gas.  CO2 retention is relatively rare in emphysema due to Alpha-1.

On a few occasions when I was severely short of breath, I horribly embarrassed myself by becoming incontinent. I can’t think of any way to prevent this in the future except by NOT getting very short of breath – easier said than done.

The most direct method of treating this is to wear an absorptive undergarment (like Depends).  Incontinence is a problem that many individuals face, either because of disease like COPD or because of age. 

I have been increasingly subject to panic attacks and claustrophobia. Till the past few years, I rarely or never suffered from any of these issues. How common are they among Alphas? Any advice that could help? Do any Alphas among your readers have experience with these things and any advice to offer?

These are common complaints among individuals with lung diseases that cause shortness of breath.  There are medications that can help prevent and relieve these episodes although I’ve found that training in breathing techniques and relaxation can be just as effective and more easily used during an attack.

Should Alpha-1 serum levels be checked before each replacement infusion to determine the dosage? Most infuse at 60 mg per Kg of weight but I have heard of some using serum level which does make sense since we all have different natural levels.

It is our recommendation that once augmentation therapy is begun, no serum levels be checked.  Ever.  There are several reasons.  First, the important level is not the serum level but the lung level of alpha-1 antitrypsin.  And the lung levels tend to be much more stable than the serum levels which, as you say, can change from day to day and week to week, even in healthy individuals.  A second reason is that we don’t really know what the best protective level actually is for a given individual.

Has any study been made as to whether there is a connection between Alpha 1 and cystic fibrosis.  I have heard of several families which include both and have always wondered.

There have been a number of families identified with both Alpha-1 and Cystic Fibrosis.  As far as we can tell right now, this is just the luck (or unluck) of the draw.  Both of these genetic conditions are more common than most people think and, by chance and marriage, these conditions can appear in the same family.  However, until large scale screen for Alpha-1 is done, we can’t be sure that there isn’t a connection of some sort.

Please explain gene therapy and its implications for our disease.  How long might it be until it can do what is needed?

It is logical to want to treat a genetic disease by replacing the defective gene itself.  But gene therapy turns out to be a bit more complicated than that.  In Alpha-1, although every gene in the body has the genetic abnormality, the majority of alpha-1 antitrypsin is made in the liver, so the place one would logically want to “put” the normal gene would be the cells of the liver.  However, since the liver is already “clogged” with abnormal alpha-1 antitrypsin, no one really knows what would happen if you tried to force normal alpha-1 antitrypsin through these already compromised cells. 

So the current approach being tested is to insert the normal alpha-1 antitrypsin gene into muscle cells, turning these cells into alpha-1 antitrypsin “factories” thus raising blood and lung levels, much like augmentation therapy.  This approach would not be expected to improve the liver disease risk since the Alpha-1-affected liver is still trying to pump out the abnormal protein.  But work is moving forward in a variety of labs to try to find ways to turn off the liver’s production of abnormal protein.If the studies prove safe and effective, it could be widely available in 5-10 years.

Within the last two months, our support group has lost two Alphas to advanced liver disease and renal failure.  They had been on augmentation therapy for many years and not being treated for liver disease.  They were aware of the Alpha-1 Disease Management Program (ADMAP) and its Long Term Treatment Plan.  What could they have done differently and what signals and appropriate action should all alphas be taking? 

While we have seen advances in our ability to detect milder and milder lung disease in Alpha-1, our ability to detect the earliest stages of liver disease is not as good.  Rarely liver disease can progress rapidly from almost no symptoms to being very severe.  As recommended by the ADMAP program, liver function tests (simple blood tests that can be performed in almost any laboratory) should be measured on a regular basis, usually a minimum of once per year in adults.  More frequent measurement is recommended if there are symptoms that suggest liver problems or if abnormal liver function tests are found.  In addition, more and more Alpha docs are starting to do routine liver ultrasounds every 3-5 years on their Alpha-1 patients.  This test can detect changes in the liver such as cirrhosis or liver cancer.  Unfortunately, once liver disease is present, there is no Alpha-1-specific therapy that can change its course.  Therapy relies on the usual treatment of liver disease and, in the most severe cases, liver transplantation.

Would a liver transplant prevent further damage to the lungs?

In Alpha-1, a liver transplant places a normal liver into the abdomen of an individual with end-stage liver disease caused by Alpha-1 Antitrypsin Deficiency.  This normal liver then starts making normal alpha-1 antitrypsin protein which is released from the liver into the blood, where it bathes all the tissues of the body, including the lungs.  If an individual with liver disease severe enough to require a transplant has no lung disease at the time of transplant, a successful liver transplant should protect that person from developing lung disease.  This is especially true for children who develop liver disease severe enough to require a transplant.

However, even if an adult has relatively normal lung function, it is possible that Alpha-1 related lung damage could have occurred prior to liver transplant that could show up later in life.  It would be expected that even if this happens, the lung disease that appears would be considerably milder than if the transplant had not been required.

A number of individuals with pulmonary symptoms and severe liver disease report that their lung problems seem to improve after their liver transplant.  Most likely this is because certain problems associated with liver failure can impair lung function such as collections of fluid in the abdomen (ascites) and around the lungs (pleural effusion), and their may be edema fluid in the lungs that impairs breathing prior to liver transplant.  Following a successful liver transplant, these problems resolve and the breathing can improve, often dramatically.

An interesting side note is that most livers from fatally injured donors are not tested for Alpha-1 (because of time constraints) and there have been very rare cases of individuals receiving livers that turn out to be PiMZ (carriers for Alpha-1).  Living related donor livers may be difficult to find in an Alpha-1 patient, because most transplant centers will not knowingly transplant a liver from an individual who is a carrier of Alpha-1, as most close relatives of an affected patient are likely to be.

I have had two bronchoscopies in the last year to remove mucous plugs that were impacting my SOB.  Is this normal?  What else should I be doing to keep from having this invasive procedure?  I use the VEST and Acapella faithfully. 

Severe mucus plugging that would require bronchoscopy to wash out the plugs is, fortunately, quite rare in Alpha-1 related lung disease.  For those who haven’t had the “pleasure” of a bronchoscopy, it is a procedure during which, after suitable sedation and cough control, a specialized flexible tube (the bronchoscope) is inserted through the nose or mouth, through the vocal cords, and down into the bronchial tubes.  The bronchoscope is a highly sophisticated instrument that allows for viewing what is at the end of tube through an eyepiece or on a video screen.  It has hand controls that allow the end of the scope to be flexed.  There are channels through the scope for flushing solutions into the lungs and for sucking those fluids back out again.  There is also a channel that lets you push miniature instruments into the lungs to take pieces of the lung or bronchial tubes and to do procedures like removing objects that have been aspirated into the lung (my favorite was a gold tooth) and for placing objected into the airways (like the experimental, non-surgical lung reduction valves).

When the airways get severely plugged with mucus, a physician may have to wash those mucus plugs out of the airways using a bronchoscope.  This is usually done only after more conservative methods have failed.  Such methods include making sure the patient is well-hydrated and drinking plenty of fluids, giving mucus thinning medications, using flutter type hand-held devices that shake mucus loose (like the Acapella), and doing chest physical therapy (like clapping the back while a patient lies in various drainage positions) or using a pulsating chest wrap, such as the Vest or one of the other devices that work similarly.  There are inhaled medications that may help in secretion clearance, as well.

Unfortunately, it sounds as if the question above is being asked by someone who is already doing most of the methods available to avoid bronchoscopy.  There is some controversy about whether repeated bronchoscopy, in the long run, is beneficial to people with severe mucus plugging, but this should be discussed with your physician.