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Ask The Medical Team
Use of this section
This document is intended for use by participants in the Alpha-1 Disease
Management and Prevention Program (ADMAPP) and is based upon questions received
from Alphas over the years. It is important to understand the questions are
ones that are frequently posed by Alphas who contact AlphaNet. These answers
are not intended to provide specific information or recommendations about any
particular case. They represent the opinions of the Medical Director of
AlphaNet to these common questions and reflect the Medical Director's best
medical judgment about these issues. This information is intended to describe,
in a general fashion, how these issues are approached in the Alpha-1 community.
If you have specific questions about how these general answers relate to your
own case, these questions will need to be addressed to your own health care
provider(s).
The followings topics are discussed in this section:
-
Augmentation Therapy
-
Laboratory and Lung Function Tests
-
Steroids
-
Therapies Other than Augmentation Therapy and Steroids
-
Infections and Exacerbations
-
Miscellaneous
Augmentation Therapy
Q: What is the primary purpose of augmentation therapy? What results can
people expect if they are taking augmentation therapy? Do these
expectations change depending on the severity of the underlying lung
disease?
A: Augmentation therapy infusions are intended to supplement
or augment the amount of Alpha-1 antitrypsin (AAT) floating in the blood and
bathing the tissues of the body in individuals with Alpha-1 Antitrypsin
Deficiency-(Alpha-1) related lung disease. Although some individuals report
that they notice improvements in their health when on augmentation therapy, and
there is some evidence for a decrease in the number of lung infections in
individuals receiving augmentation therapy, the primary aim of this therapy is
to reduce the rate of decline of lung function towards normal and, therefore,
improve the long-term quality of life and even the lifespan of individuals with
Alpha-1.
Everyone loses lung function during their adult life, whether they have Alpha-1
or not. Alphas with lung disease lose their lung function at a more rapid rate
than normal individuals. If augmentation therapy is effective, it will be
expected to slow this increased rate of decline, regardless of the severity of
the underlying lung disease.
Q: Is there any evidence that weekly, bi-weekly, or monthly infusions of
augmentation therapy are more or less efficacious?
A: Initial studies with infusions of Prolastin were only done
on a weekly basis and all subsequent products have been compared based on
weekly infusions. All currently marketed augmentation therapy products have
been approved by regulatory authorities (such as the FDA) for administration on
a weekly basis at a dose of 60 mg/kg/week.
Researchers in the 1980s found that giving Prolastin once monthly at 250
mg/kg/month seemed to maintain the lung levels of AAT so they didn't fall any
lower than the lowest level seen with weekly infusions. Other studies showed
that giving more augmentation therapy than 250 mg/kg/month did not permit
longer infusion intervals. In other words, monthly seemed to be the maximum
that individuals could go between infusions.
Based on this information, doctors began giving a variety of infusion regimens
including, in addition to weekly and monthly infusions, doses of 120 mg/kg
every two weeks and 180 mg/kg every three weeks. Soon, however, investigators
began questioning whether monthly infusions and other non-weekly schedules were
as effective as weekly dosing. Articles were published suggesting that
intervals between dosing of greater than one week might, in the long run, be
less effective at maintaining good blood and lung levels of AAT.
Thus, the current recommendations of the Medical Director of AlphaNet are:
Whenever possible, it is best to infuse augmentation therapy on a weekly basis
at a dose of 60 mg/kg/week. If weekly dosing is not possible due to scheduling
issues, travel issues, etc., then dosing at intervals of every two weeks, every
three weeks, or every month can be considered, at doses of 120 mg/kg, 180
mg/kg, and 250 mg/kg, respectively. Individuals who currently are receiving
their infusions every two or three weeks or monthly and are doing well need not
consider changing their schedules. Individuals who currently are on these
longer dosing intervals and are having continued lung function decline or
frequent lung infection might want to discuss moving to weekly infusions.
Q: What is the best infusion schedule during a shortage?
A: There is no right answer to this. Some advocate taking a
lower dose at the usual interval (for example, taking less drug but maintaining
a weekly schedule). Others suggest taking a full dose of drug but increasing
the time between doses (for example, taking a full dose every 10 to 14 days).
From a pharmacokinetic point of view, it probably doesn't make much difference
how you do it. The general consensus among members of the Medical and
Scientific Advisory Committee of the Alpha-1 Foundation has been to infuse a
full dose, but less frequently.
Some individuals try to put drug aside when they are well, in order to have
enough drug supply during a time of shortage. This is done by skipping a week
or taking a weekly dose every ten days, setting aside the medication that is
saved. In this way it may be possible to maintain the full weekly dose during
an infection or exacerbation. If this is done, it is important to monitor the
expiration dates on the saved drug so it can be used prior to expiration.
With additional augmentation therapies on the market, it is hoped shortages
will become a thing of the past.
Q: Why do people get side effects or reactions to augmentation therapy (and
why do some individuals feel better when on augmentation therapy)?
A: There are both understood and somewhat "mystical" reasons
that some people might feel worse or better on augmentation therapy. The
understood or explainable reasons people could feel worse on regular
augmentation therapy infusions center primarily on the fluid and protein load
that accompanies the dose and the extraneous proteins that are in every
augmentation therapy preparation. In terms of fluid and protein load, anyone
with heart, kidney, or severe liver problems could find those problems worsened
or revealed by the large fluid and protein amounts of an augmentation therapy
dose. Regarding the non-AAT proteins in each infusion, these may well provoke
reactions in given individuals that could lead to side effects or reactions.
Some of these reactions can be allergic in nature; others may have to do with
the function of these non-AAT proteins.
Some individuals have had true allergic reactions, sometimes severe, to
augmentation therapy. It is possible individuals with these types of reactions
(or any side effects) from one brand of augmentation therapy might have fewer
or no side effects when switched to a different brand. At the current time, our
experience with the newer products is limited in this regard. In any event, if
the reaction to one brand of product is severe and a change of product brand is
suggested, it is wise to have the initial infusions of the new therapy
administered in a health care facility with access to emergency drugs and
equipment.
Those reactions referred to as "mystical" are simply reactions or adverse
experiences that we simply aren't smart enough to figure out yet. It is even
more difficult to explain why some individuals feel that augmentation therapy
makes them feel better. It could be that the large protein load is helpful to
the patient, either as an energy source (unlikely) or as a means of pulling
edema fluid back from the tissues. It could be that the large fluid load helps
liquefy secretions and get them out of the lungs and sinuses. It could be
related to the known anti-inflammatory properties of AAT.
Q:If I have a reaction to augmentation therapy should I still infuse the
rest of that month's dosing?
A: The answer to this question depends a great deal on the
type and severity of the reaction, and whether or not a problem has been
identified with that particular lot of augmentation therapy. For common, mild
side effects, such as flu-like symptoms or lethargy (tiredness), if you and
your doctor decide to continue infusions, that should not be a problem. For
more serious side effects, you and your doctor will need to consider carefully
whether to continue or whether to try some type of premedication prior to
infusing.
Q: What steps can be taken to reduce adverse reactions to augmentation
therapy, both prior to and during the infusion?
A: Several steps can be taken to reduce the occurrence and
severity of adverse reactions to augmentation therapy. Prior to starting
augmentation therapy, Alpha-1 patients should be tested for IgA deficiency as
this relatively rare genetic disorder can lead to severe reactions to the small
amount of IgA protein in all brands of augmentation therapy. A simple blood
test for IgA level is all that is needed to test for this condition.
The most common reactions to augmentation therapy (flu-like symptoms and/or
lethargy) often can be prevented or reduced by slowing down the rate of
infusion of augmentation therapy. In some cases, the weekly infusion must be
given over as long as 2½ hours to eliminate these symptoms.
Patients with known, mild allergic reactions to augmentation therapy are
sometimes pretreated with antihistamines or even low-dose steroids (although
this latter approach is not recommended except in extreme circumstances). This
type of pretreatment will need to be discussed with your physician.
Individuals with an indwelling IV catheter (a port or a PICC line) need to be
especially observant for catheter infections "masquerading" as augmentation
therapy reactions. Symptoms that occur during or soon after an infusion,
especially accompanied by fever, should be evaluated very carefully. In
general, questions about catheter infections should be directed to your
physician, who may want to take blood cultures, especially directly from the
port or PICC line. Another useful tool to differentiate an augmentation therapy
reaction from an IV catheter infection is to infuse saline through the catheter
and see if the symptoms that occur are identical to those that occur when
receiving augmentation therapy.
Q: If not having enough AAT is damaging, could getting too much (through
augmentation therapy) also be damaging?
A: There is no evidence that receiving "too much" augmentation
therapy in an otherwise healthy, lung affected Alpha is dangerous. In some of
the studies looking at alternative dosing regimens during the 1980s,
investigators administered so much augmentation therapy that essentially all of
the proteins in the blood were replaced with AAT. No ill effects were found,
although it was noted that the AAT augmentation never lasted beyond one month,
no matter how much was given. For this reason, we advise individuals to "round
up" to the next full vial of augmentation therapy that includes your calculated
dose.
In individuals with other underlying conditions, especially heart problems,
kidney problems, and liver problems, the added protein and fluid load of
getting too much augmentation therapy could cause these conditions to worsen.
Q: How does smoking a cigarette offset the effects of augmentation
therapy?
A: The answer to this question is somewhat theoretical, but
likely to be true. AAT is very susceptible to oxidants in cigarette smoke. Once
AAT is exposed to the oxidants in cigarette smoke, its ability to block the
destructive activity of white blood cell enzymes is severely impaired. This is
one of the mechanisms by which smokers, even smokers not diagnosed with
Alpha-1, are thought to develop emphysema.
In individuals who don't have Alpha-1, the liver can replace this oxidized AAT
very quickly. In Alphas, it can take the liver days to replace this damaged
AAT. In Alphas who are receiving augmentation therapy, a single cigarette can
oxidize all the augmentation therapy in the lungs and this damaged AAT won't be
replaced until the next infusion of augmentation therapy.
Q: Should augmentation therapy be stopped when the patient has an
infection?
A: Virtually all physicians who work in Alpha-1 appreciate
that lung infections are the time when Alpha-1 patients need augmentation
therapy the most! Far from stopping augmentation therapy, Alphas receiving
augmentation therapy should be sure to take their weekly, prescribed doses of
augmentation therapy during a lung infection. In fact, some have advocated
taking higher doses or more frequent doses of augmentation therapy during times
of infection; however, there is no evidence at present to support this
practice.
Q: If I'm getting the same dose of augmentation therapy every week (60
mg/kg and my weight hasn't changed) why do I sometimes receive 4 vials of
augmentation therapy per week and 5 vials other times?
A: While your total dose hasn't changed, the amount of Alpha-1
in each vial of augmentation therapy does change from lot to lot. The largest
vial of augmentation therapy is supposed to contain approximately 1000 mg of
alpha-1 proteinase inhibitor (alpha-1 antitrypsin). Sometimes "approximately"
means it contains 823 mg, for example. Sometimes "approximately" means it
contains 1202 mg. Let's assume you weigh 143 pounds. Your weight in kilograms
would be 143 divided by 2.2, or 65 kilograms. Your calculated weekly dose of
augmentation therapy should be 65 times 60, or 3,900 mg. Since we "round up" to
the total number of vials needed that is not lower than the calculated dose, if
the lot you are using has 800 mg vials, you would need five vials to deliver
the calculated dose. You'd need only four vials if the lot being used contained
1200 mg per vial.
Q: Where does the alpha-1 antitrypsin come from that goes into making
augmentation therapy products?
A: Augmentation therapy is made from plasma donated through
plasma donor centers run by several companies. Plasma donation is distinct from
blood donation. People can donate plasma very frequently (as often as every
week) and plasma can be frozen and stored for many months. This is very
important for plasma safety as plasma centers routinely test a potential donor
for HIV/AIDS, hepatitis, etc., then take the plasma donations and freeze them.
Two to six months later, they retest the donor for the various viruses and, if
all the testing is negative, they release the plasma that was collected 2-6
months before. If the donor doesn't return for the repeat testing, the plasma
is discarded.
Q: What is the deal about augmentation therapy and IgA deficiency?
A: IgA is one of the most common hereditary immune
deficiencies. IgA deficiency, like Alpha-1, can be associated with lung and
allergic-type symptoms. It also is true that individuals with either of these
conditions (IgA deficiency or Alpha-1) can lead normal, healthy lives without
ever knowing they have one of these conditions. Individuals with severe Alpha-1
who are about to start augmentation therapy should be tested for IgA
deficiency, because giving repeated infusions of a plasma-derived product can
lead to severe allergic reactions in IgA deficient individuals. This is due to
the small amount of IgA protein contained in each vial of augmentation therapy.
Individuals with hereditary IgA deficiency have circulating antibodies to the
IgA molecule and these antibodies can cause an allergic reaction when even
small amounts of IgA protein are delivered intravenously.
Since augmentation therapy is only given to patients with lung disease due to
Alpha-1, it is hard to know whether those with IgA deficiency have worse lung
problems than those without. It is logical to assume they would. Both Alpha-1
and IgA deficiency, when they cause problems, can lead to recurrent lung
infections and bronchiectasis and there may well be some additive effects of
having both.
Laboratory And Lung Function Tests
Q: How often should AAT levels in the blood be checked?
A: It usually is not necessary to have more than one AAT level
checked during an Alpha's lifetime, just as it usually is not necessary to have
an Alpha's phenotype or genotype checked more than once in a lifetime. Having
said this, however, there are some exceptions that should be noted. When the
initial diagnosis is made, it is reasonable to recheck it, preferably at a
reference laboratory with experience in testing for Alpha-1.
Some individuals with unusual phenotypes and evidence of lung disease may have
their levels rechecked to evaluate whether their baseline level is low enough
to cause concern. It is not recommended that levels be checked following
institution of augmentation therapy. It is also important to know that
phenotype tests will be inaccurate in individuals receiving augmentation
therapy.
Q: How much do AAT levels vary?
A: AAT is one of a group of proteins, made mostly in the
liver, that is called "acute phase reactants." This means that this group of
proteins can be rapidly manufactured and released into the blood during times
of stress. This stress can be an infection, an inflammatory process, surgery,
or one of a host of other stresses including severe emotional stress. In
individuals with normal AAT, the AAT level can more than double during a time
of stress. Even individuals with severe Alpha-1 (PI*ZZ) can raise their AAT
levels above baseline by 10 to 20 mg/dl (2-3 mmol). Individuals with
heterozygote phenotypes (carriers) can often raise their AAT levels into the
normal range during times of physical stress. Of note, individuals with a Null
phenotype cannot make any AAT even under times of stress.
Q: Are there particular laboratories that provide more reliable test
results for AAT levels, liver function tests, etc?
A: Accurate laboratory results come from familiarity with
testing techniques and adequate quality control. Liver function testing is so
standardized and performed so often in every lab in the country, no special
laboratory considerations are usually needed.
On the other hand, most labs don't perform a large number of AAT levels,
phenotypes, or genotypes. It is recommended these important tests be sent to a
laboratory that does these on a routine basis, such as Mark Brantly's lab at
the University of Florida.
Q: Can I be tested for Alpha-1 when I'm pregnant?
A: While there is no problem doing a phenotype test during
pregnancy (the test that tells you the type of protein in the blood), doing a
simple alpha-1 antitrypsin level has some problems.
As described elsewhere in this Guide and in this FAQ, alpha-1 antitrypsin is an
"acute phase reactant." Acute phase reactants are a group of proteins whose
production can be boosted dramatically by the body in response to stress or
inflammation. Pregnancy is one of the most potent stimulators of this type of
response. Thus, even in an individual with Alpha-1, the level of Alpha-1 can be
doubled or even tripled during the pregnancy. During pregnancy a severely
deficient patient could, in extreme cases, have a level in the intermediate
range and a carrier could have a normal level.
Genotyping for Alpha-1 is not a problem during pregnancy. Although a small
amount of fetal DNA can be found in the mother's blood during pregnancy, this
is in insufficient quantity to affect a genotyping.
Q: Some doctors are increasing their augmentation therapy dosage based on
levels of AAT in the blood. Other doctors are getting levels each time they
infuse for informational purposes. Does this blood level testing accurately
determine the amount of AAT in the lungs and should dosing be based on these
levels?
A: It is the opinion of the Medical Director of AlphaNet that
it is not necessary to follow blood levels or to adjust doses based on blood
levels. The important level of AAT is the lung level, which can only be
obtained by bronchoscopic lavage of the alveoli. The studies that led to the
approval of augmentation therapy showed that a dose of 60 mg/kg/week provided
stable, adequate lung levels of augmentation therapy, even though blood levels
varied greatly.
Studies in the future may evaluate a variety of doses of augmentation therapy
and determine that lower doses are just as effective as current doses or they
may find that higher doses are more effective than current doses. Until such
studies are done, the current dosing recommendations remain.
Q: I had my pulmonary function tested and my FEV1 is only 37
percent of predicted. Does this mean that I have lost 63 percent of my lung
function? Does it mean that 63 percent of my lungs have been destroyed by
emphysema?
A: The two most common lung function tests that people hear
about are the Forced Vital Capacity (FVC) and the Forced Expiratory Volume in
One Second (FEV1). These two measurements are included in what is
called spirometry, the type of lung function testing that can be done with a
small, relatively inexpensive machine in a doctor's office or screening
facility. The FVC is the volume of air you can exhale from the top of a deep
breath in, to the bottom of a complete breath out, blowing out all your air as
fast and hard as you can (keep going . . . keep going . . . keep going). The
FEV1 measures how much of that top-to-bottom breath was expelled
during the very first second of the breath. People with normal lungs can get
70% to 90% of their breath out during that first second. If there is any
resistance to the normal flow of air out of the lungs, the time it takes to get
that air out is prolonged, and the FEV1 goes down.
Many things can make the FEV1 lower in addition to the emphysema of
Alpha-1. Spasm of the airway muscles (asthma) can cause increased resistance to
airflow, as can mucus in the airways and swelling of the airway walls. If
someone has small lungs, which can be due to disease (scarring in the lung or
interstitial lung disease), chest wall deformities (such as scoliosis or
curvature of the spine), or due to an unusual chest wall size, then both the
FVC and FEV1 would be lowered and the values could be below the
predicted normal range. These would not necessarily mean that your lungs had
lost a specific amount of function based on the FEV1 measurement.
Also confusing is the fact that the measurement of FEV1 is very
effort-dependent. In other words, the value can change a great deal depending
on the effort put in during the testing. If you were tired on the day of
testing or you were having a problem with your respiratory muscles, the FEV1
would be down.
If all of this information wasn't complicated enough, there is the problem that
even if you only have emphysema as the cause of a low FEV1, the
value of FEV1 is not directly related to the amount of emphysema you
have. An Alpha-1 patient can have significant emphysema on their X-rays and
more sophisticated lung function measurements, but have a normal FEV1.
Similarly, the FEV1 can be quite low with only mild emphysema. It is
thought that the change in FEV1 is most directly related to the loss
of elastic fibers holding the airways open. This "tethering" keeps the airways
from collapsing as you force air out of the lungs during exhalation.
So, the simple answer is "no" the percent predicted FEV1 does not
tell you how much emphysema you have or how much lung you have lost. Still,
this measurement, with all its complexities, is one of the best simple tests we
have to tell whether someone with obstructive lung disease is worsening,
stable, or improving. Repeated in a consistent manner, it can provide a gauge
to evaluate how someone is doing over time.
Q: Why do people with low oxygen tend to have elevated hemoglobin,
hematocrit, and/or red blood cell counts (RBC) on their blood tests?
A: When Alpha-1 causes emphysema, the lung disease can lower
the amount of oxygen that can be delivered to the blood, and, therefore, to the
tissues and organs of the body. The body compensates for this low oxygen by
making more and more red blood cells, the cells that contain the hemoglobin
that delivers oxygen to the tissues. This increase in the number of red blood
cells is called polycythemia. There are other causes of polycythemia (such as
Polycythemia Vera, which is like a mild cancer of the red blood cells), but the
polycythemia due to low oxygen (secondary polycythemia) is the type most
commonly seen in Alpha-1.
Steroids
Q: What are the side effects of long-term steroid use?
A: The long-term side effects of steroid use are quite
variable and can be severe. They include suppression of the adrenal-pituitary
axis (turning off of steroid production by the adrenal glands and/or turning
off of the signal to make steroids by the pituitary), increased appetite,
weight gain, deposition of fat in specific locations (widows hump, moon faces),
loss of calcium from bone, accentuation or appearance of diabetes, cataracts,
accentuation or appearance of high blood pressure, acute aseptic necrosis of
bone (death of bone due to loss of blood supply), increased susceptibility to
infection, appearance of infection caused by organisms that normally don't lead
to infection (opportunistic infection), activation of dormant infections (such
as TB), development of so-called steroid psychosis, steroid myopathy (loss of
muscle tissue and muscle strength), ulcers of the stomach and duodenum, poor
wound healing, low potassium, bruising, thinning of skin, changes in menstrual
cycle, acne, hair growth, anxiety, and insomnia.
One important aspect of the very first side effect mentioned above
(adrenal-pituitary suppression) is that, when stopping steroids after long-term
use, the steroid dose must be reduced gradually over a long time period. Once
steroids have been stopped in this way, the adrenal glands are able to start
making normal levels of steroid (the body needs steroids to maintain function)
but they may not be able to boost natural steroid production during times of
stress or injury. This can lead to severe medical problems, including shock.
This impairment of adrenal reserve can last for up to a year after stopping
chronic steroids. It is important to tell any physician caring for you that you
are on chronic steroids or have recently been weaned off chronic steroids so
that, in an emergency, supplemental steroids can be administered. Patients on
chronic steroids or who recently stopped chronic steroids should consider
wearing a medical alert bracelet or necklace with information about their
steroid use engraved on it.
Q: What are the potential long-term risks of inhaled steroid use?
A: Inhaled steroids were developed as an asthma therapy
designed for chronic use without the risk of the steroid side effects mentioned
above. Since their introduction, they have become the recommended first line
therapy for asthma. Many, if not most, Alphas with lung disease have an
asthmatic component and, therefore, many are given inhaled steroid medications.
Inhaled steroids have been shown to be beneficial at reducing the number and
severity of exacerbations in individuals with COPD and presumably the same
holds true for individuals with Alpha-1-related lung disease.
While initially it was thought inhaled steroids might provide the benefits of
oral steroids without the side effects, as stronger and stronger inhaled
steroid medications have been developed, it has become clear that this higher
dose therapy can cause many of the same side effects as oral steroids. Inhaled
steroids, especially at high doses should be taken with careful monitoring for
side effects and this medication should be continued only if it appears to
offer significant benefits.
Q: Is it safe to give a prednisone dose of 40 mg/day for five days and then
stop, with no tapering dose, for an exacerbation?
A: In individuals who have not been on chronic steroids and
need only a short course, it is perfectly safe to give five days of steroids at
almost any dose and then stop suddenly. Five days is, in general, not a
sufficient dosing period to cause adrenal suppression and, therefore, the
adrenal glands should be able to pick right up where they left off before the
steroids were given.
Therapies Other Than Augmentation Therapy And Steroids
Q: Why do Alphas with lung disease take asthma medicines?
A: Many people with emphysema, especially Alphas, have asthma
(also known as reversible obstructive airways disease [ROAD], hyperreactive
airways disease, or bronchospasm). One study indicates that over 70% of Alphas
with lung disease have asthma. Asthma is defined as the component of the
obstruction to the outflow (exhalation) of air from the lungs that can be
reversed with medication. The obstruction caused by emphysema itself (thought
to be due to loss of the connective tissue that holds the airways open during
exhalation) is, in general, fixed and permanent. The component of the
obstruction that can be reversed by bronchodilators, steroids, theophylline,
etc., is by definition, asthma. This component is generally thought to be due
to spasm of the muscles of the bronchial tubes (bronchospasm), inflammation of
the airways with swelling, and increased mucus production blocking the airways.
If you have lung disease from Alpha-1, you can think of the emphysema component
causing the slow steady decline in lung function that can't be reversed (with
current technology) and the asthma component as the part that gives you the
daily, weekly, or monthly ups and downs in your breathing. Augmentation
therapy, assuming it works, is designed to slow down the emphysema-related
decline. The inhalers and pills (and emergency room IVs) that people take are
designed to reverse the asthmatic side. Long-acting bronchodilators may also
reduce the number and severity of exacerbations.
Q: At what point should a person consider supplemental oxygen?
A: Individuals who have decreased oxygen levels in their blood
for a significant period out of each 24 hours should be on supplemental oxygen.
In addition, individuals whose oxygen is normal most of the time but have
severe decreases in oxygen for short periods of time, should be on oxygen
during those times of low oxygen. The actual levels of oxygen in the blood that
should prompt the use of oxygen depend on the individual's underlying
conditions. Individuals with heart disease or disease of the blood vessels in
the arms, legs, brain, or other important organs may need oxygen therapy to
treat milder decreases in oxygen than individuals without these conditions.
Most commonly, individuals begin on oxygen therapy when it is noticed that
their oxygen levels fall with exercise and/or with sleep. In general, such
individuals only use supplemental oxygen with exercise and/or sleep. Another
indication that oxygen might be necessary is the development of pulmonary
hypertension or right heart failure due to lung problems (Cor Pulmonale).
It is important to realize that under most circumstances, individuals cannot
"feel" whether their oxygen is normal or low. When one is short of breath, this
is usually because the carbon dioxide level is raised or the blood is too acid.
There isn't really a sensor in the brain for low oxygen. The only way to detect
if the oxygen level is low is with an oximeter or by drawing an arterial blood
gas (ABG).
Q: What are the advantages to the dry powder inhaled (DPI) medications,
such as Advair, as opposed to a standard metered dose inhaler (MDI)?
A: In any given individual, there may be no advantage of one
method of delivery over the other. It is really a matter of trial and error.
The main reason that many inhaled medications are being developed in powdered
form is that there is a worldwide ban on the propellants used in many MDIs, and
it is expected these types of MDIs will disappear in the near future.
Q: Many physicians seem to be switching their patients to Advair. What is
Advair, and is it better than other bronchodilators?
A: Advair is a combination of two common asthma medications,
Serevent (a long-acting beta agonist bronchodilator) and Flovent (a potent
inhaled steroid) administered as a single puff using a dry powder delivery
system. For individuals already taking Serevent and Flovent, taking this
combination inhaler is more convenient, although, at the present time, it is
also more expensive. Some individuals feel the delivery system and the
combination product work better than the individual products taken in sequence.
Q: Can low potassium levels be a result of medication usage? Does
Serevent cause your body to excrete potassium?
A: Beta agonist bronchodilators, especially Serevent and
terbutaline, are known to cause the kidneys to lose potassium into the urine.
In most individuals, this does not pose a significant problem because this loss
is so slow and is usually made up by dietary intake of potassium. However, in
individuals with poor potassium intake or individuals on other medications that
can add to potassium loss (such as some diuretics) this lowering of potassium
levels can be severe. Certain heart conditions are very sensitive to potassium
loss and individuals with rhythm problems of their hearts may need to discuss
the use of these bronchodilators with their physicians.
Infections and Exacerbations
Q: What is pseudomonas, and how common is this type of infection in
Alphas?
A: Pseudomonas is a type of bacteria. There are a number of
different species of Pseudomonas but the most common disease-causing species is
Pseudomonas aeruginosum (PA). Pseudomonas gets its name (false=pseudo;
yeast=monas) for the fact that it looks something like yeast when grown in
culture.
In general, PA only causes disease in individuals who have compromised immunity
or compromised anatomy. It is very common in individuals with cystic fibrosis.
In Alpha-1, it is primarily seen in individuals with bronchiectasis (distortion
of the bronchial tubes from chronic or recurrent infection). Bronchiectasis is
a relatively common finding in individuals with lung disease from Alpha-1. PA
can live in the damaged bronchial tubes of individuals with bronchiectasis
without causing disease. When the numbers of PA bacteria in a patient with
bronchiectasis start to rise, the individual can develop an exacerbation and,
rarely, pneumonia. PA pneumonia can be very severe because 1) the organism can
be very aggressive and release agents that cause illness, and 2) the organism
can be resistant to many common antibiotics. Fortunately, PA infections are
relatively rare in Alphas.
Q: Is there any advantage to Alphas of long-term sustained usage of
antibiotics?
A: The risks of long-term sustained use of antibiotics usually
outweigh any benefits. The primary risk is the killing off of bacteria that are
sensitive to the antibiotics being used accompanied by an overgrowth of
bacteria that are resistant to antibiotic therapy. Other risks include changing
the normal bacterial flora of the body leading to the development of
antibiotic-induced diarrhea syndromes and yeast infections.
Still, there are circumstances where what is known as chronic suppressive
antibiotic therapy may be helpful. These include in patients with
bronchiectasis who are chronically colonized with bacteria or in individuals
with extremely frequent infectious exacerbations of their lung disease. Careful
monitoring is required if this course of therapy is chosen.
Q: Should augmentation therapy be taken when the patient has an
infection?
A: See answer under "augmentation therapy."
Q: What are the best methods for fighting viral infections? What about
bacterial infections?
A: The best method for fighting viral and bacterial infections
is prevention. Avoid crowds, young children, and known infected individuals.
Practice frequent hand washing. Get flu shots and Pneumovax. Consider
immunization against Hemophilus influenzae, hepatitis B, and hepatitis A.
Once a viral infection sets in, there is often little that can be done, unless
the virus causing disease is one of the few that have a specific therapy
(Tamiflu for influenza, acyclovir for herpes, ganciclovir and others for CMV,
specific drugs for respiratory syncytial virus, etc.). Most treatments for
viral infections are symptomatic (designed to make you feel better while the
body fights the virus on its own). In Alphas who develop a viral
respiratory tract infection, it is often recommended they start immediately on
an antibiotic. Classic antibiotics do nothing to treat the virus, rather they
are used to prevent or treat the possibility that a bacterial infection will
develop in the airways already injured by the viral infection.
The best method for treating a known bacterial infection is to give an
appropriate antibiotic at the earliest possible time. No one antibiotic is
necessarily better or stronger than another; rather, a particular bacteria may
be more sensitive and better killed by one or more antibiotics than by others.
The simplest antibiotic, for instance penicillin, can be just as effective as
the latest antibiotic if the organism causing the infection is sensitive to it.
The problem is that one often doesn't know what the bacteria is that is causing
a particular infection and one often doesn't know what antibiotic it might be
sensitive to. Antibiotic resistance tends to be different in different
geographic areas, so it's important to let your physician recommend the
antibiotic that seems to have the best effect at the current time in your own
locale.
Q: What is the best philosophy for fighting exacerbations?
A: The best philosophy for fighting exacerbations is to hit
them hard and early. Know your own disease; know how your lungs react
during an exacerbation. Start early with increasing your usual medications,
perhaps starting steroids and/or antibiotics, etc., in consultation with your
own physician.
Miscellaneous
Q: I am a healthy young adult and have been diagnosed with Alpha-1 (PiZZ).
What are the chances that I will get lung or liver disease in the future?
A: First, with respect to lung disease, if you avoid cigarette
smoke, both your own smoking and second-hand smoke, if you avoid frequent lung
infections, and if you don't get involved in an occupation that exposes you to
high levels of dust or organic fumes, it appears likely you will not get
emphysema. While this is certainly reassuring, it must be noted that there are
some individuals who do everything right but still get lung disease. Most do
not, however. It is suspected that additional genes in the body affect
susceptibility to lung disease in Alpha-1.
With respect to the liver disease, some of the answers to your questions depend
upon whether you had severe childhood liver disease and whether your liver has
been scarred by it. There is an increased incidence of liver cancer in patients
with Alpha-1 but this still occurs extremely rarely. Please remember that a
majority of individuals with Alpha-1 develop some elevation of their liver
enzymes during the first two years of life. Most of the time these resolve
without any permanent damage to the liver. As Alphas get older, there may be
some liver injury that occurs, but in most individuals this does not affect
their health at all. Liver toxic agents, such as alcoholic beverages, viruses
that attack the liver like hepatitis, and some liver-metabolized drugs may
increase the severity of liver disease in some individuals. More needs to be
learned about liver disease risks.
Chances are, if you keep your knowledge of Alpha-1 current and avoid known risk
factors, you should lead a long, healthy, and normal life.
Q: Can I scuba-dive if I have Alpha-1?
A: This is a very common question! If an individual with
Alpha-1 has normal PFTs, including a normal DLCO and normal high resolution CT
scan of the chest, then there is likely to be no risk from their Alpha-1,
should they decide to scuba dive. It might be wise to repeat the pulmonary
function testing on an annual basis. Should there be a decline in lung function
on follow-up, the decision regarding diving should be reconsidered.
Many individuals dive with mild or even moderate obstructive lung disease. As
with any physical activity, if an individual is on "rescue" inhalers, they
should be taken prior to a dive. The major risks for individuals with lung
disease relate to barotrauma or injury due to pressure effects. The primary
finding that would lead one to abandon diving would be blebs or bullae in the
lungs. These air-pockets with lung tissue or on the surface of the lung can
"pop" during a dive leading to a collapsed lung, which can be catastrophic
during a dive, especially for individuals with underlying lung disease.
Individuals requiring supplemental oxygen should probably avoid scuba-diving.
Q: What are the risks of flying if I have Alpha-1 lung disease?
A: This question is related to the one above. The risks
regarding flying have to do with rapid pressure changes in the outside
environment compared with the lungs. In general, any increased risk that an
Alpha might have in this regard would be related to the potential presence of
bullae or blebs near the surface of the lung. If there are no blebs, and the
person's lung function is normal, or only mildly to moderately impaired, there
should be no problem.
An additional consideration is the use of oxygen during flying. This topic is
covered extensively in chapters on oxygen therapy and travel, elsewhere in this
Guide.
Q: What are the risks of anesthesia and surgery to Alphas? Are these
risks greater than they are for the general population?
A: There is no specific increased anesthesia or surgical risks
associated with Alpha-1. There are definite increased risks associated with
having chronic liver disease or chronic obstructive lung disease (COPD), such
as emphysema. COPD causes an increase in post-operative lung problems
(including infection, problems getting off a ventilator, problems clearing
secretions, need for prolonged oxygen, etc.) Abdominal surgery can cause
similar lung problems because of the affect on the functioning of the
diaphragm. Pre- and post-operative respiratory therapy and rehabilitation can
greatly reduce these risks.
Many think using spinal anesthesia is safer than general anesthesia in people
with lung disease. This is probably not the case.
Q: Why are stairs so difficult for Alphas to walk up?
A: Stairs represent one of the hardest challenges for
individuals with obstructive lung disease. They are everywhere; they require
that the large muscles of the legs lift the entire body weight with each step;
and they represent a measurable amount of activity. For example, you may recall
that six months ago you could reach the top of the stairs without stopping,
then have to rest and catch your breath, while now you find that you have to
stop and rest two steps from the top. It may not appear that walking up 12
steps represents considerably greater effort than walking 12 steps on the
level, but it does.
Q: Are there dental problems associated with Alpha-1?
A: There has been very little recent work into the dental
implications of Alpha-1. In the 1970s there was a fair amount of basic research
done in this area, since alpha-1 antitrypsin is the major inhibitor of
neutrophil (white blood cell) elastase and neutrophil elastase has been
implicated in the destruction of the connective tissue that binds the teeth to
the jaw. Currently, there is no indication that individuals with Alpha-1 have
any greater incidence of dental problems, but frankly, this has not been looked
at in a comprehensive manner.
Q: Is there a connection between Alpha-1 and bronchiectasis? When should
patients with bronchiectasis be treated with antibiotics?
A: The connection between Alpha-1 and bronchiectasis is 1)
statistical, and 2) biochemical. The statistical association is that, while
virtually all non-Alpha-1 bronchiectasis has an identifiable cause (most
commonly: severe childhood [or adult] lung infections, immune deficiency,
congenital abnormalities, fungal infections of the airways), people with
Alpha-1 seem to have a higher-than-expected incidence of bronchiectasis and, in
many cases, have no other reason to explain why they have it. There is
much written in medical literature regarding the association between
bronchiectasis and Alpha-1.
The biochemical association is somewhat theoretical. Since we know that alpha-1
antitrypsin blocks some of the destructive enzymes of the body's white blood
cells, and since we know these enzymes can damage the structural proteins of
the bronchi, it is not a large leap to postulate that the reason people with
Alpha-1 get bronchiectasis has to do with bronchial damage caused by white
blood cell enzymes. Why some Alphas get bronchiectasis and others do not is an
unanswered question. Perhaps it has to do with the number of bronchial
infections that an Alpha gets during their life.
Since patients with symptomatic bronchiectasis generally always have infected
sputum, the best way to decide whether it's time to treat with antibiotics is
when there is a change in the clinical status of the patient (more short of
breath, increased sputum, change in the color or consistency or odor of the
sputum). The chronic use of prophylactic or suppressive antibiotics, especially
by inhalation, has been advocated in patients with severe recurrent infections
caused by bronchiectasis.
Q: How does Alpha-1 affect the body in addition to lung and liver
disease?
A: There are several other conditions that have been associated
with Alpha-1. These include necrotizing panniculitis, a painful scarring skin
condition; vasculitis, an inflammation of the blood vessels; Wegener's
granulomatosis, an unusual type of vasculitis affecting the lungs;
bronchiectasis, a distortion and destruction of the bronchial tubes leading to
chronic infection; and hepatocellular carcinoma, a cancer of the liver cells.
There is some statistical evidence of an association with certain types of
arthritis. There may be other conditions associated with Alpha-1 that we
haven't learned of yet.
Q: Can I take lipid-lowering medication if I have Alpha-1? How about
other medications that list liver side effects on their labels?
A: Most cholesterol lowering drugs have a warning about
potential liver injury. There is currently no evidence that individuals
with Alpha-1 who have normal liver function have any greater risk of developing
liver problems from these drugs than the general population. Careful monitoring
of liver function should be performed on all patients taking these medications,
including those with Alpha-1. Many individuals with Alpha-1 take this
type of medication without any problems.
Similarly, many other medications list liver-related side effects. If such
medication is necessary in an individual with Alpha-1, careful monitoring of
liver function is probably warranted. If alternative medications without liver
toxicity are available, they should probably be considered first.
If you already have liver disease from your Alpha-1, then you and your physician
will need to carefully evaluate the risks and benefits of a particular
medication. Very close attention to liver function will be necessary if such
medications need to be prescribed for individuals with Alpha-1-related liver
disease.
Q: How does Alpha-1 cause high blood pressure in the arteries of the lung
(pulmonary hypertension) and what causes heart failure in this setting (Cor
Pulmonale)?
A: One of the effects of low oxygen in the lungs is to cause
the blood vessels of the lung to constrict. This is a good defense mechanism
under certain circumstances. Let's say you have normal lungs and you inhale a
peanut and it lodges in one of your bronchial tubes, blocking off the movement
of air into and out of that part of the lung. In response to the very low
oxygen in that area, the lung's blood vessels would constrict so that
particular area of the lung would essentially be shut down.
The problem in diseases like emphysema is that the low oxygen levels aren't
localized to a particular part of the lung, they're all over. So all the
vessels of the lung tend to constrict when the lung disease of Alpha-1 gets
severe enough to cause low oxygen levels. When most of the blood vessels of the
lungs constrict, there is increased resistance to the flow of blood being
pumped from the right ventricle, and the pulmonary artery pressures rise. If
this goes on long enough and the pressure is high enough, the right ventricle
starts to enlarge and fail. When the left ventricle has severe failure, the
blood tends to "back up" causing fluid to accumulate in the lungs (pulmonary
edema). When the right ventricle has severe failure, the blood tends to back up
causing fluid to accumulate in the liver (causing liver enlargement) and the
ankles/legs (peripheral edema). This is known as Cor Pulmonale, which implies
right heart failure due to lung disease.
When one of the heart's ventricles starts to fail, especially in the face of
high blood pressure, it tends to enlarge. In patients with hypertension severe
enough to cause the heart to fail (pump less blood than the body requires), the
enlargement is in the left ventricle, the one that pumps blood to the body. In
patients where the elevated blood pressure is in the lungs (pulmonary
hypertension), it is the right ventricle that enlarges (the one sending blood
to the lungs).
Can you easily detect the enlarged heart in these conditions? Chest X-ray is
fairly good at detecting an enlarged left ventricle but the right ventricle has
to be very enlarged before it is easily seen on chest X-ray. Even when chest
X-ray can't detect an enlarged right ventricle, it can point toward pulmonary
hypertension, which shows up as enlargement of the central vessels in the chest
and "pruning" of the peripheral branches of the lung's blood vessels. Chest CT
can often provide a very accurate picture of ventricular size and give an
indication of the pressure in the pulmonary arteries. EKG can easily detect
ventricular hypertrophy (thickening of the ventricle wall) but hypertrophy
doesn't always accompany ventricular enlargement.
Echocardiography (cardiac echo) is excellent at detecting enlargement of the
chambers of the heart and considered the standard non-invasive method of
looking for right (or left) heart enlargement. It can also provide information
about the pressures in the heart and vessels and the functioning of the heart.
Unfortunately, sometimes people with severe emphysema can't have accurate
echoes performed because the trapped air in the lungs acts as a curtain that
the echo cannot see through. The true gold standard is heart catheterization
with pressure measurement and, when necessary, dye injection.