Updated: March 7, 2004
|Synonyms and related keywords: alpha-1
antiprotease deficiency, alpha1 antiprotease deficiency, alpha-1
antitrypsin deficiency, AAT, early-onset panacinar emphysema,
hepatic cirrhosis |
|Author: Paul Fairman, MD, Medical Director of
Lung Transplant Service, Professor, Department of Internal Medicine,
Divisions of Pulmonary and Critical Care Medicine, Medical College
|Paul Fairman, MD, is a member of the following medical
societies: American College of Chest Physicians, American College of
Physicians, American Thoracic Society, and International Society for
Heart and Lung Transplantation
|Editor(s): Ryland P Byrd, Jr, MD, Chief of
Pulmonary Medicine, Medical Director of Respiratory Therapy, Quillen
VA Medical Center; Professor, Department of Internal Medicine,
Division of Pulmonary Diseases and Critical Care Medicine, Quillen
College of Medicine, East Tennessee State University;
Francisco Talavera, PharmD, PhD, Senior Pharmacy
Editor, Pharmacy, eMedicine; Om Prakash Sharma, MD,
Professor, Department of Medicine, Division of Pulmonary and
Critical Care Medicine, University of Southern California;
Timothy D Rice, MD, Associate Professor,
Departments of Internal Medicine and Pediatrics and Adolescent
Medicine, Saint Louis University School of Medicine; and Zab
Mohsenifar, MD, Director, Division of Pulmonary/Critical
Care Medicine, Department of Medicine, Cedars-Sinai Medical Center;
Professor, Department of Internal Medicine, University of California
at Los Angeles School of Medicine |
Alpha1-antitrypsin (AAT) deficiency is one of the most common
inherited disorders among whites. Its primary manifestation is early-onset
panacinar emphysema. A minority of patients develops hepatic cirrhosis.
Slowly progressive dyspnea is the primary symptom, although many patients
initially have symptoms of cough, sputum production, or wheezing.
The genetic defect in AAT deficiency
results in a molecule that cannot be released from its production site in
hepatocytes. Low serum levels of the protein result in low alveolar
concentrations, where the AAT molecule normally would serve as protection
against antiproteases. The resulting protease excess destroys alveolar
walls and causes emphysema.
- In the US: This genetic defect affects 1 per
3000-5000 individuals. AAT is 1 of the 3 most common lethal genetic
diseases among whites. The other 2 common fatal genetic defects are
cystic fibrosis and Down syndrome.
Similar rates are found among
Specific morbidity and mortality
rates are unknown. Not all patients with homozygous deficiency develop
symptomatic emphysema or cirrhosis; however, among those who develop
symptomatic disease, the mortality rate is very high.
Race: Racial groups other than whites are affected
Sex: Women and men are affected in equal numbers.
Age: The enzyme deficiency is present from birth and
can be an unusual cause of neonatal jaundice. Symptomatic emphysema
develops in the fourth decade of life in smokers and a decade later in
History: Symptoms of AAT
deficiency emphysema are limited to the respiratory system.
- Dyspnea is the symptom that characterizes and eventually dominates
- Similar to other forms of emphysema, the dyspnea of AAT deficiency
initially is evident only with strenuous exertion. Over several years,
it eventually limits even mild activities.
- Patients with AAT deficiency frequently develop dyspnea 20-30
years earlier (age 30-45 y) than smokers with emphysema and without
- Cigarette smoking accelerates the progression of emphysema in
patients with AAT deficiency; symptoms develop about 10 years earlier
in AAT-deficient individuals who smoke regularly.
- Other symptoms, including cough, sputum production, and wheezing,
may predominate in the early stages of disease.
- Symptoms initially are intermittent, and, if wheezing is the
predominant symptom, patients often are told they have asthma.
- If recurrent episodes of cough are most prominent, patients may be
treated with multiple courses of antibiotics and evaluated for
sinusitis, postnasal drip, or gastroesophageal reflux.
- By the time dyspnea becomes the dominant manifestation and a
diagnosis is established, most patients will have seen several
physicians over several years.
Physical: No single physical sign confirms a diagnosis
of AAT deficiency emphysema. Signs characteristic of increased respiratory
work, airflow obstruction, and hyperinflation eventually develop but are
dependent on the severity of emphysema at the time of diagnosis.
- Increased respiratory work is evident as tachypnea, scalene and
intercostal muscle retraction, and tripod position.
- Airflow obstruction manifests as pursed-lip breathing, wheezing, and
- Hyperinflation results in barrel chest, increased percussion note,
decreased breath sound intensity, and distant heart sounds.
- Patients with mild emphysema generally have no abnormal findings on
physical examination. Even moderate disease may be evident only when a
complicating acute intercurrent infection occurs. Most of the signs
generally considered a part of emphysema (from any cause) are signs of
moderate-to-severe disease; mild-to-moderate disease is missed easily if
the physician relies solely on the physical examination findings.
Causes: The name of this disease originated from a
deficiency of the serum antiprotease, originally called AAT. The
responsible genetic defect affects 1 in 3000-5000 individuals, making it 1
of the 3 most common lethal genetic diseases among whites. The other 2
common fatal genetic defects are cystic fibrosis and Down syndrome.
Fortunately, not every individual with AAT deficiency develops clinically
- The major biochemical activity of the AAT molecule is inhibition of
several neutrophil-derived proteases (eg, trypsin, elastase, proteinase
3, cathepsin G), and, therefore, the protein is more accurately termed
alpha1 antiprotease. However, most physicians, and virtually all
patients, refer to the disease as AAT deficiency.
- The protein is synthesized predominantly by hepatocytes. After its
release from the liver, it circulates unbound and diffuses into
interstitial and alveolar lining fluids. Its principle function in the
lung is to inactivate neutrophil elastase, an enzyme that is released
during normal phagocytosis of organisms or particulates in the alveolus.
Alpha1 antiprotease constitutes about 95% of all the antiprotease
activity in human alveoli, and neutrophil elastase is considered the
protease largely responsible for alveolar destruction.
- In healthy persons, alpha1 antiprotease serves as a protective
screen that prevents alveolar wall destruction. Individuals with the AAT
genetic defect do not release alpha1 antiprotease from the liver, and
the alveoli lack protection. The imbalance of proteases-antiproteases in
the alveolus leads to unimpeded neutrophil elastase digestion of elastin
and collagen in the alveolar walls and progressive emphysema.
- Cigarette smoking accelerates the onset of symptomatic disease by
approximately 10 years by increasing the number of neutrophils in the
alveolus and inactivating the remaining small amounts of antiprotease.
- The production of alpha1 antiprotease is controlled by a pair of
genes at the protease inhibitor (Pi) locus. Nearly 24 variants of the
alpha1 antiprotease molecule have been identified, and all are inherited
as codominant alleles. The most common (90%) allele is M (PiM), and
homozygous individuals (MM) produce normal amounts of alpha1
antiprotease (serum levels of 20-53 mmol/L).
Deficient levels of alpha1 antiprotease are associated with allele Z
(homozygous PiZ, serum level 3.4-7 mmol/L).
Serum levels greater than 11 mmol/L appear to
be protective. Emphysema develops in most (but not all) individuals with
serum levels less than 9 mmol/L.
Chronic Obstructive Pulmonary Disease
Other Problems to be Considered:
Immotile cilia syndrome
- To identify disease, determine serum AAT levels.
- Testing is readily available in most clinical laboratories and is
- Clinical features that suggest the possibility of AAT deficiency
and the need for serum testing include emphysema at an early age,
emphysema in a nonsmoker (or light smoker), a family history of
emphysema, emphysema of the lower lungs (as determined by chest
radiograph), adult-onset asthma, and recurrent bronchitis.
- Serum testing is a screening procedure. Test most patients with
chronic or recurrent respiratory symptoms (dyspnea, cough, wheezing)
at least once.
- Most hospital laboratories report serum AAT levels in mg/mL, with
a reference range of approximately 100-300 mg/mL. Levels less than 80
mg/mL suggest a significant risk for lung disease.
- Reference laboratories usually report the serum levels in
micromolar concentration, with a reference range of 20-60 mmol/L and a threshold level for emphysema at 11
- Test patients with low or borderline serum levels with
phenotyping. Use an experienced reference laboratory for this test.
- Phenotyping is required to confirm the presence of AAT deficiency.
Do not initiate AAT replacement therapy without testing.
- More than 100 different phenotypic variants of AAT deficiency have
been identified, but 1 phenotype, PiZZ, is responsible for nearly all
cases of AAT emphysema and liver disease. PiZZ phenotype serum levels
range from 3.4-7 mmol/L, about 10-20% of the
reference range levels.
- Functional assay of alpha1 antiprotease
- In rare circumstances, a third test is utilized to evaluate a
patient with clinical features that are highly suggestive of AAT
deficiency but whose serum levels are within the reference range.
- Specialized laboratories can perform a functional assay of alpha1
antiprotease, which measures the ability of the patient's serum to
inhibit human leukocyte elastase. Such a defect is rare.
- Evaluate hepatic function in patients with low or borderline levels
of AAT. Measure serum transaminases, bilirubin, albumin, and routine
clotting function (activated partial thromboplastin time and
international normalized ratio).
- AAT deficiency emphysema produces a hyperlucent appearance because
healthy tissue has been destroyed.
- The process is not uniform; certain areas are affected more than
- Affected regions also are described as oligemic because they lack
the normal rich pattern of branching blood vessels.
- An unusual characteristic in AAT emphysema is the basilar
distribution of abnormalities found in approximately 75% of PiZZ
patients; however, cigarette smoking is associated with more severe
- High-resolution CT (HRCT) scan of the chest demonstrates
widespread abnormally low attenuation areas resulting from a lack of
lung tissue. As in smoking-related emphysema, the appearance has been
described as a simplification of lung architecture. As tissue is lost,
pulmonary vessels appear smaller, fewer in number, and farther spread
- Mild forms of AAT disease can be missed by HRCT scan, but, when
the disease is moderate, discerning the panlobular nature of the
process and the characteristic lower zone predominance is possible.
- Very severe forms may be indistinguishable from severe
- The severity of emphysema is best documented with standard pulmonary
function tests. Spirometric determination of forced vital capacity (FVC)
and forced expired volume in 1 second (FEV1) are essential.
Determining lung volume (preferably by plethysmography) and measuring
diffusing capacity provide additional valuable information.
All forms of emphysema
destroy alveolar walls and leave permanent abnormal enlargement of the
airspace distal to the terminal bronchiole. In AAT deficiency, the
emphysematous areas are distributed uniformly throughout the acinus
(lobule) and, for reasons that are not known, primarily in the basilar
portions of the lung. This contrasts with centrilobular emphysema
characteristic of cigarette smoking, which predominantly affects the
respiratory bronchioles in the central portion of the lobule, usually
initially at the apex of the lung.
- Patients who are symptomatic at the time of diagnosis usually
demonstrate moderate-to-severe airflow obstruction with an
FEV1 in the range of 30-40% of the predicted value. Also,
reduced vital capacity and increased lung volumes secondary to air
trapping (residual volume >120% of predicted value) usually are
present. Diffusing capacity values are reduced substantially (<50% of
predicted value) in most symptomatic patients. AAT-deficient individuals
who are identified by screening programs or because a relative has been
diagnosed with the disease may have few or no abnormalities.
Medical Care: Preventing
or slowing the progression of lung disease is the major goal of AAT
deficiency management. Facilitate this goal by decreasing any
proinflammatory stimuli in the alveolus, including smoking, asthma, or
respiratory infection. Alternatively, augmenting or replacing the
deficient enzyme, and thereby moderating inflammatory stimuli, is
possible. Most patients are identified only after they develop lung
disease, and the goals of treating AAT deficiency emphysema are similar to
those for treating all forms of emphysema.
- Quitting smoking
- No treatment for emphysema has a greater effect on survival than
- Make a concerted effort to inform patients about the serious
consequences of smoking on AAT deficiency and provide them with one of
the many aids to help them quit.
- Remember the 4 stages in the process of helping patients become
nonsmokers—(1) ask about smoking habits; (2) advise about health
effects; (3) assist the patient with encouragement, education, and
nicotine replacement; and (4) arrange follow-up.
- Most patients with AAT deficiency quit successfully.
- Improving lung function
- Provide similar efforts to improve lung function in patients with
AAT deficiency emphysema as those provided to patients with emphysema
from the usual causes.
- Administer beta-adrenergic agents and ipratropium bromide
bronchodilators to maximize lung function. Metered-dose inhalers are
the preferred method of administration because they have a lower
incidence of adverse effects than other routes. No matter how they are
administered, no evidence indicates that these drugs have any
long-term effect on disease progression.
- Theophylline may lessen the degree of dyspnea in some individuals,
and a therapeutic trial may be indicated for selected patients. The
therapeutic range of theophylline is relatively small, and its
metabolism frequently is altered by other drugs or illness, which can
lead to frequent episodes of drug toxicity or the need for frequent
monitoring of serum levels.
- Inhaled corticosteroids have not been studied in patients with AAT
deficiency emphysema, but many patients have significant
broncho-reactivity and, in this group, inhaled steroids probably help
- Reserve oral corticosteroids for acute exacerbations with
increased cough and sputum. Long-term administration of
corticosteroids does not protect the lung from progressive emphysema,
but it is associated with a long list of detrimental adverse effects.
Limit their use to brief courses lasting 1-2 weeks. Institute therapy
to prevent osteoporosis when administering longer courses.
- Preventing respiratory infections
- Pneumonia and annual influenza vaccines will help prevent
- Aggressively treating infections that occur despite prophylaxis
may help decrease the potential for additional lung injury from an
influx of neutrophils into the alveolus.
- Pulmonary rehabilitation
- According to a National Institutes of Health (NIH) workshop,
pulmonary rehabilitation is defined as "a multi-disciplinary continuum
of services directed to persons with pulmonary disease and their
families, usually by an interdisciplinary team of specialists, with
the goal of achieving and maintaining the individual's maximum level
of independence and function in the community."
- Most programs combine education, exercise conditioning, breathing
training, chest physical therapy, and respiratory muscle training with
nutritional counseling and psychological support.
- Therapy does not improve pulmonary function test results, but
well-controlled studies documented significant improvement in exercise
endurance, exercise work capacity, level of dyspnea, quality of life,
and reducing health-related expenses.
- Reducing hypoxemia
- Hypoxemia accelerates mortality in patients with severe airflow
obstruction, and oxygen supplementation prolongs survival for this
- Oxygen also increases exercise capacity, improves mental
performance, decreases dyspnea with exercise, and improves sleep
- Stable patients with resting hypoxia benefit most if they wear
their oxygen mask continuously. The benefits for patients with
hypoxemia only during exercise or sleep are not as clear, and oxygen
may be prescribed for those intervals when the oxygen saturation is
likely to be low.
- Replacing enzymes
- AAT-deficient individuals who have or show signs of developing
significant emphysema can be treated with Prolastin, a pooled,
purified, human plasma protein concentrate replacement for the missing
enzyme that has been screened for HIV and hepatitis viruses. It also
is heat-treated as an additional precaution against transmission of
infection. Immunize patients against hepatitis regardless.
- Weekly intravenous infusions of Prolastin restore serum and
alveolar AAT concentrations to protective levels. Although other
regimens for administration have proven to provide similar serum
levels, only the weekly infusion schedule has US Food and Drug
- No controlled studies have proven that intravenous augmentation
therapy improves survival or slows the rate of emphysema progression.
Results from the NIH patient registry and a comparison of Danish and
German registries have been published, and both suggest that
augmentation therapy has beneficial effects. Although they were not
controlled treatment trials, the similarity of the results suggests
that the findings are significant.
- The NIH report described an overall death rate 1.5 times higher
for those who did not receive augmentation therapy and a rate of
FEV1 decline (54 mL/y) in AAT-deficient individuals
approximately twice that of healthy nonsmokers but approximately 50%
that of smokers (108 mL/y). Prolastin treatment did not improve the
average FEV1 decline (54 mL/y); however, participants with
moderate airflow obstruction (FEV1 35-49% of predicted
value) experienced a slower rate of decline (mean difference 27 mL/y).
These findings bolster the long-held belief that augmentation therapy
provides clinical benefit. No firm guidelines have been developed for
initiating or continuing augmentation therapy.
- Most pulmonary physicians require the serum level to be below the
threshold protective value and that the patient have 1 or more of the
following: signs of significant lung disease such as chronic
productive cough or unusual frequency of lower respiratory infection,
airflow obstruction, accelerated decline of FEV1, or chest
radiograph or CT scan evidence of emphysema.
- The American Thoracic Society recommends starting treatment when
the FEV1 is less than 80% of the patient's predicted value.
Surgical Care: Two surgical approaches may help
selected patients with AAT deficiency.
- This procedure has generated nationwide interest and hope for
patients with all types of emphysema.
- Selected patients with severe emphysema and significant air
trapping have experienced symptomatic improvement by removing the most
severely affected 20-35% of each lung. Spirometry and exercise
tolerance generally improve following postoperative recovery. Dyspnea
generally is diminished. The effects on blood gas values are variable.
- Some of the enthusiasm for the procedure has waned, even as
surgical mortality rates have diminished, because the duration of
improvement seems to be brief; an accelerated rate of FEV1
decline appears to occur after the surgery.
- A randomized controlled trial (National Emphysema Treatment Trial)
currently is recruiting patients at 17 medical centers around the
country to clarify the benefits and risks associated with the surgery.
- Because experience is limited, whether AAT deficiency emphysema
patients fare better or worse with this surgery is unknown.
- Transplantation is the second surgical option for patients with
severe AAT emphysema.
- If patients are at substantial risk of early mortality and are
otherwise healthy, they may be candidates for lung transplantation.
- Contact a local transplant center before patients become too ill
(cachexia, inactivity, frequent infections). Unfortunately, the
average waiting time for a transplant in the United States is 18-24
months, and the uncertainties of emphysema exacerbations and
complications that might prevent transplantation make it imperative
that patients be referred well in advance of need.
- Offer patients with an FEV1 less than 35% of predicted
value (5-y mortality rate of 50%), especially men or individuals with
substantial broncho-reactivity, the opportunity to discuss the option
with a transplant physician.
Consultations: The diagnosis of AAT deficiency
emphysema is not difficult, but most physicians will have no experience
treating a patient, providing counseling, or answering the questions that
an uncommon hereditary disorder generates. Several visits with a
specialist in the first year usually are enough to meet a patient's needs.
The Alpha-1 National Association, 1-800-4ALPHA-1, http://www.alpha1.org/
can facilitate locating physicians with interest and experience in caring
for these patients.
Diet: Patients with advanced chronic obstructive lung
disease are characterized by a significant reduction in fat-free muscle
mass. This pulmonary cachexia is common in patients with AAT deficiency
and is associated with a decline in clinical status. The syndrome is a
result of multiple factors, including hypermetabolism, drug therapy,
inactivity, and aging. Prolonged glucocorticoid administration accelerates
the process. Protein-calorie supplementation as one component of a
comprehensive treatment program may reverse the loss of muscle mass, and
dietary counseling may aid patients at high nutritional risk. Providing
more fat-based nonprotein calories may benefit patients with respiratory
failure who are on mechanical ventilation, but, other than this special
circumstance, little evidence exists to suggest that this dietary
manipulation aids ambulatory patients.
Activity: Dyspnea limits activity, which results in
deconditioning and further reductions in activity levels. Encourage all
patients with lung disease to maintain activity levels. Pulmonary
rehabilitation programs and patient support groups are particularly
Treat airflow obstruction and symptoms
resulting from AAT deficiency in a manner similar to emphysema.
Bronchodilators may provide relief of some symptoms. Use antibiotics to
treat bacterial complications, including pneumonia or purulent bronchitis.
Neither bronchodilators nor antibiotics demonstrate any effect on disease
progression. Similarly, corticosteroids may provide some short-term relief
but have no proven long-term benefit in inhaled or oral preparations.
Because of their long-term adverse effects, avoid oral steroids. Prescribe
oxygen if patients are hypoxemic. Consider replacement (or augmentation)
therapy to slow the progression of emphysema.
Drug Category: Respiratory enzymes -- For
chronic replacement in individuals with clinically demonstrable panacinar
|Alpha1 protease inhibitor
(Prolastin) -- Sterile, stable, lyophilized preparation of purified
human alpha1 antiprotease inhibitor prepared from pooled human
plasma. Indicated as replacement (or augmentation) for normal serum
alpha1 antiprotease to prevent progression of emphysema. Each unit
of plasma is tested for HIV, hepatitis B, and hepatitis C before
inclusion in the product. Product is heat-treated to reduce
potential risk of infectious agent transmission. To date, no cases
of viral infections have been attributed to the product. |
||60 mg/kg IV qwk |
||Not recommended |
selective IgA deficiency; known anti-IgA antibody |
||None reported |
||C - Safety for use during pregnancy
has not been established. |
||Administer within 3h of
reconstitution; do not mix with other drugs; caution in patients at
risk for circulatory overload; recipients should be immunized
against hepatitis B using a licensed hepatitis B
Further Outpatient Care:
- Measuring pulmonary function yearly permits better counseling and
planning for interventions such as initiating replacement therapy (if
not already started) or transplantation preparation.
- Repeat influenza vaccination yearly.
- AAT deficiency is a rare problem, yet it demands substantial
expertise for appropriate management and counseling. Physicians without
specific training in the management of this disease or without the time
to obtain the necessary expertise should not hesitate to transfer the
care of patients to a physician or center with the necessary experience.
The Alpha-1 National Association, 1-800-4-ALPHA-1 or
http://www.alpha1.org/ can help to identify physicians with experience
in the management of this disorder.
- Instruct patients with homozygous deficiency to avoid exposure to
cigarette smoke. Chemical exposures also might have detrimental effects
on pulmonary function, but no studies have been conducted to show a
relationship between employment and progression of airflow obstruction.
- AAT-deficient patients are subject to all the complications
characteristic of patients with chronic obstructive pulmonary disease
from cigarette smoking. Complications may include pneumothorax,
pneumonia, acute exacerbation of airflow obstruction, and respiratory
- The major manifestation of AAT deficiency in the first 2 decades of
life is liver disease; pulmonary manifestations appear later. Lung
function appears to be normal among PiZZ adolescents when compared to a
similar matched group with alpha1 antiprotease levels within the
reference range. FVC, FEV1, residual volume, and total lung
capacity measurements were not different between the 2 groups. Lung
function begins to decline at some later point. FEV1
decreases in adult PiZZ patients at 51-317 mL per year (estimated
decline in healthy patients is 30 mL/y).
- In the NIH registry, PiZZ individuals had a 16% chance of
surviving to age 60 years in contrast to an 85% chance for the general
US population. Emphysema was the most common cause of death (72%), and
chronic liver disease was second (10%).
- In the Danish registry, the outlook was better, especially for
nonindex cases involving nonsmokers. In this group, survival closely
approximated that of the healthy Danish population. The Danish
registry confirmed the poor outlook for index cases and the additional
mortality risk among smoking patients.
- Prognosis is dependent on how patients are identified. Patients
found as a result of screening often have a prognosis near that of
healthy people. Those identified because of their symptoms face a more
limited future. Specific features that portend a poorer prognosis
include the following:
- More severe degree of airflow obstruction (FEV1
>50%, 5-y mortality rate is 4%; FEV1 35-49%, 5-y
mortality rate is 12%; FEV1 <35, 5-y mortality rate is
- Significant bronchodilator response (>12% and >200 mL)
- Excellent educational resources are available through the Alpha-1
National Association. This patient advocacy group offers a telephone
hotline (1-800-4ALPHA-1), a national newsletter (Alpha-1 News), an
internet site (http://www.alpha1.org/), and local support groups that
provide information and support for patients, their families, and care
- Most patients with symptomatic AAT deficiency have seen several
physicians over several years before their underlying problem is
recognized and diagnosed. A patient could claim that (1) the physician
failed to establish a diagnosis even though diagnostic testing was
readily available and inexpensive, (2) that appropriate treatment was
delayed, (3) that specific educational and counseling opportunities were
missed, and (4) that all of these harmed the patient.
- Direct population screening studies in Sweden and the United States
identified 1 in 3000-5000 whites with the PiZZ phenotype. These studies
suggest that about 70,000-100,000 individuals in the United States may
have severe AAT deficiency, but fewer than 10,000 have been recognized,
and fewer than 50% of these are receiving replacement therapy. Most of
the 10,000 patients (approximately 80%) were identified because they
were symptomatic; the remaining 20% are relatives of index cases. If
estimates are correct, an additional 60,000-90,000 AAT-deficient
individuals remain unidentified in the country. This suggests that
physicians may be missing cases and that some affected individuals may
have not yet developed significant disease. Evidence for both of these
- Genetic screening of population groups poses several risks,
including potential adverse psychological consequences and insurance or
employment discrimination. However, it also offers the option of earlier
care for patients with mild forms of disease, the opportunity for family
and individual counseling about the risks of cigarette smoking, and
encouragement to not start the habit. Assist those patients who smoke
with efforts to stop. Genetic counseling may be particularly helpful,
but families and affected individuals derive substantial support through
the Alpha-1 National Association (http://www.alpha1.org/).
|Caption: Picture 1. Close-up
chest radiographic view of right lower zone of a 39-year-old woman
with alpha1-antitrypsin (AAT) deficiency. Normal lung markings are
absent in the costophrenic angle. Some lung markings are present in
the pericardiac region, but even these are diminished. |
|Caption: Picture 2. CT scan of
the right middle and right lower lobes in a 38-year-old patient with
alpha1-antitrypsin (AAT) deficiency. The entire middle lobe and much
of the lower lobe are emphysematous; normal lung structures have
been replaced by abnormal airspaces. Only the posterior portions of
the right lower lobe maintain a normal architecture.|
|Caption: Picture 3. This graph
outlines alpha1-antitrypsin (AAT) levels and risk of lung disease
for the 5 most common phenotypes of AAT deficiency. The dashed line
at 11 mmol/L (80 mg/mL) represents the
threshold level below which emphysema is common. |
- Alpha-1-Antitrypsin Deficiency Registry Study Group: Survival and
FEV1 decline in individuals with severe deficiency of
alpha1-antitrypsin. The Alpha-1-Antitrypsin Deficiency Registry Study
Group. Am J Respir Crit Care Med 1998 Jul; 158(1): 49-59.
- American Thoracic Society: Guidelines for the approach to the
patient with severe hereditary alpha- 1-antitrypsin deficiency. American
Thoracic Society. Am Rev Respir Dis 1989 Nov; 140(5): 1494-7.
- Brantly ML, Paul LD, Miller BH: Clinical features and history of the
destructive lung disease associated with alpha-1-antitrypsin deficiency
of adults with pulmonary symptoms. Am Rev Respir Dis 1988 Aug; 138(2):
- Celli BR: Pulmonary rehabilitation for patients with advanced lung
disease. Clin Chest Med 1997 Sep; 18(3): 521-34.
- Fishman AP: Pulmonary rehabilitation research. Am J Respir Crit Care
Med 1994 Mar; 149(3 Pt 1): 825-33.
- Seersholm N, Wencker M, Banik N: Does alpha1-antitrypsin
augmentation therapy slow the annual decline in FEV1 in patients with
severe hereditary alpha1-antitrypsin deficiency? Wissenschaftliche
Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL) alpha1-AT
study group. Eur Respir J 1997 Oct; 10(10): 2260-3.
- Seersholm N, Kok-Jensen A, Dirksen A: Survival of patients with
severe alpha 1-antitrypsin deficiency with special reference to
non-index cases [published errata appear in Thorax 1994 Nov;49(11):1184
and 1998 Jan;53(1):78]. Thorax 1994 Jul; 49(7): 695-8.
- Stoller JK, Smith P, Yang P: Physical and social impact of alpha
1-antitrypsin deficiency: results of a survey. Cleve Clin J Med 1994
Nov-Dec; 61(6): 461-7.
- Sveger T, Piitulainen E, Arborelius M Jr: Lung function in
adolescents with alpha 1-antitrypsin deficiency. Acta Paediatr 1994 Nov;
- Thelin T, Sveger T, McNeil TF: Primary prevention in a high-risk
group: smoking habits in adolescents with homozygous alpha-1-antitrypsin
deficiency (ATD). Acta Paediatr 1996 Oct; 85(10): 1207-12.