Authors Majdi Al Nabulsi MD, Pulmonary Critical Care Fellow Zeina AlMajthoub, Pulmonary Critical Care Research Associate Kathryn A. Radigan MD, Pulmonary Critical Care Attending John H. Stroger Hospital of Cook County Chicago, Illinois
Case
A 48 year-old male with past medical history significant for
hepatitis C and cirrhosis presented to the hospital for decompensated
liver disease. Pulmonary team was consulted for an abnormal CT scan of
the chest. The patient admitted to dyspnea for months which was
associated with audible wheezing. He smoked around 6 cigarettes a day
for 21 years. He denied significant occupational exposures.
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Question
What is the most appropriate test that should be requested for this patient?
A. Sweat Chloride Test B. Sputum AFB Smear & Culture C. Serum Alpha-1 Antitrypsin Level D. Serum Immunoglobulins Levels E. ANA Titer
Answer
C: Serum Alpha-1 Antitrypsin Level
Discussion
This middle age man has extensive panlobular emphysema with basilar
predominance on imaging along with liver cirrhosis. These two
conditions together raise concern for alpha-1 antitrypsin [A1AT]
deficiency. His serum A1AT level was very low at 19 mg/dL. His genotype
was positive for two copies of the Z allele (ZZ). His pulmonary
function test showed FVC 58%, FEV1 23%, and FEV1/FVC ratio of 31%
indicating a very severe obstructive ventilatory defect.
Although a highly underrecognized genetic disorder, A1AT deficiency
is relatively common. In most patients, the diagnosis is delayed for at
least a couple of years after symptoms onset. (1) The inheritance is
autosomal codominant with approximately 150 alleles [normal and
defective] that have been identified thus far leading to different
combinations in these gene loci. The phenotype and severity depend on
the level of serum A1AT produced by these alleles. Individuals with low
serum levels should be further tested with isoelectric focusing or
genotyping to confirm the diagnosis. (2,3)
Clinical manifestations include lung disease (emphysema and
bronchiectasis), liver disease (chronic hepatitis, cirrhosis, and
hepatocellular carcinoma), and rarely skin disease including necrotizing
panniculitis along with psoriasis and urticaria. Emphysema here has
early onset (typically the 4th or 5th decades) with panlobular pattern
that is characterized by disproportionate emphysematous involvement of
the lung bases and destruction of the entire alveolus (secondary
pulmonary lobule) uniformly. (2) This is different from the other more
common pattern, centrilobular emphysema, which is localized to the
proximal respiratory bronchioles with normal surrounding lung
parenchyma, focal destruction, untouched distal alveolar ducts and sacs,
and predominantly found in the upper lung zones (See the picture to
compare). (4) This latter form occurs with long-standing tobacco smoking
and dust inhalation. Although both ATS and WHO guidelines recommend
screening for A1AT deficiency in all COPD patients, its importance is
stressed in patients with early onset emphysema, bronchiectasis, liver
disease without a clear etiology, unexplained panniculitis, and in
patients with anti-proteinase-3 vasculitis. (2,5) Interestingly, some
genotypes spare the liver and cause lung disease only.
Centrilobular Emphysema pattern (For comparison)
Besides conventional COPD management, smoking cessation and pulmonary
rehabilitation, treatment also involves infusion of pooled human
alpha-1 proteinase inhibitor. This treatment is effective in reducing
frequency of exacerbations, FEV1 decline, and overall mortality in
carefully selected patients. (2,6) However, the high cost of such
treatment remains a challenge that is unaffordable by many patients.
References
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