Below is a chest x-ray film of a 56 years old female who presented with shortness of breath, productive cough and chest pain for a week’s duration. She had been having these symptoms for the last 15 years, but had exacerbated recently. She had been visiting general practitioners for her condition and would respond to the treatment given to her, commonly consisting of corticosteroids both inhaled and systemic, beta agonists, or bronchodilators.
For the last three years she had been using a ICS-LABA inhaler combination in addition to montelukast and oral theophylline. She reported that she didnt get relief from these medicines but was being prescribed these medicines. None of the family members had asthma, or any respiratory disease. She was married, a house wife and didnt smoke, although there was a history burning wood at home in the kitchen.
On examination she had coarse crackles on left side of chest best heard on back and expiratory wheezing elsewhere. Her CT Chest was done which showed early bronchiectatic changes in left lower lobe.
She was started treatment for acute severe asthma but the history was not matching, there fore the search for a clue lead to asking for serum alpha 1 antitrypsin levels. The result was unexpected. It turned out she had a serum alpha 1 antitrypsin level of 32.9 mg/dl far less than the reference value of 200 mg/dl.
So it turned out that she was having alpha 1 antitrypsin deficiency with bronchiectasis. She was started on broad specturm antibiotics in addition to chest physiotherapy and her condition improved.
What is alpha 1 anti trypsin?
Alpha 1-Antitrypsin is a protease inhibitor and it inhibits a wide variety of proteases including enzymes known as elastases. Elastases cause breakdown of Elastin which contributes to elastic property of lungs. Absence of elastin results in many characteristic diseases associated with this disease. Well known examples are : COPD, emphysema and Cirrhosis. It is also associated with a number of diseases which include:
- Wegener’s granulomatosis
- Primary Sclerosing Cholangitis
- Autoimmune Hepatitis
Although most common presentation of alpha 1 anti trypsin deficiency is emphysema, especially pan acinar emphysema , but bronchiectasis has also been reported by some researchers. ( Larsson C. Natural history and life expectancy in severe alpha1-antitrypsin deficiency, Pi Z. Acta Med Scand 1978; 204:345. & Cuvelier A, Muir JF, Hellot MF, et al. Distribution of alpha(1)-antitrypsin alleles in patients with bronchiectasis. Chest 2000; 117:415. ) The esimated prevalence of bronchiectasis varied from as low as 2 % to as high as 43 % in these studies.
Severe Alpha 1 Anti trypsin deficiency is confirmed by demonstrating a serum level below 11 micromol/L (50 to 80 mg/dL) along with a severe deficient genotype.
What are treatment options for Alpha 1 antitrypsin deficiency?
The Goal of treatment is to raise the plasma levels of alpha 1 antitrypsin to at least 11 micromol/litre or 50-80 mg/dl (depending on the assay) to protect the lung tissue and therefore to minimize the risk of developing emphysema. Alpha 1 anti trypsin levels can theoretically be increased by any of the following approaches:
- Intravenous or aerosolized augmentation therapy
- Enhancement of endogenous alpha-1 antitrypsin production
- Gene therapy
- Organ Transplantation
At present the only available approach is the first one: Intravenous augmentation therapy. The American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines about management of alpha 1 anti trypsin deficiency can be downloaded from here. Other ATS guidelines can be found here.
Currently the Alpha 1 anti trypsin has been approved for weekly administration regimen. The usual dose is 60 mg/kg once a week. Although this weekly dose is the recommended dose as approved by the FDA, US, some reaserchers have experimented with the monthly dose in which AAT is given @ 250 mg/kg monthly. These researchers found that these monthly doses were equally effective and the effect of AAT persisted much longer , usually untill the next dose. (Hubbard RC, Crystal RG. Augmentation therapy of alpha 1-antitrypsin deficiency. Eur Respir J Suppl 1990; 9:44s. & Hubbard RC, Sellers S, Czerski D, et al. Biochemical efficacy and safety of monthly augmentation therapy for alpha 1-antitrypsin deficiency. JAMA 1988; 260:1259. ).
The patient in question had to let go home on supportive treatment replacement therapy with alpha 1 antitrypsin could not be arranged for her. Alpha 1 antitrypsin is not yet available in market.