Michael Krowka, MD

I was recently diagnosed with Alpha 1 because of elevated liver enzymes. According to my pulmonologist, my lungs appear to be healthy with only minor lower lobe emphysema with some bronchiectasis. My PFT's are stable with an FEV-1 of 82%, an alpha 1 level of 54 and normal liver enzymes now. Do you think I would benefit from augmentation therapy at this point or should I continue to follow up closely with my pulmonologist yearly?  I feel good, work full time and am very active.  

Many pulmonary specialists (me included) would not initiate augmentation therapy since your FEV-1 is normal. ("normal" FEV-1 > 80% predicted).  The finding of bronchiectasis (damaged air tubes) is not uncommon with abnormal antitrypsin genetics, especially if the Z allele is present. . It is not really known whether augmentation therapy for the bronchiectasis problem in the setting of a normal FEV-1 would be an effective clinical treatment. Certainly if you are coughing out sputum everyday or blood at any time, the bronchiectasis should at least be addressed by obtaining sputum cultures to identify specific microorganisms and tailor appropriate antibiotic selection by your physician.  There is no proven role for augmentation therapy to treat the liver abnormalities associated with any degree of antitrypsin deficiency. Bottom line - in my opinion, I would do as your pulmonologist suggests. Augmentation therapy for the lung situation is not indicated, have annual follow-up and obtain a baseline ultrasound of the liver, if that has not been done.   

Is there an optimum FEV1 range for someone to received augmentation therapy?  If someone falls above or below this range, is the augmentation therapy effective?   

The evidence to date is based upon two large observation studies that do provide some guidance.  Keep in mind these studies were not randomized, controlled trials that most researchers would prefer to base their conclusions.  Patients in these studies were severely deficient in circulating alpha-1 antitrypsin protein levels (< 11.0 uM). The German-Danish study and the NHLBI Registry concluded that in individuals with moderate expiratory airflow obstruction (baseline FEV-1 less than 65% predicted, but greater than 30% predicted), the decline in annual FEV-1 would be significantly slower in those receiving augmentation therapy.  Having said that, a later analysis of German data suggested that if the FEV-1 was greater than 65%, but the decline had been accelerated (change in FEV-1 ~ 250 ml/year), those patients indeed had significant benefit from augmentation therapy to slow the decline (down to ~ 50 ml/year with therapy).  It is important to keep in mind not all change in these studies may be in a "straight line" decline. Big drops may be interspersed with little drops or no change. Regular follow-up once severe deficiency has been diagnosed, regardless of the FEV-1 level, remains a good idea. 

Can our lungs improve their function with diet, exercise and maintaining our health? I know that the lungs and liver can heal themselves somewhat. Is this true for Alphas?

Without a doubt lung function can improve with diet (weight loss effect) and exercise (keeping good cardiovascular and muscle tone). Big bellies can adversely affect the normal function of the breathing muscles (the diaphragms), impair the ability for nice deep breaths to open the airsacs (alveoli) within the lungs and simply become part of an unhealthy sedentary life style. Lose the excess weight by reducing the calorie intake and burn some calories with regular, routine exercise - under the guidance of your physician of course.  Indeed, liver function can improve by dietary change that reduces fat intake and minimizes alcohol intake. So the lungs and liver can thus “heal themselves” to some degree for Alphas, but it does take the help of some discipline with what goes into the mouth, trying to minimize excesses and insults, and letting muscles do what they like to do – exercise.

Is a liver biopsy the only true way to denote liver disease?

liver biopsy is usually considered the “gold standard” for most liver disorders, yet many disorders are strongly suggested by routine blood tests and clinical findings before a liver biopsy is accomplished. Why do the liver biopsy? It is a pathological confirmation of clinical and laboratory findings that gives your physician an added piece of information regarding a specific diagnosis that may require very special (and expensive) treatments. Can biopsies be “wrong”? Like any other tests, looking at biopsies under the microscope requires the keen eye of and interpretation by pathologists, but disagreements can exist. The science and art of medicine exists even at the level of the biopsy, with the overall clinical picture always important!

My daughter is a carrier with a level of 112, she does not smoke or drink. What chance does she have of actually developing symptoms?

As best we know, with that level alone that is normal or near normal in a carrier as described for your daughter, it would be very unlikely that lung or liver symptoms would evolve over time. The addition of another insult, however, such as acquiring infection such as hepatitis C, or having inhaled exposures (starting to smoke) over time, could lead to symptomatic liver or lung problems, respectively.  We simply do not know all of the possible environmental insults or genetic predispositions that might, in addition to the carrier state, lead to future symptoms.

When should an Alpha consider liver transplant?  What symptoms would they be experiencing to warrant the liver transplant evaluation?

Liver transplant consideration in an Alpha also involves main factors similar to those considered in the lung transplant world: severity of liver disease, age, and co-morbidities. Priority for liver transplant involves the MELD score (Model for End Stage Liver Disease), a score computed from 3 measured variables (bilirubin, INR and creatinine) and monitored by the SRTS. Symptoms such as fatigue, mental confusion and signs such as gastrointestinal bleeding, fluid in the belly (ascites), and muscle wasting would suggest advanced liver disease that warrants liver transplant consideration in adults. Most adults with MZ phenotype have an additional liver disorder that, in combination, merits liver transplant consideration; ZZ phenotypes may not have any other liver insult. Does liver transplant prevent further lung function deterioration? One would think so (the new liver now produces normal levels of alpha1 protein that enter the blood stream), but the definitive answer is unknown at this time.