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Treatment of AAT deficiency and COPD


Alpha-1 antitrypsin (AAT) deficiency is a rare inherited disorder that can lead to severe chronic obstructive pulmonary disease (COPD). While there is no cure, treatments and lifestyle changes can help you control your symptoms and protect your lungs from further damage.

COPD is a group of lung conditions that includes emphysema and chronic bronchitis. The most common symptoms that people have as lung disease due to AAT deficiency develops are:

  • wheezing
  • Difficulty breathing
  • A chronic cough with phlegm
  • repeated colds
  • Pneumonia

Ronald Crystal, MD, chair of genetic medicine at Weill Cornell Medicine, said most people are diagnosed with AAT deficiency after visiting their doctor for shortness of breath.

“They go up a flight of stairs and are short of breath. They climb the subway stairs and are short of breath. They try to run, say behind a bus or something, and they’re short of breath,” says Crystal, also a pulmonary doctor who has treated more than 500 people with the disease.

“Most people chalk it up to, they say, ‘Well, I’m getting old, I’m out of shape, I’m overweight,’ and they put it off until it continues and gets worse.

But the longer you wait for treatment, the more damage can be done to your lungs.

What is alpha-1 antitrypsin?

Alpha-1 antitrypsin is a protein made by the liver that moves throughout the body in the bloodstream. One of its main functions is to protect your body from an enzyme called neutrophil elastase. Your immune system produces this enzyme to help fight inflammation or infection. But if left unchecked by AAT, it can damage the fragile tissues of the lungs.

Without enough AAT, neutrophil elastase damages more and more lung cells. As the damage continues over the years, lung disease can develop.

The situation is worse for people who smoke. Smoking makes emphysema and other symptoms develop much faster.

“If you don’t smoke cigarettes and you have alpha-1 antitrypsin deficiency, you don’t develop emphysema until age 55 or so,” says Crystal. “But if you smoke cigarettes, or if you have smoked cigarettes, you can develop the disease between the ages of 35 and 40.”

Can AAT deficiency affect other parts of my body?

Although rare, AAT deficiency can also cause liver diseases, such as cirrhosis and liver cancer. People often develop either lung or liver disease, but not both, Crystal says.

When AAT affects the liver, it is because the alpha-1 protein made there is abnormally shaped. That means it can’t get out and accumulates in the liver. Over time, this causes damage to the organ, Crystal says.

How is ATT deficiency diagnosed?

If you are in your 30s, 40s, and 50s and develop signs of COPD, such as shortness of breath, get tested for AAT deficiency.

Your doctor will start by doing a complete exam and listening to your breathing.

If you have emphysema or another COPD not caused by AAT deficiency, it tends to affect the upper and middle lobes of the lungs. If your lung disease is due to AAT, it’s more likely to affect the lower areas of your lungs, Crystal says.

While your doctor may notice signs of AAT deficiency, you need a blood test to confirm the diagnosis.

Your doctor may also recommend imaging tests, such as X-rays and CT scans, to examine your lungs and liver for damage.

What are the treatments for AAT deficiency?

There are several treatments available to address the symptoms of COPD. But augmentation therapy (also sometimes called replacement therapy) is the only specific therapy for AAT deficiency. It uses alpha-1-antitrypsin protein from healthy human donors to increase levels of the protein. It is obtained in regular intravenous infusions.

The goal is to increase the alpha-1-antitrypsin protein in your body, so it can protect your lungs from the neutrophil elastase enzyme.

Although this treatment does not cure AAT deficiency or repair damage already done, it can help protect your lungs from further damage.

“You cannot return lung function. You cannot return normal air sacs. What you can do is protect them from deteriorating,” says Crystal, who as the former chief of the pulmonary branch of the National Heart, Lung, and Blood Institute helped develop the therapy.

While Crystal offers the treatment to its patients with severe and early-onset disease, some physicians have differing views on who should receive the therapy and when. Some only give it to people with moderate lung disease, not those with early-onset or severe disease.

“My argument for treating someone who has a serious illness is that as long as they are sitting in your office talking to you, they obviously have enough lungs to protect. So why not treat them? he said. “So I treat everyone. As long as they have evidence of emphysema, either by lung function or CT scan, I treat them.”

What else can I do for AAT deficiency?

If you have AAT deficiency, your doctor may prescribe an inhaler, oxygen therapy, or antibiotics to help with COPD flare-ups.

it is especially important not to smoke. Talk to your doctor about how you can exercise safely, especially if you have symptoms of lung disease.

If you have signs of liver disease, limit alcohol intake.

Crystal says it’s essential for people with AAT deficiency to stay up-to-date on vaccinations, including the annual flu shot.

“Make sure you get the pneumococcal vaccine and of course get the COVID vaccine because these people are much more susceptible if they have pneumonia or viral pneumonia,” he says. “Vaccines, vaccines, vaccines, they are very important.”


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