Bronchiolitis Obliterans Syndrome

obliterative bronchiolitis, constrictive bronchiolitis, popcorn lung

Bronchiolitis obliterans syndrome is a serious lung condition that causes the smallest airways in the lungs to become inflamed, damaged, and scarred, making it difficult to breathe. It most commonly occurs after organ transplants, but can also develop from breathing in harmful chemicals or after severe infections.

Table of contents

• What is Bronchiolitis Obliterans Syndrome?
• Affected Parts of the Lungs
• What Causes This Condition?
• Who Is at Risk?
• Signs and Symptoms
• How Is It Diagnosed?
• Treatment Options
• What to Expect

What is Bronchiolitis Obliterans Syndrome?

Bronchiolitis obliterans syndrome is a specific term used when bronchiolitis obliterans (inflammation and scarring of small airways) occurs after lung transplantation or hematopoietic stem cell transplantation (a procedure where stem cells from bone marrow are transferred)^[1]. In these situations, the condition is considered a form of rejection, where the body’s immune system reacts against the transplanted organ or cells^[1].

This is a type of obstructive lung disease, meaning it blocks airflow through the lungs^[1]. The condition is rare and involves fibrosis (scar tissue formation) in the terminal and distal bronchioles, which are the tiniest branches of airways in the lungs^[1]. The disease usually leads to a progressive decline in how well the lungs work and can have different outcomes for different people^[1].

When the condition occurs outside of transplantation settings, it is simply called bronchiolitis obliterans. The disease can be treated but not cured^[3].

Affected Parts of the Lungs

• Bronchioles (the smallest airways in the lungs)
• Terminal and distal bronchioles

The bronchioles are the smallest airways in your lungs, like the tiniest branches at the end of a tree^[5]. When you breathe, air travels through larger airways called bronchi, which branch into smaller and smaller passages. The bronchioles are at the end of this branching system^[5]. In bronchiolitis obliterans syndrome, these tiny airways become inflamed, damaged, and then scarred^[3].

What Causes This Condition?

Several factors can lead to the development of bronchiolitis obliterans syndrome. The condition develops differently depending on the underlying cause.

After Transplantation

Bronchiolitis obliterans syndrome is one of the most common complications that are not caused by infection after lung transplant and hematopoietic stem cell transplantation^[1]. After a lung transplant, it is considered a form of chronic rejection of the transplanted organ^[1]. In people who receive a bone marrow transplant from someone else, it represents pulmonary graft versus host disease, where the donated cells attack the recipient’s lung tissue^[1].

Toxic Chemical Exposure

Breathing in toxic fumes and gases can damage the bronchioles. These harmful substances include^[1]:

• Sulfur mustard gas (mustard gas)
• Nitrogen oxides
• Diacetyl, a chemical formerly used as popcorn flavoring (which is why the condition is sometimes called “popcorn lung”)^[3]
• Fly ash
• Fiberglass
• Chlorine
• Ammonia
• Formaldehyde
• Hydrochloric acid
• Sulfur dioxide
• Acetaldehyde

The name “popcorn lung” comes from when researchers first identified the disease among workers in a microwave popcorn factory who had breathed in diacetyl^[3]. The liquid in electronic cigarettes or vapes also contains diacetyl and other harmful chemicals^[3].

Infections

Bronchiolitis obliterans can occur after respiratory viral infections, especially in children. The viruses most commonly associated with the condition include^[1]:

• Adenovirus
• Respiratory syncytial virus (RSV)
• Influenza
• Parainfluenza
• Measles
• Varicella

Other infections linked to bronchiolitis obliterans include HIV, various bacteria, fungi, Mycoplasma pneumonia, and Human Herpes Virus 8^[1].

Autoimmune and Other Medical Conditions

The condition is also associated with autoimmune disorders, which are diseases where the body’s immune system attacks its own tissues. These include^[1]:

• Rheumatoid arthritis
• Systemic lupus erythematosus (SLE)
• Inflammatory bowel disease
• Stevens-Johnson syndrome

Rare conditions like Castleman disease and paraneoplastic pemphigus have also been associated with bronchiolitis obliterans^[1].

Who Is at Risk?

Bronchiolitis obliterans syndrome is rare in the general population^[4]. However, certain groups of people face much higher risks.

Lung Transplant Recipients

The majority of lung transplant recipients who survive long-term develop bronchiolitis obliterans syndrome. More than 50% of recipients will develop some degree of the condition within five years after transplant^[1]. About 50% of people who have lung transplants will develop bronchiolitis obliterans syndrome within five years of their transplant procedure, and about 75% by ten years following a lung transplant^[3][4]. The average time to diagnose the condition is 16 to 20 months after lung transplant, though it has been reported as early as 3 months after transplantation^[1].

Bone Marrow Transplant Recipients

About 5% to 14% of hematopoietic stem cell transplantation recipients develop bronchiolitis obliterans syndrome^[1]. About 10% of recipients of donor marrow develop the condition within five years, and up to 10% by ten years^[3][4]. This condition can present several months to years after transplantation^[1].

Workers Exposed to Chemicals

Certain people have a higher risk because they come in close contact with toxic substances in the air. These chemicals are used in some types of manufacturing, including microwave popcorn production, coffee roasting, and other flavoring industries^[3][5].

Children After Severe Infections

Bronchiolitis obliterans is a rare condition in children, and we don’t know exactly how many children get it. However, it is more likely to happen after a severe chest infection^[7]. Post-infectious bronchiolitis obliterans is the most common type in children, with adenovirus being the most common cause^[18].

Signs and Symptoms

Bronchiolitis obliterans syndrome results in breathing problems that worsen over time. Symptoms generally get worse over weeks to months^[4]. Sometimes people who have the condition don’t have symptoms initially^[3].

The main symptoms include^[3][4]:

• Dry cough, especially during and after exercise (coughs may sometimes bring up mucus)
• Shortness of breath (also called dyspnea), especially during and after exercise
• Wheezing (a whistling sound when breathing)
• Feeling tired
• Fever
• Night sweats
• Skin rash
• Difficulty breathing

The symptoms can start gradually, or severe symptoms can occur suddenly^[4]. Symptoms may not occur until two to eight weeks following toxic exposure or infection^[4]. In children, symptoms may include breathlessness, difficulty breathing, and wheezing^[7].

These symptoms represent a pattern of obstruction that does not improve with bronchodilator therapy (medications that open airways)^[4].

How Is It Diagnosed?

Diagnosis of bronchiolitis obliterans syndrome involves several different tests and examinations.

Medical History and Physical Exam

Your doctor will start by asking about your symptoms and medical history, including any transplants, exposures to toxic chemicals, or recent infections^[7].

Imaging Tests

CT scan (computed tomography scan) is an important diagnostic tool. This imaging test creates detailed three-dimensional pictures of your lungs^[1][4]. A chest CT scan can show inflammation and blockage of the small airways, air trapping (when air gets stuck in the lungs), airway widening, and damage to the airways called bronchiectasis^[4][7]. A chest X-ray is often normal in people with this condition^[4].

Pulmonary Function Tests

Spirometry and other pulmonary function tests measure how well your lungs work^[1][3]. These breathing tests show airflow obstruction, which is a hallmark of the disease. A lung function test called spirometry can determine how severe the disease is^[3]. In children older than 6 years, lung function testing can help show blockage of the small airways^[7].

Lung Biopsy

A lung biopsy may be needed to confirm the diagnosis, especially if CT scan pictures aren’t clear^[1][4][7]. During this procedure, a surgeon makes a small cut in the chest and removes a small piece of tissue from the lung. This is done under general anesthetic, so you won’t be aware of it happening^[7]. The tissue is then examined under a microscope. If the lung scan shows enough evidence of bronchiolitis obliterans, doctors may not need a lung biopsy^[7].

Treatment Options

While the disease is not reversible and cannot be cured, treatments can slow further worsening and support breathing^[1][3]. Treatment should be started as early as possible to stop more lung damage and scarring^[5].

Medications

The main goal of medication is to block inflammation in the lung. The most common medicines include^[1][5]:

• Corticosteroids (also called steroids): These can be used in large doses called “pulse steroids” that are repeated monthly. In some cases, the doctor may order steroids daily by mouth (swallowed) or by inhaler (breathed in)
• Immunosuppressive medication: These medicines suppress the immune system to reduce inflammation
• Azithromycin: An antibiotic that also has anti-inflammatory properties
• Montelukast: A medicine that fights inflammation

Your medical team will help decide which medicines to use and how long to use them. We don’t know the perfect way to treat bronchiolitis obliterans right now, and each person is a little different^[5].

Breathing Support

After the lungs are damaged, treatment is focused on supporting breathing and nutrition^[5]. People who have significant lung damage may need to use oxygen therapy at home^[5]. If the damage is severe, they may need other support for their breathing, like positive pressure ventilation^[5].

Lung Transplant

In rare cases where the lungs keep getting worse despite treatment, a lung transplant may be offered^[1][4][5].

Prevention

The most important step is avoiding further exposure to any toxins or chemicals that may have caused the condition^[5]. For children with the condition, preventing infections is important. Parents should wash hands often and ask friends and family to let them know if they are sick before being around the child. Children should get their vaccines and yearly flu shot^[18].

What to Expect

The disease progresses in stages, but not the same way for everyone who has it. One person might stay in an early stage for quite some time, while another goes quickly from one stage to another more advanced stage^[3].

Outcomes are often challenging, with the disease being potentially fatal if not treated, especially after lung transplantation^[4][5]. Most people experience months to years with the disease^[4]. However, depending on the type and cause, the outlook can range from mild to severe impairment. Some people may have mild impairment and slow progression, and others may have irreversible but stable disease^[5].

Usually, post-infectious bronchiolitis obliterans does not get worse over years—the lung damage mostly happens during the time after the infection^[18]. Some children have a mild form of the disease and can continue to live without any breathing problems or limits to their daily life. Some children may have a more severe form and need oxygen or other forms of breathing support during their life^[18].

Communicating with your health care provider will help create a comprehensive treatment plan^[5].