Introduction
Bronchiolitis obliterans is an obstructive disease that affects the bronchioles in the lungs. It is also referred to as obliterative bronchiolitis, constrictive bronchiolitis, and popcorn lung disease. It is a rare disease that causes fibrosis of the bronchioles and results in a progressive decline in lung function. It is common in people with a lung transplant.
What Is Bronchiolitis Obliterans?
The trachea (windpipe) branches off into the right and left bronchi. The bronchus further divides into smaller branches. The smallest branches that lead to the air sacs in the lungs are called bronchioles. Bronchiolitis obliterans is a lung disease that affects the bronchioles. It affects the terminal and distal bronchioles. The airway becomes inflamed and damaged, and this results in scar formation. It causes irreversible lung damage and obstruction. It is also referred to as popcorn lung disease, obliterative bronchiolitis, or constrictive bronchiolitis.
What Causes Bronchiolitis Obliterans?
It is a noninfectious disease that occurs after lung or stem cell transplantation. It occurs due to connective tissue disorder or complications after a bone marrow or heart-lung transplant. It is also caused due to exposure to inhaled toxins, gasses like acetaldehyde, methyl isocyanate, ammonia, chlorine, thionyl chloride, hydrogen fluoride, hydrogen bromide, hydrogen chloride, hydrogen sulfide, phosgene, formaldehyde, metal oxide fumes, hydrochloric acid, mustard gas, nitrogen oxide, sulfur dioxide, diacetyl gas, polyamide-amine dyes, ozone, fly ash, and fiberglass. It is associated with autoimmune disorders like rheumatoid arthritis, systemic lupus erythematosus (SLE), and inflammatory bowel disease.
It can also occur after respiratory viral infection with adenovirus, respiratory syncytial virus, influenza, human immunodeficiency virus, and cytomegalovirus. Stevens-Johnson syndrome, pneumocystis pneumonia, drug reactions, aspiration, and bronchopulmonary dysplasia can cause bronchiolitis obliterans. Other causes associated with bronchiolitis obliterans are HIV (human immunodeficiency virus), post-infectious (mycoplasma, bacteria, fungi, and human herpesvirus 8), Castleman disease, paraneoplastic pemphigus, micro carcinoid tumorlets, juvenile idiopathic arthritis, gastroesophageal reflux disease (GERD), IgA (immunoglobulin A) nephropathy, ataxia telangiectasia, and cryptogenic constrictive bronchiolitis. Aspiration of activated charcoal and consumption of a high amount of papaverine in the vegetable sauropus androgynus can cause bronchiolitis obliterans.
How Does Bronchiolitis Obliterans Occur?
Inhaled toxins or autoimmune responses cause inflammation of sub-epithelial structures and dysregulate repair mechanisms. The subepithelial cells lose the ability to regenerate the epithelial layer, which results in excess growth of cells that cause scarring. This leads to fibroproliferation and abnormal regeneration of the epithelium in the bronchioles. It involves the terminal and distal bronchioles without changes in the alveolar spaces and distal lung parenchyma. It results in hypertrophy of the smooth muscles of the bronchioles.
Peribronchiolar inflammatory infiltration, accumulation of mucus in the bronchial lumen, and bronchiolar scarring are present. The scarred tissue causes difficulty in expiration and results in air-trapping. The lumen of the bronchioles undergoes concentric narrowing due to inflammatory fibrosis, which may result in complete occlusion. The scarring is irreversible and does not improve.
Microvascular insufficiency and alloimmune responses after lung transplantation may cause airway injury and result in bronchiolitis obliterans. Cellular rejection, HLA (human leukocyte antigen) antibodies, and gastroesophageal reflux disease cause bronchiolitis obliterans after lung transplantation. Paraneoplastic pemphigus autoantibodies against desmoglein and plakin protein are present in the respiratory epithelium in bronchiolitis obliterans.
What Are the Signs and Symptoms Associated With Bronchiolitis Obliterans?
Bronchiolitis obliterans causes the following symptoms that include:
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Shortness of breath.
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Dry cough.
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Wheezing.
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Fatigue.
It is also associated with inhalation damage, post-transplant autoimmune injury, post-infectious disease, drug reactions, and autoimmune diseases.
What Are the Complications Associated With Bronchiolitis Obliterans?
Individuals with bronchiolitis obliterans develop complications like lung infections which include bronchitis and pneumonia. These infections become severe and worsen respiratory symptoms. It also results in respiratory failure and impairs the oxygen supply to the body. Bronchiolitis obliterans that develop after toxin exposure also causes a skin rash.
How Is Bronchiolitis Obliterans Diagnosed?
The diagnosis is based on the symptoms. Various tests are performed to diagnose bronchiolitis obliterans, including:
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Pulmonary Function Test - Spirometry tests are performed to diagnose the presence of obstructive patterns. Lung volume tests detect hyperinflation in the lungs due to air trapping. Diffusing capacity of the lung tests is normal in the initial stages of bronchiolitis obliterans.
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Radiographic Imaging - The chest radiograph is usually normal in the initial stages, but hyperinflation of the lungs is seen. Reticular pattern with airway wall thickening may be present with disease progression. High-resolution computed tomography imaging shows air-trapping, thickening of the airway, and haziness. It also shows patchy areas of decreased lung density due to air-trapping. This is described as a mosaic pattern.
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Lung Biopsy - Transthoracic lung biopsies are performed to diagnose bronchiolitis obliterans. Bronchiolitis obliterans can be constructive or proliferative. Constrictive bronchiolitis shows peribronchiolar cellular infiltrates that damage the airway and result in subepithelial fibrosis. Trichrome staining is used to identify bronchial muscle fibrosis. Proliferative bronchiolitis causes bronchial plugging due to intraluminal buds called Masson bodies that fill the lumen. Constrictive and proliferative bronchiolitis can be differentiated based on the extent of lesions. Constrictive and proliferative bronchiolitis are localized from the small bronchi to the membranous bronchi. The lesions are intermittent in constrictive bronchiolitis and continuous in proliferative bronchiolitis.
How Is Bronchiolitis Obliterans Treated?
Bronchiolitis obliterans is an irreversible disease, but it can be treated to slow down the worsening of the disease. Corticosteroids or immunosuppressive drugs like tacrolimus, cyclosporine, mycophenolate mofetil, and prednisone are given to treat bronchiolitis syndrome after transplant. Oxygen therapy is given to patients with breathing difficulties.
Routine vaccinations prevent complications from secondary infections due to pneumonia or influenza. Azithromycin is given to decrease the occurrence of bronchiolitis obliterans and improve lung function.
Triple therapy with inhaled Fluticasone, oral Montelukast, and Azithromycin is used to reduce the decline in lung function. Re-transplantation is performed in severe bronchiolitis obliterans. Extracorporeal photopheresis is performed to decrease the decline in lung function. Cough suppressants, inhaled bronchodilators, and oxygen therapy are given to treat toxic inhalation and post-infection symptoms.
Conclusion
Bronchiolitis obliterans is a non-curable irreversible disease that is progressive. It is an obstructive disease of the bronchioles. It is a rare disease that causes fibrosis and results in airway obstruction. Early detection and treatment can be helpful in the prevention of worsening symptoms.
