Bronchiolitis Obliterans: Symptoms, Types, Causes and Treatment

Bronchiolitis obliterans (BO), sometimes called "popcorn lung," is an uncommon but serious lung disease that affects people of all ages. Whether triggered by infection, inhaled toxins, or as a complication of transplantation, this condition leads to damage and scarring in the small airways, often causing persistent breathing difficulties. Understanding the symptoms, different types, underlying causes, and available treatments is crucial for patients, caregivers, and clinicians alike.

Symptoms of Bronchiolitis Obliterans

Bronchiolitis obliterans can be insidious, with symptoms that often mimic those of other lung diseases. Recognizing these early signs is vital to prompt diagnosis and management.

Symptom	Description	Frequency/Notes	Source
Cough	Typically dry, persistent	Seen in ~53–94% of cases	1, 2, 3
Dyspnea	Shortness of breath, exertional	Occurs in over half of patients	1, 2, 3
Fever	Often low-grade, may be absent	Present in ~63% (BOOP); less common in classic BO	1, 2
Crackles	Inspiratory crackles on exam	Detected in up to 78% of BOOP cases	2, 15
Wheezing	Less common, may indicate obstruction	Noted especially in constrictive/OB type	4, 10
Asymptomatic	No symptoms, found incidentally	About 13% present this way	2

Table 1: Key Symptoms

Common Presenting Features

Most patients with bronchiolitis obliterans develop a persistent dry cough and progressive shortness of breath (dyspnea). These symptoms often develop over weeks to months and may not improve with standard antibiotic therapy for presumed infections 1, 2, 3.

Additional Physical Findings

• Inspiratory crackles are frequently heard on lung auscultation, especially in bronchiolitis obliterans organizing pneumonia (BOOP/OP) 2, 15.
• Wheezing is more associated with constrictive/obliterative bronchiolitis, reflecting airflow obstruction 4, 10.
• Some patients may experience chest discomfort, mild fever, or even present with no symptoms, especially if the disease is detected incidentally during imaging for another reason 2.

Disease Progression

In some cases, symptoms may escalate rapidly, leading to severe respiratory failure requiring mechanical ventilation 2. However, progression is usually gradual, with patients reporting increasing difficulty performing physical activities.

Mimicking Other Diseases

BO symptoms can overlap with those of infectious pneumonia, asthma, or chronic obstructive pulmonary disease (COPD), which can delay diagnosis. A notable clue is lack of response to antibiotics and persistent symptoms despite standard treatment 3.

Types of Bronchiolitis Obliterans

Bronchiolitis obliterans is not a single disease but a spectrum with several distinct types, each with unique clinical features, causes, and outcomes.

Type	Core Features	Prognosis/Response to Treatment	Source
BOOP/Organizing Pneumonia	Inflammation + granulation tissue in airways/alveoli	Good, responds to steroids	1, 2, 3, 7, 15
Constrictive/Obliterative BO	Fibrosis/scarring of small airways, airflow obstruction	Poor, often irreversible	4, 5, 6, 9, 10
Postinfectious BO	After severe lower respiratory infection	Variable, often children	10, 11
Transplant-Related BO (BOS)	Post lung or stem cell transplant, chronic rejection	Poor, progressive	5, 6, 9, 14, 16
Cryptogenic BO	No identifiable cause	Variable	4

Table 2: Main Types of Bronchiolitis Obliterans

BOOP / Organizing Pneumonia

Bronchiolitis obliterans organizing pneumonia (BOOP), now often called organizing pneumonia (OP), is characterized by inflammation and granulation tissue plugs in the small airways and alveoli. Unlike other forms, BOOP often responds well to corticosteroid therapy and has a favorable prognosis 1, 2, 3, 7, 15.

Constrictive (Obliterative) Bronchiolitis

Also known as classic bronchiolitis obliterans, this type involves fibrosis and narrowing of the bronchioles, leading to fixed, often irreversible airflow obstruction. It is notoriously resistant to therapy and carries a poor prognosis, especially when associated with lung transplantation or occupational exposures 4, 5.

Postinfectious Bronchiolitis Obliterans

Most commonly seen in children following a severe respiratory infection (often adenovirus), postinfectious BO can lead to chronic, sometimes nonprogressive, obstructive lung disease. In adults, rare pathogens like Legionella can also trigger this form 10, 11.

Transplant-Related BO (BOS)

Bronchiolitis obliterans syndrome (BOS) is a major cause of chronic graft failure following lung or hematopoietic stem cell transplantation. It manifests as rapidly progressive airflow limitation and is a leading cause of late mortality post-transplant 5, 6, 9, 14, 16.

Cryptogenic Bronchiolitis Obliterans

When no underlying cause can be identified, the condition is termed cryptogenic. This form is less common and may have a variable clinical course 4.

Causes of Bronchiolitis Obliterans

Bronchiolitis obliterans arises from diverse insults to the lower respiratory tract, which initiate inflammation and scarring of the small airways.

Cause Category	Example Triggers	Notes/Outcomes	Source
Infection	Adenovirus, Legionella, Mycoplasma	Common in children, post-infectious	10, 11
Transplant-Related	Lung/Heart-lung, HSCT, chronic GVHD	Major cause in adults, high risk	5, 6, 9, 14, 16
Connective Tissue Disease	Rheumatoid arthritis, SLE	Associated in some cases	4, 5
Inhalation Injury	Toxic fumes, chemicals, flavoring agents	Occupational risk	4
Drug Reactions	Chemotherapy, antibiotics, others	Rare, reversible if recognized early	4, 2
Radiation Therapy	Post-breast cancer, other tumors	Rare, often BOOP pattern	2
Idiopathic	No cause identified	“Cryptogenic” cases	4, 2

Table 3: Causes and Triggers

Infectious Triggers

• Viral infections, especially adenovirus in children, are common causes of postinfectious BO 10. Legionella, Mycoplasma, and other pathogens have also been implicated 11.
• Infections often lead to airway injury, followed by scarring and narrowing.

Transplant-Related Causes

• Lung and heart-lung transplantation: Chronic rejection is the leading cause of BO in adults, often termed BOS. Acute rejection episodes and infections further increase risk 5, 6, 9.
• Hematopoietic stem cell transplantation (HSCT): BO is a manifestation of chronic graft-versus-host disease (GVHD) and is associated with high morbidity and mortality 14, 16.

Connective Tissue Diseases

Autoimmune conditions such as rheumatoid arthritis and systemic lupus erythematosus can lead to BO through immune-mediated airway injury 4, 5.

Inhalation and Environmental Exposures

• Occupational exposure to toxic fumes (e.g., diacetyl in popcorn factories), chemicals, and dust can damage bronchioles and trigger BO 4.
• In some Asian countries, dietary factors (e.g., eating uncooked Sauropus androgynus leaves) have been reported 4.

Drug and Radiation-Induced BO

• Certain medications (e.g., chemotherapy, antibiotics) and radiation therapy, particularly after breast cancer treatment, have been linked to BO, often with a BOOP/OP pattern 2, 4.

Idiopathic (Cryptogenic) Bronchiolitis Obliterans

When exhaustive evaluation fails to identify a cause, the term cryptogenic is used. These cases are less well understood and may represent a distinct form of the disease 4, 2.

Treatment of Bronchiolitis Obliterans

Management of bronchiolitis obliterans is challenging and depends on the underlying cause and disease type. While some forms respond well to therapy, others are resistant and progressive.

Treatment	Indications/Use Case	Outcome/Notes	Source
Corticosteroids	BOOP/OP, early disease	Good response in BOOP, not in OB	1, 2, 3, 15
Immunosuppressants	Transplant-related BO (BOS)	Essential, but incomplete effect	13, 14, 16
Macrolide Antibiotics	BOS, especially lung transplant	May improve lung function in some	12, 14
FAM Regimen (Fluticasone, Azithromycin, Montelukast)	BOS, post-HSCT	Halts decline, reduces steroid need	14, 16
Supportive Care	All forms	Oxygen, pulmonary rehab, infection control	10, 16
Lung Transplantation	End-stage or refractory disease	Last resort in severe cases	14, 16
Removal of Triggers	Drug/Exposure-induced cases	May halt progression	4, 2

Table 4: Treatment Approaches

Corticosteroid Therapy

• The mainstay for BOOP/OP, with up to 80% cure rates. Rapid clinical and radiographic improvement is typical 1, 2, 3, 15.
• Not effective in classic constrictive bronchiolitis or advanced BOS 4.

Immunosuppressive Agents

• Used in transplant-related BO (BOS), including augmented regimens (e.g., antithymocyte globulin, OKT3) 13.
• May slow decline but rarely halt disease progression completely. Long-term survival remains poor for many 13, 16.

Macrolide Antibiotics

• Azithromycin has shown benefit in some patients with BOS, improving lung function and quality of life, especially in lung transplant recipients 12, 14.
• Works through anti-inflammatory effects rather than antimicrobial action.

Novel Combination Regimens

• The FAM regimen (inhaled fluticasone, azithromycin, montelukast) plus a short steroid pulse has shown promise in newly diagnosed BOS after hematopoietic cell transplantation, reducing steroid exposure and halting disease progression in many patients 14, 16.

Supportive Care

• Includes supplemental oxygen, pulmonary rehabilitation, and prompt treatment of infections 10, 16.
• For children and those with postinfectious BO, long-term supportive care is often the cornerstone, as the disease tends to be nonprogressive but permanent 10.

Lung Transplantation

• Considered for patients with advanced, refractory disease unresponsive to other therapies 14, 16.
• Outcomes depend on underlying cause, comorbidities, and transplant-related factors.

Trigger Removal

• In cases caused by drugs or occupational exposures, identification and elimination of the offending agent can halt or reverse disease progression 4, 2.

Conclusion

Bronchiolitis obliterans is a complex syndrome with diverse presentations, causes, and outcomes. Early recognition of symptoms, understanding the specific type, identifying the underlying cause, and prompt institution of tailored therapies are key to improving patient outcomes.

Key Points:

• Bronchiolitis obliterans presents most commonly with persistent dry cough, shortness of breath, and sometimes fever or crackles; a minority may be asymptomatic 1, 2.
• Distinct types include BOOP/organizing pneumonia (steroid responsive), constrictive/obliterative bronchiolitis (often irreversible), postinfectious BO, transplant-related BOS, and cryptogenic forms 1, 2, 3, 4, 5.
• Causes range from infections and transplantation to autoimmune diseases, inhalation of toxins, drugs, and idiopathic cases 4, 5, 10.
• Treatment for BOOP/OP is usually corticosteroids with excellent outcomes, while BOS and classic OB often require immunosuppression, macrolide therapy, or even lung transplantation 1, 2, 12, 14, 16.
• Supportive care and avoidance of triggers play an essential role, especially in postinfectious and exposure-related cases 10.
• Newer combination therapies (e.g., FAM regimen) show promise in certain groups, but prognosis remains guarded for advanced or transplant-related disease 14, 16.

Understanding bronchiolitis obliterans and its management empowers patients and clinicians to act promptly and optimize care, improving both quality and length of life.