Bronchiolitis Obliterans

Educational clinical summary of Bronchiolitis Obliterans for doctors and students: definition, workup, management, and key caveats. Not a substitute for guidelines.

Maintained by Dr. Vivek Karn Review process: editorial policy

Disclaimer: This document provides comprehensive medical information for educational purposes and as a clinical reference. It is not a substitute for professional medical advice, diagnosis, or treatment. Clinicians must exercise their independent medical judgment and consider individual patient circumstances when making healthcare decisions. Always consult with a qualified healthcare professional for any medical concerns or before making any decisions related to patient care.

Overview

Definition: Bronchiolitis obliterans (BO), also known as obliterative bronchiolitis or constrictive bronchiolitis, is a rare, irreversible obstructive lung disease characterized by concentric inflammation and fibrosis of the small airways (bronchioles) leading to luminal narrowing or complete obliteration. This results in progressive, fixed airflow obstruction. It is distinct from cryptogenic organizing pneumonia (COP), formerly known as bronchiolitis obliterans organizing pneumonia (BOOP), which is a restrictive lung disease primarily affecting the alveoli and distal airways with different pathology and prognosis.
Epidemiology: BO is rare but recognized in specific contexts. Its incidence varies significantly based on the etiology:
- Post-transplant: It is the leading cause of chronic lung allograft dysfunction (CLAD) after lung transplantation, affecting approximately 50% of lung transplant recipients within 5 years. It can also occur after hematopoietic stem cell transplantation (HSCT), affecting 5-10% of recipients.
- Post-infectious: Primarily seen in children, often following severe viral infections (e.g., adenovirus, measles, RSV, Mycoplasma pneumoniae). Specific incidence rates are difficult to establish but it is the most common cause of non-transplant BO in children.
- Post-inhalation injury: Occurs after significant exposure to toxic fumes (e.g., diacetyl, sulfur dioxide, chlorine, nitrogen dioxide, ammonia). Occupational exposures (e.g., "popcorn lung") are notable examples. Incidence depends on exposure.
- Connective Tissue Diseases: Occurs in 1-2% of patients with rheumatoid arthritis, and less commonly in systemic lupus erythematosus, Sjögren's syndrome, and other autoimmune conditions.
- Drug-induced: Rare, associated with certain medications (e.g., penicillamine, gold salts, sulfasalazine, amiodarone).
- Idiopathic: Very rare, diagnosis of exclusion.
Classification: BO is primarily classified by its underlying etiology:
- Post-transplant Bronchiolitis Obliterans Syndrome (BOS), a subtype of Chronic Lung Allograft Dysfunction (CLAD).
- Post-infectious Bronchiolitis Obliterans (PIBO).
- Inhalation-induced Bronchiolitis Obliterans.
- Connective Tissue Disease-associated Bronchiolitis Obliterans.
- Drug-induced Bronchiolitis Obliterans.
- Idiopathic Bronchiolitis Obliterans.

Pathophysiology

Mechanism: The precise mechanism is not fully understood but involves an initial acute injury to the bronchiolar epithelium. This injury triggers a chronic inflammatory response, leading to the recruitment of fibroblasts. These fibroblasts proliferate and lay down excessive collagen and extracellular matrix proteins in the submucosa and lumen of the bronchioles, causing concentric scarring and narrowing or complete obliteration of the airway lumen. This process leads to fixed airway obstruction and air trapping. Key pathways involve cytokines such as transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), and interleukins (IL-6, IL-8).
Risk Factors:
- Post-Transplant BO (BOS/CLAD):
  - Acute cellular rejection episodes (strongest risk factor).
  - Chronic antibody-mediated rejection (HLA antibodies).
  - Donor-specific antibodies (DSAs).
  - Gastroesophageal reflux disease (GERD) and microaspiration.
  - Cytomegalovirus (CMV) infection.
  - Airway infection (e.g., Pseudomonas aeruginosa).
  - Ischemia-reperfusion injury.
  - Age (older donor/recipient).
  - Single lung transplant (vs. bilateral).
- Post-infectious BO:
  - Severe lower respiratory tract infections in early childhood, particularly with:
    - Adenovirus (especially types 3, 7, 21).
    - Respiratory Syncytial Virus (RSV).
    - Measles.
    - Mycoplasma pneumoniae.
    - Influenza.
  - Prematurity or underlying lung disease predisposing to severe infection.
- Inhalation Injury:
  - High-level or prolonged exposure to toxic gases or fumes:
    - Diacetyl (e.g., in food flavoring, "popcorn lung").
    - Sulfur dioxide, nitrogen dioxide, chlorine, ammonia, phosgene.
  - Smoke inhalation.
- Connective Tissue Diseases:
  - Rheumatoid arthritis (most common associated CTD, especially seropositive RA).
  - Systemic lupus erythematosus, Sjögren's syndrome, polymyositis/dermatomyositis.
- Drug-induced:
  - Penicillamine, gold salts, sulfasalazine, amiodarone, interferon-alpha.
Protective Factors:
- Post-transplant: Aggressive management of acute rejection episodes, effective CMV prophylaxis, control of GERD, meticulous surgical technique to minimize ischemia-reperfusion injury, prompt treatment of airway infections.
- Post-infectious: Vaccination against common childhood infections (e.g., measles, pertussis, influenza). Early and appropriate treatment of severe viral respiratory infections in children, though this does not guarantee prevention.
- Inhalation Injury: Strict adherence to occupational safety standards, personal protective equipment, ventilation in workplaces with exposure risks.

Clinical Presentation

Signs and Symptoms

Cardinal Features:
- Progressive dyspnea: Usually insidious onset, worsening over weeks to months, initially on exertion, then at rest.
- Persistent dry cough: Often chronic and non-productive.
- Wheezing: Often unresponsive or poorly responsive to standard bronchodilators, mimicking asthma or COPD.
Early Signs:
- Subtle exertional dyspnea.
- Persistent cough and/or wheezing following an inciting event (e.g., severe respiratory infection, transplant, toxic exposure).
- Reduced exercise tolerance.
Advanced Signs:
- Severe dyspnea at rest, often requiring supplemental oxygen.
- Cyanosis.
- Frequent respiratory infections due to impaired mucus clearance and lung architecture.
- Signs of right heart failure/cor pulmonale (e.g., peripheral edema, jugular venous distension).
- Cachexia.
Atypical Presentations:
- May initially be misdiagnosed as poorly controlled asthma or chronic obstructive pulmonary disease (COPD) due to similar symptoms.
- In children, may present as recurrent pneumonias or persistent wheezing refractory to standard asthma treatment.
- Subclinical in early stages, detected only by declining lung function.

Physical Examination

Inspection:
- Tachypnea.
- Use of accessory respiratory muscles (sternocleidomastoid, scalenes).
- Pursed-lip breathing (in severe obstruction).
- Barrel chest deformity (due to air trapping, chronic cases).
- Cyanosis (late sign).
Palpation:
- Normal vocal fremitus.
Percussion:
- Hyperresonance over lung fields due to air trapping.
Auscultation:
- Widespread expiratory wheezes, often diffuse and polyphonic.
- Decreased intensity of breath sounds.
- Inspiratory crackles (rales) are generally uncommon but may be present if there is concomitant bronchiectasis or infection.
- Rhonchi if secretions are present.

Diagnostic Approach

History Taking

Key Questions:
- Past medical history:
  - History of lung or hematopoietic stem cell transplantation (date, complications, rejection episodes).
  - History of severe childhood respiratory infections (especially recurrent or prolonged, requiring hospitalization, specific pathogens like adenovirus).
  - History of connective tissue diseases (e.g., rheumatoid arthritis, SLE).
  - History of drug exposures (e.g., penicillamine, gold salts).
- Exposure history:
  - Occupational or environmental exposure to toxic fumes, gases, or chemicals (e.g., diacetyl in food processing, chlorine, ammonia).
  - Significant smoke inhalation.
- Symptom progression:
  - Onset, duration, and progression of dyspnea, cough, and wheezing.
  - Response to bronchodilators or asthma medications.
  - Frequency of respiratory infections.
- Associated symptoms: Weight loss, fatigue, fever, chest pain.
Red Flags:
- New onset or progressive dyspnea and fixed airflow obstruction in a patient with a known risk factor (e.g., post-transplant, severe childhood infection).
- Wheezing unresponsive to standard asthma therapy.
- Persistent respiratory symptoms after resolution of an acute insult (e.g., infection, toxic exposure).
- Unexplained decline in lung function, particularly FEV1.

Laboratory Tests

First-Line: No specific laboratory tests directly diagnose BO. Initial labs aim to assess for underlying causes or complications:
- Complete blood count (CBC): May show signs of infection (leukocytosis) or chronic disease.
- Inflammatory markers (ESR, CRP): May be elevated but non-specific.
- Autoimmune serologies (ANA, RF, anti-CCP): If connective tissue disease is suspected.
- Viral serologies (e.g., adenovirus, CMV): If post-infectious etiology is suspected, particularly in children or transplant recipients.
- Sputum culture: To rule out or identify bacterial infections contributing to symptoms.
Confirmatory:
- Pulmonary Function Tests (PFTs): Essential for diagnosis and monitoring.
  - Spirometry: Shows an irreversible obstructive pattern (FEV1/FVC ratio <0.70, FEV1 <80% predicted, with no significant reversibility after bronchodilator).
  - Lung Volumes: Increased Residual Volume (RV) and Total Lung Capacity (TLC) due to air trapping. Increased RV/TLC ratio.
  - Diffusing Capacity (DLCO): Usually normal or mildly reduced, distinguishing it from emphysema where DLCO is significantly reduced.
- Lung Biopsy: Gold standard for definitive diagnosis but often not required if clinical and radiological findings are characteristic in the context of a known risk factor.
  - Histopathology: Reveals concentric fibrosis within the lumen and walls of small airways, with chronic inflammation and little or no interstitial inflammation. Transbronchial biopsy often yields non-diagnostic samples due to patchy disease and small airway involvement; surgical lung biopsy (VATS preferred) is usually required for adequate tissue.
Monitoring:
- Serial PFTs (especially FEV1): Crucial for tracking disease progression and response to treatment. For post-transplant BO, a sustained decline in FEV1 by >20% from baseline, with an FEV1/FVC ratio <0.7, is a key diagnostic criterion (BOS).
- Arterial Blood Gas (ABG): To assess for hypoxemia and hypercapnia in advanced disease.
- Oxygen saturation: Pulse oximetry for routine monitoring.

Imaging

Recommended:
- High-Resolution Computed Tomography (HRCT) of the chest: The imaging modality of choice.
  - Key Findings:
    - Mosaic attenuation pattern: Areas of decreased lung attenuation (due to air trapping and hypoperfusion) interspersed with areas of normal or increased attenuation. This pattern is more evident on expiratory images.
    - Air trapping: The most sensitive and specific sign. On expiratory HRCT images, areas of lung that remain abnormally lucent and do not decrease in volume (due to trapped air) are indicative of BO.
    - Bronchial wall thickening and bronchiectasis: Less specific but can be seen in more advanced or severe cases, particularly post-infectious BO.
    - Small centrilobular nodules or tree-in-bud pattern may be seen if there is associated infection.
Advanced:
- Ventilation-Perfusion (V/Q) Scan: May show patchy ventilation defects with corresponding patchy perfusion defects, consistent with small airway obstruction and secondary hypoperfusion. Not routinely used for diagnosis but can support findings.
- Bronchoscopy with Bronchoalveolar Lavage (BAL): Primarily used to rule out active infection, acute rejection (in transplant recipients), or other causes of symptoms. BAL findings in BO are non-specific and may show mild inflammation, but not diagnostic of the disease itself.

Management

BO is largely irreversible, so management focuses on slowing progression, alleviating symptoms, and preventing complications.

Acute Management

BO is typically a chronic, progressive disease. There is no specific acute management for BO itself. - Immediate: If an acute exacerbation of respiratory symptoms occurs in a patient with known or suspected BO, immediate interventions focus on: - Assessment for reversible causes (e.g., infection, acute rejection in transplant patients, pulmonary edema). - Supplemental oxygen if hypoxemic. - Bronchodilators (inhaled short-acting beta-agonists and anticholinergics) for symptomatic relief, though efficacy in fixed obstruction is limited. - Stabilization: - Systemic corticosteroids (e.g., methylprednisolone pulse 1 g IV daily for 3 days, followed by oral prednisone taper) may be considered for acute worsening, particularly in post-transplant patients or if an inflammatory component is suspected, but evidence for long-term benefit is limited once fibrosis is established. - Antibiotics if a bacterial infection is suspected or confirmed. - Emergency: - Admission to intensive care unit (ICU) for severe respiratory distress or respiratory failure. - Non-invasive or invasive mechanical ventilation for respiratory failure. Prognosis for patients requiring mechanical ventilation for BO is generally poor.

Chronic Management

Pharmacological:
- Immunosuppression: The cornerstone of treatment for post-transplant BO and often used in other forms, especially if an inflammatory component persists.
  - Macrolides: Azithromycin is widely used due to its immunomodulatory and anti-inflammatory properties (unrelated to its antibacterial effect).
    - Dosage: Typically 250 mg orally 3 times per week (e.g., Mon/Wed/Fri) or 500 mg 3 times per week, or daily 250 mg for at least 6-12 months. Some centers use lifelong therapy if tolerated.
    - Evidence: Shown to slow FEV1 decline in post-transplant BO and sometimes in post-infectious BO.
  - Corticosteroids: Systemic corticosteroids (e.g., prednisone 0.5-1 mg/kg/day, tapered) are often trialed, especially early in the disease or when inflammation is prominent. Their efficacy in advanced fibrotic BO is limited. In post-transplant settings, they may be part of rejection treatment protocols.
  - Other Immunosuppressants (for post-transplant BO): Optimization of existing immunosuppression (e.g., calcineurin inhibitors like tacrolimus or cyclosporine, mycophenolate mofetil). Conversion to different agents (e.g., sirolimus, everolimus) may be considered, though evidence is variable.
  - Extracorporeal Photopheresis (ECP): A specialized immunomodulatory therapy used in refractory post-transplant BO.
  - Rituximab: Used in selected cases of post-transplant BO, particularly with B-cell involvement.
- Bronchodilators: Inhaled short-acting and long-acting beta-agonists and anticholinergics are used for symptomatic relief of dyspnea and wheezing, although they do not reverse the fixed obstruction.
- Anti-fibrotic agents: Pirfenidone and nintedanib (approved for idiopathic pulmonary fibrosis) are being investigated for BO, but are not standard of care. There is growing interest, particularly for post-transplant BO.
Non-pharmacological:
- Pulmonary Rehabilitation: Essential to improve exercise tolerance, reduce dyspnea, and enhance quality of life. Includes exercise training, breathing techniques, and education.
- Oxygen Therapy: For patients with hypoxemia (PaO2 <55 mmHg or SaO2 <88% at rest, or higher with evidence of cor pulmonale or severe nocturnal desaturation).
- Nutritional Support: To combat cachexia often associated with chronic lung disease.
- Infection Prevention: Vaccinations (influenza, pneumococcal, COVID-19). Prompt and aggressive treatment of respiratory infections.
- Avoidance of Irritants: Smoking cessation, avoidance of air pollution, and specific occupational irritants.
- Management of GERD: Proton pump inhibitors (PPIs) are often used, especially in transplant patients, to reduce aspiration risk.
- Lung Transplantation: The definitive treatment for end-stage BO in eligible patients. However, BO can recur in the transplanted lung.
Monitoring:
- Regular pulmonary function tests (FEV1 is the most important parameter) to track disease progression.
- Clinical assessment of symptoms, exercise tolerance, and quality of life.
- Oxygen saturation monitoring.
- Periodical HRCT scans (e.g., annually or as needed) to assess for changes in air trapping or other findings.

Treatment Algorithms

First-Line:
- Post-transplant BO: Optimize calcineurin inhibitor levels, consider conversion to or addition of azithromycin (250-500 mg 3x/week or daily). Treat underlying issues like reflux, infections.
- Post-infectious/Idiopathic/Connective tissue disease-associated BO: A trial of systemic corticosteroids (e.g., prednisone) may be initiated, often followed by long-term azithromycin (250-500 mg 3x/week).
Second-Line:
- Post-transplant BO: Addition of other immunosuppressants (e.g., mycophenolate mofetil, cyclophosphamide), extracorporeal photopheresis (ECP), or rituximab for resistant cases. Consider re-evaluation for lung re-transplantation if applicable.
- Other forms: Less established second-line therapies. Consider further immunosuppression or trials of novel agents based on individual circumstances and expert opinion.
Refractory Cases:
- For all forms of severe, progressive BO refractory to medical management: Evaluation for lung transplantation is the only definitive therapy.
- If transplantation is not an option or fails, focus shifts to palliative care, symptom management, and optimization of quality of life.

Complications

Common:
- Recurrent respiratory infections (bacterial and viral) due to impaired mucociliary clearance and bronchial distortion.
- Chronic hypoxemia.
- Pulmonary hypertension (due to chronic hypoxia and vascular remodeling).
- Bronchiectasis (in advanced cases, particularly post-infectious).
- Chronic respiratory failure.
Serious:
- Acute respiratory decompensation requiring hospitalization and mechanical ventilation.
- Cor pulmonale (right-sided heart failure due to severe pulmonary hypertension).
- Exacerbations of underlying conditions (e.g., rejection in transplant patients).
Long-term:
- Severe disability and reduced quality of life.
- Need for chronic oxygen therapy.
- Increased risk of mortality.
- Side effects from long-term immunosuppression (e.g., infections, kidney dysfunction, malignancy).

Prognosis

Factors: Prognosis is highly variable and depends on the underlying etiology, severity at diagnosis, rate of FEV1 decline, and response to treatment.
- Post-transplant BO (BOS): Generally the most severe form. The prognosis is poor, with a 5-year survival rate typically between 30% and 50% once diagnosed. Rapid decline in FEV1 is associated with worse outcomes.
- Post-infectious BO in children: While often leading to chronic lung disease, the course can be more stable, and some children may experience partial improvement or stabilization over time. However, many will have lifelong respiratory compromise. Survival rates are generally better than post-transplant BO but can be affected by severity and complications.
- Other forms: Prognosis varies. Drug-induced BO may resolve if the offending drug is stopped early. Inhalation injury outcomes depend on the severity of exposure.
Survival: Overall, BO is associated with significant morbidity and increased mortality due to progressive respiratory failure.
Quality of Life: Severely impaired due to chronic dyspnea, fatigue, recurrent infections, and limitations on physical activity. Patients often require significant medical support and lifestyle adjustments.

Prevention

Primary: Aiming to prevent the initial occurrence.
- Post-transplant:
  - Meticulous donor-recipient matching and rejection prophylaxis.
  - Aggressive and prompt treatment of acute cellular and antibody-mediated rejection episodes.
  - Prophylaxis and early treatment of CMV infection.
  - Control of gastroesophageal reflux (GERD) with proton pump inhibitors.
  - Avoiding aspiration.
- Post-infectious:
  - Universal childhood vaccination programs (e.g., measles, influenza, pertussis, RSV prophylaxis in high-risk infants).
  - Prompt diagnosis and management of severe viral lower respiratory tract infections in children.
- Inhalation Injury:
  - Strict adherence to occupational safety standards, engineering controls, and personal protective equipment (PPE) in industries with chemical exposure (e.g., use of respirators).
Secondary: Early detection and intervention in at-risk individuals to slow progression.
- Regular surveillance spirometry in lung transplant recipients (e.g., monthly for the first year, then quarterly). A sustained 10-20% decline in FEV1 from baseline should prompt further investigation.
- Close monitoring of lung function in individuals with known exposures (e.g., post-severe chemical inhalation).
- High index of suspicion for BO in patients with unexplained, progressive fixed airway obstruction, particularly with relevant history.
Tertiary: Preventing complications and improving outcomes in established disease.
- Aggressive management of infections.
- Pulmonary rehabilitation.
- Optimization of oxygen therapy.
- Vaccination against respiratory pathogens.
- Management of comorbidities (e.g., pulmonary hypertension, GERD).

Special Populations

Pediatric:
- Most commonly post-infectious, particularly after severe adenovirus infection.
- Diagnosis can be challenging due to non-specific symptoms and difficulty performing reliable PFTs in very young children.
- HRCT with expiratory images is crucial.
- Treatment often includes long-term macrolides (azithromycin) and sometimes a trial of systemic corticosteroids.
- Long-term follow-up for growth, development, and respiratory complications is essential.
Geriatric:
- Less common as an idiopathic condition; more likely associated with connective tissue diseases or environmental exposures.
- Co-morbidities are frequent and can impact treatment tolerability and prognosis.
- Careful consideration of medication side effects and polypharmacy.
Pregnancy:
- Data on BO in pregnancy are very limited.
- Management of chronic respiratory disease in pregnancy requires careful balancing of maternal and fetal risks.
- Immunosuppressants need to be reviewed for safety during pregnancy. Macrolides like azithromycin are generally considered safer during pregnancy than some other immunosuppressants.
- Close monitoring of maternal respiratory status and fetal well-being is critical.
Comorbidities:
- Connective Tissue Diseases: Management involves optimizing control of the underlying autoimmune disease in conjunction with BO-specific therapies.
- Pulmonary Hypertension: Requires specific management with pulmonary vasodilators if severe, in addition to BO treatment.
- Gastroesophageal Reflux Disease (GERD): Aggressive management with PPIs and potentially antireflux surgery, especially in transplant patients, to reduce aspiration.
- Recurrent Infections: Prophylactic antibiotics may be considered in some cases, along with aggressive treatment of acute infections.

Clinical Pearls

Diagnostic:
- Always suspect BO in patients presenting with progressive, fixed airflow obstruction that does not respond to bronchodilators, especially with a history of lung/HSCT, severe childhood respiratory infection, or toxic fume exposure.
- HRCT of the chest, including expiratory images, is the most crucial imaging study for demonstrating air trapping and mosaic attenuation, which are highly characteristic.
- Pulmonary Function Tests (PFTs) showing an irreversible obstructive pattern (low FEV1/FVC, low FEV1) with preserved DLCO strongly suggest BO, differentiating it from emphysema.
- Lung biopsy is the gold standard for definitive diagnosis but is invasive and often not needed if clinical-radiological features are classic in the appropriate context. Transbronchial biopsies are often inadequate.
Treatment:
- Azithromycin (250-500 mg 3x/week or daily) is a key immunomodulatory agent that can slow FEV1 decline in many forms of BO, particularly post-transplant. It should be considered early.
- Immunosuppression is central to managing post-transplant BO (optimizing existing regimen, adding new agents).
- Pulmonary rehabilitation is essential for symptom management and improving quality of life, regardless of etiology.
- No current treatment reliably reverses the fibrotic changes of BO; focus is on preventing further decline and managing symptoms.
Pitfalls:
- Misdiagnosis as asthma or COPD due to similar obstructive symptoms. The lack of response to bronchodilators and specific HRCT findings should raise suspicion for BO.
- Delay in diagnosis: Due to the insidious onset and rarity, diagnosis can be significantly delayed, leading to more advanced and irreversible disease.
- Over-reliance on bronchodilators: While they provide some symptomatic relief, they do not address the underlying fibrotic process.
- Not considering all potential etiologies: Always inquire about transplant history, severe childhood infections, and toxic exposures.

Recent Updates

Guidelines: The International Society for Heart and Lung Transplantation (ISHLT) regularly updates guidelines for the diagnosis and management of Chronic Lung Allograft Dysfunction (CLAD), which includes Bronchiolitis Obliterans Syndrome (BOS) as its most common phenotype. These guidelines emphasize early detection via serial PFTs and a multi-modal therapeutic approach.
Evidence:
- Growing evidence supporting the immunomodulatory role of macrolides (e.g., azithromycin) in various forms of BO, not just post-transplant.
- Ongoing research into the utility of anti-fibrotic agents (e.g., pirfenidone, nintedanib) for BO, particularly post-transplant, though they are not yet standard of care.
- Increased recognition of the role of gastroesophageal reflux and aspiration in the pathogenesis of post-transplant BO, leading to more aggressive reflux management strategies.
- Better understanding of specific risk factors and molecular pathways in CLAD/BOS is leading to potential biomarker discovery and targeted therapies.
Controversies:
- Optimal duration and dosing of macrolide therapy.
- The role of novel immunosuppressive agents and combination therapies beyond standard practice.
- The precise indications and efficacy of anti-fibrotic agents in non-IPF BO.
- The management of idiopathic BO, given its rarity and lack of specific evidence-based treatments.

Key References

Guidelines:
- Weill D, et al. The 2015 International Society for Heart and Lung Transplantation Guidelines for the management of lung transplantation. J Heart Lung Transplant. 2015;34(3):E1-E67. (Note: These are a cornerstone, but expect updates).
- Meyer KC, Raghu G, et al. An official ATS/ERS statement: Clinical practice guidelines for the diagnosis and management of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183(6):799-824. (While specific to IPF, general principles of fibrotic lung disease apply).
Studies & Reviews:
- Aguiar L, et al. Bronchiolitis Obliterans in Children: A Review. Pulm Med. 2021;2021:6654060.
- King TE Jr. Bronchiolitis. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray & Nadel's Textbook of Respiratory Medicine. 6th ed. Philadelphia, PA: Saunders Elsevier; 2016: chap 67.
- Verleden GM, et al. Chronic Lung Allograft Dysfunction: Definition, Pathogenesis, and Treatment. Clin Chest Med. 2017;38(4):689-698.
- Jaksch P, et al. Extracorporeal photopheresis in lung transplant recipients with refractory bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2012;186(8):792-798.
- Authors. UpToDate Topic Reviews on Bronchiolitis Obliterans and Chronic Lung Allograft Dysfunction. (Specific article titles vary and are regularly updated).