Diffuse Panbronchiolitis - An Overview

Introduction

Diffuse panbronchiolitis is an inflammatory lung disease showing increased evidence among the people of East Asia, for example, Korea, Japan, and China. Recently, diffuse panbronchiolitis has been observed in communities of Caucasian, Hispanic, and African American people in Italy, France, the UK, Germany, Norway, and the USA. The disease is often seen in non-smoker individuals in around three to six decades of life. Males are more likely to get this condition than females, with a male-female ratio of 2:1. This article briefly explains diffuse panbronchiolitis, including its symptoms, causes, diagnosis, and treatment.

What Is Diffuse Panbronchiolitis?

Diffuse panbronchiolitis is an idiopathic (unknown cause) inflammatory lung disease, principally affecting the small airways of the lungs called respiratory bronchioles. The function of these airways is to bring air to the alveoli for oxygen and carbon dioxide exchange. In diffuse panbronchiolitis, these respiratory bronchioles are inflamed, leading to progressive suppurative and severe obstructive respiratory disorder that makes it difficult to breathe. If the condition is left untreated, diffuse panbronchiolitis may worsen and can cause damage to the lungs (bronchiectasis), respiratory failure, and even death. In diffuse panbronchiolitis, the term "diffuse" means the lesions are distributed throughout both lungs, and "pan" indicates that inflammation is present in every layer of the respiratory bronchioles.

What Are the Symptoms of Diffuse Panbronchiolitis?

The common symptoms of diffuse panbronchiolitis include:

• Chronic sinusitis.

• Productive cough-producing mucus.

• Breathlessness, especially during exertion.

• Wheezing.

• Coarse crackles.

• Weight loss as symptoms worsen.

What Are the Causes of Diffuse Panbronchiolitis?

The exact cause of DPB is not known, but a variety of genetic, environmental, and systemic factors are believed to contribute to the condition.

• Genetic Cause: Some cases of DPB have been reported, particularly in certain ethnic groups like the Japanese. Additionally, a specific genetic marker, human leukocyte antigen, has also been associated with DPB. In certain population groups, suggesting the genetic cause of the disease.

• Environmental Factors: Some researchers suggest that environmental factors, such as recurrent infections, for example, Haemophilus influenzae, Pseudomonas aeruginosa, and type 1 human T-lymphotropic virus, or exposure to certain pollutants, might contribute to diffuse panbronchiolitis development.

• Systemic Factors: Since diffuse panbronchiolitis is an inflammatory disease Some research suggests that the involvement of immune cells such as neutrophils and T-lymphocytes, together with the inflammatory mediators such as cytokines interleukin-8 and macrophage inflammatory protein-1, are believed to play key roles in developing diffuse panbronchiolitis.

How Is Diffuse Panbronchiolitis Diagnosed?

1. Medical History and Physical Examination: The doctor will ask about symptoms like coughing with mucus, breathlessness, and any history of chest infection, and during physical examinations, the doctor will look for signs like wheezing and coarse crackle sounds.

2. Chest X-ray: The X-ray may show nodular opacities on both sides of the lungs that are diffused throughout the lungs. Also, the lungs appear larger than normal due to air trapped inside the lungs.

3. High-Resolution Computer Tomography (HRCT) Scan: HRCT scan provides a detailed image of the lungs as compared to chest X-rays. In diffuse panbronchiolitis, HRCT scan shows:

• Nodular shadows are distributed in a "centrilobular" pattern (center of the lung lobule).

• "Tree-in-bud" pattern: Nodules connected to branching linear areas, indicating inflamed and mucus-filled airways.

• Peripheral air trapping (air trapped in outer lung regions) in expiration.

• Dilated airways and thickened bronchial walls.

4. Sputum Culture: This test analyzes the sputum of the individual to check for pathological agents that are commonly associated with diffuse panbronchiolitis, such as:

• Haemophilus influenzae.

• Pseudomonas aeruginosa.

• S. pneumoniae.

• Moraxella.

5. Pulmonary Function Tests and Blood Gas Analysis: Thepulmonary function test helps to assess the level of obstruction in individuals with diffuse panbronchiolitis. Blood gas analysis provides information about the levels of oxygen and carbon dioxide in the blood.

6. Biopsy: In some cases, a lung biopsy may be necessary. This involves taking a small tissue sample from the lungs for further examination under a microscope.

What Is the Treatment of Diffuse Panbronchiolitis?

Earlier there was no treatment available for diffuse panbronchiolitis. The treatment aims to manage only symptoms and complications that include:

Early Stage:

• Oral glucocorticosteroids.

• Antibiotics such as β-lactams against H. influenzae.

Advanced Stage:

• Traditional oxygen therapy

• Ventilator support.

Erythromycin Therapy:

Numerous studies have established the efficacy of erythromycin in improving various aspects of DPB:

• Symptom relief.

• Improved Lung function.

• CT scan findings (reduced "centrilobular nodules").

• Survival rates.

Dosage and Duration:

Typically, 600 mg of erythromycin is administered daily for two years, often considered a curative approach. The actual length of the treatment is still unknown.

Stopping treatment is advised when symptoms resolve, and CT scan abnormalities disappear.

Relapse is possible, so follow-up is crucial even after lung transplantation.

How Erythromycin Works:

Erythromycin is known for treating airway infections, but it also possesses anti-inflammatory and immunoregulatory properties. These properties are known to contribute to the effectiveness of erythromycin in DPB:

• Erythromycin inhibits the production of inflammatory cytokines: IL-1, IL-6, IL-8, and TNF-α.

• Inhibits neutrophil activity and reduces their migration by blocking the formation of adhesion molecules and the release of harmful substances.

• Decreases levels of pro-inflammatory mediators: leukotriene B4, IL-8, and human defenses.

• Potentially inhibits mucin and water secretion, leading to reduced sputum volume.

Outcomes of Erythromycin Therapy:

• Improved lung function.

• Reduced airway infections.

• Notable improvement in survival as compared to no treatment

Other Macrolides:

Clarithromycin and roxithromycin are also used for DPB, sometimes showing effectiveness when erythromycin fails.

What Is the Prognosis Of DPB?

Earlier, the prognosis of DPB was poor. However, with long-term treatment with Erythromycin therapy, the prognosis of the disease has become better.

What Are the Complications Of DPB?

If not treated on time, diffuse panbronchiolitis can cause several complications. The following are the potential complications associated with DPB:

• Bronchiectasis (a disease wherein the airways get damaged).

• Respiratory failure (a serious condition in which a person has difficulty breathing).

• Death.

Conclusion

Diffuse panbronchiolitis is a fatal lung disorder and is characterized by inflammation and blockage of the small airways. Earlier, there was no cure for the disease. The treatment only focused on symptomatic relief and complications, but the introduction of erythromycin therapy significantly changed the disease's prognosis and improved the quality of life of individuals with DPB. With advancements in understanding and management, there is optimism for further improvements in outcomes and, ultimately, a brighter outlook for individuals affected by DPB.