Respiratory Bronchiolitis-Associated Interstitial Lung Disease - An Overview

Introduction

Respiratory bronchiolitis (RB) is the inflammation of the small airways of the lungs, mostly associated with increased tobacco smoking. Patients usually experience exertional dyspnea (difficulty breathing) and chronic cough. Interstitial lung disease (ILD) is an umbrella term used to describe chronic lung disorders that cause inflammation and fibrosis (scarring) of the lungs. These complex and diverse groups of conditions may cause significant morbidity and mortality due to severe lung damage. They can be idiopathic (unknown cause) or occur due to drug toxicity, environmental exposures, and autoimmune disorders.

Respiratory bronchiolitis-associated interstitial lung disease is a combined condition that includes RB and ILD, mainly affects smokers, and has certain specific histologic and radiographic characteristics. Therefore, understanding the association between these two conditions and the consequences of smoking is integral for accurate diagnosis and management.

What Is Respiratory Bronchiolitis-Associated Interstitial Lung Disease?

Respiratory bronchiolitis-associated interstitial lung disease (RBILD) is a rare and mild inflammatory pulmonary disorder that may potentially lead to pulmonary fibrosis (scarring and thickening of the lung tissues). It mainly affects heavy tobacco or cigarette smokers with a male-to-female ratio of 2:1 and a mean age of 36 years. It is a form of idiopathic interstitial pneumonia (inflammation of the lung tissues without a known cause), which may often improve after cessation of smoking.

RB-ILD was first described in 1974 in young asymptomatic cigarette smokers who exhibited certain specific histological findings and chronic inflammation of the bronchial walls. In 1987, Myers observed an accumulation of pigmented macrophages in surgical biopsy samples that were severe enough to cause physiological, clinical, and imaging features of interstitial lung disease and termed the condition RBILD. This condition has been recognized primarily in smokers and is very rarely found in non-smokers.

What Are the Common Symptoms of Respiratory Bronchiolitis-Associated Interstitial Lung Disease?

The exact incidence and prevalence of respiratory bronchiolitis-associated interstitial lung disease is not clearly understood; however, it is typically seen in individuals between 30 and 60 years of age with no significant gender predilection. The condition's onset is usually slow and subtle, but it progresses gradually and may be difficult to diagnose. Most patients mainly present with persistent cough, which is non-productive and develops over a few weeks or months, and breathing difficulty on exertion.

Clubbing of the fingers, chest pain and discomfort, bluish discoloration of skin and lips, and loss of appetite are a few associated symptoms. Studies have also reported that RBILD can be associated with fever, sweats, and hemoptysis (coughing of blood) in acute lower respiratory tract infection cases. It is not a disabling disease, as some patients may be asymptomatic or exhibit only mild symptoms.

How Is Respiratory Bronchiolitis-Associated Interstitial Lung Disease Diagnosed?

Respiratory bronchiolitis-associated interstitial lung disease exhibits an exaggerated respiratory bronchiolytic response to cigarette smoke. It is suspected in heavy smokers, and evaluation includes various imaging tests and a lung biopsy. RB-ILD is diagnosed depending on the patient's smoking history, symptoms, clinical signs, severity of the disease, associated medical conditions, lung function abnormalities, and histological features. Bibasilar end-inspiratory crackles are the condition's most common signs and the only physical finding. RBILD can also be diagnosed in asymptomatic patients with impairment in lung function by radiographic images and high-resolution computed tomography.

• Lung function tests indicate mainly obstructive abnormalities, hyperinflation, and a mild to moderate reduction in carbon monoxide diffusion capacity (DLco); however, this may be normal in some patients as RB-ILD is heterogeneous. In severe cases of RBILD, an isolated increase in residual volume may occasionally be observed, along with airway obstruction and restriction.

• Histological tests reveal an accumulation of yellow-brown pigmented macrophages inside the lumens of alveolar ducts and respiratory bronchioles with submucosal and peribronchiolar chronic inflammation patches. Mild alveolar fibrosis with expansion and thickening of the alveolar septa and centrilobular emphysema can also be observed.

• Chest radiographs show reticulonodular interstitial opacities and high-resolution computed tomography (HRCT) reveals centrilobular nodules, central and peripheral bronchial wall thickening, and patchy areas of hazy ground-glass opacities with upper lobe centrilobular emphysema.

• A surgical lung biopsy or an open lung biopsy may be indicated in some cases if the diagnosis is challenging or the cessation of smoking has not minimized the symptoms.

What Is the Treatment for Respiratory Bronchiolitis-Associated Interstitial Lung Disease?

Management of respiratory bronchiolitis-associated interstitial lung disease mainly involves cessation of smoking and avoiding even passive exposure to tobacco smoke. The treatment and prognosis have been focused in various studies, and quitting smoking along with certain medications can be beneficial. Immunosuppressive therapy and corticosteroid treatment are recommended in a majority of patients with RBILD, along with smoking cessation. However, symptomatic and physiologic improvements are relatively uncommon in RBILD regardless of the smoking status. Hence, it is not understood whether smoking cessation alone can improve the outcome or whether corticosteroids can be helpful to patients based on the natural history of the disease.

A study reported that a follow-up HRCT showed a reduction in the extent of bronchial wall thickening, ground-glass opacities, and centrilobular nodules in about 43 percent of patients following corticosteroid therapy and smoking cessation, while emphysema (damage to the air sacs of the lungs) was irreversible. However, several other studies presented cases with no change or improvement despite corticosteroid treatment or discontinuation of therapy, along with the absence of smoking.

The prognosis of RBILD is favorable, with prolonged survival in most cases. Still, clinical worsening and deterioration of spirometry results and gas exchange were typical regardless of smoking status and corticosteroid treatment.

Conclusion

Cigarette smoking is the most commonly encountered risk factor for various lung diseases, and respiratory bronchiolitis-associated interstitial lung disease is one among them. It is a rare and mild inflammatory condition but a distinct clinical syndrome mainly seen in heavy smokers. RBILD is characterized by persistent cough and breathlessness on exertion, similar to other interstitial lung disorders.

Various imaging tests, an open lung biopsy, and a thorough clinical evaluation may be recommended to confirm the diagnosis. The disease course varies among patients; some may experience progression despite treatment. The effectiveness of immunotherapy or corticosteroid medications is inconsistent for many patients, as significant functional improvements were not observed. However, cessation of smoking is the mainstay and highly essential for an excellent clinical outcome.