Diffuse Panbronchiolitis

Diffuse panbronchiolitis (DPB) is an inflammatory lung disease and was first identified in 1969. It was mostly reported from East Asian countries such as Japan, China, and Korea.[1] The name, DPB, was proposed to distinguish it from chronic bronchiolitis. “Diffuse” refers to “presence of lesions in both the lungs,” and “pan” refers to “inflammation in all layers of bronchioles.” In the years following the initial description of the DPB in Japan, cases were also identified in other parts of Asia, including China, India, and Taiwan. Over the years, DPB cases have been reported from globally.[2] To the best of our knowledge, only three proven cases have been reported from India till now.[3] Different ethnic background of the Indian population (Caucasians, not Asians) might be one reason for low DPB reporting in the Indian subcontinent, despite being the part of Asia. However, the effects of DPB underreporting in India due to a lack of awareness and recognition, leading to misdiagnosis and delayed treatment, cannot be ignored. The prognosis of DPB has significantly improved after the introduction of long-term and low-dose macrolide therapy in 1985.[4] DPB is an idiopathic inflammatory disease characterized by bronchiolitis and sinusitis. This entity principally affects the respiratory bronchioles, causing progressive suppurative and severe obstructive respiratory disorder.[5] Untreated DPB can lead to respiratory failure within a few years, with nearly 50% of untreated patients dying within 5 years of diagnosis.[6] Symptoms are often progressive and mimic common respiratory illnesses such as bronchitis and bronchiolitis, and the diagnosis is made through a combination of clinical symptoms, imaging, and occasionally histopathology.[7] There are no specific laboratory or radiographic abnormalities that are diagnostic for DPB. Diagnosis is made through characteristic findings that raise the suspicion for DPB, including recurrent Haemophilus influenzae or Pseudomonas aeruginosa infections, an obstructive ventilatory defect, and diffuse tree-in-bud nodularity. The clinical profile typically involves patients in the age group of 2nd–5th decades of life with a history of chronic paranasal sinusitis. The typical order of symptom onset includes cough with sputum, followed by the onset of exertional dyspnea. Physical examination may reveal crackles or wheeze or both.[5] Plain chest radiography may reveal bilateral, diffuse, and small nodular shadows with pulmonary hyperinflation. In advanced cases, ring-shaped or tramline shadows can be observed, which may suggest bronchiectasis [Figure 1]. High-resolution computed tomography (HRCT) scans often show a “tree-in-bud” pattern, bronchiolar wall thickening, and bronchiectasis.[8]Figure 1: Bronchial wall thickening, bronchiectasis (a), nodular lesions, and tree in bud lesions (b) on both sidesA characteristic laboratory feature is the persistent elevation of cold agglutinins, as seen in the test for Mycoplasma pneumoniae.[5] Markedly high levels of the “tumour-associated” carbohydrate antigens sialyl stage-specific embryonic antigen-1 and Sialyl Lewis (a) have been demonstrated in the serum and bronchoalveolar lavage fluid of patients with DPB.[8] Pulmonary function tests show a significant airflow limitation, which is relatively resistant to bronchodilators.[9] Analysis of arterial blood gas usually shows hypoxaemia (partial pressure of arterial oxygen <80 mmHg). The diffusing capacity is variably reduced. In advanced DPB, P. aeruginosa is superinfected, reducing the lungs’ capacity for gas exchange, which brings about the progression of hypoxaemia and later hypercapnia. This eventually results in the development of pulmonary hypertension, leading to cor pulmonale and consequent death due to chronic respiratory failure in most cases.[5] The diagnostic criteria on biopsy include severe inflammation in all the layers of the respiratory bronchioles and lung tissue lesions that appear as nodules within the terminal and respiratory bronchioles in both lungs.[5] A significant improvement in the prognosis of this potentially fatal disease has been reported with the use of long-term macrolide therapy, the effect of which is attributed to anti-inflammatory and immunoregulatory action.[5] Because appropriate macrolide therapy results in a dramatic improvement in prognosis (>90% 10-year survival rate), a clinician should consider the diagnosis of DPB despite its rarity and nonspecific presentation. In certain circumstances, obtaining a biopsy may not be feasible, and modalities such as HRCT thorax and response to treatment may be considered a tool for appropriate diagnosis. To conclude, the diagnosis of DPB should be entertained in appropriate clinical settings despite its rarity and nonspecific presentation. In certain circumstances, obtaining a biopsy may not be feasible, and diagnostic modalities such as HRCT thorax and response to treatment may be considered to arrive at an appropriate diagnosis. The advent of macrolide therapy has significantly changed the prognosis and clinical outcome of the disease; hence, an accurate diagnosis can have a substantial impact on the quality of life and prognosis of the patient.