BACKGROUND: Diffuse panbronchiolitis (DPB) is a rare, chronic inflammatory lung disease marked by chronic cough, breathlessness, and preceding sinusitis. Symptoms often persist for years and can be misdiagnosed as asthma, particularly in children. This report describes a DPB case resolved with long-term azithromycin therapy, emphasizing the need for a timely and accurate diagnosis. CASE SUMMARY: A 12-year-old girl, diagnosed with asthma at age five and managed with inhaled corticosteroids and long-acting beta-2 agonists, developed a history of chronic productive cough and chronic sinusitis for a year. On examination, she exhibited wheezing and coarse crackles. Despite receiving treatment for an asthma exacerbation, her symptoms did not improve. A chest X-ray revealed reticulonodular infiltration in both lower lungs, prompting further evaluation with high-resolution computed tomography (HRCT). The HRCT confirmed centrilobular nodule opacities, a 'tree-in-bud' pattern, and non-tapering bronchi, suggesting DPB. Elevated cold hemagglutinin titers at 128 further supported the diagnosis. Her cough and sinusitis resolved within a month after starting azithromycin therapy, chosen for its anti-inflammatory and immunomodulatory effects. Follow-up HRCT scans after 1 year of continuous treatment showed complete normalization. CONCLUSION: This case highlights the importance of early diagnosis and prompt treatment in achieving favorable outcomes for DPB.