A 76-year-old man with a 37.5 pack-year history of smoking was admitted to our hospital for the assessment of a right upper lung mass observed on chest CT (Fig. 1A). The chest CT also revealed right axillary lymphadenopathy and diffuse small pulmonary nodules (Fig. 1B), indicating extra- and intrapulmonary metastases. Biopsy of the axillary lymph nodes revealed lung adenocarcinoma. He was treated with carboplatin and nab-paclitaxel as the first line chemotherapy.
After four weeks of treatment, his chest radiography revealed rapid enlargement of a right axillary lymph node (Fig. 2A), suggesting progression of the lung cancer. Immunohistochemistry performed with 22C3 pharmDx (Agilent, Tokyo, Japan) on the tumor biopsy specimen revealed a programmed death-ligand 1 (PD-L1) tumor proportion score of >=95%. Based on these results, second-line treatment with pembrolizumab (2 mg/kg, every 3 weeks) was initiated. Although the lesions appeared to increase in size as revealed by chest radiographs obtained during the first course, this radiological finding was thought to represent pseudo-progression, and treatment with pembrolizumab was continued. During the second course, chest radiography revealed reduction in the lesion size, and the treatment with pembrolizumab was continued for a total of five courses.
After the fifth course, the patient started experiencing dry cough. His body temperature was 36.7  C, blood pressure was 140/63 mmHg, heart rate was 88 bpm, and percutaneous oxygen saturation was 97%. Physical examination, including chest auscultation, was unremarkable. Peripheral blood and serum tests results indicated slight inflammation based on the elevated serum C-reactive protein levels; however, the patient's white blood cell count and serum Krebs von den Lungen-6 levels were normal (Table 1). Pulmonary function tests results indicated the worsening of obstruction [FVC, 2.57 L (83.0%); FEV1, 1.51 L/s; FEV1/FVC, 58.8%; %FEV1, 60.5%] compared with the results before treatment with pembrolizumab [FVC, 2.99 L (96.6%); FEV1, 1.99 L/s; FEV1/FVC, 66.6%; %FEV1, 79.5%]. Chest CT revealed diffuse micronodules (Fig. 2B), suggesting diffuse bronchiolitis. The patient was treated with azithromycin for 3 days; however, neither his cough nor the micronodules on chest radiography improved. Bronchoscopy was performed, and cytology of the bronchoalveolar lavage fluid (BALF) revealed an increased number of neutrophils in the BALF. Histologically, transbronchial lung biopsy specimens contained inflammatory cell infiltrates in the bronchioles, including lymphocytes; however, there were no specific histological characteristics of OP, NSIP, DAD, or diffuse panbronchiolitis (DPB) (Fig. 2C). No bacteria, including acid-fast bacilli and Mycobacterium tuberculosis, were isolated from the BALF or sputum. Based on all these findings, the patient was diagnosed with bronchiolitis type of ICI-ILD. Treatment with pembrolizumab was discontinued, and he was treated with low-dose erythromycin (400 mg/day). As the patient complained of persistent cough, he was treated with a long-acting muscarinic antagonist and a long-acting beta2 agonist. An inhaled corticosteroid was subsequently administered when the cough only slightly improved. With this regimen, the cough finally resolved. The lung mass decreased in size, and the micronodules suggesting bronchiolitis also improved (Fig. 3).
Chest computed tomography before treatment showing right upper lung mass and diffuse small pulmonary nodules.