Diagnosis, treatment, and potential causative mutations of cryptogenic plastic bronchitis

To the Editor: Plastic bronchitis (PB) is a rare pulmonary disease characterized by the production of branching bronchial casts that fill the airways. It is less common in adults than in children, and occurs after 1% to 4% of Fontan surgeries.^[1]

A 26-year-old man was evaluated in a local hospital for cough, sputum, and intermittent fever. Computed tomography (CT) scanning revealed bilateral lung consolidation and ground-glass opacity [Figure 1A], and yellowish-white fibrinoid secretions were seen in his bronchoalveolar lavage fluid (BALF).

Figure 1: Chest CT scan, and electronic bronchoscopy manifestation of the PB patient. (A) CT scan showing diffuse lesions (long arrows) in both lungs on initial examination. (B) Solid sputum. (C) Electric bronchoscopy showing bronchial casts from multiple bronchi. (D) CT scan showing diffuse lesions (long arrows) in both lungs, and iodide oil (short arrow) infiltrating the lungs from the thoracic duct post-lymphangiography. (E) Potential causative mutations. (F) The results of gene ontology functional enrichment analysis showed that the identified genes were mainly involved in biological process of organ development. (G) CT scan showing that multiple nodules and patches were mostly absorbed, and pleural thickening and pleural effusion had improved one-month post-ligation of the thoracic duct. (H) CT scan showing that pulmonary plaques and pleural effusion had dissipated one year after ligation of the thoracic duct. CT: Computed tomography; GMP: Guanine monophosphate; GTP: guanosine triphosphate; PB: Plastic bronchitis.

Examination after his admission to our hospital revealed a temperature of 37°C; blood pressure of 122/77 mmHg; heart rate of 100 beats/min; respiratory rate of 25 breaths/ min; and oxygen saturation of 64.4% breathing room air. After breathing nasal oxygen at 4 L/min, his oxygen saturation increased to 89%. He also presented with peripheral cyanosis and bronchial casts [Figure 1B], inspira-tory and expiratory wheezing, and moist rales.

The first electric bronchoscopy (EB) at our hospital showed that multiple bronchi were filled with white neoplasms, which were removed through freezing and shown to be bronchial casts [Figure 1C]. His symptoms and oxygenation index were initially alleviated by this, but worsened again 3 days later. Five days later, posteroanterior chest radiographs revealed partial atelectasis in the right upper lung. A second EB showed multiple bronchi filled with bronchial casts. BALF was positive for chyle, suggesting lymphatic leakage in the lung which can be determined by lymphangiography.^[2] Ultrasound-guided lymphangiogra-phy via the left inguinal lymph node showed that iodide oil had infiltrated both lungs from the thoracic duct [Supplementary video 1], but was not visible from the left venous angle; this was verified by CT scanning [Figure 1D]. Based on previously reported diagnostic criteria,^[3] the patient was diagnosed with cryptogenic PB.

Because the patient's condition had deteriorated, thoracic duct ligation was chosen as the best treatment option.^[4] Thoracotomy was performed via a right posterolateral incision. After freeing the lower lung ligaments and conducting a pleurotomy behind the middle–lower segment of the esophagus, the thoracic duct was identified and separated between the descending aorta and the azygos vein. It was then ligated at a level 2 cm above the diaphragm [Supplementary Figure 1, https://links.lww.com/CM9/B25].

The patient had no other diseases, including congenital cardiac conditions or corrective surgical procedures, which might have caused PB. Therefore, he and his parents underwent genetic screening, which identified mutations in integrin subunit alpha 3 (ITGA3) (the patient and his mother), caspase recruitment domain family member 11 (the patient and his father), serum amyloid A1 (the patient and his parents), and coiled-coil domain-containing protein 103 (the patient and his father) genes that may be causative of PB [Figure 1E]. The ITGA3/beta-1, a major receptor for laminin 5, is involved in the maintenance of epithelial integrity, and can bind to anchoring filaments and endothelial cells in initial lymphatics of human skin.^[5] However, there have been no reported associations between the three genes and lymphatic disease. The results of gene ontology (GO) functional enrichment analysis showed that these genes were mainly involved in the biological process of organ development [Figure 1F].

The patient's symptoms gradually disappeared after surgery, and subsequent follow-up chest CT scans showed the dissipation of pulmonary plaques and pleural effusion [Figure 1G and H]. This report outlines the diagnosis and successful treatment of PB in this individual, and identifies potentially causative mutations of cryptogenic PB patho-genesis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Acknowledgements

We thank the patient, nurses, and clinical staff at Shanghai Pulmonary Hospital Tongji University School of Medicine.

Funding

This study was supported in part by grants from the Project of the National Natural Science Foundation (No. 81925001) and the Cultivation Project (No. fkzr2017) of Shanghai Pulmonary Hospital.

Conflicts of interest

None.