In order to find out the cause of bronchiectasis and treat it, we asked in detail about clinical symptoms and past medical history, and conducted a series of tests. Initially, we asked about the child's previous pathological symptoms. The caregiver clearly stated that the child did not have recurrent cough, expectoration, hemoptysis, chest pain, bloody sputum, fever, night sweats, fatigue, weight loss, nausea, acid reflux, heartburn, postnasal drip, salty skin or sinusitis. His growth and development were similar to those of his peers, but his athletic endurance was not as good as theirs. He had no history of tuberculosis, measles, whooping cough, GERD and hospitalization for respiratory infection, nor had he been exposed to pollution and toxic gases. He had only one history of mild and chronic cough, and the symptoms lasted for about 1 month when he was four years old. After several outpatient visits and taking oral medication, he gradually recovered. A pediatric chest x-ray showed inflammation in the right lower lung, but no signs of bronchiectasis. He did not undergo a HRCT of the chest at that time. What's more, he had a history of Pendred syndrome. He suffered from hearing loss at the age of 2 and received a cochlear implant surgery at the age of 3 and a half. He had a mild enlarged goiter, but no thyroid dysfunction.
We performed extensive diagnostic tests on this child. A complete blood count, C-reactive protein, results of kidney- and liver- function tests, serum procalcitonin, tuberculin test and interferon-gamma release assays were normal. A test for antineutrophil cytoplasmic antibody was negative, as were tests for some viruses which could cause secondary immunodeficiency, such as human immunodeficiency virus. Immunoglobulin level and absolute lymphoblastic counts in serum were also normal. The detection of allergen-specific IgE revealed a mild positive reaction to dust mites. Moreover, we performed fiberoptic bronchoscopy, bronchoalveolar lavage (BALF), and bronchial biopsy. Bronchoscopy revealed condensed secretions in the right lower lobe bronchus. The results of next-generation sequencing of BALF revealed Tropheryma whipplei (sequence number 13,200). Electron microscopy of bronchial biopsy showed mild inflammatory changes in cilia, without typical ultrastructural pathological changes of PCD (Figures 2A-C). We also tested for CF and alpha1-antitrypsin deficiency related mutant genes. These results were negative. Because infection was the most common cause of bronchiectasis, and a large number of bacteria called Tropheryma whipplei were shown in BALF, we first considered whether bronchiectasis was caused by Whipple's disease. Common signs and symptoms of Whipple's disease included diarrhea, stomach cramping and pain, inflamed joints, weakness, and anemia. Obviously, the child did not meet the diagnosis criteria. Secondly, we analyzed other common causes of bronchiectasis. The evidence for the diagnosis of the above-mentioned causes of bronchiectasis in this child was also insufficient. So far, a definitive diagnosis of the child has not been determined.
Considering the importance of medical history in making an accurate diagnosis, we inquired the child's medical history again and recommended a genetic test for this child. The caregiver supplemented the medical history and stated that the child was found to have hearing loss at the age of 2. Genetic testing for hearing loss showed a heterozygous mutation in the SLC26A4 gene, and the mutation site was IVS7-2A > G (Table 1). We learned that IVS7-2A > G may lead to the deletion of exons surrounding the splice site. Mutations in the SLC26A4 gene alter the structure or function of pendrin, which disrupts ion transport. In the inner ear, pendrin dysfunction affects Cl- transport, leading to vestibular aqueduct enlargement and sensorineural hearing loss. Goiter is mainly related to the reduction of pendrin-mediated transport of I-. Pendrin also plays an important role in airway defense and airway homeostasis in vitro. We questioned the link between SLC26A4 mutation and bronchiectasis. The loss of pendrin function could cause airway acidification, impair airway epithelial defense, and increase of the volume of ASL. In the case of infection (even opportunistic pathogens), patients may not be able to effectively eliminate the infection, but show persistent chronic infection and inflammation. Chronic airway inflammation and airway blockage interact with each other, and finally lead to irreversible tracheal dilatation. Based on the above analysis, we speculated that mutations in the SLC26A4 (pendrin) may cause non-CF bronchiectasis. Unfortunately, our conclusions were speculative. And the proposed mechanism has not been verified by experimental researches. To the best of our knowledge, no similar cases have been reported in other clinical studies. The root causes of this phenomenon is worth further exploration. We explained the analysis and speculative conclusions to the patient's family members and get their recognition. Bronchiectasis possibly caused by pendrin dysfunction, like bronchiectasis caused by other causes, may be currently incurable. However, studies have shown that the expression of pendrin in the endolymphatic sac can be successfully restored in mice by transgenic technology. Perhaps the function of pendrin in the airway could be restored in the future. Therefore, we gave the child a series of treatments, including inhalation of bronchodilators and corticosteroids, taking oral apophlegmatisant and antibiotics, and mechanical vibration expectoration. And he was taught to avoid respiratory tract infection, get the pneumonia vaccine, master the ability of airway clearance and regularly follow up. After 1 month of treatment, the child returned to our outpatient clinic and performed a CT of the chest. The images showed that the inflammation disappeared, but the tracheal dilatation remained. Figure 3 showed timeline of clinical events, diagnostics, and treatments of the patient.