A 52-year-old female was admitted to the hospital due to recurrent cough, expectoration, and shortness of breath for more than 10 years. In her hometown, she frequently presented to the hospital with lung infections and was treated with antibiotics. She received a pulmonary function test in September 2021 in Shanghai, which indicated obstructive ventilatory dysfunction because FEV1/FVC was less than 70%. Consequently, she was diagnosed with chronic obstructive pulmonary disease (COPD). She was treated with long-acting beta2-receptor agonist (LABA) + long-acting cholinergic receptor antagonist (LAMA) (Olexin) inhalation for about 2 months. Two days prior to the current admission, she was presented with increased cough and yellow sputum. She had no fever, chills, fatigue, night sweats, progressive emaciation, chest pain, or other symptoms. She had a history of spontaneous pneumothorax because of ruptured bullae of the lung. However, she could not provide the X-ray and a detailed history of the previous therapies. Although clear that she had situs inversus, she was treated as a common pulmonary disease. She denied any history of PCD in any of her parents or risk factors such as inbreeding. She has a son and a daughter, both of them are healthy with no apparent signs of lung disease. There is no other person with similar symptoms in her family.
On a physical examination, her blood pressure was 140/90 mmHg, pulse rate of 107 beats/min, respiratory rate of 15 times/min, and oxygen saturation of 98% at room air. On cardiovascular examination, heartbeats were audible on the right side of the chest. There were not any coarse crackles in both lungs. An initial investigation revealed a white cell count of 3,290/muL and a C reactive protein level of less than 1 mg/L. The arterial blood gas analysis showed her PO2 level was 111 mmHg when she received an oxygen flow rate of 3 L/min. There were not significant abnormal findings in liver and kidney functions, electrolytes, ESR, procalcitonin, peripheral blood lymphocyte subsets, markers of autoimmunity, and antinuclear antibody.
In sputum smear, Gram-positive cocci, suspected to be Streptococcus was identified. The bronchial alveolar lavage fluid (BALF) was obtained to perform metagenomic sequencing and Nocardia gelsenkircheni was identified. Chest X-ray (posteroanterior view) showed a cardiac shadow on the right side (Figure 1). Many tree-in-buds on both sides of lung lobes were found in Chest computed tomography (CT) (Figure 2). Abdominal CT confirmed complete situs inversus totalis (Figure 3). Otitis media tympanitis with effusion was found by an otolaryngologic examination (Figure 4). Fiberoptic bronchoscopy showed total bronchial inversion and bronchial mucosal inflammations in both lungs (Figure 5).
Given the history of repeated respiratory infections and situs inversus, combined with the physical examinations, she was suspected to have PCD. Following the European Respiratory Society (ERS) guidelines for the diagnosis of PCD, we intended to evaluate nasal nitric oxide (nNO) levels and perform a high-speed video analysis (HSVA). Unfortunately, we were unable to conduct those tests because of our technical limitations. We then performed genetic testing of her peripheral blood to confirm the diagnosis, according to the diagnostic criteria of the Chinese Expert Consensus on the Diagnosis and Treatment of Primary Ciliary Dyskinesia.
We performed whole-exome sequencing to detect the presence of any mutation(s). Two milliliters of peripheral venous blood preserved in an ethylenediamine tetraacetic acid (EDTA) coated tube was sent to the Shenzhen BGI Medical Test Laboratory. The sequencing was performed by capture high-throughput chip technology. Sanger sequencing was used to verify the mutations. The results showed that two suspected pathogenic mutations were located on chromosome 17; CHR17:11513858-11513859 and CHR17:11593470 (Figure 6), and detected in DNAH9 gene associated with PCD type 40, which was partially related to the phenotype of the subjects with PCD. One of the mutations, DNAH9 (NM_001372.3, c.760_761delTT, p.Phe254Leufs*6) is a frame-shift mutation caused by the deletion of two nucleotide TT at nucleotide positions 760-761 of the coding sequence of the gene, resulting in the phenylalanine codon at position 254 being changed to leucine, and a stop codon at position 260. The c.760_761delTT mutation is mentioned in ClinVar. Another mutation, DNAH9 (NM_001372.3C, c.4331G > A, chr17:11593470) is a nonsense mutation caused by the substitution of nucleotide A with G, resulting in the leucine codon at position Trp being changed to a stop codon. We could not get blood samples of her parents or children for the gene analysis, but they had no clinical manifestation of PCD. This study was approved by Shanghai Ethical Review Board (2022-047).
Ampicillin tazobactam was administered to treat the infection, ambroxol hydrochloride was administered to reduce sputum, albuterol, and acetylcysteine were inhaled to dilate the airways and promote sputum excretion. After treatment, the symptoms were relieved, and she was discharged. The patient was then prescribed fordostine to eliminate phlegm and urmetrium bromide and verranterol for inhalation therapy.