On July 8th, 2014, a 37-year-old male was admitted to our departmentwith persistent cough for two years, and chest distress and fatigue for more than one year. He felt progressive dyspnea after activity, but no wheezing, joint changes, chest pain or rash in the previous 2 years. Confuingly, he had developed left pneumothorax twice (in May 2013 and June 2014) without any injury, and recovered after thoracic drainage. The doctor arranged an X-ray but not thoracic Computed Tomography (CT) for him when the first pneumothorax occurred. After the first pneumothorax episode, the patient gradually felt the onset of chest distress, dyspnea and fatigue. Unfortunately, the patient was not diagnosed with disease until after the second pneumothorax episode on June 9th 2014. According to the thoracic CT done in June 2014, there are only find bilateral pulmonary diffuse changes with panlobular emphysema. He was diagnosed with pulmonary emphysema. The patient's local doctors suggested the patient stop smoking and prescribed montelukast. Half of a month later, the patient continued to have chest distress and dyspnea, especially post-activity. The patient came to the Department of Respiratory Medicine at the First Affiliated Hospital of Zhejiang for help. He had no previous history of Hepatitis, tuberculosis, diabetes or hypertension. He had previously smoked for 10 years, and had a smoking index of 200 (smoking cessation less than 2 months). He works as a clerk, denied alcohol addiction, and has no special gas and toxic substance exposure history. His wife and his son are healthy.
On examination, his temperature was 36.9 C, his blood pressure was 121/82 mmHg, his pulse 70 beats per minute, his respiratory rate was 19 beats per minute and his oxygen saturation was 97% without oxygen inhalation. There was no cyanosis, no distension of jugular vein and no clubbing. The trachea position was normal, and there was normal breath movement and sound with no crackle. There was no lower extremity edema. The remainder of the examination was normal. Blood gas analysis showed PaO2 76.7 mmHg,PaCO2 44.2 mmHg, SPO2 95.7%,HCO3-24.9 mmol/L,and BE-0.2 mmol/L. Liver and renal function tests were normal, as were blood levels of glucose, calcium, total protein, albumin and globulin. White cell count, hemoglobin and platelet count were normal. Anti-Nuclear Antibody (ANA) and Anti-Neutrophil Cytoplasmic Antibodies (ANCA) were normal. Thyroid Function, erythrocytesedimentationrate (ESR) and immunoglobulin were normal. The thoracic HRCT done on 08-July-2015 showed a bilateral diffuse cyst, especially in upper lobe and middle lobe (Figure 1). Magnetic Resonance Imaging (MRI) of the hypophysis was normal. Cardiac and abdominal ultrasounds were normal. Lung function (assessed on 08-July-2014) was FVC 1.22L (28.1% pred), FEV1 0.48L (13.8% pred), FVC/FEV1 (39.8% pred), TCL 5.60L (89.4% pred), RV 3.26L (186.3% pred), RV/TCL 208% pred, and DLCO (30.5%pred). The results of the lung function tests showed severe obstruction of mixed ventilation dysfunction and severe diffusion dysfunction.
After admittance, our initial diagnosis was Bilateral Pulmonary Diffuse Change, potentially with PLCH. To diagnose the patient definitively, we conducted bronchoscopy and video-assisted thoracicscopic surgery. The bronchoscopy did not find neoplasms or the other abnormal lesions except bilateral mucus congestion. During the bronchoscopy, we collected bronchoalveolar lavage (BAL) and analyzed the cell differential. The Left lingual BAL showed: Macrophage 23%, Neutrophil 57%, Lymphocyte 11% and Eosinophil's 9%. The Right Middle Lobe (RML) BAL showed: Macrophage 84%, Neutrophil 5%, Lymphocyte 10% and Eosinophil's 1%. A diagnosis could not be made from the BAL results due to a lack of CD1a expression. The patient was consented for Video-Assisted Thoacoscopic Surgery (VATS) for a biopsy to assist in making a diagnosis.
Histopathology of the biopsy showed inflammatory cell infiltration in the left upper lobe and fiber-vessel proliferation (Figure 2). The specimen pathology showed a section of lung tissue with a honeycomb appearance. Microscopic pathology showed alveolar atrophy, island-like fibroplasia and inflammatory cell infiltration. The immunohistochemistry (IHC) results were P53 (-), Ki-67 (-), Des (-), CD34 (+), S-100 (-), CD1a(-), TTF-1 (+),SMA (+), CK7 (+), CD34 (-), CD68 (-), CD163 (-), CD31 (+), CD14 (+) and Masson (+). The final pathology report diagnosed smoking-related interstitial lung disease, but could not distinguish the definite kind. After the biopsy, we consulted with Professor FanQing Meng, a pathologist at Nanjing Drum Tower Hospital. Professor Meng agreed with our pathologist's assessment.
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After discharge from hospital, the patient stopped smoking and only use Spiriva when needed to dilate the bronchia. Two months later, the patient returned to clinic to have his lung function evaluated and a thoracic HRCT. He felt better than he had the previous July; he could walk a little faster than before and climb 2 floors of stairs. His lung function showed improvement (Table 1). We prescribed Spiriva and advised him to use unceasingly.
We followed up the patient by phone 6 months after his discharge from hospital. He reported that he took Spiriva everyday and felt better and back to normal. The patient refused to return to the First Affiliated Hospital of Zhejiang as it is a far distance from his home. After 1 year, we called him again. He had already returned to work with a reduced work load. He continued to take Spiriva. He again refused to return to the hospital for further follow up. We suggested him to continue not smoking and taking Spiriva. He accepted.
Two months after the patient was discharged from the hospital, we consulted Professor Ulrich Costabel, the world-famous expert in ILD, about the case and diagnosis. Prof. Costabel diagnosed PLCH from the patient's recurrent pneumothorax and the other clinical manifestation, HRCT, follow-up presentation after smoking cessation and using Spiriva.