Ruie Feng

Pulmonary Manifestations of Sjögren’s Syndrome

Background: Primary Sjögren’s syndrome (PSS) is associated with various histological patterns of interstitial lung disease. Although chest images and lung function studies showed that lung involvement predominantly occurs in small airways, pathological findings were not consistent with the results of high-resolution CT (HRCT) and lung function tests. Objectives: To investigate the pathological characteristics of PSS-associated interstitial lung disease (PSS-ILD) and their relationship with HRCT lung function tests. Methods: Fourteen patients diagnosed as PSS who underwent surgical lung biopsy in Peking Union Medical College Hospital from October 2000 to October 2006 were reviewed. Histopathologic findings, radiologic findings and lung function tests were analyzed. Results:The study included 13 women. The median age was 46 years. Most patients presented with dyspnea and cough. CT scans revealed bilateral ground-glass, consolidative, reticular and nodular opacities and cyst lesions. The histological patterns included nonspecific interstitial pneumonia (NSIP) cellular pattern associated with organizing pneumonia (OP), NSIP mixed pattern associated with OP, noncaseating granulomas, chronic bronchiolitis, follicular bronchiolitis, constrictive bronchiolitis, lymphocytic interstitial pneumonia associated with follicular bronchiolitis, NSIP mixed pattern associated with follicular bronchiolitis, NSIP mixed pattern coexisting with chronic bronchiolitis, OP associated with chronic bronchiolitis, and noncaseating granulomas coexisting with OP. Treatment included prednisone and cyclophosphamide. During the follow-up period (median 38 months), most patients improved or remained stable. The patient with constrictive bronchiolitis died from progression of primary disease. Conclusions: The histopathologic patterns of PSS-ILD included lung interstitial involvement and small airway involvement or both. Corticosteroid therapy combined with cyclophosphamide was administered with a favorable response in the majority of patients.

SPC-Cre-ERT2 transgenic mouse for temporal gene deletion in alveolar epithelial cells.

Although several Cre-loxP-based gene knockout mouse models have been generated for the study of gene function in alveolar epithelia in the lung, their applications are still limited. In this study, we developed a SPC-Cre-ERT2 mouse model, in which a tamoxifen-inducible Cre recombinase (Cre-ERT2) is under the control of the human surfactant protein C (SPC) promoter. The specificity and efficiency of Cre-ERT2 activity was first evaluated by crossing SPC-Cre-ERT2 mouse with ROSA26R mouse, a β-galactosidase reporter strain. We found that Cre-ERT2 was expressed in 30.7% type II alveolar epithelial cells of SPC-Cre-ERT2/ROSA26R mouse lung tissues in the presence of tamoxifen. We then tested the tamoxifen-inducible recombinase activity of Cre-ERT2 in a mouse strain bearing TSC1 conditional knockout alleles (TSC1fx/fx). TSC1 deletion was detected in the lungs of tamoxifen treated SPC-Cre-ERT2/TSC1fx/fx mice. Therefore this SPC-Cre-ERT2 mouse model may be a valuable tool to investigate functions of genes in lung development, physiology and disease.

A case report: The efficacy of pirfenidone in a Chinese patient with progressive systemic sclerosis-associated interstitial lung disease: A CARE-compliant article.

AbstractSystemic sclerosis (SSc)-associated interstitial lung disease (SSc-ILD) has become the leading SSc-related cause of death. Although various types of immunosuppressive therapy have been attempted for patients with SSc-ILD, no curative or effective treatment strategies for SSc-ILD have been developed. Therefore, management of patients with SSc-ILD remains a challenge. Here, we report a Chinese, female, SSc-ILD patient who was negative for Scl-70 and showed an excellent response to pirfenidone without obvious adverse effects. She had been suffered from dry cough and exertional dyspnea for 2 months. The chest computed tomography manifestation was consistent with a pattern of fibrotic nonspecific interstitial pneumonia. The pulmonary function test showed isolated impaired diffusion. After 11 weeks of administration of pirfenidone, the dry cough and dyspnea had disappeared. Both of the lung shadows and the pulmonary diffusion function were improved. Pirfenidone might be an effective option for early SSc-ILD treatment. A well-controlled clinical trial is expected in the future.

Diffuse Cystic Lung Diseases: Diagnostic Considerations

Diffuse cystic lung disease (DCLD) is a group of heterogeneous diseases that present as diffuse cystic changes in the lung on computed tomography of the chest. Most DCLD diseases are rare, although they might resemble common diseases such as emphysema and bronchiectasis. Main causes of DCLD include lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, pulmonary Langerhans cell histiocytosis, lymphoid interstitial pneumonia, amyloidosis, light-chain deposition disease, Sjögren syndrome, and primary or metastatic neoplasm. We discuss clinical factors that are helpful in the differential diagnosis of DCLDsuch as sex and age, symptoms and signs, extrapulmonary presentations, cigarette smoking, and family history. Investigations for DCLD include high-resolution computed tomography, biochemical and histopathological studies, genetic tests, pulmonary function tests, and bronchoscopic and video-assisted thoracoscopic biopsies. A proposed diagnostic algorithm would enhance ease of diagnosing most cases of DCLD.

Clinical Features and Prognosis in 21 Patients with Extrinsic Allergic Alveolitis

OBJECTIVE To assess the spectrum of causes, clinical features, differences between disease phases, and prognosis of extrinsic allergic alveolitis (EAA). METHODS Patients with EAA diagnosed at Peking Union Medical College Hospital from August 1983 to May 2007 were analyzed retrospectively. Their medical records were examined to gather clinical, laboratorial, radiological, and histopathological data. Patients were divided to three phases (acute, subacute, and chronic) according to clinical presentations. Follow-up data regarding treatment response, subsequent radiological and pulmonary function studies, and clinical outcomes were collected. RESULTS A total of 21 cases were enrolled. Among them, 11 were subacute, 10 were chronic. The most common exposure was pet birds (6 cases, 28.6%). The primary abnormality of pulmonary function was restriction and/or reduction in diffusing capacity (12 cases, 63.2%). The most common findings on high-resolution computed tomography (HRCT) were ground-glass opacities (13 cases, 68.4%) and centrilobular nodules (8 cases, 42.1%). Airway obstruction in pulmonary function test, emphysema, lung cysts, and fibrosis on HRCT were more frequently seen in chronic than in subacute patients, though the differences were not statistically significant. Bronchoalveolar lavage fluid (BALF) showed lymphocytosis. The total cell count and the percentage of neutrophils were significantly higher in subacute than in chronic patients (P<0.05). Nonnecrotizing granulomas were seen in 8 (47.1%) cases. Improvement or normalization in symptoms, radiography, and pulmonary function test after treatment were seen in all 18 patients with available follow-up data. Five patients recurred. CONCLUSIONS The characteristic abnormalities of pulmonary function, findings on HRCT, and pathology are essential for all phases of EAA, and the atypical manifestations such as obstruction and fibrosis can also be present frequently, particularly in chronic cases. Differential cell counts of BALF are related to the phase of the disease. The treatment response and prognosis of EAA are good.

Recurrent pulmonary mucormycosis after lobectomy in a non-smoking patient without predisposing risk factors

Pulmonary mucormycosis is a very rare clinical condition in patients without underlying risk factors. A limited number of cases have been reported in predominantly elderly patients; history of smoking appears to be a common feature. A case of non-smoking male who developed pulmonary mucormycosis with the longest reported follow-up is presented. In addition, this is also the first reported case with disease recurrence after lobectomy (two years) in an immunocompetent host. Treatment with an additional lobectomy and amphotericin B was successful in this patient.

Impaired lipid metabolism in idiopathic pulmonary alveolar proteinosis

BackgroundIt is well known that lipids abnormally accumulate in the alveoli during idiopathic pulmonary alveolar proteinosis (PAP). It is unclear, however, whether lipids also abnormally accumulate in serum. This study investigated the serum lipid panels in idiopathic PAP patients and explored the relationships between serum levels and the severity of idiopathic PAP.Methods and ResultsClinical data including the level of serum lipids were evaluated in 33 non-diabetic idiopathic PAP patients and 157 healthy volunteers. Serum levels of triglyceride were higher in PAP patients than in healthy subjects (median: 192.00 mg/dl (P25: 104.36, P75: 219.00) vs 119.56 mg/dl (P25: 78.81, P75: 193.03), P < 0.05), while high-density lipoprotein cholesterol (HDL-C) levels were lower in patients than in the control group (42.50 ± 10.30 vs 51.34 ± 12.06 mg/dl, P < 0.01). Forced expiratory volume in one second and forced vital capacity in hypertriglyceridemia patients were lower than those in patients with normal triglyceride. Serum LDL-C and HDL-C ratio correlated negatively with PaO2 (r = -0.403, P < 0.05) and positively with lactate dehydrogenase (r = 0.381, P < 0.05).ConclusionsPAP associates with high triglyceride and low HDL levels in the serum, and these lipids provide potential intervention strategy for treatment.

Pathological and High Resolution CT Findings in Churg-Strauss Syndrome

OBJECTIVE To investigate the Churg-Strauss syndrome (CSS) associated lung involvement, concentrating on clinical characteristics, pathological findings of lung involvements, response to treatment, and prognosis. METHODS We retrospectively analyzed the characters of the clinical manifestations, thin-section CT and pathological findings of CSS. The study involved 16 patients. Clinical data were obtained by chart review. All patients underwent transbronchial lung biopsy (TBLB). Six of them underwent surgical lung biopsy as well. RESULTS The patients included 7 men and 9 women, aged from 14 to 61 years (median, 47.5 years). Extrathoracic organs involved included nervous system (7/16) and skin (5/16). Respiratory symptoms included cough (12/16), exertional dyspnea (11/16), hemoptysis (4/16), and chest pain (3/16). CT findings included bilateral ground-glass opacities (12/16), bilateral patchy opacities (12/16), and centrilobular nodules (6/16). The pathological findings of TBLB demonstrated increased eosinophils (3/16), vasculitis (3/16), and interstitial pneumonia (16/16). The pathological findings of surgical lung biopsy of 6 cases showed necrotizing vasculitis in 4 cases, capillaries in 5, eosinophilic pneumonia in 3, granulomas in 2, and airway abnormalities in 3. All patients improved in symptoms after therapy during the study period (range, 3 to 51 months; median, 15 months). CONCLUSIONS Asthma may be present in CSS patient when there is bronchial involvement. Ground-glass opacities and consolidation seen on high-resolution CT reflect the presence of eosinophilic pneumonia, vasculitis, and pulmonary alveolar hemorrhage. TBLB has significant limitations for the diagnosis of CSS. Early diagnosis and therapy can result in satisfactory prognosis.

Clinical and genetic characteristics of chinese patients with Birt-Hogg-Dubé syndrome

BackgroundBirt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder, the main manifestations of which are fibrofolliculomas, renal tumors, pulmonary cysts and recurrent pneumothorax. The known causative gene for BHD syndrome is the folliculin (FLCN) gene on chromosome 17p11.2. Studies of the FLCN mutation for BHD syndrome are less prevalent in Chinese populations than in Caucasian populations. Our study aims to investigate the genotype spectrum in a group of Chinese patients with BHD.MethodsWe enrolled 51 patients with symptoms highly suggestive of BHD from January 2014 to February 2017. The FLCN gene was examined using PCR and Sanger sequencing in every patient, for those whose Sanger sequencing showed negative mutation results, multiplex ligation-dependent probe amplification (MLPA) testing was conducted to detect any losses of large segments.Main resultsAmong the 51 patients, 27 had FLCN germline mutations. In total, 20 mutations were identified: 14 were novel mutations, including 3 splice acceptor site mutations, 2 different deletions, 6 nonsense mutations, 1 missense mutation, 1 small insertion, and 1 deletion of the whole exon 8.ConclusionsWe found a similar genotype spectrum but different mutant loci in Chinese patients with BHD compared with European and American patients, thus providing stronger evidence for the clinical molecular diagnosis of BHD in China. It suggests that mutation analysis of the FLCN gene should be systematically conducted in patients with cystic lung diseases.

Organizing pneumonia components in non-specific interstitial pneumonia (NSIP): a clinicopathological study of 33 NSIP cases

To review the clinical, radiological and pathological features of non‐specific interstitial pneumonia (NSIP), mainly to characterize organizing pneumonia (OP) components in NSIP.