Objective To study the prevalence of combined pulmonary fibrosis and emphysema (CPFE) in a community-based lung cancer screening program in Shanghai. Methods From June 2018 to July 2019, eligible participants who were assessed through a high-risk lung cancer questionnaire in Xuhui, Shanghai underwent low-dose computed tomography of the lungs. The suspected CPFE patients were invited to provide medical history and blood for analysis, and received high-resolution CT (HRCT) scanning for confirmation. Results Of the 15 cases of suspected CPFE from a total of 4478 participants in which 1704 males and 2774 females, 4 declined further examination and 11 received further examine. Eight subjects were confirmed as CPFE, and all were male, of whom two were ex-smokers and six were active smokers. These CPFE patients had cough, chest tightness and dyspnea. There were 3 cases of centrilobular emphysema, 2 cases of paraseptal emphysema, 1 case of panlobular emphysema and 2 cases of mixed emphysema. There were 2 cases of usual interstitial pneumonia, 3 cases of non-specific interstitial pneumonia, 2 cases of airspace enlargement with fibrosis and 1 case of unclassifiable smoking-related interstitial fibrosis. The KBILD scores were 61.7±7.5 and mMRC scores were 1.5±0.8. Serum Krebs von den Lungen-6 concentration was (380.75±212.05)U/mL. Lung function test showed normal or mild restrictive ventilatory function, and mild-moderate impairment in diffusion capacity. Conclusions The prevalence of CPFE is 1.79‰ in a community-based lung cancer screening population, and is 4.69‰ in male lung cancer screening population.
Objective To improve the awareness of acute exacerbation of idiopathic pulmonary fibrosis ( AEIPF) and discuss its clinical characteristics, diagnosis, treatment and outcome. Methods The clinical data of patients with AEIPF from June 2006 to June 2011 in 11 hospitals in Jiangsu were collected and analyzed. Resluts There were 18 males and 3 females in the AEIPF patients with mean age of ( 67.4 ± 8.1) years. The duration from IPF diagnosis was ( 7.4 ±8.2) months. The duration of acute symptom before admission was ( 7.0 ±5.3) days. The distribution pattern of new groud-glass opacity was peripheral in 3 patients,multifocal in 5 patients, and diffuse in13 patients. All patients were treated with corticosteroid pulse therapy. Nine patients survived and 12 patients died. The mortality rate was 57.1% . Conclusions AEIPF progresses quickly and the mortality rate is very high. Corticosteroid pulse therapy is the mainstay of therapy in AEIPF patients.
Objective To investigate the preventive therapeutic effects of CPD1, a novel phosphodiesterase 5 inhibitor, on lung pathological phenotype and interstitial fibrosis of lung in pulmonary fibrosis model rats caused by bleomycin (BLM). Methods Rats were randomly divided into a sham surgery group (n=10), a model group (n=14), a CPD1 treatment group (n=13), and a nintedanib positive control drug treatment group (n=13). Pulmonary fibrosis model was constructed by slowly instilling BLM (3 mg/kg) into the left bronchus in the model group and two treatment groups. Two hours after BLM infusion, the rats were treated with CPD1 (20 mg·kg–1·d–1), or positive control drug nintedanib (50 mg·kg–1·d–1) by intragastric administration, respectively, for 2 weeks. To observe the effect of CPD1 treatment on pathological structural damage, collagen deposition, and the expression of fibronectin (Fn), α-smooth muscle actin (α-SMA), Collagen Ⅰ, and E-cadherin (E-Cad) in the affected lung tissues of unilateral pulmonary fibrosis rats. Moreover, to further observed the effects of CPD1 intervention on the expression of transforming growth factor β1 (TGF-β1) and Smad3 in the cell model of human alveolar basal epithelial A549 cells. Results Compared with the control group, the lung tissue structure was seriously damaged in the BLM group, and with expansion of the alveolar space, collapse of the alveolar lumen. Significant widening of the alveolar septum and thickening of the alveolar wall were observed in the BLM group. There was a marked increase in collagen deposition in the thickened walls of the BLM group. Moreover, the expressions of Fn, α-SMA, Collagen Ⅰ, TGF-β and Smad3 were increased, while the expression of E-Cad significantly decreased in the BLM group (all P<0.05). Compared with the BLM group, the lung tissue damage was significantly improved in the CPD1 group rats. Furthermore, CPD1 inhibit the expression of Fn, α-SMA, Collagen Ⅰ, TGF-β and Smad3, and upregulate the expression of E-Cad (all P<0.05). Conclusions Prophylactic treatment with phosphodiesterase 5 inhibitor CPD1 strongly attenuates BLM-induced pulmonary fibrosis by inhibiting the lung injury and inflammation response via targeting TGF-β/Smad pathway, reducing the deposition of extracellular matrix.
ObjectiveTo determine the diagnostic value of serum KL-6 level in patients with interstitial lung diseases (ILD). MethodsAll the ILD patients enrolled were hospitalized from April 2013 to April 2014. Patients with other pulmonary diseases and healthy subjects were chosen as control groups simultaneously. Serum KL-6 concentrations were measured by chemiluminescent enzyme immunoassay. The association with serum KL-6 level and pulmonary function was analyzed. ResultsThere were 149 ILD patients, 155 patients with other pulmonary diseases, and 64 healthy subjects. The average serum levels of KL-6 were (1 801.86±2 831.36) U/mL, (267.00±124.41) U/mL, (201.28±81.18) U/mL in the patients with ILD, the patients with other pulmonary diseases and the healthy controls, respectively. The sensitivity and the specificity of the serum KL-6 for the diagnosis of ILD was 83.89% and 92.24% respectively when the cut-off level was set at 500 U/mL. The Kappa value was 0.767 (P < 0.001). The best cut-off value of KL-6 was 469.5 U/mL. Serum KL-6 levels in the patients with ILD were significantly higher compared with the patients with chronic obstructive pulmonary disease, pneumonia, tuberculosis, bronchiectasis and the healthy controls, respectively (all P < 0.001). The KL-6 levels in the pulmonary alveolar proteinosis patients were significantly higher compared with the patients with cryptogenic organizing pneumonia (COP), the patients with idiopathic pulmonary fibrosis (IPF) and the patients with connective tissue disease (CTD-ILD) (all P < 0.001). While the KL-6 concentration in IPF and CTD-ILD were significantly higher than that in COP (P=0.003 and P=0.008, respectively). Significant negative correlations were found between the levels of serum KL-6 and vital capacity as a percentage of the predicted value, forced vital capacity as a percentage of the predicted value, forced expiratory volume in one second as a percentage of the predicted value and carbon monoxide diffusing capacity as a percentage of the predicted value (all P < 0.001). Follow-up study showed the levels of serum KL-6 were consistent with clinical efficacy. ConclusionSerum KL-6 level is a reliable serum marker for ILD, and is related with the severity of disease and clinical efficacy.
Objective To improve the knowledge and diagnostic accuracy of combined pulmonary fibrosis and emphysema (CPFE) syndrome in connective tissue diseases (CTD) by summarizing the clinical characteristics of 20 CTD patients with CPFE and reviewing literatures. Methods The medical records of 20 CTD patients with CPFE from January 2011 to June 2015 were retrospectively analyzed. Results There were 11 males and 9 females. The average age was 47 years. Among them, 4 patients were smokers and 15 patients were nonsmokers. The average duration of CTD was 3.5 years with an average onset age of 41 years. Respiratory symptoms were reported in 17 patients and Velcro rale was found in 9 patients; The most common type of CTD disease in these 20 patients was inflammatory myopathy (9 patients, 45%) followed by systemic sclerosis (SSc) (4 patients, 20%). High resolution computerized tomography of lung showed typical radiological features of CPFE containing fibrosis lesions predominantly distributed in the subpleural (14 patients) and basal (18 patients) parts and emphysema mainly located in upper zones. Relatively normal results of lung volume and ventilation function, and markedly reduced carbon monoxide transfer capacity were observed. One patient was confirmed with pulmonary hypertension and 1 patient died from severe inflammation and acute respiratory distress syndrome. Conclusions The CPFE syndrome can be identified in CTD patients as an entity with male predominance, especially among patients with inflammatory myopathy and SSc. Higher risk of secondary pulmonary hypertension and acute lung injury in these patients may increase mortality. Early differentiation of CPFE from pure interstitial lung disease in CTD patients could be helpful in improving prognosis.
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic at the end of December 2019, more than 85% of the population in China has been infected. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly affects the respiratory system, especially the lungs. The mortality rate of patients with severe infection is high. A percentage of 6% to 10% of patients will eventually develop into COVID-related acute respiratory distress syndrome (CARDS), which requires mechanical ventilation and extracorporeal membrane oxygenation (ECMO) support. Some patients who survive acute lung injury will subsequently develop post COVID-19 pulmonary fibrosis (PCPF). Both fully treated CARDS and severe PCPF are suitable candidates for lung transplantation. Due to the special course, evaluation strategies are different from those used in patients with common end-stage lung disease. After lung transplantation in COVID-19 patients, special treatment is required, including standardized nucleic acid testing for the novel coronavirus, adjustment strategy of immunosuppressive drugs, and rational use of antiviral drugs, which is a big challenge for the postoperative management of lung transplantation. This consensus was evidence-based written and was reached by experts after multiple rounds of discussions, providing reference for assessment and postoperative management of patients with interstitial pneumonia after COVID-19 infection.
Objective To analyze the clinical presentations and radiological characteristics of acute exacerbation of idiopathic pulmonary fibrosis ( IPF) . Methods Clinical and radiological data of 2 patients with acute exacerbation of IPF from April 2006 to July 2008 were retrospectively analyzed and literatures were reviewed. Results Both patients were senior male patients over 60 years old. Dyspnea, cough and inspiratory crackles were the major symptoms and signs. Two patients were experiencing an exacerbation of dyspnea for one week and half of month, respectively. PaO2 /FiO2 of both patients was less than225 mm Hg. In both patients, high-resolution computed tomography ( HRCT) scans at the exacerbation showed typical signs of IPF including peripheral predominant, basal predominant reticular abnormality, with honeycombing and traction bronchiectasis and bronchiolectasis, and newly developing alveolar opacity. HRCT scan showed peripheral area of ground-glass attenuation adjacent to subpleural honeycombing in one patient, and diffusely distributed ground-glass opacity in another patient. Two patients had received corticosteroid treatment. For one patient, the symptoms improved, and ground-glass attenuation adjacent to subpleural honeycombing had almostly resolved. The other patient died of respiratory failure. Conclusions Some acute exacerbation in idiopatic pulmonary fibrosis can be idiopathic. The clinical presentations mainly include the worsening of dyspnea within short time. HRCT generally demonstrates new bilateral ground-glass abnormality with or without areas of consolidation, superimposed on typical changes of IPF.
After pirfenidone and nintedanib showed efficacy, drug treatment for idiopathic pulmonary fibrosis began to focused on anti-fibrosis. Current research on idiopathic pulmonary fibrosis mainly focus on the pathogenesis and therapeutic targets, and more targeted drugs are gradually entering clinical trials. This article summarizes the results of recent studies on the treatment of idiopathic pulmonary fibrosis with pirfenidone and nintedanib alone or in combination by searching the literature, and reviews the mechanism and test results of the new target anti-fibrosis drugs based on molecular biology that are currently undergoing clinical research in various phases, and aims to provide a basis for how to choose drugs to treat idiopathic pulmonary fibrosis.
美國胸科協會(ATS)和歐洲呼吸學會(ERS)聯合發表的共識中，將特發性肺纖維化(IPF)定義為原因不明并以普通型間質性肺炎(UIP)為特征性病理改變的一種慢性纖維化性間質性肺疾病。在2000年ATS／ERS的IPF共識意見 及2003年中華醫學會呼吸病學分會IPF的診斷和治療指南(草案) 中均推薦的治療方案為糖皮質激素，或與細胞毒制劑(環磷酰胺及硫唑嘌呤)聯合使用。但目前尚缺乏循證醫學證據支持該治療方案能夠提高IPF患者生活質量或生存率 。近年來隨著對IPF的發病機制認識的深入，越來越多的臨床醫師和研究者對IPF患者是否需要用糖皮質激素等藥物的治療提出了質疑。
Objective To clarify the specific clinical predictive efficacy of CT and serological indicators for the progression of connective tissue disease-associated interstitial lung disease (CTD-ILD) to progressive pulmonary fibrosis (PPF). Methods Patients who were diagnosed with CTD-ILD in Chest Hospital of Zhengzhou University Between January 2020 and December 2021 were recruited in the study. Clinical data and high-resolution CT results of the patients were collected. The patients were divided into a stable group and a progressive group (PPF group) based on whether PPF occurred during follow-up. COX proportional hazards regression was used to identify risk factors affecting the progression of CTD-ILD to PPF, and a risk prediction model was established based on the results of the COX regression model. The predictive efficacy of the model was evaluated through internal cross-validation. Results A total of 194 patients diagnosed with CTD-ILD were enrolled based on the inclusion and exclusion criteria. Among them, 34 patients progressed to PPF during treatment, and 160 patients did not progress. The variables obtained at lambda$1se in LASSO regression were ANCA associated vasculitis, lymphocytes, albumin, erythrocyte sedimentation rate, and serum ferritin. Multivariate COX regression analysis showed that the extent of fibrosis, serum ferritin, albumin, and age were independent risk factors for the progression of CTD-ILD to PPF (all P<0.05). A prediction model was established based on the results of the multivariate COX regression analysis. The area under the receiver operator characteristic curve at 6 months, 9 months, and 12 months was 0.989, 0.931, and 0.797, respectively, indicating that the model has good discrimination and sensitivity, and good predictive efficacy. The calibration curve showed a good overlap between predicted and actual values. Conclusions The extent of fibrosis, serum ferritin, albumin, and age are independent risk factors for the progression of CTD-ILD to PPF. The model established based on this and externally validated shows good predictive efficacy.