Pulmonary rehabilitation protocols in urgent lung transplantation patients

BACKGROUND:Prolonged invasive respiratory support and extracorporeal membrane oxygenation(ECMO)in patients requiring urgent lung transplantation(ULTx)present signifi cant challenges to clinical practice due to severe underlying diseases and complex conditions.The aim of the study was to report the clinical outcomes of patients who received ULTx and followed the perioperative rehabilitation protocol implemented in a lung transplant center.METHODS:A retrospective analysis was conducted in ULTx patients who required preoperative invasive mechanical ventilation(IMV)and ECMO between January 2018 and January 2023.Data were retrieved from electronic medical records at our lung transplant center.RESULTS:Fourteen patients(mean age 57.43±10.97 years;12 males,2 females)underwent ULTx with bridging ECMO and IMV.The mean body mass index was 23.94±3.33 kg/m²,and the mean Acute Physiology and Chronic Health Evaluation(APACHE)II score was 21.50±3.96.The Nutritional Risk Screening 2002(NRS 2002)scores were≥3.ULTx was performed after an 8.5-day waiting period(interquartile interval[IQR]5.0-26.5 d).Following the surgeries,the average lengths of ECMO and IMV were 1.0(IQR 1.0-2.0)d and 5.0(IQR 3.0-7.3)d,respectively.The total length of hospital stay was 60.1±30.8 d,with an average intensive care unit stay of 38.3±22.9 d and post-operative hospitalization stay of 45.8±26.1 d.Two patients died within 30 d after ULTx,with a 30-day survival rate of 85.71%.CONCLUSION:Patients receiving ULTx showed an acceptable short-term survival rate,validating the practicality and safety of the treatment protocols implemented in our center.

Drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene a4 hydrolase and blocking LTB4 biosynthesis

OBJECTIVE Leukotriene B4(LTB4)biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury(ALI)or idiopathic pulmonary fibrosis(IPF).To provide a potential strategy for the treatment of ALI or IPF,we identified potent inhibitors of Leukotriene A4 hydrolase(LTA4H),a key enzyme in the biosynthesis of LTB4.METHODS In this study,we identified two known histone deacetylase(HDAC)inhibitors,suberanilohydroxamic acid(SAHA)and its analogue 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide(M344),as effective inhibitors of LTA4H using enzymatic assay,thermofluor assay,and X-ray crystallographic investigation.We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay.A murine experimental model of ALI was induced by lipopolysaccharide(LPS)inhalation.Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA.We next examined m RNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using q RT-PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA.We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin(BLM)-induced IPF model.RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H,significantly decrease LTB4 levels in neutrophil,and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose.CONCLUSION Collectively,SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.

Identification of potential biomarkers for idiopathic pulmonary fibrosis and validation of TDO2 as a potential therapeutic target

BACKGROUND Idiopathic pulmonary fibrosis(IPF)is a progressive interstitial lung disease with a high mortality rate.On this basis,exploring potential therapeutic targets to meet the unmet needs of IPF patients is important.AIM To explore novel hub genes for IPF therapy.METHODS Here,we used public datasets to identify differentially expressed genes between IPF patients and healthy donors.Potential targets were considered based on multiple bioinformatics analyses,especially the correlation between hub genes and carbon monoxide diffusing capacity of carbon monoxide,forced vital capacity,and patient survival rate.The mRNA levels of the hub genes were determined through quantitative real-time polymerase chain reaction.RESULTS We found that TDO2 was upregulated in IPF patients and predicted poor prognosis.Surprisingly,single-cell RNA sequencing data analysis revealed significant enrichment of TDO2 in alveolar fibroblasts,indicating that TDO2 may participate in the regulation of proliferation and survival.Therefore,we verified the upregulated expression of TDO2 in an experimental mouse model of transforming growth factor-β(TGF-β)-induced pulmonary fibrosis.Furthermore,the results showed that a TDO2 inhibitor effectively suppressed TGF-β-induced fibroblast activation.These findings suggest that TDO2 may be a potential target for IPF treatment.Based on transcription factors-microRNA prediction and scRNA-seq analysis,elevated TDO2 promoted the IPF proliferation of fibroblasts and may be involved in the P53 pathway and aggravate ageing and persistent pulmonary fibrosis.CONCLUSION We provided new target genes prediction and proposed blocking TGF-βproduction as a potential treatment for IPF.

Multicenter cooperative observational study of idiopathic pulmonary fibrosis with non-small cell lung cancer

AIM: To research the natural course of idiopathic pulmonary fibrosis(IPF) with advanced non-small cell lung cancer(NSCLC) and the association between acuteMETHODS: From May 2007 through April 2011, 17 CT naive patients with IPF and advanced NSCLC were enrolled. Patients were classified into best supportive care(BSC) group or CT group based on the patient's preference. Patients in the CT group received carboplatin(CBDCA)(AUC 5-6) plus paclitaxel(PTX)(175-200 mg/m2) on day 1 of each 21-d cycle as first-line therapy.RESULTS: All patients but one chose the CT group. In the CT group, the objective response rate was 38%. The most frequent toxicity ≥ grade 3 was neutropenia(88%). Two patients(12.5%) developed AE-IPF. The median progression-free survival, the median survival time and the 1-year survival rate were 4.1 mo, 8.7 mo and 35%, respectively. Second-line CT-related AE and CT-unrelated AE occurred in 2 and 3 patients(1: BSC group; 2: CT group), respectively. Seven(41%) of all patients developed AE-IPF throughout the clinical course, and 6 of 7 patients with AE-IPF died within one month.CONCLUSION: The incidence of AE-IPF was higher among IPF patients with advanced NSCLC than among those without NSCLC. CBDCA plus PTX regimen was tolerable and effective. However, AE-IPF has a fatal toxicity with or without CT in IPF patients with advanced NSCLC.

Risk of Major Hemorrhage in Bilateral Lung Transplantation for Chronic Thromboembolic Pulmonary Hypertension: A Case Report

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the indications for lung transplantation. When patients with CTEPH undergo transplantation, massive bleeding can occur because of severe pleural adhesions and collateral vessels that develop from the thoracic wall to the lungs. However, there has been no previous case report that has discussed the bleeding risk in detail. We report the case of a patient having CTEPH who underwent bilateral lung transplantation with massive blood loss (11,730 mL) in the first operation and required repeat operations for hemostasis. The patient underwent left upper lobectomy because compromised blood flew to the left upper lobe. He recovered from the operations by postoperative day 9;however, he died from pyothorax from an intractable air leak 56 days after transplantation.

Preventive approach against drug-induced pulmonary fibrosis through the suppression of epithelial-mesenchymal transition

A number of drugs induce pulmonary injury and subsequently lead to serious lung diseases such as pulmonary fibrosis as the adverse drug reactions.However,an effective preventive approach against drug-induced pulmonary fibrosis has not been established due to poor understanding of common preventive targets in a variety of drugs showing pulmonary toxicity.Epithelial-mesenchymal transition(EMT),a cellular phenotypic change of the epithelial to mesenchymal state,contributes to the development of pulmonary fibrosis through the conversion of damaged alveolar epithelium into myofibroblasts.As several drugs with pulmonary toxicity have been reported to induce EMT,EMT serves as a bridge between the drugs and pulmonary fibrosis.Accumulated evidence supports the potential of EMT as a preventive target against drug-induced pulmonary fibrosis.Additionally,since there are mechanistic differences between the main pharmacological effect and EMT induced by the drug,prevention based on EMT suppression would be possible and would contribute to continuous clinical treatment with the drug to avoid EMT-mediated serious pulmonary fibrosis.Furthermore,targeting EMT seems to be adequate for exerting a preventive effect since EMT in damaged alveolar epithelial cells occurs prior to the development of the pathophysiological state of the whole lung in a bleomycin-induced lung injury rat model.This viewpoint deals with the benefits and perspectives of preventive approaches against druginduced pulmonary fibrosis through the suppression of EMT,which has rarely been addressed.

A New Variant of Combined Pulmonary Fibrosis and Emphysema from Long-Term High-Dose of Glucocorticoid Therapy: A Case Report

Recent studies have described the combination of both pulmonary emphysema and idiopathic interstitial lung disease (ILDs) by means of high-resolution computed axial tomography (HRCT). Definition of this syndrome was first named by Cottin as combined pulmonary fibrosis and emphysema (CPFE). Functional and radiological findings have showed that these patients are suffering from severe breathlessness, but whose pulmonary functional tests revealed no signs of obstruction, normal static lung volumes, and depressed DLco, most with a history of smoking [1] [2]. The radiological and endoscopic studies especially show that these patients have both areas of upper-lobe predominant emphysema and lesions compatible with fibrosis in both lung bases [3]. No prior research has reported any cases of such condition in person with no prior history of smoking as well as long-term high-dose of glucocorticoid therapy. In this case report, we discuss the presentation, diagnosis, and management of a 53-year-old non-smoker with increasing shortness of breath with a long-term high-dose of glucocorticoid therapy discovered to have an abnormal variant or presentation of CPFE. The cause of disease was attributed to a certain history of smoking in most studies;other potential risk factors have yet to be properly analyzed. This clinical report features a special case about the problem and solution surrounding this issue.

Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis

Background:Critical patients with the coronavirus disease 2019(COVID-19),even those whose nucleic acid test results had turned negative and those receiving maximal medical support,have been noted to progress to irreversible fatal respiratory failure.Lung transplantation(LT)as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.Methods:From February 10 to March 10,2020,three male patients were urgently assessed and listed for transplantation.After conducting a full ethical review and after obtaining assent from the family of the patients,we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.Results:Two of the three recipients survived post-LT and started participating in a rehabilitation program.Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved.The pathological results of the explanted lungs were concordant with the critical clinical manifestation,and provided insight towards better understanding of the disease.Government health affair systems,virology detection tools,and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.Conclusions:LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis.If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT,LT provided the final option for these patients to avoid certain death,with proper protection of transplant surgeons and medical staffs.By ensuring instant seamless care for both patients and medical teams,the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

Idiopathic pulmonary fibrosis will increase the risk of lung cancer

Objective To review the studies investigating the increased risk of lung cancer in patients with idiopathic pulmonary fibrosis （IPF）.Data sources Data cited in this review were obtained mainly from PubMed and Medline from 1999 to 2013 and highly regarded older publications were also included.Study selection We identified,retrieved and reviewed the information on the frequency,risk factors,anatomical features,histological types,clinical manifestations,computed tomography findings and underlying mechanisms of lung cancer in IPF patients.Results The prevalence rates of lung cancer in patients with IPF （4.8％ to 48％） are much higher than patients without IPF （2.0％ to 6.4％）.The risk factors for lung cancer in IPF include smoking,male gender,and age.Lung cancers often occur in the peripheral lung zones where fibrotic changes are predominant.Adenocarcinoma and squamous cell carcinoma are the most common types of lung cancer in patients with IPF.Radiologic features of these patients include peripherally located,ill-defined mass mimicking air-space disease.The underlying mechanisms of the development of lung cancer in patients with IPF have not been fully understood,but may include the inflammatory response,epithelial injury and/or abnormalities,aberrant fibroblast proliferation,epigenetic and genetic changes,reduced cell-to-cell communication,and activation of specific signaling pathways.Conclusions These findings suggest that IPF is associated with increased lung cancer risk.It is necessary to raise the awareness of lung cancer risk in IPF patients among physicians and patients.

Macrophage exosomes transfer angiotensin Ⅱ type 1 receptor to lung fibroblasts mediating bleomycin-induced pulmonary fibrosis

Background:Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis,partially by activating lung fibroblasts.However,how macrophages communicate with lung fibroblasts is largely unexplored.Exosomes can mediate intercellular communication,whereas its role in lung fibrogenesis is unclear.Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis.Methods:In vivo,bleomycin(BLM)-induced lung fibrosis model was established and macrophages infiltration was examined.The effects of GW4869,an exosomes inhibitor,on lung fibrosis were assessed.Moreover,macrophage exosomes were injected into mice to observe its pro-fibrotic effects.In vitro,exosomes derived from angiotensin Ⅱ(Ang Ⅱ)-stimulated macrophages were collected.Then,lung fibroblasts were treated with the exosomes.Twenty-four hours later,protein levels ofα-collagen I,angiotensin Ⅱ type 1 receptor(AT1R),transforming growth factor-β(TGF-β),and phospho-Smad2/3(p-Smad2/3)in lung fibroblasts were examined.The Student's t test or analysis of variance were used for statistical analysis.Results:In vivo,BLM-treated mice showed enhanced infiltration of macrophages,increased fibrotic alterations,and higher levels of Ang Ⅱ and AT1R.GW4869 attenuated BLM-induced pulmonary fibrosis.Mice with exosomes injection showed fibrotic features with higher levels of Ang Ⅱ and AT1R,which was reversed by irbesartan.In vitro,we found that macrophages secreted a great number of exosomes.The exosomes were taken by fibroblasts and resulted in higher levels of AT1R(0.22±0.02 vs.0.07±0.02,t=8.66,P=0.001),TGF-β(0.54±0.05 vs.0.09±0.06,t=10.00,P<0.001),p-Smad2/3(0.58±0.06 vs.0.07±0.03,t=12.86,P<0.001)andα-collagen I(0.27±0.02 vs.0.16±0.01,t=7.01,P=0.002),and increased Ang Ⅱ secretion(62.27±7.32 vs.9.56±1.68,t=12.16,P<0.001).Interestingly,Ang Ⅱ increased the number of macrophage exosomes,and the protein levels of Alix(1.45±0.15 vs.1.00±0.10,t=4.32,P=0.012),AT1R(4.05±0.64 vs.1.00±0.09,t=8.17,P=0.001),and glyceraldehyde-3-phosphate dehydrogenase(2.13±0.36 vs.1.00±0.10,t=5.28,P=0.006)were increased in exosomes secreted by the same number of macrophages,indicating a positive loop between Ang Ⅱ and exosomes production.Conclusions:Exosomes mediate intercellular communication between macrophages and fibroblasts plays an important role in BLM-induced pulmonary fibrosis.

Pulmonary arterial stent for pulmonary trunk stenosis after size-mismatched lung transplantation

To the Editor: Appropriate donor-to-recipient size matching is of crucial importance in lung transplantation. Although tailoring of the lung has been described as a successful means of overcoming size disparities, its merits and demerits remain unclear. Here, we present a case of recurrent hypoxemia after unmatched single lung transplantation.

Pre-Lung transplant reflux testing demonstrates high prevalence of gastroesophageal reflux in cystic fibrosis and reduces chronic rejection risk

BACKGROUND Gastroesophageal reflux(GER)has been associated with poor outcomes after lung transplantation for chronic lung disease,including increased risk of chronic rejection.GER is common in cystic fibrosis(CF),but factors influencing the likelihood of pre-transplant pH testing,and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown.AIM To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF.METHODS This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung transplant.Patients with pretransplant anti-reflux surgery were excluded.Baseline characteristics(age at transplantation,gender,race,body mass index),self-reported GER symptoms prior to transplantation,and pre-transplant cardiopulmonary testing results,were recorded.Reflux testing consisted of either 24-h pH-or combined multichannel intraluminal impedance and pH monitoring.Post-transplant care included a standard immunosuppressive regimen,and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic patients.The primary outcome of chronic lung allograft dysfunction(CLAD)was defined clinically and histologically per International Society of Heart and Lung Transplantation criteria.Statistical analysis was performed with Fisher’s exact test to assess differences between cohorts,and time-to-event Cox proportional hazards modeling.RESULTS After applying inclusion and exclusion criteria,a total of 60 patients were included in the study.Among all CF patients,41(68.3%)completed reflux monitoring as part of pre-lung transplant evaluation.Objective evidence of pathologic reflux,defined as acid exposure time>4%,was found in 24 subjects,representing 58%of the tested group.CF patients with pre-transplant reflux testing were older(35.8 vs 30.1 years,P=0.01)and more commonly reported typical esophageal reflux symptoms(53.7%vs 26.3%,P=0.06)compared to those without reflux testing.Other patient demographics and baseline cardiopulmonary function did not significantly differ between CF subjects with and without pre-transplant reflux testing.Patients with CF were less likely to undergo pre-transplant reflux testing compared to other pulmonary diagnoses(68%vs 85%,P=0.003).There was a decreased risk of CLAD in patients with CF who underwent reflux testing compared to those who did not,after controlling for confounders(Cox Hazard Ratio 0.26;95%CI:0.08-0.92).CONCLUSION Pre-transplant reflux testing revealed high prevalence of pathologic reflux in CF patients and was associated with decreased risk of CLAD.Systematic reflux testing may enhance outcomes in this patient population.

Single-lung transplantation for pulmonary alveolar microlithiasis: A case report

BACKGROUND Pulmonary alveolar microlithiasis(PAM)is a rare idiopathic lung disease characterized by the accumulation of innumerable microliths.Currently,effective therapeutics for PAM are not available,and the only treatment for end-stage lung disease is lung transplantation(LuTx).Further,there are few reports that focus on LuTx for the treatment of PAM,and the follow-up reports of postoperative imaging are even rarer.CASE SUMMARY A 52-year-old man presented to Shanghai Pulmonary Hospital in 2017 after experiencing shortness of breath and exacerbation.The patient was diagnosed with PAM and referred for single-LuTx(SLuTx)on March 14,2018.Preoperative imaging results from a chest X-ray demonstrated bilateral,diffuse,symmetrical,sandstorm-like radiopaque micronodules,and pneumothorax and a computed tomography scan revealed minute,calcified military nodules in both lungs.We performed a left SLuTx,and intraoperative pathology was consistent with PAM.One week after surgery,a chest X-ray revealed slight exudation of the left lung,and one month later,the left transplanted lung exhibited good dilation,mild pulmonary perfusion injury with local infection,and left pleural effusion.Fiberoptic bronchoscopy revealed left hyperplastic granulation at the left bronchial anastomosis.Multiple sputum cultures suggested the presence of Klebsiella pneumoniae and Acinetobacter baumannii.The last follow-up was conducted in April 2019;the patient recovered well.CONCLUSION This case presents the imaging findings of a patient with PAM before and after LuTx and confirms the effectiveness of LuTx for the treatment of this disease.

Genetic characterization of a Chinese family with familial idiopathic pulmonary fibrosis

Background Idiopathic pulmonary fibrosis （IPF） is a chronic inflammatory interstitial lung disease with an unknown cause. Recent studies have shown that genetic factors play an important role in the pathogenesis of IPF. Methods To explore the genetic background of patients with IPF, a candidate gene approach was employed to screen for mutations in seven genes among members with familial IPF in mainland of China. Results Within six of the candidate genes, a total of 31 point mutations were identified. Among the missense mutations, the SFTPA1 exon 6 CAG〉AAG （GIn238Lys） and SFTPB exon 2 CAC〉CCC （His2Pro） mutations caused changes in the physical and chemical properties of amino acids. Each sequence alteration was identified in sporadic IPF patients, control specimens （pneumonia patients and healthy persons）. Genotype frequencies and allele frequencies of codon 238 in exon 6 of SFTPA1 were noted significantly higher in patients with IPF than those in other two control subjects. The computational protein structure prediction by protein homology modeling confirmed differences in three-dimensional structure between mutant SFTPA1 and original SFTPAI. Conclusions Although the functions of the mutant candidate genes vary, these genes may ultimately result in damage to alveolar epithelial cells, initiating the progress of pulmonary fibrosis. In particular, while pathophysiological mechanisms need to be illustrated, the GIn238Lys missense variant of exon 6 in the SFTPA1 may have potential susceptibility in the development of IPF, which was shown in patients with sporadic IPF with a statistically higher frequency.

Acute exacerbation of interstitial lung disease in the intensive care unit:Principles of diagnostic evaluation and management

Interstitial lung disease(ILD)is typically managed on an outpatient basis.Critical care physicians manage patients with ILD in the setting of an acute exacerbation(ILD flare)causing severe hypoxia.The principles of management of acute exacerbation of ILD are different from those used to manage patients with acute respiratory distress syndrome from sepsis,etc.Selected patients may be candidates for aggressive measures like extracorporeal membrane oxygenation and lung transplantation,while almost all patients will benefit from early palliative care.This review focused on the types of ILD,diagnosis,and management pathways for this challenging condition.

巨噬细胞向肌成纤维细胞转化促进LPS诱导的急性肺损伤模型小鼠肺纤维化

目的探讨巨噬细胞向肌成纤维细胞转化(MMT)在脂多糖(LPS)诱导的急性肺损伤小鼠肺纤维化过程中的作用。方法将21只小鼠分为7组:对照组、不同时间点LPS诱导小鼠早期肺纤维化(LPS-PF)模型组和不同时间点氯磷酸二钠脂质体(CL-LIP)干预组(n=3)。用HE、Masson染色评估各组肺纤维化程度;用免疫荧光检测MMT过程中CD68和α-平滑肌动蛋白(α-SMA)共标记阳性细胞数量。骨髓来源巨噬细胞(BMDMs)分为对照(Ctrl)组和转化生长因子-β1(TGF-β1)刺激组(n=3);用RT-qPCR检测各组α-SMA、纤连蛋白(FN)、人I型胶原蛋白(Col1)表达水平。用Western blot检测各组间α-SMA以及Smad同源物3(Smad3)、磷酸化的Smad3(p-Smad3)蛋白表达量。结果LPS-PF模型小鼠肺组织第7天Ashcroft评分较对照(Ctrl)组显著增高(P<0.01);但在CL-LIP组中肺纤维化程度较LPS-PF组明显减轻(P<0.05)。肺组织免疫荧光染色发现,CL-LIP组CD68α-SMA共标记阳性细胞数较LPS-PF组对应时间点明显减少(P<0.01)。体外实验中,TGF-β1刺激组48 h、96 h后α-SMA、FN、Col1较对应时间点表达量明显增加(P<0.01)。检测体内、体外实验中Smad3、p-Smad3的蛋白表达量,发现LPS-PF组(第7天、第10天)和TGF-β1刺激组(48 h和96 h)均较各自对照(Ctrl)组明显增加(P<0.01)。结论MMT具有促进LPS诱导模型小鼠肺纤维化的作用,其转化过程可能经Smad3调节。

王书臣教授辨证治疗肺痿经验

特发性肺间质纤维化(Idiopathic pulmonary fibrosis, IPF)已成为国际化难题,患者多病情进展迅速、生活质量低下、生存期短,单用西医激素和免疫抑制剂或细胞因子抑制剂治疗,难以延缓或逆转肺纤维化的进展,同时诸多药物反应限制其应用。通过中医辨证论治结合现代中药药理,王书臣教授对特发性肺间质纤维化的中医病名、病因病机及治疗原则形成了自己独特的见解,认为重症患者当以“肺痿”命名更佳,提出“治肺痿如治中风”“治肺痿当祛风”“治痿当兼顾脾胃”“肺肾同治”等观点,临床中用于患者治疗,疗效确切,为提高患者生活质量提供了宝贵经验。

CTD-ILD合并肺部感染患者肺部微生物菌群特点及对肺纤维化的影响

目的探讨结缔组织病相关间质性肺疾病(CTD-ILD)合并肺部感染患者肺部微生物菌群特点及对肺纤维化的影响。方法选取2021年2月至2022年5月在医院治疗的45例CTD-ILD合并肺部感染患者作为观察组,同时选取45例CTD-ILD未合并肺部感染患者作为对照组,比较两组肺功能、高分辨CT(HRCT)肺纤维化评分,同时分析观察组病原菌分布情况。结果观察组用力肺活量占预计值百分比(FVC%pred)、第1秒用力呼气容积占预计值百分比(FEV 1%pred)、一氧化碳弥散量占预计值百分比(DLCO%pred)、用力肺活量(FVC)、最大呼气流量(MEF)和残气容积(RV)低于对照组(P<0.05);观察组HRCT影像学斑片状、支气管扩张比率高于对照组(P<0.05),CT纤维化评分高于对照组(P<0.05)。观察组病原菌分布:细菌分布中以肺炎克雷伯菌、铜绿假单胞菌为主,分别占24.44%和15.56%,病毒检出巨细胞病毒、人类疱疹病毒,分别占11.11%和6.67%,真菌检出白念珠菌,占11.11%。观察组年龄≥60岁患者CT纤维化评分高于年龄<60岁患者(P<0.05)。结论CTD-ILD合并肺部感染患者以细菌感染为主;相比较未合并肺部感染患者,合并肺部感染患者肺纤维化较重。

活血通络汤治疗类风湿关节炎致肺间质纤维化的疗效观察

目的探讨活血通络汤治疗类风湿关节炎(rheumatoid arthritis,RA)致肺间质纤维化的疗效及对患者肺功能和疾病相关指标的影响。方法采用随机数字表法将于2019年12月—2022年3月在汉中市人民医院接受治疗的126例RA致肺间质纤维化患者分为A组和B组,各63例。A组给予强的松,B组在A组基础上给予活血通络汤。两组疗程均为3个月。比较两组治疗3个月后的临床疗效,治疗前、治疗3个月后的临床症状和体征改善情况、肺功能及血清细胞因子,治疗期间的安全性。结果B组和A组治疗3个月后的总有效率分别为87.30%(55/63)、69.84%(44/63),与A组相比,B组较高,差异有统计学意义(P<0.05)。两组治疗3个月后的关节肿胀指数、关节压痛指数、关节功能障碍指数、血清C反应蛋白(C-reactive protein,CRP)、白细胞介素-1β(interleukin-1β,IL-1β)、类风湿因子(rheumatoid factor,RF)、转化生长因子-β(transforming growth factor-β,TGF-β)水平均比治疗前低,且与A组相比,B组较低;两组晨僵时间均比治疗前短,且与A组相比,B组较短;两组第1秒用力呼气容积(forced expiratory volume in one second,FEV1)、用力肺活量(forced vital capacity,FVC)、肺总量及弥散量均比治疗前高,且与A组相比,B组较高,差异有统计学意义(P<0.05)。B组和A组治疗期间的不良反应发生率比较,差异无统计学意义[7.94%(5/63)vs 12.70%(8/63),P>0.05]。结论活血通络汤可有效缓解RA致肺间质纤维化临床症状,减轻患者炎症反应,抑制肺成纤维细胞增殖,进一步改善患者肺功能,进而提高治疗效果,且安全性良好。

从肺脑共病生物学基础探讨中医“肺藏魄”理论

中医“肺藏魄”指人的本能和动作以及某些自身感觉与肺密切相关。中医学将神按照五行归类分为魂、神、意、魄、志。魄在精神活动中负责感觉和支配动作,魄是指先天所具有的本能反应、知觉与动作,如与耳朵相关的听觉,与眼睛相关的视觉,以及皮肤的痛痒皆属“魄”的范畴,人的自我感觉以及本能动作与精气盛衰密切相关。脑是人体生命活动的主宰,是人体生命活动的中枢,对于维持人体生命活动起到重要作用,五脏所藏认为五脏与人的精神、情志、意识、思维活动之间存在密切的关系,并且也都在脑的主宰下进行活动以及发挥相关作用,肺与脑二者在中医方面有紧密联系。“肺藏魄”对于人体的日常生命活动起到了重要作用。而现代医学研究证实,一些肺部感染性疾病除了能导致肺部的炎症以外,还会引起全身性的炎症反应,出现肺部以外器官相关功能的损害,肺与脑之间的关系复杂,这些研究进一步论证了肺与脑之间的相关性。该文从肺脑共病生物学基础的角度来探讨中医的“肺藏魄”相关理论,为中医治疗肺脑相关疾病提供相关参考。