Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality all over the world. Acute exacerbation of COPD (AECOPD) not only accelerates the progression of disease, but also causes hospital administration and death events. Epidemiologic studies have shown air pollution is a high risk factor of AECOPD. However, there are rare technics or treatment strategies recommended to reduce severe air pollution related AECOPD. This is a multi-center, prospective, randomized and standard treatment parallel control clinical trial. Seven hundred sixty-four stable COPD patients in group B, C and D according to GOLD 2017 will be recruited and equally divided into two parallel groups, salvational intervention (SI group) and control group (CT group). Original treatments for participants include tiotropium (18μg once q.d), budesonide/formoterol (160μg/4.5μg once or twice b.i.d) or budesonide/formoterol (160μg/4.5μg once or twice b.i.d) with tiotropium (18μg once q.d). The savational intervention for SI group is routine treatment plus budesonide/formoterol (160μg/4.5μg once b.i.d) from the first day after severe air pollution (air quality index, AQI ≥200) to the third day after AQI < 200. CT group will maintain the original treatment. The intervention will last for 2 years. Primary outcome is the frequency of AECOPD per year and the secondary outcomes include the incidence of unplanned outpatient visits, emergency visits, hospitalization, medical cost and mortality associated with AECOPD per year. The salvational intervention is a novel strategy for COPD management under severe air pollution. Results of the present study will provide reference information to guide clinical practice in reducing the air pollution related exacerbation of COPD. This study has been registered at www.ClinicalTrials.gov (registration identifier: NCT03083067 ) in 17 March, 2017.
Abstract Background Primary care plays an important role in the management of respiratory diseases and primary care physicians’ ability is the cornerstone. Methods An e-questionnaire was distributed to attendees of respiratory diseases academic conferences in China from July, 2017 to December, 2018 to assess primary care physicians’ knowledge level of asthma, CAP, COPD and influenza in China. Results The feedback rate was 100%, including 4815 valid questionnaires, 3802 (79.0%) from community hospitals and 1013 (21.0%) from township hospitals. The average score of the questionnaire was 83.31(± 20.397) and 72.12(± 20.898) in township and community hospitals ( P ༜0.05), respectively. 61.4%, 48.7% and 42.5% of the primary care physicians were aware of clinical manifestations of COPD, asthma and simple influenza. 85.7%, 8.1%, 16.1% and 1.0% knew how to diagnose COPD, asthma, CAP and influenza, respectively. 94.4% of the physicians didn’t know bronchodilators for COPD; 53.7% knew non-pharmacological treatments for COPD. 73.6% were unable to deal with asthma attacks. 65.1% didn’t know what the most essential and important treatment for influenza was. 92% physicians didn’t know the management for stable COPD; 3.0% knew all prevention and management measures for asthma. 37.9% knew all the preventive measures for CAP. 44.9% didn’t know the important role of influenza vaccine in preventing influenza and its complications. Conclusions Primary care physicians in China had a poor knowledge on asthma, CAP, COPD and influenza, but township hospitals physicians had a better knowledge than community hospitals physicians.
Objective
To investigate the association of single nucleotide polymorphisms (SNP) in PDE4D gene with COPD.
Methods
Seventy-one COPD patients and 65 control patients of a community in Beijing, aged 40-80 years, were enrolled in the study.Eight SNPs in PDE4D gene were selected SNP1=rs11740402, SNP2=rs17528473, SNP3=rs17780213, SNP4=rs1529843, SNP5=rs11743928, SNP6=rs26956, SNP7=rs35387, SNP8=rs35386.DNA specimens were all extracted from frozen blood and primers of two ends were designed to amplify their unique targets under a defined set of reaction conditions.Genotyping was done by Sanger sequencing.The difference of genotype and the variation of allele frequencies were analyzed by Chi-square test.Association between SNPs and COPD was examined by unconditioned logistic regression analysis.
Results
The polymorphisms of the 8 SNPs in COPD and control patients were all on Hardy-Weinberg balance.The Linkage Disequilibrium analysis revealed a genetic disequilibrium at SNP1 and SNP2, which made LD block 1, and the other genetic disequilibrium at SNP6, SNP7 and SNP8, which made LD block 2.The genotype of SNP5 was A/A in all the patients of the two groups.There was no difference in haplotypes and the frequencies of alleles in the 8 SNPs between the two groups.However, significant difference between the two groups was found at SNP8 (P<0.05) in the analysis of genotype frequencies.In further unconditional logistic regression analysis, SNP8 showed significant difference in Ressessive model (P<0.05, OR=4.07, 95%CI=1.26-13.18) and the frequency of genotype G/G was 20.3% and 6.3% in COPD and control group respectively.
Conclusions
It was suggested that genetic variants of PDE4D gene might be associated with COPD in the Chinese population.
Key words:
Chronic obstructive pulmonary disease; Gene; Single nucleotide polymorphisms; Phosphodiesterase
A 75-year-old Han Chinese man presented with a 1-day history of acute shortness of breath. His medical history included lung adenocarcinoma, hepatitis B virus (carrier), hypertension, previous deep vein thrombosis (DVT), smoking for 45 years, and drinking for 35 years. He underwent dissection of his right upper and middle lobes and mediastinal lymph nodes 5 years previously and developed pleural and multiple pulmonary metastasis 3 months postoperatively. Molecular tests for epidermal growth factor receptor, KRAS, and anaplastic lymphoma kinase rearrangement were negative. He received 33 cycles of chemotherapy and 2 sessions of radiotherapy for lung metastases. However, he still developed bilateral lung metastases and multiple thoracic and lumbar vertebral metastases. Six weeks before the current presentation, he received nivolumab (3 mg/kg every 2 weeks, three cycles). Physical examination revealed 92% oxygen saturation on room air, clubbed fingers, rales in the right lower lung, a higher second sound in the pulmonary than aortic area, and symmetrical edema of the lower limbs. Laboratory tests demonstrated a D-dimer level of 18.9 mg/L (normal, <0.24 mg/L), brain natriuretic protein level of 343 pg/ml (normal, <100 pg/ml), and cardiac troponin I level of 0.113 ng/ml (normal, <0.03 ng/ml). Platelet aggregation tests showed an increased adenosine diphosphate level of 75.36% (normal, 42–68%), Col level of 77.1% (normal, 56–75%), and Ris level of 85.9% (normal, 58–76%). Arterial blood gas analysis showed a pH of 7.405, PaCO2 of 37.3 mmHg (1 mmHg = 0.133 kPa), and PaO2 of 75.8 mmHg while breathing 5 L/min of oxygen by nasal cannula. Computed tomography pulmonary angiography (CTPA) showed pulmonary artery emboli at multiple left segments and right anterior basal segments [Figure 1]. Doppler ultrasound showed right popliteal vein thrombosis and left lower-limb calf vein thrombosis. Echocardiography showed an enlarged right atrium and right ventricle, and the systolic pulmonary artery pressure was 63 mmHg. Intravenous infusion of 50 mg of recombinant tissue plasminogen activator (rt-PA) followed by low-molecular-weight heparin was administered. The patient's dyspnea was significantly improved 8 h after treatment.Figure 1: Chest computed tomography. (a and b) Pulmonary embolism (arrow) and metastasis (triangle) on the day of admission. (c) New bilateral infiltration and ground-glass attenuations on day 8 after admission. (d) The infiltration resolved 2 weeks after methylprednisolone treatment.From days 5–7, the patient developed increasingly worsening respiratory distress. Repeat CTPA [Figure 1] on day 7 showed extensive bilateral infiltration and ground-glass attenuations, the pulmonary artery thrombosis had been significantly absorbed. Laboratory tests demonstrated a white blood cell count of 12,500/ml with 89.1% neutrophils and 3.2% lymphocytes, a C-reactive protein level of 303.8 mg/L (normal, <3 mg/L), and lactate dehydrogenase level of 306 U/L (normal, 100–240 U/L). Piperacillin/sulbactam was initiated on day 8. Sputum smears and culture revealed no microorganisms. Cytomegalovirus DNA and Epstein–Barr virus DNA in the blood were negative, and the procalcitonin level was <0.25 ng/ml. The patient was diagnosed with acute respiratory distress syndrome (ARDS) secondary to nivolumab treatment (Grade 4). Intravenous high-dose methylprednisolone (mPSL) therapy (160 mg/d for 1 day, 200 mg/d for 2 days) and gamma globulin therapy (20 g/d for 3 days) were initiated. Three days later, his respiratory status began to improve. The mPSL was continued for 4 days (120 mg/d for 1 day, 80 mg/d for 3 days), and oral prednisolone was begun at a dose of 1 mg·kg−1·d−1 and gradually tapered. Chest CT showed that the infiltration had absorbed 2 weeks after treatment [Figure 1]. He was discharged 2 months after admission. Drug-related pneumonitis is a rare but clinically serious and potentially life-threatening adverse reaction to programmed cell death 1 (PD-1) inhibitors. In one study, the incidence of all-grade pneumonitis was 2.7% (95% confidence interval [CI], 1.9–3.6%) and that of Grade 3–4 pneumonitis was 0.8% (95% CI, 0.4–1.2%). The incidence of all-grade pneumonitis (4.1% vs. 1.6%) and Grade ≥3 pneumonitis (1.8% vs. 0.2%) was higher in patients with nonsmall cell lung carcinoma than those of melanoma.[1] The median time from therapy initiation to pneumonitis was 2.6 months. The most common radiographic pattern was cryptogenic-organizing pneumonia, acute interstitial pneumonia(AIP)/ARDS represents the pattern of Grade 3-4 pneumonitis.[2] Our patient developed Grade 4 pneumonitis 6 weeks after nivolumab treatment, and the radiographic pattern was AIP/ARDS. Management guidelines for immune-mediated adverse reactions include discontinuation of nivolumab, with the addition of corticosteroids and immunosuppressants (infliximab, cyclophosphamide, intravenous immunoglobulin, or mycophenolate mofetil) in patients with Grade 3 or 4 pneumonitis. Our patient's respiratory status improved within 3 days of receiving high-dose corticosteroid and immunoglobulin therapy; therefore, we did not administer other immunosuppressants. Nishino et al. reported two patients with Grade 3 pneumonitis with melanoma who had received nivolumab. Both patients received glucocorticoids, infliximab, and antibiotic agents. One patient required intubation and improved over the course of 10 weeks, and the other died 4 weeks after diagnosis.[3] Watanabe et al. recently reported nivolumab-induced Grade 4 pneumonitis in a patient with melanoma. The patient continued to worsen for 3 days after mPSL pulse therapy, and cyclophosphamide with repeat mPSL pulse therapy resolved her condition.[4] Our patient had multiple risk factors for venous thromboembolism (VTE), including end-stage lung cancer, metastasis, hypertension, old age, increased platelet aggregation, and previous DVT. A recent large cohort study in Europe showed that people with lung cancer had a 3.92% overall incidence of VTE, and independent factors associated with VTE were metastatic disease, the adenocarcinoma subtype, chemotherapy, and diagnosis via emergency hospital admission.[5] Therefore, the acute pulmonary embolism probably resulted from the primary disease (lung cancer with widespread metastasis); whether it can be an adverse effect of nivolumab requires further observation. In summary, we have described a patient who developed late-onset Grade 4 pneumonitis after nivolumab treatment accompanied by acute pulmonary embolism; rt-PA, high-dose corticosteroid therapy, and intravenous immunoglobulin therapy were lifesaving. The association between VTE and PD-1 inhibitors requires further investigation. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
China has a huge population with respiratory diseases, these diseases should be managed well in primary care, however, primary care physicians' knowledge level of these diseases were unknown. The aim of the study was to assess primary care physicians' knowledge of asthma, CAP, COPD, and influenza in China. An e-questionnaire was distributed to attendees of respiratory diseases academic conferences in China from July, 2017 to December, 2018. 7391 questionnaires were returned and 4815 valid questionnaires were analyzed, 3802 (79.0%) from community health service centers and 1013 (21.0%) from township hospitals. The average score of the questionnaire was 83.3 (±20.397) and 72.1 (±20.898) in township and community hospitals, respectively (P < 0.05). 61.4%, 48.7%, and 42.5% of the primary care physicians were aware of clinical manifestations of COPD, asthma, and simple influenza. 85.7%, 8.1%, 16.1%, and 1.0% knew how to diagnose COPD, asthma, CAP and influenza, respectively. 94.4% of the physicians lacked the knowledge of treating COPD with bronchodilators; 53.7% knew non-pharmacological treatments for COPD. 73.6% were unable to deal with asthma attacks. 65.1% did not know what the most essential and important treatment for influenza was. 92% of physicians did not know the management for stable COPD; 3.0% knew all prevention and management measures for asthma. 37.9% knew all the preventive measures for CAP. 44.9% did not know the important role of influenza vaccine in preventing influenza and its complications. Primary care physicians in China had a poor knowledge of CAP, asthma, Influenza, COPD. There is a need for improved training of common respiratory diseases.
Background: There are no relevant studies on whether hsCRP can be a predictor of FEV1%pred. The study was to assess the association of hsCRP with FEV1%pred in a middle-aged and elderly population without underlying lung disease.Methods: Data for this study were obtained from a prospective cohort study of 1047 middle-aged and elderly citizens aged 40-75 years with FEV1/FVC >70% after inhaled bronchodilators in Beijing without any evidence of underlying lung diseases. The baseline analysis of the subjects from May 30, 2018, to October 31, 2018. The nonlinear correlation of hsCRP with FEV1/FEV6 and FEV1%pred was explored by Restricted cubic spline regression, and multivariate linear regression models was used to assesse the linear association of hsCRP with FEV1/FEV6 and FEV1%pred.Findings: 851 subjects acquired hsCRP value except 196 subjects (18.7%) for missing data. hsCRP measurements defined as normal range were available for 713 (83.8%). A non-linear association was found between hsCRP in the normal range and FEV1/FEV6. hsCRP was linearly and negatively correlated with FEV1%pred, and each 1 SD increase in hsCRP was significantly associated with a exp (2.4% ) decrease in FEV1%pred. In the male and female subgroups, the values of the effect of CRP on FEV1/FEV6 changes were 0.2% and 1.2%, respectively, with significantly higher FEV1/FEV6 changes in women than in men (P=0.011 for interaction).Interpertation: In those with normal hsCRP, hsCRP had a nonlinear association with FEV1/FEV6 and a linear negative association with FEV1%pred. Our study implies that hsCRP can be used to predict FEV1%pred, which can be used to predict the development of COPD. hsCRP has a greater effect on lung function in women relative to men.Trial Registration Details: This study has been registered at www.ClinicalTrials.gov (registration identifier: NCT03532893) on 21 May 2018, https://register.clinicaltrials.gov.Funding Information: The work is supported by the grants fromNational Key Research and Development Plan (No.2017YFC1309500) and Beijing Health Technologies Promotion Program (BHTPP202053).Declaration of Interests: None of the authors have conflicts of interest to disclose. None of the authors have financial relationships relevant to this article to disclose.Ethics Approval Statement: Community residents in Beijing were recruited with incidental sampling by the community health service center as the protocol published. Ethical approval was obtained from the Biomedical Research Ethics Committee of Peking University First Hospital. The cross-sectional questionnaire, lung function tests and laboratory data were collected by the medical staff of the Department of Respiratory Medicine at Peking University First Hospital and the local community health center. Informed consent was acquired from the participants before enrollement.
AbstractEpidemiologic studies have reported the association between fine particles (aerodynamic diameter ≤ 2.5 μm; PM2.5) and health effects, but the immunological mechanisms are not clear. To investigate the dose and time-dependent role of toll-like receptor (TLR) and Th1/Th2 shift in local and systemic inflammation induced by PM2.5, mice were subjected to intratracheal instillation of 2.5, 5, or 10 mg/kg PM2.5 in this study. After 24 h, 72 h, 7 days, and 14 days, mice were sacrificed to measure TLR2 and TLR4 expressions and Th1/Th2 related cytokines in bronchoalveolar lavage fluid (BALF) and peripheral blood. Histopathological changes in lung were also examined. Inflammatory infiltration and macrophages with engulfed particles were found by lung histopathology after PM2.5 exposure. TLR4 positive cells decreased in BALF but increased in blood at 24 h after the exposure. The low percentage of TLR4 positive cells continued to day 14 in BALF, but recovered at day 7 and decreased further to lower than the control value at day 14 in blood. TLR2 positive cell changed similar to TLR4 in BALF on the dose effects. In BALF at 24 h after the exposure, the Th2 related cytokines IL-5 and IL-10 increased dose-dependently; and in blood, the Th2 related cytokines IL-4, IL-5, and IL-10 also increased. These results suggest that acute exposure of PM2.5 leads to acute inflammatory responses locally and systemically in mice. TLR2 and TLR4 are involved in this process and PM2.5 can drive a Th2-biased immune response.Keywords:: Inflammationparticulate matterPM2.5Th1/Th2 shifttoll-like receptorView correction statement:Correction to: Involvement of TLR2 and TLR4 and Th1/Th2 shift in inflammatory responses induced by fine ambient particulate matter in mice AcknowledgmentsWe thank our colleagues who contributed to this study. We appreciate the assistance of Central Laboratory, Laboratory of Electron Microscopy and Animal Facilities of Peking University First Hospital.Declaration of interestThis work was supported by a grant from the Natural Science Foundation of China (80170006). The authors report no conflicts of interest.
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