Defining an exacerbation of pulmonary disease in cystic fibrosis

Despite the importance of pulmonary exacerbations in CF in both clinical and research settings, both published evidence and consensus are lacking concerning the criteria used to define an exacerbation. The use of hospitalization as a surrogate measure presupposes uniformity among clinicians in diagnosis and treatment of exacerbations. Our aims were to evaluate consensus among clinicians about the variables considered helpful in diagnosing an exacerbation requiring treatment. A comprehensive list of symptoms, signs, and investigations used to define exacerbations was compiled from published trials. A written self-administered questionnaire included the list in age-appropriate groups to survey opinion about the helpfulness of each item, and the estimated proportion of patients admitted within a month of diagnosis of an exacerbation. This was sent to all clinicians managing CF patients in Australia. There were replies from 59/91 clinicians (65%), 41/60 (68%) from those managing children and 18/31 (58%) from those managing adults. Responses of those managing children and adults differed for 7/32 variables (Mann-Whitney test, P < 0.05). Clinic grouping did not show greater consensus among responses of pediatricians (Kruskal-Wallis test, P = 0.362). Consensus, >74% or <26% of respondents rating a variable helpful/very helpful, was found in only 50% of variables listed. Estimated admission rate within a month of diagnosis was 61% (30-100%) for those managing adults and 48% %5-100%) for pediatricians. A lack of consensus was found among clinicians managing CF about the variables considered in diagnosing an exacerbation. The estimated proportion admitted within a month of diagnosis was very variable. This demonstrated inhomogeneity in approach to diagnosis and management of an exacerbation suggests a significant heterogeneity of clinical care.     

慢性牙周炎和慢性阻塞性肺疾病急性加重患者血清PCT水平及其与疾病关系探讨

目的 通过比较慢性阻塞性肺疾病急性加重（acute exacerbation of chronic obstructive pulmonary disease,AECOPD）患者和稳定期患者的牙周、肺功能状况及血清降钙素原（serum procalcitonin,PCT）水平,探究AECOPD和牙周炎的内在联系。方法 选择AECOPD、慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）稳定期共90例患者为研究对象,根据患者的牙周炎分期分为8组：AECOPD伴Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期牙周炎和COPD稳定期伴Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期牙周炎。对各组患者的一般信息、牙周袋探诊深度（pocket probing depth,PPD）、临床附着丧失（clinical attachment loss,CAL）、菌斑指数（plaque index,PLI）、龈沟出血指数（sulcus bleeding index,SBI）、第1秒用力呼气容积占用力肺活量百分比（percentage of 1 second expiratory volume to forced vital capacity,FEV1/FVC%）、第1秒用力呼气的容积占预计值的百分比（percentage of the estimated volume of forced exhalation in the first second,FEV1%pred）以及血清降钙素原水平进行统计分析。结果 AECOPD和稳定期患者年龄、性别、BMI、吸烟状况均无统计学意义（P>0.05）;AECOPD患者Ⅲ期、Ⅳ期牙周炎比例明显高于稳定期患者（P＜0.05）;Ⅰ期牙周炎患者中AECOPD组PPD、SBI显著高于稳定期组;Ⅱ期牙周炎患者中AECOPD组PPD、CAL显著高于稳定期组;Ⅲ期牙周炎患者中AECOPD组SBI、CAL显著高于稳定期组;Ⅳ期牙周炎患者中AECOPD组PLI、CAL显著高于稳定期组（P＜0.05）。AECOPD及稳定期患者随着牙周炎严重程度增加,FEV1/FVC%、FEV1%pred依次降低（P＜0.01）。AECOPD组患者血清中不同牙周状况下PCT水平均显著高于稳定期组患者（P＜0.01）;血清中的PCT水平与PPD（r=0.60,P＜0.01）、CAL（r=0.58,P＜0.01）、SBI（r=0.31,P=0.03）成显著正相关,与FEV1/FVC%（r=-0.79,P＜0.01）、FEV1%pred（r=-0.80,P＜0.01）成显著负相关。结论 本研究结果提示牙周炎与AECOPD可能存在相互促进作用,血清PCT可能在一定程度上反映COPD患者牙周炎严重程度及急性加重风险。     

Retinoic acid receptor alpha: One of plasma biomarkers associated with exacerbation of chronic obstructive pulmonary disease

Background: Exacerbation of COPD is a major risk factor for bad prognosis of COPD. A few plasma proteins have been discovered to associate with hospital admission due to exacerbation up to date. We tried to find new plasma biomarkers to predict the exacerbation of COPD. Methods: We examined the plasma of normal control (n = 8) and COPD stable (n = 8) and exacerbation (n = 8) using 2-Dimentional Electrophoresis. The differentially expressed protein spots were identified by MALDI-TOF. ELISA were performed for quantitative measurement of RARα in plasma from normal control (n = 37) and COPD (n = 35). Results: 17 proteins were differentially expressed in plasma between stable and exacerbation state in the subjects with COPD. Identification using MALDI-TOF showed that retinoic acid receptor alpha, ninein, isoform CRA_a, alpha-1 antitrypsin, fibrinogen gamma, tyrosyl-DNA phosphodiesterase 2, and T cell receptor delta chain were increased in exacerbation of COPD, while fibrin beta, Crystal Structure Of An Autoimmune Complex Between A Human Igm RF* And Igg1 Fc, transferrin, serpin peptidase inhibitor member 6, complement factor B preproprotein, Chain B, Crig Bound To C3c, and WD repeat-containing protein 1 isoform 1 were decreased. Quantitative measurement showed that RARα plasma levels significantly increased in exacerbation state compared to stable state of COPD (n = 14). In the plasma of stable state, the COPD subjects (n = 14) having more than 0.4 time/yr of admission had very high levels of RAR alpha protein and those (n = 11) having less than 0.4 times/yr of admission had the intermediate levels compared to those having no exacerbation (n = 10). ROC analysis of RAR alpha levels to frequency of admission showed an area under the curve of 0.844. A cut-off of 0.154 ng/ml of RAR alpha predicted hospital admission with a sensitivity of 71.4% and a specificity of 92.8%. Conclusion: The proteomic analysis of plasma indicates that alteration of several proteins may be associated with admission of COPD. Among them, plasma RAR alpha level may predict hospital admission with a sensitivity of 71.4% and a specificity of 92.8%.     

Asthma prevalence and exacerbations in children: is there an association with childhood vaccination?

Infections and vaccinations may have a potential role in the normal maturation of the immune system, in the development and balance of regulatory pathways, and in the development and exacerbations of asthma. Asthma exacerbations often result from respiratory viral infections, and, while vaccination towards common viral infections may reduce the occurrence of such exacerbations, there has been concern that vaccinations can increase the risk of asthma. Current studies show that childhood vaccines, including inactivated influenza vaccine, are generally safe. However, there is some concern regarding possible exacerbations in infants or children with frequent wheezing or persistent asthma who are given live-attenuated influenza vaccination. Although severe allergic adverse events attributable to vaccination are extremely rare, all serious allergic reactions should be further assessed to detect the likely causative vaccine component, such as egg protein or gelatin. The risks of not vaccinating children far outweigh the risks of allergy and asthma exacerbations. Therefore, childhood vaccination should remain an essential part of child health programs and should not be withheld, even from children with asthma or those predisposed to allergy.     

Effect of Maximal Oxygen Pulse on Patients with Chronic Obstructive Pulmonary Disease

ObjectiveThis study evaluated the effect of maximal oxygen pulse (O₂P_max) on patients with chronic obstructive pulmonary disease (COPD) and confirmed the predictive effect on acute exacerbations of COPD (AECOPD).MethodsThis retrospective study included 91 participants who underwent cardiopulmonary exercise testing (CPET), lung function testing, a dyspnea scale assessment, and a 3-year follow-up. The participants were divided into two groups according to the O₂P_max value. Exercise capacity, ventilatory conditions, gas exchange efficiency, and dyspnea symptoms were compared, and the correlations between O₂P_max and these indices were evaluated. The ability of O₂P_max to predict AECOPD was examined.ResultsExercise capacity, ventilatory conditions, and gas exchange efficiency were lower, and dyspnea symptom scores were higher in the impaired O₂P_max group (P < 0.05). O₂P_max was positively correlated with forced vital capacity (FVC)%, forced expiratory volume in 1 sec (FEV-₁)%, FEV₁/FVC%, anaerobic threshold (AT), work rate (WR)%, aximal oxygen uptake (VO_2max)%, VO₂/kg_max, VO₂/kg_max%, WR_AT, WR_max, VO_2AT, VO_2max, and V_Emax, and was negatively correlated with EqCO_2AT, and EqCO_2max (P < 0.05). Most importantly, O₂P_max could be used to predict AECOPD, and the best cut-off value was 89.5% (area under the curve, 0.739; 95% CI, 0.609–0.869).ConclusionO₂P_max reflected exercise capacity, ventilation capacity, gas exchange capacity, and dyspnea symptoms in patients with COPD and may be an independent predictor of AECOPD.