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Vol.81 No.2

Sinthia Zrinka Bosnic-Anticevich,B.Pharm.(University of Sydney) pp.91-98
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Abstract

When it comes to the use in inhalers in the management of chronic obstructive pulmonary diseases, there are many options, considerations and challenges, which health care professionals need to address. Considerations for prescribing and dispensing, administering and following up, education, and adherence; all of these factors impact on treatment success and all are intrinsically linked to the device selected. This review brings together relevant evidence, real-life data and practice tools to assist health care professionals in making decisions about the use of inhalers in the management of chronic obstructive pulmonary diseases. It covers some of the key technical device issues to be considered, the evidence behind the role of inhalers in disease control, population studies which link behaviors and adherence to inhaler devices as well as practice advice on inhaler technique education and the advantages and disadvantages in selecting different inhaler devices. Finally, a list of key considerations to aid health care providers in successfully managing the use of inhaler devices are summarized.

; ; ; pp.99-105
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Abstract

Acute exacerbation(s) of chronic obstructive pulmonary disease (AECOPD) tend to be critical and debilitating events leading to poorer outcomes in relation to chronic obstructive pulmonary disease (COPD) treatment modalities, and contribute to a higher and earlier mortality rate in COPD patients. Besides pro-active preventative measures intended to obviate acquisition of AECOPD, early recovery from severe AECOPD is an important issue in determining the longterm prognosis of patients diagnosed with COPD. Updated GOLD guidelines and recently published American Thoracic Society/European Respiratory Society clinical recommendations emphasize the importance of use of pharmacologic treatment including bronchodilators, systemic steroids and/or antibiotics. As a non-pharmacologic strategy to combat the effects of AECOPD, noninvasive ventilation (NIV) is recommended as the treatment of choice as this therapy is thought to be most effective in reducing intubation risk in patients diagnosed with AECOPD with acute respiratory failure. Recently, a few adjunctive modalities, including NIV with helmet and helium-oxygen mixture, have been tried in cases of AECOPD with respiratory failure. As yet, insufficient documentation exists to permit recommendation of this therapy without qualification. Although there are too few findings, as yet, to allow for regular andr routine application of those modalities in AECOPD, there is anecdotal evidence to indicate both mechanical and physiological benefits connected with this therapy. High-flow nasal cannula oxygen therapy is another supportive strategy which serves to improve the symptoms of hypoxic respiratory failure. The therapy also produced improvement in ventilatory variables, and it may be successfully applied in cases of hypercapnic respiratory failure. Extracorporeal carbon dioxide removal has been successfully attempted in cases of adult respiratory distress syndrome, with protective hypercapnic ventilatory strategy. Nowadays, it is reported that it was also effective in reducing intubation in AECOPD with hypercapnic respiratory failure. Despite the apparent need for more supporting evidence, efforts to improve efficacy of NIV have continued unabated. It is anticipated that these efforts will, over time, serve toprogressively decrease the risk of intubation and invasive mechanical ventilation in cases of AECOPD with acute respiratory failure.

José M. Porcel(IRBLleida) pp.106-115
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Abstract

Chest tube insertion is a common procedure usually done for the purpose of draining accumulated air or fluid in the pleural cavity. Small-bore chest tubes (≤14F) are generally recommended as the first-line therapy for spontaneous pneumothorax in non-ventilated patients and pleural effusions in general, with the possible exception of hemothoraces and malignant effusions (for which an immediate pleurodesis is planned). Large-bore chest drains may be useful for very large air leaks, as well as post-ineffective trial with small-bore drains. Chest tube insertion should be guided by imaging, either bedside ultrasonography or, less commonly, computed tomography. The so-called trocar technique must be avoided. Instead, blunt dissection (for tubes >24F) or the Seldinger technique should be used. All chest tubes are connected to a drainage system device: flutter valve, underwater seal, electronic systems or, for indwelling pleural catheters (IPC), vacuum bottles. The classic, three-bottle drainage system requires either (external) wall suction or gravity (“water seal”) drainage (the former not being routinely recommended unless the latter is not effective). The optimal timing for tube removal is still a matter of controversy; however, the use of digital drainage systems facilitates informed and prudent decision-making in that area. A drain-clamping test before tube withdrawal is generally not advocated. Pain, drain blockage and accidental dislodgment are common complications of small-bore drains; the most dreaded complications include organ injury, hemothorax, infections, and re-expansion pulmonary edema. IPC represent a firstline palliative therapy of malignant pleural effusions in many centers. The optimal frequency of drainage, for IPC, has not been formally agreed upon or otherwise officially established.

Jinsong Zhang(The 2nd Affiliated Hospital of Kunming Medical University) ; Anastasia Miller(University of Central Florida) ; Yongxia Li(The 2nd Affiliated Hospital of Kunming Medical University) ; Qinqin Lan(University of Central Florida) ; Ning Zhang(Seton Hall University) ; Yanling Chai(The 2nd Affiliated Hospital of Kunming Medical University) ; Bing Hai(The 2nd Affiliated Hospital of Kunming Medical University) pp.116-122
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Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a serious chronic condition with a global impact. Symptoms of COPD include progressive dyspnea, breathlessness, cough, and sputum production, which have a considerable impact on the lives of patients. In addition to the human cost of living with COPD and the resulting death, COPD entails a huge economic burden on the Chinese population, with patients spending up to one-third of the average family income on COPD management in some regions is clinically beneficial to adopt preventable measures via prudent COPD care utilization, monetary costs, and hospitalizations. Methods: Toward this end, this study compared the relative effectiveness of six indices in predicting patient healthcare utilization, cost of care, and patient health outcome. The six assessment systems evaluated included the three multidimensional Body mass index, Obstruction, Dyspnea, Exercise capacity index, Dyspnea, Obstruction, Smoking, Exacerbation (DOSE) index, and COPD Assessment Test index, or the unidimensional measures that best predict the future of patient healthcare utilization, cost of care, and patient health outcome among Chinese COPD patients. Results: Multiple linear regression models were created for each healthcare utilization, cost, and outcome including a single COPD index and the same group of demographic variables for each of the outcomes. Conclusion: We conclude that the DOSE index facilitates the prediction of patient healthcare utilization, disease expenditure, and negative clinical outcomes. Our study indicates that the DOSE index has a potential role beyond clinical predictions.

; ; ; ; ; ; ; ; ; pp.123-131
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Abstract

Background: Chronic obstructive pulmonary disease (COPD) may cause changes in the shape of the thoracic cage by increasing lung volume and hyperinflation. This study investigated changes in thoracic cage dimensions and related factors in patients with COPD. Methods: We enrolled 85 patients with COPD (76 males, 9 females; mean age, 70.6±7.1 years) and 30 normal controls. Thoracic cage dimensions were measured using chest computed tomography at levels 3, 6, and 9 of the thoracic spine. We measured the maximal transverse diameter, mid-sagittal anteroposterior (AP) diameter, and maximal AP diameter of the right and left hemithorax. Results: The average AP diameter was significantly greater in patients with COPD compared with normal controls (13.1±2.8 cm vs. 12.2±1.13 cm, respectively; p=0.001). The ratio of AP/transverse diameter of the thoracic cage was also significantly greater in patients with COPD compared with normal controls (0.66±0.061 vs. 0.61±0.86; p=0.002). In COPD patients, the AP diameter of the thoracic cage was positively correlated with body mass index (BMI) and 6-minute walk test distance (r=0.395, p<0.001 and r=0.238, p=0.028) and negatively correlated with increasing age (r=–0.231, p=0.034). Multiple regression analysis revealed independent correlation only between BMI and increased ratio of AP/transverse diameter of the thoracic cage (p<0.001). Conclusion: Patients with COPD exhibited an increased AP diameter of the thoracic cage compared with normal controls. BMI was associated with increased AP diameter in these patients.

pp.132-137
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Abstract

Background: The pathophysiology of chronic obstructive pulmonary disease (COPD) includes inflammation, oxidative stress, an imbalance of proteases and antiproteases and apoptosis which has been focused on lately. Abnormal apoptotic events have been demonstrated in both epithelial and endothelial cells, as well as in inflammatory cells including neutrophils and lymphocytes in the lungs of COPD patients. An increased propensity of activated T lymphocytes to undergo apoptosis has been observed in the peripheral blood of COPD patients. Therefore, the apoptosis of T lymphocytes without activating them was investigated in this study. Methods: Twelve control subjects, 21 stable COPD patients and 15 exacerbated COPD patients were recruited in the study. The T lymphocytes were isolated from the peripheral blood using magnetically activated cell sorting. Apoptosis of the T lymphocytes was assessed with flow cytometry using Annexin V and 7-aminoactinomycin D. Apoptosis of T lymphocytes at 24 hours after the cell culture was measured so that the T lymphocyte apoptosis among the control and the COPD patients could be compared. Results: Stable COPD patients had increased rates of CD4+ T lymphocyte apoptosis at 24 hours after the cell culture, more than the CD4+ T lymphocyte apoptosis which appeared in the control group, while the COPD patients with acute exacerbation had an amplified response of CD4+ T lymphocyte apoptosis as well as of CD8+ T lymphocyte apoptosis at 24 hours after the cell culture. Conclusion: Stable COPD patients have more apoptosis of CD4+ T lymphocytes, which can be associated with the pathophysiology of COPD in stable conditions.

; ; ; ; pp.138-147
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Abstract

Background: Recent studies show that mitophagy, the autophagy-dependent turnover of mitochondria, mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure and contributes to the development of emphysema in vivo during chronic cigarette smoke (CS) exposure, although the underlying mechanisms remain unclear. Methods: In this study, we investigated the role of mitophagy in the regulation of CSE-exposed lung bronchial epithelial cell (Beas-2B) death. We also investigated the role of a phosphodiesterase 4 inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death. Results: Our results demonstrated that CSE induces mitophagy in Beas-2B cells through mitochondrial dysfunction and increased the expression levels of the mitophagy regulator protein, PTEN-induced putative kinase-1 (PINK1), and the mitochondrial fission protein, dynamin-1-like protein (DRP1). CSE-induced epithelial cell death was significantly increased in Beas-2B cells exposed to CSE but was decreased by small interfering RNA-dependent knockdown of DRP1. Treatment with roflumilast in Beas-2B cells inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting the expression of phospho-DRP1 and -PINK1. Roflumilast protected against cell death and increased cell viability, as determined by the lactate dehydrogenase release test and the MTT assay, respectively, in Beas-2B cells exposed to CSE. Conclusion: These findings suggest that roflumilast plays a protective role in CS-induced mitophagy-dependent cell death.

; ; ; pp.148-155
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Abstract

Background: Although targeted therapy and immuno-oncology have shifted the treatment paradigm for lung cancer, platinum-based combination is still the standard of care for advanced non-small cell lung cancer (NSCLC). Pemetrexed continuation maintenance therapy has been approved and increasingly used for patients with nonsquamous NSCLC. However, the efficacy of this strategy has not been proven in patients without driving mutations. The objective of this study was to compare the clinical benefit of pemetrexed continuation maintenance to conventional platinum-based doublet in epidermal growth factor receptor ( EGFR )‒negative lung adenocarcinoma. Methods: A total of 114 patients with EGFR -negative lung adenocarcinoma who were treated with platinum doublet were retrospectively enrolled. We compared the survival rates between patients received pemetrexed maintenance after four-cycled pemetrexed/cisplatin and those received at least four-cycled platinum doublet without maintenance chemotherapy as a first-line treatment. Results: Forty-one patients received pemetrexed maintenance and 73 received conventional platinum doublet. Median progression-free survival (PFS), which was defined as the time from the day of response evaluation after four cycles of chemotherapy to disease progression or death, was significantly higher in the pemetrexed maintenance group compared to conventional group (5.8 months vs. 2.2 months, p<0.001). Median overall survival showed an increasing trend in the pemetrexed maintenance group (22.3 months vs. 16.1 months, p=0.098). Multivariate analyses showed that pemetrexed maintenance chemotherapy was associated with better PFS (hazard ratio, 0.73; 95% confidence interval, 0.15–0.87). Conclusion: Compared to conventional platinum-based chemotherapy, premetrexed continuation maintenance treatment is associated with better clinical outcome for the patients with EGFR wild-type lung adenocarcinoma.

; ; ; ; ; ; ; pp.156-162
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Abstract

Background: Eosinophilia is well recognized in specific conditions. The objective of the present study was to determine clinico-radiologic characteristics of eosinophilia and changes in prevalence over 10 years in recipients of private health screening program at a tertiary hospital in Korea. Methods: Data of private health screening program recipients at the health promotion center of Chung-Ang University Hospital from 2004 to 2013 were collected. Health-related questionnaires and laboratory findings of private health screening program with possible relation with eosinophilia were reviewed. Results of enzyme-linked immunosorbent assay (ELISA) for parasite, chest computed tomography, and pulmonary function test were also reviewed. Results: The cumulative prevalence of eosinophilia was 4.0% (1,963 of 48,928). Prevalence of eosinophilia showed a decreased trend from 2004 to 2013. Most cases (96.6%) had mild degree of eosinophilia. Eosinophilic subjects were older and male-predominant. They showed lower levels of forced expiratory volume in 1 second (FEV1%), forced vital capacity (FVC%), and FEV1/FVC than those without eosinophilia. Eosinophilic subjects showed higher positive rate for common parasite in ELISA than those without eosinophilia. On radiologic findings, consolidation and ground glass opacities were positively associated with the degree of eosinophilia. When eosinophil was classified based on severity, statistically significant correlation between the severity of eosinophil and radiologic abnormalities was found. Conclusion: Eosinophilia is uncommon in healthy population. It usually occurs at a mild degree. Eosinophilic patients have more radiologic abnormalities compared to those without eosinophilia. Such radiologic abnormalities are associated with the severity of eosinophilia.

Sergio Alejandro Gómez Ochoa(Researcher GERMINA-UIS Group) ; Blanca Beatriz Espín Chico(Escuela Politécnica Superior de Chimborazo) pp.163-165

Tuberculosis & Respiratory Diseases