Cardiac MDCT requires contrast media to discriminate the ventricular cavity, and its temporal resolution is inferior to either electron beam CT or MRI. 27 Ritchie et al. 28 reported that a temporal resolution of about 20 milliseconds is needed to completely avoid any motion artifact incardiac imaging by CT. Thus, the limited temporal resolution used in our study may have been insufficient to acquire precise end systolic volume. Furthermore, in COPD patients, dyspnea often limits breath-holding for more than 10 seconds, and stair step artifact can affect ventricular function evaluation. It is hoped that, with technological developments, image quality will further improve and imaging time will be shortened. Another limitation is radiation exposure. Total radiation dose was calculated to be approximately 4 to 6 mSv depending on scan range and patient's body weight.
In the primary meta-analysis of CB COPD relative to smoking controls, we found the strongest signal within FAM13A rather than the other known COPD suscepti- bility genes, and permutation testing confirmed that ORs of FAM13A SNPs were significantly higher than those for non-CB COPD. While COPD is a complex disease with marked phenotypic heterogeneity, most previous genetic studies have dealt with COPD sub- jects as one homogeneous group [20-22]. The current study suggests that previously identified COPD risk al- leles might have different effects on the development of different COPD subtypes.
tomatic patients who could not tolerate a washout period of 2 weeks before enrollment. Consequently, only 2% of GOLD stage IV patients were included in the study. This difference in sub- jects’ inclusion may affect the characteristics of the study popu- lation which were different to that of the other studies. Although it was not statistically significant, it had a weak trend that the known risk factors be positive predictors to future exacerbation in our result. We believe that our findings would be more sig- nificant if such patients had been included in our study. Fourth, responder group included more current smokers than nonre- sponder group. We analyzed multivariate model including smok- ing history. It was not a significant risk factor for acute exacer- bation. In recent studies, it is controversial whether current smo- king is a risk factor for exacerbation or not (7, 24, 25). Fifth, the enrolled COPD patients were consistently confirmed the air- flow limitation on the registration and the 3-month follow up.
Peer Reviewers’ Commentary
본 논문은 전 세계적으로 높은 유병률과 사망률을 보이는 만성 폐쇄질환(chronicobstructivepulmonarydisease, COPD)의 가 장 중심적인 흡입치료의 최신지견에 대해 기술한 논문이다. 우 리나라의 COPD 진료지침의 약물치료 소개와 보험 기준 및 장단 점을 기술하였다. 국내에서 흡입치료제의 사용의 증가 및 폐기능 검사의 활성화가 중요한 시점에서 COPD를 진단, 치료하는 의사 들에게 적절한 정보를 제공하였다는 점에서 의의가 있는 논문이 라 판단된다.
노모그램은 질병의 위험 요인과 예측 확률을 쉽게 이해할 수 있도록 시각적으로 표현하는 통계적 도구이다. 본 논 문은 만성 폐쇄성 폐질환(chronicobstructivepulmonarydisease)의 위험 요인을 이용하여 로지스틱 회귀모형과 순수 베이지안 분류기 모형의 노모그램을 구축하고 이를 비교하였다. 분석 데이터는 국민건강영양조사 6기(2013–
The present study has several limitations. First, this study was performed only in an university hospital and was not a multicenter study. However, the study hospital was an average university hospital located in a city. Therefore, the characteristics of the study population might be similar to that in other urban hospitals. Second, some important factors affecting the development of malignant potential, such as alcohol history, family history of colon cancer, other gastro- intestinal diseases, and use of NSAIDs, were not collected due to the limitations of a retrospective study. The main aim of the present study was to evaluate the association between colorectal adenomatous polyps and COPD patients (defined by a spirometric criterion). Therefore, this limitation will be supported by a prospective randomized study including the individual history. Third, no clinical diagnosis of COPD was made in the present study. However, most early-stage COPD patients do not feel respiratory symptoms and the spirometric criteria may be an objective method for diagnosis of COPD in a population-based study. Fourth, most of the COPD subjects were male patients. The low prevalence of COPD patients among Korean females is due to small incidence of female smokers.
The present study had several limitations. The diagnosis of bronchiectasis was based on a questionnaire about history of diagnosis by a physician without radiologic information.
For this reason, the real number of patients with bronchiecta- sis might be greater compared with our data. In addition, the definition of COPD was based on the prebronchodilator FEV 1 /FVC ratio. Although patients with asthma diagnosed by physicians were excluded in this study, it is possible that undiagnosed asthma patients were mingled with the COPD patients. The questionnaires in this study did not measure biomass smoke or biologic dust exposure. The direct relation- ship between environmental exposure and COPD could not be analyzed, which was also a limitation. In addition, due to the small numbers of several variable categories such as male individuals and underweight subjects, the contribution of these risk factors toward developing COPD might be less obvious. Nevertheless, this study tried to clarify the impact of several socioeconomic factors and comorbidities on never-smoker COPD and examined their relationship. A low
1995년에 이르러 미국과 유럽의 흉부의학회는 연합위원회를 구성하여 COPD에 대하여 체계적인 연구를 진행하고, 가치 있 는 보고서를 출간하기 시작하였다. 한편 1998년에는 COPD의 진단, 치료 및 예방에 관하여 전세계적인 표준을 개발하고자 global initiative for chronicobstructive lung disease; GOLD라 는 전문위원회가 조직되었고, 2001년에 첫번째 보고서 (3) 를, 2006년에 두 번 째 보고서 (4) 를 출판하였다.
. Dropouts were defined as subjects who did not partic-
ipate in more than 3 of the 16 sessions. Assuming a dropout rate of about 30%, 30 subjects were considered necessary.
Among 556 patients who were treated for COPD at our hos- pital between August 2017 and August 2018, 59 patients were referred to the Department of Rehabilitation Medicine for this study. After applying the following inclusion cri- teria: 1) >40 years, 2) symptoms such as dyspnea or exercise intolerance in their daily lives, 3) Non-smoker or patient who has quit smoking for 3 months, 4) post-bronchodilator FEV 1 /forced vital capacity (FVC) <0.7 inpulmonary func- tion test, and 5) adequate pharmacological treatment follow- ing the Global Initiative for Chronic Obstructive Lung Dis- ease COPD strategy , 30 patients were included. Based on the exclusion criteria: 1) difficulty walking or any disease preventing improvement in walking ability, 2) uncontrolled extrapulmonary disease that could lead to hemodynamic in- stability during exercise (for example, angina pectoris, ar- rhythmia, or uncontrolled diabetes mellitus), 3) participa- tion in other clinical studies, 4) resting hypoxemia due to se- vere respiratory failure (SpO 2 <90%), we excluded 29 pa- tients. Consequently, we enrolled 30 patients in the study.
There are several limitations in the present study. First, the number of samples was small and therefore insufficient for the results to be statistically significant. In particular, the number of smokers was extremely small. Recently, Hancock et al. 38 performed a genome- wide joint meta-analysis to examine the association between genetic variations and lung function, following the investigation of SNP-by-smoking interactions. In another study, stratified genetic association analyses were conducted, according to smoking intensity, to evaluate the association between SNPs and the susceptibility to COPD. 39 However, because of the small number of samples, these analyses were not performed in this study. Second, all participants in this study were of East-Asian descent. Therefore, the types and frequencies of the genetic variations could be ethnic-specific. Finally, we could not measure whether the ability of MERTK to remove apoptotic cells is affected in its variants. It is well known that the function of proteins such as enzymes, transporters, and receptors can be impaired, even when their expression remains unaffected. For example, Gautherot et al. 40 reported that two nonsynonymous mutations in the multidrug resistance 3 (MDR3) transporter, encoded by the ATP-binding cassette, subfamily B, member 4 gene (ABCB4) led to a significant decrease in its transport ability, although none of these variations affected the expression of MDR3. It was subsequently found that the phosphorylation of ABCB4 was impaired by these mutations.
The current study has several limitations. First, whe- ther the associated regions play a functional role has not been investigated. Second, a replication analysis has not been performed in additional populations even though this was a meta-analysis of three GWASs using the lar- gest COPD cohorts to date. Third, TLC is only one pos- sible indicator of hyperinflation. There is no standard marker of hyperinflation and each indicator has its ad- vantages and disadvantages. Besides TLC, RV, the ratio of RV/TLC, functional residual capacity (FRC), inspira- tory capacity (IC) and the ratio of IC/TLC are all used to assess the severity of hyperinflation . Most of these measures are obtained by helium dilution testing or plethysmography, which are challenging to implement in a large population study. TLC may be normal until the late stages of COPD and therefore may not be the best
Neither adiponectin and leptin nor the leptin/adiponectin ratio was related to lung function decline over 3 years. On the contrary, a study involving the Hokkaido COPD Cohort and COPD Quantiﬁcation by Computed Tomography, Biomarkers, and Quality of Life (CBQ) study has shown that the ratio of leptin to adiponectin was associated with lung function decline (30). Compared with the reports based on the Hokkaido COPD Cohort and CBQ Study, the subjects with COPD in the present study had more severe airﬂow limitation, leading to slower lung function decline. This might result in a lack of signiﬁcant association of adipokine levels with lung function decline. Another explanation would be the selection of adjustment factors.
최근 미세먼지 농도가 올라감에 따라 사람들은 호흡기 질환에 큰 관심을 가지고 있다. 본 연구는 인구학적 및 임상 적 특징을 통한 만성 폐쇄성 폐질환(chronicobstructivepulmonarydisease)의 위험요인을 선별하고 이에 따른 노 모그램을 구축하였다. 먼저 국민건강영양조사(KNHANES) 6기 (2013–2015)의 인구학적 및 임상적 특징, 폐기능 검사 결과를 사용하여 로지스틱 회귀분석을 실시 하였고 비전공자들도 분석 결과에 대한 해석을 쉽게 할 수 있도록 만성 폐쇄성폐질환의 위험 요 인을 시각화한 노모그램을 구축하였다. 또한 ROC curve와 Calibration plot을 이용 하여 만성 폐쇄 성 폐질환의 노모그램을 검증하였다.
Baseline clinical data were obtained after cessation of the fol- lowing respiratory medications: an ICS for 2 weeks, an inhaled LABA for 2 days, an inhaled short-acting β 2 -agonist or inhaled short-acting anti-cholinergic for 12 hr. The baseline clinical data included demographic data, smoking history, chronic bronchitis history, wheezing history, pulmonary function tests, chest radi- ography and volumetric computed tomography (CT). Chronic bronchitis was defined as cough and sputum production on most days for a minimum of 3 months per year for at least 2 yr (9). Wheezing history was obtained through the following ques- tion: “Have you had wheezing or whistling in your chest at any time in the last year?” (10) Atopic status was assessed by a skin prick test to 11 common allergens, with a 10% histamine and saline control. Patients were considered to be atopic if they re- acted with a wheal of larger than the histamine control for more than one of the allergens. After obtaining baseline data, patients were treated with a salmeterol/fluticasone propionate 50/500 µg dry powder inhaler twice per day for 3 months, and then spi- rometry and lung volume measurement were performed again after the morning medication. During the 3-month treatment period, only salbutamol was allowed as needed. Adherence to the treatment medication monitored and recorded by research coordinators.
The limitation of our study is lack of measuring quality of life by using specific questionnaire either asthma-related quality of life questionnaire or St. George Respiratory Questionnaire.
Neither serum total IgE nor blood eosinophils count distinguishes ACOS from asthma and COPD in Thai cohort. This finding is different from previous study of biomarker study in ACOS which shown role of these biomarkers [5, 21]. However, FeNO was significant higher in isolated COPD than ACOS and isolated asthma. The increased FeNO in our COPD group may relate to tobacco smoke inhibits nitric oxide synthase and the presence of Th2 inflammation in COPD with atopy may lead to increased FeNO. For these, reason, FeNO cannot be recommended for differentiating asthma from COPD . Moreover, we found that atopic status could be a confounding variable for high FeNO level in Thai COPD. Since allergen sIgE is recommended for defining atopy and it was used with FeNO for diagnosed ACOS in Japanese cohort . Nevertheless, Thai ACOS had the higher serum total IgE and FENO in comparison with Japanese population. Different biomarkers may reflect the different racial basis and atopic background. For this reason the current biomarkers including lung function bronchodilator reversibility, total IgE, and FeNO are limited in terms of ACOS diagnosis across the different ethnicities and their role needs to be further investigated.
The erectile function of the subjects included in the current study tented to improve in the first year and then deteriorate again. As there have been no prior stud- ies on the longitudinal analysis of erectile function in male COPD patients, various interpretations are pos- sible. The subjects included in the study were first diag- nosed with COPD by a physician and enrolled in the cohort, and then visited outpatient clinics of medical facilities regularly to receive optimal treatment including non-pharmacological treatments. In this study, the GOLD A group with few symptoms comprised 37.8% of the patients, and 68.2% corresponded to GOLD stage 1 and 2 based on the FEV 1 values. Therefore, it is likely that interventions such as health education and correc- tion of health-related lifestyle habits including smoking cessation were more frequent in the first year of diagno- sis. This may also be the result of the limitations of self- administered questionnaires. If the subjects in the cohort report severe erectile dysfunction, this may be the result of a regression to the mean if erectile dysfunction is a fluctuating condition. It may also be due to the Haw- thorne effect occurring in the interaction with the physi- cians during enrolment. To more accurately observe these fluctuations, it would be beneficial to analyze the difference in erectile function changes according to the time of diagnosis (early-stage vs. end-stage).
deviation  . Data for categorical variables are presented as the numbers and percentages. Differences in baseline characteristics and comorbidities between the COPD group and non-COPD controls were analyzed with independent t-tests and χ 2
tests, as appropriate. Incidence rates of IBD were calculated by dividing the number of events by 1000000 person-years of follow-up for each group. Cox proportional hazard regression models considering time-varying covariates were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of IBD in patients with COPD compared to controls  . The cumulative incidences of IBD were compared between the groups with the Kaplan-Meier method and the log-rank test. A P value < 0.05 was considered statistically significant.
Some studies have reported that muscle mass was asso- ciated with mortality in elderly adults and with functional outcome in critically ill patients. 21,22 HGS is known as a simple assessment tool for nutritional status, systemic muscle mass and overall muscular strength because of its correlation with several muscular strength measurements such as knee and elbow extension. 23–25 Therefore, many researchers have studied the association between HGS and mortality and have reported associations between the two. 26–28 A recent systemic review of HGS has also reported that HGS is associated with increased risk of cardiovascular disease mortality in diverse populations. 29 One longitudinal study showed that HGS was a predictor of all causes of mortality. 26 However, the relation- ships between COPD and HGS in terms of lung function, severity of COPD and mortality are still controversial. 10–13
In this study, the logistic regression analysis, even after adjusting several factors such as age, gender, type of health insurance, and COPD severity, showed that the presence of GERD was independently associated with COPD exacerbation such as hospitalization or frequent ER visits. Since lung function data were not available in the present study, definition of severe COPD was based upon medication information and health care resource utilization. Although the degree of airflow limitation has been used as one of the most important criteria of COPD severity, it does not always reflect dyspnea, exer- cise capacity, quality of life, or exacerbation frequency . Recently updated Global initiative for chronic Ob- structive Lung Disease (GOLD) emphasizes combined assessment of COPD, which includes symptoms and risk of exacerbations as well as degree of airflow limitation . To supplement our weakness, patients with severe COPD were defined as those who satisfied both of the followings. One is that they used a tertiary health care resource, which means respiratory specialist’s care, and the other is that they received medications for maximum effect such as triple therapy (ICS + LABA + LAMA) or OCS-containing long-acting bronchodilator, which may mean medication for exacerbations. These are possible under nationwide health insurance system of Korea, which divide health care resources into primary, second- ary and tertiary and recommend people to use those step by step. Previous studies observed very small number of patients and simply compared frequency of exacerbation in COPD patients with GERD with in those without GERD [6,7,23,24]. They did not fully consider clinically important confounding factors such as age, gender, and COPD severity. Moreover, in two reports of them, COPD patients with GERD showed lower lung function as well as higher frequency of exacerbation than did those without GERD [23,24]. Therefore it might be hard to conclude whether frequent exacerbation was related to the presence of GERD or severe airflow limitation.