Ming-Shian Lin

Prevalence of Asymptomatic Peripheral Arterial Disease and Related Risk Factors in Younger and Elderly Patients in Taiwan

We determined the prevalence of asymptomatic peripheral arterial disease (PAD) and cardiovascular risk factors in Taiwan. Ambulatory participants (n = 1915) without symptoms of PAD were enrolled (mean age of 61.2 years). The ankle-brachial index (ABI) was used to detect the PAD (ABI < 0.90). The overall prevalence of asymptomatic PAD was 5.4% (2.8% in the younger participants [<65 years of age, n = 1021] and 8.4% in the elderly participants [≥65 years of age, n = 894]). Younger participants with asymptomatic PAD had a significantly higher rate of hypertension (55.2% vs 30%) and obesity (31% vs 13.3%) than those without asymptomatic PAD (P < .05). Elderly participants with asymptomatic PAD had a significantly higher rate of diabetes mellitus (36% vs 21.2%) and hypertension (69.3% vs 55.4%) than those without asymptomatic PAD (P < .05). Asymptomatic PAD is prevalent among elderly Taiwanese individuals. Overall, age was the strongest risk factor for the development of asymptomatic PAD.

Prevalence and Risk Factors of Asymptomatic Peripheral Arterial Disease in Patients with COPD in Taiwan

Aim Chronic obstructive pulmonary disease (COPD) is an independent risk factor for cardiovascular morbidity and mortality. The aim of this study was to determine the prevalence of asymptomatic peripheral arterial disease (PAD) and the associated risk factors for patients with COPD. Methods This prospective cross-sectional study enrolled 427 COPD patients (mean age: 70.0 years) without PAD symptoms consecutively. Demographic data, lung function and cardiovascular risk factors were recorded. The ankle-brachial index (ABI) was used to detect PAD (ABI<0.90). Results The overall prevalence of asymptomatic PAD in the COPD patients was 8% (2.5% in the younger participants (<65 years of age, n = 118) and 10% in the elderly participants (≥65 years of age, n = 309). The COPD patients with asymptomatic PAD had a significantly higher rate of hyperlipidemia (47.1% vs. 10.4%) and hypertension (79.4% vs. 45.8%) than those without asymptomatic PAD (p<0.05). There was no significant difference in lung function (forced vital capacity and forced expiratory volume in one second) between the two groups. In multivariate logistic regression, hyperlipidemia was the strongest independent factor for PAD (odds ratio (OR): 6.89, p<0.005), followed by old age (OR: 4.80), hypertension (OR: 3.39) and smoking burden (pack-years, OR: 1.02). Conclusions The prevalence of asymptomatic PAD among COPD patients in Taiwan is lower than in Western countries. Hyperlipidemia, old age, hypertension, and smoking burden were the associated cardiovascular risk factors. However, there was no association between lung function and PAD in the COPD patients.

Is asymptomatic peripheral arterial disease associated with walking endurance in patients with COPD

Objective Symptomatic peripheral arterial disease (PAD) is associated with impaired walking endurance in patients with chronic obstructive pulmonary disease (COPD). However, it is unknown whether asymptomatic PAD is associated with impaired walking endurance in patients with COPD. Methods This prospective cross-sectional study enrolled 200 COPD patients (mean age: 70.9 years) who volunteered to perform ankle-brachial index (ABI) and 6-minute walk test (6MWT) consecutively. Demographic data, lung function, dyspnea scales, and cardiovascular risk factors were recorded. The ABI was used to detect PAD (ABI <0.90). All patients were free of PAD symptoms at enrollment. Results Of the 200 COPD patients, 17 (8.5%) were diagnosed with asymptomatic PAD. The COPD patients without asymptomatic PAD did not walk significantly further on the 6MWT than the COPD patients with asymptomatic PAD (439±86 m vs 408±74 m, P=0.159). The strongest correlation with the distance walked on the 6MWT was Medical Research Council dyspnea scale (r2=−0.667, P<0.001), followed by oxygen-cost diagram (r2=0.582, P<0.001) and forced expiratory volume in 1 second (r2=0.532, P<0.001). In multivariate linear regression analysis, only age, forced expiratory volume in 1 second, and baseline pulse oximetry were independently correlated with the distance covered on the 6MWT (P<0.05). However, body mass index, baseline heart rate, and ABI were not correlated with the distance covered on the 6MWT. Conclusion Asymptomatic PAD is not associated with walking endurance in patients with COPD. Therefore, it is important to detect and treat asymptomatic PAD early so that COPD patients do not progress to become exercise intolerant. Limited by the small sample size and predominantly male (99%) population in the study, further large-scale prospective studies are needed to verify the results.

Severe hypoalbuminemia is a strong independent risk factor for acute respiratory failure in COPD: a nationwide cohort study

Background Acute respiratory failure (ARF) is a life-threatening event, which is frequently associated with the severe exacerbations of chronic obstructive pulmonary disease (COPD). Hypoalbuminemia is associated with increased mortality in patients with COPD. However, to date, little is known regarding whether or not hypoalbuminemia is a risk factor for developing ARF in COPD. Methods We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan. A total of 42,732 newly diagnosed COPD patients (age ≥40 years) from 1997 to 2011 were enrolled. Among them, 1,861 (4.36%) patients who had received albumin supplementation were defined as hypoalbuminemia, and 40,871 (95.6%) patients who had not received albumin supplementation were defined as no hypoalbuminemia. Results Of 42,732 newly diagnosed COPD patients, 5,248 patients (12.3%) developed ARF during the 6 years follow-up period. Patients with hypoalbuminemia were older, predominantly male, had more comorbidities, and required more steroid treatment and blood transfusions than patients without hypoalbuminemia. In a multivariable Cox regression analysis model, being elderly was the strongest independent risk factor for ARF (adjusted hazard ratio [HR]: 4.63, P<0.001), followed by hypoalbuminemia (adjusted HR: 2.87, P<0.001). However, as the annual average dose of albumin supplementation was higher than 13.8 g per year, the risk for ARF was the highest (adjusted HR: 11.13, 95% CI: 10.35–11.98, P<0.001). Conclusion Hypoalbuminemia is a strong risk factor for ARF in patients with COPD. Therefore, further prospective studies are required to verify whether or not albumin supplementation or nutritional support may help to reduce the risk of ARF in patients with COPD.

Incidence and Outcomes of Acute Respiratory Distress Syndrome: A Nationwide Registry-Based Study in Taiwan, 1997 to 2011

AbstractMost epidemiological studies of acute respiratory distress syndrome (ARDS) have been conducted in western countries, and studies in Asia are limited. The aim of our study was to evaluate the incidence, in-hospital mortality, and 1-year mortality of ARDS in Taiwan.We conducted a nationwide inpatient cohort study based on the Taiwan National Health Insurance Research Database between 1997 and 2011. A total of 40,876 ARDS patients (68% male; mean age 66 years) were identified by International Classification of Diseases, 9th edition coding and further analyzed for clinical characteristics, medical costs, and mortality.The overall crude incidence of ARDS was 15.74 per 100,000 person-years, and increased from 2.53 to 19.26 per 100,000 person-years during the study period. The age-adjusted incidence of ARDS was 15.19 per 100,000 person-years. The overall in-hospital mortality was 57.8%. In-hospital mortality decreased from 59.7% in 1997 to 47.5% in 2011 (P < 0.001). The in-hospital mortality rate was lowest (33.5%) in the youngest patients (age 18–29 years) and highest (68.2%) in the oldest patients (>80 years, P < 0.001). The overall 1-year mortality rate was 72.1%, and decreased from 75.8% to 54.7% during the study period. Patients who died during hospitalization were older (69 ± 17 versus 62 ± 19, P < 0.001) and predominantly male (69.8% versus 65.3%, P < 0.001). In addition, patients who died during hospitalization had significantly higher medical costs (6421 versus 5825 US Dollars, P < 0.001) and shorter lengths of stay (13 versus 19 days, P < 0.001) than patients who survived.We provide the first large-scale epidemiological analysis of ARDS incidence and outcomes in Asia. Although the overall incidence was lower than has been reported in a prospective US study, this may reflect underdiagnosis by International Classification of Diseases, 9th edition code and identification of only patients with more severe ARDS in this analysis. Overall, there has been a decreasing trend in in-hospital and 1-year mortality rates in recent years, likely because of the implementation of lung-protective ventilation.

Genetic diversity of the Mycobacterium tuberculosis East African–Indian family in three tropical Asian countries

BACKGROUND The Beijing lineage of Mycobacterium tuberculosis (MTB) is the most predominant MTB strain in Asian countries and is spreading worldwide, however, the East African-Indian (EAI) lineage is also particularly prevalent in many tropical Asian countries. The evolutionary relationships among MTB EAI isolates from Taiwan and those of tropical Asian countries remain unknown. METHODS The EAI strains collected from patients in Taiwan were analyzed using spacer oligonucleotide typing and mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) typing, and compared with published profiles from Cambodia and Singapore to investigate potential epidemiological linkages. RESULTS Among the three countries, the EAI lineage was most prevalent in Cambodia (60%; Singapore, 25.62%; and Taiwan, 21.85%), having also the highest rates of multidrug resistance and lowest rates of clustering of MTB isolates. We describe a convenient method using seven selected MIRU-VNTR loci for first-line typing to discriminate Beijing and EAI lineages. A potential epidemiological linkage in these tropical Asian countries is also discussed based on a minimum-spanning tree constructed using 24 MIRU-VNTR loci of MTB EAI strains. CONCLUSION This study identified evolutionary relationships among MTB EAI isolates from Taiwan and those of two other tropical Asian countries, Cambodia and Singapore.

Genomics Study of Mycobacterium tuberculosis Strains from Different Ethnic Populations in Taiwan

To better understand the transmission and evolution of Mycobacterium tuberculosis (MTB) in Taiwan, six different MTB isolates (representatives of the Beijing ancient sublineage, Beijing modern sublineage, Haarlem, East-African Indian, T1, and Latin-American Mediterranean (LAM)) were characterized and their genomes were sequenced. Discriminating among large sequence polymorphisms (LSPs) that occur once versus those that occur repeatedly in a genomic region may help to elucidate the biological roles of LSPs and to identify the useful phylogenetic relationships. In contrast to our previous LSP-based phylogeny, the sequencing data allowed us to determine actual genetic distances and to define precisely the phylogenetic relationships between the main lineages of the MTB complex. Comparative genomics analyses revealed more nonsynonymous substitutions than synonymous changes in the coding sequences. Furthermore, MTB isolate M7, a LAM-3 clinical strain isolated from a patient of Taiwanese aboriginal origin, is closely related to F11 (LAM), an epidemic tuberculosis strain isolated in the Western Cape of South Africa. The PE/PPE protein family showed a higher dn/ds ratio compared to that for all protein-coding genes. Finally, we found Haarlem-3 and LAM-3 isolates to be circulating in the aboriginal community in Taiwan, suggesting that they may have originated with post-Columbus Europeans. Taken together, our results revealed an interesting association with historical migrations of different ethnic populations, thus providing a good model to explore the global evolution and spread of MTB.

Combining molecular typing and spatial pattern analysis to identify areas of high tuberculosis transmission in a moderate-incidence county in Taiwan

In total, 303 randomly selected clinical Mycobacterium tuberculosis (MTB) isolates from 303 patients (collected January to December 2012) in central Taiwan were examined. The major lineages found were Beijing (N = 114, 37.62%), Haarlem (N = 76, 25.08%) and East African–Indian (EAI) (N = 42, 13.86%). Notably, younger persons (≤30 years old) were 6.58 times more likely to be infected with a Beijing genotype compared to older persons (>70 years) (p < 0.05). Combining molecular typing methods and geographical information system (GIS) analysis, we uncovered a twofold higher incidence of Beijing strains in a hotspot area (33%) compared to non-hotspot areas (17%). By 24 MIRU-VNTR typing, persons in clustered groups were 1.96 times more likely to be infected with a Beijing strain compared with non-clustered persons, suggesting recent spread and emergence of MTB. Finally, we observed a trend in which TB incidence increased as the density/concentration of analyzed environmental factors increased, suggesting that environmental factors are associated with TB transmission; however, only population density was found to be significantly associated with increased risk of TB (p < 0.05). Molecular typing methods combined with spatial analysis suggest possible TB transmission. Early intervention to interrupt transmission may be most effective if targeted to hot zones of TB.

Trend of Incidence of Second Primary Malignancies following Breast Cancer in Taiwan: A 12-year Nationwide Cohort Study.

To the Editor: The incidence and mortality rates of breast cancer progressively increase with age worldwide (1,2). In Taiwan, breast cancer is the most common female cancer and the fourth cause of death in women (3). The average age of diagnosis in Taiwan is 51 years, less than that in European and North American countries (3). The reason for this disparity is not fully understood, but could include a variety of factors such as lifestyle, hormone use, ethnic differences in clinical presentation, and other biologic factors (1). As advances in early diagnosis and treatment, breast cancer has become an increasingly survivable disease, resulting in a large population of long-term survivors. Therefore, newly diagnosed malignancies following breast cancer are becoming a major issue that clinicians, patients, and their families must address. With modifications to lifestyle and advances in medical technology, the incidence and patterns of malignancies have changed in Taiwan. However, over the past decade, the risk and incidence of second primary malignancies following breast cancer in Taiwan have not been well documented. In this study, a total of 67,134 newly diagnosed breast cancer patients were identified between 2000 and 2011. Patients who had had a prior diagnosis of breast cancer or who underwent surgery for breast cancer between 1997 and 1999 were excluded. An age distribution analysis revealed that half of the patients were older than 50 years (54.5%), whereas 40.8% of the patients were between 35 and 49 years. In total, 47,778 newly diagnosed breast cancer patients (71.2%) received a mastectomy. To investigate the incidence of second primary malignancies following breast cancer, we evaluated the frequency of new malignancies registered in Registry for Catastrophic Illness Patients Data base at least 1 year after an initial breast cancer diagnosis compared to those in the general population. The standardized incidence ratios (SIRs) of second primary cancers among 67,134 women with newly diagnosed breast cancer for the period of 2000–2011 were calculated. As shown in Table 1, the risks of the following second cancers significantly increased: kidney cancer (SIR 4.10; 95% confidence interval [CI]: 3.26–5.03), thyroid gland cancer (SIR 2.46; 95% CI: 2.09–2.87), nasopharynx carcinoma (SIR 1.98; 95% CI: 1.39– 2.67), ovary and other uterine adnexal cancer (SIR 1.79; 95% CI: 1.46–2.16), and body of uterus cancer (SIR 1.79; 95% CI: 1.56–2.10). Notably, the risks of the following second cancers significantly decreased: Non-Hodgkin lymphoma (SIR 0.15; 95% CI: 0.06– 0.27); liver cancer (SIR 0.49; 95% CI: 0.41–0.58); pancreas cancer (SIR 0.51; 95% CI: 0.32–0.73); trachea, bronchus, and lung cancers (SIR 0.67; 95% CI: 0.57–0.77); rectal cancer (SIR 0.76; 95% CI: 0.62– 0.91); stomach cancer (SIR 0.78; 95% CI: 0.61–0.97); and colon cancer (SIR 0.85; 95% CI: 0.73–0.97). To the best of our knowledge, this is the largest cohort of patients used over the past decade to evaluate the risk and incidence of second primary cancer following breast cancer in Taiwan. Our data demonstrated that the overall incidence of second primary cancers was 446 per 10 patient-years. The most common second primary cancer was colon cancer. Compared with the general population, patients were at the highest risk of developing kidney cancer after breast cancer, even when adjusted by age. Compared with previous results (1979–2003), nasopharyngeal cancer is now an emerging second primary cancer in breast cancer patients. Starting in 1994, free breast cancer screening programs have been offered in Taiwan for high-risk Address correspondence and reprint requests to: Wei Chen, MD, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, #539 Jhongsiao Road, Chiayi, Taiwan, or e-mail: peteral fa2004@yahoo.com.tw

Ring-like calcifications of the kidney

A 76-year-old man with a history of liver cirrhosis was admitted for investigation of a right renal mass. He had a 2-month history of right-sided upper abdominal pain and intermittent fever. Abdominal ultrasound showed a large right renal mass with hydronephrosis. X-ray and abdomen computed tomography showed enlargement of the right renal contour, which was replaced by a necrotic mass and some calcified lymph nodes in the hilar region (Figure 1). With the presumptive diagnosis of a renal malignancy, he underwent right radical nephrectomy, adrenalectomy, and lymph node dissection. Grossly, the affected kidney was enlarged, and demonstrated caseous necrosis and calcification in the cortex and medullary regions. On pathological examination, chronic granulomatous inflammation, with granuloma, caseous necrosis, and Langhan’s giant cells (Figure 2) were seen. In addition, acid-fast bacilli were found. He was treated with anti-tuberculosis agents.