Airflow limitation as a risk factor for vascular stiffness.

BACKGROUND: Cardiovascular disease is one of the main causes of mortality in patients with chronic obstructive pulmonary disease (COPD), and atherosclerosis is a cause of cardiac comorbidities in COPD. However, it is not clear whether airflow limitation is associated with atherosclerosis irrespective of smoking.OBJECTIVE: To investigate whether airflow limitation is independently associated with vascular stiffness.METHODS: We enrolled 18 893 participants (male 70.5%; mean age 47.5 ± 9.8 years; never smokers 44.2%) who underwent spirometry and brachial-ankle pulse wave velocity (baPWV) as part of a standard health examination at Ajou University Hospital, Suwon, South Korea, from January 2010 to December 2015.We defined vascular peripheral atherosclerosis as baPWV ≥ 1400 cm/s and airflow limitation as pre-bronchodilator ratio of forced expiratory volume in 1 sec (FEV1) to forced vital capacity (FVC) <70%.RESULTS: Mean baPWV was higher in subjects with airflow limitation (1477.6 ± 331.7 cm/sec, n = 638) than in those without airflow limitation (1344.1 ± 231.8 cm/sec, n = 18255, P < 0.001). In multivariate logistic regression analysis, the following were independent predictors associated with peripheral atherosclerosis (P < 0.05): age, male sex, fasting serum glucose, mean blood pressure, serum leukocyte count, serum low density lipoprotein level and FEV1.CONCLUSION: Airflow limitation was an independent predictor of vascular stiffness irrespective of smoking history, which suggests that airflow limitation is linked with atherosclerosis.

The Model for End-stage Liver Disease score is potentially a useful predictor of hyperkalemia occurrence among hospitalized angiotensin receptor blocker users.

WHAT IS KNOWN AND OBJECTIVE: Angiotensin receptor blockers (ARBs) are medications commonly used for treating conditions such as hypertension. However, ARBs are frequently associated with hyperkalemia, a potentially critical adverse event, in high-risk patients. Although both the liver and the kidney are major elimination routes of ARBs, the relationship between hepatorenal function and ARB-related hyperkalemia has not yet been investigated. The purpose of this study was to evaluate the risk of hyperkalemia, in terms of various hepatorenal functions, for hospitalized patients newly initiated on ARB treatment. METHODS: We evaluated ARB-related hyperkalemia in a cohort of 5530 hospitalized patients, who had not previously used ARBs, between 12 April 2004 and 31 May 2012. Hepatorenal function was assessed by the Model for End-stage Liver Disease (MELD) score. Hyperkalemia risk was assessed by hepatorenal function, risks were categorized into the four MELD scoring groups, and the groups were compared with one another. RESULTS AND DISCUSSION: The MELD score was significantly different between the hyperkalemic and non-hyperkalemic groups (independent t-test, P < 0.001). The MELD score 10-14, 15-19 and ≥ 20 groups showed higher risks of hyperkalemia than the lowest MELD score group {log-rank test, P < 0.001; multiple Cox proportional hazard model, hazard ratios 1.478 (P = 0.003), 2.285 (P < 0.001) and 3.024 (P < 0.001), respectively}. WHAT IS NEW AND CONCLUSION: The MELD score showed a stronger predictive performance for hyperkalemia than either serum creatinine or estimated glomerular filtration rate alone. Furthermore, the MELD score showed good predictive performance for ARB-related hyperkalemia among hospitalized patients. The clinical implications and reasons for these findings merit future investigation.

Emphysematous phenotype is an independent predictor for frequent exacerbation of COPD.

SETTING: Frequent exacerbation is an important phenotype in chronic obstructive pulmonary disease (COPD), while emphysema is associated with many comorbidities and lung function decline. OBJECTIVE: To investigate unique features of frequent exacerbators and test the hypothesis that emphysematous phenotype is associated with frequent exacerbations of COPD. METHODS: A total of 380 COPD patients were recruited from 16 hospitals in Korea from June 2005 to April 2012 for analysis. We searched for independent predictors of frequent exacerbators in comparison with non-exacerbators. RESULTS: As the severity of emphysema increased, forced expiratory volume in 1 s (FEV1), and FEV1/FVC (forced volume capacity) worsened; hyperinflationary features characterised by higher total lung capacity (TLC) were observed (P < 0.05). Frequent exacerbators had lower body mass index (BMI), higher St George's Respiratory Questionnaire (SGRQ) scores, higher residual volume (RV)/TLC, more severe airflow limitation (lower FEV1 and FEV1/FVC), lower carbon monoxide diffusion capacity, lower serum protein levels and a higher emphysema index than non-exacerbators (P < 0.05). In multivariate analysis, frequent exacerbators were independently associated with a higher emphysema index, lower serum protein levels and higher RV/TLC (P < 0.05). CONCLUSION: Our data show that the severity of emphysema, severe static hyperinflation and serum lower protein levels are independent predictors of frequent exacerbations in COPD patients.

Onset time of hyperkalaemia after angiotensin receptor blocker initiation: when should we start serum potassium monitoring?

WHAT IS KNOWN AND OBJECTIVE: Angiotensin receptor blockers (ARBs) frequently induce hyperkalaemia in high-risk patients. Early detection of hyperkalaemia can reduce the subsequent harmful effects. This study was performed to examine the onset time of hyperkalaemia after ARB therapy. METHODS: We carried out a retrospective analysis to determine the onset time of hyperkalaemia (serum potassium >5·5 mm) among hospitalized patients newly starting ARB therapy between 2004 and 2012, in a tertiary teaching hospital. Predefined possible risk factors and concomitant medications were evaluated. RESULTS AND DISCUSSION: During the 97-month study period, a total of 4267 hospitalized patients started ARBs as new drugs and 225 patients showed hyperkalaemia. A significantly increased risk of hyperkalaemia was detected among patients with a high baseline potassium [odds ratio (OR) 6·0] and those who took non-potassium-sparing diuretics (OR 2·2) or potassium supplements (OR 1·6). A high glomerular filtration rate (GFR) was associated with a lower risk of hyperkalaemia (OR 0·992). Fifty-two percentage of hyperkalaemic events occurred within the first week after initiation of ARB therapy. The highest frequency of hyperkalaemia occurred on the first day after initiation of ARBs. Hyperkalaemia occurred earlier in patients with a high baseline serum potassium level, reduced GFR, diabetes and in those without heart failure. WHAT IS NEW AND CONCLUSION: Hyperkalaemia occurs most frequently at the beginning of ARB therapy in hospitalized patients. Monitoring of serum potassium and estimated GFR after initiation of ARBs should be started within a few days or not later than 1 week, especially in patients with risk factors.

Different therapeutic responses in chronic obstructive pulmonary disease subgroups.

SETTING: Eleven referring hospitals in South Korea. OBJECTIVE: To compare therapeutic responses in chronic obstructive pulmonary disease (COPD) subgroups, classified by diffusing capacity of the lung for carbon monoxide (DL(CO)) and lung volume. DESIGN: A total of 130 stable male COPD patients were classified into four subgroups according to baseline DL(CO) and residual volume/total lung capacity (RV/TLC) ratio. We compared therapeutic responses to short acting ß(2)-agonist (SABA) and 3-month combined inhalation of long-acting ß(2)-agonist (LABA) and corticosteroid among patients with these subgroups. RESULTS: Among the 130 COPD patients, 41 (31.5%) had normal DL(CO) and RV/TLC, 28 (21.5%) low DL(CO) and normal RV/TLC, 31 (23.8%) normal DL(CO) and high RV/TLC, and 30 (23.1%) low DL(CO) and high RV/TLC. The normal DL(CO)/high RV/TLC subgroup showed a significantly larger flow response (changes in forced expiratory volume in 1 s) to salbutamol than the normal DL(CO)/RV/TLC subgroups, and a larger volume response (changes in forced vital capacity) than the two normal RV/TLC subgroups. The normal DL(CO)/high RV/TLC subgroup also showed significantly larger flow and volume response to 3-month combined inhalation of LABA and corticosteroid than the two normal RV/TLC subgroups. CONCLUSION: COPD subgroups classified by DL(CO) and RV/TLC may have different pulmonary function responses to pharmacological treatment.

Pulmonary artery pressure in chronic obstructive pulmonary disease without resting hypoxaemia.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) can lead to pulmonary hypertension and cor pulmonale, which are predictors of mortality. OBJECTIVE: To identify predictors of increased pulmonary artery pressure (PAP) in COPD patients without resting hypoxaemia, and to characterise COPD patients with increased PAP. DESIGN: A study of 117 COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort who had measurable tricuspid regurgitant flow under transthoracic Doppler echocardiography and no resting hypoxaemia. RESULTS: The mean patient age was 67 years. Mean forced expiratory volume in 1 second (FEV(1)) was 47% predicted, mean haemoglobin (Hb) concentration was 145 g/l and mean systolic PAP (sPAP) was 33 mmHg. Multiple linear regression analysis showed that Hb was the only factor independently associated with sPAP (beta = -1.752, P = 0.005). Cluster analysis using FEV(1)% predicted, sPAP and Hb concentration as variables indicated three patient clusters: Cluster 1 (n = 36; mean FEV(1) 44% predicted, mean sPAP 39 mmHg, mean Hb 132 g/l), Cluster 2 (n = 45; FEV(1) 35% predicted, sPAP 31 mmHg, Hb 154 g/l), and Cluster 3 (n = 36; FEV(1) 65% predicted, sPAP 29 mmHg, Hb 148 g/l). CONCLUSION: Elevated PAP was linked to low haemoglobin levels in COPD without resting hypoxaemia.

Three phenotypes of obstructive lung disease in the elderly.

SETTING: Eleven referring hospitals in South Korea. OBJECTIVE: To classify the phenotypes in elderly subjects with obstructive lung disease (OLD). METHODS: We analysed 191 subjects aged ≥ 60 years with chronic respiratory symptoms and either obstructive spirometry or bronchial hyperresponsiveness. Factor analysis was performed using commonly measured variables and revealed four significant variables: 1) the ratio of inspiratory capacity to total lung capacity, 2) the total score on the St George's Respiratory Questionnaire, 3) the volume fraction of the lung less than 950 Hounsfield Unit at full inspiration on volumetric computed tomography and 4) post-bronchodilator forced expiratory volume in 1 second (FEV(1)) changes. We performed a cluster analysis on these four variables. RESULTS: The mean age was 68.5 (± 5.2 SD) years and the mean post-bronchodilator FEV(1) was 52.4% (± 16.5) predicted. Three clusters with the following phenotypes were identified: Cluster 1 included subjects with moderate to severe airflow obstruction and bronchodilator reversibility; Cluster 2 subjects had moderate airflow obstruction without bronchodilator reversibility, and Cluster 3 subjects had severe airflow obstruction without bronchodilator reversibility. CONCLUSIONS: We identified three phenotypes in elderly subjects with OLD. Follow-up studies are needed to explore the clinical significance of each phenotype.

The addition of induction chemotherapy with etoposide, ifosfamide, and cisplatin failed to improve therapeutic outcome of concurrent chemoradiotherapy in patients with locally advanced non-small cell lung cancer -- single institution retrospective analysis.

Although chemoradiotherapy (CRT) is a standard treatment for unresectable locally advanced non-small cell lung cancer (NSCLC), the optimal sequencing remains to be determined. We retrospectively compared the treatment results of induction chemotherapy followed by concurrent CRT (induction group, 32 patients) with those of concurrent CRT alone (concurrent group, 41 patients) in unresectable stage IIIA/IIIB NSCLC patients. In induction group, 2 cycles of induction chemotherapy (etoposide/ifosfamide/cisplatin: 24 patients, others: 8 patients) were followed by concurrent CRT (60 Gy/30 fractions, 6 mg/m2 of cisplatin daily), while the same concurrent CRT was administered in concurrent group. Clinicopathologic characteristics including age, weight loss, histologic types, and clinical stage did not show significant differences between two groups except for a higher proportion of patients with ECOG performance status 2 in concurrent group (3% vs. 27%, p=0.015). Overall toxicity was generally acceptable with 1 treatment-related death from tracheoesophageal fistula in induction group. The response rates after concurrent CRT were 41% for induction group and 54% for concurrent group, which showed no significant difference (p=0.560). With median follow-up of 13 (1-92) months, there was a trend toward an advantage for concurrent group in median progression-free survival (6 months vs 8.3 months, p=0.067) and overall survival (12 months vs. 14.5 months, p=0.059). In multivariate analysis, only more than 10% weight loss within 6 months was significantly associated with poor survival (p=0.001). In conclusion, the addition of induction chemotherapy to concurrent CRT did not show any advantage over concurrent CRT alone in locally advanced NSCLC.