Prediction of first acute exacerbation using COPD subtypes identified by cluster analysis.

Purpose: In patients with COPD, acute exacerbation (AE) is not only an important determinant of prognosis, but also an important factor in choosing therapeutic agents. In this study, we evaluated the usefulness of COPD subtypes identified through cluster analysis to predict the first AE. Patients and methods: Among COPD patients in the Korea COPD Subgroup Study (KOCOSS) cohort, 1,195 who had follow-up data for AE were included in our study. We selected seven variables for cluster analysis - age, body mass index, smoking status, history of asthma, COPD assessment test (CAT) score, post-bronchodilator (BD) FEV1 % predicted, and diffusing capacity of carbon monoxide % predicted. Results: K-means clustering identified four clusters for COPD that we named putative asthma-COPD overlap (ACO), mild COPD, moderate COPD, and severe COPD subtypes. The ACO group (n=196) showed the second-best post-BD FEV1 (75.5% vs 80.9% [mild COPD, n=313] vs 52.4% [moderate COPD, n=345] vs 46.7% [severe COPD, n=341] predicted), the longest 6-min walking distance (424 m vs 405 m vs 389  m vs 365 m), and the lowest CAT score (12.2 vs 13.7 vs 15.6 vs 17.5) among the four groups. ACO group had greater risk for first AE compared to the mild COPD group (HR, 1.683; 95% CI, 1.175-2.410). The moderate COPD and severe COPD group HR values were 1.587 (95% CI, 1.145-2.200) and 1.664 (95% CI, 1.203-2.302), respectively. In addition, St. George's Respiratory Questionnaire score (HR: 1.019; 95% CI, 1.014-1.024) and gastroesophageal reflux disease were independent factors associated with the first AE (HR: 1.535; 95% CI, 1.116-2.112). Conclusion: Our cluster analysis revealed an exacerbator subtype of COPD independent of FEV1. Since these patients are susceptible to AE, a more aggressive treatment strategy is needed in these patients.

Genome-wide association study identifies ALLC polymorphisms correlated with FEV1 change by corticosteroid.

OBJECTIVES: Asthma can be suppressed by inhaled corticosteroids (ICS). However, response to ICS shows marked inter-individual variability. This study is aimed to identify the genetic variants associated with the change in the percentage of forced expiratory volume in 1second (%ΔFEV1) following ICS treatment. METHODS: A genome-wide association study was performed in a Korean asthmatic cohort. To further investigate these genetic associations, 11 additional single-nucleotide polymorphisms (SNPs) on the allantoicase (ALLC) gene were selected from the HapMap database and genotyped in the same asthmatic patients in the follow-up study. RESULTS: In a genome-wide study, we identified the lowest P-value in ALLC, but none of the SNPs met the genome-wide association criteria (P<1.0×10(-8)). However, among 25 SNPs on ALLC in the follow-up study, 6 variants showed significant associations with the mean %ΔFEV1 in the study subjects (P<3.73×10(-6)). CONCLUSIONS: Although the associated signals could not overcome the genome-wide multiple correction due to small sample size (n=189), our results suggest that associated SNPs of ALLC might be genetic predictors of response to ICS, at least with respect to ΔFEV1 in Korean asthmatics.

Clinical implications of the ethane in exhaled breath in patients with acute paraquat intoxication.

STUDY OBJECTIVES: Pulmonary fibrosis due to lipid peroxidation is a major symptom of paraquat intoxication. Ethane in the expired breath (exEth) reflects lipid peroxidation and may be a measure of the damage effected by oxygen radicals in acute lung injury. The purpose of this study was to evaluate the clinical efficacy of exEth as a measure of exposure to paraquat and as an indicator of lung damage. DESIGN: Exposure levels were evaluated by the amount ingested, semiquantitative measurement of urine paraquat levels, and plasma paraquat concentration. End-tidal breath was collected for measurement of ethane 24 h after paraquat ingestion. Renal function and blood gas analyses were conducted on the same day as the breath collection, and the final clinical outcome was defined as either recovery or death. Associations between exEth and paraquat exposure profiles and clinical outcomes were assessed using linear regression models. PATIENTS: Twenty-one patients poisoned by paraquat were selected for the study during 2001 and 2002. RESULTS: exEth could not be used as a predictor of laboratory parameters such as Pa(O2), Pa(CO2), serum creatinine, and lung injury (as graded by high-resolution CT). A logistical analysis revealed that only the amount of paraquat ingested was a significant predictor of fatality (p = 0.021). The strength of the association between exEth and fatality was unaffected by the addition of potential confounders such as age, sex, and time interval and paraquat concentration. CONCLUSION: exEth cannot be used as either an independent predictor of survival or a specific marker of lung injury in patients with acute paraquat poisoning.

A simple and easy home-based pulmonary rehabilitation programme for patients with chronic lung diseases.

BACKGROUND AND AIM: To develop a simple and easy home-based pulmonary rehabilitation programme and investigate its effectiveness. METHODS: Patients with stable chronic lung disease were divided into a rehabilitation group (n = 25) and a control group (n = 18). Rehabilitation consisted of education and 12 weeks of enforced aerobic and muscle-strengthening exercises. Aerobic exercise training was performed mostly by walking based on the functional capacity of the patients assessed by the maximal incremental exercise test. Patients visited hospital every two weeks for evaluation and a new exercise regimen. RESULTS: Five patients dropped out of the rehabilitation group but three were due to development of unrelated diseases, five controls did not co-operate in the second evaluation. After 12 weeks of rehabilitation, exercise capacity (maximum work load and VO2max), exercise endurance, 6-minute walking distance, and quality of life measured by the St. George Respiratory Questionnaire had significantly improved in the rehabilitation group but not in the controls. At a follow-up evaluation one year after the rehabilitation, some exercise parameters were still significantly higher than baseline in the rehabilitation group. CONCLUSIONS: We developed a simple home-based pulmonary rehabilitation programme, which seems to be clinically feasible and effective.