Accuracy of forced oscillation technique to assess lung function in geriatric COPD population.

INTRODUCTION: Performing lung function test in geriatric patients has never been an easy task. With well-established evidence indicating impaired small airway function and air trapping in patients with geriatric COPD, utilizing forced oscillation technique (FOT) as a supplementary tool may aid in the assessment of lung function in this population. AIMS: To study the use of FOT in the assessment of airflow limitation and air trapping in geriatric COPD patients. STUDY DESIGN: A cross-sectional study in a public hospital in Hong Kong. ClinicalTrials.gov ID: NCT01553812. METHODS: Geriatric patients who had spirometry-diagnosed COPD were recruited, with both FOT and plethysmography performed. "Resistance" and "reactance" FOT parameters were compared to plethysmography for the assessment of air trapping and airflow limitation. RESULTS: In total, 158 COPD subjects with a mean age of 71.9±0.7 years and percentage of forced expiratory volume in 1 second of 53.4±1.7 L were recruited. FOT values had a good correlation (r=0.4-0.7) to spirometric data. In general, X values (reactance) were better than R values (resistance), showing a higher correlation with spirometric data in airflow limitation (r=0.07-0.49 vs 0.61-0.67), small airway (r=0.05-0.48 vs 0.56-0.65), and lung volume (r=0.12-0.29 vs 0.43-0.49). In addition, resonance frequency (Fres) and frequency dependence (FDep) could well identify the severe type (percentage of forced expiratory volume in 1 second <50%) of COPD with high sensitivity (0.76, 0.71) and specificity (0.72, 0.64) (area under the curve: 0.8 and 0.77, respectively). Moreover, X values could stratify different severities of air trapping, while R values could not. CONCLUSION: FOT may act as a simple and accurate tool in the assessment of severity of airflow limitation, small and central airway function, and air trapping in patients with geriatric COPD who have difficulties performing conventional lung function test. Moreover, reactance parameters were better than resistance parameters in correlation with air trapping.

Frequent Exacerbator: The Phenotype at Risk of Depressive Symptoms in Geriatric COPD Patients.

INTRODUCTION: Depression is associated with a poorer quality of life and higher rate of COPD exacerbations and mortality. However, with multiple confounding factors, 'independent' risk factor for depression among COPD patients remains ambiguous. Our study aims to identify independent risk factors for depression by specifically evaluating for any independent relationship between frequent exacerbations and various domains of the BODE index on depression. METHODS: This study is a cross-sectional study, conducted in Hong Kong SAR. Age and comorbidity-matched COPD and control subjects were recruited. Depressive symptoms were measured by a validated Chinese version of the Geriatric Depression Scale (GDS-15 items). Prevalence rates of depressive symptoms were compared between COPD and control groups. Predictors for depression (GDS ≥ 8) were determined using univariate and multivariate analyses. RESULTS: A total of 161 patients (89 and 72 patients, mean ages 75.2 and 75.6 in COPD and control group, respectively) were recruited. Higher prevalence rate of significant depressive symptoms was seen in COPD patients (20.2 vs. 4.2 %, p = 0.006*). Univariate analysis suggested that predictors for depression in COPD patients included (i) exacerbation frequencies in prior year, (ii) dyspnea level, (iii) BMI, (iv) functional status (Barthel index, 6MWD, activity domain of SGRQ), and (v) BODE index. In multivariate analysis, only the 'exacerbation frequencies in prior year' (OR 1.46, p = 0.042*) and 'dyspnea level' (MMRC) (OR 2.75, p = 0.001*) remained significant independent predictors for depression in COPD patients. CONCLUSIONS: A high prevalence of depressive symptoms was observed in COPD patients. 'Frequent exacerbation phenotype' remained a significant independent predictor for depressive symptoms in COPD. Among the BODE index domains, dyspnea level is the most important predictor for depression in COPD patients.

Update on the pathological processes, molecular biology, and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common and morbid disease characterized by high oxidative stress. Its pathogenesis is complex, and involves excessive oxidative stress (redox imbalance), protease/antiprotease imbalance, inflammation, apoptosis, and autoimmunity. Among these, oxidative stress has a pivotal role in the pathogenesis of COPD by initiating and mediating various redox-sensitive signal transduction pathways and gene expression. The protective physiological mechanisms of the redox balance in the human body, their role in the pathogenesis of COPD, and the clinical correlation between oxidative stress and COPD are reviewed in this paper. N-acetylcysteine (NAC) is a mucolytic agent with both antioxidant and anti-inflammatory properties. This paper also reviews the use of NAC in patients with COPD, especially the dose-dependent properties of NAC, eg, its effects on lung function and the exacerbation rate in patients with the disease. Earlier data from BRONCUS (the Bronchitis Randomized on NAC Cost-Utility Study) did not suggest that NAC was beneficial in patients with COPD, only indicating that it reduced exacerbation in an "inhaled steroid-naïve" subgroup. With regard to the dose-dependent properties of NAC, two recent randomized controlled Chinese trials suggested that high-dose NAC (1,200 mg daily) can reduce exacerbations in patients with COPD, especially in those with an earlier (moderately severe) stage of disease, and also in those who are at high risk of exacerbations. However, there was no significant effect on symptoms or quality of life in patients receiving NAC. Further studies are warranted to investigate the effect of NAC at higher doses in non-Chinese patients with COPD.

Benefits of high-dose N-acetylcysteine to exacerbation-prone patients with COPD.

BACKGROUND: Although high-dose N-acetylcysteine (NAC) has been suggested to reduce COPD exacerbations, it is unclear which category of patients with COPD would benefit most from NAC treatment. The objective of this study was to compare the effect of high-dose NAC (600 mg bid) between high-risk and low-risk Chinese patients with COPD. METHODS: Patients with spirometry-confirmed stable COPD were randomized to treatment with either NAC 600 mg bid or placebo in addition to their usual treatments. Patients were followed up every 16 weeks for a total of 1 year. Further analysis was performed according to each patient's exacerbation risk at baseline as defined by the current GOLD (Global Initiative for Chronic Obstructive Lung Disease) strategy to analyze the effect of high-dose NAC in high-risk and low-risk patients. RESULTS: Of the 120 patients with COPD randomized (men, 93.2%; mean age, 70.8 ± 0.74 years; prebronchodilator FEV1, 53.9 ± 2.0%; baseline characteristics comparable between treatment groups), 108 (NAC, 52; placebo, 56) completed the 1-year study. For high-risk patients (n = 89), high-dose NAC compared with placebo significantly reduced exacerbation frequency (0.85 vs 1.59 [P = .019] and 1.08 vs 2.22 [P = .04] at 8 and 12 months, respectively), prolonged time to first exacerbation (P = .02), and increased the probability of being exacerbation free at 1 year (51.3% vs 24.4%, P = .013). This beneficial effect of high-dose NAC vs placebo was not significant in low-risk patients. CONCLUSIONS: High-dose NAC (600 mg bid) for 1 year reduces exacerbations and prolongs time to first exacerbation in high-risk but not in low-risk Chinese patients with COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01136239; URL: www.clinicaltrials.gov.

Integrated use of virtual bronchoscopy and endobronchial ultrasonography on the diagnosis of peripheral lung lesions.

Endobronchial ultrasound (EBUS) improves bronchoscopic diagnosis of peripheral lung lesions (PLLs). The procedure time is lengthened by the search through multiple bronchial branches to PLLs. Virtual bronchoscopy (VB) provides endobronchial views that simulate findings at bronchoscopy. An open source software can be employed to study VB and hence the endobronchial route to a PLL. It allows VB to be studied in a Macintosh platform such as a laptop computer. Our purpose was to test if VB generated by this software could shorten procedure time of EBUS-guided bronchoscopy as compared with no VB assistance. The most feasible route to a PLL was manually selected using this software to study VB (VB group). For non-VB group, 2D CT axial +/- coronal images were reviewed to plan bronchoscopy. Before bronchoscopic biopsies, the location of PLL was confirmed by EBUS. Thirty-three subjects were recruited including 16 in VB group and 17 in non-VB group. The mean EBUS examination time and mean total procedure time were reduced in the VB group compared with non-VB group: 5.3 versus 10.5 minutes (P=0.04) and 22.4 versus 29.9 minutes (P=0.044), respectively. There was no complication in the VB group. Although the diagnostic yield was higher in the VB group than non-VB group, our study was not powered to test the difference. This pilot study suggests that VB assistance is safe and shortens procedural time of EBUS-guided bronchoscopy for PLL. Further study is warranted to confirm these findings.

High-dose N-acetylcysteine in stable COPD: the 1-year, double-blind, randomized, placebo-controlled HIACE study.

BACKGROUND: The mucolytic and antioxidant effects of N-acetylcysteine (NAC) may have great value in COPD treatment. However, beneficial effects have not been confirmed in clinical studies, possibly due to insufficient NAC doses and/or inadequate outcome parameters used. The objective of this study was to investigate high-dose NAC plus usual therapy in Chinese patients with stable COPD. METHODS: The 1-year HIACE (The Effect of High Dose N-acetylcysteine on Air Trapping and Airway Resistance of Chronic Obstructive Pulmonary Disease-a Double-blinded, Randomized, Placebo-controlled Trial) double-blind trial conducted in Kwong Wah Hospital, Hong Kong, randomized eligible patients aged 50 to 80 years with stable COPD to NAC 600 mg bid or placebo after 4-week run-in. Lung function parameters, symptoms, modified Medical Research Council (mMRC) dyspnea and St. George's Respiratory Questionnaire (SGRQ) scores, 6-min walking distance (6MWD), and exacerbation and admission rates were measured at baseline and every 16 weeks for 1 year. RESULTS: Of 133 patients screened, 120 were eligible (93.2% men; mean age, 70.8±0.74 years; %FEV1 53.9±2.0%). Baseline characteristics were similar in the two groups. At 1 year, there was a significant improvement in forced expiratory flow 25% to 75% (P=.037) and forced oscillation technique, a significant reduction in exacerbation frequency (0.96 times/y vs 1.71 times/y, P=.019), and a tendency toward reduction in admission rate (0.5 times/y vs 0.8 times/y, P=.196) with NAC vs placebo. There were no significant between-group differences in mMRC dypsnea score, SGRQ score, and 6MWD. No major adverse effects were reported. CONCLUSION: In this study, 1-year treatment with high-dose NAC resulted in significantly improved small airways function and decreased exacerbation frequency in patients with stable COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01136239; URL: www.clinicaltrials.gov.