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.

Significance of lung nodules detected on chest CT among adult Aboriginal Australians - a retrospective descriptive study.

INTRODUCTION: There are limited data on chest computed tomography (CT) findings in the assessment of lung nodules among adult Aboriginal Australians. In this retrospective study, we assessed lung nodules among a group of adult Aboriginal Australians in the Northern Territory of Australia. METHODS: Patients who underwent at least two chest CT scans between 2012 and 2020 among those referred to undergo lung function testing (spirometry) were included. Chest CT scans were assessed for the number, location, size and morphological characteristics of lung nodules. RESULTS: Of the 402 chest CTs assessed, 75 patients (18.7%) had lung nodules, and 57 patients were included in the final analysis with at least two CT scans available for assessment over a median follow-up of 87 weeks. Most patients (68%) were women, with a median age of 58 years and smoking history in 83%. The majority recorded only a single nodule 43 (74%). Six patients (10%) were diagnosed with malignancy, five with primary lung cancer and one with metastatic thyroid cancer. Of the 51 (90%) patients assessed to be benign, 64 nodules were identified, of which 25 (39%) resolved, 38 (59%) remained stable and one (1.8%) enlarged on follow-up. Nodules among patients with malignancy were typically initially larger and enlarged over time, had spiculated margins and were solid, showing no specific lobar predilection. CONCLUSIONS: Most lung nodules in Aboriginal Australians are likely to be benign. However, a proportion could be malignant. Further prospective studies are required for prognostication and monitoring of lung nodules in this population.

Detection of EGFR mutations in patients with suspected lung cancer using paired tissue-plasma testing: a prospective comparative study with plasma ddPCR assay.

Detecting EGFR mutations in plasma using droplet digital PCR (ddPCR) assay offers a promising diagnostic tool for lung cancer patients. The performance of plasma-based ddPCR assay relative to traditional EGFR mutation testing in tissue biopsies among Asian patients with suspected lung cancer remains underexplored. Consecutive patients admitted for diagnostic workup for suspected lung cancer were recruited. Peripheral blood samples were collected on the same day of tissue biopsies. Tissue samples were subjected to EGFR mutation analysis via real-time PCR, whereas plasma samples were processed for ddPCR assay to evaluate for EGFR mutation status. The tissue re-biopsy rate was 43.8% while 0.7% of patients failed blood taking. Despite repeat biopsy, 15.2% of patients could not achieve histological diagnosis. Of the 202 patients newly diagnosed with lung cancer, EGFR mutations were detected in 13.4% of plasma samples, compared to 44.3% in tissue samples. Plasma ddPCR for EGFR mutations detection were barely detectable in stages I and II non-small cell lung cancer (NSCLC), but the sensitivity was 25.0%, 56.3%, and 75.0% in stages III, IVA, and IVB NSCLC, respectively. Plasma EGFR mutations were highly specific among all stages of lung cancer. Concordance rates of plasma ddPCR assay also rose with more advanced stages, recorded at 41.9% for stages I and II, 71.9% for stage III, 86.3% for stage IV. In stage IV lung cancer, the false negative rate for the plasma ddPCR assay was 34.4%, whereas that for the tissue testing was 19.2% due to insufficient tissue samples. Plasma-based EGFR genotyping using ddPCR is a non-invasive method that offers early diagnosis and serves as a valuable adjunct to tissue-based testing for patients with advanced-stage lung cancer. However, its usefulness is limited in the context of early-stage lung cancer, indicating a need for further research to improve its accuracy in these patients.

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.

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.

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.