Nguyen Van Tho

Asthma–COPD overlap syndrome (ACOS): A diagnostic challenge

Asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is characterized by persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD. ACOS may be a special phenotype of a spectrum of chronic obstructive airway diseases, in which asthma and COPD are at the two opposite ends. The prevalence of ACOS varies considerably due to differing criteria being applied for diagnosis. Patients with ACOS utilize a large proportion of medical resources. They are associated with more frequent adverse outcomes than those with asthma or COPD alone. ACOS is currently a diagnostic challenge for physicians because there are no specific biomarkers to differentiate ACOS from asthma or COPD. The approach to diagnosing ACOS depends on the population from which the patient originated. The management of ACOS should be individualized to ensure the most effective treatment with minimal side effects. In this paper, we review the diagnostic criteria of ACOS used in previous studies, propose practical approaches to diagnosing and managing ACOS and raise some research questions related to ACOS.

Radiological Approach to Asthma and COPD-The Role of Computed Tomography

Asthma and chronic obstructive pulmonary disease (COPD) are among the most prevalent lung diseases. In both asthma and COPD, airway inflammation leads to airway remodeling. Parenchyma of the lung is also influenced by disease conditions. Airway wall thickening/lumen narrowing and parenchymal destruction occur in COPD. In asthma, airway remodeling contributes to the lung parenchyma. Computed tomography (CT) has been widely used as an imaging tool for lung diseases. With the technical advancement of CT, together with the development of analysis software, it is now possible to analyze the lung parenchymal change and airway remodeling quantitatively using CT. This article reviews the role of CT in assessing the lung structure and functions of patients with asthma and COPD.Asthma and chronic obstructive pulmonary disease (COPD) are among the most prevalent lung diseases. In both asthma and COPD, airway inflammation leads to airway remodeling. Parenchyma of the lung is also influenced by disease conditions. Airway wall thickening/lumen narrowing and parenchymal destruction occur in COPD. In asthma, airway remodeling contributes to the lung parenchyma. Computed tomography (CT) has been widely used as an imaging tool for lung diseases. With the technical advancement of CT, together with the development of analysis software, it is now possible to analyze the lung parenchymal change and airway remodeling quantitatively using CT. This article reviews the role of CT in assessing the lung structure and functions of patients with asthma and COPD.

Recent findings in chronic obstructive pulmonary disease by using quantitative computed tomography

Chronic obstructive pulmonary disease (COPD) is characterized by an incompletely reversible airflow limitation that results from a combination of airway wall remodeling and emphysematous lung destruction. Forced expiratory volume in 1s (FEV(1)) has been considered the gold standard for diagnosis, classification, and follow-up in patients with COPD, but it has certain limitations and it is still necessary to find other noninvasive modalities to complement FEV(1) to evaluate the effect of therapeutic interventions and the pathogenesis of COPD. Quantitative computed tomography (CT) has partly met this demand. The extent of emphysema and airway dimensions measured using quantitative CT are associated with morphological and functional changes and clinical symptoms in patients with COPD. Phenotyping COPD based on quantitative CT has facilitated interventional and genotypic studies. Recent advances in COPD findings with quantitative CT are discussed in this review.

A Mixed Phenotype of Airway Wall Thickening and Emphysema Is Associated with Dyspnea and Hospitalization for Chronic Obstructive Pulmonary Disease

RATIONALE Quantitative computed tomography (CT) has been used to phenotype patients with chronic obstructive pulmonary disease (COPD). A mixed phenotype is defined as the presence of both airway wall thickening and emphysema on quantitative CT. Little is known about patients with COPD with the mixed phenotype. OBJECTIVES To propose a method of phenotyping COPD based on quantitative CT and to compare clinically relevant outcomes between patients with COPD with the mixed phenotype and those with other CT-based phenotypes. METHODS Each of 427 male smokers (187 without COPD, 240 with COPD) underwent a complete medical interview, pulmonary function testing, and whole-lung CT on the same day. The percentage of low-attenuation volume at the threshold of -950 Hounsfield units (%LAV) and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10) were measured. Patients with COPD were classified into four distinct phenotypes based on the upper limits of normal for %LAV and Pi10, which were derived from the data of smokers without COPD by using quantile regression. MEASUREMENTS AND MAIN RESULTS Of 240 patients with COPD, 52 (21.7%) were classified as CT-normal phenotype, 39 (16.3%) as airway-dominant phenotype, 103 (42.9%) as emphysema-dominant phenotype, and 46 (19.2%) as mixed phenotype. Patients with COPD with the mixed phenotype were associated with more severe dyspnea than those with each of the remaining CT-based phenotypes (P < 0.01 for all comparisons). The number of hospitalizations for COPD exacerbations during the preceding year was 2.0 to 3.6 times higher in patients with the mixed phenotype than in those with each of the remaining CT-based phenotypes (P < 0.05 for all comparisons). Findings persisted after adjustment for age, pack-years of smoking, smoking status, body mass index, and FEV1. CONCLUSIONS Patients with COPD with the mixed phenotype are associated with more severe dyspnea and more frequent hospitalizations than those with each of the remaining CT-based phenotypes. Thus, patients with COPD with the mixed phenotype may need more attention and interventions.

Factors Affecting Time to Sputum Culture Conversion in Adults with Pulmonary Tuberculosis: A Historical Cohort Study without Censored Cases

Background In patients with pulmonary tuberculosis (TB), shortening the time to sputum culture conversion is desirable to reduce the likelihood of mycobacterial transmission. A persistent positive sputum culture after 2 months of treatment is reported to be associated with the presence of cavitation and the extent of disease on chest X-ray, high colony count, diabetes mellitus, and smoking. However, little is known about factors affecting the time to sputum culture conversion. This study was conducted to evaluate factors affecting the time to sputum culture conversion throughout the course of treatment in adults with pulmonary TB. Methods This study was performed using a database of the medical records of patients with active pulmonary TB who were treated at Hirakata Kohsai Hospital in Hirakata City, Osaka, Japan, from October 2000 to October 2002. Cox proportional-hazards analysis was used to evaluate factors affecting the time to sputum culture conversion after adjusting for potential confounders. Results The data of 86 patients with pulmonary TB were analyzed. The median time to sputum culture conversion was 39 days, and the maximum time was 116 days. The Cox proportional-hazards analysis showed that a higher smear grading (HR, 0.40; 95%CI, 0.23–0.71) and a history of ever smoking (HR, 0.48; 95%CI, 0.25–0.94) were associated with delayed sputum culture conversion. Conclusion High smear grading and smoking prolonged the time to sputum culture conversion in adults with pulmonary TB. To effectively control TB, measures to decrease the cigarette smoking rate should be implemented, in addition to early detection and timely anti-TB treatment.

Airway wall area derived from 3-dimensional computed tomography analysis differs among lung lobes in male smokers.

Background It is time-consuming to obtain the square root of airway wall area of the hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), a comparable index of airway dimensions in chronic obstructive pulmonary disease (COPD), from all airways of the whole lungs using 3-dimensional computed tomography (CT) analysis. We hypothesized that √Aaw at Pi10 differs among the five lung lobes and √Aaw at Pi10 derived from one certain lung lobe has a high level of agreement with that derived from the whole lungs in smokers. Methods Pulmonary function tests and chest volumetric CTs were performed in 157 male smokers (102 COPD, 55 non-COPD). All visible bronchial segments from the 3rd to 5th generations were segmented and measured using commercially available 3-dimensional CT analysis software. √Aaw at Pi10 of each lung lobe was estimated from all measurable bronchial segments of that lobe. Results Using a mixed-effects model, √Aaw at Pi10 differed significantly among the five lung lobes (R2 = 0.78, P<0.0001). The Bland-Altman plots show that √Aaw at Pi10 derived from the right or left upper lobe had a high level of agreement with that derived from the whole lungs, while √Aaw at Pi10 derived from the right or left lower lobe did not. Conclusion In male smokers, CT-derived airway wall area differs among the five lung lobes, and airway wall area derived from the right or left upper lobe is representative of the whole lungs.

Relative contributions of emphysema and airway remodelling to airflow limitation in COPD: Consistent results from two cohorts

The relative contributions of emphysema and airway remodelling to airflow limitation remain unclear in chronic obstructive pulmonary disease (COPD). We aimed to evaluate the relative contributions of emphysema and airway wall thickness measured by quantitative computed tomography (CT) to the prediction of airflow limitation in two separate COPD cohorts.

Quantitative CT analysis of honeycombing area in idiopathic pulmonary fibrosis: Correlations with pulmonary function tests

OBJECTIVES The 2011 official statement of idiopathic pulmonary fibrosis (IPF) mentions that the extent of honeycombing and the worsening of fibrosis on high-resolution computed tomography (HRCT) in IPF are associated with the increased risk of mortality. However, there are few reports about the quantitative computed tomography (CT) analysis of honeycombing area. In this study, we first proposed a computer-aided method for quantitative CT analysis of honeycombing area in patients with IPF. We then evaluated the correlations between honeycombing area measured by the proposed method with that estimated by radiologists or with parameters of PFTs. MATERIALS AND METHODS Chest HRCTs and pulmonary function tests (PFTs) of 36 IPF patients, who were diagnosed using HRCT alone, were retrospectively evaluated. Two thoracic radiologists independently estimated the honeycombing area as Identified Area (IA) and the percentage of honeycombing area to total lung area as Percent Area (PA) on 3 axial CT slices for each patient. We also developed a computer-aided method to measure the honeycombing area on CT images of those patients. The total honeycombing area as CT honeycombing area (HA) and the percentage of honeycombing area to total lung area as CT %honeycombing area (%HA) were derived from the computer-aided method for each patient. RESULTS HA derived from three CT slices was significantly correlated with IA (ρ=0.65 for Radiologist 1 and ρ=0.68 for Radiologist 2). %HA derived from three CT slices was also significantly correlated with PA (ρ=0.68 for Radiologist 1 and ρ=0.70 for Radiologist 2). HA and %HA derived from all CT slices were significantly correlated with FVC (%pred.), DLCO (%pred.), and the composite physiologic index (CPI) (HA: ρ=-0.43, ρ=-0.56, ρ=0.63 and %HA: ρ=-0.60, ρ=-0.49, ρ=0.69, respectively). CONCLUSIONS The honeycombing area measured by the proposed computer-aided method was correlated with that estimated by expert radiologists and with parameters of PFTs. This quantitative CT analysis of honeycombing area may be useful and reliable in patients with IPF.

Increased Epicardial Adipose Tissue Is Associated with the Airway Dominant Phenotype of Chronic Obstructive Pulmonary Disease

Background Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD). It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD). However, little is known about which phenotypes of COPD are associated with increased EAT. Methods One hundred and eighty smokers who were referred to the clinic were consecutively enrolled. A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT. These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the EAT area, respectively. The same measurements were made on 225 Vietnamese COPD patients to replicate the results. Results Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV1/FVC<0.70. The EAT area was significantly associated with age, BMI, FEV1 (%predicted), FEV1/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and √Aaw at Pi10 in COPD patients. The multiple regression analyses showed that only BMI, self-reported CVD and √Aaw at Pi10 were independently associated with the EAT area (R2 = 0.51, p<0.0001). These results were replicated in the Vietnamese population. Conclusions The EAT area is independently associated with airway wall thickness. Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD.

Simian virus 40 may be associated with developing malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is associated with a history of heavy, long-term exposure to asbestos. However, MPM may also be associated with simian virus 40 (SV40), a polyomavirus. The association between SV40 and MPM remains unclear. The present study was conducted in order to investigate the proportion of SV40 presence in the histological specimens of Vietnamese patients with MPM. Histological specimens were obtained from 45 patients (19 men and 26 women) with MPM at the Pham Ngoc Thach Hospital in Ho Chi Minh City, Vietnam. The specimens were processed and examined in order to detect the presence of the SV40 large T antigen (SV40 Tag) expression using immunohistochemistry. Of the 45 patients, 23 (51%) were epithelioid, 7 (16%) were biphasic, 6 (13%) were sarcomatoid, 4 (9%) were desmoplastic, 4 (9%) were well-differentiated papillary and 1 (2%) was the anaplastic subtype. In total, 9/45 patients (20%) demonstrated SV40 Tag expression. The proportion of patients that demonstrated SV40 Tag expression was not significantly different between the epithelioid subtype and the other subtypes (22 vs. 18%; P=1.000) or between the patients with stage IV disease and other stages (20 vs. 20%; P=1.000). The median survival time was not significantly different between the patients with or without SV40 Tag expression (196 vs. 236 days, P=0.8949). In summary, a 5th of the Vietnamese patients with MPM were associated with infection with SV40. SV40 may be a potential cause of MPM in Vietnam and this potential association requires additional studies.