Novel Respiratory Impedance-Based Phenotypes Reflect Different Pathophysiologies in Chronic Obstructive Pulmonary Disease Patients.

Purpose: The forced oscillation technique (FOT) is a non-invasive method to measure respiratory impedance, the respiratory resistance (Rrs) and reactance (Xrs). The disease probability measure (DPM) is a useful computed tomography (CT) imaging variable for the assessment of gas trapping and emphysema in patients with chronic obstructive pulmonary disease (COPD) using pairs of inspiratory and expiratory CT images. We aimed to develop FOT-based phenotypes and determine whether the phenotypes and their imaging characteristics could facilitate the understanding of COPD pathophysiology. Patients and methods: FOT and spirometry were examined in 164 COPD patients and 22 non-COPD smokers. COPD patients were divided into four FOT-based phenotypes (NL, normal group; RD, resistance-dominant group; XD, reactance-dominant group; and MIX, mixed group) based on the 3rd quartile values of R5 (Rrs at 5Hz) and X5 (Xrs at 5Hz) in the non-COPD group. The emphysematous lesions and the airway lesions were quantitatively assessed in CT images by low attenuation volume and the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), respectively. DPM imaging analysis was also performed in 131 COPD patients. We investigated the differences in COPD parameters between the FOT-based phenotypes. Results: √Aaw at Pi10 were significantly higher in the RD, XD, and MIX groups than in the NL group. The XD group showed lower pulmonary function and higher dyspnea scores than the RD group. No significant changes in DPM values were observed between the RD and the NL groups. The gas-trapping area was significantly higher in the XD group than in the NL group. The MIX group showed the highest dyspnea score, most emphysematous lesions, and the lowest forced expiratory volume in 1 s % predicted value. Conclusion: The FOT-based phenotyping may be useful to assess pathophysiological changes of COPD with CT assessments.

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.

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.

Behavioral Changes in General Practitioners towards Chronic Obstructive Pulmonary Disease Over Five Years: An Observational Study.

OBJECTIVE: Early detection of chronic obstructive pulmonary disease (COPD) is critical for preventing progression; however, the disease is rarely detected in the early stages. One reason for this is that COPD is not generally recognized and diagnosed by general practitioners (GPs). The objective of this study was to observe changes in the knowledge and behavior of GPs regarding the diagnosis and treatment of COPD over a five-year period. METHODS: The surveys were performed using identical and anonymous questionnaires in 2005, 2006 and 2010. During this period, various educational campaigns were conducted. MATERIALS: All members of the Shiga Medical Association working as GPs in Shiga Prefecture. RESULTS: The number of questionnaires collected was 216 of 711, 269 of 731 and 326 of 856, respectively. Throughout the study period, the number of doctors who prescribed inhaled long-acting muscarinic antagonists (LAMAs) significantly increased (p<0.001). However, there were no significant changes in the rate of possession of spirometers or recognition of COPD guidelines. When we focused on the data for internists, the rate of recognition of the guidelines increased significantly (p<0.01), despite a lack of change in the rate of possession of spirometers. Furthermore, the results of the multivariate analysis revealed that increased knowledge concerning COPD was associated with the doctor's specialty, ownership of a spirometer, number of COPD patients attending their clinic and their level of recognition of the guidelines. CONCLUSION: During the study period, the GPs prescribed more inhaled LAMAs. The rate of recognition of COPD guidelines was also increased among internists. Educational campaigns may be more effective if the backgrounds of the GPs are taken into consideration.

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.

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

BACKGROUND AND OBJECTIVE: 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. METHODS: Pulmonary function tests and whole-lung CT were performed in 250 male smokers with COPD, including 167 from University Medical Center at Ho Chi Minh City, Vietnam, and 83 from Shiga University of Medical Science Hospital, Japan. The same CT analysis software was used to measure the percentage of low attenuation volume (%LAV) at the threshold of -950 Hounsfield units and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10). The standardized coefficients in multiple linear regressions were used to evaluate the relative contributions of %LAV and Pi10 to predictions of FEV1 /FVC and FEV1 % predicted. RESULTS: Both %LAV and Pi10 independently predicted either forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) or FEV1 % predicted (P ≤ 0.001 for all standardized coefficients). However, the absolute values of the standardized coefficients were 2-3 times higher for %LAV than for Pi10 in all prediction models. The results were consistent in the two COPD cohorts. CONCLUSIONS: %LAV predicts both FEV1 /FVC and FEV1 better than Pi10 in patients with COPD. Thus, emphysema may make a greater contribution to airflow limitation than airway remodelling in COPD.

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 (R(2) = 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.

[A case of extranodal NK/T-cell lymphoma, nasal type, with skin ulceration and multiple nodules in the lung].

We report a rare case of extranodal NK/T-cell lymphoma, nasal type, with skin ulceration and multiple nodules in the lung, and will compare this case with others in the literature. A 54-year-old man was troubled with flare and swelling of his right arm for one month. He was referred to our hospital because of subcutaneous nodules with ulceration on the right arm, fever, and general fatigue. Chest radiograph revealed multiple nodular shadows in both lungs. The patient was admitted for further evaluation. Chest computed tomography revealed multiple nodules in both lungs with ground-glass opacities around some of them. Some nodules seemed to be clustered in the right lower lobe. Biopsy specimens of subcutaneous nodules and transbronchial biopsy specimens of pulmonary tissue demonstrated only extensive necrosis. A VATS lung biopsy from the right S9 was then taken. Pathological and immunohistological findings suggested a diagnosis of extranodal NK/T-cell lymphoma, nasal type (WHO classification), stage IVB. The patient was transferred to the department of hematology in another hospital for systemic chemotherapy, but died 2 months later.

[A case of hypersensitivity pneumonitis resulting from inhalation of Aspergillus niger in a greenhouse worker who raised roses].

A 57-year-old woman was referred because of exertional dyspnea, fever, and cough in June 2006. She had been employed to culture roses in greenhouses since 1991 and had developed a cough during the summer from 2003. Chest CT scan revealed diffuse centrilobular micronodules. Transbronchial lung biopsy specimens demonstrated alveolitis with lymphocytes and non-necrotizing epithelioid cell granulomas. After admission, both the patient's symptoms and laboratory data improved without medication. However, upon her return to work in the greenhouse, cough and exertional dyspnea reappeared. Aspergillus niger was detected in the greenhouse. Her serum was assayed for precipitating antibodies against various antigens, and precipitating antibodies against Aspergillus fumigatus, Aspergillus flavus, Aspergillus glaucus, and Aspergillus niger were demonstrated. In a double immunodiffusion test, cross-reactivity between Aspergillus niger and other Aspergillus species was indicated. Consequently, she was diagnosed as having hypersensitivity pneumonitis resulting from the inhalation of Aspergillus niger.

[A case of sarcoidosis with pleural involvement but with no mediastinal or hilar lymph node enlargement].

A 66-year-old woman was referred to our hospital because of right chest pain on inspiration. Chest X-ray film revealed diffuse opacities, predominantly in the lower lung field, and right pleural thickening. Serum ACE and lysozyme levels were elevated. Chest CT revealed diffuse ground-glass opacity, centrilobular granular nodules, bronchovascular bundle irregular thickening and right pleural irregular thickening over the right inferior lobe, but bilateral hilar lymph node enlargement was not present. Bronchoalveolar lavage (BAL) fluid demonstrated increased numbers of total cells and CD4 T-helper lymphocytes. The transbronchial lung biopsy specimen revealed non-caseating epithelioid cell granulomas. From these findings, we established a diagnosis of type III sarcoidosis with pleural involvement. The patient has been observed without treatment, and 10 months later the lung involvement and pleural thickening have disappeared.