[Characteristics of chronic obstructive pulmonary disease phenotypes based on high-resolution CT and the relationship with interleukin-6].
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Abstract:
Objective
To classify the high-resolution CT (HRCT) phenotypes of COPD, and to investigate the clinical characteristics of various phenotypes and the relationship with airway inflammation.
Methods
Chest HRCT and pulmonary function tests were performed in 84 COPD patients. The patients were classified into 3 phenotypes according to the visual HRCT findings. Exhaled breath condensate was gathered from 30 patients and the interleukin (IL)-6 level was measured by ELISA.
Results
The COPD patients were classified into 3 phenotypes: Phenotype A, absence of emphysema, with or without bronchial wall thickening (n=34); Phenotype E, emphysema without bronchial wall thickening (n=23); and Phenotype M, emphysema with bronchial wall thickening (n=27). The 3 phenotypes of COPD showed different characteristics in several aspects. Patients with phenotype A showed a higher body mass index [(25.1±4.4) kg/m2vs phenotype E (22.5±4.1) kg/m2 and phenotype M (21.3±3.4) kg/m2,F=6.732, P<0.01]. The prevalence of patients with milder dyspnea was lower in phenotype A compared with others (15/34) vs phenotype E (2/23) and phenotype M (6/27), χ2 =9.097, P<0.05. The patients who complained of severe expectoration in phenotype E were fewer than those in other groups (0/23) vs phenotype A (2/34) and phenotype M (4/27), χ2=8.702, P<0.05. The FEV1/FVC and FEV1% in phenotype M [(53±14)% and (51±25)%] were significantly lower as compared with those in other phenotypes [ (67±11)% and (72±24)% in phenotype A, and (53±14)% and (52±26)% in phenotype E], F=10.252, F=6.508, P<0.01. The ratio of inspiratory capacity to total lung capacity (IC/TLC) in phenotype A was higher [phenotype A (41±17)%, phenotype E (33±13)%, phenotype M (28±13)%, F=5.964, P<0.01], while the ratio of residual volume to total lung capacity (RV/TLC) was lower [phenotype A (37±9)%, phenotype E (44±10)%, phenotype M (45±8)%, F=6.954, P<0.01]. Patients with different phenotypes showed various levels of IL-6 in exhaled breath condensate [phenotype A (19.9±6.3) ng/L, phenotype E (16.7±2.1) ng/L, phenotype M (25.6±4.4) ng/L, F=7.749, P<0.01].
Conclusion
Various morphological phenotypes of COPD based on HRCT showed different clinical characteristics and airway inflammation.
Key words:
Pulmonary disease, chronic obstructive; Tomography, X-ray computed; Respiratory function tests; Interleukin-6Keywords:
Air trapping
Clinical phenotype
Air trapping
Perimeter
Airway obstruction
Respiratory tract
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Sputum and blood eosinophils are proposed as candidate biomarkers for the identification of chronic obstructive pulmonary disease (COPD) patients at risk for exacerbation and treatment response. In this study, we evaluated the associations of eosinophils with the presence of emphysema in COPD patients. Induced sputum and blood eosinophil measurements were performed in consecutive COPD patients. Patients underwent lung function testing and high resolution computed tomography (HRCT) of the chest and the presence of emphysema was quantified. Patients with emphysematous lesions in ≥15% of the pulmonary parenchyma were considered having significant emphysema. Ninety-eight patients were included in the study. Patients with significant emphysema had lower blood eosinophil counts compared to patients without emphysema [median (IQR) 34.6 (0.0, 63.0) vs. 169.0 (110.0, 260.0) cells/µL, p < 0.001]; similar results were observed for the percentage (%) of blood eosinophils, but no difference was observed for sputum eosinophils. The differences were evident in frequent and non-frequent exacerbators and irrespective of the use of inhaled corticosteroids (ICS). Patients with significant emphysema in HRCT present lower levels of blood eosinophils and these differences were present irrespective of the frequent exacerbator history or the use of ICS. Blood eosinophils may not represent a clinically relevant biomarker in the presence of emphysema.
High-resolution computed tomography
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Objective To evaluate the characteristics of airway inflammation in patients with the emphysema phenotype of chronic obstructive pulmonary disease (COPD).Methods Fifty-two outpatients with stable COPD were examined.For each subject,the clinical data were collected,and HRCT scanning and lung function tests were performed.Sputum cells were counted and the supernants were processed for measurement of IL-6,IL-8,TNF-α,VEGF,MMP-9 and TIMP-1.The subjects were divided into 2 groups:an emphysema group (n =29) and a non-emphysema group (n =23) based on the HRCT emphysema index (EI).Results There was no difference between the 2 groups in sex,age,body mass index,time course of cough and wheeze,and smoking (all P ＞0.05).FEV1 ％pred,DLCO％pred,and DLCO/VA％ pred were significantly decreased in the emphysema group as compared to the nonemphysema group [(48.21± 13.44)％ vs (57.04± 12.61)％,P =0.019; (48.57± 16.76)％ vs (65.64±12.48)％,P=0.001;(59.52±15.33)％ vs (82.99±16.31) ％,P＜0.001],but RV/TLC and RV％pred were significantly increased in the emphysema group [(53.86± 10.98)％ vs (44.93 ±6.72)％,P =0.003;(129.95±18.88)％ vs (118.77±13.16)％,P =0.037].The number and the percentage of sputum eosinophils were higher in the emphysema group [0.05 (0.00,0.13) × 109/L vs 0.00(0.00,0.01) × 109/L,P =0.032;0.50(0.00,2.00)％ vs 0.00(0.00,0.25)％,P =0.033].Moreover,the percentage of sputum eosinophils was positively correlated with emphysema index (B =1.248,P =0.007).However,there was no difference between the 2 groups in the number or percentage of sputum neutrophils,lymphocytes and macrophages.The sputum level of TNF-αtended to be higher in the emphysema group as compared to the non emphysema group [221.72(100.00,351.57) ng/L vs 144.85(54.51,269.16) ng/L,P =0.063],but the levels of IL-8,IL-6,VEGF,MMP-9,TIMP-1 and the ratio of MMP 9/TIMP-1 were not different between groups.Conclusions Patients with the emphysema phenotype of COPD in this study tended to have higher airway eosinophils and TNF-α,suggesting a differenct inflammatory profile which needed to be further explored.
Key words:
Chronic obstructive pulmonary disease; Phenotype; Emphysema; Airway inflammation
DLCO
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Objective
To study the correlation between CT features and pulmonary function indexes in different chronic obstructive pulmonary diseases(COPD).
Methods
Collection of COPD patients with 80 cases were collected,, the correlation analysis of COPD CT features(pixel index)and pulmonary function, including one second forced expiratory volume(FEV1), one second forced expiratory volume accounted for the percentage of forced vital capacity(FVC)and residual volume/lung total ratio(RV/TLC)were examined by pulmonary function testing(PFT)and multislice spiral CT(MSCT).
Results
According to CT,the regional area of lung density(LAA%)and airway wall thickness/lumen area were measured,COPD was divided into 56 cases of emphysema phenotype,13 case of airway phenotype and 11 case of mixed phenotype.The emphysema phenotype index,FEV1,FEV1/FVC pixels,RV/TLC=27.68%,(32.19±16.78)%,(43.69±11.23),(55.67±15.49),airway phenotype were 5.23%,(55.67±23.12)%,(52.30±10.67),(49.48±13.27),respectively,mixed phenotype were 22.47%(41.23±12.55)%,(47.31±9.98),(54.19±16.29),FEV 1,FEV1/FVC,pixel index, RV/TLC COPD CT in different phenotypic differences were statistically significant(χ2=19.013,F=6.234,7.854,6.389,all P 0.05).
Conclusion
CT features can be regarded as the reference to diagnosis the COPD phenotype and evaluate the effect of treatment, it is necessary to re-examine PFT in emphysema and airway phenotypes.
Key words:
Pulmonary disease, Chronic obstruction; Tomography, X-ray computer
Vital capacity
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Alpha 1-antitrypsin deficiency
Alpha (finance)
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ABSTRACT Background and objective Chronic exposure to biomass smoke ( BS ) can significantly compromise pulmonary function and lead to chronic obstructive pulmonary disease ( COPD ). To determine whether BS exposure induces a unique phenotype of COPD from an early stage, with different physiopathological features compared with COPD associated with smoking (cigarette‐smoke (CS) COPD ), we assessed the physiopathology of early COPD associated with BS exposure ( BS COPD ) by incorporating spirometry, high‐resolution computed tomography ( HRCT ) imaging, bronchoscopy and pathological examinations. Methods In this cross‐sectional study, we recruited 29 patients with BS COPD , 31 patients with CS COPD and 22 healthy controls, including 12 BS ‐exposed subjects who did not smoke and 10 healthy smokers without BS exposure. Spirometry, HRCT scans, bronchoscopy and bronchial mucosa biopsies were performed to assess lung function, emphysema and air trapping, as well as the pathological characteristics and levels of inflammatory cells in bronchoalveolar lavage fluid ( BALF ). Results Among COPD patients with mild‐to‐moderate airflow limitation, BS exposure caused greater small airway dysfunction in BS COPD patients, although these patients had less emphysema and air trapping, as detected by HRCT ( P < 0.05). We also observed significantly thicker basement membranes and greater endobronchial pigmentation in BS COPD than in CS COPD ( P < 0.05). Moreover, patients with BS COPD exhibited greater macrophage and lymphocyte infiltration but reduced neutrophil infiltration in their BALF ( P < 0.05). Conclusion We used both radiology and pathology to document a distinct COPD phenotype associated with BS exposure. This is characterized by small airway disease.
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We have been engaged in the analysis of the distribution of low attenuation area (LAA) representing emphysema, and the measurement of airway dimensions using CT images from the view point of phenotyping of COPD. (1) L AA% (area ratio of LAA to all lung area) did not correlate with reversibility to bronchodilators, whereas WA% (area ratio of bronchial wall to cross section of bronchus) positively correlated with reversibility. Thus, bronchodilators may be effective in proportional to the extent of airway disorders. (2) The incidence of Gc*1F(+) was significantly higher in patients with severe emphysema. These results indicate that the patients with Gc*1F(+) have rapid development of emphysema. (3) Polymorphism of MMP-9 (C -1562T) was associated with upper lung dominant emphysema in patients with COPD. (4) CT measurements of emphysema were greater in the patients with anorexia nervosa than in historical control subjects (p<0.001). Furthermore, there were significant correlations between the body mass index and the CT measures of emphysema. These data demonstrate that emphysema-like changes are present in the lungs of patients who are chronically malnourished.
Pulmonary emphysema
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DLCO
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Objective: The Global Initiative for Obstructive Lung Disease characterizes COPD as airflow limitation caused by parenchymal destruction and/or small airway disease. This report characterizes the clinical features of these two phenotypes of COPD in Japan. Methodology: COPD was diagnosed by spirometric airflow limitation (FEV 1 /FVC < 70%), and all subjects underwent chest CT scanning. Patients with diffuse low attenuation areas (LAA) on CT scan were categorized as the emphysema‐dominant phenotype; those with little LAA were categorized as the airway disease‐dominant phenotype. The two groups were compared to identify significant clinical or demographic differences. Results: Of the 1438 patients analysed, 1294 (90%) were classified as having an emphysema‐dominant phenotype and 144 (10%) as having an airway disease‐dominant phenotype. The airway disease‐dominant phenotype was: more common than the emphysema‐dominant phenotype in women (15% vs. 7%, P < 0.01) and in non‐smokers (6% vs. 2%, P < 0.05); was more commonly complicated by asthmatic features (35% vs. 21%, P < 0.01); and had higher IgE and eosinophil levels ( P < 0.05) and less lung function impairment. Conclusion: This analysis is the first to clinically define two phenotypes of COPD in a Japanese epidemiological survey. There appear to be striking differences as well as overlap between these two groups. Further research is warranted to determine the significance of COPD phenotypes.
Air trapping
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Abstract Background The difference in expression of sputum cells types between the two main types of chronic obstructive pulmonary disease (COPD) is largely unknown. This study aims to investigate the difference and then wants to depend on sputum cells sorting to direct the treatment of COPD. Methods A total of 218 patients with stable COPD (FEV1 < 80%) were selected. Stable COPD patients ( n = 218) were classified as eosinophilic (A phenotype) or noneosinophilic (B phenotype); sometimes, the subjects were separated into cough group (C phenotype) and dyspnea group (D phenotype). Cross‐sectional analysis was conducted comparing demographics and clinical characteristics. Receiver‐operating characteristic curve was used to assess predictive ability of sputum eosinophils for D phenotype. Results The A phenotype showed a higher correlation with the patients complaining of presenting with dyspnea on exertion, the dyspnea group (D phenotype). The B phenotype showed a higher prevalence of those who cough and product sputum, this was cough group (C phenotype). Sputum eosinophil and macrophages counts were significantly higher in patients with dyspnea ( n = 95) compared to those with cough ( P < .05), and neutrophils were significantly lower in patients with dyspnea ( n = 95) compared to those with cough ( P < .05). Percentage sputum eosinophil count was predictive of dyspnea (D phenotype) COPD with area under curve (AUC) of 0.831 (95% confidence interval (CI) 0.77‐0.89; P ≤ .001). Neutrophils were also predictive of dyspnea (D phenotype) COPD with AUC of 0.276 (95% CI 0.204–0.347; P ≤ .001). Conclusion These findings suggest that the morphological phenotypes of COPD show several clinical characteristics and different sputum cell sorting.
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