Exercise capacity predicts health status in alpha(1)-antitrypsin deficiency

Resting lung function is only weakly related to health status in chronic obstructive pulmonary disease, reflecting the multifactorial causes of impairment and the heterogeneous nature of the condition. The current study examined whether density mask analysis of high-resolution computed tomography (HRCT) or exercise capacity were better surrogates for health status in a well-defined, homogeneous group of patients with alpha(1)-antitrypsin deficiency (PiZ). Twenty-nine patients with predominantly lower zone emphysema on HRCT were studied. Exercise was assessed by incremental treadmill (V O(2) peak) and shuttle walking tests (ISWT) and health status by the St. George's Respiratory Questionnaire (SGRQ) and SF-36. Although lower zone expiratory HRCT was related to exercise capacity (rho = -0.64 and -0.63 for V O(2) peak and ISWT, respectively, p < 0.001), multiple regression analysis suggested that FEV(1) was a marginally better predictor (rho = -0.64 and -0.65, p < 0.001). HRCT also related significantly to health status (rho = -0.37 for SGRQ activity, p < 0.05), although again FEV(1) showed a stronger relationship (rho = -0.43, p = 0.01). However, exercise capacity was the best predictor of health status with the ISWT accounting for up to 55% of the variability seen in SGRQ total and up to 53% of the SF-36 domain scores (physical functioning). Although both HRCT and lung function relate to health status, exercise capacity is the best predictor of patients disability in these patients with predominantly lower zone emphysema.     

Relationship between extent of pulmonary emphysema by high-resolution computed tomography and lung elastic recoil in patients with chronic obstructive pulmonary disease

We investigated the relationship between the extent of pulmonary emphysema, assessed by quantitative high-resolution computed tomography (HRCT), and lung mechanics in 24 patients with chronic obstructive pulmonary disease (COPD). The extent of emphysema was quantified as the relative lung area with CT numbers < -950 Hounsfield Units (HU). Patients with COPD had severe airflow obstruction (FEV(1) 35 +/- 15% pred) and severe reduction of CO diffusion constant (DCO/VA 37 +/- 19% pred). Maximal static elastic recoil pressure (Pst(max)) averaged 54 +/- 24% predicted, and the exponential constant K of pressure-volume curves was 258 +/- 116% predicted. Relative lung area with CT numbers < -950 HU averaged 21 +/- 11% (range 1 to 38%). It showed a highly significant negative correlation with DCO/VA (r = -0.84, p < 0.0001), a weak correlation with FEV(1)% predicted, and no correlation with either Pst(max) or constant K. A significant relationship was found between the natural logarithm of K and the full width at half maximum of the frequency distribution of CT numbers, taken as an index of the heterogeneity of lung density (r = 0.68, p < 0.0005). We conclude that currently used methods of assessing the extent of emphysema by HRCT closely reflect the reduction of CO diffusion constant, but cannot predict the elastic properties of the lung tissue.     

Mixed infiltrative and obstructive disease on high-resolution CT: differential diagnosis and functional correlates in a consecutive series

Fourteen of 400 consecutive patients having high-resolution computed tomography (HRCT) with expiratory images showed findings of infiltrative lung disease on inspiratory HRCT and air trapping on expiratory CT. Diagnoses included hypersensitivity pneumonitis, sarcoidosis, atypical infection, and pulmonary edema. The extent of infiltrative abnormalities and air trapping were correlated with pulmonary function tests (PFT) in 11 patients. PFT indicated a mixed pattern in five, an obstructive pattern in three, and a restrictive pattern in three. Forced expiratory volume (FEV) in 1 second/forced vital capacity (FVC) correlated significantly with the extent of air-trapping (r = 0.60; p = 0.05). The extent of infiltrative abnormalities correlated significantly and negatively with forced vital capacity (r = -0.82, p = 0.002), FEV1 (r = -0.59, p = 0.05), total lung capacity (TLC) (r = -0.67, p = 0.05), and DLCO (r = -0.75, p = 0.02). Findings of lung infiltration on inspiratory HRCT scans and air trapping on expiratory CT correlated respectively with PFT measures of restrictive and obstructive lung disease.     

Matrix metalloproteinase-9 promoter polymorphism associated with upper lung dominant emphysema

RATIONALE: Matrix metalloproteinase 9 (MMP-9) has proteolytic activity against connective tissue proteins and appears to play an important role in the development of chronic obstructive pulmonary disease (COPD). The functional polymorphism of MMP-9 (C-1562T) is considered as one of the candidate genes in the susceptibility to COPD. OBJECTIVES: To determine if MMP-9 (C-1562T) is related to the development of COPD in the Japanese population and whether it is associated with development of pulmonary emphysema assessed by high-resolution computed tomographic (HRCT) parameters. METHODS: MMP-9 (C-1562T) genotypes of 84 patients with COPD and 85 healthy smokers (control subjects) were determined by the restriction fragment length polymorphism method. We investigated the relationship between the genotypes using automatically analyzed HRCT parameters, such as percentage of low attenuation area (LAA%) and average computed tomography (CT) value density (Hounsfield units; mean CTv) in upper, middle, and lower lung fields in all patients with COPD. MEASUREMENTS AND MAIN RESULTS: There was no difference in polymorphism of MMP-9 (C-1562T) between patients with COPD and control subjects. In the HRCT study, patients with COPD with a T allele (C/T or T/T) showed larger LAA% (95% confidence interval of difference, 0.5-18.7; p = 0.04), and smaller mean CTv (confidence interval, -34.3 to -1.0; p = 0.04) in the upper lung compared with patients without T alleles (C/C). However, pulmonary function tests showed no difference between the two patient groups. Patients with a T allele showed a decrease in LAA% and an increase in mean CTv from upper to lower lung fields (p = 0.006 and p = 0.002, respectively). CONCLUSIONS: Polymorphism of MMP-9 (C-1562T) was associated with upper lung dominant emphysema in patients with COPD.     

Pulmonary function tests, high-resolution computerized tomography, α1-antitrypsin measurement, and early detection of pulmonary involvement in patients with systemic sclerosis

OBJECTIVE: Pulmonary disease represents a major complication of systemic sclerosis (SSc). However, pulmonary involvement is commonly silent. In this study, we investigated the relationship between serum alpha1-antitrypsin and other means of assessing pulmonary involvement. METHODS: Twenty-two patients affected by SSc were studied (mean age 37.6+/-14.3 years, mean duration of disease 9.9+/-11.9 years). Fourteen had the diffuse form of disease (dSSc) and eight had the limited form (lSSc). All patients underwent pulmonary function tests, high-resolution computed tomography (HRCT) of the lungs, echocardiography, and serum assessment of alpha1-antitrypsin. RESULTS: Mean percentage of predicted values of forced vital capacity was lower in patients with dSSc than with lSSc (72.3+/-17.8 vs 74.5+/-8, P=NS). Mean percentage of predicted values of forced expiratory volume in 1-s forced vital capacity (FEV1/FVC) was lower in patients with lSSc (79.8+/-7.5 for lSSc vs 84.4+/-7.8 for dSSc, P= NS). The overall HRCT score was 5.6+/-5.9 with no significant difference between disease subgroups. Pulmonary hypertension was detected in two cases, both with dSSc. Alpha1-antitrypsin was significantly higher in patients than in controls (P < 0.01), with no significant difference between disease subgroups, and correlated significantly with ground glass opacities in H RCT (P < 0.05) and the detection of diffusion defects (r= -0.61, P<0.01). No significant correlation was observed between skin score or degree of dyspnea with HRCT score, lung volume, or carbon monoxide diffusing capacity. CONCLUSION: Restrictive lung disease was more pronounced in patients with dSSc. Alpha1-antitrypsin levels correlated significantly with ground glass opacities, an early finding of pulmonary involvement in SSc. Extent and severity of skin involvement and degree of dyspnea were not related to pulmonary involvement.     

National Emphysema Treatment Trial state of the art: genetics of emphysema

Although a hereditary contribution to emphysema has been long suspected, severe alpha1-antitrypsin deficiency remains the only conclusively proven genetic risk factor for chronic obstructive pulmonary disease (COPD). Recently, genome-wide linkage analysis has led to the identification of two promising candidate genes for COPD: TGFB1 and SERPINE2. Like multiple other COPD candidate gene associations, even these positionally identified genes have not been universally replicated across all studies. Differences in phenotype definition may contribute to nonreplication in genetic studies of heterogeneous disorders such as COPD. The use of precisely measured phenotypes, including emphysema quantification on high-resolution chest computed tomography scans, has aided in the discovery of additional genes for clinically relevant COPD-related traits. The use of computed tomography scans to assess emphysema and airway disease as well as newer genetic technologies, including gene expression microarrays and genome-wide association studies, has great potential to detect novel genes affecting COPD susceptibility, severity, and response to treatment.     

Normal diffusing capacity in patients with PiZ alpha(1)-antitrypsin deficiency, severe airflow obstruction, and significant radiographic emphysema

alpha(1)-Antitrypsin deficiency is usually suspected clinically in young adults with irreversible airflow obstruction that is out of proportion to their smoking history. Many patients with alpha(1)-antitrypsin deficiency receive an initial diagnosis of asthma or chronic bronchitis. Measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) has been recommended as a way to help distinguish emphysema from asthma and chronic bronchitis. In this article, we describe four patients with severe alpha(1)-antitrypsin deficiency, each of whom had a repeatedly normal DLCO despite having a significant component of fixed airway obstruction and prominent panacinar emphysema on high-resolution CT scan (HRCT). Each patient also demonstrated significant bronchodilator responsiveness, and two patients received an initial diagnosis of asthma. Potential explanations for these findings are discussed. We report these findings to illustrate the limitations of DLCO in this setting. alpha(1)-Antitrypsin deficiency should be considered in patients with fixed airway obstruction that is out of proportion to their age and smoking history, regardless of their diffusing capacity and response to bronchodilators.     

Quantitative computed tomography and aerosol morphometry in COPD and alpha1-antitrypsin deficiency.

Relative area of emphysema below -910 Hounsfield units (RA-910) and 15th percentile density (PD15) are quantitative computed tomography (CT) parameters used in the diagnosis of emphysema. New concepts for noninvasive diagnosis of emphysema are aerosol-derived airway morphometry, which measures effective airspace dimensions (EAD) and aerosol bolus dispersion (ABD). Quantitative CT, ABD and EAD were compared in 20 smokers with chronic obstructive pulmonary disease (COPD) and 22 patients with alpha1-antitrypsin deficiency (AAD) with a similar degree of airway obstruction and reduced diffusion capacity. In both groups, there was a significant correlation between RA-910 and PD15 and pulmonary function tests (PFTs). A significant correlation was also found between EAD, RA-910 and PD15 in the study population as a whole. Upon separation into two groups, the significance disappeared for the smokers with COPD and strengthened for those with AAD, where EAD correlated significantly with RA-910 and PD15. ABD was similar in the two groups and did not correlate with PFT and quantitative CT in either group. In conclusion, based on quantitative computed tomography and aerosol-derived airway morphometry, emphysema was significantly more severe in patients with alpha1-antitrypsin deficiency compared with patients with usual emphysema, despite similar measures of pulmonary function tests.     

Computed-tomography findings of emphysema: correlation with spirometric values

PURPOSE OF REVIEW: There is increasing interest in using multichannel computed-tomography scanning in the characterization of subjects with chronic obstructive pulmonary disease. Three distinct components - emphysema, large-airway inflammation and small-airway abnormality - have been evaluated using qualitative and quantitative approaches. Here we highlight computed-tomography findings of chronic obstructive pulmonary disease and correlation with spirometric values. RECENT FINDINGS: A considerable percentage of the subjects with emphysema detected by computed-tomography screening had normal spirometry. Severity of emphysema varies widely, even with same disease stage in chronic obstructive pulmonary disease. Studies of the relationship between high-resolution computed-tomography lung-attenuation measurements acquired under spirometric control of inspiratory and expiratory lung volume and pulmonary function showed that inspiratory measurements assess the extent of emphysema and that expiratory measurements reflect airflow limitation and air trapping. The evaluation using three-dimensional computed tomography demonstrates that airflow limitation is more closely related to the dimensions of small airways than large airways. SUMMARY: Volumetric computed-tomography scans allow diagnosis and quantification of the individual small airway and emphysema phenotypes present in people with chronic obstructive pulmonary disease. New computed-tomography scanning techniques should provide new insights into further understanding of the heterogeneity of chronic obstructive pulmonary disease.     

Chronic obstructive pulmonary disease, with and without alpha-1-antitrypsin deficiency: management practices in the U.K.

Alpha-1-antitrypsin deficiency is a common genetic defect associated with the development of severe and rapidly progressive lung disease. This study was undertaken to determine whether respiratory physicians manage patients with alpha-1-antitrypsin (AAT) deficiency differently from patients with chronic obstructive pulmonary disease (COPD) without alpha-1-antitrypsin deficiency. In addition we obtained physicians' views on who should be tested for AAT deficiency. A questionnaire was administered to 88 respiratory physicians based throughout the U.K. (44 in teaching hospitals). The main outcome measures were pulmonary function tests, radiological assessment, frequency of repeat testing, follow-up and screening protocol for alpha-1-antitrypsin deficiency. Subjects with homozygous (PiZ) AAT deficiency were more likely to: 1. have baseline and full pulmonary function testing including dynamic flow rates, static lung volumes, and gas transfer; 2. have more comprehensive assessment with high resolution computed tomography (HRCT) thorax and repeated radiological assessment (with annual chest radiography); 3. be followed-up routinely; and 4. have family members tested for alpha-1-antitrypsin deficiency. Testing remains limited for AAT deficiency and is mainly restricted to young patients with COPD. COPD assessment and management is influenced by the presence of AAT deficiency, which may reflect the poorer prognosis of such patients due to more rapid decline. Assessment and monitoring could be simplified to forced expired manoeuvres, although limited HRCT thorax and tests of gas transfer may prove more sensitive to progression of emphysema. Testing for AAT deficiency in the U.K. remains restricted, which will influence the detection rate for AAT deficiency. A wider policy of testing was advocated by the WHO will detect more patients and also influence our understanding of the natural history of the condition.     

Ventilation inhomogeneity in alpha1-antitrypsin-deficient emphysema.

The slope of phase III of the single-breath nitrogen wash-out test (sbN2-test) measures ventilation inhomogeneity and, in smokers, is strongly associated with small airways pathology. The present authors aimed to study ventilation inhomogeneity in emphysema related to type Z alpha1-antitrypsin (AAT) and to assess its relationship with indices of parenchymal damage and airways obstruction. A total of 18 subjects, consisting of ex-smokers with type Z AAT and emphysema (confirmed by computed tomography scan), were studied in a cross-sectional design. Post-bronchodilation flow-volume curves and gas transfer parameters were measured; sbN2-test curves were obtained and the slope of phase III was determined. The mean value of the slope (4.6+/-1.3% N2 x L(-1)) was higher than reference values +2sd; it was significantly correlated with the transfer factor of the lung for carbon monoxide (R = -0.75) and the transfer coefficient of the lung for carbon monoxide (R = -0.58), but not with airways obstruction. There was no correlation between phase III slope values and cumulative smoking. In patients with type Z alpha1-antitrypsin emphysema, the increased ventilation inhomogeneity predominantly reflects parenchymal abnormalities, demonstrating that measurement of airways obstruction is not sufficient to characterise the disease. Determination of the sensitivity of the single-breath nitrogen wash-out test slope in detecting disease progression may give complementary information to spirometry.     

Pulmonary abnormalities on high-resolution computed tomography in ankylosing spondylitis: relationship to disease duration and pulmonary function testing

The aim of this study was to identify the pulmonary abnormalities on high-resolution computed tomography (HRCT) in patients with ankylosing spondylitis (AS) and to examine the relationship with the duration of disease and pulmonary function test (PFT) results. Twenty male AS patients with a mean age of 37.1?±?9.4?years were enrolled in this study. The patients were assigned into 2 groups according to disease duration: patients with disease duration <10?years (n?=?10) and ≥10?years (n?=?10). All patients underwent clinical examination, PFT and HRCT. HRCT revealed abnormalities in 14 patients (70%). The most common findings were apical fibrosis (45%) and emphysema (25%). HRCT findings were more prominent in late AS patients (disease duration ≥10?years) (P?=?0.015). PFT were considered as abnormal in 4 patients (20%). While 3 patients had a restrictive type pulmonary deficiency, one patient had a mild obstructive pattern. Three of these patients had concomitant HRCT abnormalities. On the other hand, 10 patients with normal PFT had abnormalities on HRCT. These findings suggest that pulmonary involvement in AS patients without respiratory symptoms could be sensitively detected by HRCT. However, the clinical significance of these radiological abnormalities should be examined in further prospective studies.     

Functional and radiological impairment in women highly exposed to indoor biomass fuels

OBJECTIVE: The aim of this study was to describe the lung function and the computed tomographic features in a selected group of non-smoking women with chronic obstructive pulmonary disease and biomass fuel exposure. METHODOLOGY: Thirty female patients currently exposed to biomass smoke were prospectively investigated for further evaluation using high resolution computed tomography (HRCT), pulmonary function tests and blood gas analysis. RESULTS: The mean age was 59 +/- 11 years. The patients were exposed to biomass smoke for 37.4 +/- 10 years. Pulmonary function tests revealed severe obstruction. The most common HRCT findings were increased lung volume or diffuse emphysema, thickening of interlobular septae, focal emphysematous areas, increased cardiothoracic ratio, and increased bronchovascular arborization. CONCLUSION: Biomass fuel has deleterious effects on pulmonary function and structure leading to obstructive and restrictive pathologies.     

Alveolar volume determined by single-breath helium dilution correlates with the high-resolution computed tomography-derived nonemphysematous lung volume

BACKGROUND: The alveolar volume (V(A)), determined by single-breath helium dilution, is a measure for the total lung capacity (TLC) that is very sensitive to ventilatory disturbances. In chronic obstructive pulmonary disease (COPD), the emphysematous lung parts are less accessible to test gas; therefore, the V(A) is smaller than TLC measured by multiple-breath helium dilution (TLC(He)). OBJECTIVES: The aim of this study was to investigate whether the V(A) represents the nonemphysematous lung parts. METHODS: We measured V(A) as part of the diffusing capacity for carbon monoxide (DL(CO)), TLC(He) and spirometry in 50 patients with COPD. High-resolution computed tomography (HRCT) scans of all subjects were analyzed with the density mask method, where parts with an attenuation of less than -950 Hounsfield units were considered as emphysematous. RESULTS: A strong correlation was observed between the V(A) (mean 5.2 liters) and nonemphysematous HRCT lung volume (mean 5.2 liters, r(2) = 0.9) and between the TLC(He) (mean 6.6 liters) and total HRCT lung volume (mean 6.4 liters, r(2) = 0.9). Bland-Altman plots showed considerable disagreement between the V(A) and the nonemphysematous HRCT lung volume. A weak correlation between the forced expiratory volume in 1 s (mean 46% predicted) and DL(CO) (mean 46% predicted) versus the HRCT emphysema ratio (nonemphysematous/total HRCT lung volume) was observed (r(2) = 0.3 and 0.3, respectively). CONCLUSION: We concluded that the V(A) correlates with the nonemphysematous HRCT lung volume, although the two measurements are not equivalent, possibly due to technical factors.     

Characteristics of COPD phenotypes classified according to the findings of HRCT

The present study was performed to clarify the clinical characteristics of chronic obstructive pulmonary disease (COPD) patients classified into phenotypes according to the dominancy of emphysema and the presence of bronchial wall thickening evaluated by chest high-resolution computed tomography (HRCT). Eighty-five patients with stable COPD (FEV1 < or = 80%) were examined by chest HRCT. Emphysematous changes and bronchial wall thickening were evaluated visually, and COPD patients were classified into three phenotypes: absence of emphysema, with little emphysema with or without bronchial wall thickening (A phenotype), emphysema without bronchial wall thickening (E phenotype), and emphysema with bronchial wall thickening phenotype (M phenotype). Clinical characteristics were compared among the three phenotypes. The A phenotype group showed a higher prevalence of subjects who had never smoked and patients with wheezing, higher values of body mass index (BMI) and DLco, milder lung hyperinflation, and greater reversibility of airflow limitation responsive to inhaled beta2-agonist as compared with the other phenotypes. The degree of emphysema was significantly associated with Brinkman index, lower BMI, decrease in DLco, lower FEV1/FVC. The presence of bronchial wall thickening in A- and M- phenotype was significantly associated with reversibility responsive to treatment with inhaled corticosteroid and sputum eosinophilia. These findings suggest that the morphological phenotypes of COPD show several clinical characteristics and different responsiveness to treatment with bronchodilators and inhaled corticosteroids.     

Alpha-1-antitrypsin replacement therapy: current status

PURPOSE OF REVIEW: Alpha-1-antitrypsin deficiency is a relatively common genetic disease that predisposes to the development of early-onset emphysema and, in some instances, liver disease. The use of alpha-1-antitrypsin replacement therapy in the treatment of alpha-1-antitrypsin deficiency related emphysema is much debated and the purpose of this review is to examine the results of recent studies. We will comment briefly on the pathogenesis and epidemiology of the disease together with new therapeutic approaches currently under intense research. RECENT FINDINGS: Several nonrandomized observational studies and one meta-analysis on the clinical effectiveness of alpha-1-antitrypsin replacement treatment showed a favourable result towards reducing forced expiratory volume in 1 s (FEV1) deterioration in alpha-1-antitrypsin-deficient individuals with moderate lung disease or accelerated FEV1 decline. Improved ways of monitoring disease progression, including computed tomography scanning and exacerbations, are being proposed as primary endpoints. Apart from one small randomized, placebo-controlled trial using computed tomography scanning, which showed a trend toward preservation of lung density on scanning with treatment, the literature lacks proof of effectiveness from large randomized trials. SUMMARY: There might be a possible, but so far unproven, role of alpha-1-antitrypsin augmentation therapy in reducing the progression of emphysema in subsets of patients with alpha-1-antitrypsin deficiency. Placebo-controlled, randomized clinical trials are required to draw firm conclusions. Recent advances in the understanding of the molecular pathology provide opportunities for development of new therapeutic targets for this genetic disorder.     

Plasma leptin is related to proinflammatory status and dietary intake in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a syndrome of chronic wasting, in part associated with a chronic inflammatory response. The aim of this study was to investigate cross-sectionally and prospectively the potential role of leptin in relation to systemic inflammation in the regulation of the energy balance in COPD. Body composition by deuterium dilution, resting energy expenditure (REE) by indirect calorimetry, and plasma concentrations of leptin and soluble tumor necrosis factor (TNF) receptors (sTNF-R) 55 and 75 by ELISA were measured in 27 male patients with emphysema and 15 male patients with chronic bronchitis (disease-subtype defined by high-resolution computed tomography [HRCT]). Emphysematous patients were characterized by a lower body mass index due to a lower fat mass (FM) (p = 0.001) and by lower mean (detectable) leptin concentrations (p = 0.020) compared with bronchitic patients. Leptin was exponentially related to FM in emphysema (r = 0.74, p < 0.001) and in chronic bronchitis (r = 0.80, p = 0.001). Furthermore, a significant partial correlation coefficient between leptin and sTNF-R55 adjusted for FM and oral corticosteroid use was seen in emphysema (r = 0.81, p < 0.001) but not in chronic bronchitis. In 17 predominantly emphysematous depleted male patients with COPD, baseline plasma leptin divided by FM was in addition logarithmically inversely related to baseline dietary intake (r = -0.50, p = 0.047) and to the degree of weight change after 8 wk of nutritional support (r = -0.60, p = 0.017). This proposed cytokine-leptin link in pulmonary cachexia may explain the poor response to nutritional support in some of the cachectic patients with COPD and may open a novel approach in combating this significant comorbidity in COPD. Schols AMWJ, Creutzberg EC, Buurman WA, Campfield LA, Saris WHM, Wouters EFM. Plasma leptin is related to proinflammatory status and dietary intake in patients with chronic obstructive pulmonary disease.     

Pattern of emphysema distribution in alpha1-antitrypsin deficiency influences lung function impairment

FEV(1) is fundamental to the diagnosis and staging of chronic obstructive pulmonary disease. In emphysema, airflow obstruction usually coexists with impairment of gas exchange, but discordance is not infrequent. We hypothesized that variations in the distribution of emphysema would be associated with functional differences and therefore account for discordant physiology. We used quantitative computed tomography to assess emphysema severity and distribution in 119 subjects with alpha1-antitrypsin deficiency (PiZ phenotype) and grouped them according to distribution pattern. In the 102 subjects with emphysema, 65 had a predominantly basal pattern ("basal"), but 37 (36%) had greater involvement of the upper regions ("apical"). Subjects from each group were matched for total volume of emphysema and age, and matched pairs analysis was used to relate emphysema distribution to clinical phenotype. Basal distribution was associated with greater impairment of FEV(1) (mean difference, 9.9% predicted; 95% confidence interval, 3.8 to 16.0; p = 0.002) but less impairment of gas exchange (Pa(O(2)) mean difference, 0.5 kPa, 0.03 to 0.1; p = 0.016) and alveolar-arterial oxygen gradient (mean difference, 0.7 kPa; 0.2 to 1.2; p = 0.007) than the apical distribution. Emphysema distribution correlated with physiologic discordance (r = -0.409, p < 0.001). The use of single physiologic parameters as a surrogate measure of emphysema severity may introduce systematic bias in the staging of subjects with emphysema.     

吸入激素联合治疗COPD的有效亚型及茶碱的逆转作用

目的 COPD治疗的关键是抗炎、缓解症状、延缓肺功能恶化.敏感性是影响糖皮质激素疗效的主要原因,故有必要筛选激素治疗敏感的COPD亚型并对不敏感者采取相应措施.研究发现茶碱可提高组蛋白去乙酰化酶2活性,进而改善激素的抗炎作用.因此本研究拟进一步探讨小剂量茶碱对激素不敏感的逆转作用.方法 采用高分辨率CT (high-resolution computed tomography,HRCT)对63例稳定期COPD患者行病理改变的综合评估分型,A型:无肺气肿或轻微肺气肿合并或不合并支气管管壁增厚;E型:肺气肿不合并支气管管壁增厚;M型:肺气肿合并支气管管壁增厚.各型患者分为吸入激素或联合口服茶碱治疗组.监测12周、24周治疗后患者的临床症状评分及肺功能变化.结果 各型COPD患者临床特征和肺功能检查结果存在差异.A型患者联合治疗后的临床症状评分优于E型;E型患者联合治疗后的临床症状评分显著改善;M型患者吸入激素治疗后的临床症状评分显著改善.A型患者吸入激素或联合治疗后的肺功能及改善率均高于其余2型患者;E型患者联合治疗后肺功能及改善率均高于单一吸入激素治疗.结论 HRCT分型中A型、M型可能是糖皮质激素治疗COPD的有效亚型,而联合茶碱治疗可提高激素疗效.     

The relationship between pulmonary function tests, thorax HRCT, and quantitative ventilation-perfusion scintigraphy in chronic obstructive pulmonary disease

We have evaluated the relationship between pulmonary function tests (PFT), thorax high resolution computed tomography (HRCT) images and quantitative ventilation-perfusion (V/Q) scintigraphic studies in 16 male patients (mean age 65.6 +/- 5.5 years) with chronic obstructive pulmonary disease (COPD). The mean forced vital capacity (FVC) value of the patient group was 2352 +/- 642 mL (65.4 +/- 15.8%), whereas mean forced expiratory volume in one second (FEV(1)) was found to be 1150 +/- 442 mL (40.8 +/- 14.9%). The ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA) was 3.17 +/- 0.88 mL/min/mmHg/L, and the mean partial oxygen (PaO(2)) and carbon dioxide (PaCO(2)) pressures were 68.5 +/- 11.04 mmHg and 38.9 +/- 5.8 mmHg respectively. For each patient, thorax HRCT and V/Q scintigraphic images of both lungs were divided into upper, mid and lower zones during examination. Visual scoring for the assessment of emphysema on thorax HRCT were used and images were graded from mild to severe (< or = 25% - > or = 76%). Emphysema scores were found to be higher on upper zones with accompanying lowest V/Q ratios. DLCO/VA, DLCO, total emphysema scores, and individual emphysema scores of the upper, mid and lower zones were found to be correlated. As a conclusion, it can be stated that emphysematous changes in COPD patients are more apparent in the upper lung zones, which also have the lowest V/Q ratios.