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Idiopathic pulmonary fibrosis: evaluation with positron emission tomography.

BACKGROUND: The pathogenesis of interstitial lung disease remains under investigation, but may be related to increased inflammatory or cellular activity. This activity may be detectable with physiologic imaging. OBJECTIVES: We investigated the role of physiologic imaging using (18)F-2-fluoro-2-deoxy-D-glucose ((18)FDG)-positron emission tomography (PET) scans in idiopathic pulmonary fibrosis (IPF). METHODS: Seven male patients with histologically confirmed IPF underwent (18)FDG-PET scans. Scans were analyzed qualitatively and interpreted as positive or negative. Patients also underwent pulmonary function tests and computed tomography (CT) scans. RESULTS: The average total lung capacity was 71 +/- 22% predicted (mean +/- SD) and diffusing capacity for carbon monoxide was 44 +/- 14% predicted. All had changes consistent with IPF on chest CT and 2 patients had ground glass attenuation. Six of seven patients (86%) had a positive (18)FDG-PET scan. Changes in the (18)FDG-PET scan were seen in 1 patient corresponding to changes in clinical status. CONCLUSIONS: Our findings suggest that (18)FDG-PET scans may be helpful in the evaluation of IPF. Increased activity suggests active disease and changes in response to therapy.

Aged↗

Nonuniformity of diffusing capacity from small alveolar gas samples is increased in smokers.

BACKGROUND: Although centrilobular emphysema, and small airway, interstitial and alveoli inflammation can be detected pathologically in the lungs of smokers with relatively well preserved lung function, these changes are difficult to assess using available physiological tests. Because submaximal single breath washout (SBWSM) manoeuvres improve the detection of abnormalities in ventilation inhomogeneity in the lung periphery in smokers compared with traditional vital capacity manoeuvres, SBWSM manoeuvres were used in this study to measure temporal differences in diffusing capacity using a rapid response carbon monoxide analyzer. OBJECTIVE: To determine whether abnormalities in the lung periphery can be detected in smokers with normal forced expired volumes in 1 s using the three-equation diffusing capacity (DLcoSB-3EQ) among small alveolar gas samples and whether the abnormalities correlate with increases in peripheral ventilation inhomogeneity. PARTICIPANTS AND DESIGN: Cross-sectional study in 21 smokers and 21 nonsmokers all with normal forced exhaled flow rates. METHODS: Both smokers and nonsmokers performed SBWSM manoeuvres consisting of slow inhalation of test gas from functional residual capacity to one-half inspiratory capacity with either 0 or 10 s of breath holding and slow exhalation to residual volume (RV). They also performed conventional vital capacity single breath (SBWVC) manoeuvres consisting of slow inhalation of test gas from RV to total lung capacity and, without breath holding, slow exhalation to RV. DLcoSB-3EQ was calculated from the total alveolar gas sample. DLcoSB-3EQ was also calculated from four equal sequential, simulated aliquots of the total alveolar gas sample. DLcoSB-3EQ values from the four alveolar samples were normalized by expressing each as a percentge of DLcoSB-3EQ from the entire alveolar gas sample. An index of variation (DI) among the small-sample DLcoSB-3EQ values was correlated with the normalized phase III helium slope (Sn) and the mixing efficiency (Emix). RESULTS: For SBWSM, DI was increased in smokers at 0 s of breath holding compared with nonsmokers, and correlated with age, smoking pack-years and Sn. The decrease in DI with breath holding was greater in smokers and correlated with the change in Sn with breath holding. For SBWVC manoeuvres, there were no differences due to smoking in Sn or Emix, but DI was increased in smokers and correlated with age and smoking pack-years, but not with Sn. CONCLUSIONS: For SBWSM manoeuvres the increase in DI in smokers correlated with breath hold time-dependent increases in Sn, suggesting that the changes in DI reflected the same structural alterations that caused increases in peripheral ventilation inhomogeneity. For SBWVC manoeuvres, the increase in DI in smokers was not associated with changes in ventilation inhomogeneity, suggesting that the effect of smoking on DI during this manoeuvre was due to smoke-related changes in alveolar capillary diffusion, rather than due solely to alterations in the distribution of ventilation.

Adult↗

Structural aspects of gas exchange.

The lung is composed of several million small air spaces, lined by a delicate tissue membrane separating air from capillary blood. The design features of the gas exchange region in the lung are optimal for gaseous diffusion, by having a very extensive contact surface but with a minimal tissue barrier composed of an epithelial and endothelial layer separating an interstitial layer. The extent of the gas exchange surface in adult lungs is determined by general maturation which in turn is influenced by metabolic requirements of the organism. Environmental factors can modulate the pattern of ultimate lung development. Lung inflation causes air spaces to expand mainly by a process of tissue unfolding beneath an extremely thin layer of alveolar surfactant. This ensures cellular integrity during extreme deformations while at the same time providing a reserve of gas exchange surface so that functional diffusion capacity at all lung volumes is less than the structural maximum.

Animals↗

Pulmonary function, smoking habits, and high resolution computed tomography (HRCT) early abnormalities of lung and pleural fibrosis in shipyard workers exposed to asbestos.

To evaluate the presence of asbestos-related pleural and parenchymal abnormalities and their correlation with pulmonary function and smoking habits, 119 asbestos-exposed asymptomatic workers (mean age, 46.2 years; mean duration of asbestos exposure, 8.6 years; mean latency time, 21.6 years) with normal standard P.A chest radiographs were submitted to HRCT, CO-diffusing capacity and pulmonary function tests. HRCT scans were normal only in 31 (26%) examined workers; 31 (26%) subjects showed both pleural and parenchymal involvement, and 50 (42%) and seven (6%) had exclusively pleural and parenchymal abnormalities, respectively. Based on CO-diffusing capacity and pulmonary function tests, no significant difference was demonstrated between workers with pleural lesions and subjects with normal pleura; however, lower values of FVC were observed in the nonsmoking workers with parenchymal abnormalities in comparison with nonsmoking subjects with normal parenchyma (78.2 vs. 89.7% of predicted values; p = 0.03 by student's two-tailed t test), and lower values of FEV1/FVC in the smokers with parenchymal lesions with respect to smokers with normal parenchyma (93.7 vs. 100.2% of predicted values; p = 0.005 by students' two-tailed t test). In conclusion, our results demonstrate that HRCT may detect early parenchymal abnormalities which correlate with exposure to asbestos and respiratory function impairment, including a reduction in obstructive indices in smokers occupationally exposed to asbestos, without any clinically evident disease.

Adult↗

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.

Adult↗

Determination of pulmonary tissue volume, pulmonary capillary blood flow and diffusing capacity of the lung before and after hemodialysis.

In order to better understand changes in lung function before and after dialysis, we studied eight patients with end-stage renal disease undergoing chronic hemodialysis. Pulmonary tissue volume (Vt), pulmonary capillary blood flow (Qc), the diffusion capacity for carbon monoxide (DLCO), arterial blood gases and body weight were measured before and after dialysis. A single breath, constant expiratory flow technique for determination of of DLCO, Qc and Vt was used. DLCO, Qc, arterial carbon dioxide, and body weight were reduced post dialysis (P less than or equal to .01) while Vt failed to change. The alveolar-arterial oxygen difference rose 123 mmHg (P = .01). These results are consistent with pulmonary microembolization during dialysis with deterioration of gas exchange and Qc. These changes appear to occur independent of significant changes in Vt. Possible physiologic mechanisms are discussed.

Adult↗

Micronodules and emphysema in coal mine dust or silica exposure: relation with lung function.

The aim of this study was to investigate the respective effects of micronodules and pulmonary emphysema, detected by computed tomography (CT), on lung function in workers exposed to silica and coal mine dust. Eighty-three subjects exposed to silica (n=35) or to coal mine dust (n=48), without progressive massive fibrosis, were investigated by high-resolution and conventional CT scans to detect micronodules and to quantify pulmonary emphysema by measuring the relative area of the lung with attenuation values lower than -950 Hounsfield units. Sixty-six (54.5%) subjects had evidence of micronodules on CT scans. Smokers had micronodules more rarely than nonsmokers. Significant correlations were found between the forced expiratory volume in one second (FEV(1); % predicted) (r=-0.41, p<0.001), FEV1/vital capacity (VC) (r=-0.61, p<0.001), diffusing capacity of the lung for carbon monoxide (DL,CO) (r=-0.36, p<0.001) and the extent of emphysema. No difference was demonstrated in the linear relationships between the extent of emphysema and the pulmonary function according to the type of exposure or the presence of micronodules on CT scans. This study suggests that micronodules detected by computed tomography have no influence, by themselves, on pulmonary function and that they should only be considered as a marker of exposure.

Adult↗

Oxygen diffusing capacity estimates derived from measured VA/Q distributions in man.

Data from eighteen subjects, studied in hypoxia (minimum PIO2 = 80 Torr) both at rest and during exercise, were analyzed using computer models which estimate O2 diffusing capacity from measured VA/Q distributions (obtained using the multiple inert gas elimination technique 'MIGET') and measured O2 exchange. Two of these models assigned the distribution of the diffusing capacity (D) in proportion to either the perfusion (DLO2-Qwt) or ventilation (DLO2-Vwt) distributions from MIGET, and thus modeled the effects of VA/Q and D/Q beta (where Q beta is the perfusive conductance) inequalities respectively. The third model (DLO2-3C) assigned all the diffusing capacity to a single homogeneous compartment. At rest DLO2 was 41.1 +/- 4.8, 41.1 +/- 5.4 and 30.2 +/- 2.1 ml X min-1 X Torr-1 for the Qwt, Vwt and 3C models respectively. These rose to 93.7 +/- 2.6, 109.3 +/- 4.5 and 81.1 +/- 1.9 ml X min-1 X Torr-1 respectively at maximal exercise, all significantly different from rest (P less than 0.001 for each). The effects of measured VA/Q and theoretical D/Q beta inhomogeneities on diffusing capacity estimates were significant even in normal lungs. Both types of inequality caused an appreciable underestimation of DLO2. These multi-compartment model estimates, using real data, are consistent with published theoretical predictions of the effects of V, Q and D inequalities. The results during exercise come close to morphometric predictions of maximal oxygen diffusing capacity in man.

Blood Gas Analysis↗

Effects of body position on the carbon monoxide diffusing capacity in patients with chronic heart failure: relation to hemodynamic changes.

OBJECTIVE: Pulmonary diffusion has been found to be reduced in patients with congestive heart failure. The effects of postural changes on the diffusing capacity had been evaluated in healthy subjects, but not in patients with heart failure. The aim of this study was to evaluate the posture-induced changes in diffusing capacity in patients with chronic heart failure and their relation to the hemodynamic profile. METHODS: The pulmonary carbon monoxide diffusing capacity (DLCO) was measured in the supine position, with 20 degrees passive head elevation, and in the sitting position, both postures maintained for 10 min, in a group of 32 male patients with mild to moderate chronic heart failure due to left ventricular systolic dysfunction (ejection fraction <35%). On a separate day, in the absence of any changes in clinical status and therapy, the hemodynamic parameters were measured by right-heart catheterization. The sequence of postures was assigned randomly. RESULTS: The mean values of DLCO were slightly reduced and did not differ in the two positions (20.3 +/- 5.7 vs. 19.4 +/- 5.6 ml/min/mm Hg, 77 +/- 23 vs. 75 +/- 20% of predicted, respectively). The patients were then subdivided according to changes in DLCO from the supine to the sitting position: DLCO increased (+23%) in 9 patients (28%, group 1), decreased (-17.5%) in 17 patients (53%, group 2), and remained within the coefficient of reproducibility ( +/- 5 %) in 6 patients (group 3). As compared with group 2, group 1 patients showed a significant increase in mean pulmonary artery pressure (+7 vs. -15%, p < 0.01) and pulmonary capillary wedge pressure (+8 vs. -22%, p < 0.005) from the supine to the sitting position, while the cardiac index showed a smaller - but not significant - decrease in group 1 (-5 vs. -12%). The percent changes in DLCO significantly correlated with changes in pulmonary capillary wedge (r = 0.54, p < 0.0005) and mean pulmonary artery (r = 0.47, p < 0.005) pressures. CONCLUSIONS: In chronic heart failure postural changes may induce different responses in diffusing capacity. To a greater extent than in healthy subjects, the most common response is a decrease in DLCO in the sitting as compared with the supine position. The DLCO changes correlate with variations in pulmonary circulation pressure, probably due to changes in pulmonary vascular recruitment and pulmonary capillary blood volume.

Adult↗

A rebreathing method for measuring carbon monoxide diffusing capacity. A supplement to the single-breath method.

A rebreathing method for measuring carbon monoxide diffusing capacity is described. The method can be used in patients whose vital capacity is too small, or whose cooperation is inadequate, for the single-breath method. The apparatus is simple and the same gas mixtures are used as for the single-breath method. The results obtained by the rebreathing method are similar to those by the single-breath method (80% of the results by the rebreathing method lie within 20% of the value by the single-breath method). The rebreathing method also provides a measurement of the functional residual capacity.

Carbon Monoxide↗