Cyclophosphamide pulse therapy in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive disorder with poor prognosis. Response to treatment is infrequent and the use of immunosuppressive agents other than corticosteroids is the subject of ongoing discussion because of uncertain efficacy and side-effects. To determine the efficacy and safety of cyclophosphamide pulse therapy in IPF, this study retrospectively analysed 18 patients with progressive IPF who were treated with intermittent i.v. cyclophosphamide (1-13 g x month(-1)) and additional oral prednisolone for 1 yr. Static lung volumes, arterial oxygen tension (Pa,O2) at rest, clinical symptoms and potential treatment-related side-effects were recorded. Cyclophosphamide had to be stopped in one patient, owing to repeated pulmonary infection; 11 patients were responders (five improving, six stabilizing) and six patients deteriorated. The change in vital capacity (VC) of responders was +6.7+/-18.0% (mean +/-SD), compared with -20.6+/-18.2% in nonresponders (p=0.008). Pa,O2 remained constant in responders (+0.13+/-0.88 kPa (+1.0+/-6.6 mmHg)), while it decreased in nonresponders (-2.08+/-1.92 kPa (-15.6+/-14.4 mmHg, p=0.008)). Additional prednisolone was reduced by 19.1+/-13.4 mg in responders, compared with 6.7+/-16.3 mg in nonresponders (p=0.02). VC at initiation of therapy was higher in responders (60.2+/-10.2 versus 40.3+/-12.9% predicted; p=0.004). No side-effects occurred, other than respiratory tract infection. These data demonstrate that intravenous cyclophosphamide pulse therapy may be a favourable regimen for certain patients with progressive idiopathic pulmonary fibrosis. Patients with a vital capacity of more than 50% predicted and a shorter duration of disease may benefit most.     

Assessment of the progression of emphysema by quantitative analysis of spirometrically gated computed tomography images

RATIONALE AND OBJECTIVES: The authors assessed the progression of pulmonary emphysema by means of quantitative analysis of computed tomography images. METHODS: Twenty-three patients suffering from emphysema due to an alpha 1-antitrypsin deficiency, aged 45 +/- 7 years and exsmokers, were scanned twice with a 1-year time interval. At 90% of the vital lung capacity, slices with a thickness of 1.5 mm were acquired at the level of the carina and 5 cm above the carina; slices with a thickness of 1 cm were acquired 5 cm below the carina. The entire lung was scanned spirally at a respiratory status, corresponding with 75% of the total lung capacity at baseline. The mean lung densities (MLD) were calculated in an objective manner with new analytic software featuring automated detection of the lung contours. RESULTS: Mean lung densities decreased by 14.2 +/- 12.0 Hounsfield units (HU; P < 0.001) above the carina, by 18.1 +/- 14.4 HU (P < 0.001) at the carina level, by 23.6 +/- 15.0 HU (P < 0.001) below the carina, and by 12.8 +/- 22.2 HU (P < 0.01) for the entire lung. The decrease in MLD was most obvious in the lower lung lobes. For the same patient group, the annual decrease in the forced expiratory volume (FEV1) and the carbon monoxide-diffusion were 120 +/- 190 mL (P < 0.01) and 10 +/- 70 mmol/kg/minute ( P < 0.2), respectively. No significant correlation was found between the decrease in MLD and the decrease in FEV1. CONCLUSIONS: Progression of emphysema can be assessed in an objective manner based on the mean lung density (MLD), measured from computed tomography volume scans as well as from single-slice scans. Mean lung density has proved to be more sensitive than FEV1 and carbon monoxide-diffusion.     

Antibodies to prothrombin crossreact with plasminogen in patients developing myocardial infarction

This study aimed to determine the differences in haemodynamic responses to a standard incremental exercise test between outpatients with chronic obstructive pulmonary disease (COPD) and age-matched controls and to discover the relationship between severity of airflow obstruction and exercise haemodynamics in COPD. Twenty-two male patients with COPD (forced expiratory volume in one second (FEV1)/vital capacity (VC))<80% predicted) and 20 age-matched male controls performed an incremental exercise test (10 W x min(-1)) with ventilatory function and changes in stroke volume (deltaSV) and cardiac output (deltaCO) measured by means of electrical impedance cardiography (EIC). Submaximal deltaSV and deltaCO were lower in COPD patients. Peak exercise deltaSV were equal in patients and controls (128+/-33 versus 129+/-29%, p=0.98), whereas peak deltaCO was lower in patients (COPD versus controls: 232+/-71 versus 289+/-54%, p<0.005). In COPD patients, FEV1 (% pred) was significantly correlated to deltaSV at all submaximal exercise intensities, to peak exercise deltaSV and to peak exercise deltaCO. FEV1/VC (% pred) was significantly correlated to deltaSV at 30 and 60 W. In conclusion, in chronic obstructive pulmonary disease an aberrant haemodynamic response to exercise was found, especially in patients with severe airflow obstruction. This aberrant response is related to the degree of airflow obstruction and may limit exercise performance in patients with severe chronic obstructive pulmonary disease.     

Latex hypersensitivity/glove component reaction as a contributing factor to osteomyelitis of the hand: a case report and review of the literature

High-resolution computed tomography (HRCT) can be used to diagnose and quantify emphysema noninvasively, as significant correlations have been found between the histological grade on resected lung specimens and quantified (q) computed tomography (CT). In this study, we performed thin section qHRCT in patients with severe hereditary alpha-1-antitrypsin (AAT) deficiency. AAT deficiency is the most common genetic cause of emphysema in adults, and exercise intolerance is the most disabling, distressing consequence of emphysema for the majority of patients. qHRCT was used to quantify precisely the alterations in the lung parenchyma due to pulmonary emphysema. Up until now, the important relationship between the severity of emphysema and the reduced exercise capacity has received little attention. Therefore the purpose of the study was to investigate the relationship between emphysema as displayed by qHRCT and cardiopulmonary exercise testing (CPX) in patients with severe cardiopulmonary impairment. - qHRCT was performed in 21 patients with homozygous AAT deficiency. CT scans were obtained at three spirometrically standardized levels at the carina and (5 cm above and below the carina). The mean lung density at 50% of vital capacity and a quantitative histogram analysis of the frequencies of CT values were determined. All patients underwent symptom-limited CPX to analyse simultaneously cardiovascular and ventilatory systems responses. - In all patients, qualitative CT assessment demonstrated panlobular emphysema with large and extensive areas of uniform low attenuation, characteristically with a lower-lobe distribution. Mean CT density values of the patients (-845 +/- 6.9 (mean +/- SEM)) were significantly correlated with work capacity (r = 0.55, p <0.01), oxygen-pulse (r = 0.54, p <0.01) and functional dead space ventilation (r = -0.54, p <0.01). Moreover, severe emphysema index (CT values below a threshold value of 950 HU) correlated positively with functional dead space ventilation (r = 0.60, p <0.01) and alveolar-arterial oxygen difference (r = 0.70, p <0.001). - These results clearly demonstrate that CPX parameters, indicating a disturbed pulmonary gas exchange and a ventilation-perfusion-mismatch during exercise, are significantly related to the extent of lung emphysema.     

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INTRODUCTION: High-resolution computed tomography (HRCT) with iodinated contrast material has been used by many authors to study solitary pulmonary nodules (SPNs). The degree of enhancement was correlated with the nodule malignancy. MATERIAL AND METHODS: Forty adult patients were examined, before and after contrast agent administration, with incremental dynamic CT. We selected 22 patients with SPNs (3-30 mm phi, except one with 40 mm phi). The CT numbers of the inner nodule were calculated before and 1, 2 and 3 minutes after the i.v. administration of a weight-related dose (1.5 mL/kg/min) of nonionic iodinated contrast agent. A dose of 100 mL contrast agent was used in the first 6 patients. The difference in CT numbers between unenhanced images and the images with maximum enhancement (max. attenuation) was also calculated. RESULTS: Histologic diagnoses included 4 tuberculomas, 3 hamartomas and 15 malignant tumors (9 adenocarcinomas, 5 squamous cell carcinomas and 1 non-Hodgkin lymphoma). The CT numbers (in Hounsfield units, HU) of malignant nodules ranged 12-31 HU (mean: 21.5 HU) before contrast agent administration; the "long-standing" tuberculomas ranged 11-22 HU (mean: 16.5 HU) and the hamartomas had a mean density of 10.5 HU. We excluded for the study two "fresh" tuberculomas, one of which was surrounded by a low-attenuation infiltrate (the halo sign). We selected a threshold value of 20 HU on enhanced CT images to distinguish malignant (> or = 20 HU) from benign (< or = 20 HU) nodules. All lung cancers had complete enhancement (mean density: 35.5 HU). With 20 HU as the threshold value for a positive test, sensitivity was 100%, specificity 85.7%, positive predictive value 93.8% and negative predictive value 100%; test bias was 1.067. CONCLUSION: Positron emission tomography (PET) with 2-[fluorine-18] fluoro-2-deoxy-D glucose is reported to be as accurate as enhanced HRCT, but it does not provide accurate morphological information, is not widely available and it is quite expensive: therefore, in our opinion, CT should be preferred. After examining over 100 patients, we may use our results in the decision analysis comparing surgical risk with cancer risk.     

The role of neutrophils in the pathogenesis of idiopathic pulmonary fibrosis

STUDY OBJECTIVES: The prognostic value of the neutrophil count in BAL fluid (BALF) has been controversial. The role of neutrophils in this inflammatory lung disease, therefore, was evaluated in this study by additional measures. MATERIALS AND METHODS: We performed BAL in 22 patients with idiopathic pulmonary fibrosis (IPF) diagnosed by open lung biopsy specimen. Percent polymorphonuclear leukocyte (PMN) in BALF and absolute neutrophil counts were compared with those of normal nonsmokers. Elastase complexed to alpha-1-proteinase inhibitor (alpha1-PI) in plasma and BALF was measured as a marker of elastase burden, and neutrophil distribution in 22 lung tissues was observed by immunohistochemistry using antineutrophil elastase antibody. RESULTS: Percent PMN and absolute neutrophil counts in BALF did not increase in patients with IPF as compared with normal nonsmokers (n=15); the plasma elastase-alpha1-PI complex value (mean+/-SE) of patients with IPF (668.5+/-112.4 ng/mL) was significantly high as compared with that of normal nonsmokers (130.3+/-21.3, p<0.001). In addition, the BALF elastase-alpha1-PI complex value (mean+/-SE) of patients with IPF was also significantly high (333.1+/-87.0 ng/mg albumin) as compared with that of normal nonsmokers (83.1+/-29.3 ng/mg albumin, p<0.05). Immunohistochemistry demonstrated considerable numbers of neutrophils infiltrating the lung parenchyma in biopsy specimens obtained by open lung biopsy. CONCLUSIONS: These results suggested that although the neutrophil count in BALF could not represent the distribution of neutrophil in the lung, high levels of neutrophil elastase were demonstrated in lung parenchyma and also in both BALF and sera. Therefore, neutrophils might indeed play an important role in the pathogenesis of IPF.     

Interstitial lung disease: A quantitative study using the adaptive multiple feature method

We have previously described an adaptive multiple feature method (AMFM) for the objective assessment of global and regional changes in pulmonary parenchyma to detect emphysema. This computerized method uses a combination of statistical and fractal texture features for characterization of lung tissues based upon high resolution computed tomography (HRCT) scans. This present study was a substantial extension of the AMFM to simultaneously discriminate between multiple pulmonary disease processes. Normal subjects and those with emphysema, idiopathic pulmonary fibrosis (IPF), or sarcoidosis were studied. The AMFM was compared with two currently utilized computer-based methods: mean lung density (MLD) and the histogram analysis (HIST). Globally, when comparing two-subject groups the AMFM overall accuracy was 2 to 18% better than the overall accuracy of MLD and as much as 36% better than the accuracy of the HIST methods. In three-subject group discrimination tasks, the AMFM performed 7 to 27% better than the MLD and 4 to 36% better than the HIST methods. Finally, in discriminating all four subject groups at a time, the AMFM overall accuracy was 81%, which was 21% better than the MLD and 25% better than the HIST method. In most three-subject group comparisons and in the four-subject group comparison, the AMFM was significantly (p < 0.01) better than the MLD and HIST methods. Next, the AMFM was applied to local discrimination between normal and each disease group individually. The normal versus emphysema, normal versus IPF, and normal versus sarcoidosis samples were discriminated with an accuracy of 95, 86, and 77%, respectively. The AMFM is an objective quantitative method that can be adapted for successful discrimination of multiple parenchymal lung diseases.     

Setting Priorities in Occupational Health Research in Vietnam

It is well known that silica exposure leads in an experimental model to the development of an acute fibrotic process. In human beings two main observations have already been done: (1) silica exposure is frequently associated with the development of connective tissue disease (CTD), especially progressive systemic sclerosis; (2) 10 to 20% patients with CTD developed pulmonary fibrosis. In this context we report 26 cases of coal miners who presented with clinical, radiological, biological and functional characteristics mimicking idiopathic pulmonary fibrosis (IPF), with or without associated coal worker's pneumoconiosis (CWP). All were men; mean age was 68 +/- 9.2 years. Twenty-three were smokers. Duration of exposure was 28.8 +/- 9.1 years. All the patients had dyspnea (stage III, IV in the NHYA classification) and diffuse crackles. Eleven out of 26 had finger clubbing. Computed tomography showed honeycombing (23 cases), and/or ground glass opacities (6 cases) with bronchiectasis (3 cases) predominant in the lower lobes; 19 had radiological signs of CWP, micronodules (n = 16) and nodules (n = 3) predominant in the upper lobes. BAL exhibited an increased % of neutrophils (11.9 +/- 16.1%). Lung function demonstrated a restrictive pattern (TLC = 73 +/- 15.6% and VC = 80 +/- 18% of predicted values) associated with a decreased DLCO (51.8 +/- 23.6% of predicted values) and hypoxemia (at rest = 66.5 +/- 11.2 mmHg, upon effort = 56 +/- 12 mmHg). Lung biopsies were performed in four cases and demonstrated interstitial fibrosis of intraalveolar septum with an accumulation of immune and inflammatory cells similar to the one described in IPF. The association between IPF and silica exposure with or without associated CWP points out the problem of legal recognition of idiopathic-like pulmonary fibrosis as a complication of the occupational exposure of coal workers.     

6-Hydroxycatecholine, a choline-mimicking analogue of the selective neurotoxin, 6-hydroxydopamine

The purpose of this prospective study was to verify whether the percentage area of lung occupied by lowest attenuation values on high-resolution computed tomography (HRCT) scans reflects microscopic emphysema and to compare this quantification with the information yielded by the most widely used pulmonary function tests (PFT). Preoperative HRCT scans were obtained with 1-cm intervals in 38 subjects. With a semiautomatic evaluation procedure, the percentage areas occupied by attenuation values inferior to thresholds ranging from -900 Hounsfield units (HU) to -970 HU were calculated for the lobe or lung to be resected. Emphysema was microscopically quantified by using a computer-based method, measuring the perimeters and interwall distances of alveoli and alveolar ducts. The strongest correlation was found for -950 HU. As a second step, we evaluated possible correlations between PFT and microscopic measurements. Finally, considering the microscopic measurements as a standard, we tried to investigate their relationships with each of the PFT and with the relative area occupied by attenuation values lower than -950 HU for both lungs. This revealed that the diffusing capacity for carbon monoxide associated with HRCT quantification is sufficient to predict microscopic measurements. We concluded that the percentage area of lung occupied by attenuation values lower than -950 HU is a valid index of pulmonary emphysema.     

Diagnosis of emphysema in patients with chronic bronchitis: a new approach

Aerosol-derived airway morphometry (ADAM) and aerosol bolus dispersion (D) are altered in patients or animal models with lung emphysema. This study was performed to examine the sensitivity and specificity of ADAM and D in the detection of emphysema in vivo compared with conventional lung function parameters. The study comprised patients with chronic obstructive bronchitis (COB) without emphysema (group COB; n=19, age 56+/-8 yrs, forced expiratory volume in one second (FEV1)/vital capacity (VC) 66+/-12% predicted) and patients with chronic bronchitis with high-resolution computed tomography-confirmed emphysema (group COB-E; n=20), age 65+/-7 yrs, FEV1/VC 44+/-16% pred). Using monodisperse aerosol particles ADAM assessed the calibres of peripheral airspaces, while D measured convective gas mixing. Among all lung function parameters, ADAM and D showed the highest sensitivity and specificity for separating patients with COB from those with COB-E (area under the receiver operating characteristics curve (pROC) 0.99 and 1.0, respectively). In patients with COB aerosol parameters did not differ from those found in the control group, whereas patients with COB-E exhibited a two-fold increase in peripheral airspace dimensions compared with subjects with COB (0.86+/-0.07 versus 0.37+/-0.02 mm, p=0.0001) and an increase in D by >50% (541+/-74 versus 345+/-42 cm3, p=0.0001). In conclusion, aerosol-derived airway morphometry and aerosol bolus dispersion are powerful tools in the differential diagnosis of chronic obstructive pulmonary disease.     

Relationship between abnormalities on high-resolution CT and pulmonary function in systemic sclerosis

STUDY OBJECTIVES: To determine the predictive value of abnormalities on high-resolution CT (HRCT) on pulmonary disease in systemic sclerosis. PATIENTS: Fifty-two patients suffering from systemic sclerosis. DESIGN: Pulmonary disease was defined by pulmonary function test abnormalities, ie, total lung capacity (TLC) <80% of predicted value and/or diffusion of carbon monoxide (DLCO) <75% of predicted value, without any pulmonary event other than systemic sclerosis in the medical history. Patients were divided in two groups, group A with pulmonary disease (29 patients) and group B without pulmonary disease (23 patients). HRCT abnormalities were scored on whole lungs. A decision matrix was constructed to determine sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates. A receiver operating characteristic curve was constructed to determine the best compromise between sensitivity and specificity. RESULTS: HRCT total scores were higher in group A (9.0+/-4.3) than in group B (5.0+/-2.8) (p < 0.001) and they correlated with TLC (r =-0.39, p < 0.005) and DLCO (r = -0.50, p < 0.0002). An HRCT score of 7 corresponded to the best compromise between sensitivity (0.60) and specificity (0.83), with a positive predictive value of 0.82. Taking into account a value of 10 for the HRCT score increased specificity to 1 but decreased sensitivity to 0.41. CONCLUSION: A minimum score of 7 would be required to consider HRCT abnormalities in systemic sclerosis as predictive of pulmonary disease. An HRCT score of 10 makes it possible to establish the diagnosis of lung involvement severe enough to impair pulmonary function.     

Measurement of CT lung density in patients with chronic asthma

Evidence for the presence of emphysema in patients with asthma is controversial. We have previously shown that decreased lung density, measured by computed tomographic (CT) scanning, preoperatively, correlates with morphometric measurements of microscopic emphysema in subsequently resected lungs. The aim of this study was to compare CT lung density, in 17 patients with chronic asthma (forced expiratory volume in one second (FEV1) 1.98 (SD 0.77) L), 17 patients with chronic bronchitis and emphysema (FEV1 0.97 (0.56) L) and seven normal subjects (FEV1 3.5 (034) L). All subjects underwent CT scanning of the lungs and respiratory function testing within 2 days of each other. In five of the asthmatic patients a CT scan was performed on two occasions before and after treatment with nebulized bronchodilator. In a different group of five asthmatics these measurements were performed at the end of and 6 weeks after an exacerbation. The mean value of the lowest fifth percentile of the CT lung density in the patients with chronic obstructive pulmonary disease (COPD) was -942 (SD 36) Hounsfield units (HU), in the 17 asthmatic patients was -912 (34) HU, and in normal subjects was -880 (13). Despite a significant increase in peak expiratory flow rate from 266 (SD 102) to 406 (83) L x s(-1) (p<0.02) following nebulized beta2-agonist in five patients with chronic asthma, there was no significant change in CT lung density (p>0.05) Our study indicates that at least some patients with chronic, stable asthma develop a reduction in computed tomography lung density, similar to that in patients with emphysema.     

Pulmonary infection with Mycobacterium avium-intracellulare leads to air trapping distal to the small airways

To clarify the structure and function of the airways in Mycobacterium avium-intracellulare (MAI) infection, we performed pulmonary function tests and high-resolution computed tomography (HRCT) of the thorax in female patients 61 +/- 9 yr of age (n = 12) with pulmonary MAI infection without predisposing lung disease and compared their data with those of normal female volunteers 54 +/- 8 yr of age (n = 9). We calculated the E/I ratio, i.e., the average ratio of HRCT number at full expiration to that at full inspiration, as an index for the evaluation of air trapping distal to the small airways. Patients showed significant increases in residual volume and slope of phase III (DeltaN2) of the single-breath nitrogen test, and significant decreases in flow at 50 and 25% of FVC, suggesting hyperinflation and obstruction of the small airways. HRCT of patients revealed the small nodules and ectasis of bronchioles and small bronchi located mainly in segments (S) S2, S3, S4, and S5. The E/I ratio was significantly elevated in patients, and especially higher in the upper lung field than in the lower lung field, suggesting air trapping distal to the small airways. The difference of E/I ratio between the upper and lower field is probably related to the segmental distribution of CT abnormalities. These findings suggest that MAI infection can lead to air trapping distal to the small airways.     

On segmentation of lung parenchyma in quantitative computed tomography of the lung

Our purpose in this study was to investigate the influence of segmentation threshold and number of erosions on parameters used in quantitative computed tomography (CT) of the lung (erosions are shrink operations on the segmented area). Parameters assessed were mean lung density, area of the segmented lung, two percentiles, and the pixel index, which is the relative area of the histogram below -905 Hounsfield Units (HU). We analyzed images of ten emphysematous and ten nonemphysematous patients, that had been scanned at carina level in inspiration and expiration, using sections of 1, 2, 3, 5, and 10 mm in combination with a standard, a smooth, and an ultrasmooth reconstruction kernel. The lungs were segmented using pixel tracing at thresholds of -200, -400, and -600 HU with 0-4 erosions, followed by histogram analysis. The area of the segmented lungs decreased with 0.9%-3.2% per 100 HU decrease in threshold and with 2.2%-3.1% per erosion, dependent on patient group and respiratory status. Estimated mean lung density changed up to 30% by changing the threshold and the number of erosions. The pixel index and the 10th percentile depended only slightly on threshold and number of erosions, but the 90th percentile showed a strong dependence of up to 40%. It is concluded that the segmentation protocol can have a large impact on densitometric parameters and that standardization is mandatory for obtaining comparable results. Ideally a threshold equal to the average of the densities of lung and soft tissue should be used, but -400 HU will do in a limited but common density range (-910 to -790 HU). For densitometry two erosions are recommended, for volumetry zero erosions should be used.     

Lung volume reduction or lung transplantation for end-stage pulmonary emphysema?

OBJECTIVE: As the waiting period for lung transplant (LT) candidates with end-stage pulmonary emphysema (COPD) continues to increase, there is a need for alternative treatments to reduce the morbidity and mortality associated with COPD. We hypothesized that lung reduction (LR) may avoid the need for subsequent LT in patients on the waiting list that are also candidates for LR. METHODS: From July 1994 to December 1995, 20 patients received LR as alternative to LT. The average age was 58 +/- 7 years; 11 were males. Eighteen patients had primary COPD and two had alpha-1 antitrypsin deficiency. Eighteen LRs were thoracoscopic (two bilateral and 16 unilateral) and two were done through a median sternotomy. RESULTS: At a follow-up of 32 +/- 4 months, 19 patients are alive (19/20 = 95%). Fifteen patients (15/20 = 75%) are currently off the LT list and doing well: FEV1 is 40 +/- 18% predicted at 2 years compared with 22.7 +/- 6% before LR (P < 0.001); FVC is 84 +/- 13% at 2 years compared with 55 +/- 7% (P < 0.001) and the RV is 145 +/- 59% compared with 270 +/- 58% (P < 0.001). One patient (5%) required extra-corporeal membrane oxygenation (ECMO) after LR to the contralateral side of the first procedure and subsequently died. Two patients (10%) are currently listed for LT because of persistent symptoms. One patient (5%) in whom deterioration was secondary to exposure to toxic fumes, underwent successful LT. One patient (5%) is doing well from the pulmonary standpoint but is being worked up for new severe coronary artery disease (CAD). The freedom from LT is 95% (19/20) and the freedom from repeat LR is 85% (17/20). CONCLUSIONS: LR has the potential to offer an effective palliative alternative to LT in 75% of selected patients up to 32 months of follow-up. Widespread use of bilateral LR is anticipated to further improve the results.     

Lung volume and effectiveness of inspiratory muscles

We related inspiratory muscle activity to inspiratory pressure generation (Pmus) at different lung volumes in five seated normal subjects. Integrated electromyograms were recorded from diaphragmatic crura (Edi), parasternals (PS), and lateral external intercostals (EI). At 20% increments in the vital capacity (VC) subjects relaxed and then made graded and maximal inspiratory efforts against an occluded airway. At any given level of pressure generation, Edi, PS, and EI increased with increasing lung volume. The Pmus generated at total lung capacity as a fraction of that at a low lung volume (between residual volume and 40% VC) was 0.39 +/- 0.15 (SD) for the diaphragm, 0.20 +/- 0.06 for PS, and 0.22 +/- 0.04 for the lateral EI muscles. Our results indicate a lesser volume dependence of the Pmus-EMG relationship for the diaphragm than for PS and EI muscles. This difference in muscle effectiveness with lung volume may reflect differences in length-tension and/or geometric mechanical advantage between the rib cage muscles and the diaphragm.     

Possible existence of quaternary structure in the high-affinity serotonin transport complex

During exercise, dynamic hyperinflation-induced intrinsic positive end-expiratory pressure (PEEPi) and decreased dynamic lung compliance (CL,dyn) of patients with chronic obstructive pulmonary disease (COPD) increase the elastic work of inspiration (Wi) more than would be predicted from the increase in tidal volume (VT). This contributes significantly to their exertional breathlessness. In 10 stable patients with COPD, the dynamic Wi was measured during incremental bicycle exercise to exhaustion. The total Wi was then partitioned into the portion required to overcome PEEPi (Wi,PEEPi) and nonPEEPi elastic load (Wi,nonPEEPi). The latter is used to overcome the increase in the total respiratory system elastance during inflation. From resting breathing to peak exercise, Wi more than doubled (p<0.001). This increase was largely due to Wi,PEEPi, which significantly rose from 1.7+/-0.3 to 5.3+/-0.8 L x cm H2O(-1) (p<0.001). In comparison, Wi,nonPEEPi increased from only 3.0+/-0.4 to 5.1+/-0.5 L x cm H2O(-1) (p<0.01). Consequently, Wi,PEEPi as a fraction of total Wi increased from 35.5+/-5.6 to 51.0+/-3.3% (p<0.02). In addition, the measured Wi,nonPEEPi at peak exercise, when expressed as a percentage of its value during resting breathing, was 25% more than that predicted from the increase in VT alone. Assuming a constant chest wall compliance, this can be attributed to the exercise-induced decrease in CL,dyn, which was 0.27+/-0.04 and 0.17+/-0.02 L x cm H2O(-1) (p<0.01), respectively, during resting breathing and peak exercise. In conclusion, the dynamic hyperinflation-induced intrinsic positive end-expiratory pressure is more important than the increase in tidal volume in raising the work of inspiration during exercise in patients with chronic obstructive pulmonary disease; the decrease in dynamic lung compliance plays a definite but less important role.     

Lung density for assessment of hydration status in hemodialysis patients using the computed tomographic densitometry technique

The density of the lung reflects the total mass of fluid, air, and dry lung tissue per unit volume of the lung. Lung density can be measured by evaluation of attenuation of an electron beam with computed tomography (CT). This technique has been shown to be sufficiently reliable and sensitive to distinguish normal from abnormal lung water. The aim of this study was to find out whether lung density properly reflects the hydration status in hemodialysis patients in comparison with other standard methods. Fourteen hemodialysis patients, with an ultrafiltration ranging from 0.3 to 4.5 liters per session, underwent CT measurements of lung density, ultrasonographic measurements of the diameter of the inferior vena cava after quiet expiration (IVCe) and quiet inspiration (IVCi), and measurements of the hematocrit and plasma levels of the biochemical hydration markers cyclic guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP). These measurements were performed before and 3.5 to 4 hours after termination of dialysis. Quantitative estimates of lung density were obtained within pixels with CT numbers ranging between -1000 and -100 Hounsfield Units (HU), and compared with normal data from 18 normal controls. In normal controls, the lung density ranged from -800 to -730 HU. In hemodialysis patients, lung density was significantly higher than normal before dialysis (-678 +/- 96 HU, P < 0.01) and significantly decreased after dialysis (-706 +/- 92 HU, P < 0.05), indicating a decrease in fluid content of the lung. The density was normalized in 5 patients. A significant correlation was found between lung density and IVCe both before and after dialysis (r = 0.8, P < 0.01 for both). Change in density was significantly correlated to amount of ultrafiltration (r = 0.67, P < 0.01) and percent change in blood volume (r = 0.63, P < 0.05), indicating that lung density is greatly affected by changes in the extracellular fluid volume, mainly the intravascular volume. In conclusion, lung water reflects the hydration status in hemodialysis patients and can be monitored by measuring the lung density by CT. Accordingly, normalization of lung density can help to achieve a proper dry weight in these patients.     

Digital color imaging colposcopy: a matter of choice

PURPOSE: The objective of this study was to correlate the findings of sarcoidosis on high resolution CT (HRCT) with indexes of disease activity as measured with 67Ga scan, bronchoalveolar lavage (BAL), and serum angiotensin-converting enzyme (SACE) assay. METHOD: Twenty-nine patients with proven sarcoidosis underwent HRCT scan, 67Ga scan, BAL, and SACE assay within a 1 month period. The extent of parenchymal involvement by nodules, consolidation, ground-glass attenuation, and linear opacities was quantified to the nearest 10% of surface area affected on the CT examination. Whole-lung gallium uptake was quantified and the percentage of BAL-recovered lymphocytes (BAL-%LC) and SACE levels obtained by chart review. CT scores of disease extent were correlated with measured indexes of activity using the Spearman rank correlation coefficient. RESULTS: The mean extent of nodules, consolidation, ground-glass attenuation, and linear opacities on HRCT images was 15.1 +/- 16.6, 1.6 +/- 4.0, 17.5 +/- 25.4, and 7.6 +/- 9.6%, respectively. The extent of nodules and consolidation correlated with the intensity of lung gallium uptake (r = 0.46, p < 0.02), BAL-%LC (r = 0.50, p < 0.01), and SACE levels (r = 0.38, p < 0.05). No significant correlation was found between extent of ground-glass attenuation or linear opacities with any indexes of disease activity. CONCLUSION: On HRCT scan, nodules and consolidation in sarcoidosis reflect disease activity as measured by 67Ga scan, BAL, and SACE assay.     

Validation of air plethysmography, photoplethysmography, and duplex ultrasonography in the evaluation of severe venous stasis

PURPOSE: The purpose of this study was to validate the diagnostic capabilities of the most commonly used noninvasive modalities for evaluation of chronic venous insufficiency. METHODS: Twenty limbs in 20 patients were studied with air plethysmography (APG), photoplethysmography (PPG), and duplex ultrasonography. Ten limbs (group 1) were clinically without any venous disease. Group 2 consisted of 10 limbs with severe, class 3 venous stasis. Duplex ultrasonography, complemented with Doppler color-flow imaging was used to examine the superficial and deep venous systems to identify reflux. RESULTS: Ultrasonography identified deep venous reflux in eight of 10 limbs in group 2. Severe superficial reflux was identified in the two remaining limbs. Seven limbs with deep reflux also demonstrated severe superficial reflux. Superficial venous reflux was identified in one leg in group 1. APG accurately separated normal limbs from those with reflux. Parameters that were significantly different (p < 0.05) between the two groups were the venous filling index, (group 1 = 1.37 +/- 1.16 ml/sec, group 2 = 29.5 +/- 6.2 ml/sec.), venous volume (group 1 = 107 +/- 10.1 ml, group 2 = 220 +/- 22.5 ml), ejection fraction (group 1 = 52.5% +/- 2.3%, group 2 = 32.5% +2- 4.6%), and residual volume fraction (group 1 = 21.4 +/- 2.0%, group 2 = 52.1% +/- 2.5%). PPG refill times were significantly shortened in group 2 versus those of group 1 (6.4 +/- 0.89 sec vs 20.2 +/- 1.1 sec). The sensitivity of PPG refill times to identify reflux was 100%, but the specificity was only 60%, whereas the sensitivity and specificity for the residual volume fraction was 100%. The venous filling index was able to identify reflux and determine whether only superficial reflux was present with a sensitivity of 100% and a specificity of 90%. The kappa coefficient of agreement between duplex scanning and APG was 0.83, whereas between duplex and PPG it was only 0.47. CONCLUSION: APG accurately identifies limbs with and without venous reflux when compared with duplex ultrasonography. APG is a better method of evaluating clinically significant venous reflux than PPG. PPG is a sensitive method of detecting reflux, but the specificity is poor, and PPG refill times cannot accurately predict the location of reflux. The combination of APG and duplex ultrasonography provides the best means of assessing venous reflux.