Gastro-oesophageal reflux and interstitial lung disease.

BACKGROUND: Interstitial lung disease is a heterogeneous entity, which encompasses a large number of pulmonary disorders, including idiopathic pulmonary fibrosis. Gastro-oesophageal reflux appears to be more prevalent in idiopathic pulmonary fibrosis than in controls and in patients with secondary pulmonary fibrosis, but its contribution to interstitial lung disease remains unsettled. AIMS: To prospectively evaluate gastro-oesophageal reflux in patients with interstitial lung disease and to define acid reflux patterns in patients with idiopathic and secondary forms of pulmonary fibrosis. MATERIALS AND METHODS: Twenty-eight patients (15M, median age 66 years, interquartile range 60-71) were studied by history taking, pulmonary function tests, high resolution computed tomography, oesophageal manometry and 24h oesophago-gastric pH monitoring. RESULTS: Sixteen patients (57%) had typical reflux symptoms. All patients completed 24h pH metry and 14 underwent oesophageal manometry. An abnormal oesophageal acid exposure was observed in 19 patients (68%), 13 of which complained of predominant typical reflux symptoms. A diagnosis of idiopathic pulmonary fibrosis was made in 18 patients, while the remaining 10 patients were classified as secondary pulmonary fibrosis. Secondary pulmonary fibrosis patients had more restrictive lung defect, as expressed as Tiffeneau index (p<0.05) and greater acid reflux at nighttime (p<0.05) than idiopathic pulmonary fibrosis patients. CONCLUSIONS: The prevalence of abnormal acid reflux in interstitial lung disease patients is high and, in particular, patients with secondary pulmonary fibrosis show higher oesophageal acid exposure than those with idiopathic form.

Spiral CT evaluation of pulmonary emphysema using a low-dose technique.

PURPOSE: To evaluate the diagnostic accuracy and clinical acceptability of low-dose spiral CT for determining pulmonary volumes and emphysema extension in patients with pulmonary emphysema, in comparison with studies based on spiral CT at conventional dose. MATERIALS AND METHODS: We prospectively evaluated eighteen patients, current or former smokers, with a clinical diagnosis of chronic obstructive pulmonary disease. All the patients underwent: HRCT with three scans at predetermined levels; quantitative spiral CT, with two inspiratory scans, one conventional scan at 240 mA, and the second one a low-dose scan at 80 mA. We used the following parameters: 120 kV, rotation time 0.8", scan time less than 20" (single inspiratory breath-hold), layer thickness 7.5 mm, pitch 6 (high speed), interpolation algorithm at 180 degrees. A 3D reconstruction was performed, with segmentation of the lungs and automatic quantification of pulmonary volumes. We compared the volumes of absolute and percent emphysema and the ratings of the dose delivered to the patient (CTDIw and DLP) obtained with the two spiral CT scans with each other and with the respiratory function tests. RESULTS: The average total lung capacity (TLC) obtained by conventional-dose spiral CT (CTs1) was 6889.4 cc (SD +/-1813.2), and the capacity with low-dose spiral CT (CTs2) was 6929.4 cc (SD +/-1811.6). The percentage of emphysema was 39.7% (range: 2.2-63.5%; SD: +/-19.9) for the CTs1 and 41.1% (range: 2.1-66.4%; SD: +/-20). The CTDIw corresponding to CTs1 was 12.2 mGy (range: 11.9-16.4; SD: +/-1), the one corresponding to CTs2, 3.6 mGy (range: 3.6-4.9; SD: +/-0.3). The DLP corresponding to CTs1 was 391.7 mGy x cm (range: 333.3-518.9; SD: +/-46.7), the one corresponding to CTs2 was 117.8 mGy x cm (range: 100.3-156; SD: +/-14). As for the respiratory function tests, the total lung capacity (TLC) obtained by body plethysmography was 7061 cc (SD: +/-2029.7); the percent TLC was 115.9 (range: 66-165; SD: +/-27.6), the forced expiratory volume at one second (FEV1%, percentage of predicted value) was 46.7% (range: 17-123; SD: +/-27.3), residual volume (RV%) as a percentage of predicted value was 186.3 (range: 84-359; SD: +/-80.7), the Tiffeneau index (TI) was 46% (range: 25-71; SD: +/-15.7). We observed a very significant correlation between radiological and functional TLC for both CT methods. The percentage scores for emphysema obtained with the two methods correlated significantly with the functional indexes. The pixel index of CTs1 correlated with TLC% (r=0.87; p<0.0001), FEV1% (r=-0.53; p<0.02), RV% (r=0.76; p=0.004), TI (r=-0.79; p=0.0001). The pixel index of CTs2 correlated with TLC% (r=0.87; p<0.0001), FEV1% (r=-0.56; p=0.01), RV% (r=0.78; p=0.003), TI (r=-0.8; p=0.0001). The adoption of the method with low tube current entailed a highly significant reduction in the estimated dose delivered to patients (CTDIw and DLP) with r=0.9 and p < 0.0001. DISCUSSION AND CONCLUSIONS: Quantitative low-dose spiral CT is a very good method to quantify pulmonary volumes and calculate the extension of the anatomic emphysema. The reduction of mA from 240 to 80 lowers the estimated dose by 30%, without compromising the accuracy of the results. Our study achieved a highly significant correlation between the results obtained with the two spiral CT techniques and between these results and the respiratory function tests. In clinical practice, the easiest way to reduce the dose in spiral CT of the lung is to reduce the tube current. The low-dose method allows a significant reduction in radiation exposure. Further studies are required to establish to what extent the dose can be reduced without increasing in quantum noise and thereby compromising the quality of the study.

[Longitudinal follow-up evaluation of pulmonary emphysema using high-resolution Computed Tomography (HRCT) study and pulmonary function tests]. / Valutazione evolutiva dell'enfisema polmonare. Correlazioni fra lo studio con tomografia computerizzata con elevata risoluzione (HRCt) e i test funzionali.

PURPOSE: To evaluate the usefulness of HRCT in the identification of longitudinal progression of emphysema and to establish the sensitivity of HRCT compared with functional tests. MATERIAL AND METHODS: 15 ex-smokers with chronic obstructive lung disease were studied, using two consecutive HRCT examinations (t1 and t2); emphysema was evaluated by HRCT visual score and, at the same time, pulmonary function tests. RESULTS: As a whole, the extension of emphysema with HRCT presented a good correlation with Tiffeneau index (IT). At t1 a significant correlation between HRCT and IT was almost reached; it was achieved between HRCT and PaCO2, FEV1 and IT. At t2, there was a significant correlation between HRCT and IT, FEV1 and IT, FEV1 and PaO2, FEV1 and PaCO2, IT and PaO2. In the interval between t1 and t2 there was a significant worsening of HRCT visual score and IT, with no modification of FEV1, PaO2 and PaCO2. The change in HRCT visual score had a significant correlation with FEV1. DISCUSSION AND CONCLUSIONS: HRCT is able not only to identify and quantify anatomic emphysema, but also to evaluate progression of the disease. In the middle-short term anatomic emphysema worsens significantly and visual score HRCT is more sensitive than functional tests for longitudinal evaluation because emphysematous destruction is faster than decline in function. Furthermore emphysematous destruction in smokers progresses even after smoking cessation. The usefulness of combining HRCT with functional tests in the follow-up remains to be established. Longitudinal examination by HRCT could allow us to identify the smokers that tend to develop earlier and more seriously the symptoms of chronic obstructive lung disease.

[Automatic evaluation of total lung capacity and of emphysema involvement with spiral computerized tomography (CT) in obstructive pneumonia]. / Valutazione automatica della capacità polmonare totale e dell'estensione dell'enfisema mediante Tomografia Computerizzata (TC) spirale nella pneumopatia ostruttiva.

OBJECTIVE: To evaluate, in patients with chronic obstructive lung disease or chronic bronchitis, inspiratory helical CT with 3D postprocessing, to measure lung volumes and the amount of emphysema and to compare these measurements with lung function tests. MATERIAL AND METHODS: Seventeen patients with chronic obstructive lung disease disease or chronic bronchitis underwent pulmonary function tests and helical CT after a full inspiration with 3D postprocessing (lower threshold -1024 HU, upper thresholds -200, -300 and -400 HU). Lung inspiratory volumes (TLC-CT) were determined for each model; the amount of emphysema was evaluated by means of an automatic score and a visual score with HRCT. RESULTS: There is a good correlation between automatic and visual scores (p < 0.001); the automatic score had a good correlation with lung function tests, above all with total lung capacity (r = -0.56; p = 0.01) but the visual score had a much closer correlation with DLCO (r = -0.70; p < 0.001). TLC-CT had a significant correlation with pletismographic TLC (TLC-P); the upper threshold -200 HU was more correct (TLC-P = 8011 cc.; TLC-CT 200 = 7138 cc.; r = 0.83; p < 0.001). The volume change of 3D model was about 230 cc. per 100 HU (p < 0.001) modifying upper thresholds, but no change was observed in the volume occupied by emphysema and the percentage of emphysema presented minimal, clinically non significant modifications. DISCUSSION AND CONCLUSIONS: In emphysematous patients, the helical CT with 3D model construction is a good technique to evaluate lung volumes and to quantify emphysema with automatic score; this one, however, probably underscores the extent of pathology; therefore, the addition of a visual score with HRCT is probably worthwhile.

Vertebrate orthologues of the Drosophila region-specific patterning gene teashirt.

In Drosophila the teashirt gene, coding for a zinc finger protein, is active in specific body parts for patterning. For example, Teashirt is required in the trunk (thorax and abdomen) tagmata of the embryo, parts of the intestine and the proximal parts of appendages. Here we report the isolation of vertebrate cDNAs related to teashirt. As in Drosophila, human and murine proteins possess three widely spaced zinc finger motifs. Additionally, we describe the expression patterns of the two murine genes. Both genes show regionalized patterns of expression, in the trunk, in the developing limbs and the gut.

Characterization of the two zebrafish orthologues of the KAL-1 gene underlying X chromosome-linked Kallmann syndrome.

The gene underlying X chromosome-linked Kallmann syndrome, KAL-1, has been identified for several years, yet its role in development is still poorly understood. In order to take advantage of the zebrafish as a model in developmental genetics, we isolated the two KAL-1 orthologues, kal1.1 and kal1.2, in this species. Comparison of deduced protein sequences with the human one shows 75.5 and 66.5% overall homology, respectively. The most conserved domains are the whey acidic protein-like domain and the first of four fibronectin-like type III repeats. However, kal1.2 putative protein lacks the basic C-terminal domain (20 residues) found in kal1.1 and KAL-1. The expressions of kal1.1 and kal1.2 were studied in the embryo between 6 and 96 hours post fertilization using whole-mount in situ hybridization. Although a few structures express both genes, kal1.1 and kal1.2 expression patterns are largely non-overlapping. Taken together, these patterns match fairly well those previously reported for human KAL-1 and chicken kal1. As regards the olfactory system, kal1.1 is expressed, from 37 h.p.f. onward, in the presumptive olfactory bulbs, whereas kal1.2 transcript is only detected, from 48 h.p.f., in the epithelium of the nasal cavity. The relevance of the zebrafish as an animal model for studying both the function of KAL-1 in normal development and the developmental failure leading to the olfactory defect in Kallmann syndrome, is discussed.

The role of Teashirt in proximal leg development in Drosophila: ectopic Teashirt expression reveals different cell behaviours in ventral and dorsal domains.

Localised transcription factors specify the identity of developmental domains. Here we analyse the function of the Teashirt zinc finger protein, which is expressed in the proximal domain of the Drosophila leg. By ectopic expression of a teashirt transgene we show that Teashirt contributes to the differences in cell-cell adhesion between proximal and distal leg cells. Whereas clones of cells expressing the teashirt transgene survive in the endogenous Teashirt domain, most cells expressing Teashirt in an ectopic distal position are lost from the epithelium. In clones which were recovered in the distal domain, different effects were seen dependent on position with respect to the dorsal-ventral axis. In the ventral region, where Wingless is signalling, surviving clones express Teashirt and cause abnormalities in the adult leg. Contrarily, lateral and dorsal clones generally do not accumulate Teashirt and have no effect on patterning. One exception to the differential dorsal-ventral effects occurs at the boundary between Teashirt-expressing and -nonexpressing cells. Both ectopic and hypomorphic loss of teashirt affects patterning at all positions at the boundary, suggesting that Teashirt plays a crucial role in boundary formation. The results are discussed with respect to the roles of transcriptional and posttranscriptional mechanisms in proximal-distal axis patterning of the Drosophila legs.

The levels of the bancal product, a Drosophila homologue of vertebrate hnRNP K protein, affect cell proliferation and apoptosis in imaginal disc cells.

We have characterized the Drosophila bancal gene, which encodes a Drosophila homologue of the vertebrate hnRNP K protein. The bancal gene is essential for the correct size of adult appendages. Reduction of appendage size in bancal mutant flies appears to be due mainly to a reduction in the number of cell divisions in the imaginal discs. Transgenes expressing Drosophila or human hnRNP K are able to rescue weak bancal phenotype, showing the functional similarity of these proteins in vivo. High levels of either human or Drosophila hnRNP K protein in imaginal discs induces programmed cell death. Expression of the antiapoptotic P35 protein suppresses this phenotype in the eye, suggesting that apoptosis is the major cellular defect caused by overexpression of K protein. Finally, the human K protein acts as a negative regulator of bancal gene expression. We propose that negative autoregulation limits the level of Bancal protein produced in vivo.

[Role of emphysema in the etiology of functional impairment in patients with severe chronic obstructive pulmonary disease. Study with high resolution computerized tomography]. / Contributo dell'enfisema alla genesi del danno funzionale nei pazienti con grave broncopneumopatia cronica ostruttiva. Studio con Tomografia Computerizzata con elevata risoluzione.

PURPOSE: To investigate whether high-resolution CT (HRCT) can detect the subjects with massive emphysematous destruction in a group of patients with severe chronic obstructive pulmonary disease (COPD) and therefore be of help in selecting the candidates to surgical lung volume reduction. MATERIAL AND METHODS: We examined 40 former smokers with severe COPD (FEV1, < or = 40% of the predicted value, with no major improvement after inhalation of bronchodilators). Clinico-functional assessment included: a flow/volume loop (mean FEV1 = 28.6% of predicted), arterial blood gas analysis at rest breathing room air (mean values: PaO2 = 65.2 mmHg, PaCO2 = 47.4 mmHg), hematocrit value (mean: 45.2%) and the body mass index (mean value: 23.8). The patients were divided into two groups, namely bronchitic (21) and dyspneic (19) subjects, according to onset symptoms. All the patients underwent HRCT with evaluation of emphysema presence, type, site and extent: centrilobular emphysema was seen in 11 cases, panlobular emphysema in 3 and mixed emphysema in 26 cases; the site was superior in 75%, inferior in 7.5% and diffuse in 17.5% of cases; the mean visual score was 40.8%. The presence, type, site and severity of airways disease were also studied, as well as the pathologic dilatation of the pulmonary artery. The patients were divided into three groups (mild, moderate, severe) according to emphysema extent and they were considered to have bronchial disease in the presence of at least 2 of the 6 signs of bronchial involvement. RESULTS: The emphysema extent score was significantly correlated with the hematocrit value and Tiffeneau index (p < .2) in all the 40 patients. The severity of bronchial obstruction was the same in bronchitic and dyspneic patients. The subjects with chronic bronchitis had milder emphysema (mean extent 35% versus 47% in the dyspneic subjects) and a higher frequency of bronchial involvement. A decrease in FEV1 was significantly correlated with emphysema extent (p < .1) in dyspneic, but not in bronchitic, patients. Moreover, the former had better arterial blood gas and lower hematocrit values. CONCLUSIONS: HRCT is a useful tool in diagnosing the presence of emphysema in vivo and in assessing its extent in COPD patients because it permits to divide the patients into two groups which roughly correspond to the clinical patterns of types A (dyspneic) and B (bronchitic). Severe emphysema patients are the best candidates to surgical lung volume reduction. Airways involvement might play a major role in causing bronchial obstruction in the subjects with mild emphysema. In our series HRCT did assess the severity of emphysema in COPD subjects, but our lung function screening failed to predict emphysema extent.

The C-terminal domain of armadillo binds to hypophosphorylated teashirt to modulate wingless signalling in Drosophila.

Wnt signalling is a key pathway for tissue patterning during animal development. In Drosophila, the Wnt protein Wingless acts to stabilize Armadillo inside cells where it binds to at least two DNA-binding factors which regulate specific target genes. One Armadillo-binding protein in Drosophila is the zinc finger protein Teashirt. Here we show that Wingless signalling promotes the phosphorylation and the nuclear accumulation of Teashirt. This process requires the binding of Teashirt to the C-terminal end of Armadillo. Finally, we present evidence that the serine/threonine kinase Shaggy is associated with Teashirt in a complex. We discuss these results with respect to current models of Armadillo/beta-catenin action for the transmission of the Wingless/Wnt pathway.

[Idiopathic interstitial pneumonitis presenting with Wells grade III. Can imaging methods help predict further progression of disease?]. / Fibrosi polmonare idiopatica con grado III di Wells all'esordio. Possono le metodiche di diagnostica per immagini aiutare a predire la progressione ulteriore della malattia?

PURPOSE: Three different grades of idiopathic pulmonary fibrosis can be identified by HRCT pattern. Patients with predominant ground-glass opacity (grade I) usually improve after treatment and may have a better prognosis. The subjects with a predominant reticular pattern and honeycombing (grade III) have irreversible fibrosis and usually do not improve after immunosuppressive therapy. Nevertheless, these patients may worsen even in the absence of HRCT features of the so-called alveolitis. We investigated the predictive role of some noninvasive imaging methods (HRCT with visual score of disease extent; Gallium scintigraphy; DTPA scintigraphy) in patients with idiopathic fibrosis and a prevalent macroscopic fibrosis at HRCT study. MATERIAL AND METHODS: Fourteen former smokers with grade III idiopathic fibrosis were examined. None of the patients had been treated. They were all submitted to HRCT, lung function studies, Gallium and DTPA scintigraphy, both at presentation (T0) and follow-up sessions (T1: mean one year post-diagnosis). The HRCT extent of disease was evaluated by means of the visual score as the fraction of the total lung volume. The patients were divided into two groups, using a cut-off value of 50%. All the patients underwent a Gallium scintiscan (using a fixation index of 160 as cut-off) and a ventilatory scintigraphy with DTPA-aerosol, with radionuclide clearance assessment. The lung function tests considered were vital capacity (VC), arterial blood oxygen partial pressure (PaO2) and the diffusing lung capacity for carbon monoxide (DLCO). RESULTS: After one year of follow-up, the HRCT extent score increased (from 46.6% to 50%) and lung function worsened (VC from 66.8% to 63.4% of predicted; DLCO from 37.6% to 27.1%; PaO2 from 77 to 71 mmHg). The patients presenting with HRCT extension score > 50% had a worse lung function at T0 and showed a significant deterioration of PaO2 and HRCT at T1. On the other hand, VC and DLCO significantly worsened in the subjects with HRCT score < 50% at presentation. The patients with a Gallium fixation index > 160 significantly deteriorated in HRCT score, VC and DLCO. Those with Gallium index < 160 had major worsening only for diffusing lung capacity for carbon monoxide. Thirteen of 14 patients had an abnormal value of DTPA clearance at presentation. No variation was observed at T1. DISCUSSION AND CONCLUSIONS: The majority of patients with idiopathic fibrosis are grade III at presentation. They can further deteriorate both in HRCT extent of disease and lung function impairment. After one year of follow-up HRCT extent score increased in 64% of the patients, with a mean increase of 5%. HRCT worsening was more apparent in the patients with a HRCT score > 50% at presentation. In the remaining patients, the worsening of lung function tests was more apparent than the anatomoradiological changes. DTPA clearance had no predictive value in this series. Gallium scintigraphy was a useful prognostic index. The patients with Gallium fixation index > 160 had better lung function and lower HRCT extent score at T0 but significantly deteriorated at T1. A positive Gallium scan at presentation could be considered a useful index of persisting active "alveolitis" in patients with grade III disease, not visible at HRCT study, due to overwhelming fibrosis. These patients, who were untreated, exhibit quicker radiological and functional worsening.

Mapping of topoisomerase II alpha epitopes recognized by autoantibodies in idiopathic pulmonary fibrosis.

Autoantibodies against DNA topoisomerase II alpha have been identified in the sera of patients with idiopathic pulmonary fibrosis (IPF). To map topoisomerase II autoepitopes, we tested by ELISA and immunoblotting the IPF anti-topoisomerase II-positive sera against a series of recombinant proteins which covered the full length of topoisomerase II alpha. Specific patterns of reactivity were observed, indicating the existence of multiple epitopes on topoisomerase II, either highly complex or conformational/discontiguous or conformational/contiguous ones. The latter resided in amino acid residues 854-1147 and 1370-1447. A detailed analysis of these regions was undertaken, but we were not able to pinpoint a sequential peptide-sized epitope, or any significant homology with foreign pathogens. Further, we observed a significant correlation between the progression from a contiguous to a quaternary/tertiary structure-dependent autoepitope and the disease duration but not with the disease severity. Therefore, this result supports the hypothesis that anti-topoisomerase II autoreactivity evolves following an antigen-driven process.

Trunk-specific modulation of wingless signalling in Drosophila by teashirt binding to armadillo.

BACKGROUND: One function of the Wingless signal cascade is to determine the 'naked' cuticle cell-fate choice instead of the denticled one in Drosophila larvae. Wingless stabilises cytoplasmic Armadillo, which may act in a transcriptional activator complex with the DNA-binding protein T-cell factor (also known as Pangolin). As these components are critical for all Wingless-dependent patterning events, the problem arises as to how specific outputs are achieved. RESULTS: The Teashirt zinc finger protein was found to be necessary for a subset of late Wingless-dependent functions in the embryonic trunk segments where the teashirt gene is expressed. Teashirt was found to be required for the maintenance of the late Wingless signalling target gene wingless but not for an earlier one, engrailed. Armadillo and Teashirt proteins showed similar Wingless-dependent modulation patterns in homologous parts of each trunk segment in embryos, with high levels of nuclear Teashirt and intracellular Armadillo within cells destined to form naked cuticle. We found that Teashirt associates with, and requires, Armadillo in a complex for its function. CONCLUSIONS: Teashirt binds to, and requires, Armadillo for the naked cell-fate choice in the larval trunk. Teashirt is required for trunk segment identity, suggesting that Teashirt provides a region-specific output to Armadillo activity. Further modulation of Wingless is achieved in homologous parts of each trunk segment where Wingless and Teashirt are especially active. Our results provide a novel, cell-intrinsic mechanism to explain the modulation of the activity of the Wingless signalling pathway.

[Quantitative assessment of pulmonary emphysema with computerized tomography. Comparison of the visual score and high resolution computerized tomography, expiratory density mask with spiral computerized tomography and respiratory function tests]. / Valutazione quantitativa dell'enfisema polmonare mediante tomografia computerizzata. Confronto tra il punteggio visivo con alta risoluzione nell'inspirazione, maschera della densità automatica con Tomografia Computerizzata spirale nell'espirazione ed esami funzionali respiratori.

CT is the most accurate method to detect pulmonary emphysema in vivo. We compared prospectively two different methods for emphysema quantitation in 5 normal volunteers and 20 consecutive patients with chronic obstructive pulmonary disease (COPD). All subjects were submitted to function tests and HRCT; three scans were acquired at preselected levels during inspiration. The type and extent of pulmonary emphysema were defined, using the time-honored visual score system, by two independent observers under blind conditions. Disagreements were subsequently settled by consent. All subjects were also examined with expiratory spiral CT, using a density mask program, at two different cut-off levels (-850, -900 HU). Visual score and expiratory spiral density mask values (-850 HU) were significantly correlated (r = 0.86), but the visual extent of emphysema was always higher than shown by expiratory spiral CT. The emphysema extent assessed with both CT methods correlated with the function result of expiratory airflow obstruction and gas diffusion impairment (visual score versus forced expiratory volume in one second: r = -0.81, versus single breath carbon monoxide diffusion: r = -0.78. Spiral expiratory density mask -850 HU versus forced expiratory volume in one second: r = -0.85, versus single breath carbon monoxide diffusion: r = -0.77). When -900 HU was used as the cut-off value for the expiratory density mask, the correlation with single breath carbon monoxide diffusion worsened (r = -0.56). Visual score and expiratory density mask -850 HU gave similar results and permitted COPD patients to be clearly distinguished from normal controls (p < 0.01). Residual lung volume, measured with expiratory spiral CT correlated significantly with residual volume measured with the helium dilution technique (r = 0.66), but CT values were always higher than function results. We believe the true residual volume should lie somewhere in between the CT value and the function results with the helium dilution technique and conclude that the extent of pulmonary emphysema can be confidently assessed with CT methods. Finally, the simple visual score may be as reliable as such highly sophisticated new methods as the spiral expiratory density mask. Expiratory studies offer new insights into different normal and abnormal features of COPD and respiratory impairment.

Assessment of the severity of pulmonary emphysema by computed tomography.

Pulmonary emphysema is defined as an abnormal enlargement of alveolar spaces distal to the terminal bronchioles, with alveolar wall disruption and without obvious fibrosis. Clinico-functional evaluation and chest radiographic diagnosis are not highly accurate in detecting emphysema and in establishing the extent of the process of alveolar destruction. Several computed tomography (CT) techniques are now available for detection and quantitative assessment of emphysema. The results appear to correlate significantly better than chest radiography with functional impairment and pathological score. Many options have been proposed by different authors regarding CT technique. The choice, however, is essentially between inspiratory high resolution CT (HRCT) with a visual scoring system, and automated quantitative evaluation by means of a "density mask" (DM) program. This paper presents the state of the art on CT quantification of pulmonary emphysema and briefly discusses the technical options and parameters to be used, together with the problems to be solved.