Lung function in idiopathic pulmonary fibrosis--extended analyses of the IFIGENIA trial.

BACKGROUND: The randomized placebo-controlled IFIGENIA-trial demonstrated that therapy with high-dose N-acetylcysteine (NAC) given for one year, added to prednisone and azathioprine, significantly ameliorates (i.e. slows down) disease progression in terms of vital capacity (VC) (+9%) and diffusing capacity (DLco) (+24%) in idiopathic pulmonary fibrosis (IPF). To better understand the clinical implications of these findings we performed additional, explorative analyses of the IFGENIA data set. METHODS: We analysed effects of NAC on VC, DLco, a composite physiologic index (CPI), and mortality in the 155 study-patients. RESULTS: In trial completers the functional indices did not change significantly with NAC, whereas most indices deteriorated with placebo; in non-completers the majority of indices worsened but decline was generally less pronounced in most indices with NAC than with placebo. Most categorical analyses of VC, DLco and CPI also showed favourable changes with NAC. The effects of NAC on VC, DLco and CPI were significantly better if the baseline CPI was 50 points or lower. CONCLUSION: This descriptive analysis confirms and extends the favourable effects of NAC on lung function in IPF and emphasizes the usefulness of VC, DLco, and the CPI for the evaluation of a therapeutic effect. Most importantly, less progressed disease as indicated by a CPI of 50 points or lower at baseline was more responsive to therapy in this study.

Multidisciplinary interobserver agreement in the diagnosis of idiopathic pulmonary fibrosis.

The purpose of the present study was to evaluate the accuracy of the diagnosis of idiopathic pulmonary fibrosis (IPF) by respiratory physicians in six European countries, and to calculate the interobserver agreement between high-resolution computed tomography reviewers and histology reviewers in IPF diagnosis. The diagnosis of usual interstitial pneumonia (UIP) was assessed by a local investigator, following the American Thoracic Society/European Respiratory Society consensus statement, and confirmed when a minimum of two out of three expert reviewers from each expert panel agreed with the diagnosis. The level of agreement between readers within each expert panel was calculated by weighted kappa. The diagnosis of UIP was confirmed by the expert panels in 87.2% of cases. A total of 179 thoracic high-resolution computed tomography scans were independently reviewed, and an interobserver agreement of 0.40 was found. Open or thoracoscopic lung biopsy was performed in 97 patients, 82 of whom could be reviewed by the expert committee. The weighted kappa between histology readers was 0.30. It is concluded that, although the level of agreement between the readers within each panel was only fair to moderate, the overall accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis in expert centres is good (87.2%).

Percutaneous needle biopsy of the lung and its impact on patient management.

Percutaneous needle biopsy (PNB) of the lung is a commonly performed procedure, mainly used for the investigation of solitary pulmonary nodules. Developments in imaging, particularly computed tomography (CT), have enable accurate preliminary assessment and targeting of lesions. Improvements in needle design ensure the provision of diagnostic samples for both cytologic and histologic assessment; and the development of immunocytochemistry and immunohistochemistry have allowed improved accuracy in diagnosis. A significant improvement in diagnostic accuracy for benign lesions has been associated with the use of cutting needles that provide cores for histologic diagnosis, in contrast to cytologic analysis from fine-needle aspiration. The complications of PNB are well recorded and have not changed significantly with the newer imaging techniques and needles. The preliminary assessment of solitary pulmonary nodules, and the pretest likelihood of malignancy, has improved using contrast-enhanced CT and positron emission tomography; the latter modality is increasingly having a major impact on the investigation of patients with suspected malignancy. The performance of PNB must always be determined on an individual case basis and when the result is likely to affect management. The complementary roles of PNB, bronchoscopic biopsy, and video-assisted thoracoscopic biopsy continue to evolve.

Airway complications after lung transplantation: treatment and long-term outcome.

BACKGROUND: Airway complications are a significant cause of morbidity after lung transplantation. Effective treatment reduces the impact of these complications. METHODS: Data from 123 lung (99 single, 24 bilateral) transplants were reviewed. Potential risk factors for airway complications were analyzed. Stenoses were treated with expanding metal (Gianturco) stents. RESULTS: Mean follow-up was 749 days. Thirty-five complications developed in 28 recipients (complication rate: 23.8%/anastomosis). Mean time to diagnosis was 47 days. Only Aspergillus infection and airway necrosis were significantly associated with development of complications (p < 0.00001 and p < 0.03, respectively). Stenosis was diagnosed an average of 42 days posttransplant. Average decline in forced expiratory volume in 1 second (FEV1) was 39%. Eighteen patients (13 single and 5 bilateral) required stent insertion. Mean increase in FEV1 poststenting was 87%. Two stent patients died from infectious complications. Six patients required further intervention. Long-term survival and FEV1 did not differ from nonstented patients. CONCLUSIONS: Aspergillus and airway necrosis are associated with the development of airway complications. Expanding metal stents are an effective long-term treatment.

An investigation into causative factors in patients with bronchiectasis.

Bronchiectasis is a pathologic description of lung damage characterized by inflamed and dilated thick-walled bronchi. These findings may result from a number of possible causes and these may influence treatment and prognosis. The aim of this study was to determine causative factors in 150 adults with bronchiectasis (56 male, 94 female) identified using high-resolution computerized tomography. Relevant factors were identified in the clinical history; cystic fibrosis gene mutation analysis was performed; humoral immune defects were determined by measuring immunoglobulins, IgG subclasses and functional response to Pneumovax II vaccine; assessment was made of neutrophil function (respiratory burst, adhesion molecule expression, and chemotaxis); ciliary function was observed and those likely to have allergic bronchopulmonary aspergillosis (ABPA) were identified. Causes identified were: immune defects (12 cases), cystic fibrosis (4), Young's syndrome (5), ciliary dysfunction (3), aspiration (6), panbronchiolitis (1), congenital defect (1), ABPA (11), rheumatoid arthritis (4), and early childhood pneumonia, pertussis, or measles (44). Intensive investigation of this population of patients with bronchiectasis led to identification of one or more causative factor in 47% of cases. In 22 patients (15%), the cause identified had implications for prognosis and treatment.

Percutaneous needle biopsy of the pleura.

Percutaneous needle biopsy of the pleura and thoracic wall is a relatively simple, minimally invasive, and safe technique that may be performed in an outpatient setting under local anesthesia. Image guidance, combined with the use of core biopsy needles and immunohistochemical techniques, have lead to increased diagnostic yield and overall accuracy. Open and thoracoscopic biopsies are reserved for a minority of patients in whom pleural fluid cytology and percutaneous needle biopsy are nondiagnostic.

Clinical and radiological characteristics of lung disease in inflammatory bowel disease.

The pulmonary associations of inflammatory bowel disease (IBD) are poorly characterized. The clinical, physiological and high-resolution computed tomographic thorax characteristics of the lung disease in patients with IBD presenting with respiratory symptoms are described. Detailed clinical information was obtained and standard pulmonary physiological tests and thorax high-resolution computed tomography performed on 14 patients with ulcerative colitis (UC) and three with Crohn's disease (CD), 10 male, aged 38-83 yrs. Respiratory symptoms had been present for 2-50 yrs and extraintestinal manifestations were present in three (17.6%). Normal pulmonary physiology (six patients) was associated with the high resolution computed tomographic changes of bronchiectasis, mosaic perfusion and air trapping suggestive of obliterative bronchiolitis and a pattern of centrilobular nodules and branching linear opacities ("tree in bud" appearance) suggestive of either cellular bronchiolitis or bronchiolectasis with mucoid secretions. Bronchiectasis was found in 13 patients (11 UC, 2 CD), 11 had air trapping and five had a "tree in bud" appearance on computed tomography. One patient had a predominantly peripheral reticular pattern at the lung bases similar to that found in cryptogenic fibrosing alveolitis and one patient had a mixed reticular and ground-glass pattern in the midzones with a patchy distribution in the central and peripheral portions of the lungs with air trapping. Eleven patients (three with alveolitis) exhibited a clinical and/or physiological response to steroids. Pulmonary abnormalities in ulcerative colitis and Crohn's disease can present years after the onset of the bowel disease and can affect any part of the lungs. Early recognition is important as they can be strikingly steroid-responsive.

Linear opacities on HRCT in bronchiolitis obliterans organising pneumonia.

The aim of this study was to report the high-resolution computed tomography (HRCT) appearances of linear opacities that may occur in isolation or in combination with other changes in bronchiolitis obliterans organising pneumonia (BOOP). Eleven patients with BOOP and linear opacities on HRCT were identified at three independent teaching hospitals. The HRCT images and clinical course of each patient were reviewed. Two distinct types of linear opacity were identified. The type-1 opacity extended in a radial manner along the line of the bronchi towards the pleura and was usually intimately related to bronchi. The type-2 opacity occurred in a sub-pleural location and bore no relationship to the bronchi. Both types occurred most commonly in the lower lobes, frequently were associated with multi-focal areas of consolidation and usually completely resolved with treatment. There was no associated bronchiectasis, irreversible volume loss or a reticular or honeycomb pattern. In 2 patients linear opacities were the sole abnormality on HRCT. Bronchiolitis obliterans organising pneumonia may occur in a pure "linear form" or HRCT may demonstrate linear opacities in addition to multi-focal consolidation.

Imaging the airways. Hemoptysis, bronchiectasis, and small airways disease.

Advances in technology have increased the contribution of radiology in understanding and evaluating diseases of the airways. In patients with hemoptysis, CT is now established as a complementary technique to bronchoscopy, or as an alternative to bronchoscopy in selected cases. The introduction of high-resolution CT has improved the detection and assessment of bronchiectasis and small airways disease, allowed better correlation between pathologic changes and radiologic appearances, and provided new insights into possible links between small airways disease and bronchial disease.

Lemierre syndrome: forgotten but not extinct--report of four cases.

Four cases of Lemierre syndrome are reported in which metastatic abscesses resulted from septic thrombosis of the internal jugular vein secondary to bacterial pharyngitis. While chest radiographic findings were nonspecific, results of computed tomography (CT) of the thorax in each case were highly suggestive of septic pulmonary emboli. Internal jugular venous thrombosis was demonstrated at ultrasonography and contrast material-enhanced CT.

How reliable is modern breast imaging in differentiating benign from malignant breast lesions in the symptomatic population?

AIM: To assess the ability of mammography and ultrasound individually and in combination to predict whether a breast abnormality is benign or malignant in patients with symptomatic breast disease. MATERIALS AND METHODS: Patients included were those in whom histological confirmation of the abnormality following surgical excision was available. Mammographic and ultrasound appearances were prospectively classified using a four-point scale (1 = no significant lesion, 2 = benign lesion, 3 = possibly malignant, 4 = probably malignant). RESULTS: Histological confirmation following surgical excision was available in 559 patients, of which 303 were benign and 256 were malignant. The imaging classification was correlated with histology in these 559 lesions. In predicting final histology, the sensitivity and specificity of mammography alone were 78.9 and 82.7%, respectively, of ultrasound alone were 88.9 and 77.9%, respectively, and of mammography and ultrasound in combination were 94.2 and 67.9%, respectively. Only one patient had both a mammogram and ultrasound reported as normal (category 1 for both tests) in whom subsequent histology revealed a carcinoma (0.4% of all carcinomas). CONCLUSION: We found that the extensive use of ultrasound increases the cancer detection rate in this selected population by 14%.

Granulomatous interstitial pneumonitis in association with primary hypogammaglobulinemia: computed tomography appearances.

The authors describe the computed tomographic appearances of nonspecific granulomatous interstitial pneumonitis in two patients with primary hypogammaglobulinemia. Their purpose is to show that it is important to consider this entity in the differential diagnosis of multiple pulmonary nodules in patients with this disease.

High-resolution computed tomographic appearance of MALToma of the lung.

MALToma of the lung is rare and advances in molecular techniques have only recently allowed accurate diagnostic classification of the previously termed "pseudolymphomas" by demonstrating that many are monoclonal B-cell proliferations of MALT tissue and therefore true low-grade lymphomas. No significant previous contribution was found in the literature regarding the high-resolution CT appearance (HRCT) of these tumours. We describe the high-resolution CT appearances in five cases presenting to our institution from 1994 to 1997. The HRCT scans (1-mm sections at 10- to 15-mm intervals) were performed as the opacities seen radiographically were thought to be part of a diffuse lung process. In one patient a spiral sequence was performed through the main airway. Multifocal, ill-defined nodules containing air bronchograms were seen in four cases and focal lobar consolidation in one case. Interlobular septal thickening, centrilobular micronodules and bronchial wall thickening were seen in two cases. Mediastinal lymphadenopathy and pleural reaction do not appear to be characteristic features. The appearance of multifocal consolidation is similar to that seen in bronchoalveolar cell carcinoma and cryptogenic organising pneumonia.

Tracheal involvement in Wegener's granulomatosis: evaluation using spiral CT.

OBJECTIVE: To describe the computed tomography (CT) appearances of tracheal stenosis in Wegener's granulomatosis (WG) and to assess the additional value of reformatted images. PATIENTS AND METHODS: Ten patients with tracheal involvement by WG were assessed with spiral CT and both coronal and three-dimensional surface shaded images were generated. Fibreoptic bronchoscopy was also performed in all patients. RESULTS: Ninety per cent of lesions were situated in the subglottic region. In all cases there was circumferential mucosal thickening, in nine cases extending over a relatively short distance (mean 2.4 cm). The degree of narrowing of the axial luminal diameter ranged from 23% to 100%. In three patients there was contiguous involvement of the vocal cords evident on CT, two further cases with mild vocal cord inflammation were identified bronchoscopically. Other CT findings included mucosal irregularity and ulceration (50%), and involvement of the tracheal cartilages (20%). CONCLUSION: Wegener's granulomatosis may involve the trachea with resultant stenosis. Spiral CT is an easily performed, non-invasive technique which provides accurate assessment of tracheal lesions and is complementary to bronchoscopy. The main additional advantage of coronal reformatted images was our added confidence in defining the upper and lower limits of lesions and in the evaluation of vocal cord involvement.

Aspergillus infection of the respiratory tract after lung transplantation: chest radiographic and CT findings.

The objective of our study was to assess radiographic and CT findings in lung transplant patients with evidence of Aspergillus colonization or infection of the airways and correlate the findings with clinical, laboratory, bronchoalveolar lavage, biopsy and autopsy findings. The records of 189 patients who had undergone lung transplantation were retrospectively reviewed for evidence of Aspergillus colonization or infection of the airways. Aspergillus was demonstrated by culture or microscopy of sputum or bronchoalveolar lavage fluid or histologically from lung biopsies or postmortem studies in 44 patients (23 %). Notes and radiographs were available for analysis in 30 patients. In 12 of the 30 patients (40 %) chest radiographs remained normal. In 11 of 18 patients with abnormal radiographs pulmonary abnormalities were attributed to invasive pulmonary aspergillosis (IPA) in the absence of other causes for pulmonary abnormalities (8 patients) or because of histological demonstration of IPA (3 patients). In these 11 patients initial radiographic abnormalities were focal areas of patchy consolidation (8 patients), ill-defined pulmonary nodules (2 patients) or a combination of both (1 patient). In some of the lesions cavitation was demonstrated subsequently. At CT a "halo" of decreased density was demonstrated in some of the nodules and lesion morphology and location were shown more precisely. Demonstration of Aspergillus from the respiratory tract after lung transplantation does not necessarily reflect IPA but may represent colonization of the airways or semi-invasive aspergillosis. The findings in patients with IPA did not differ from those described in the literature in other immunocompromised patients, suggesting that surgical disruption of lymphatic drainage and nervous supply or effects of preservation and transport of the transplant lung do not affect the radiographic appearances.

A randomized trial of spiral CT and ventilation perfusion scintigraphy for the diagnosis of pulmonary embolism.

PURPOSE: To compare spiral computed tomographic pulmonary angiography (SCTA) with lung ventilation-perfusion scintigraphy (VQS) as the initial investigation of patients with suspected pulmonary embolism (PE). MATERIALS AND METHODS: Prospective randomized trial of 78 patients with suspected pulmonary embolism. Patients underwent either SCTA or lung VQS as their initial investigation for PE. Cross-over between groups meant that 50 patients received both examinations. The clinicians' assessment of overall clinical likelihood of PE was also collected. RESULTS: (1) It was possible to make a confident diagnosis in a significantly larger proportion of patients when SCTA was used as the initial investigation (35/39, 90%) compared with using VQS first (21/39, 54% P<0.001). The main difference between the two groups was that SCTA demonstrated lesions other than pulmonary embolism considered responsible for the patients' symptoms in 13/39 patients (33%) randomized to SCTA as the initial investigation and following a non-diagnostic VQS in 10/39 patients (25%) randomized to VQS as the initial investigation. (2) There was no difference in the prevalence or detection of PE in the two groups. SCTA demonstrated pulmonary emboli in 6/39 patients (16%) in the SCTA first group and VQS was high probability for PE in 5/39 patients (13%) in the VQS first group. SCTA detected PE in a further two patients in the VQS first group. CONCLUSION: It is proposed that, where logistically feasible, SCTA should replace VQS as the initial investigation for PE in patients with an underlying cardio-respiratory disorder.

Churg-Strauss syndrome: the spectrum of pulmonary CT findings in 17 patients.

OBJECTIVE: The aim of this study was to evaluate the pulmonary CT findings in patients with Churg-Strauss syndrome to determine the frequency and nature of parenchymal abnormalities. MATERIALS AND METHODS: CT examinations performed at the time of diagnosis in 17 patients with Churg-Strauss syndrome were retrospectively evaluated by two observers who reached a decision by consensus about the presence and nature of parenchymal abnormalities. High-resolution CT (1- to 3-mm collimation) was performed in 14 patients and conventional CT (6- to 10-mm collimation) was performed in three cases. RESULTS: Predominant CT findings consisted of parenchymal opacification (consolidation or ground-glass attenuation) (n = 10), pulmonary nodules (n = 2), bronchial wall thickening or dilatation (n = 2), interlobular septal thickening (n = 1), and normal anatomy (n = 2). Parenchymal opacification was predominantly peripheral (n = 6) or random in distribution (n = 4). CONCLUSION: The most common CT finding in patients with Churg-Strauss syndrome consists of areas of parenchymal opacification that may be random or peripheral in distribution. These findings are nonspecific.