Interstitial Abnormalities Research Articles

Automated quantification of radiological patterns predicts survival in idiopathic pulmonary fibrosis

Accurate assessment of prognosis in idiopathic pulmonary fibrosis remains elusive due to significant individual radiological and physiological variability. We hypothesised that short-term radiological changes may be predictive of survival. We explored the use of CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating), a novel software tool developed by the Biomedical Imaging Resource Laboratory at the Mayo Clinic Rochester (Rochester, MN, USA) for the analysis and quantification of parenchymal lung abnormalities on high-resolution computed tomography. We assessed baseline and follow-up (time-points 1 and 2, respectively) high-resolution computed tomography scans in 55 selected idiopathic pulmonary fibrosis patients and correlated CALIPER-quantified measurements with expert radiologists' assessments and clinical outcomes. Findings of interval change (mean 289 days) in volume of reticular densities (hazard ratio 1.91, p=0.006), total volume of interstitial abnormalities (hazard ratio 1.70, p=0.003) and per cent total interstitial abnormalities (hazard ratio 1.52, p=0.017) as quantified by CALIPER were predictive of survival after a median follow-up of 2.4 years. Radiologist interpretation of short-term global interstitial lung disease progression, but not specific radiological features, was also predictive of mortality. These data demonstrate the feasibility of quantifying interval short-term changes on high-resolution computed tomography and their possible use as independent predictors of survival in idiopathic pulmonary fibrosis.

The lung in paracoccidioidomycosis: new insights into old problems

OBJECTIVES:Chronic paracoccidioidomycosis can diffusely affect the lungs. Even after antifungal therapy, patients may present with residual respiratory abnormalities due to fungus-induced lung fibrosis.METHODS:A cross-sectional analysis of 50 consecutive inactive, chronic paracoccidioidomycosis patients was performed using high resolution computed tomography, pulmonary function tests, ergospirometry, the six-minute walk test and health-related quality of life questionnaires.RESULTS:Radiological abnormalities were present in 98% of cases, the most frequent of which were architectural distortion (90%), reticulate and septal thickening (88%), centrilobular and paraseptal emphysema (84%) and parenchymal bands (74%). Patients typically presented with a mild obstructive disorder and a mild reduction in diffusion capacity with preserved exercise capacity, including VO2max and six-minute walking distance. Patient evaluation with the Saint-George Respiratory Questionnaire showed low impairment in the health-related quality of life, and the Medical Research Council questionnaire indicated a low dyspnea index. There were, however, patients with significant oxygen desaturation upon exercise that was associated with respiratory distress compared with the non-desaturated patients. The initial counterimmunoelectrophoresis of these patients was higher and lung emphysema was more prominent; however, there were no differences in the interstitial fibrotic tomographic abnormalities, tobacco exposure, functional responses, exercise capacity or quality of life.CONCLUSIONS:Inactive, chronic paracoccidioidomycosis patients show persistent and disseminated radiological abnormalities by high resolution computed tomography, short impairments in pulmonary function and low impacts on aerobic capacity and quality of life. However, there was a subset of individuals whose functional impairment was more severe. These patients present with higher initial serology and more severe emphysema, stressing the importance of adequate treatment associated with tobacco exposure cessation.

Decline in pulmonary function during chronic hepatitis C virus therapy with modified interferon alfa and ribavirin

Rare interstitial lung disease cases have been reported with albinterferon alfa-2b (albIFN) and pegylated interferon alfa-2a (Peg-IFNα-2a) in chronic hepatitis C virus (HCV) patients. Systematic pulmonary function evaluation was conducted in a study of albIFN q4wk vs Peg-IFNα-2a qwk in patients with chronic HCV genotypes 2/3. Three hundred and ninety-one patients were randomly assigned 4:4:4:3 to one of four, open-label, 24-week treatment groups including oral ribavirin 800 mg/d: albIFN 900/1200/1500 μg q4wk or Peg-IFNα-2a 180 μg qwk. Standardized spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded at baseline, weeks 12 and 24, and 6 months posttreatment, and chest X-rays (CXRs) at baseline and week 24. Baseline spirometry and DLCO were abnormal in 35 (13%) and 98 (26%) patients, respectively. Baseline interstitial CXR findings were rare (4 [1%]). During the study, clinically relevant DLCO declines (≥15%) were observed in 173 patients (48%), and were more frequent with Peg-IFNα-2a and albIFN 1500 μg; 24 weeks posttreatment, 57 patients (18%) still had significantly decreased DLCO, with a pattern for greater rates with albIFN vs Peg-IFNα-2a. One patient developed new interstitial CXR abnormalities, but there were no clinically relevant interstitial lung disease cases. The risk of persistent posttreatment DLCO decrease was not related to smoking, alcohol, HCV genotype, sustained virologic response, or baseline viral load or spirometry. Clinically relevant DLCO declines occurred frequently in chronic HCV patients receiving IFNα/ribavirin therapy and commonly persisted for ≥6 months posttherapy. The underlying mechanism and clinical implications for long-term pulmonary function impairment warrant further research.

Combined pulmonary fibrosis and emphysema in connective tissue disease

This review discusses combined pulmonary fibrosis and emphysema (CPFE) in the setting of connective tissue disease. CPFE is a recently identified syndrome in smokers or ex-smokers characterized by dyspnea often severe, preserved lung volumes, severely impaired gas exchanges, and an increased risk of pulmonary hypertension associated with a dismal prognosis, and possibly lung cancer. It may be encountered in the setting of connective tissue diseases, especially rheumatoid arthritis and systemic sclerosis, with generally similar features as 'idiopathic' (tobacco-related) CPFE. The diagnosis is based on the presence of both emphysema predominating in the upper lobes and frequently paraseptal, and interstitial abnormalities suggesting pulmonary fibrosis in the lower lung zones with velcro crackles at auscultation. Pathologic radiological correlations are difficult owing to various pathology and difficulties in identifying honeycombing at chest high-resolution computed tomography in the setting of coexistent emphysema. Tobacco smoking is associated with an increased risk of developing most of the individual components of the syndrome (i.e. emphysema, pulmonary fibrosis, pulmonary hypertension, rheumatoid arthritis, and pulmonary fibrosis among patients with rheumatoid arthritis). CPFE impacts modalities of follow-up for pulmonary function and detection of pulmonary hypertension especially in systemic sclerosis. The syndrome of CPFE is a distinct pulmonary manifestation in the spectrum of lung diseases associated with connective tissue diseases, especially in smokers or ex-smokers.

Renal effects of long-term darbepoetin alpha treatment in hypertensive TGR(mRen2)27 rats

Erytropoietin (EPO) has cytoprotective and angiogenic properties and has a beneficial effect in ischaemic conditions. Since the development of renal interstitial abnormalities are often associated with ischaemia, we studied the effects of the long-acting EPO analogue darbepoetin alpha (DA) on kidney damage in TGR(mRen2)27 (Ren2) rats. Ren2 rats were randomised to DA or vehicle (VEH) or to DA + angiotensin converting enzyme inhibitor (ACEi) or VEH + ACEi. Sprague Dawley (SD) rats served as controls. Blood pressure was measured weekly and 24-h urine was collected to measure proteinuria. Blood samples were collected for creatinine and haematocrit. Kidneys were studied for inflammation and pre-fibrosis. Renal mRNA expression was studied for EPO, EPO-receptor, collagen-3α1 and kidney injury molecule-1 (KIM-1). DA had no effect on SBP, serum creatinine and proteinuria. Interstitial and glomerular α-SMA expression was significantly increased in Ren2. ACEi but not DA improved the increased renal inflammatory and pro-fibrotic profile in Ren2 rats. DA on top of ACEi further reduced glomerular α-SMA and KIM-1 expression. Long-term DA treatment has no beneficial effects on renal structural and functional changes in TGR(mRen2)27 rats in the time frame studied and the dose provided.

Chronic Diseases, Chromosomal Abnormalities, and Congenital Malformations as Risk Factors for Respiratory Syncytial Virus Hospitalization: A Population-Based Cohort Study

Little is known about how chronic conditions other than prematurity, heart disease, and Down syndrome affect the risk and severity of hospitalization for respiratory syncytial virus (RSV). We assess the risk and severity of RSV hospitalization in children with chronic conditions in this register-based, population-based cohort study. Data on RSV tests, maternal smoking, siblings, single parenthood, mode of delivery, gestational age at birth, major surgery, asthma diagnosis, chronic conditions, and hospitalization and discharge dates were obtained from the Danish RSV database, the National Patient and Birth Registries, and the Civil Registration System. Cox regression models were used to estimate incidence rate ratios (IRRs) for RSV hospitalization between groups stratified by sex and date of birth. Duration of RSV hospitalization was analyzed in a linear regression and reported as geometric mean ratios. A total of 391 983 children aged 0-23 months were included in the analysis. A total of 10,616 (2.7%) had a diagnosis for chronic disease. IRRs (95% confidence intervals) for RSV hospitalization in children with any congenital or acquired chronic condition were 2.18 (2.01-2.36) and 2.25 (1.94-2.61), respectively. Several new risk factors for RSV hospitalization, including malformations, interstitial lung disease, neuromuscular disease, liver disease, chromosomal abnormalities, congenital immunodeficiencies, and inborn errors of metabolism, were identified. Duration of RSV hospitalization was increased in many chronic conditions. Chronic disease per se is an important risk factor for RSV hospitalization.

Descriptive analysis of the respiratory health status of persons exposed to Libby amphibole asbestos

ObjectiveDescribe respiratory health and quality of life in persons exposed to Libby amphibole asbestos (LAA) contaminated vermiculite.DesignCross-sectional descriptive.SettingAsbestos-related disease clinic in Libby, Montana USA.Participants329 individuals exposed to LAA; mostly men,...

Prevalence and characteristics of lung involvement on high resolution computed tomography in patients with ankylosing spondylitis: a systematic review.

To determine the prevalence of lung involvement and the spectrum of abnormalities revealed on HRCT in patients with AS, a systematic literature review was conducted in the Medline database up to May 2009 and in the abstracts of rheumatology scientific meetings (2006–2008). A hand search of references was also performed. Among the 264 selected articles, 10 articles (303 patients) allowed a calculation of the prevalence of lung abnormalities on thoracic HRCT in AS. A total of 185 patients (61%) had an abnormal thoracic HRCT: upper lobe fibrosis in 21 (6.9%), emphysema in 55 (18.1%), bronchiectasis in 33 (10.8%), and ground glass attenuation in 34 (11.2%). Non specific interstitial abnormalities were observed in 101 (33%) patients. The most common observed abnormalities were pleural thickening (52%), parenchymal bands (45%) and interlobular septal thickening (30%). Only the prevalence of upper lobe fibrosis increased significantly with disease duration (3 studies). Mild and non-specific interstitial abnormalities on thoracic HRCT are common in patients with AS, even in patients with early disease and without respiratory symptoms.

Tumoral cavitation in patients with non-small-cell lung cancer treated with antiangiogenic therapy using bevacizumab

Rationale and objectives: To investigate the frequency and radiographic patterns of tumoral cavitation in patients with non-small cell lung cancer (NSCLC) treated with bevacizumab, and correlate the imaging findings with the pathology, clinical characteristics and outcome. Materials and methods: Seventy-two patients with NSCLC treated with bevacizumab therapy were identified retrospectively. Baseline and follow-up chest computed tomography scan were reviewed to identify tumoral cavitation and subsequent filling in of cavitation. Radiographic cavitation patterns were classified into 3 groups. The clinical and outcome data were correlated with cavity formation and patterns. Results: Out of 72 patients, 14 patients developed cavitation after the initiation of bevacizumab therapy (19%; median time to event, 1.5 months; range 1.0–24.8 months). Three radiographic patterns of tumoral cavitation were noted: (1) development of cavity within the dominant lung tumor (n = 8); (2) development of non-dominant cavitary nodules (n = 3); and (3) development of non-dominant cavitary nodules with adjacent interstitial abnormalities (n = 3). Eleven patients (79%) demonstrated subsequent filling in of cavitation (the time from the cavity formation to filling in; median 3.7 months; range 1.9–22.7 months). No significant difference was observed in the clinical characteristics, including smoking history, or in the survival between patients who developed cavitation and those who did not. Smoking history demonstrated a significant difference across 3 radiographic cavitation patterns (P = 0.006). Hemoptysis was noted in 1 patient with cavity formation and 4 patients without, with no significant difference between the 2 groups. Conclusion: Tumoral cavitation occurred in 19% in patients with NSCLC treated with bevacizumab and demonstrated 3 radiographic patterns. Subsequent filling in of cavitation was noted in the majority of cases.

Mesothelial cell and anti-nuclear autoantibodies associated with pleural abnormalities in an asbestos exposed population of Libby MT

Despite data linking amphibole asbestos exposure with production of autoantibodies, the role of autoantibodies in subsequent disease is unknown. Residents of Libby, Montana have experienced significant exposure to amphibole asbestos due to the mining of asbestos-contaminated vermiculite near the community over several decades. This population predominantly exhibits pleural disease, and an autoimmune-like disorder that has yet to be well defined. This study sought to determine whether autoantibodies from asbestos-exposed subjects were associated with pleural lesions. Serum samples of subjects from Libby were evaluated for anti-nuclear antibodies (ANA) and mesothelial cell autoantibodies (MCAA) using cell based ELISA. The presence of radiographic abnormalities detected during the time frame of serum collection was determined from screening records. In accord with previous studies, 61.3% (76/124) of the Libby samples were ANA positive, a frequency much higher than expected for a healthy population. The odds of having pleural or interstitial abnormalities in Libby was nearly 3.55 times greater for individuals that tested positive for ANA compared with individuals negative for ANA ( p = 0.004). MCAA were also detected at a strikingly high frequency (18.5%; 23/124) in samples from Libby. Individuals with MCAA had 4.9 times the risk of having pleural abnormalities compared to MCAA-negative subjects ( p = 0.044). In conclusion, ANA and MCAA were elevated in a study population that was known to have chronic exposure to asbestos, and these autoantibodies were associated with pleural abnormalities, the predominant finding in the asbestos-exposed population of Libby. Additional research is needed to determine the role these autoantibodies may play in pulmonary disease.

Getting to the heart of cardiac remodeling; how collagen subtypes may contribute to phenotype

The objective of this study was to investigate the nature and biomechanical properties of collagen fibers within the human myocardium. Targeting cardiac interstitial abnormalities will likely become a major focus of future preventative strategies with regard to the management of cardiac dysfunction. Current knowledge regarding the component structures of myocardial collagen networks is limited, further delineation of which will require application of more innovative technologies. We applied a novel methodology involving combined confocal laser scanning and atomic force microscopy to investigate myocardial collagen within ex-vivo right atrial tissue from 10 patients undergoing elective coronary bypass surgery. Immuno-fluorescent co-staining revealed discrete collagen I and III fibers. During single fiber deformation, overall median values of stiffness recorded in collagen III were 37±16% lower than in collagen I [p<0.001]. On fiber retraction, collagen I exhibited greater degrees of elastic recoil [p<0.001; relative percentage increase in elastic recoil 7±3%] and less energy dissipation than collagen III [p<0.001; relative percentage increase in work recovered 7±2%]. In atrial biopsies taken from patients in permanent atrial fibrillation (n=5) versus sinus rhythm (n=5), stiffness of both collagen fiber subtypes was augmented (p<0.008). Myocardial fibrillar collagen fibers organize in a discrete manner and possess distinct biomechanical differences; specifically, collagen I fibers exhibit relatively higher stiffness, contrasting with higher susceptibility to plastic deformation and less energy efficiency on deformation with collagen III fibers. Augmented stiffness of both collagen fiber subtypes in tissue samples from patients with atrial fibrillation compared to those in sinus rhythm are consistent with recent published findings of increased collagen cross-linking in this setting.

Asbestos-related diseases in automobile mechanics.

Automobile mechanics have been exposed to asbestos in the past, mainly due to the presence of chrysotile asbestos in brakes and clutches. Despite the large number of automobile mechanics, little is known about the non-malignant respiratory diseases observed in this population. The aim of this retrospective multicenter study was to analyse the frequency of pleural and parenchymal abnormalities on high-resolution computed tomography (HRCT) in a population of automobile mechanics. The study population consisted of 103 automobile mechanics with no other source of occupational exposure to asbestos, referred to three occupational health departments in the Paris area for systematic screening of asbestos-related diseases. All subjects were examined by HRCT and all images were reviewed separately by two independent readers; who in the case of disagreement discussed until they reached agreement. Multiple logistic regression models were constructed to investigate factors associated with pleural plaques. Pleural plaques were observed in five cases (4.9%) and interstitial abnormalities consistent with asbestosis were observed in one case. After adjustment for age, smoking status, and a history of non-asbestos-related respiratory diseases, multiple logistic regression models showed a significant association between the duration of exposure to asbestos and pleural plaques. The asbestos exposure experienced by automobile mechanics may lead to pleural plaques. The low prevalence of non-malignant asbestos-related diseases, using a very sensitive diagnostic tool, is in favor of a low cumulative exposure to asbestos in this population of workers.

Subclinical Interstitial Lung Abnormalities in Stable Renal Allograft Recipients in the Era of Modern Immunosuppression

Background Interstitial lung abnormalities have been detected in up to 24% of kidney transplant patients receiving traditional immunosuppressive therapies (eg, cyclosporine, azathioprine); they usually occur early after transplantation and tend to resolve over time. Newer immunosuppressants such as mycophenolic acid and, particularly, mammalian target of rapamycin (mTOR) inhibitors (eg, sirolimus) may cause significant lung toxicity. However, the prevalence and severity of interstitial lung lesions in long-term, stable kidney transplant patients receiving either traditional or newer immunosuppressants is not known. Methods We conducted a prospective, cross-sectional study examining high-resolution lung computed tomography (CT) scans in 63 stable kidney transplant recipients whose immunosuppressive therapy had remained unchanged for over 24 months. We compared CT findings of patients taking newer (mycophenolic acid and mTOR inhibitors) and traditional (calcineurin inhibitors and azathioprine) immunosuppressive drugs. Results Interstitial lung alterations were observed in only 3/63 patients (4.8%); the prevalence was 11.5% (3/26) versus 0% (0/37) among the newer versus traditional immunosuppressive therapy groups, respectively ( P = .065). The CT patterns were usual interstitial pneumonia and nonspecific interstitial pneumonia-like. The median time between transplant and CT was 49 months in the three patients with CT alterations and 95 months in the remaining 23 patients on newer immunosuppressants. It was 75 months for all patients on newer immunosuppressive drugs and 133 months for those on traditional therapies ( P = .0015). A follow-up CT, performed in 2/3 patients with interstitial abnormalities, showed that the lesions were stable in one, while they had disappeared in the other. Conclusions Interstitial lung abnormalities are infrequent and mild in stable kidney transplant patients treated with newer as well as traditional immunosuppressive drugs. As such abnormalities were detected in patients screened earlier after transplantation, the time since transplantation rather than the drug type is probably the major determinant.

Do asbestos-related pleural plaques on HRCT scans cause restrictive impairment in the absence of pulmonary fibrosis?

BackgroundIt is uncertain whether isolated pleural plaques cause functional impairment.ObjectiveTo analyse the relationship between isolated pleural plaques confirmed by CT scanning and lung function in subjects with occupational exposure to...

Prenatally diagnosed submicroscopic familial aberrations at 18p11.32 without phenotypic effect

BackgroundRecent development of MLPA (Multiplex-Ligation-dependent Probe Amplification, MRC-Holland) and microarray technology allows detection of a wide range of new submicroscopic abnormalities. Publishing new cases and case reviews associated with both clinical abnormalities and a normal phenotype is of great value.Findings/resultsWe report on two phenotypically normal foetuses carrying a maternally-inherited interstitial submicroscopic abnormality of chromosome 18p11.32. Both abnormalities were found with the aneuploidy MLPA kit P095 during rapid aneuploidy detection, which was offered along with conventional karyotyping. Foetus 1 and its mother have a 1,7 Mb deletion and foetus 2 and its mother have a 1,9 Mb duplication. In both cases normal babies were born. We used the HumanCytoSNP-12 array of Illumina to visualize the CNVs and map the breakpoints.ConclusionsWe suggest that a CNV at 18p11.32 (528,050-2,337,486) may represent a new benign euchromatic variant.

Lung diffusing capacity relates better to short‐term progression on HRCT abnormalities than spirometry in mild asbestosis

Pulmonary function tests (PFT), particularly spirometry and lung diffusing capacity for carbon monoxide (DL(CO) ), have been considered useful methods for the detection of the progression of interstitial asbestos abnormalities as indicated by high-resolution computed tomography (HRCT). However, it is currently unknown which of these two tests correlates best with anatomical changes over time. In this study, we contrasted longitudinal changes (3-9 years follow-up) in PFTs at rest and during exercise with interstitial abnormalities evaluated by HRCT in 63 ex-workers with mild-to-moderate asbestosis. At baseline, patients presented with low-grade asbestosis (Huuskonen classes I-II), and most PFT results were within the limits of normality. In the follow-up, most subjects had normal spirometry, static lung volumes and arterial blood gases. In contrast, frequency of DL(CO) abnormalities almost doubled (P < 0.05). Twenty-three (36.5%) subjects increased the interstitial marks on HRCT. These had significantly larger declines in DL(CO) compared to patients who remained stable (0.88 vs. 0.31 ml/min/mm Hg/year and 3.5 vs. 1.2%/year, respectively; P < 0.05). In contrast, no between-group differences were found for the other functional tests, including spirometry (P > 0.05). These data demonstrate that the functional consequences of progression of HRCT abnormalities in mild-to-moderate asbestosis are better reflected by decrements in DL(CO) than by spirometric changes. These results might have important practical implications for medico-legal evaluation of this patient population.

The chest features of patients with the novel influenza type A H1N1 on high resolution CT

Objective To explore the chest features of patients with the novel influenza type A H1N1 on HRCT. Methods One hundred and seventy-two chest HRCT examinations on 163 cases with Influenza type A H1N1 (9 cases were reexamed) were retrospectively analyzed using standard pulmonary window and mediastinal window, respectively. HRCT imaging appearances were summarized. Results Ninety-seven cases showed normal on chest HRCT, while the others showed abnormalities of parenchymal and interstitial. Among them, HRCT identified ground-glass opacity in 35 cases (53.0%), centrilobular nodules in 30 cases (45.5%), thickening of intralobular septa in 31 cases (47.0%), intralobular thin reticulation and micro-nodule in 8 cases (12.1%), single-lobular inflammation in 19 cases (28.8%), consolidation of lung(the large consolidation and multiple small consolidations)in 15 cases (22.7%), pulmonary atelectasis in 3 cases (4.5%), and irregular lines in 2 cases (3.0%). Pleurisy was also revealed including 8 cases with right pleurisy, 5 cases with left pleurisy, and 19 cases with bilateral pleurisy. Mediastinal and axillary lymphadenopathy were found in 7 cases, who were spared of pleural effusion. All above abnormalities resolved quickly after anti- virus treatment. Conclusion Parenchymal and interstitial abnormalities, mediastinum and axillary fossa lymphadenopathy, and pleural effusion were the common findings on HRCT in patients with Influenza type A H1N1, which were similar to those of other viral pneumonia. Key words: Influenza, human; Thoracic diseases; Tomography, X-ray computed

Asbestosis: demonstration of distinctive interstitial fibroelastosis

Asbestosis has long been defined as a diffuse interstitial "fibrotic" process, in similarity to other chronic interstitial pulmonary diseases. To address the hypothesis (which was based on morphological nuances) that the interstitial connective tissue response in asbestosis may be fibroelastotic rather than fibrotic, a comparative characterization of the connective response in cases of asbestosis and other forms of interstitial lung disease was performed. Archival open lung biopsies or autopsy specimens of pulmonary diseases featuring interstitial connective tissue abnormalities (15 of asbestosis, 21 of organizing pneumonia, 15 usual interstitial pneumonitis/idiopathic pulmonary fibrosis [IPF], 9 organizing diffuse alveolar damage, 9 "nonspecific" interstitial pneumonitis, 4 sarcoidosis, 3 each of desquamative interstitial pneumonia and chronic amiodarone toxicity, 2 cryptogenic organizing pneumonias, and 1 each of chronic hypersensitivity pneumonitis and chronic eosinophilic pneumonitis [85 total]) were stained histochemically with hematoxylin and eosin, Perl's method, Gomori's trichrome procedure, and the Verhoeff-van Gieson technique. Representative subsets of the cases (n = 20) were also studied immunohistologically using an antibody to elastin. Fibroelastosis in each of the samples was assessed for the degree of response and its location using a 3-tiered scale. The degree of fibroelastosis in the 15 cases of asbestosis was variable, with the pattern being peribronchial and perivascular in all instances; at least 2 asbestos bodies were identified in fibroelastotic foci in each of the 15 cases as highlighted with Perl's stain. Forty-seven cases of nonasbestotic lung disease (71%) showed interstitial fibrosis with a variable (usually modest) amount of admixed elastic tissue; when present, elastic fibers were distributed in a diffuse interstitial pattern, with or without perivascular accentuation. All cases of IPF also showed areas of fibroelastosis, but those foci were confined to regions of overt "honeycomb" change. No asbestos bodies were seen in any disease except asbestosis, and a predominantly peribronchial pattern of fibroelastosis was not identified in any nonasbestotic interstitial lung disease in this study. The authors conclude that the types and patterns of pulmonary connective tissue response in interstitial lung diseases may provide additional diagnostic clues to the presence of asbestosis.

Age‐dependent pattern of connexin43 expression in testes of European bison (Bison bonasus, L.)

Morphology and the expression of connexin43 (Cx43) was investigated in testes of immature, prepubertal, and adult European bison bulls by means of routine histology, immunohistochemistry, and Western blotting, respectively. Testes were collected from culled animals living in Bialowieza and Borecka Forests, Poland. Histological examination of testicular tissue of immature and prepubertal males revealed normal structure, whereas of adult individuals either normal testicular structure with advanced spermatogenesis or varying degrees of tubule and interstitial tissue abnormality were seen. Immunohistochemical studies revealed Cx43 signal mostly at Leydig cell membrane appositions. In testes of immature males heterogeneous staining was observed; its intensity markedly increased in prepubertal males reaching almost two times more intense staining in adults. Strong Cx43 signal between Leydig cells was also observed in testes with structural alterations; however, sporadically it was of weak linear pattern. In the tubules of the latter, the intensity of Cx43 staining was weak to moderate or it was even absent. Immunohistochemical qualitative analysis was confirmed by quantitative image analysis in which the staining intensity was expressed as relative optical density of diaminobenzidine deposits. Data from Western blot analyses confirmed the results obtained by immunohistochemistry; immunodetectable Cx43 protein as a band of 43 kDa was detected in all testes samples. Overall, the increase in Cx43 level in testes along the bison postnatal development may be capable of a better exchange of metabolites and coordinating Leydig cell activity during maturation. A relationship between homozygosity occurring in European bison and altered intercellular communication is suggested.

Drs. Mori and Cho reply

We thank Dr. Georgiadis and colleagues for their comments on our study1. We are pleased that our findings have attracted the interest of readers, and we offer the following response. First, Georgiadis, et al state that we reported no significant differences in HRCT findings between patients with early RA and those with longstanding RA, but we think that this is a misinterpretation. We performed HRCT on a total of 126 patients with either early RA (n = 65) or longstanding RA (n = 61). Abnormalities on HRCT imaging were categorized, and the frequency of each finding and its extent in the lungs were compared between the 2 patient populations. We found that the frequency of interstitial abnormalities such as ground-glass attenuation, reticulation, honeycombing, and consolidation was not significantly different between the 2 groups. Yet it is important to recall that, in contrast, there were significant differences in the frequencies of parenchymal micronodules and bronchial wall thickening, both of which are indicative of small-airway diseases; specifically, these conditions were more prominently observed in the patients with longstanding RA, which tendency apparently contributed to the higher incidence of the bronchiolitis pattern in this group. We therefore concluded that the incidence of bronchiolar abnormalities is associated with the duration of RA. The longstanding RA group appeared to be predisposed to complications … Address reprint requests to Dr. S. Mori, Clinical Research Center for Rheumatic Disease and Department of Rheumatology, Kumamoto Saishunsou National Hospital, 2659 Suya, Kohshi, Kumamoto 861-1196, Japan. E-mail: moris{at}saisyunsou1.hosp.go.jp