Biomedical subjects

Andrew G Nicholson

Publications and source records attributed to Andrew G Nicholson.

At least 37 records · Page 2Linked to original sources

PubMed2005

Nature of airway inflammation and remodeling in chronic cough.

BACKGROUND: Chronic cough may be a result of asthma and non-asthma causes, but it is unclear whether there are specific inflammatory or remodeling changes. OBJECTIVE: We determined airway mucosal changes in patients presenting with asthmatic cough and cough associated with non-asthmatic causes. METHODS: Patients with chronic cough of non-asthmatic (n=33; postnasal drip/rhinitis in 6, gastroesophageal reflux in 5, bronchiectasis in 3, and idiopathic in 19) and asthmatic (n=14) causes and 15 healthy controls underwent fiberoptic bronchoscopy. Morphometry of bronchial biopsies and capsaicin cough sensitivity were assessed. RESULTS: Compared with controls, submucosal eosinophils and neutrophils were increased in patients with asthmatic cough (P<.005) and submucosal mast cells in patients with non-asthmatic cough (P=.01). Sub-basement membrane thickness, goblet cell area, vascularity, and vessel size were also increased in both groups. Smooth muscle area was higher only in patients with non-asthmatic cough (P=.0007 vs control and P=.019 vs asthmatic cough). None of the pathologic changes were related to the duration of coughing. Cough sensitivity was heightened in patients with non-asthmatic cough compared with controls and patients with asthmatic cough. The degree of goblet cell hyperplasia and epithelial shedding positively correlated with cough sensitivity in patients with non-asthmatic cough (r=0.43; P=.01; and r=0.40; P=.02, respectively). CONCLUSION: Features of airway wall remodeling are prominent in the airways with non-asthmatic as well as asthmatic cough. These are linked to chronic cough rather than to asthma. Mast cell hyperplasia rather than eosinophilia is distinctive for non-asthmatic cough.

Adult↗

PubMed2005

The impact of stage and cell type on the prognosis of pulmonary neuroendocrine tumors.

OBJECTIVE: In pulmonary neuroendocrine tumors the realization that the extent of nodal disease is related to cell type has led to a controversy as to which is the dominant prognostic factor, stage or morphology. To clarify this relationship, we studied patients treated at our institution over a 23-year period. METHODS: This is a historical cohort study of patients with confirmed pulmonary neuroendocrine tumors who underwent lung resection from 1980 through 2003. Survivors were contacted by telephone, and recurrences were confirmed by means of histopathology. Cox proportional hazards regression was used to ascertain the joint influence of several risk factors on survival. RESULTS: The mean age of the cohort was 54 years (standard deviation, 15 years), and 100 (57%) were men. The cell types for the 177 eligible patients were typical carcinoid in 89 (50%), atypical carcinoid in 15 (8%), large cell in 22 (13%), and small cell in 51 (29%). The median time to follow-up was 7 years (first to third quartile, 2-12 years), and overall 5- and 10-year survivals were 86% (79%-90%) and 81% (74%-87%), respectively. The univariable predictors of survival were age (P = .001), nodal stage (P = .01), and cell type (P < .001). In the final multivariable model only age (P = .04) and cell type (P < .001) remained as independent predictors. The hazard of death among patients with large cell or small cell lung cancer was highest in the first year and a half after diagnosis, reducing drastically thereafter. CONCLUSIONS: In pulmonary neuroendocrine tumors cell type is the predominant determinant of survival. The survival of patients with each cell type is sufficiently diverse to warrant different management strategies. Conservative resection is feasible for typical carcinoids, but the effects of adjuvant chemotherapy need to be evaluated for the other subgroups.

Cohort Studies↗

PubMed2005

Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis.

The hallmark of idiopathic pulmonary fibrosis (IPF) is the myofibroblast, the cellular origin of which in the lung is unknown. We hypothesized that alveolar epithelial cells (AECs) may serve as a source of myofibroblasts through epithelial-mesenchymal transition (EMT). Effects of chronic exposure to transforming growth factor (TGF)-beta1 on the phenotype of isolated rat AECs in primary culture and a rat type II cell line (RLE-6TN) were evaluated. Additionally, tissue samples from patients with IPF were evaluated for cells co-expressing epithelial (thyroid transcription factor (TTF)-1 and pro-surfactant protein-B (pro-SP-B), and mesenchymal (alpha-smooth muscle actin (alpha-SMA)) markers. RLE-6TN cells exposed to TGF-beta1 for 6 days demonstrated increased expression of mesenchymal cell markers and a fibroblast-like morphology, an effect augmented by tumor necrosis factor-alpha (TNF-alpha). Exposure of rat AECs to TGF-beta1 (100 pmol/L) resulted in increased expression of alpha-SMA, type I collagen, vimentin, and desmin, with concurrent transition to a fibroblast-like morphology and decreased expression of TTF-1, aquaporin-5 (AQP5), zonula occludens-1 (ZO-1), and cytokeratins. Cells co-expressing epithelial markers and alpha-SMA were abundant in lung tissue from IPF patients. These results suggest that AECs undergo EMT when chronically exposed to TGF-beta1, raising the possibility that epithelial cells may serve as a novel source of myofibroblasts in IPF.

Actins↗

PubMed2005

Factor XII auto-antibodies present in a patient with a B-cell lymphoma.

A 64-year-old woman was transferred for investigation of a mediastinal mass, biopsy of which showed a diffuse large B-cell lymphoma. She was also found to have an antiphospholipid antibody. The pre-operative coagulation screen showed a prolonged activated partial thromboplastin time, 71.3 s (normal range, 26-36 s), which was not corrected by the addition of normal plasma. The dilute Russell's viper venom time was positive. Anti-cardiolipin assay was strongly positive, immunoglobulin M was 153 AU; immunoglobulin G was normal, 3.1 AU. Assays of factors VIII, IX and XI showed higher concentrations with increasing dilutions in one-stage factor assays from 1: 10 to 1: 80 suggestive of an inhibitor. Factor XII was 9 U/dl and results were unaffected by increasing dilution, suggesting specific antibodies to factor XII. The factor XII antigen was 40 U/dl. The patient had immunoglobulin M auto-antibodies to factor XII.

Autoantibodies↗

PubMed2005

Feasibility of the detection of the sentinel lymph node in peripheral non-small cell lung cancer with radio isotopic and blue dye techniques.

STUDY OBJECTIVES: The objective of this study was to evaluate the feasibility of the sentinel lymph node (SLN) biopsy in peripheral clinically stage I or II non-small cell lung cancer (NSCLC) using (99m)Tc colloid and a hand-held gamma detection probe, associated with a blue dye technique. DESIGN: Prospective study. SETTING: Royal Brompton Hospital, London, UK; and Hopital Nord, Saint Etienne, France. METHODS: After thoracotomy, a total of 2 mL patent blue dye mixed with 1,600 muCi (99m)Tc-albumin or (99m)Tc-colloid was injected into each quadrant of lung tissue immediately surrounding the tumor. Routine lymphadenectomy was carried out. The first lymph nodes to stain blue or radioactive, if any, were considered SLNs. RESULTS: Twenty-four patients were evaluated. We successfully identified 17 SLNs in 13 patients (detection rate, 54.2%). Mean time from injection to identification of SLNs was 18 min (range, 5 to 30 min). In nine cases, the SLN was blue and radioactive, in six cases only blue, and in two cases only radioactive. The pathologic status of the SLN reflected the pathologic status of other nodes of the routine lymphadenectomy except one case of false-negative SLN (14%). Four SLNs were in N2 stations (23.5%). CONCLUSIONS: The sentinel node mapping in NSCLC with blue dye and radioisotopic techniques is feasible, but the detection rate has to be improved. This technique is an accurate method of identifying the first node draining a tumor, although it is not yet sufficiently sensitive to have a role in reducing the extent of nodal dissection.

Adult↗

PubMed2004

Pulmonary manifestations of primary Sjogren's syndrome: a clinical, radiologic, and pathologic study.

RATIONALE: Clinicopathologic pulmonary manifestations associated with primary Sjogren's syndrome have yet to be reviewed in a large series since the recognition of nonspecific interstitial pneumonia (NSIP) as a distinct histologic pattern. OBJECTIVES: To determine clinical presentations, high-resolution computed tomographic (HRCT) and histologic findings of the lung disease associated with primary Sjogren's syndrome in the light of NSIP, and to analyze prognosis of the disease. METHODS: On the basis of 33 cases (31 surgical lung biopsies and 2 autopsies) collected consecutively from multiple centers, we have retrospectively evaluated clinical, radiologic, and pathologic manifestations of the disease. Prognostic factors were identified by univariate and multivariate analysis. MEASUREMENTS AND MAIN RESULTS: We found that NSIP was the most frequently seen histologic pattern (20 of 33 cases [61%], 19 fibrosing and 1 cellular). Bronchiolar diseases and amyloid and malignant lymphoma were seen less frequently. HRCT-pathologic correlation resulted in a 94% positive predictive value of CT-NSIP pattern for pathologic diagnosis of NSIP, whereas the diagnostic value of HRCT was low (15%) with an HRCT pattern other than NSIP, data that may influence the decision to biopsy. The 5-year survival rate was 84% overall and 83% in patients with NSIP. Multivariate analysis on all patients showed that low Pa(O(2)) (p = 0.02) and presence of microscopic honeycombing (p = 0.04) were independently associated with survival. Patients with NSIP showed lower vital capacity (mean +/- SD: 68.5 +/- 16.6%pred) than patients without NSIP (92.5 +/- 18.6%pred; p < 0.001). CONCLUSION: Among a diversity of pulmonary lesions in primary Sjogren's syndrome, NSIP was the commonest histologic pattern and had a favorable prognosis.

Biopsy↗

PubMed2004

Gene expression profiling reveals novel TGFbeta targets in adult lung fibroblasts.

BACKGROUND: Transforming growth factor beta (TGFbeta), a multifunctional cytokine, plays a crucial role in the accumulation of extracellular matrix components in lung fibrosis, where lung fibroblasts are considered to play a major role. Even though the effects of TGFbeta on the gene expression of several proteins have been investigated in several lung fibroblast cell lines, the global pattern of response to this cytokine in adult lung fibroblasts is still unknown. METHODS: We used Affymetrix oligonucleotide microarrays U95v2, containing approximately 12,000 human genes, to study the transcriptional profile in response to a four hour treatment with TGFbeta in control lung fibroblasts and in fibroblasts from patients with idiopathic and scleroderma-associated pulmonary fibrosis. A combination of the Affymetrix change algorithm (Microarray Suite 5) and of analysis of variance models was used to identify TGFbeta-regulated genes. Additional criteria were an average up- or down- regulation of at least two fold. RESULTS: Exposure of fibroblasts to TGFbeta had a profound impact on gene expression, resulting in regulation of 129 transcripts. We focused on genes not previously found to be regulated by TGFbeta in lung fibroblasts or other cell types, including nuclear co-repressor 2, SMAD specific E3 ubiquitin protein ligase 2 (SMURF2), bone morphogenetic protein 4, and angiotensin II receptor type 1 (AGTR1), and confirmed the microarray results by real time-PCR. Western Blotting confirmed induction at the protein level of AGTR1, the most highly induced gene in both control and fibrotic lung fibroblasts among genes encoding for signal transduction molecules. Upregulation of AGTR1 occurred through the MKK1/MKK2 signalling pathway. Immunohistochemical staining showed AGTR1 expression by lung fibroblasts in fibroblastic foci within biopsies of idiopathic pulmonary fibrosis. CONCLUSIONS: This study identifies several novel TGFbeta targets in lung fibroblasts, and confirms with independent methods the induction of angiotensin II receptor type 1, underlining a potential role for angiotensin II receptor 1 antagonism in the treatment of lung fibrosis.

Cells, Cultured↗

PubMed2004

LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription.

LIM domains-containing protein 1 (LIMD1) is encoded at chromosome 3p21.3, a region commonly deleted in many solid malignancies. However, the function of LIMD1 is unknown. Here we show that LIMD1 specifically interacts with retinoblastoma protein (pRB), inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. LIMD1 blocks tumor growth in vitro and in vivo and is down-regulated in the majority of human lung cancer samples tested. Our data indicate that LIMD1 is a tumor-suppressor gene, the protein product of which functionally interacts with pRB and the loss of which promotes lung carcinogenesis.

Animals↗

PubMed2004

Lung cancer: intragenic ERBB2 kinase mutations in tumours.

The protein-kinase family is the most frequently mutated gene family found in human cancer and faulty kinase enzymes are being investigated as promising targets for the design of antitumour therapies. We have sequenced the gene encoding the transmembrane protein tyrosine kinase ERBB2 (also known as HER2 or Neu) from 120 primary lung tumours and identified 4% that have mutations within the kinase domain; in the adenocarcinoma subtype of lung cancer, 10% of cases had mutations. ERBB2 inhibitors, which have so far proved to be ineffective in treating lung cancer, should now be clinically re-evaluated in the specific subset of patients with lung cancer whose tumours carry ERBB2 mutations.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

Regulation of TGF-beta 1-induced connective tissue growth factor expression in airway smooth muscle cells.

Transforming growth factor (TGF)-beta may play an important role in airway remodeling, and the fibrogenic effect of TGF-beta may be mediated through connective tissue growth factor (CTGF) release. We investigated the role of MAPKs and phosphatidylinositol 3-kinase (PI3K) and the effects of inflammatory cytokines on TGF-beta-induced CTGF expression in human airway smooth muscle cells (ASMC). We examined whether Smad signal was involved in the regulatory mechanisms. TGF-beta 1 induced a time- and concentration-dependent expression of CTGF gene and protein as analyzed by real-time RT-PCR and Western blot. Inhibition of ERK and c-jun NH(2)-terminal kinase (JNK), but not of p38 MAPK and PI3K, blocked the effect of TGF-beta 1 on CTGF mRNA and protein expression and on Smad2/3 phosphorylation. T helper lymphocyte 2-derived cytokines, IL-4 and IL-13, attenuated TGF-beta 1-stimulated mRNA and protein expression of CTGF and inhibited TGF-beta 1-stimulated ERK1/2 and Smad2/3 activation in ASMC. The proinflammatory cytokines tumor necrosis factor-alpha and IL-1 beta reduced TGF-beta 1-stimulated mRNA expression of CTGF but did not inhibit TGF-beta-induced Smad2/3 phosphorylation. TGF-beta 1-stimulated CTGF expression is mediated by mechanisms involving ERK and JNK pathways and is downregulated by IL-4 and IL-13 through modulation of Smad and ERK signals.

Bronchi↗

PubMed2004

Discovery of BRL 50481 [3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene], a selective inhibitor of phosphodiesterase 7: in vitro studies in human monocytes, lung macrophages, and CD8+ T-lymphocytes.

The biochemical and pharmacological characteristics in human proinflammatory cells of BRL 50481 [3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene], a novel and selective inhibitor of phosphodiesterase (PDE) 7, are described. BRL 50481 inhibited the activity of hrPDE7A1 expressed in baculovirus-infected Spodoptera frugiperda 9 cells in a competitive manner (Ki value of 180 nM) and was 416 and 1884 times less potent against PDE3 and 38 and 238 times less potent against PDE4 at a substrate concentration of 1 microM and 50 nM cAMP, respectively. Western blotting identified HSPDE7A1 but not HSPDE7A2 in three human cell types that are implicated in the pathogenesis of chronic obstructive lung disease, namely, CD8+ T-lymphocytes, monocytes, and lung macrophages. BRL 50481 had no effect on the proliferation of CD8+ T-lymphocytes and only marginally (approximately 2-11%) reduced the generation of tumor necrosis factor (TNF)alpha from blood monocytes and lung macrophages. However, in the presence of BRL 50481 the inhibitory effect of rolipram was enhanced on all three cell types. The expression of HSPDE7A1 was increased in a time-dependent manner in monocytes that were "aged" in culture medium. Under this condition, BRL 50481 now inhibited TNFalpha generation in a concentration-dependent manner. In aged monocytes, rolipram, Org 9935 (a PDE3 inhibitor), and prostaglandin E2 inhibited TNFalpha generation in a concentration-dependent manner and interacted additively with BRL 50481. BRL 50481 is the first fully documented PDE7 inhibitor that has acceptable selectivity for in vitro studies. Furthermore, although BRL 50481 had only a modest inhibitory effect per se on the proinflammatory cells studied, it acted at least additively with other cAMP-elevating drugs, especially when HSPDE7A1 was up-regulated.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2004

Atypical goblet cell hyperplasia in congenital cystic adenomatoid malformation as a possible preneoplasia for pulmonary adenocarcinoma in childhood: A genetic analysis.

Congenital cystic adenomatoid malformation (CCAM) of the lung is a congenital lesion that is sometimes complicated by bronchioloalveolar adenocarcinoma (BAC). In some cases foci of atypical goblet cell hyperplasia (AGCH) can be found within the cysts. It has been proposed that CCAM and AGCH predispose to the development of BAC. The present study used comparative genomic hybridization (CGH) to screen 22 cases of CCAM (epithelium, surrounding normal lung tissue, and both preneoplastic and neoplastic lesions) for chromosomal imbalances. Of these 22 cases, 10 were CCAM type 1, 10 were type 2, and 2 were type 3. Of the 10 cases of CCAM type 1, 2 were associated with AGCH, 1 was associated with atypical adenomatous hyperplasia (AAH) and associated tubular adenocarcinoma (AC), and 2 were associated with BAC (1 mucinous and 1 predominantly nonmucinous). The present study also involved immunohistochemistry for interleukin (IL)-13, IL-4 receptor-alpha (IL-4r alpha), cytokines involved in the differentiation of goblet cells, and mucin 2 protein (Muc2). Chromosomal aberrations were not detected in the epithelium or the surrounding normal lung tissue, whereas varying aberrations were found in the neoplastic lesions. The most frequent genomic imbalances observed in both AGCH and the carcinomas were gains in chromosomes 2 and 4. Interestingly, a predominance of gains was also reported in AC of nonsmokers. Chromosomal aberrations in AGCHs arising in CCAMs support their preneoplastic status. Nuclear expression of IL-13, IL-4r alpha, and Muc2 was detected in AGCH, whereas a cytoplasmic and nuclear reaction was seen in normal epithelium. This likely reflects an association with goblet cell differentiation, but it also drives proliferation in AGCH.

Adenocarcinoma↗

PubMed2004

TTF-1 expression is specific for lung primary in typical and atypical carcinoids: TTF-1-positive carcinoids are predominantly in peripheral location.

Thyroid transcription factor (TTF)-1 expression in neuroendocrine tumors (NETs) has not been studied as widely as that in non-NETs, with the exception of small cell carcinomas, in which TTF-1 is highly sensitive but not specific for a primary lung tumor. The reported incidence of TTF-1 expression in pulmonary carcinoids has also been highly variable in the literature. To evaluate the expression of TTF-1 in NETs and potential value of TTF-1 in distinguishing pulmonary NETs from those of extrapulmonary origin, we performed an immunohistochemical study by using semiquantitative analysis on formalin-fixed, paraffin-embedded sections from 111 NETs, including 80 pulmonary (11 carcinoid tumorlets [TLs] or foci of neuroendocrine cell hyperplasia [NEH], 36 typical carcinoids [TCs], 17 atypical carcinoids [ACs], 16 large cell neuroendocrine carcinomas [LCNECs]), 13 thymic (3 TCs, 8 ACs, 2 LCNECs), 17 gastrointestinal or pancreatic (13 TCs, 4 ACs), and 1 ovarian (LCNEC). Pulmonary carcinoids were subdivided into those with central and those with peripheral location. TTF-1 positivity was seen exclusively in pulmonary NETs and was significantly higher in NEH or TLs (72.7%) than in TCs (27.8%), ACs (29.4%), and LCNECs (37.5%; P = 0.03). All extrapulmonary NETs were uniformly negative for TTF-1 staining. Interestingly, 12 of 14 TTF-1-positive pulmonary TCs and ACs had a peripheral location with spindle cell morphology, as did all cases of TL, a purported precursor of peripheral carcinoids. In conclusion, TTF-1 expression was 100% specific, though not so sensitive, for the lung primary in TCs and ACs and possibly also in LCNECs. Prevalent TTF-1 positivity in TLs and peripheral carcinoids suggest that they may be histogenetically distinct from the central carcinoids, which are typically composed of TTF-1-negative, more rounded cells.

Aged↗

PubMed2004

Intraoperative pleural lavage cytology is an independent prognostic indicator for staging non-small cell lung cancer.

OBJECTIVES: For patients undergoing lung resection for cancer, macroscopic evidence of metastasis is clearly associated with adverse prognosis. However, less is known about the significance of tumor cells detected by using tests such as pleural lavage cytology. To ascertain the frequency and quantify the effect of this finding on survival, we performed a prospective study of intraoperative pleural lavage cytology. METHODS: Pleural lavage cytology consisted of cytologic analysis of 100 mL of saline irrigated over the lung surface immediately after thoracotomy. Patients were excluded if they had an existing effusion, extreme adhesions, or lateral chest wall invasion or if resection was not performed. Survival was calculated by means of Kaplan-Meier analysis and compared by using log-rank tests. Cox regression was used to ascertain independent predictors of prognosis. RESULTS: From 1995 through 2003, we performed pleural lavage cytology on 292 patients undergoing thoracotomy for lung cancer. The mean age was 64 (SD, 10) years, and 196 (67%) patients were men. Of 292 samples, 13 (4.5%) showed evidence of malignant cells. The median time to follow-up was 15 months (interquartile range, 1-40 months), with a median survival of 49 months for patients with negative pleural lavage cytology results and 13 months for patients with positive pleural lavage cytology results (P =.002). Univariate prognostic predictors were positive pleural lavage cytology status (P =.03), stage (P =.03), adenocarcinoma (P =.06), and parietal pleural involvement (P =.01). In the final multivariate model only positive pleural lavage cytology status (P =.006) and stage (P =.03) remained significant. CONCLUSIONS: Intraoperative pleural lavage cytology is a simple addition to intrathoracic staging and an independent predictor of prognosis. Positive results potentially affect survival by upstaging patients to stage IIIB or greater.

Adenocarcinoma↗

PubMed2004

Lung heme oxygenase-1 is elevated in acute respiratory distress syndrome.

OBJECTIVE: We aimed to quantify concentrations of inducible heme oxygenase (HO)-1 in the lungs of patients with acute respiratory distress syndrome (ARDS) and to investigate its role as a source of ferrous iron and as a signaling agent for iron regulation. Control of such processes by heme oxygenase has implications for the onset, progression, and resolution of ARDS. DESIGN: Retrospective analysis of archived samples. SETTING: Adult intensive care unit of a postgraduate teaching hospital. PATIENTS: Patients admitted to the adult intensive care unit who fulfilled the American-European Consensus Conference criteria for ARDS. INTERVENTIONS: Biochemical and immunohistochemical studies using bronchoalveolar lavage fluid or lung tissue were performed in patients with established ARDS and in those undergoing lung resection (controls). MEASUREMENTS AND MAIN RESULTS: Concentrations of heme oxygenase protein were significantly elevated in lung tissue (193.7 +/- 13.27 vs. 81.0 +/- 16.0%, p < .01) and in bronchoalveolar lavage fluid (2.4 x 10(5) vs. 1.4 x 10(5) densitometric units, p = .047) taken from patients with ARDS compared with controls. Concentrations of heme oxygenase protein in bronchoalveolar lavage fluid from patients with ARDS correlated positively and significantly with changes in the concentrations of ferritin (r = .697, p = .02) and the iron saturation of transferrin (r = .8, p = .014) but correlated negatively and significantly with concentrations of bleomycin-detectable (redox-active) iron (r = -.73, p = .031). Significantly elevated (p < .05) concentrations of heme oxygenase staining in cell types expressing this protein were detected in patients with ARDS, compared with concentrations in the same cells taken from controls undergoing lung resection. CONCLUSIONS: Heme oxygenase protein is elevated in the lungs of patients with ARDS and may contribute to the changes in iron mobilization, signaling, and regulation seen in this condition.

Adult↗

PubMed2004

CT features of lung disease in patients with systemic sclerosis: comparison with idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia.

PURPOSE: To evaluate computed tomographic (CT) patterns of lung disease in patients with systemic sclerosis (SSc) and compare them with CT appearance in patients with biopsy-proved idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (NSIP). MATERIALS AND METHODS: The CT features of consecutive patients with SSc (n = 225; male patients, 44; female patients, 181; median age, 47 years; age range, 16-78 years), IPF (n = 40; men, 26; women, 14; median age, 54.5 years; age range, 36-77 years) and NSIP (n = 27; men, 18; women, nine; median age, 53 years; age range, 32-68 years) were quantified separately by two observers. The extent of interstitial lung disease, ground-glass opacification, emphysema, and the coarseness of a reticular pattern were quantified. Group comparisons were made nonparametrically with the Wilcoxon rank sum test. Differences in CT features were identified with multiple logistic regression analysis. RESULTS: The coarseness of fibrosis was similar in patients with SSc and idiopathic NSIP but strikingly different between patients with SSc (median coarseness score, 5.5; range, 0.0-13.3) and IPF (median coarseness score, 8.8; range, 2.5-15.0) (P <.001). The proportion of ground-glass opacification at CT was similar in patients with SSc and idiopathic NSIP but differed significantly between patients with SSc (median proportion, 49.9%; range, 0.0%-100.0%) and IPF (median proportion, 23.5%; range, 0.0%-97.2%) (P <.001). At logistic regression analysis, there were no differences in the CT features between patients with SSc and those with NSIP after controlling for age, disease extent, and the percentage predicted forced vital capacity and carbon monoxide diffusing capacity. CONCLUSION: Interstitial lung disease in patients with SSc is less extensive, less coarse, and characterized by a greater proportion of ground-glass opacification than that in patients with IPF. The CT features of lung disease in patients with SSc closely resemble those in patients with idiopathic NSIP.

Adolescent↗

PubMed2004

Prognostic implications of histologic patterns in multiple surgical lung biopsies from patients with idiopathic interstitial pneumonias.

STUDY OBJECTIVES: To determine the prevalence and prognostic significance of histologic discordance in multiple lung biopsy specimens obtained from patients investigated for suspected cryptogenic fibrosing alveolitis (CFA)/idiopathic pulmonary fibrosis (IPF). METHODS: and results: Between 1984 and 2001, 64 patients undergoing investigation for CFA/IPF were identified in whom multiple biopsies were performed that showed either a pattern of usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP). These cases were classified into three groups: concordant UIP-UIP (n = 25, 39.1%), discordant UIP-NSIP (n = 8,12.5%), and concordant NSIP-NSIP (n = 31, 48.4%). The discordant UIP group had survival, clinical, and physiologic features similar to those of the concordant UIP group, and prognosis in both concordant and discordant UIP groups was significantly worse than that of the concordant NSIP group (p = 0.02 and p = 0.04, respectively). The age of the concordant UIP group was higher than that of the concordant NSIP group, with the mean age of the discordant group being intermediate. There were no significant differences among the three groups in smoking history, duration of dyspnea, presence or absence of crackles, FVC, diffusion capacity of the lung for carbon monoxide, or PaO(2). CONCLUSIONS: Patients with discordant UIP-NSIP results on multiple biopsies show clinical behavior similar to those with concordant UIP-UIP and should be regarded as having CFA/IPF in the correct clinical context, rather than "idiopathic NSIP" for the purposes of management. Multiple biopsies should be considered in all patients in order to improve the prognostic information provided by lung biopsy.

Age Factors↗

PubMed2003

Asbestosis and idiopathic pulmonary fibrosis: comparison of thin-section CT features.

PURPOSE: To identify differences, if any, in thin-section computed tomographic (CT) features between asbestosis and idiopathic pulmonary fibrosis (IPF) and to test the findings in a subset of histopathologically proved cases of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). MATERIALS AND METHODS: Consecutive patients with a diagnosis of IPF (n = 212) or asbestosis (n = 74) were included. The relationships derived from the initial comparison were tested in a separate group of biopsy-proved UIP (n = 30) and NSIP (n = 23) cases. Two observers independently scored thin-section CT images for extent, distribution, and coarseness of fibrosis; proportion of ground-glass opacification; severity of traction bronchiectasis; and extent of emphysema. RESULTS: After controlling for extent of fibrosis, patients with asbestosis had coarser fibrosis than those with IPF (odds ratio, 1.52; 95% CI: 1.25, 1.84; P <.001). Compared with the biopsy-proved cases, the asbestosis cases involved coarser fibrosis (after controlling for disease extent) than the NSIP cases (odds ratio, 2.48; 95% CI: 1.49, 4.11; P <.001) but fibrosis similar to that in the UIP cases. A basal and subpleural distribution of disease was usual in all subgroups but significantly more prevalent (P, <.01 to.001) with asbestosis than with UIP or NSIP. CONCLUSION: The thin-section CT pattern of asbestosis closely resembles that of biopsy-proved UIP and differs markedly from that of biopsy-proved NSIP.

Asbestosis↗