A 12-Year-Old Girl Presenting With Recurrent Dyspnea and Pulmonary Ground-Glass Opacities.

CASE PRESENTATION: A 12-year-old girl presented with shortness of breath with exercise for 2 weeks. Her oxygen saturation was 85% during exercise. Birth and family histories were unremarkable. The girl was healthy until 7.1 years of age, when she suffered a "pneumonia" with fever, dyspnea, and hypoxemia, which diminished after a 19-day treatment with antibiotics and methylprednisolone. These symptoms relapsed 8 months later, and she was diagnosed with rapidly progressive interstitial lung disease (ILD) and a Mycoplasma pneumoniae infection. At that time, her symptoms failed to respond to a course of antibiotic therapy but resolved with IV methylprednisolone at 2.7 mg/kg/day. She remained on a tapering dose of methylprednisolone plus methotrexate for the next 18 months until withdrawal of these medications because of return of almost normal lung imaging. She had never had myalgia, muscle weakness, arthritis, rashes, mechanic's hands, Raynaud's phenomenon, dry mouth, or dry eyes.

Heme Oxygenase-1 in Patients With Interstitial Lung Disease: A Review of the Clinical Evidence.

The clinical course and rate of progression of interstitial lung disease (ILD) are extremely variable among patients. For the purpose of monitoring disease activity, ILD diagnosis, and predicting disease prognosis, there are various biomarkers, including symptoms, physiological, radiological, and pathological findings, and peripheral blood and bronchoalveolar lavage fluid results. Of these, blood biomarkers such as sialylated carbohydrate antigen, surfactant proteins-A and -D, CC-chemokine ligand 18, matrix metalloprotease-1 and -7, CA19-9, and CA125 have been previously proposed. In the future, heme oxygenase-1 (HO-1) may also become a candidate ILD biomarker; it is a 32-kDa heat shock protein converting heme to carbon monoxide, biliverdin/bilirubin, and free iron to play a role in the pulmonary cytoprotective reaction in response to various stimuli. Recent research suggests that HO-1 can increase in lung tissues of patients with ILD, reflecting anti-inflammatory M2 macrophage activation, and the measurement of HO-1 levels in peripheral blood can be useful for evaluating the severity of lung damage in ILD and for predicting subsequent fibrosis formation.

Two cases with autoantibodies to small ubiquitin-like modifier activating enzyme: A potential unique subset of dermatomyositis-associated interstitial lung disease.

The presence of anti-aminoacyl tRNA synthetase (ARS) or anti-melanoma differential-associated gene 5 (MDA5) is strongly related to interstitial lung disease (ILD) in patients with dermatomyositis (DM). Several studies suggest a potential relationship between ILD and anti-small ubiquitin-like modifier activating enzyme (SAE) antibody in DM patients, but detailed clinical characteristics of anti-SAE-associated ILD still remain unknown. We have experienced 2 cases who were positive for anti-SAE antibody, who presented with ILD in the context of clinically amyopathic DM. These 2 patients had the following common ILD characteristics: an insidious course with preserved pulmonary function; a limited extent of pulmonary lesions with subpleural peripheral-dominant small ground glass opacity/consolidation on high-resolution computed tomography; and a favorable treatment response. These findings suggest that anti-SAE-associated ILD is unique in terms of clinical and imaging features and differs from ILD associated with anti-ARS or anti-MDA5 antibody.

Association between Pepsin in Bronchoalveolar Lavage Fluid and Prognosis of Chronic Fibrosing Interstitial Lung Disease.

Chronic fibrosing interstitial lung disease (ILD)s are characterized by chronic progressive fibrosis of lung which include idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), and connective tissue disease-associated interstitial lung disease (CTD-ILD). IPF is an irreversible fibrotic lung disease which results in respiratory failure. Although NSIP and CTD-ILD can be improved or stable by treatment with corticosteroid or immunosuppressant, some of them progress to fibrotic lung diseases. Aspiration of gastric contents is suggested as an aggravating factor of ILDs. We measured pepsin, a marker of gastric aspiration, in bronchoalveolar lavage (BAL) fluid of chronic fibrosing ILD patients to evaluate the association between BAL fluid pepsin and prognosis of chronic fibrosing ILDs. Patients with chronic fibrosing ILDs, who underwent bronchoscopy between December 2010 and April 2015 were prospectively enrolled. Pepsin levels were measured using a commercial ELISA kit. Clinical characteristics, lung function data, and mortality were analyzed. Fifty-one patients with chronic fibrosing ILDs were enrolled (26 with IPF, 15 with NSIP, and 10 with CTD-ILD). Pepsin levels in BAL fluid were 69.87 ± 74.16 ng/mL in IPF, 110.68 ± 94.93 ng/mL in NSIP, and 101.87 ± 88.44 ng/mL in CTD-ILDs. There were no statistically significant differences in BAL fluid pepsin levels among patients with the different chronic fibrosing ILDs. In multivariate regression analysis, higher BAL pepsin levels were associated with higher mortality (adjusted odds ratio [aOR] = 1.021, p = 0.025). BAL fluid pepsin may be used as a prognostic marker for predicting mortality in chronic fibrosing ILD patients.

Síndrome antisintetasa: análisis de 11 casos / Antisynthetase syndrome: Analysis of 11 cases

Introducción: El síndrome antisintetasa (ASA) se caracteriza por manifestaciones clínicas como miositis, fiebre, manos de mecánico y enfermedad pulmonar intersticial (EPI) asociadas a la positividad ante anticuerpos antisintetasa. La presencia de EPI será la que, en gran medida, marcará la respuesta al tratamiento y el pronóstico. Pacientes y métodos: Se describen 11 pacientes con ASA y afectación pulmonar en seguimiento en una consulta monográfica de Neumología de un hospital de tercer nivel. Resultados: Nueve pacientes presentaron positividad para anticuerpos anti-Jo y 2 para anti-PL12. Cuatro pacientes mostraron en TCAR patrón NINE, 4 NIU, uno NOC y 2 en vidrio deslustrado. El 73% se acompañaron de bronquiectasias y bronquiolectasias y el 27%, de panalización. Funcionalmente resalta la DLCO, con hasta el 45% con un test de la marcha positivo. Destaca la corticodependencia, con necesidad en muchas ocasiones de tratamiento inmunodepresor, tanto en exacerbaciones como de forma crónica. Todos los pacientes mantuvieron buen pronóstico hasta el momento. Conclusiones: Los pacientes con EPI deberían tener al menos una determinación de anticuerpos antisintetasa para así identificar esta enfermedad, de mejor pronóstico que otras afecciones intersticiales como la fibrosis pulmonar idiopática (AU)

Introduction: Antisynthetase syndrome (ASS) is characterised by a series of clinical manifestations such as myositis, fever, mechanic’s hands and diffuse interstitial lung disease (ILD), all associated with positivity to antisynthetase antibodies. The presence of ILD will be that, to a great extent it will mark the response to treatment and prognosis. Patients and methods: Eleven cases of patients with ASS and pulmonary involvement in monitoring at a Pulmonary monographic consult in a third level hospital consult are described. Results: Nine patients presented positivity to anti-Jo antibody and 2 to anti-PL12. Four patients’ HRCT pattern showed NSIP, four UIP, one COP and 2 ground-glass opacity. A percentage of 73 were accompanied by bronchiectasis and bronchiolectasis and 27% honeycombing. Functional exploration was mainly affected by DLCO with up to 45% of the positive walking test. Corticodependence is highlighted, often requiring immunosuppressive treatment both chronically and in exacerbations. All patients maintain good prognosis so far. Conclusions: Patients with interstitial lung disease should have at least a determination of antisynthetase antibodies in order to identify this disease, better prognosis than other interstitial diseases such as idiopathic pulmonary fibrosis (AU)

Glutathione peroxidase 3 localizes to the epithelial lining fluid and the extracellular matrix in interstitial lung disease.

Aberrant antioxidant activity and excessive deposition of extracellular matrix (ECM) are hallmarks of interstitial lung diseases (ILD). It is known that oxidative stress alters the ECM, but extracellular antioxidant defence mechanisms in ILD are incompletely understood. Here, we extracted abundance and detergent solubility of extracellular antioxidant enzymes from a proteomic dataset of bleomycin-induced lung fibrosis in mice and assessed regulation and distribution of glutathione peroxidase 3 (GPX3) in murine and human lung fibrosis. Superoxide dismutase 3 (Sod3), Gpx3, and Gpx activity were increased in mouse BALF during bleomycin-induced lung fibrosis. In lung tissue homogenates, Gpx3, but not Sod3, was upregulated and detergent solubility profiling indicated that Gpx3 associated with ECM proteins. Immunofluorescence analysis showed that Gpx3 was expressed by bronchial epithelial cells and interstitial fibroblasts and localized to the basement membrane and interstitial ECM in lung tissue. As to human ILD samples, BALF of some patients contained high levels of GPX3, and GPX3 was upregulated in lung homogenates from IPF patients. GPX3 expression in primary human bronchial epithelial cells and lung fibroblasts was downregulated by TNF-α, but more variably regulated by TGF-ß1 and menadione. In conclusion, the antioxidant enzyme GPX3 localizes to lung ECM and is variably upregulated in ILD.

Therapeutic plasma exchange in antisynthetase syndrome with severe interstitial lung disease.

Antisynthetase syndrome (ASS) is a rare condition characterized by interstitial lung disease (ILD), inflammatory myositis, fever, Raynaud phenomenon, mechanic's hand, and inflammatory polyarthritis in the setting of antibodies to amino acyl-transfer RNA synthetases, with anti-Jo-1 antibody being the most common. Prognosis is very poor especially when there is associated ILD. To date, there is no standardized treatment for ILD associated ASS. Therapy is based on the use of steroids alone or in combination with other immunosuppressive agents, especially in severe or refractory cases. The role of therapeutic plasma exchange (TPE) in the management of this rare condition has not been established. Here, we report a case of severe ILD associated ASS in a 41-year-old woman who did not show clinical or laboratory response after six doses of high dose steroids and a dose of IV cyclophosphamide. Because of the aggressive nature of her disease and poor prognostic indices present, a decision was made to add TPE to her treatment. She underwent five sessions of TPE. At the end of the 5th session, the anti-Jo-1 antibody levels dropped to 3.6 AI (antibody index) and her creatinine kinase (CK) level from 875 to 399 U L(-1) (Units per liter) with overall improvement in her respiratory status. This case suggests TPE may be a promising treatment option in patients with ILD associated ASS refractory to steroids and other immunosuppressive therapy, particularly those with severe disease.

Tissue concentrations of estrogens and aromatase immunolocalization in interstitial pneumonia of human lung.

Interstitial pneumonia (IP) is characterized by various degrees of pulmonary fibrosis and inflammation. Estrogens have been demonstrated to play important roles in physiological and pathological conditions of human lung, but significance of estrogens has remained unknown in human IP. Therefore, we measured estrogen concentrations and immunolocalized aromatase and estrogen receptor ß (ERß) in IP tissues. Estradiol concentration was significantly (2.8-fold) higher in IP than normal lung tissues, and aromatase activity evaluated by estradiol/testosterone ratio was also significantly (7.2-fold) elevated in IP tissues. Aromatase immunoreactivity in alveolar epithelial cells was significantly frequent in IP than normal lung or inflammatory lung disease other than IP, and it was positively associated with ERß immunoreactivity in these cells of IP. These results suggest that estradiol concentration is locally increased in human IP tissue by aromatase, and increased estrogens may play an important role in the development of IP through ERß in the alveolar epithelial cells.

Prevalence of underlying lung disease in smokers with epidermal growth factor receptor-mutant lung cancer.

The prevalence of underlying lung diseases, such as emphysema and interstitial lung disease in smokers with epidermal growth factor receptor (EGFR)-mutant lung cancer remains unclear. This study aimed to clarify the correlation between the EGFR mutation status and the prevalence of underlying lung disease in smokers with lung cancer. A total of 88 consecutive smokers with non-small cell or non-squamous cell lung cancer who underwent surgical resection at our hospital from January 2007 through December 2010 were included in this study. The patients were divided into two groups on the basis of the EGFR mutation status: the mutation-positive group (n=19) and the wild-type group (n=69). The results of radiographic assessment via computed tomography (CT) and pulmonary function analysis were compared between the two groups. In the radiological evaluation, CT images at three levels were evaluated by two reviewers. Radiographic assessment revealed that the mutation-positive group tended to have milder emphysematous changes and a lower prevalence of interstitial changes compared with the wild-type group (P=0.13, 0.06). When the analysis was limited to the ipsilateral lung at the nearest CT level to the tumor, emphysematous changes were found to be less common in the mutation-positive group (P=0.02). The prevalence of the emphysematous and/or interstitial changes in the ipsilateral lung at the nearest CT level to the tumor was lower in the mutation-positive group compared to the wild-type group (P=0.005). In the pulmonary function test, the results were comparable between the two groups. In conclusion, according to our results, EGFR-mutant lung cancer was commonly observed in the areas where emphysematous and interstitial changes were absent. EGFR-mutant lung cancer may develop in radiographically normal areas of the lungs, even in smokers. It would be of importance to evaluate the EGFR mutation status in patients with no emphysematous or interstitial changes in the ipsilateral lung near the tumor, regardless of their smoking history. These results should be confirmed in a future prospective study.

The clinical characteristics of two anti-OJ (anti-isoleucyl-tRNA synthetase) autoantibody-positive interstitial lung disease patients with polymyositis/dermatomyositis.

We herein report the clinical and laboratory characteristics of two anti-OJ (anti-isoleucyl-tRNA synthetase) autoantibody-positive interstitial lung disease patients with polymyositis/dermatomyositis (PM/DM). We compared these characteristics with previously published findings. Previous reports and our present cases show that anti-OJ autoantibody-positive interstitial lung disease (ILD) patients with PM/DM lack the manifestations of Raynaud's phenomenon and sclerodactyly and show good prognoses and responses to glucocorticoid therapy. These results indicate that the presence of anti-OJ autoantibodies may be useful for predicting the prognosis of ILD and its clinical course in PM/DM patients.

Pilot study of interleukin-27 in pathogenesis of dermatomyositis and polymyositis: associated with interstitial lung diseases.

OBJECTIVE: To determine whether interleukin (IL)-27 is involved in dermatomyositis (DM) and polymyositis (PM). METHODS: Serum IL-27, IL-18 and interferon-γ (IFN-γ) levels in 37 DM and 15 PM were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum IL-27, IL-18 and IFN-γ levels were significantly higher in DM and PM patients than in healthy controls. Significant higher levels of IL-27 were found in high creatine kinase (CK) level group and in patients with interstitial lung disease (ILD). Level of IL-27 was correlated with global 100-mm visual analog scales (VASs) score in patients with PM. CONCLUSION: These data supports the hypothesis that IL-27 maybe involved in DM and PM pathogenesis.

Chitinase 1 is a biomarker for and therapeutic target in scleroderma-associated interstitial lung disease that augments TGF-ß1 signaling.

Interstitial lung disease (ILD) with pulmonary fibrosis is an important manifestation in systemic sclerosis (SSc, scleroderma) where it portends a poor prognosis. However, biomarkers that predict the development and or severity of SSc-ILD have not been validated, and the pathogenetic mechanisms that engender this pulmonary response are poorly understood. In this study, we demonstrate in two different patient cohorts that the levels of chitotriosidase (Chit1) bioactivity and protein are significantly increased in the circulation and lungs of SSc patients compared with demographically matched controls. We also demonstrate that, compared with patients without lung involvement, patients with ILD show high levels of circulating Chit1 activity that correlate with disease severity. Murine modeling shows that in comparison with wild-type mice, bleomycin-induced pulmonary fibrosis was significantly reduced in Chit1⁻/⁻ mice and significantly enhanced in lungs from Chit1 overexpressing transgenic animals. In vitro studies also demonstrated that Chit1 interacts with TGF-ß1 to augment fibroblast TGF-ß receptors 1 and 2 expression and TGF-ß-induced Smad and MAPK/ERK activation. These studies indicate that Chit1 is potential biomarker for ILD in SSc and a therapeutic target in SSc-associated lung fibrosis and demonstrate that Chit1 augments TGF-ß1 effects by increasing receptor expression and canonical and noncanonical TGF-ß1 signaling.

A therapeutic role for matrix metalloproteinase inhibitors in lung diseases?

Disruption of the balance between matrix metalloproteinases (MMPs) and their endogenous inhibitors is considered a key event in the development of pulmonary diseases such as chronic obstructive pulmonary disease, asthma, interstitial lung diseases and lung cancer. This imbalance often results in elevated net MMP activity, making MMP inhibition an attractive therapeutic strategy. Although promising results have been obtained, the lack of selective MMP inhibitors, together with limited knowledge regarding the exact functions of a particular MMP, hampers clinical application. This review discusses the involvement of different MMPs in lung disorders and future opportunities and limitations of therapeutic MMP inhibition.

Cathepsin-K is a sensitive immunohistochemical marker for detection of micro-granulomas in hypersensitivity pneumonitis.

UNLABELLED: Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that occurs upon exposure to a variety of inhaled organic antigens. The presence of small non-caseating granulomas and isolated giant cells is not specific, but is considered a relevant histological feature for HP. The detection of granulomas is widely considered as easy on standard histological stains, but microgranuloma detection can be difficult and/or time consuming, especially in chronic HP cases. Cathepsin K (Cath-K) is a potent cysteine protease expressed at high levels in activated macrophages (osteoclasts, and epithelioid cells in granulomas), but is not expressed in resident macrophages thus representing a promising marker to rapidly detect and quantitatively evaluate microgranulomas in interstitial lung diseases. We analyzed the expression of Cath-K by immunohistochemistry in 22 subacute and chronic HP cases, using semi-quantitative scores. Control samples included normal lung tissue, and a variety of interstitial lung diseases: 3 Wegener's granulomatosis, 3 sarcoidosis, 3 tuberculosis, 1 berylliosis, 20 idiopathic pulmonary fibrosis (IPF), 2 Langerhans' cell histiocytosis, 5 nonspecific-interstitial pneumonia (NSIP), 5 cryptogenic organising-pneumonia (COP), 2 Airway-Centered Interstitial Fibrosis (ACIF), 5 desquamative interstitial pneumonia (DIP), 3 respiratory bronchiolitis interstitial lung disease (RB-ILD). Intense expression of Cath-K was demonstrated in epithelioid and giant cells in all cases containing granulomas (HP, sarcoidosis, Wegener's granulomatosis, berylliosis, tuberculosis). Among HP cases 19/22 (86.3%) contained granulomas that could be semiquantitatively evaluated. In all HP and control cases alveolar macrophages did not express Cath-K, including cases characterised by large collections of alveolar macrophages such as DIP and RB-ILD. CONCLUSIONS: Cath-K represents a sensitive and specific marker to detect and quantitate granulomatous reactions in interstitial lung diseases, and is particularly useful in chronic HP cases.

Antisynthetase syndrome presenting as rheumatoid-like polyarthritis.

BACKGROUND: The antisynthetase syndrome is a systemic inflammatory disease associated with anti-tRNA synthetase antibodies and consisting of the clinical features of inflammatory myopathy arthritis, interstitial lung disease (ILD), fever, Raynaud syndrome, and rash. It rarely presents with symmetric arthritis as the initial manifestation of the disease. OBJECTIVE: The aim of the study was to describe the clinical, laboratory, and radiographic characteristics of patients with antisynthetase syndrome who presented with symptoms of inflammatory arthritis, mimicking rheumatoid arthritis (RA) at the time of initial evaluation. METHODS: Six cases derived from a single university-based rheumatology clinic in Wisconsin are presented. The major clinical, laboratory, radiographic, and histopathologic data are described. RESULTS: All 6 patients demonstrated symmetric synovitis involving the hands. Five patients met the American College of Rheumatology classification criteria for RA. Three patients had nail-fold capillary abnormalities, and 4 patients were observed to have Raynaud phenomenon. Three patients demonstrated a cytoplasmic pattern when testing for antinuclear antibodies by immunofluorescent assay, and all had t-RNA synthetase antibodies. Two patients had positive rheumatoid factors, but none had strongly positive cyclic citrullinated peptide antibodies. None of the patients demonstrated radiographic erosions. All patients had evidence of ILD by imaging or pulmonary function testing. Prognosis was generally favorable, although disease severity and treatment varied considerably. CONCLUSION: In patients who present with features mimicking but atypical for RA, such as early ILD, nail-fold capillary abnormalities, Raynaud phenomenon, cytoplasmic antinuclear antibody pattern, negative cyclic citrullinated peptide antibody status, and nonerosive arthritis, the antisynthetase syndrome should be considered.

[Assessment of smoking related pathologic changes and MMP-9, TIMP-1 expressions of the lung]. / Akcigerde sigaraya bagli patolojik degisimler, MMP-9 ve TIMP-1 ekspresyonlarinin degerlendirilmesi.

The impact of smoking on the peripheral airways, the determining field of respiratory functions in the lungs, is well known. Fifty two cases were included in the study; autopsy cases of non-cardiopulmonary related deaths with a smoking history, and cases with lung resection, known as smokers. Ten cases without a smoking history and a systemic disease were used as a control group at the histopathological examination. Parenchymal samples were taken from the central and peripheral airways (1st, 2nd, 3rd division) and from each lob. In addition, age, gender, amount and duration of smoking (package/year) were considered and histopathological changes of the lung are evaluated under the light microscope. The relations of all parameters to each other are evaluated and compared with the control group. On the distal airways with small diameter, Respiratory Bronchiolitis (RB) was determined in 14 (26.9%) cases, and Respiratory Bronchiolitis-associated interstitial lung disease (RB-ILD) in 16 (30.7%) cases. Two (3.8%) cases were diagnosed as Desquamative Interstitial Pneumonia (DIP). MMP-9, a matrix metalloproteinase known for its role in the development and repair of obstructive diseases of the lung related to smoking, and TIMP-1, an inhibitor, were used on the lung samples by means of immunohistochemical method. MMP-9 and TIMP-1 expressions of all cases were compared statistically with the existing pathological findings and the control group. MMP-9, TIMP-1 were expressed from the alveolar macrophages, endothelial and epithelial cells. Considering the MMP-9 and TIMP-1 density of alveolar macrophages, no statistically significant differences were found among the RB, RBILD and DIP case groups. However; despite of the significant MMP-9 expression of the DIP cases, TIMP-1 expression could not be determined. Compared to the control group, a more intensive and widespread positive reaction on MMP-9 was found in the alveolar macrophages. In conclusion, although there was no significant relation between the level and duration of smoking and the MMP-9 and TIMP-1 expressions, alveolar macrophages were found to be more important in lung damage related to smoking and the MMP-9 expression from these cells to be more intensive than the control group.

Nonspecific interstitial pneumonia (NSIP) associated with anti-KS antibody: differentiation from idiopathic NSIP.

We report two cases of biopsy-proven nonspecific interstitial pneumonia (NSIP) with anti-KS (asparaginyl-tRNA) antibody. Anti-KS antibody is the sixth anti-aminoacyl-tRNA synthetase (ARS) antibody. They showed interstitial pneumonia without clinical symptoms, and high resolution computed tomography (HRCT) of the chest demonstrated consolidation along bronchovascular bundles and volume loss in the bilateral lower lobes, which were suggestive of connective tissue diseases (CTD). One case of cellular NSIP responded to corticosteroid, but the other case of fibrotic NSIP required corticosteroid and cyclosporin. In patients with these HRCT findings, the measurement of anti-ARS antibodies could be helpful even in the absence of clinical symptoms suggestive of CTD.

[Assessment of glutathione peroxidase activity (GPX) in the diagnosis of diffuse pulmonary parenchymal changes]. / Ocena aktywnosci peroksydazy glutationowej (GPX) w diagnostyce rozsianych zmian miazszowych pluc.

UNLABELLED: DNA damage caused by free radicals is one of the mechanisms which are responsible for the occurrence of lung tumors, especially in case of cigarette smokers.Their tumors are radiologically often disseminated changes. AIM OF THIS STUDY: To define the correlation between GPX activity in erythrocyte hemolysate and pulmonary parenchymal extract and the etiology of diffuse pulmonary parenchymal changes. MATERIAL AND METHODS: The study group comprised 40 subjects classified to VTS due to diffuse pulmonary parenchymal changes. The control group included 40 clinically healthy subjects. In the examined group GPX activity in erythrocyte hemolysate and pulmonary parenchymal extract was marked. The material was 5.4 ml of vein blood taken one-time from all subjects and a sample of pulmonary parenchyma obtained during VTS or toracotomy in patients with pulmonary parenchymal changes. RESULTS: Lower values of GPX activity in erythrocyte hemolysate and pulmonary parenchymal extract which are statistically significant were observed compared with the control group. CONCLUSIONS: Higher GPX activity in erythrocyte hemolysate and healthy pulmonary parenchymal extract compared with pulmonary parenchymal changes can show the influence of GPX on the development of disease process. Higher GPX activity in erythrocte hemolysate and pulmonary parenchymal extract in the "sarcoidosis group" compared with the "lung carcinoma group" can be an additional marker in differential dignostics. The determination of GPX activity in erythrocyte hemolysate can be used as a supplementary laboratory test which will facilitate diagnosis of pulmonary parenchymal changes.

AKR1B10 in usual interstitial pneumonia: expression in squamous metaplasia in association with smoking and lung cancer.

The incidence of lung cancer (LC) is markedly increased among patients with usual interstitial pneumonia (UIP), and tobacco smoking is its superimposed risk factor. AKR1B10 (aldo-keto reductase 1B10) is frequently overexpressed in pulmonary squamous cell carcinoma and adenocarcinoma in smokers. To investigate the role of AKR1B10 in the pulmonary carcinogenesis in UIP with correlation to tobacco smoking, we examined 13 UIP cases with LC, 13 UIP cases without LC, and 30 cases of non-UIP LC using AKR1B10 immunohistochemistry. AKR1B10 immunoreactivity was confined to squamous metaplasia in honeycomb lesions of UIP and neoplastic cells of LC. Squamous metaplastic foci showed AKR1B10 immunoreactivity more frequently in UIP with LC (24/36 foci, 67%) than in UIP without LC (16/44 foci, 37%) (P<0.01). AKR1B10 expression in UIP was also more frequent in squamous metaplastic foci in smokers (38/67 foci, 57%) than in non-smokers (2/13 foci, 15%) (P<0.01). AKR1B10 expression was frequently observed in both UIP-associated LC (10/13 foci, 77%) and non-UIP LC (18/30 foci, 60%). Ki-67 labeling index was significantly higher in AKR1B10-positive squamous metaplasia of UIP than in AKR1B10-negative squamous metaplasia of UIP. Our results demonstrate that AKR1B10 is involved in the development of LC in UIP in association with smoking. AKR1B10 might be useful as a new marker for identification of high LC risk patients in UIP.