Interstitial Lung Disease in Rheumatoid Arthritis: A Prospective Study at a Tertiary Care Center

Objective: The objective of this study was to evaluate the presence of interstitial lung disease (ILD) in rheumatoid arthritis (RA) and to determine the role of clinical, spirometry, and high-resolution computed tomography (HRCT) findings to facilitate early detection of ILD in RA. Materials and methods: This is a prospective study at a tertiary care hospital from February 2016 to June 2019. All patients satisfying the American College of Rheumatology (ACR) criteria for RA and having respiratory symptoms or signs were included. All patients had detailed history, clinical examination, laboratory evaluation, spirometry, and HRCT chest. Results: A total of 280 patients of RA with respiratory symptoms were evaluated, out of which 82 (29.29%) had pulmonary involvement. There were 70 women and 12 men. Rheumatoid factor was positive in 90.2% of patients while anti-CCP antibody was positive in 43.9%. Chest X-ray (CXR) showed bilateral haziness in 36.9%. HRCT findings revealed a usual interstitial pneumonia (UIP) pattern in 73.2% patients and 24% had an nonspecific interstitial pneumonia (NSIP) pattern. Spirometric evidence of lung involvement was present in 84.2% of these cases. 2D Echo showed pulmonary hypertension (PH) in 46.3% of patients. Conclusion: Screening for respiratory symptoms and signs is essential in the clinical evaluation of RA. CXR, HCRT chest, and spirometry can be used effectively to diagnose RA-ILD early.

HISTOLOGICAL SPECTRUM OF NON-NEOPLASTIC LESIONS IN THE LUNG-A RETROSPECTIVE STUDY DONE ON LOBECTOMY SPECIMENS

To study the histolopathological spectrum of non-neoplastic lesions of lung and to evaluate in relation to age, gender and clinico-radiological findings. This study is done over a period of 1 year (Nov 2020 to Nov 2021) in the Department of Pathology, LNMC, Bhopal. Total of 33 lobectomy specimens were studied. Specimens were fixed in formalin and paraffin embedded H&E-stained tissue sections were studied. Special stains (Gomorri's methenamine silver stain and Periodic acid Schiff stain) were done where ever required. Non-neoplastic lesions from 3 (9.09%) women and 30 (90.90%) men, with a median age of 43.86 (Interquartile range: 23-60 years) were collected. Fibrotic interstitial changes comprised the most common category of histologic findings, noted in 20 (60.6%) patients. Most cases consisted of usual interstitial pneumonia (UIP) (30.30%), followed by smoking related interstitial fibrosis/SRIF (desquamative interstitial pneumonia like patterns and respiratory bronchiolitis like pattern) (12.12%), non-specific interstitial pneumonia (NSIP) (9.09%) and patterns of “undefined” fibrosis (6.06%) such as peribronchial fibrosis, organizing pneumonias and other patterns of fibrosis that did not fall into a recognized category of idiopathic interstitial pneumonia. Granulomatous pathology was identified in 4 (10.81%) patients. On chest X-ray/CT scan chest, majority of lung lesions presented as diffuse and patchy opacities with honeycombing and bronchiectasis. Cigarette smoking was associated with 4 lung lesions. Histopathologic classification plays an important role in separating variable forms of non-neoplastic lung lesions & further subcategorising idiopathic interstitial pneumonia into clinically meaningful categories have important differences in natural history, prognosis, and treatment

Usual interstitial pneumonia - secondary vs idiopathic pulmonary fibrosis

Background: Interstitial Lung Diseases is a group of disorders where the pulmonary interstitium, alveolar structures and the small airways are affected. Identification of a specific pattern on HRCT, with a thorough clinical evaluation can help a physician in narrowing down the differential diagnosis for the underlying cause. Usual Interstitial Pneumonia (UIP) is a frequently identified pattern. Differentiating patients with definite UIP pattern, into IPF and non-IPF spectrums is important. Aim of this study is to compare UIP patients with a secondary cause vs Idiopathic Pulmonary Fibrosis.Methods: Statistically 33 patients having UIP pattern on HRCT were evaluated based on the history of extrapulmonary symptoms, environmental exposure, drugs and subsequent serology testing. Patients were divided into two groups - IPF and UIP with a secondary cause. Both groups were compared on various clinical parameters. Inferences were drawn from the same.Results: Total 66.6% patients were identified to have Idiopathic Pulmonary Fibrosis, 33.3% had UIP with a secondary cause. Majority of patients with a secondary cause had Connective Tissue Disorder (90.9%) and one patient of Chronic Hypersensitivity Pneumonitis (HP).Conclusions: Absence of extrapulmonary symptoms in UIP patients need no further investigations and can be diagnosed as a case of IPF. However, presence of extrapulmonary symptoms needs further evaluation to diagnose the underlying disease and start treatment for the same.

Padrões de tomografia computadorizada de alta resolução na doença pulmonar intersticial (DPI): prevalência e prognóstico / High resolution computed tomography patterns in interstitial lung disease (ILD): prevalence and prognosis

RESUMO Objetivo Correlacionar a prevalência e o prognóstico de cada padrão de TCAR de pneumonia intersticial usual (PIU) típica, provável e indeterminada com o diagnóstico clínico multidisciplinar de doença pulmonar intersticial (DPI). Métodos Incluímos todos os pacientes com diagnóstico multidisciplinar de DPI com padrão de TCAR de PIU típica, PIU provável ou indeterminada para PIU. Dados clínicos e histopatológicos, teste de função pulmonar e status de sobrevida foram obtidos retrospectivamente. O diagnóstico final foi validado por uma equipe multidisciplinar. Resultados Foram incluídos no estudo 244 pacientes, com média de idade de 68 ± 13 anos sendo 52,5% do sexo masculino. Em um total de 106 pacientes com padrão típico de PIU, 62% tiveram o diagnóstico multidisciplinar de FPI, 20% de pneumonia por hipersensibilidade crônica (PHC) e 10% de DPI relacionada à doença do tecido conjuntivo (DPI-DTC). Dos 114 casos com provável PIU, DPI-DTC correspondeu a 39%, FPI a 31%, pneumonia intersticial descamativa a 11%, doença pulmonar relacionada a medicamentos a 9% e PHC a 8%. Nos 24 pacientes com TC indeterminada para PIU, o DPI-DTC foi o diagnóstico final em 33%, seguido por pneumonia intersticial descamativa (21%) e FPI (13%). Pacientes com PIU típica apresentaram maior probabilidade de morrer ou realizar transplante de pulmão no seguimento (17,9% e 11,3%, respectivamente). Conclusões FPI, PHC e DPI-DTC foram os principais diagnósticos diferenciais em pacientes com padrão de TCAR de PIU típica, provável e indeterminada. Pacientes com padrão de PIU típico na TCAR tiveram maior probabilidade de morrer ou realizar transplante de pulmão no seguimento.

ABSTRACT Objective To correlate the prevalence and prognosis of each HRCT pattern of typical, probable, and indeterminate usual interstitial pneumonia (UIP) with the clinical multidisciplinary diagnosis of interstitial lung disease (ILD). Methods We included all patients with a multidisciplinary diagnosis of ILD with an HRCT pattern of typical UIP, probable UIP, or indeterminate for UIP. Clinical and histopathological data, pulmonary function tests, and survival status were retrospectively obtained. The final diagnosis was validated by a multidisciplinary team. Results A total of 244 patients were included in the study, with a mean age of 68 ±13 years and being 52.5% males. In a total of 106 patients with typical UIP pattern, 62% had the multidisciplinary diagnosis of IPF, 20% had chronic hypersensitivity pneumonitis (CHP), and 10% had connective tissue disease-related ILD (CTD-ILD). Out of the 114 cases with probable UIP, CTD-ILD corresponded to 39%, IPF to 31%, desquamative interstitial pneumonia to 11%, drug-related lung disease to 9%, and CHP to 8%. In the 24 patients with CT indeterminate for UIP, CTD-ILD was the final diagnosis in 33%, followed by desquamative interstitial pneumonia (21%), and IPF (13%). Patients with typical UIP were more likely to die or had lung transplantation in the follow-up (17.9% and 11.3%, respectively). Conclusion IPF, CHP, and CTD-ILD were the main differential diagnoses in patients with HRCT patterns of typical, probable and indeterminate UIP. Patients with HRCT typical UIP pattern were more likely to die or had lung transplantation in the follow-up.

Interpretation of the guidelines for clinical diagnosis of idiopathic pulmonary fibrosis in 2018 / 中国实用内科杂志

Idiopathic pulmonary fibrosis(IPF) is a specific form of interstitial lung diseases(ILDs) with unknown causes. In 2018, the international expert panel of interstitial lung diseases updated the diagnostic criteria of IPF based on the imaging and histopathology published in 2011. We will interpret the new 2018 version of diagnostic guidelines for IPF.

Neumonitis por hipersensibilidad: Serie de nueve casos con biopsia pulmonar quirúrgica / Hypersensitivity pneumonitis. A series of nine cases with surgical lung biopsy

En una serie de nueve pacientes con diagnóstico histopatológico de neumonitis por hipersensibilidad, se revisaron en forma retrospectiva la historia clínica, los factores de exposición, las pruebas de función pulmonar y las tomografías computarizadas de tórax. La función pulmonar evidenció principalmente compromiso restrictivo con disminución de la difusión de monóxido de carbono. Las tomografías de tórax mostraron patrones fibróticos en la mayoría de los casos; áreas de vidrio esmerilado con patrón en mosaico y áreas de consolidación en el resto. Pudo detectarse exposición a antígenos aviarios, granos de cereales y acondicionadores de aire contaminados con esporas de hongos y bacterias, en dos tercios de los casos. Dado que no existen características únicas que permitan diferenciar la neumonitis por hipersensibilidad de otras enfermedades del intersticio pulmonar, se requiere de un alto índice de sospecha clínica y de una detallada búsqueda de exposición ambiental que deberán complementarse con los datos clínicos, radiológicos y de anatomía patológica para llegar al diagnóstico.

In a series of nine patients with histopathological diagnosis of hypersensitivity pneumonitis, we retrospectively evaluated clinical data, exposure related factors, pulmonary function tests and chest computed tomography scans. A restrictive abnormality with reduction of diffusion capacity for carbon monoxide was mainly found. Chest scans showed fibrotic patterns in most cases; ground glass attenuation areas with mosaic pattern and consolidation in the rest. Exposure to avian antigens, cereal grains and air conditioners contaminated with fungi yeasts and bacteria, were suspected from clinical data in two-thirds of the cases. Since there are no unique features that allow differentiation from other interstitial lung diseases, a high clinical suspicion is required and a careful search of environmental exposure to possible antigens is needed that, together with clinical, radiological and pathological data, may lead to diagnosis.

Supervivencia en pacientes con neumonía intersticial usual en contexto de fibrosis pulmonar idiopática y enfermedad del tejido conectivo / Survival in Patients with Usual Interstitial Pneumonia Secondary to Idiopathic Pulmonary Fibrosis and Connective Tissue Disease

Introducción: La neumonía intersticial usual (NIU) es un patrón histológico que conlleva mal pronóstico. Sin embargo, en los últimos años se ha sugerido que la NIU asociada a las enfermedades del tejido conectivo (NIU-ETC) puede tener un comportamiento diferente a la asociada a la fibrosis pulmonar idiopática (FPI). Objetivos: Conocer si existen diferencias en la severidad y supervivencia entre los pacientes con NIU asociada a FPI y los pacientes con NIU en contexto de ETC, incluyendo esclerosis sistémica, artritis reumatoidea, polidermatomiositis y enfermedad mixta del tejido conectivo. Materiales y métodos: Fueron evaluadas las características clínicas y la supervivencia de 102 pacientes (81 con FPI y 21 con NIU-ETC) diagnosticados en base a biopsia quirúrgica o una tomografía computada de alta resolución (TCAR) con NIU definida. Resultados: La media de seguimiento fue de 24 meses (0 a 146 meses). Cuarenta y cuatro pacientes murieron durante el seguimiento, una proporción significativamente mayor entre los pacientes con FPI que entre los pacientes con NIU-ETC (49.4 vs 19.0%, p = 0.014) y la supervivencia a 3 y 5 años fue mayor en pacientes con NIU asociada a ETC que en pacientes con FPI. Los pacientes con NIU-ETC tuvieron una tasa de mortalidad a los 3 y 5 años de 19.5% y 20.0%, respectivamente, comparado con pacientes con FPI que tuvieron una tasa de mortalidad a 3 y 5 años de 35.0%, y 65.9% respectivamente (p = 0,014). Los pacientes con FPI fueron mayores que los pacientes con NIU-ETC (edad 67.95 ± 9.4 vs 57.78 ± 14.5, p = 0.021), con una proporción mayor de pacientes de sexo masculino (67.9% vs 33.3%, p = 0.006). No hubo diferencias significativas en la función pulmonar basal, la cantidad de pacientes con disnea en el momento del diagnóstico, el tiempo de inicio de síntomas al diagnóstico o en número de pacientes biopsiados entre ambos grupos. En el análisis multivariado, la DLCO y el diagnóstico de FPI fueron los únicos factores pronósticos independientes. Conclusiones: Nuestro estudio sugiere que los pacientes con NIU-ETC se asocian con una mejor supervivencia que aquellos pacientes con FPI, a pesar de presentar la misma severidad de enfermedad al momento del diagnóstico.

Background: Usual interstitial pneumonia (UIP) is a histologic pattern that implies poor prognosis. However, some studies have suggested that UIP associated to connective tissue diseases (CTD-UIP) may have a different outcome than that associated with idiopathic pulmonary fibrosis (IPF). Objectives: To compare disease severity and survival between IPF and UIP associated to connective tissue diseases including scleroderma, rheumatoid arthritis, polymyositis and mixed CTD. Methods: The study included the analysis of clinical features and survival of 102 patients (81 with IPF and 21with CTD-UIP) diagnosed through surgical biopsy or high resolution computed tomography (HRCT) in patients with definitive UIP. Results: Median follow-up was 24 months (0 to 146 months). Forty-four patients died during the follow-up; the proportion of deaths was significantly higher amongst patients with IPF than amongst patients with CTD-UIP (49.4 vs 19.0%, p = 0.014). The 3 and 5 year survival was higher in patients with UIP secondary to CTD than in patients with IPF. Patients with CTD-UIP showed 3 and 5-year case fatality rate of 19.5% and 20.0% respectively, compared to 3 and 5-year case fatality rate of 35.0%, and 65.9% respectively in patients with IPF (p = 0.014). Patients with IPF were older than patients with CTD-UIP (age 67.95 ±9.4 vs 57.78 ±14.5, p = 0.021) and were more likely to be male (67.9% vs 33.3%, p = 0.006). There were no significant differences among baseline lung function, time between onset of symptoms and diagnosis, number of patients biopsied and the proportion of patients with dyspnea at the time of diagnosis between IPF and CTD-UIP patients. By multivariate analysis, the diffusing capacity of the lung for carbon monoxide (DLCO) and the presence of IPF were independent prognostic factors. Conclusions: Our data suggest that patients with UIP associated to CTD have a better survival than patients with IPF related UIP despite similar disease severity at the time of the diagnosis.

Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia

Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis.

High resolution computed tomography (HRCT) in diagnosis and management of usual interstitial pneumonia.

Background & Objectives: The aim of our article is to explain utility of high resolution CT scan in detection of usual interstitial pneumonia which has grave prognosis .Materials & Methods: Study opulation comprises 19 women and 11 men. Inclusion criteria were patients presenting with breathlessness, reticular patternon chest xray or restrictive pattern on pulmonary function tests. All patients were subjected to high resolution computed tomography (HRCT) examination. Findings of HRCT & chest x-ray were compared. Results: Study showed that (1)Septal thickening with honeycombing is core finding in UIP.(2)Lower lobe involvement, sub pleural & peripheral distribution of lesions were characteristic.(3)Ground glass opacity & traction bronchiectasis were other findings. Conclusion: In conclusion, HRCT is having high degree of accuracy in diagnosing usual interstitial pneumonia. The disease itself is having worst prognosis. Early detection is possible with HRCT, in late stages changes can be picked up easily without need of lung biopsy.

An approach to interstitial lung disease in India.

Interstitial lung diseases are common and have varied etiology, clinical presentation, clinical course and outcome. They pose a diagnostic challenge to physicians and pulmonologists. Patients present with dry cough, exertional dyspnoea, interstitial lesions on X-ray of the chest and restrictive ventilatory defect on spirometry. A sharp decline in oxygen saturation with exercise is characteristic. Careful evaluation of the history of the patient and physical examination help in narrowing down diagnostic probabilities. HRCT of the chest has emerged as an important tool in the evaluation of these disorders. Idiopathic Interstitial Pneumonias (IIP) are a group of conditions which are classified into several types based on pathological features. Bronchoscopic procedures are helpful in diagnosis of certain disorders but are of limited value in classification of IIP which requires surgical biopsy. Usual Interstitial Pneumonia (UIP), also referred to as Idiopathic Pulmonary Fibrosis, has a progressive course and an unfavourable outcome. Certain new drugs have recently become available for treatment of UIP. Our approach towards diagnosis and management of interstitial lung diseases based on personal experience over the past three decades is reported here.

Aumento na expressão de telomerase por fibroblastos ocorre precocemente à expressão de alfa-actina de músculo liso por miofibroblastos no processo de remodelamento da pneumonia intersticial usual / Increased telomerase expression in fibroblasts occurs earlier than myofibroblast alfa-smooth muscle actin expression in the remodeling process of usual interstitial pneumonia

Objetivo: Identificar potenciais marcadores associados à expressão de telomerase em fibroblastos e de α-actina de músculo liso (α-AMS) em miofibroblastos de pulmões de pacientes com fibrose pulmonar idiopática/pneumonia intersticial usual (FPI/PIU). Métodos: Utilizamos cortes histológicos de 34 biópsias cirúrgicas de pulmão de pacientes com FPI, caracterizados, à histopatologia, pelo padrão de PIU. As expressões de telomerase por fibroblastos, de α-AMS por miofibroblastos e tecidual deinterleucina-4 (IL-4), de fator de crescimento transformador-β (TGF- β) e de fator de crescimento de fibroblastos básico (bFGF) foram avaliados por imunohistoquímica e quantificadas pela técnica de contagem de pontos nas áreas pulmonares de colapso (COL),de fibrose mural (FM) e de faveolamento (FV). Resultados: Aexpressão de telomerase foi significativamente maior nas áreasde COL que nas áreas de FM e FV. O mesmo foi observado para a expressão de bFGF. Interleucina-4 e α-AMS tiveram expressão significativamente maior nas áreas de FM. A expressão de TGF-β foi maior nas áreas de COL e FV. Observamos uma associação positiva entre expressão de telomerase e bFGF nas áreas COL, FM e FV. O mesmo ocorreu com a expressão de α-AMS e IL-4. Nas áreas de FM, houve uma correlação negativa entre IL-4e bFGF, e TGF-β apresentou tendência a associação positiva com α-AMS. Análise multivariada revelou que a expressão de IL-4 e α-AMS nas áreas de FM são indicadores independentes de menor sobrevida em modelo estatístico significante incluindo idade, tabagismoe FVC (capacidade vital forçada). Pacientes com expressão de IL-4 menor que 13,5% nas áreas de FMapresentaram melhor sobrevida. O mesmo foi observado para expressão de α-AMS menor que 8,5%. Conclusão: Fibroblastos, com capacidade multiplicativa caracterizada pela expressão de telomerase e de bFGF tecidual, tendem a predominar no estágio precoce de remodelamento da FPI/PIU...

Objective: To identify potential markers associated with fibroblast telomerase and interstitial myfibroblast alpha-smooth muscle actin (α-AMS) expression in patients with idiopathic pulmonary fibrosis/usual intersticial pneumonia (IPF/UIP). Methods:Pulmonary specimens included 34 surgical lung biopsies, histologicallyclassified as UIP, from patients clinically diagnosed with IPF. Fibroblast telomerase expression, interstitial myofibroblast α-AMSexpression and IL-4 (interleukin 4), TGF-β (transforming growth factor beta) and bFGF (basic fibroblast growth factor) tissue expressionwere evaluated by immunohistochemistry and quantifiedin collapsed (COL), mural fibrosis (MF) and honeycombing areas (HC). Results: Telomerase expression was significantly higher in COL areas than in MF and HC areas. The same was observed for b-FGF. Interleukin-4 and α-AMS expression were significantly higher in MF areas. TGF-β expression ws higher in COL and HC areas. We observed a positive correlation between telomerase and bFGF expression in COL, MF and HC areas. The same was noted for α-AMS and IL-4. In MF areas, a negative correlation between IL-4 and b-FGF was obtained and TGF-β tended to positively correlate with α-AMS. In multivariate analysis, IL-4 tissue andα-AMS myofibroblast expression in MF areas were independently predictive of mortality in a statistically significant model including age, tobacco use and FVC (full vital capacity). Patients with IL-4 expression lower than 13.5% in MF areas had better survival. The same was noted for α-AMS expression lower than 8.5%. Conclusion: Fibroblast multiplicative capacity, characterized by telomerase expression and associated with bFGF tissue expression, seems to predominate in the early remodeling process of IPF/UIP, whereas myofibroblast differentiation, characterized by alpha-smooth muscleactin expression and associated with IL-4 tissue expression, seems to lead to the later fibrotic response...

A Case Report of Usual Interstitial Pneumonia after Treatment of Bronchopneumonia / 가정의학회지

Usual interstitial pneumonia (UIP) is one type of idiopathic interstitial pneumonia, characterized by its poor prognosis and gradual deterioration of clinical course. So it is important to distinguish UIP from other interstitial pneumonia. Defi nitive histological diagnosis of UIP requires lung biopsy. The criteria for diagnosis of UIP in the absence of a surgical lung biopsy were recently defi ned. We report a case of 75-year-old man who was diagnosed as bronchopneumonia with chief complaint of fever, dyspnea on fi rst visit, then fi nally diagnosed as UIP through the remaining of chest abnormality after treatment.

Clinical Year in Review of Interstitial Lung Diseases: Focused on Idiopathic Interstitial Pneumonia / 결핵및호흡기질환

Interstitial lung disease (ILD) is a group of diseases characterized by pulmonary interstitial inflammation. Finally the inflammation results in pulmonary fibrosis and impairment of oxygen transportation. The causes of idiopathic interstitial pneumonia (IIP) are unknown. Diagnosis of IIP is not easy, especially distinguising between nonspecific interstitial pneumonia and usual interstitial pneumonia (UIP). First line treatments of IIP include corticosteroids and immune modulators, which have limited effect. Currently, several drugs are being researched to prevent and treat fibrosis. Newer drugs that may useful to treat pulmonary fibrosis include endothelin receptor antagonist, recombinant soluble TNF receptor antagonist, and cotrimoxazole. The causes of IIP are largely unknown, treatment is not specific, and prognosis is poor. Recent studies are underway to investigate the pathogenesis and treatment of IIP and pulmonary fibrosis. As the pathogenesis of IIP is elucidated, better treatments will emerge.

HRCT Findings and Clinical Features in Non-specific and Usual Interstitial Pneumonia with Connective Tissue Diseases / 대한류마티스학회지

OBJECTIVE: The purpose of this study is to assess the clinical characteristics and the serial changes of high resolution CT (HRCT) findings and to correlate those with the results of clinical parameters in biopsy proven nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP) with connective tissue diseases (CTD). METHODS: Retrospective analysis was made of forty patients with CTD diagnosed of NSIP and UIP from a single tertiary hospital between January 1996 and February 2006. RESULTS: UIP was common in rheumatoid arthritis, systemic sclerosis and Sjogren's syndrome, while NSIP was frequent in polymyositis/dermatomyositis. No significant difference was found in the clinical characteristics of patients with NSIP and UIP. In initial HRCT findings, extents of honeycombing and reticulation pattern were significantly more in UIP-CTD than in NSIP-CTD. In bronchoalveolar lavage (BAL) results, proportion of alveolar macrophages was significantly higher in NSIP-CTD than in UIP-CTD. In NSIP-CTD, significant increment in the extent of reticulation and honeycombing was noted in the serial HRCT findings despite the aggressive treatment. Significant correlation was found between leukocytosis and honeycombing change in NSIP-CTD. Despite no significant difference of survival between two groups, patients with UIP-CTD seem to have a higher mortality than those with NSIP-CTD. CONCLUSION: It is suggested that chest HRCT and BAL fluid analysis may be helpful in the differential diagnosis of NSIP- and UIP-CTD and leukocytosis in initial blood test might be predictive of honeycombing progression in NSIP-CTD. Further study will be required to compare with the prognosis of NSIP- and UIP-CTD.

Short-term Clinical Experience on Interferon gamma-1b Therapy for Idiopathic Pulmonary Fibrosis / 결핵

BACKGROUND: Corticosteroids in combination with cytotoxic drugs are the mainstays of therapy for idiopathic pulmonary fibrosis (IPF). However, there has been no regimen showing any survival benefit. The aim of this study was to describe a short-term clinical experience on interferon gamma-1b (IFN-gamma1b) therapy for IPF, as an antifibrotic agent. METHODS: Medical records of 27 patients who were treated with IFN-gamma1b (2 million IU, 3 times a week, subcutaneous injection) were retrospectively reviewed. Treatment response was assessed using ATS/ERS criteria in 17 patients who received IFN-gamma1b for more than 6 months. In addition, we compared the efficacy of IFN-gamma1b therapy with that of cyclophosphamide+/-prednisolone therapy (n=26). RESULTS: The median age of IFN-gamma treated group (M:F=19:8) was 59 years (44-74 years). Compared to the patients who showed a stable response at 6 months (n=12), the deteriorated group (n=5) had worse baseline lung function (FVC, 55.4+/-11.3% vs. 70.7+/-10.9%, p=0.019; DLco, 50.3+/-7.3% vs. 76.9+/-19.6%, p=0.014). Lower baseline PaO2 on room air breathing was observed in the deteriorated group (68.6+/-7.8mmHg vs. 91.4+/-6.6mmHg p=0.001). Subcutaneous IFN-gamma1b did not show better efficacy than prednisolone. Five patients discontinued IFN-gamma because of severe side effects. ARDS developed in one patient, who eventually died. CONCLUSION: The administration of IFN-gamma1b is not desirable for patients diagnosed with IPF with poor lung function. Long-term and large-scaled clinical studies are needed for its efficacy in IPF.

Cyclophosphamide in the Treatment of Idiopathic UIP and NSIP / 결핵

BACKGROUND: Although corticosteroid and cytotoxic agent such as cyclophosphamide have been used for the treatment of idiopathic interstitial pneumonia (IIP), efficacy of these toxic drugs are unclear because previous reports included the patients who did not undergo surgical lung biopsy and none evaluated the response according to histopathologic entities of IIP. To answer this, we retrospectively analyzed the treatment response and side effects of corticosteroids and cyclophosphamide therapy in patients with idiopathic UIP and NSIP. METHODS: Among 61 patients with UIP and 26 patients with NSIP diagnosed by surgical lung biopsy at Samsung Medical Center from July 1996 to June 2002, those who received corticosteroid or cyclophosphamide therapy for at least 6 months and were followed for at least one year after the initiation of treatment were enrolled (32 UIP, 23 NSIP). Treatment response of 55 patients was assessed by ATS response criteria (clinical symptoms, pulmonary function test and radiological findings).Adverse reactions to either agent (42 cases of cyclophosphamide+/-low-dose prednisolone, 49 cases of prednisolone alone) were also analyzed. RESULTS: Irrespective of treatment regimen, NSIP showed more favorable response than UIP (6 months: 78.3% vs. 9.4%, 12 months: 69.6% vs. 9.4%, p<0.001). Cyclophosphamide showed comparable response to corticosteroid in NSIP while its efficacy was as poor as those of corticosteroid therapy in UIP. Significant adverse reaction to drug more frequently occurred in corticosteroid group (35.7%) than cyclophosphamide group (14.3%) (p=0.017). CONCLUSION: Cyclophosphamide is effective and more tolerable than corticosteroids in the treatment of idiopathic nonspecific interstitial pneumonia.

The Expression of Clara Cell Secretory Protein in BAL Fluid of Patients with Idiopathic Interstitial Pneumonia / 결핵

BACKGROUND: Idiopathic interstitial pneumonia is characterized by chronic inflammation and pulmonary fibrosis. The clara cell 10 kD protein (CC10, also designated CC16) is synthesized by the bronchial epithelium and has been suggested to have a potent anti-inflammatory effect. Therefore, CC-10 might be a candidate for controlling the inflammatory events in patients with idiopathic interstitial pneumonia. The aim of this study was to determine if the degrees of pulmonary fibrosis in idiopathic interstitial pneumonia is associated with CC-10 in the BAL fluid. METHODS: The BAL fluid was collected from 29 patients and 10 controls. Densitometric analysis of the western blot assay for the CC-10 was subsequently performed. The RI (relative intensity) of each band was compared according to the diagnosis, the radiological degrees of pulmonary fibrosis and the relative proportion of inflammatory cells in the BAL fluid. RESULTS: There were no differences in the CC-10 expression levels in the BAL fluid between the patients (RI 77.5+/-75.8%) and the controls (70.7+/-39.8%) (p>0.05). In addition, the degrees of pulmonary fibrosis and airway inflammation in patients with usual interstitial pneumonia were not associated with CC-10 expression in the BAL fluid (p>0.05). CONCLUSION: This study suggests that CC-10 expression is not associated with the degrees of pulmonary fibrosis in patients with usual interstitial pneumonia.

Prognostic Value of Fibroblastic Foci in Patients with Usual Interstitial Pneumonia / 결핵

BACKGROUND: Usual interstitial pneumonia (UIP) is a progressive disorder characterized by a poor response to conventional immunosuppressive agents and significant mortality. The histologic hallmark of UIP is patchy subpleural fibrosis with interposed fibroblastic foci(FBF) and relatively normal appearing lung. FBF is a collection of actively proliferating myofibroblasts, which may represent the activity of IPF. However, there were contradictory reports about the correlation between the degree of FBF and survival. The objective of this study was to investigate the roles of FBF as prognostic marker of UIP. METHOD: This was a retrospective study on the 46 patients(M:F=33:13, mean age:59+/-12 years) who had the surgical lung biopsy done at the Asan Medical Center, Seoul, Korea between 1990 and 2000 and had follow-up of more than a year. All the biopsy specimens were reevaluated and diagnosed as UIP according to the new classification. Semiquantitative grading of FBF(absent, 0; mild 1; moderate 2; marked 3) was performed by the experienced pathologists and compared to the clinical data and the follow up course. RESULTS: Thirteen patients(28.2%) died of UIP progression during the study period. The median survival time of all the subjects was 26 months after the biopsy. The FVC, DLco, smoking history and the grade of FBF were significantly related to the risk of death. The survival was longer in subjects with lesser degrees of FBF, higher DLco, higher FVC and history of smoking .The multivariate analysis with Cox regression test showed the extent of FBF was the only independent prognostic marker of UIP. CONCLUSION: These data suggested that the extent of FBF on the surgical lung biopsy can be used as a prognostic marker of UIP.

Clinical Features and Treatment Response in 18 Cases with Idiopathic Nonspecific Interstitial Pneumonia / 결핵

BACKGROUND: Nonspecific interstitial pneumonia (NSIP) has been reported recently to show much better response to medical treatment and better prognosis compared with idiopathic UIP. However, clinical characteristics of idiopathic NSIP discriminating from UIP have not been defined clearly. METHOD: Among 120 patients with biopsy-proven diffuse interstitial lung diseases between July 1996 and March 2000 at Samsung Medical Center, 18 patients with idiopathic NSIP were included in this study. Retrospective chart review and radiographic analysis were performed. RESULTS: 1) At diagnosis, 17 patients were female and average age was 55.2 +/-8.4 years (44~73 years). The average duration from development of respiratory symptom to surgical lung biopsy was 9.9+/-17.1 months. Increase in bronchoalveolar lavage fluid lymphocytes (23.0 +/-13.1%) was noted. On HRCT, ground glass and irregular linear opacity were seen but honeycombing was absent in all patients. 2) Corticosteroids were initially given to 13 patients of whom medication was stopped in 3 patients due to severe side effects. Further medical therapy was impossible in 1 patient who experienced streroid-induced psychosis. Herpes zoster (n=3), tuberculosis (n=1), avascu lar necrosis of hip (n=1), cataract (n=2) and diabetes mellitus (n=1) developed during prolonged corticosteroid administration. Of 7 patients receiving oral cyclophosphamide therapy, hemorrhagic cystitis hindered one patient from continuous medication. 3) After medical treatment, 14 of 17 patients improved and 3 patients remained stable (mean w-up ; 24.1+/-11.2 months). FVC increased by 20.2 +/-11.2% of predicted value and the extent of ground glass opacity on HRCT decreased significantly (15.7+/-14.7%). 4) Of 14 patients who had stopped medication, 5 showed recurrence of NSIP and 2 aggravated during steroid tapering. All patients with recurrence showed deterioration within one year after completion of initial treatment. CONCLUSION: Since idiopathic NSIP has unique clinical profiles and shows a good prognosis, differential diagnosis from UIP and aggressive medical treatment are needed.

Short-Term Efficacy of Steroid and Immunosuppressive Drugs in Patients with Idiopathic Pulmonary Fibrosis and Pre-treatment Factors Associated with Favorable Response / 결핵

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a diffuse inflammatory and fibrosing process that occurs within the interstitium and alveolus of the lung with invariably poor prognosis. The major problem in management of IPF results from the variable rate of disease progression and the difficulties in predicting the response to therapy. The purpose of this retrospective study was to evaluate the shortterm efficacy of steroid and immunosuppressive therapy for IPF and to identify the pre-treatment determinants of favorable response. METHOD: Twenty patients of IPF were included. Diagnosis of IPF was proven by thoracoscopic lung biopsy and they were presumed to have active progressive disease. The baseline evaluation in these patients included clinical history, pulmonary function test, bronchoalveolar lavage (BAL), and chest high resolution computed tomography (HRCT). Fourteen patients received oral prednisolone treatment with initial dose of 1mg/kg/day for 8 to 12 weeks and then tapering to low-dose prednis olone (0.5mg/kg/day). Six patients who previously had experienced significant side effects to steroid received 2mg/kg/day of oral cyclophosphamide with or without low-dose prednisolone. Follow-up evaluation was performed after 6 months of therapy. If patients met more than one of followings, they were considered to be responders: (1)improvement of more than one grade in dyspnea index, (2)improvement in FVC or TLC more than 10% or improvement in DLco more than 20% (3) decreased extent of disease in chest HRCT findings. RESULT: One patient died of extrapulmonary cause after 3 month of therapy, and another patient gave up any further medical therapy due to side effect of steroid. Eventually medical records of 18 patients were analyzed. Nine of 18 patients were classified into responders and the other nine patients into nonresponders. The histopathologic diagnosis of the responders were all nonspecific interstitial pneumonia (NSIP) and that of nonresponders were all usual interstitial pneumonia (UIP) (p<0.001). The other significant differences between the two groups were female predominance (p<0.01), smoking history (p<0.001), severe grade of dyspnea (p<0.05), lymphocytosis in BAL fluid (23.8+/-16.3% vs 7.83+/-3.6%, p < 0.05), and less honeycombing in chest HRCT findings (0% vs 9.22+/-2.3%, p < 0.001). CONCLUSION: Our results suggest that patients with histopathologic diagnosis of NSIP or lymphocytosis in BAL fluid are more likely to respond to steroid or immunosuppressive therapy. Clinical results in large numbers of IPF patients will be required to identify the independent variables.