Multidisciplinary Approach to the Diagnosis of Idiopathic Interstitial Pneumonias: Focus on the Pathologist's Key Role.

Idiopathic Interstitial Pneumonias (IIPs) are a heterogeneous group of the broader category of Interstitial Lung Diseases (ILDs), pathologically characterized by the distortion of lung parenchyma by interstitial inflammation and/or fibrosis. The American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary consensus classification of the IIPs was published in 2002 and then updated in 2013, with the authors emphasizing the need for a multidisciplinary approach to the diagnosis of IIPs. The histological evaluation of IIPs is challenging, and different types of IIPs are classically associated with specific histopathological patterns. However, morphological overlaps can be observed, and the same histopathological features can be seen in totally different clinical settings. Therefore, the pathologist's aim is to recognize the pathologic-morphologic pattern of disease in this clinical setting, and only after multi-disciplinary evaluation, if there is concordance between clinical and radiological findings, a definitive diagnosis of specific IIP can be established, allowing the optimal clinical-therapeutic management of the patient.

Interstitial lung disease: a review of classification, etiology, epidemiology, clinical diagnosis, pharmacological and non-pharmacological treatment.

Interstitial lung diseases (ILDs) refer to a heterogeneous and complex group of conditions characterized by inflammation, fibrosis, or both, in the interstitium of the lungs. This results in impaired gas exchange, leading to a worsening of respiratory symptoms and a decline in lung function. While the etiology of some ILDs is unclear, most cases can be traced back to factors such as genetic predispositions, environmental exposures (including allergens, toxins, and air pollution), underlying autoimmune diseases, or the use of certain medications. There has been an increase in research and evidence aimed at identifying etiology, understanding epidemiology, improving clinical diagnosis, and developing both pharmacological and non-pharmacological treatments. This review provides a comprehensive overview of the current state of knowledge in the field of interstitial lung diseases.

Autoimmune pulmonary alveolar proteinosis during the treatment of nonspecific interstitial pneumonia complicated by clinically amyopathic dermatomyositis: A case report.

A 46-year-old male was treated with corticosteroids for nonspecific interstitial pneumonia (NSIP). He was referred to our hospital and admitted for worsening dyspnea and diffuse ground-glass opacity on chest computed tomography (CT) during corticosteroid treatment. Gottron's sign was observed, and the patient was diagnosed with clinically amyopathic dermatomyositis on skin biopsy. We increased the corticosteroid dose and added immunosuppressive agents; however, the opacity on the chest CT worsened. Based on periodic-acid-Schiff-positive granular material in the bronchoalveolar lavage fluid and the presence of anti-GM-CSF antibodies, the patient was diagnosed with autoimmune pulmonary alveolar proteinosis (APAP). The concentration of anti-GM-CSF antibodies in preserved serum was also elevated when the patient was diagnosed with NSIP. Thus, we assumed that NSIP and APAP coexisted, and that APAP manifested during immunosuppressive therapy. When exacerbation is observed during the treatment of interstitial pneumonia with immunosuppressive agents, it is necessary to consider APAP.

[Interstitial lung diseases : From imaging to treatment]. / Interstitielle Lungenerkrankungen : Vom Bild zur Therapie.

BACKGROUND: The role of radiology in the diagnosis of interstitial lung diseases (ILDs) has evolved over time, in part replacing histology. Radiology now represents a pillar of diagnostics and monitoring in ILDs. OBJECTIVE: To what extent does radiology influence diagnostics and treatment in ILDs? MATERIALS AND METHODS: A literature review was conducted, and current findings were discussed in the context of clinical data. RESULTS: Radiology plays a crucial role in the diagnosis of ILDs. Within the framework of the multidisciplinary conference, it provides specific CT patterns such as usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and organizing pneumonia (OP), or helps in identifying cystic lung diseases. Multicompartment diseases can be detected, and pulmonary hypertension or extrapulmonary involvement of the respective diseases can be suspected. Progressive pulmonary fibrosis requires radiologic assessment as one of the required criteria. Interstitial lung abnormalities are usually detected by radiological studies performed for an unrelated indication. CONCLUSION: Radiology plays an important role within the multidisciplinary conference to determine both diagnosis and treatment with antifibrotic or anti-inflammatory drugs, or a combination of both.

Histopathological significance of connective tissue disease-associated interstitial lung disease in transbronchial lung cryobiopsy specimens.

Differentiating between idiopathic interstitial pneumonia (IIP) and secondary interstitial pneumonia, particularly connective tissue disease-associated interstitial lung disease (CTD-ILD), can be challenging histopathologically, and there may be discrepancies among pathologists. While surgical lung biopsy has traditionally been considered the gold standard for diagnosing interstitial pneumonia, the usefulness of transbronchial lung cryobiopsy (TBLC) has been reported. If TBLC could effectively distinguish between primary and secondary diseases, it would provide a less invasive option for patients. The aim of this study was to identify specific pathologic findings in TBLC specimens that could assist in distinguishing CTD-ILD from IIP. A total of 93 underwent TBLC at Tenri Hospital between 2018 and 2022. We retrospectively reviewed cases of CTD-ILD exhibiting a nonspecific interstitial pneumonia (NSIP) pattern (CTD-NSIP) and cases of NSIP with an unknown etiology (NSIP-UE), as determined through multidisciplinary discussion. Nineteen patients with CTD-NSIP and 26 patients with NSIP-UE were included in the study for clinicopathological analysis. The CTD-NSIP group had a significantly higher proportion of female patients compared to the NSIP-UE group (79% vs. 31%; p = 0.002). The presence of both fresh and old intraluminal fibrosis within the same TBLC specimen was significantly more frequent in CTD-NSIP group than in the NSIP-UE group (p = 0.023). The presence of an NSIP pattern with co-existing fresh and old intraluminal fibrosis in TBLC specimens raised suspicion for CTD-ILD.

Radiological and histopathological features and treatment response by subtypes of interstitial pneumonia with autoimmune features: A prospective, multicentre cohort study.

BACKGROUND: Patients with idiopathic interstitial pneumonia (IIP) have a favourable prognosis when they have interstitial pneumonia with autoimmune features (IPAF). However, precise IPAF-related findings from high-resolution computed tomography (HRCT) and lung histopathological specimens and the treatment response have not been fully determined. Therefore, this study was conducted to evaluate the relationship between findings on HRCT or lung histopathological specimens and the progression of interstitial pneumonia in patients with IPAF. METHODS: This multicentre cohort study prospectively enrolled consecutive patients with IIP. At the diagnosis of IIP, we systematically evaluated 74 features suggestive of connective tissue diseases and followed them up. HRCT, lung specimens, serum antibodies, and the clinical course were also evaluated. RESULTS: Among 222 patients with IIP, 26 (11.7%) fulfilled the IPAF criteria. During a median observation period of 36 months, patients with IPAF showed better survival than those without IPAF (p = 0.034). While histopathological findings were not related to IPAF, nonspecific interstitial pneumonia (NSIP) with organizing pneumonia (OP) overlap was the most prevalent HRCT pattern (p < 0.001) and the consolidation opacity was the most common radiological finding in IPAF (p = 0.017). Furthermore, in patients with IPAF, the diagnosis of COP or NSIP with OP overlap was associated with a higher increase in %FVC in 1 year than in those with idiopathic pulmonary fibrosis, NSIP, or unclassifiable IIP (p = 0.002). CONCLUSIONS: This study shows the presence of consolidation opacity on HRCT and the diagnosis of COP or NSIP with OP overlap are associated with IPAF and its favourable treatment response in patients with IPAF.

Imaging of Pulmonary Manifestations of Connective Tissue Disease.

The majority of connective tissue diseases (CTDs) are multisystem disorders that are often heterogeneous in their presentation and do not have a single laboratory, histologic, or radiologic feature that is defined as the gold standard to support a specific diagnosis. Given this challenging situation, the diagnosis of CTD is a process that requires the synthesis of multidisciplinary data which may include patient clinical symptoms, serologic evaluation, laboratory testing, and imaging. Pulmonary manifestations of connective tissue disease include interstitial lung disease as well as multicompartmental manifestations. These CT imaging patterns and features of specific diseases will be discussed in this article.

Plasma extracellular vesicle proteins as promising noninvasive biomarkers for diagnosis of idiopathic pulmonary fibrosis.

High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCT making the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five-protein signature derived from mass spectrometry data showed an area under the receiver operating characteristic curve of 0.915 (95%CI: 0.819-1.011) and 0.958 (95%CI: 0.882-1.034) for differentiating IPF from other ILDs and from healthy subjects, respectively. Stepwise backwards elimination yielded a model with 3 and 2 proteins for discriminating IPF from other ILDs and healthy subjects, respectively, without compromising diagnostic accuracy. In summary, we discovered and validated EV protein biomarkers for differential diagnosis of IPF in independent cohorts. Interestingly, the biomarker panel could also distinguish IPF and healthy subjects with high accuracy. The biomarkers need to be evaluated in large prospective cohorts to establish their clinical utility.

Factores asociados al desarrollo de enfermedad pulmonar intersticial en esclerosis sistémica / Factors associated with the development of interstitial lung disease in patients with systemic sclerosis

Resumen Introducción: el compromiso pulmonar intersticial se presenta en 80% de las tomografías de tórax de pacientes con esclerosis sistémica (ES) y tiene gran impacto en la morbimortalidad. El objeti vo de este trabajo fue describir factores asociados al desarrollo de enfermedad pulmonar intersticial (EPI) en pacientes con diagnóstico de ES de nuestra división. Métodos: Se realizó un estudio retrospectivo, casos y controles, de pacientes seguidos entre 2005-2021 que cumplían criterios de ES. Se definió EPI al hallazgo de manifestaciones intersticiales en tomografía de tórax con cortes de alta resolución (TACAR): patrón neumonía intersticial no específica (NINE) o neumonía intersticial usual (NIU), y/o hallazgos en pruebas de función pulmonar (CVF menor al 80% y DLCO menor al 80%). Se identificaron pacientes con EPI (casos) y sin ella (controles). Se analizaron variables demográficas, clínicas y serológicas. Se calcularon medidas de porcentaje, media (DS) y mediana (RIQ) en cada variable. Se efectuó análisis univariado y multivariado, mediante regresión logística para establecer su asociación con EPI. Resultados: Se incluyeron 79 pacientes con ES, 31 con EPI. El análisis univariado demostró que el subtipo de esclerosis (según clasific ación Le Roy), las medidas de función pulmonar y positividad del anticuerpo anticentrómero fueron factores asociados en forma estadísticamente significativa con EPI. En el análisis multivariado solo la presencia de anticuerpos anti-centrómero fue estadísticamente significativa. Discusión: el análisis de los factores de riesgo para determinar desarrollo y progresión de daño pulmonar tiene vital importancia para una implementación temprana del tratamiento, lo que impactaría en la tasa de mortalidad de los pacientes con ES.

Abstract Introduction: interstitial lung involvement occurs in 80% of chest CT scans of patients with systemic sclerosis (SS) and has a great impact on morbidity and mortality. The aim of the study was to describe factors associated with the development of interstitial lung disease (ILD) in patients diagnosed with SS in our division. Methods: a retrospective case-control study of patients followed up between 2005-2021 who met the classification criteria for SS was performed. ILD was defined as the finding of interstitial manifestations on high-resolution chest tomography (HRCT): non-specific interstitial pneumonia pattern (NSIP) or usual interstitial pneumonia (UIP), and/or findings on pulmonary function tests (FVC less than 80% and DLCO less than 80%). Patients with ILD (cases) and without it (controls) were identified. Demographic, clinical and serological variables were analyzed. Percentage, mean (SD) and median (IQR) measurements were calculated for each variable. A univariate and multivariate analysis was performed using logistic regression to establish its association with ILD. Results: Seventy nine patients with SS were included, 31 with ILD. Univariate analysis showed that sclerosis subtype (according to Le Roy classification), lung function measures, and anticentromere antibody positivity were factors associated with ILD in a statistically significant way. In the multivariate analysis, only the presence of anti-centromere antibodies was statistically significant. Discussion: the analysis of risk factors to determine the development and progression of lung damage is of vital importance for an early implementation of treatment, which would impact the mortality rate of patients with SS.

Clinical risk factors in patients with interstitial lung disease associated with anti-MDA5 autoantibodies / Factores de riesgo clínicos en pacientes con enfermedad pulmonar intersticial con anticuerpos anti-MDA5

Introduction The anti-MDA5-associated autoimmune disease represents a poorly understood entity. The study's objectives were to describe a cohort of interstitial lung disease (ILD) patients who were positive for anti-MDA5 autoantibody and identify clinical risk factors associated with survival. Methods This single-center cohort study included ILD patients positive for anti-MDA5 autoantibody. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. Results Fifty-three ILD-MDA5 positive patients were included; twelve died during follow-up due to rapidly progressive interstitial lung disease (RP-ILD). Dermatological signs of anti-MDA5 (Gottron papules, Gottron sign, palmar papules, V-neck sign, facial dermatomyositis rashes, and skin ulcers) were strongly associated with death secondary to RP-ILD (HR: 3.7, 95% CI: 1.02–13.35). Patients with dermatological signs were younger, had higher anti-MDA5 autoantibodies titers, more frequent inflammatory patterns in HRCT evaluation, and less fibrosis extent in HRCT. Conclusion Dermatological manifestation in ILD patients to anti-MDA5 autoantibodies are associated with RP-ILD and short-term fatal outcomes. Dermatological signs may identify a subgroup of ILD-positive to anti-MDA5 patients with a high risk of RP-ILD (AU)

Introducción La enfermedad autoinmune asociada a los anticuerpos anti-MDA5 es una entidad poco estudiada. Los objetivos de este estudio son describir una cohorte de sujetos con enfermedad pulmonar intersticial (EPI) positivos al anticuerpo anti-MDA5 e identificar los factores clínicos de riesgo asociados con la supervivencia. Métodos Estudio de cohorte de un solo centro de pacientes con EPI y positivos al anticuerpo anti-MDA5. Se registraron las características clínicas basales y se realizó un análisis de supervivencia para identificar los factores de riesgo asociados con la supervivencia. Resultados Se incluyeron 53 pacientes con EPI y positivos a anti-MDA5; 12 pacientes fallecieron por una enfermedad intersticial rápidamente progresiva (EPI-RP). Los signos dermatológicos asociados a anti-MDA5 (pápulas de Gottron, signo de Gottron, pápulas palmares, signo de la V del escote, eritema facial de dermatomiositis y úlceras cutáneas) se asociaron fuertemente con la EPI-RP (HR: 3,7, IC 95%: 1,02-13,35). Los pacientes con manifestaciones dermatológicas eran más jóvenes, tenían mayores títulos de anticuerpos anti-MDA5, tenían mayor frecuencia de patrones inflamatorios en la tomografía de tórax de alta resolución y menor extensión de la fibrosis en la TCAR. Conclusión Las manifestaciones dermatológicas en los pacientes con EPI positivos a anticuerpos anti-MDA5 están asociados a EPI-RP y a desenlaces fatales al corto plazo. Los signos dermatológicos pueden identificar un subgrupo de pacientes positivos a anti-MDA5 con mayor riesgo de EPI-RP (AU)

Comparative study of clinical and HRCT findings between idiopathic nonspecific interstitial pneumonia and connective tissue disease-associated nonspecific interstitial pneumonia / 实用医学杂志

Objective To investigate the difference in clinical features and chest HRCT findings between idiopathic nonspecific interstitial pneumonia(INSIP)and connective tissue disease-associated nonspecific interstitial pneumonia(CTD-NISP). Methods Totally 73 cases of NISP from 2011 to 2016 were retrospectively reviewed ,whose final diagnosis all were made after clinico-radiologic-pathologic discussion and 52 cases of them were diag-nosed as INSIP and 21 cases as CTD-NSIP. Clinical features ,lung function test results and chest HRCT findings of INSIP and CTD-NSIP were compared. Results Common underlying diseases of CTD-NSIP were poly-/dermato-myositis(PM/DM),rheumatoid arthritis(RA)and Sjogren syndrome(SS). The mean age of CTD-NSIP[(47.14 ± 9.24)y]was younger than that of INSIP[(59.09 ± 11.20)y](P<0.05). Compared to CTD-NSIP,expectoration was more common in patients with INSIP,while dry mouth/eyes,arthralgia and erythra were less common in INSIP (P < 0.05). Lung function test1 showed restrictive ventilatory dysfunction with dispersion function decline was found in both groups. There were no significant differences in lung function test results between INSIP and CTD-NSIP. In HRCT,the subpleural vertical line was more common in INSIP than that in CTD-NSIP,while patchy consolidation,subpleural curvilinear shadow,pleural effusion and esophageal dilation were less common in INSIP(P<0.05). Conclusions Specific difference of clinical and HRCT features between CTD-NSIP and INSIP are conducive to differentiating the two from each other.

Radiologic Approach to the Idiopathic Interstitial Pneumonias / 대한내과학회지

Idiopathic interstitial pneumonias (IIP), a heterogeneous group of diffuse parenchymal lung diseases, include seven clinicopathologic entities: idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), acute interstitial pneumonia (AIP), respiratory bronchiolitis (RB)-associated interstitial lung disease (ILD), desquamative interstitial pneumonia (DIP), and lymphoid interstitial pneumonia (LIP). Each of these entities has a typical histologic pattern that correlates well with imaging features. Thus, imaging plays an essential role in classifying and differentiating this group of diseases. The characteristic HRCT findings of IPF are reticular opacity with honeycombing and traction bronchiectasis in a predominantly basal and peripheral distribution. NSIP manifests as basal ground-glass opacity and reticular opacity. Honeycombing is rare. COP is characterized by patchy peripheral or peribronchovascular consolidation. AIP appears as extensive, mixed ground-glass opacity and consolidation. RB-ILD and DIP are smoking-related diseases associated with CT features of poorly defined centrilobular nodules and ground-glass opacity. LIP is a rare disease characterized by ground-glass opacity sometimes associated with perivascular cysts. Although some of idiopathic interstitial pneumonias may show diagnostic CT features, the final diagnosis of IIPs is usually made by means of evaluation of all the combined clinical, radiologic, and pathologic findings.

Clinical Significance of Serum Autoantibodies in Idiopathic Interstitial Pneumonia

Although autoantibodies are routinely screened in patients with idiopathic interstitial pneumonia, there are no reliable data on their clinical usefulness. The aim of this study was to investigate the prognostic value of autoantibodies for predicting the development of new connective tissue disease in these patients and also mortality. We conducted retrospective analysis of the baseline, and follow-up data for 688 patients with idiopathic interstitial pneumonia (526 with idiopathic pulmonary fibrosis, 85 with nonspecific interstitial pneumonia, and 77 with cryptogenic organizing pneumonia) at one single tertiary referral center. The median follow-up period was 33.6 months. Antinuclear antibody was positive in 34.5% of all subjects, rheumatoid factor in 13.2%, and other specific autoantibodies were positive between 0.7%-6.8% of the cases. No significant difference in patient survival was found between the autoantibody-positive and -negative groups. However, the presence of autoantibodies, especially antinuclear antibody with a titer higher than 1:320, was a significant predictor for the future development of new connective tissue diseases (relative risk, 6.4), although the incidence was low (3.8% of all subjects during follow-up). In conclusion, autoantibodies are significant predictors for new connective tissue disease development, although they have no prognostic value.

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.

A Case of Nonspecific Interstitial Pneumonia Complicated with Spontaneous Pneumomediastinum, Subcutaneous Emphysema and Pneumatosis Interstinalis / 결핵및호흡기질환

Pneumatosis intestinalis or spontaneous pneumomediastinum are rarely associated with nonspecific interstitial pneumonia (NSIP). However, the development of both conditions in the same patient simultaneously has not been reported previously. A 56-year-old man with NSIP developed spontaneous pneumomediastinum accompanied by subcutaneous emphysema and pneumatosis intestinalis after the treatment with intravenous high dose steroid. The development of spontaneous pneumomediastinum, subcutaneous emphysema and pneumatosis intestinalis in this patient was possibly due to the factors such as NSIP, high dose steroid therapy and subclinical dermatomyositis. Treatment with corticosteroid and cyclosporin gradually improved his exacerbated NSIP and pneumomediastinum, subcutaneous emphysema, pneumatosis intestinalis.

A Case of Nonspecific Interstitial Pneumonia in a Patient with Ulcerative Colitis / 결핵및호흡기질환

Pulmonary complications of ulcerative colitis are relatively uncommon and may present as a variety of disorders. Ulcerative colitis-related interstitial lung disease is extremely rare. There are a few case reports of nonspecific interstitial pneumonia in ulcerative colitis worldwide but none in Korea. We report a patient with ulcerative colitis related biopsy-proven nonspecific interstitial pneumonia, who responded to prednisolone (1 mg/kg) and mesalazine therapy

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.

A Case of Nonspecific Interstitial Pneumonia in a Child

Interstitial pneumonia is a heterogenous group of inflammatory and fibrosing lesions that manifest themselves as infiltrative lung disease. Of these, nonspecific interstitial pneumonia is characterized as a variable degree of interstitial inflammation with or without fibrosis and is distinguished from usual interstitial pneumonia and desquamative interstitial pneumonia, histologically. The influx of inflammatory cells and the responses of immune effector cells injury to the alveolar wall and these initial injuries results in alveolitis and fibrosis. Consequently, the gas exchange throughout the alveolar wall is impaired and the patients suffer from lung diseases of a restrictive pattern. The chief complaints represented are dyspnea and dry cough. We experienced a case of nonspecific interstitial pneumonia in a 10-year old girl. The patient had been healthy and had not been exposed to organic dusts or other toxic materials. The pathology of lung biopsy tissue showed that the alveoli were thickened by a mixture of chronic inflammatory cells and collagen type fibrosis. High resolution computed tomography(HRCT) found the patchy areas of ground-glass opacity with patchy consolidation and irregular reticular opacity, and diffuse distribution without zonal predominance. The forced vital capicity(FVC) was 31%, forced expiratory volume in one second (FEV1) 29% and FEV1/FVC 90%, so a restrictive pulmonary insufficiency was found.

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.

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.