Disfunciones del metabolismo del surfactante pulmonar: caso clínico pediátrico / Pulmonary surfactant metabolism dysfunction: A pediatric clinical case report

Las enfermedades pulmonares intersticiales son patologías poco frecuentes en pediatría. Dentro de ellas, se incluyen las disfunciones del metabolismo del surfactante pulmonar, molécula anfipática cuya función es disminuir la tensión superficial y evitar el colapso alveolar. Se presenta el caso de un lactante de 6 meses, en seguimiento por bajo peso, que presentó dificultad respiratoria aguda y cianosis; la radiografía de tórax evidenció infiltrado intersticial, neumomediastino y neumotórax bilateral. Al interrogatorio, surgió antecedente materno de internación al año de vida, con requerimiento de oxigenoterapia prolongada y diagnóstico desconocido; presenta signos de hipoxia crónica. El paciente cursó internación con requerimiento de oxigenoterapia. Se realizaron estudios complementarios en búsqueda de etiología, sin resultados positivos. La tomografía de tórax evidenció opacidades en vidrio esmerilado, engrosamiento del intersticio septal y áreas de atrapamiento aéreo; con resultado de biopsia pulmonar y estudio genético se llegó al diagnóstico de disfunción del metabolismo del surfactante pulmonar.

Interstitial lung diseases are rare in pediatrics. They include dysfunctions in the metabolism of pulmonary surfactant, an amphipathic molecule that reduces surface tension and prevents alveolar collapse. Here we describe the case of a 6-month-old infant controlled for low weight, who presented with acute respiratory distress and cyanosis; his chest X-ray showed interstitial infiltrate, pneumomediastinum, and bilateral pneumothorax. During history-taking, it was noted that his mother had a history of hospitalization at 1 year old with unknown diagnosis, requiring prolonged oxygen therapy; she now shows signs of chronic hypoxia. The patient was hospitalized and required oxygen therapy. Ancillary tests were done to look for the etiology of the condition, with no positive results. A chest computed tomography showed groundglass opacities, thickening of the septal interstitium, and areas of air trapping; based on the results of a lung biopsy and a genetic study, pulmonary surfactant metabolism dysfunction was diagnosed.

Manifestaciones pulmonares al diagnóstico de 170 pacientes con vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos: cohorte retrospectiva de un centro universitario / Pulmonary manifestations at the diagnosis of 170 patients with vasculitis associated with anticytoplasmic neutrophil antibodies: retrospective cohort of a university center

INTRODUCCIÓN: Las Vasculitis Asociadas a Anticuerpos Anticitoplasma de Neutrófilos (VAA) son infrecuentes, pero de amplio espectro de presentación. Si bien el consenso de clasificación de Chapel Hill del año 2012, sigue vigente, la tendencia actual es clasificarlas de acuerdo al marcador inmunológico: anti-Proteinasa 3 (PR3) o anti-mieloperoxidasa (MPO). Las manifestaciones pulmonares clásicas son la hemorragia alveolar y los nódulos pulmonares. En los últimos 10 años se ha descrito la enfermedad pulmonar difusa (EPD). Los estudios epidemiológicos son escasos, y suelen representar en su mayoría poblaciones norteamericanas o europeas. El objetivo es describir las características del compromiso pulmonar al debut en VAA en un centro universitario. PACIENTES Y MÉTODO: De un total de 190 pacientes con diagnóstico de VAA se incluyeron 170 en seguimiento en nuestro centro. Se revisaron aspectos clínicos, demográficos, laboratorio e imagenológicos de los pacientes incluidos. RESULTADOS: De los 170 pacientes, 112 (65,88%) presentaron compromiso pulmonar. 106 (94,64%) de los pacientes fueron anticuerpos anti citoplasma de neutrófilos (ANCA) positivos; de estos, 56 (53,27%) MPO (+) y 39 (36,45%) PR-3 (+). Un tercio de los pacientes de ambos grupos presentó hemorragia alveolar. En los pacientes MPO (+) predomina la EPD (53,5%) y en PR-3 (+) los nódulos pulmonares (69,23%). Destaca la baja frecuencia de patología obstructiva asociada. CONCLUSIONES: El compromiso pulmonar en las VAA es prevalente y heterogéneo. En nuestra serie, destaca la frecuencia de EPD en VAA MPO (+), lo que releva la importancia del estudio con ANCA en paciente con diagnóstico y seguimiento por EPD.

INTRODUCTION: Antineutrophil Cytoplasmic Antibodies (ANCA) associated vasculitis (AAV) are uncommon, but of broad spectrum of presentation. Although the 2012 Chapel Hill classification consensus remains valid, the current trend is to classify them according to the immunological marker: anti-Proteinase 3 antibody (PR-3) or anti-Myeloperoxidase antibody (MPO). The classic pulmonary manifestations are alveolar hemorrhage and pulmonary nodules. Interstitial lung disease (ILD) has been described in the last 10 years. Epidemiological studies are scarce, and they usually represent mostly North American or European populations. The objective is to describe the characteristics of lung involvement upon debut in AAV in a university center. PATIENTS AND METHODS: Of a total of 190 patients diagnosed with AAV, 170 were included in follow-up at our center. Clinical, demographic, laboratory and imaging aspects of the included patients were reviewed. RESULTS: Of the 170 patients, 112 (65.88%) had lung involvement. 106 (94.64%) of the patients were ANCA (+); of these, 56 (53.27%) MPO (+) and 39 (36.45%) PR-3 (+). One third of the patients in both groups had alveolar hemorrhage. In MPO (+) patients, ILD predominates (53.5%) and in PR-3 (+) pulmonary nodules (69.23%). The low frequency of associated obstructive pathology stands out. CONCLUSIONS: Pulmonary manifestations in AAVs are frequent and heterogeneous. Locally, the association of ILD and AAV MPO (+) stands out, which highlights the importance of ANCA study in patients with diagnosis and follow-up by ILD.

Clinical characteristics and related factors of systemic lupus erythematosus with interstitial pneumonia / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical features, radiologic scores and clinically relevant risk factors prognosis of secondary interstitial lung disease (ILD) in patients with systemic lupus erythematosus (SLE).@*METHODS@#In this study, 60 SLE patients in Department of Rheumatology of the First Affiliated Hospital of Baotou Medical College and Taizhou First People's Hospital from January 2015 to March 2019 were retrospectively analyzed. All of those 60 patients with SLE underwent lung high resolution computed tomography (HRCT) examination. We used a 1 ∶1 case-control study. There was a matching of age and gender between the two groups. Thirty patients with SLE related ILD (SLE-ILD) were in the case group, and 30 patients with SLE without ILE (SLE non-ILD) were in the control group. The clinical features, pulmonary function test, radiologic characteristic of SLE patients were collected and were used to analyze SLE-ILD.@*RESULTS@#In this study, we reached the following conclusions: First, there were statistically significant differences in chest tightness/shortness of breath, Raynaud's phenomenon, and Velcro rale between SLE-ILD and SLE non-ILD patients (both P < 0.05); Second, hemoglobin (Hb) and albumin (ALB) in the patients of SLE-ILD had a significant decrease compared with the patients of SLE non-ILD. Blood urea nitrogen (BUN), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) increased in SLE-ILD patients compared with SLE non-ILD patients, the difference had statistical significance (P < 0.05); Third, for SLE-ILD patients, the most common type was non-specific interstitial pneumonia (NSIP), followed by usual interstitial pneumonia and lymphocytic interstitial pneumonia; Fourth, there was no significant difference in clinical-radiology-physiology scores between the different ILD types (P>0.05), similarly, the lung HRCT score and lung function between different ILD types had no significant difference (P>0.05); Fifth, multivariate Logistic regression analysis showed that decreased albumin and chest tightness/shortness of breath might be the risk factor for SLE-ILD.@*CONCLUSION@#There are statistically significant differences between the SLE-ILD group and SLE non-ILD group in terms of chest tightness/shortness of breath, Velcro rale and Raynaud's phenomenon. Decreased albumin and chest tightness/shortness of breath in SLE patients should be alerted to the occurrence of ILD. NSIP is the most common manifestation of SLE-ILD.

Recent research on myositis-specific autoantibodies in juvenile dermatomyositis / 中国当代儿科杂志

Juvenile dermatomyositis (JDM) is an autoimmune disease manifesting as proximal muscle weakness and skin rash and can involve multiple systems and visceral organs. Myositis-specific autoantibodies (MSAs) are highly associated with various complications and prognosis in JDM. Patients with anti-Mi-2 antibodies tend to have good prognosis and typical clinical symptoms. Patients with anti-MDA5 antibodies often have diffuse interstitial lung disease and skin ulcer, with mild symptoms of myositis. Patients with anti-NXP2 antibodies often have calcinosis, and such antibodies are associated with gastrointestinal bleeding and perforation. Patients with anti-TIF1-γ antibodies have diffuse and refractory skin lesions. Anti-SAE antibodies are rarely detected in children, with few reports of such cases. This article reviews the features of clinical phenotypes in JDM children with these five types of MSAs, so as to provide a basis for the clinical treatment and follow-up management of children with JDM.

Ventilation distribution as a contributor to the functional exercise capacity in patients with systemic sclerosis-associated interstitial lung disease without pulmonary hypertension

Phenotypic differences have been described between patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) and SSc-associated pulmonary hypertension, including performance differences in the 6-min walk test (6MWT). Moreover, the correlations between the 6MWT and traditional pulmonary function tests (PFTs) are weak, indicating the need to search for new parameters that explain exercise performance. Thus, our objective was to evaluate the impact of ventilation distribution heterogeneity assessed by the nitrogen single-breath washout (N2SBW) test and peripheral muscle dysfunction on the exercise capacity in patients with SSc-ILD and limited involvement of the pulmonary parenchyma. In this cross-sectional study, 20 women with SSc-ILD and 20 matched controls underwent PFTs (including spirometry, diffusing capacity for carbon monoxide (DLco), and the N2SBW test) and performed the 6MWT and knee isometric dynamometry. The 6-min walking distance (6MWD, % predicted) was strongly correlated with the phase III slope of the single-breath nitrogen washout (phase III slopeN2SBW) (r=−0.753, P<0.0001) and reasonably correlated with the forced vital capacity (FVC) (r=0.466, P=0.008) and DLco (r=0.398, P=0.011). The peripheral oxygen saturation (SpO2) during exercise was not significantly correlated with any of the pulmonary or muscle function parameters. The phase III slopeN2SBW was the only predictive variable for the 6MWD, whereas quadriceps strength and FVC/DLco were predictive variables for SpO2. Ventilation distribution heterogeneity is one factor that contributes to a lower 6MWD in SSc-ILD patients. In addition, muscle dysfunction and abnormal lung diffusion at least partly explain the decreased SpO2 of these patients.

The relation between interstitial lung disease and chronic HCV infection

Background and study aim: Interstitial lung disease (ILD) includes a variety group of about 200 conditions that insult the lung parenchyma with different patterns of inflammation and fibrosis. Hepatitis C virus (HCV)is Flavivirus with diverse hepatic and extrahepatic diseases. Its direct and indirect pathogenic association with many pulmonary manifestations-including interstitial lung disease-has been suggested yet needs more elucidation.Patients and Methods: A case control study was conducted with a total of 50 chronic hepatic patients. They were equally divided into two groups, HCV positive group (group 1= 25 patients) and HCV negative group (group 2= 25 patients). Group 1 was subdivided into two subgroups, without-idiopathic interstitial pneumonias patients (without IIPs subgroup A= 13 patients) and with idiopathic interstitial pneumonias patients (IIPs subgroup B = 12 patients). Both groups were subjected to thorough history taking, clinical examination, and routine investigations. The diagnosis of HCV was confirmed by viral markers including HCV antibodies and PCR. Other chronic hepatic liver diseases were confirmed by abdominal ultrasound and ultrasound- guided liver biopsy. Arterial blood gases, auto antibodies, Computerized pulmonary function tests and radiological studies including plain X ray chest and heart and HRCT scanning were also done. All patients with idiopathic pulmonary fibrosis (IPF) had fulfilled the ATS/ ERS diagnostic guidelines. Both groups were matched according to age, sex and body mass index.Results: The HCV positive group was found to have a significantly higher frequency of ILD than the HCV negative group with also more restrictive pattern hypoxemia and higher scores of IPF (by computed tomography).Conclusion: ILD is more frequent in patients with chronic HCV infection with higher grades of fibrosis and hypoxemia.HCV infection may be predisposing factor for IPF

Caracterización de pacientes con enfermedades autoinmunes del tejido conectivo e hipertensión de arteria pulmonar atendidos en Hospital San Juan de Dios / Patients characterization with autoimmune diseases of the connective tissue and high blood pressure in the pulmonary artery seen in hospital San Juan de Dios

La hipertensión de la arteria pulmonar (HAP) es una grave complicación que pue-den presentar los pacientes con enfermedades autoinmunes del tejido conectivo de prevalencia variable según cada país. Habitualmente su diagnóstico es tardío lo que influye negativamente en su pronóstico y respuesta terapéutica. En el pre-sente trabajo se ha iniciado una revisión en conjunto entre la Unidad de Hemodi-namia y de Reumatología del Hospital San Juan de Dios, con el propósito de tener una caracterización de los pacientes con HAP y enfermedades autoinmunes del tejido conectivo y poder así elaborar planes de manejo de acuerdo a las caracte-rísticas clínicas de estos pacientes e intentar obtener un diagnostico precoz, para mejorar la sobrevida de los portadores de estas enfermedades.

High blood pressure in the pulmonary artery (HAP) is a serious complication that may occur in patients with autoimmune diseases of the connective tissue of vari-able prevalence according to each country. Diagnosis is usually late which affects negatively their prognosis and therapeutic response. In the present work has been initiated a review in conjunction between the unit of Hemodynamic and Rheumatology of the Hospital San Juan de Dios, with the purpose of having a characterization of patients with PAH and autoimmune diseases of the connective tissue and can thus develop management plans according to the clinical features of these patients and try to get an early diagnosis, to improve the survival of the carriers of these diseases.

Anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus

Abstract: Background: The clinical significance of anti-neutrophil cytoplasmic antibodies in patients with new-onset systemic lupus erythematosus, especially in systemic disease accompanied by interstitial lung disease remains to be elucidated. Objectives: This study was designed to investigate the role of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients. Methods: A hundred and seven patients with new-onset SLE were enrolled. Presence of anti-neutrophil cytoplasmic antibodies in the sera was assessed by indirect immunofluorescence as well as enzyme linked immunosorbent assay against proteinase-3 and myeloperoxidase. Clinical features and laboratory parameters of patients were also recorded. All patients were subjected to chest X-ray, chest high-resolution computed tomography and pulmonary function test. Results: Forty-five systemic lupus erythematosus patients (45/107, 42%) were seropositive for anti-neutrophil cytoplasmic antibodies. Compared with anti-neutrophil cytoplasmic antibodies-negative patients, the anti-neutrophil cytoplasmic antibodies-positive patients had significantly higher incidence of renal involvement, anemia, and Raynaud's phenomenon as well as decreased serum level of complement 3/complement 4 and elevated erythrocyte sedimentation rate. In addition, there was a positive correlation between serum anti-neutrophil cytoplasmic antibodies level and disease activity of systemic lupus erythematosus. Furthermore, prevalence of interstitial lung disease in the anti-neutrophil cytoplasmic antibodies -positive patients (25/45, 55.6%) was obviously higher than that in the anti-neutrophil cytoplasmic antibodies-negative patients (15/62, 24.2%). Study limitations: The sample size was limited and the criteria for screening new-onset systemic lupus erythematosus patients might produce bias. Conclusions: The level of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients correlates positively with the disease activity and the prevalence of interstitial lung disease.

Pleuroparenchymal fibroelastosis: report of two cases in Brazil / Fibroelastose pleuroparenquimatosa: relato de dois casos no Brasil

ABSTRACT Pleuroparenchymal fibroelastosis (PPFE) is a rare lung disease. It can be idiopathic or associated with any one of various conditions. To our knowledge, this is the first report of two cases of PPFE in Brazil. Our first patient presented with pleural and subpleural fibrosis in the upper lobes; a spiculated nodule in the left upper lobe; and a mild reticular pattern in the lower lobes. Surgical lung biopsy revealed PPFE in the upper lobes, including the nodule, and unclassified interstitial pneumonia in the left lower lobe. Our second patient had a history of exposure to domestic birds, indicating a risk of hypersensitivity pneumonitis, and presented with advanced lung disease, predominantly in the upper lobes, together with subpleural fibrosis.That patient underwent lung transplantation. In the explant specimen, PPFE and granulomas were identified, suggesting hypersensitivity pneumonitis as an associated cause.

RESUMO A fibroelastose pleuroparenquimatosa (FEPP) é uma doença pulmonar rara, podendo ser idiopática ou associada a diversas condições. Pelo que sabemos, este é o primeiro relato de dois casos de FEPP no Brasil. Nosso primeiro paciente apresentava fibrose pleural e subpleural nos lobos superiores, um nódulo espiculado no lobo superior esquerdo e um padrão reticular discreto nos lobos inferiores. A biópsia pulmonar cirúrgica demonstrou FEPP nos lobos superiores, incluindo no nódulo, e pneumonia intersticial não classificada no lobo inferior esquerdo. Nosso segundo paciente tinha história de exposição a aves domésticas, indicando um risco de pneumonite de hipersensibilidade, e doença pulmonar avançada predominando em lobos superiores, com fibrose subpleural. Esse paciente foi submetido a transplante pulmonar. No espécime do explante, FEPP e granulomas foram identificados, sugerindo pneumonite de hipersensibilidade como causa associada.

Perfil clínico radiológico de 18 pacientes con síndrome antisintetasas atendidos en Policlínico de Pulmón Reumatológico, Instituto Nacional del Tórax / Clinic and radiologic profile of 18 patients with antisynthetase syndrome, treated in a Rheumatologic Lung Disease Clinic, Instituto Nacional del Torax

Connective Tissue Diseases (CTD) can manifest as Interstitial lung disease (ILD). ILD is a common manifestation of Anti-synthetase syndrome (AS). The main pattern of ILD in AS is nonspecific interstitial pneumonia (NSIP) with or without elements of organizing pneumonia (OP). Other less common forms include usual interstitial pneumonia (UIP) and nonspecific forms. Objectives: Describe radiological and clinical profile of 18 patients with ILD due to AS, evaluated in Instituto Nacional del Torax (INT) between 2013 and 2015. Highlighting the importance of Myositis Panel in patients being evaluated for ILD. Methods: Review of clinical records and lung CT of 76 patients with ILD and suspected AS, seen at INT between august 2013 and July 2015. Results: The diagnosis of AS was made in 18 of 76 patients, with female predominance and mean age of 46.5 years . In most patients the diagnosis of AS and ILD was simultaneous. The most frequent AS antibody was Jo-1, followed by PL-12. Less than half had ANA (+). The predominant radiographic pattern was NSIP / OP. Half of the patients had myositis. Conclusions: AS should be suspected in patients under study for ILD, especially NSIP / OP, and may occur without myositis and with negative ANA. It is essential to have new immunological tests such as a Myositis Panel, which will allow us to diagnose AS with subtle clinical features and negative or inconclusive serology...

Las Enfermedades del tejido conectivo (ETC) se pueden manifestar como Enfermedad Pulmonar Difusa (EPD). El Síndrome Antisintetasas (SAS) con mucha frecuencia presenta EPD. La forma de expresión más frecuente en SAS es la neumonía intersticial no específica (NSIP) con o sin elementos de neumonía en organización (OP). Otras formas menos frecuentes son la neumonía intersticial usual (UIP) y formas inespecíficas. Objetivos: Describir el perfil clínico radiológico de 18 pacientes con EPD secundaria a SAS, atendidos en el Instituto Nacional del Tórax (INT) entre los años 2013 y 2015. Destacar la importancia del Panel de Miositis en pacientes con EPD en estudio. Métodos: Revisión de ficha clínica y TAC pulmonar de 76 pacientes con EPD y sospecha de SAS, atendidos en INT entre agosto 2013 y julio 2015. Resultados: En 18 de 76 pacientes se hizo el diagnóstico de SAS, predominio femenino, edad promedio 46,5 años. En la mayoría el diagnóstico reumatológico y pulmonar fue simultáneo, el anticuerpo antisintetasa más frecuente fue Jo-1, seguido de PL 12. Menos de la mitad tuvo ANA (+). El patrón radiológico predominante fue NSIP/OP. La mitad de los pacientes no presentaron miositis. Conclusiones: El SAS debe ser sospechado en el estudio de pacientes con EPD, especialmente NSIP/OP y se puede presentar sin miositis y ANA (-). Es indispensable contar con nuevos exámenes inmunológicos como el Panel de Miositis, que permite diagnosticar SAS con clínica sutil y serología habitual negativa o no concluyente...

A Study on Pulmonary Complications of Systemic Sclerosis in Eastern India.

Aim. This study was undertaken to find out the characteristics of clinical, radiological and functional changes affecting the respiratory system in patients with systemic sclerosis (SSc) from eastern India, and the association of these characteristics with pulmonary hypertension. Methods. This was a cross-sectional, observational study involving 46 patients. Other than the routine tests, anti-nuclear antibody (ANA), spirometry, diffusing capacity of lung for carbon monoxide (DLCO) measurement, chest radiograph, highresolution computed tomography (HRCT) of thorax, 6-minute walk test and echocardiography were done. Results. Out of a total of 46 patients, 27 patients had diffuse cutaneous SSc (dcSSc) and 19 had limited cuteaneous SSc (lcSSc). Eleven patients had pulmonary hypertension. The HRCT revealed diffuse parenchymal lung disease (DPLD) in 32 (65%) cases. The ANA was positive in 83% cases. Anti-Scl70 was found in 41% of patients with dcSSc and anti-centromere antibody was found in 47% of patients with lcSSc. Spirometry revealed restrictive pattern in 30 patients; 9 had obstruction; and the rest were normal. The DLCO was abnormal in 38 patients. A strong correlation was found between reduction in DLCO and pulmonary artery systolic pressure (PASP). Also, a strong association was observed between a drop of >4% in oxygen saturation on 6-minute walk test and presence of pulmonary arterial hypertension (PAH). Conclusions. Majority of the patients with SSc had restrictive lung disease with abnormal DLCO and features resembling non-specific interstitial pneumonia. Nucleolar ANA was predominantly found in patients having PAH. Presence of DPLD had a negative association with presence of anti-centromere antibody. Reduction in DLCO and a fall of >4% in oxygen saturation on 6-minute walk test may be used as predictors of PAH in asymptomatic individuals.

Rheumatoid arthritis associated interstitial lung disease: a review / La artritis reumatoide asociada a la enfermedad intersticial pulmonar: una revisión

Rheumatoid arthritis is a common inflammatory disease affecting about 1% of the population. Interstitial lung disease is a serious and frequent complication of rheumatoid arthritis. Rheumatoid arthritis associated interstitial lung disease (RA-ILD) is characterized by several histopathologic subtypes. This article reviews the proposed pathogenesis and risk factors for RA-ILD. We also outline the important steps involved in the work-up of RA-ILD and review the evidence for treatment and prognosis.

La artritis reumatoide es una enfermedad inflamatoria común, que afecta cerca del 1% de la población. La enfermedad pulmonar intersticial es una complicación frecuente y seria de la artritis reumatoide y esta asociación está caracterizada por diferentes subtipos histológicos. Este artículo analiza la patogénesis y los factores de riesgo de esta asociación. Además señala los esfuerzos realizados y las evidencias para el diagnóstico y tratamiento.

Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

Because histopathological changes in the lungs of patients with systemic sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI-1) synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS) and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS) related significantly to staining of septal cells for interleukin (IL)-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc-NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04), septal IL-13 (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.

Pneumonia intersticial associada à esclerose sistêmica: avaliação da função pulmonar no período de cinco anos / Systemic sclerosis-associated interstitial pneumonia: evaluation of pulmonary function over a five-year period

OBJETIVO: Avaliar as alterações da função pulmonar em portadores de pneumonia intersticial associada à esclerose sistêmica no intervalo de cinco anos. MÉTODOS: Foi realizado um estudo longitudinal no qual foram avaliados 35 pacientes não tabagistas com esclerose sistêmica e sem história de doença pulmonar prévia. Na primeira avaliação, realizada na época do diagnóstico da pneumonia intersticial, os pacientes foram submetidos à TCAR, espirometria e medida de DLCO. Os pacientes foram subdivididos em dois grupos de acordo com a presença ou não de faveolamento na TCAR. Aproximadamente cinco anos após a primeira avaliação, os pacientes foram submetidos a espirometria e medida da DLCO apenas. RESULTADOS: Dos 35 pacientes, 34 eram mulheres, com média de idade de 47,6 anos. A média de tempo entre as duas avaliações foi de 60,9 meses. O faveolamento foi demonstrado por TCAR em 17 pacientes. Na amostra total, após cinco anos do diagnóstico, CVF, VEF1 e DLCO reduziram significativamente (81,3 ± 18,2 por cento vs. 72,1 ± 22,2 por cento; 79,9 ± 17,8 por cento vs. 72,5 ± 20,6 por cento; e 74,0 ± 20,5 por cento vs. 60,7 ± 26,8 por cento, respectivamente; p = 0.0001 para todos), enquanto a relação VEF1/CVF aumentou significativamente (98,5 ± 7,2 por cento vs. 101,9 ± 7,8 por cento; p = 0,008). No mesmo período, os valores de CVF, VEF1 e DLCO foram significativamente menores nos pacientes com faveolamento do que naqueles sem faveolamento na TCAR (p = 0,0001). CONCLUSÕES: Na esclerose sistêmica com doença pulmonar intersticial associada, a detecção de faveolamento na TCAR é determinante para predizer uma deterioração acelerada da função pulmonar.

OBJECTIVE: To evaluate alterations in pulmonary function in patients with systemic sclerosis-associated interstitial pneumonia over a five-year period. METHODS: This was a longitudinal study involving 35 nonsmoking patients with systemic sclerosis and without a history of lung disease. At the first evaluation, performed at the time of the diagnosis of interstitial pneumonia, the patients were submitted to HRCT, spirometry, and measurement of DLCO. The patients were subdivided into two groups by the presence or absence of honeycombing on the HRCT scans. Approximately five years after the first evaluation, the patients were submitted to spirometry and measurement of DLCO only. RESULTS: Of the 35 patients, 34 were women. The mean age was 47.6 years. The mean time between the two evaluations was 60.9 months. Honeycombing was detected on the HRCT scans in 17 patients. In the sample as a whole, five years after the diagnosis, FVC, FEV1 and DLCO significantly decreased (81.3 ± 18.2 percent vs. 72.1 ± 22.2 percent; 79.9 ± 17.8 percent vs. 72.5 ± 20.6 percent; and 74.0 ± 20.5 percent vs. 60.7 ± 26.8 percent, respectively; p = 0.0001 for all), and the FEV1/FVC ratio significantly increased (98.5 ± 7.2 percent vs. 101.9 ± 7.8 percent; p = 0.008). In the same period, FVC, FEV1, and DLCO values were significantly lower in the patients with honeycombing on the HRCT scans than in those without (p = 0.0001). CONCLUSIONS: In systemic sclerosis-associated interstitial lung disease, the detection of honeycombing on HRCT is crucial to predicting accelerated worsening of pulmonary function.

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...

An Adult Case of Chronic Active Epstein-Barr Virus Infection with Interstitial Pneumonitis

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment.

Sono e doenças pulmonares crônicas: pneumopatias intersticiais difusas, asma brônquica e DPOC / Sleep and chronic lung diseases: diffuse interstitial lung diseases, bronchial asthma, and COPD

As doenças pulmonares crônicas podem ser agravadas por inúmeros fatores e comorbidades, inclusive pelos distúrbios respiratórios do sono. Embora alterações na qualidade de vida de pacientes com doenças pulmonares crônicas sejam normalmente determinadas a partir de variáveis diurnas, as alterações fisiopatológicas no sono pioram a qualidade de sono e interferem na história natural dessas doenças. Alterações da arquitetura do sono parecem ser um mecanismo comum entre essas doenças. Durante o sono, as vias respiratórias inferiores estão mais interligadas às vias respiratórias superiores, quando as alterações de resistências das vias aéreas superiores durante o sono somam-se às graves alterações resistivas de vias aéreas inferiores devido a asma e DPOC. Além disso, surgem complexas interações mecânicas e ventilatórias. O reconhecimento dessas interações possibilita uma melhor avaliação das exacerbações e da evolução dessas doenças.

Chronic lung diseases can be aggravated by various factors and comorbidities, including sleep-disordered breathing. Although changes in the quality of life of patients with chronic lung disease are usually related to daytime variables, the physiological changes in sleep impair the quality of sleep and interfere with the natural history of the disease. Alterations in sleep architecture appear to be a common mechanism in these diseases. During sleep, the upper and lower airways are more interconnected: changes in upper airway resistance during sleep are added to the severe resistive alterations in the lower airways due to asthma and COPD. In addition, there are complex mechanical and ventilatory interactions. The recognition of these interactions allows better assessment of the exacerbations and the progression of chronic lung diseases.

Compromiso intersticial pulmonar en la artritis reumatoidea / Intersticial lung disease in rheumatoid arthritis

Objetivos: Detectar en pacientes con Artritis Reumatoidea (RA) la presencia de enfermedad pulmonar intersticial asociada (RA-ILD), analizando los factores de riesgo reportados por la literatura y sus repercusiones clínico-funcionales. Material y métodos: Se estudiaron prospectivamente pacientes con el diagnóstico de RA buscando la presencia de RA-ILD por Tomografía Computada de Alta Resolución (TACAR).Se realizó en los mismos evaluación neumonológica y reumatológica, estudiosfuncionales respiratorios y se indagaron los factores de riesgo que se consideran asociados al desarrollo de RA-ILD. Se compararon los grupos con o sin ILD asociada. Resultados: Se reclutaron treinta y seis pacientes de los cuales en 11 se detectó compromiso intersticial (30.5%). Ni los síntomas respiratorios ni los factores de riesgo asociadosmostraron presencia significativa en el grupo con ILD. El grupo con RA-ILD mostró alteraciones funcionales significativas respecto al grupo sin ILD en la Difusión de CO (DLCO) y en la caída de Saturación de O2 (Sat. O2) en el test de marcha de 6 minutos (6MWT). Tres de los once pacientes con ILD (27%) no tuvieron alteraciones clínicas ni funcionales. Discusión: La RA-ILD detectada por TACAR no se asoció significativamente a ninguno de los factores de riesgo reportados. En concordancia con lo descripto en la literatura, vemos que el espectro de nuestro grupo de pacientes con RA-ILD detectada por TACAR puede ir desde serias manifestaciones respiratorias que aumentan la morbimortalidad de la RA hasta aquellos sin manifestaciones clínico-funcionales (RA-LD “preclínica”).El significado y la evolución de este último grupo no se conoce.

Objectives: To determine in patients with rheumatoid arthritis (RA) the prevalence of associated interstitial lung disease (RA-ILD), its risk factors and clinical-functional manifestations.Materials and methods: Patients with diagnosis of RA were prospectively studied searching for interstitial involvement on high resolution computerized tomography (HRCT). The research methods included pulmonary and rheumatoid evaluations, pulmonaryfunction tests and identification of risk factors considered to be associated to the development of ILD. Groups of RA patients with and without ILD were compared. Results: Among 36 RA patients included in the study, pulmonary interstitial involvementwas detected in 11 (30.5%). Neither respiratory symptoms nor risk factors had a significant presence in the group of patients with ILD in comparison with the group of patients without ILD. However, the RA-ILD group showed significant functional alterations, as evidenced in the test of diffusing capacity of the lung for carbon monoxide (DLCO) and the drop of the oxygen saturation in the 6 minute walk test. Three of the 11 RA-ILD patients (27%) did not have clinical or functional alterations. Discussion: RA-ILD detected on HRCT was not significantly associated to any of the risk factors reported. In agreement with the published literature, the clinical spectrum of the group of patients with RA-ILD involvement on HRCT varied from serious respiratory manifestations that increase RA morbidity and mortality to lack of clinical and functionalmanifestations (“preclinical” RA-ILD). The significance and prognosis of ILD involvement in this last group is unknown.

Doença pulmonar por metal duro em trabalhador da indústria petrolífera / Hard metal lung disease in an oil industry worker

A doença pulmonar por metal duro é uma pneumonia intersticial por células gigantes relacionada com a exposição à poeira composta por metais duros. Neste artigo é relatado o caso de um profissional da indústria petrolífera, diagnosticado com doença pulmonar por metal duro com base na documentação clínica, radiológica, funcional pulmonar e anatomopatológica.

Hard metal lung disease, which manifests as giant cell interstitial pneumonia, is caused by exposure to hard metal dust. We report the case of an oil industry worker diagnosed with hard metal lung disease. The diagnosis was based on the clinical, radiological and anatomopathological analysis, as well as on pulmonary function testing.

Pulmonary manifestations in connective tissue disorders: Hospital-based study at a Tertiary Care Hospital.

Background. The pleuro-pulmonary manifestations frequently occur in patients with the connective tissue disorders (CTDs), and limited data are available on this topic from India. Methods. Between January 2002 and December 2006, 195 patients with various CTDs having respiratory symptoms were evaluated for respiratory system involvement. Results. Interstitial lung disease (ILD) was the commonest (38.5%) presentation of CTDs. It was observed in nearly threefourth of the cases with scleroderma followed by rheumatoid arthritis (RA) cases (44.5%). Pulmonary arterial hypertension was observed in 53.8% and 60% of cases with scleroderma and mixed connective tissue disorder (MCTD), respectively. In RA and systemic lupus erythematosus (SLE), pulmonary hypertension was a rare presentation. Pulmonary function tests were abnormal in all the patients with MCTD, 89.9% patients with RA, 84.6% patients with scleroderma and nearly one-third patients with SLE. Restrictive defect was the most common abnormality [RA (88.7%), scleroderma (72.7%), SLE (66%)]. High resolution computed tomography revealed reticulonodular lesions (n=78); pleural effusion (n=15, mainly in patients with RA and SLE); honeycomb appearance (n=14; mainly in patients with RA and scleroderma); and bronchiectasis (n=9, mainly in patients with RA). Conclusions. Pulmonary manifestations are common in patients with CTDs, ILD being the most common pulmonary involvement. All patients with CTDs should be systematically evaluated and monitored for pulmonary involvement.