Evaluation of the extent of pulmonary cysts and their association with functional variables and serum markers in lymphangioleiomyomatosis (LAM).

PURPOSE: Although computed tomography (CT) has been used previously to assess disease severity in lymphangioleiomyomatosis (LAM), the associations between the extent of pulmonary cysts on CT and six-minute walk test (6MWT), matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF-D) are not well established. We performed a cross-sectional study to quantify the extent of pulmonary cysts in CT and to establish their correlations with pulmonary function tests (PFTs), 6MWT results, including a composite index (desaturation-distance ratio, DDR), and levels of VEGF-D and MMPs in LAM. METHODS: Twenty-three LAM patients underwent CT scanning to automatically quantify the extent of pulmonary cysts and performed PFTs and 6MWT. Serum levels of MMP-2, MMP-9, and VEGF-D were also measured. RESULTS: The severity of pulmonary cystic involvement was mild (the extent of cysts was 6.8 %) and correlated best with FEV1/FVC (r = -0.84), residual volume (r = 0.66), DLCO (r = -0.82), the DDR index (r = 0.77), and desaturation during the 6MWT (r = -0.81). There was a weak correlation with VEGF-D (r = 0.45), but no association was found with MMP-2 and MMP-9. CONCLUSIONS: The severity of pulmonary cystic involvement was mild in this sample of LAM patients and correlated best with airway obstruction, air trapping, reduced DLCO, the DDR index, and desaturation during the 6MWT. Serum VEGF-D cannot be completely defined as a valuable marker of disease severity and there may be a mechanism independent of MMPs to explain the formation of pulmonary cysts.

Pulmonary involvement in rheumatoid arthritis: evaluation by radiography and spirometry.

OBJECTIVE: To determine whether simple diagnostic methods can yield relevant disease information in patients with rheumatoid arthritis (RA). METHODS: Patients with RA were randomly selected for inclusion in a cross-sectional study involving clinical evaluation of pulmonary function, including pulse oximetry (determination of SpO2, at rest), chest X-ray, and spirometry. RESULTS: A total of 246 RA patients underwent complete assessments. Half of the patients in our sample reported a history of smoking. Spirometry was abnormal in 30% of the patients; the chest X-ray was abnormal in 45%; and the SpO2 was abnormal in 13%. Normal chest X-ray, spirometry, and SpO2 were observed simultaneously in only 41% of the RA patients. A history of smoking was associated with abnormal spirometry findings, including evidence of obstructive or restrictive lung disease, and with abnormal chest X-ray findings, as well as with an interstitial pattern on the chest X-ray. Comparing the patients in whom all test results were normal (n = 101) with those in whom abnormal test results were obtained (n = 145), we found a statistically significant difference between the two groups, in terms of age and smoking status. Notably, there were signs of airway disease in nearly half of the patients with minimal or no history of tobacco smoke exposure. CONCLUSIONS: Pulmonary involvement in RA can be identified through the use of a combination of diagnostic methods that are simple, safe, and inexpensive. Our results lead us to suggest that RA patients with signs of lung involvement should be screened for lung abnormalities, even if presenting with no respiratory symptoms.

Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features.

OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD). METHODS: This was a retrospective study of patients with interstitial lung disease (ILD), positive antinuclear antibody (ANA) results (≥ 1/320), with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD). RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89%) and anti-SSA (anti-Ro, 27%). The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05). Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis.

The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs). There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD.

Clinical course and characterisation of lymphangioleiomyomatosis in a Brazilian reference centre.

BACKGROUND AND OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare disease that promotes pulmonary cystic destruction and impairs pulmonary function. We aim to describe features and clinical course of LAM patients from Brazil. METHODS: We described the clinical and functional features, performance in six minute walk test (6MWT), management details, survival and clinical course of 84 LAM patients followed in a Brazilian reference centre. RESULTS: All subjects were women, the average age at onset of symptoms was 38 years, and the average at diagnosis was 42 years. The major symptoms during the course of the disease were dyspnoea and pneumothorax. The patients experienced impaired quality of life, with worse scores in the physical and emotional domains. The most common abnormalities in pulmonary function tests were an obstructive pattern and reduced diffusion capacity, whereas a quarter of the patients had normal spirometric results. In the 6MWT, although patients had preserved exercise capacity, more than half of the patients had significant desaturation. Hormonal blockage and doxycycline were the most common treatment modalities employed in our patients. The survival probability from diagnosis was 90% at 5 years, whereas the mean annual rate of decline in FEV1 was 60 ± 78 mL. CONCLUSIONS: Clinical and functional features of the LAM patients from our centre are similar to those from other countries. Our sample showed preserved exercise capacity, with desaturation in the 6MWT, and impaired quality of life. Survival was similar, whereas the annual rate of decline of FEV1 was slightly lower than in recent studies.

Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease.

The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease.

Pulmonary involvement in rheumatoid arthritis: evaluation by radiography and spirometry / Doença pulmonar em pacientes com artrite reumatoide: avaliação radiográfica e espirométrica

AbstractObjective: To determine whether simple diagnostic methods can yield relevant disease information in patients with rheumatoid arthritis (RA).Methods: Patients with RA were randomly selected for inclusion in a cross-sectional study involving clinical evaluation of pulmonary function, including pulse oximetry (determination of SpO2, at rest), chest X-ray, and spirometry.Results: A total of 246 RA patients underwent complete assessments. Half of the patients in our sample reported a history of smoking. Spirometry was abnormal in 30% of the patients; the chest X-ray was abnormal in 45%; and the SpO2 was abnormal in 13%. Normal chest X-ray, spirometry, and SpO2 were observed simultaneously in only 41% of the RA patients. A history of smoking was associated with abnormal spirometry findings, including evidence of obstructive or restrictive lung disease, and with abnormal chest X-ray findings, as well as with an interstitial pattern on the chest X-ray. Comparing the patients in whom all test results were normal (n = 101) with those in whom abnormal test results were obtained (n = 145), we found a statistically significant difference between the two groups, in terms of age and smoking status. Notably, there were signs of airway disease in nearly half of the patients with minimal or no history of tobacco smoke exposure.Conclusions: Pulmonary involvement in RA can be identified through the use of a combination of diagnostic methods that are simple, safe, and inexpensive. Our results lead us to suggest that RA patients with signs of lung involvement should be screened for lung abnormalities, even if presenting with no respiratory symptoms.

ResumoObjetivo: Determinar se métodos diagnósticos de baixa complexidade podem fornecer informações relevantes sobre doença pulmonar em pacientes com artrite reumatoide (AR).Métodos: Pacientes com AR foram selecionados aleatoriamente para um estudo transversal envolvendo avaliação clínica pulmonar, oximetria de pulso (SpO2) em repouso, radiografia de tórax e espirometria.Resultados: Um total de 246 pacientes foi submetido à avaliação completa. Metade dos pacientes na amostra relatou história de tabagismo. A proporção de pacientes com resultados anormais na espirometria, radiografia de tórax e SpO2 foi de, respectivamente, 30%, 45% e 13%. Resultados normais em radiografia de tórax, espirometria e SpO2 foram observados simultaneamente em apenas 41% dos pacientes com AR. História de tabagismo foi associada a achados espirométricos anormais, de doença pulmonar obstrutiva e de doença pulmonar restritiva, assim como radiografia de tórax anormal e com padrão intersticial. Na comparação dos pacientes com exames normais (n = 101) com aqueles com exames com alguma alteração (n = 145), houve uma diferença estatisticamente significante entre os dois grupos em relação a idade e história de tabagismo. Interessantemente, sinais de doença de vias aéreas foram observados em quase metade dos pacientes com relato de baixa exposição ao tabagismo ou de nunca ter sido fumante.Conclusões: O comprometimento pulmonar na AR pode ser identificado através de uma combinação de métodos diagnósticos simples, seguros e de baixo custo. Nossos resultados sugerem que pacientes com AR e sinais de acometimento pulmonar devem ser avaliados quanto a possíveis anormalidades pulmonares, mesmo na ausência de sintomas respiratórios.

Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features / Colagenose pulmão dominante em pacientes com doença pulmonar intersticial: prevalência, estabilidade funcional e manifestações extratorácicas comuns

OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD). METHODS: This was a retrospective study of patients with interstitial lung disease (ILD), positive antinuclear antibody (ANA) results (≥ 1/320), with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD). RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89%) and anti-SSA (anti-Ro, 27%). The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05). Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria. .

OBJETIVO: Descrever as características de uma coorte de pacientes com colagenose pulmão dominante (CPD). MÉTODOS: Estudo retrospectivo de pacientes com doença pulmonar intersticial (DPI), anticorpo antinuclear (ANA) positivo (≥ 1/320), com ou sem autoanticorpos específicos, e com a presença de ao menos uma manifestação clínica sugestiva de doença do tecido conjuntivo (DTC). RESULTADOS: Dos 1.998 avaliados, 52 preencheram inicialmente os critérios para o diagnóstico de CPD: 37% eram homens; a média de idade ao diagnóstico era de 56 anos e a mediana do tempo de seguimento era de 48 meses. Durante o seguimento, 8 pacientes preencheram os critérios para um diagnóstico definitivo de DTC. Os 44 pacientes restantes formaram o grupo CPD, no qual as manifestações extratorácicas mais prevalentes foram artralgia, doença do refluxo gastroesofágico e fenômeno de Raynaud. Os autoanticorpos mais prevalentes nesse grupo foram ANA (89%) e anti-SSA (anti-Ro, 27%). A média de CVF no início e na última avaliação foi de 69,5% e 74,0% do predito, respectivamente (p > 0,05). Pneumonia intersticial não específica e pneumonia intersticial usual foram identificadas em 45% e 9% das TCARs, respectivamente; 36% das TCARs eram não classificáveis. Uma prevalência semelhante foi identificada na histologia. Dilatação esofágica difusa foi identificada em 52% das TCARs. Capilaroscopia subungueal foi realizada em 22 pacientes; 17 apresentavam um padrão de esclerodermia. CONCLUSÕES: No grupo CPD, houve predominância feminina, e os pacientes apresentaram alterações espirométricas leves ao diagnóstico, com diferentes padrões de DPI, em sua maioria não classificáveis, tanto em TCAR como na histologia. Estabilidade funcional foi identificada no seguimento. A dilatação esofágica em TCAR e o padrão de esclerodermia na capilaroscopia subungueal foram achados frequentes que poderiam servir como critérios diagnósticos. .

Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis / Doença pulmonar intersticial aguda induzida por adalimumabe em paciente com artrite reumatoide

The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs). There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD.

O uso de imunobiológicos no tratamento das doenças autoimunes é cada vez mais frequente na prática médica. Terapias anti-TNF têm sido cada vez mais utilizadas nas doenças autoimunes refratárias, especialmente na artrite reumatoide, com resultados promissores. Entretanto, o uso dessas terapias está relacionado ao aumento do risco do desenvolvimento de outras doenças autoimunes. Adicionalmente, o uso de agentes anti-TNF pode determinar repercussões pulmonares, como a reativação de infecções por micobactérias e fungos e o desenvolvimento de sarcoidose e de outras doenças pulmonares intersticiais (DPIs). A associação de DPI e uso dos agentes anti-TNF, em especial infliximabe e etanercepte, já foi descrita. O adalimumabe é a mais nova droga dessa classe, e algumas publicações sugerem que seu uso pode determinar a indução ou mesmo a exacerbação de DPIs preexistentes. Neste estudo, relatamos o primeiro caso de DPI aguda secundária à utilização de adalimumabe, em uma paciente portadora de artrite reumatoide sem DPI prévia no Brasil.

Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease / Interpretacao da positividade de autoanticorpos na doenca pulmonar intersticial e colagenose pulmao dominante

The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease.

A avaliação inicial de pacientes com doença pulmonar intersticial (DPI) envolve primordialmente a busca ativa e detalhada por uma etiologia. A pesquisa rotineira de autoanticorpos é comum em diferentes centros e permite sugerir a presença de alguma doença do espectro reumatológico. Quando o acometimento pulmonar intersticial é a condição que permite o diagnóstico firmado de uma colagenose bem estabelecida, preenchendo os critérios clássicos, há pouco debate. Entretanto, ainda existe muita discussão sobre o significado, a relevância, a especificidade e o papel fisiopatológico da autoimunidade nos pacientes que tenham prioritariamente acometimento respiratório e apenas algum indício leve ou frustro de colagenose. O propósito dessa revisão foi apresentar o conhecimento atual e discutir possibilidades de interpretação da positividade de autoanticorpos em pacientes com DPI que não tenham associações etiológicas inequívocas, assim como aumentar o entendimento da história natural de uma possível nova doença e descrever possíveis implicações prognósticas. Discutimos ainda a proposição de uma nova terminologia na classificação das DPIs, a colagenose pulmão dominante.