Connective tissue disease-associated interstitial lung disease.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren's syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD.

Relative incidence of interstitial lung diseases in Brazil.

OBJECTIVE: To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. METHODS: This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. RESULTS: The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). CONCLUSIONS: Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

Relative incidence of interstitial lung diseases in Brazil / Incidência relativa de doenças pulmonares intersticiais no Brasil

ABSTRACT Objective: To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. Methods: This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. Results: The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). Conclusions: Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

RESUMO Objetivo: Avaliar a frequência relativa de casos incidentes de doenças pulmonares intersticiais (DPI) no Brasil. Métodos: Levantamento retrospectivo de casos novos de DPI em seis centros de referência entre janeiro de 2013 e janeiro de 2020. O diagnóstico de DPI seguiu os critérios sugeridos por órgãos internacionais ou foi feito por meio de discussão multidisciplinar (DMD). A condição foi caracterizada como DPI não classificável quando não houve um diagnóstico final específico após a DMD ou houve discordância entre dados clínicos, radiológicos ou histológicos. Resultados: A amostra foi composta por 1.406 pacientes (média de idade = 61 ± 14 anos), sendo 764 (54%) do sexo feminino. Dos 747 casos expostos a antígenos para pneumonite de hipersensibilidade (PH), 327 (44%) tiveram diagnóstico final de PH. Houve relato de história familiar de DPI em 8% dos casos. Os achados de TCAR foram indicativos de fibrose em 74% dos casos, incluindo faveolamento, em 21%. Autoanticorpos relevantes foram detectados em 33% dos casos. Biópsia transbrônquica foi realizada em 23% dos pacientes, e biópsia pulmonar cirúrgica, em 17%. Os diagnósticos finais foram: DPI associada à doença do tecido conjuntivo (em 27%), PH (em 23%), fibrose pulmonar idiopática (em 14%), DPI não classificável (em 10%) e sarcoidose (em 6%). Os diagnósticos variaram significativamente entre os centros (c2 = 312,4; p < 0,001). Conclusões: Nossos achados mostram que DPI associada à doença do tecido conjuntivo é a DPI mais comum no Brasil, seguida pela PH. Esses resultados destacam a necessidade de uma estreita colaboração entre pneumologistas e reumatologistas, a importância de fazer perguntas detalhadas aos pacientes a respeito da potencial exposição a antígenos e a necessidade de campanhas de saúde pública destinadas a enfatizar a importância de evitar essa exposição.

Connective tissue disease-associated interstitial lung disease / Doença pulmonar intersticial associada a doença do tecido conjuntivo

ABSTRACT Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren's syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD.

RESUMO Doença pulmonar intersticial associada à doença do tecido conjuntivo (DPI-DTC) representa um grupo de distúrbios autoimunes sistêmicos caracterizados por disfunção de órgãos imunomediada. Esclerose sistêmica, artrite reumatoide, miosite inflamatória idiopática e síndrome de Sjögren são as DTC mais comuns que apresentam acometimento pulmonar, bem como pneumonia intersticial com achados autoimunes. A frequência de DPI-DTC varia de acordo com o tipo de DTC, mas a incidência total é de 15%, causando um impacto importante na morbidade e mortalidade. A decisão sobre qual paciente com DTC deve ser investigado para DPI não é clara para muitas DTC. Além disso, o espectro clínico pode variar desde achados assintomáticos em exames de imagem até insuficiência respiratória e morte. Parte significativa dos pacientes apresentará doença mais grave e progressiva, e, para esses pacientes, imunossupressão com corticosteroides e medicamentos citotóxicos são a base do tratamento farmacológico. Nesta revisão, resumimos a abordagem do diagnóstico e tratamento de DPI-DTC, destacando os recentes avanços na terapêutica para as diversas formas de DTC.

Sleep parameters in patients with chronic hypersensitivity pneumonitis: a case-control study.

OBJECTIVE: To compare patients with chronic hypersensitivity pneumonitis (cHP) and controls with normal spirometry in terms of their sleep characteristics, as well as to establish the prevalence of obstructive sleep apnea (OSA) and nocturnal hypoxemia. Secondary objectives were to identify factors associated with OSA and nocturnal hypoxemia; to correlate nocturnal hypoxemia with the apnea-hypopnea index (AHI) and lung function, as well as with resting SpO2, awake SpO2, and SpO2 during exercise; and to evaluate the discriminatory power of sleep questionnaires to predict OSA. METHODS: A total of 40 patients with cHP (cases) were matched for sex, age, and BMI with 80 controls, the ratio of controls to cases therefore being = 2:1. The STOP-Bang questionnaire, the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index, the Berlin questionnaire and the Neck circumference, obesity, Snoring, Age, and Sex (NoSAS) score were applied to all cases, and both groups underwent full-night polysomnography. RESULTS: The patients with cHP had longer sleep latency, lower sleep efficiency, a lower AHI, a lower respiratory disturbance index, fewer central apneas, fewer mixed apneas, and fewer hypopneas than did the controls. The patients with cHP had significantly lower nocturnal SpO2 values, the percentage of total sleep time spent below an SpO2 of 90% being higher than in controls (median = 4.2; IQR, 0.4-32.1 vs. median = 1.0; IQR, 0.1-5.8; p = 0.01). There were no significant differences between cases with and without OSA regarding the STOP-Bang questionnaire, NoSAS, and ESS scores. CONCLUSIONS: The prevalence of OSA in cHP patients (cases) was high, although not higher than that in controls with normal spirometry. In addition, cases had more hypoxemia during sleep than did controls. Our results suggest that sleep questionnaires do not have sufficient discriminatory power to identify OSA in cHP patients.

Sleep parameters in patients with chronic hypersensitivity pneumonitis: a case-control study / Parâmetros do sono em pacientes com pneumonite de hipersensibilidade crônica: estudo de caso-controle

ABSTRACT Objective: To compare patients with chronic hypersensitivity pneumonitis (cHP) and controls with normal spirometry in terms of their sleep characteristics, as well as to establish the prevalence of obstructive sleep apnea (OSA) and nocturnal hypoxemia. Secondary objectives were to identify factors associated with OSA and nocturnal hypoxemia; to correlate nocturnal hypoxemia with the apnea-hypopnea index (AHI) and lung function, as well as with resting SpO2, awake SpO2, and SpO2 during exercise; and to evaluate the discriminatory power of sleep questionnaires to predict OSA. Methods: A total of 40 patients with cHP (cases) were matched for sex, age, and BMI with 80 controls, the ratio of controls to cases therefore being = 2:1. The STOP-Bang questionnaire, the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index, the Berlin questionnaire and the Neck circumference, obesity, Snoring, Age, and Sex (NoSAS) score were applied to all cases, and both groups underwent full-night polysomnography. Results: The patients with cHP had longer sleep latency, lower sleep efficiency, a lower AHI, a lower respiratory disturbance index, fewer central apneas, fewer mixed apneas, and fewer hypopneas than did the controls. The patients with cHP had significantly lower nocturnal SpO2 values, the percentage of total sleep time spent below an SpO2 of 90% being higher than in controls (median = 4.2; IQR, 0.4-32.1 vs. median = 1.0; IQR, 0.1-5.8; p = 0.01). There were no significant differences between cases with and without OSA regarding the STOP-Bang questionnaire, NoSAS, and ESS scores. Conclusions: The prevalence of OSA in cHP patients (cases) was high, although not higher than that in controls with normal spirometry. In addition, cases had more hypoxemia during sleep than did controls. Our results suggest that sleep questionnaires do not have sufficient discriminatory power to identify OSA in cHP patients.

RESUMO Objetivo: Comparar pacientes com pneumonite de hipersensibilidade crônica (PHc) e controles com espirometria normal quanto às características do sono, bem como estabelecer a prevalência de apneia obstrutiva do sono (AOS) e hipoxemia noturna. Os objetivos secundários foram identificar fatores associados à AOS e hipoxemia noturna; correlacionar a hipoxemia noturna com o índice de apneias e hipopneias (IAH), função pulmonar, SpO2 em repouso, SpO2 em vigília e SpO2 durante o exercício; e avaliar o poder discriminatório de questionários do sono para predizer AOS. Métodos: Um total de 40 pacientes com PHc (casos) foram emparelhados por sexo, idade e IMC com 80 controles (2:1). O questionário STOP-Bang, a Escala de Sonolência de Epworth (ESE), o Índice de Qualidade do Sono de Pittsburgh, o questionário de Berlim e o escore Neck circumference, obesity, Snoring, Age, and Sex (NoSAS, circunferência do pescoço, obesidade, ronco, idade e sexo) foram aplicados a todos os casos, e ambos os grupos foram submetidos a polissonografia de noite inteira. Resultados: Os pacientes com PHc apresentaram maior latência do sono, menor eficiência do sono, menor IAH, menor índice de distúrbio respiratório, menos apneias centrais, menos apneias mistas e menos hipopneias do que os controles. Os pacientes com PHc apresentaram SpO2 noturna significativamente menor; a porcentagem do tempo total de sono com SpO2 < 90% foi maior que nos controles (mediana = 4,2; IIQ: 0,4-32,1 vs. mediana = 1,0; IIQ: 0,1-5,8; p = 0,01). Não houve diferenças significativas entre os casos com e sem AOS quanto à pontuação no questionário STOP-Bang, no NoSAS e na ESE. Conclusões: A prevalência de AOS em pacientes com PHc (casos) foi alta, embora não tenha sido maior que a observada em controles com espirometria normal. Além disso, os casos apresentaram mais hipoxemia durante o sono do que os controles. Nossos resultados sugerem que os questionários do sono não têm poder discriminatório suficiente para identificar AOS em pacientes com PHc.

Prognostic features of sarcoidosis course in a Brazilian cohort.

OBJECTIVE: To identify predictive features associated with the course of sarcoidosis at initial evaluation and to develop a predictive score. METHODS: This was a retrospective study involving pulmonary sarcoidosis patients, classified as having a self-limited or persistent course of disease, comparing data between the outcomes by univariate analysis. Features related to persistent disease were selected by multivariate analysis and a prognostic score was designed. RESULTS: The sample comprised 200 patients (mean age = 49 years). The median duration of symptoms to diagnosis was 12 months, and delayed diagnosis (> 12 months) was found in 43% of the cases. The most common radiological stage was II; 37% had reduced FVC. Relevant systemic involvement was detected in 37% of the patients. Treatment for tuberculosis was prescribed in 44 patients prior to sarcoidosis diagnosis. Treatment for sarcoidosis was required in 77% of the sample, and the disease course was persistent in 115 cases. Excluding 40 patients with fibrotic disease, prognostic factors to persistent disease were parenchymal involvement, delayed diagnosis, dyspnea, relevant systemic involvement, and reduced FVC. On the basis of the analysis, a 3-letter scoring system (A, B and C) was developed according to the selected factors. The positive predictive values for persistent course for A (≤ 1 point) and C scores (≥ 4 points) were 12.5% and 81.8%, respectively. CONCLUSIONS: A score can be derived by selected features at initial evaluation, allowing the prediction of outcomes in a significant number of sarcoidosis patients.

Prognostic features of sarcoidosis course in a Brazilian cohort / Características prognósticas da evolução da sarcoidose em uma coorte brasileira

ABSTRACT Objective: To identify predictive features associated with the course of sarcoidosis at initial evaluation and to develop a predictive score. Methods: This was a retrospective study involving pulmonary sarcoidosis patients, classified as having a self-limited or persistent course of disease, comparing data between the outcomes by univariate analysis. Features related to persistent disease were selected by multivariate analysis and a prognostic score was designed. Results: The sample comprised 200 patients (mean age = 49 years). The median duration of symptoms to diagnosis was 12 months, and delayed diagnosis (> 12 months) was found in 43% of the cases. The most common radiological stage was II; 37% had reduced FVC. Relevant systemic involvement was detected in 37% of the patients. Treatment for tuberculosis was prescribed in 44 patients prior to sarcoidosis diagnosis. Treatment for sarcoidosis was required in 77% of the sample, and the disease course was persistent in 115 cases. Excluding 40 patients with fibrotic disease, prognostic factors to persistent disease were parenchymal involvement, delayed diagnosis, dyspnea, relevant systemic involvement, and reduced FVC. On the basis of the analysis, a 3-letter scoring system (A, B and C) was developed according to the selected factors. The positive predictive values for persistent course for A (≤ 1 point) and C scores (≥ 4 points) were 12.5% and 81.8%, respectively. Conclusions: A score can be derived by selected features at initial evaluation, allowing the prediction of outcomes in a significant number of sarcoidosis patients.

RESUMO Objetivo: Identificar características preditivas associadas à evolução da sarcoidose na avaliação inicial e desenvolver um escore preditivo. Métodos: Estudo retrospectivo com pacientes com sarcoidose pulmonar, classificados como tendo evolução autolimitada ou persistente da doença, comparando dados entre os desfechos por meio de análise univariada. Características relacionadas à doença persistente foram selecionadas por meio de análise multivariada, e foi desenvolvido um escore prognóstico. Resultados: A amostra foi composta por 200 pacientes (média de idade = 49 anos). A mediana da duração dos sintomas até o diagnóstico foi de 12 meses, e houve diagnóstico tardio (> 12 meses) em 43% dos casos. O estádio radiológico mais frequente foi o II; 37% apresentavam redução da CVF. Envolvimento sistêmico relevante foi detectado em 37% dos pacientes. Tratamento para tuberculose foi prescrito em 44 pacientes antes do diagnóstico de sarcoidose. Tratamento para sarcoidose foi necessário em 77% da amostra, e a evolução da doença foi persistente em 115 casos. Com a exclusão de 40 pacientes com doença fibrótica, os fatores prognósticos para doença persistente foram comprometimento parenquimatoso, diagnóstico tardio, dispneia, comprometimento sistêmico relevante e redução da CVF. Com base na análise, foi desenvolvido um sistema de pontuação por letras (A, B e C) de acordo com os fatores selecionados. Os valores preditivos positivos para evolução persistente para as pontuações A (≤ 1 ponto) e C (≥ 4 pontos) foram de 12,5% e 81,8%, respectivamente. Conclusões: É possível derivar um escore por meio de características selecionadas na avaliação inicial, permitindo a predição de desfechos em um significativo número de pacientes com sarcoidose.

Carbohydrate antigen 15-3 as a marker of disease severity in patients with chronic hypersensitivity pneumonitis.

OBJECTIVE: Biomarkers associated with mucin 1, such as Krebs von den Lungen-6 and carbohydrate antigen (CA) 15-3, are increased in various interstitial lung diseases. Our aim was to determine whether CA 15-3 could be considered a biomarker of disease severity in patients with chronic hypersensitivity pneumonitis (cHP). METHODS: This was a prospective observational study involving adult patients with cHP. Serum levels of CA 15-3 were measured and were correlated with variables related to disease severity and extension. HRCT scans were quantitatively analyzed using a computational platform and an image analysis tool (Computer Aided Lung Informatics for Pathology Evaluation and Rating). CA 15-3 levels were normalized by logarithmic transformation. RESULTS: The sample comprised 41 patients. The mean age of the patients was 60.1 ± 11.6 years. The mean FVC in % of predicted was 70.3% ± 17.3%, and the median of the serum level of CA 15-3 was 48.1 U/mL. CA 15-3 levels inversely correlated with FVC in % of predicted (r = -0,30; p = 0,05), DLCO in % of predicted (r = -0,54; p < 0,01), and SpO2 at the end of a 4-min step test (r = -0,59; p < 0,01), but they directly correlated with total quantitative HRCT scores (r = 0,47; p = 0,004), especially regarding ground-glass opacities (r = 0.58; p < 0,001). CONCLUSIONS: CA 15-3 is likely to be a biomarker of disease severity of patients with cHP, particularly regarding gas exchange abnormalities.

Carbohydrate antigen 15-3 as a marker of disease severity in patients with chronic hypersensitivity pneumonitis* / Antígeno carboidrato 15-3 como marcador de gravidade da doença em pacientes com pneumonite de hipersensibilidade crônica

ABSTRACT Objective: Biomarkers associated with mucin 1, such as Krebs von den Lungen-6 and carbohydrate antigen (CA) 15-3, are increased in various interstitial lung diseases. Our aim was to determine whether CA 15-3 could be considered a biomarker of disease severity in patients with chronic hypersensitivity pneumonitis (cHP). Methods: This was a prospective observational study involving adult patients with cHP. Serum levels of CA 15-3 were measured and were correlated with variables related to disease severity and extension. HRCT scans were quantitatively analyzed using a computational platform and an image analysis tool (Computer Aided Lung Informatics for Pathology Evaluation and Rating). CA 15-3 levels were normalized by logarithmic transformation. Results: The sample comprised 41 patients. The mean age of the patients was 60.1 ± 11.6 years. The mean FVC in % of predicted was 70.3% ± 17.3%, and the median of the serum level of CA 15-3 was 48.1 U/mL. CA 15-3 levels inversely correlated with FVC in % of predicted (r = −0,30; p = 0,05), DLCO in % of predicted (r = −0,54; p < 0,01), and SpO2 at the end of a 4-min step test (r = −0,59; p < 0,01), but they directly correlated with total quantitative HRCT scores (r = 0,47; p = 0,004), especially regarding ground-glass opacities (r = 0.58; p < 0,001). Conclusions: CA 15-3 is likely to be a biomarker of disease severity of patients with cHP, particularly regarding gas exchange abnormalities.

RESUMO Objetivo: Biomarcadores associados à mucina-1, tais como Krebs von den Lungen-6 e carbohydrate antigen (CA, antígeno carboidrato) 15-3, encontram-se aumentados em diversas doenças pulmonares intersticiais. Nosso objetivo foi determinar se CA 15-3 poderia ser considerado um biomarcador de gravidade de doença em pacientes com pneumonite de hipersensibilidade crônica (PHc). Métodos: Estudo prospectivo observacional envolvendo pacientes adultos com PHc. Os níveis séricos de CA 15-3 foram medidos e correlacionados com variáveis relacionadas à gravidade e extensão da doença. As imagens de TCAR foram analisadas quantitativamente utilizando uma plataforma computacional e uma ferramenta de análise de imagem (Computer-Aided Lung Informatics for Pathology Evaluation and Rating). Os níveis de CA 15-3 foram normalizados por transformação logarítmica. Resultados: A amostra foi composta por 41 pacientes. A média de idade dos pacientes foi de 60,1 ± 11,6 anos. A média da CVF em % do previsto foi de 70,3% ± 17,3%, e a mediana do nível sérico de CA 15-3 foi de 48,1 U/mL. Os níveis de CA 15-3 se correlacionaram inversamente com CVF em % do previsto (r = −0,30; p = 0,05), DLCO em % do previsto (r = −0,54; p < 0,01) e SpO2 ao final de um teste de degrau de 4 minutos (r = −0,59; p < 0,01), mas se correlacionaram diretamente com a pontuação quantitativa total da TCAR (r = 0,47; p = 0,004), especialmente quanto a opacidades em vidro fosco (r = 0,58; p < 0,001). Conclusões: É provável que o CA 15-3 seja um biomarcador de gravidade de doença em pacientes com PHc, particularmente quanto a anormalidades nas trocas gasosas.

Nonlife-Threatening Sarcoidosis.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. The outcome is quite variable and is mainly related to persistent inflammatory processes and the development of fibrosis. Many prognostic factors have been described, but the disease evolution is not yet entirely known. The nonthreatening course is characterized by spontaneous involution or stability after treatment withdrawal. Löfgren's syndrome is a subset within the spectrum of sarcoidosis phenotypes, composed of acute onset of fever, bilateral hilar lymphadenopathy, erythema nodosum and/or bilateral ankle periarticular inflammation/arthritis, specifically characterized by a self-limiting disease course. In contrast, advanced fibrotic sarcoidosis with pulmonary hypertension phenotype is correlated with a poor prognosis. Further studies are necessary to detail phenotypes to better understand the mechanisms of the disease and plan future clinical therapeutic studies.

Reference values for the carbon monoxide diffusion (transfer factor) in a brazilian sample of white race. / Valores de referência para a difusão do monóxido de carbono (fator de transferência) em uma amostra brasileira da raça branca.

OBJECTIVE: To derive reference values from white race adults, for DCO in a sample from different sites in Brazil, through the same equipment model (Sensormedics), and compare the results with the derivatives from Crapo, Miller, Neder equations and from the Global Lung Initiative (GLI) proposal. METHODS: The tests were performed according to the norms suggested by ATS/ERS in 2005 in six Brazilian cities, with 120 adult volunteers of each gender, non-smokers, without referred anemia and without lung or cardio diseases. The expected values were derived from linear regressions and the differences between the values forecasted by some authors and the ones observed in the current study were calculated. RESULTS: Among men, the age varied between 25 and 88 years old, and the height varied between 140 and 176 cm. DCO was correlated significantly and positively with the height and negatively with the age. The values forecasted by Crapo, Neder, and Miller equations were higher in comparison with the ones obtained by the current study (p<0.01) in both genders. Among men, the values did not differ when compared to the ones calculated by GLI (p=0.29); among women, the values derived by GLI were slightly higher: 0.99 ml/min/mmHg (p<0.01). CONCLUSION: new values forecasted for DCO were derived in a sample of white adults in Brazil. The forecasted values are similar to the ones complied by GLI equations and differ from the previously proposed equations.

OBJETIVO: Derivar valores de referência em adultos brancos para a difusão do monóxido de carbono (DCO) em uma amostra de diferentes locais do Brasil por um mesmo modelo de equipamento (Sensormedics) e comparar os resultados com os derivados pelas equações de Crapo, Miller e Neder, e da proposta pelo Global Lung Initiative (GLI). MÉTODOS: Os testes foram realizados de acordo com as normas sugeridas pela ATS/ERS, em 2005, em seis cidades brasileiras, em 120 voluntários adultos de cada sexo, não fumantes, sem anemia referida e sem doenças pulmonares ou cardíacas. Os previstos foram derivados por regressões lineares e as diferenças entre os valores previstos por alguns autores e os observados no estudo atual foram calculadas. RESULTADOS: Nos homens, a idade variou de 25 a 88 anos e a estatura, de 156 a 189 cm. Nas mulheres, a idade variou de 21 a 92 anos e a estatura, de 140 a 176 cm. A DCO se correlacionou de maneira significativa positivamente com a estatura e negativamente com a idade. Os valores previstos pelas equações de Crapo, Neder e Miller foram maiores em comparação aos obtidos pelo estudo atual (p<0,01) em ambos os sexos. Nos homens, os valores não diferiram quando comparados aos calculados pelo GLI (p=0,29); nas mulheres, os valores derivados pelo GLI foram levemente maiores: 0,99 mL/min/mmHg (p<0,01). CONCLUSÕES: Novos valores previstos para a DCO foram derivados em uma amostra de adultos brancos no Brasil. Os valores previstos são semelhantes aos compilados pelas equações GLI e diferem de equações propostas anteriormente.

Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil. / Segurança e tolerabilidade de Nintedanibe em pacientes com fibrose pulmonar idiopática no Brasil.

OBJECTIVE: Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. METHODS: Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. RESULTS: The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. CONCLUSION: In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

OBJETIVO: Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. MÉTODOS: Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. RESULTADOS: O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. CONCLUSÕES: No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.

Reference values for pulmonary volumes by plethysmography in a Brazilian sample of white adults.

OBJECTIVE: To derive reference values for healthy white Brazilian adults who have never smoked and to compare the obtained values with reference values derived by Crapo and by Neder. METHODS: Reference equations by quantile regressions were derived in 122 men and 122 women, non-obese, living in seven cities in Brazil. Age ranged from 21 to 92 years in women and from 25 to 88 years in men. Lung function tests were performed using SensorMedics automated body plethysmographies according ATS/ERS recommendations. Lower and upper limits were derived by specific equations for 5 and 95 percentiles. The results were compared to those suggested by Crapo in 1982, and Neder in 1999. RESULTS: Median values for total lung capacity (TLC) were influenced only by stature in men, and by stature and age in women. Residual volume was influenced by age and stature in both genders. Weight was directly related to inspiratory capacity and inversely with functional residual capacity and expiratory reserve volume in both genders. A comparison of observed TLC data with values predicted by Neder equations showed significant lower values by the present data. Mean values were similar between data from present study and those derived by Crapo. CONCLUSION: New predicted values for lung volumes were obtained in a sample of white Brazilians. The values differ from those derived by Neder, but are similar to those derived by Crapo.

Segurança e tolerabilidade de Nintedanibe em pacientes com fibrose pulmonar idiopática no Brasil / Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil

RESUMO Objetivo Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. Métodos Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. Resultados O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. Conclusões No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.

ABSTRACT Objective Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.