RESUMO
BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny. CASE PRESENTATION: A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14 months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10 months later, both values were significantly higher than normal. CONCLUSIONS: This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind.
Assuntos
Doenças Autoimunes , Dermatite , Dermatomiosite , Doenças Pulmonares Intersticiais , Proteinose Alveolar Pulmonar , Feminino , Humanos , Pessoa de Meia-Idade , Proteinose Alveolar Pulmonar/complicações , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/tratamento farmacológico , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Autoanticorpos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Dermatite/complicações , Helicase IFIH1 Induzida por InterferonRESUMO
BACKGROUND: Some patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD) progress to pulmonary fibrosis over their disease course despite initial improvement, potentially indicating a poor prognosis. Transbronchial lung cryobiopsy (TBLC) is a new bioptic approach used in diffuse parenchymal lung diseases. This study of CTD-ILD assessed the utility of TBLC in determining therapeutic decision-making strategies. METHODS: We analyzed medical records of 31 consecutive CTD-ILD patients who underwent TBLC focusing on radio-pathological correlation and disease course. A TBLC-based usual interstitial pneumonia (UIP) score was used that assessed three morphologic descriptors: i) patchy fibrosis, ii) fibroblastic foci, and iii) honeycombing. RESULTS: Among the patients with CTD-ILD, 3 had rheumatoid arthritis, 2 systemic sclerosis, 5 polymyositis/dermatomyositis, 8 anti-synthetase syndrome, 6 Sjögren's syndrome, and 5 had microscopic polyangiitis. Pulmonary function test results showed a mean %FVC of 82.4% and %DLCO of 67.7%. Among the 10 CTD patients and TBLC-proven pathological UIP, 3 patients had prominent inflammatory cells in addition to a framework of UIP, and pulmonary function of most patients improved with anti-inflammatory agents. Six (40%) of 15 patients with TBLC-based UIP score ≥ 1 had a progressive disease course during follow-up, of whom 4 patients received anti-fibrotic agents. CONCLUSIONS: TBLC in patients with CTD-ILD can help determine an appropriate medication strategy, particularly when UIP-like lesions are present. TBLC may be useful when judging which agents to prioritize, anti-inflammatory or anti-fibrotic, is difficult. Moreover, additional information from TBLC may be beneficial when considering early intervention with anti-fibrotic agents in clinical practice.
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Doenças do Tecido Conjuntivo , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Humanos , Antifibróticos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/complicações , Pulmão , Doenças do Tecido Conjuntivo/tratamento farmacológico , Progressão da DoençaRESUMO
INTRODUCTION: Cisplatin-based chemotherapy was established in the 1980s, and it has been improved by the development of a short hydration protocol in lung cancer therapy. However, cisplatin-based chemotherapy is still associated with renal toxicity. Because 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) is known to be a mitochondrial activator and a heme oxygenase-1 (HO-1) inducer, 5-ALA with SFC is speculated to mitigate cisplatin-induced renal inflammation. METHODS: We investigated the effects of oral administration of 5-ALA with SFC for preventing cisplatin-based nephrotoxicity in patients with lung cancer and evaluated its benefits for patients who received cisplatin-based chemotherapy. The primary endpoint was the significance of the difference between the serum creatinine (sCr) levels of the patients administered 5-ALA with SFC and those given placebo after course 1 of chemotherapy. The difference in the estimated glomerular filtration rate (eGFR) between the two groups was also evaluated as the secondary endpoint. RESULTS: The double-blind, randomized two-arm studies were conducted at 15 medical facilities in Japan; 54 male and 20 female patients with lung cancer who received cisplatin-based chemotherapy between the ages of 42 and 75 years were included in the study. The compliance rate was greater than 94% in the primary assessment and subsequent drug administration periods. All enrolled patients completed the four cycles of cisplatin-based chemotherapy with short hydration. The average level of sCr on day 22 of course 1 was 0.707 mg/dL in the group treated with 5-ALA and SFC and 0.735 mg/dL in the placebo group, respectively, and the sCr in the test group was significantly lower than that in the placebo group (p = 0.038). In addition, the eGFR was significantly higher in the SPP-003 group than in the placebo group up to day 1 of course 3 (84.66 and 75.68 mL/min/1.73 m2, respectively, p = 0.02) and kept better even after the last administration of the study drug (82.37 and 73.49 mL/min/1.73 m2, respectively, p = 0.013). CONCLUSIONS: The oral administration of 5-ALA with SFC is beneficial to patients undergoing cisplatin-based chemotherapy for lung cancer with short hydration.
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Ácido Aminolevulínico , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Ácido Aminolevulínico/uso terapêutico , Ácido Aminolevulínico/farmacologia , Cisplatino , Ácido Cítrico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
BACKGROUND: Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) is often positive in patients with interstitial lung disease (ILD), which is also often present in patients with microscopic polyangiitis (MPA). A possible association between MPO-ANCA, MPA, and idiopathic ILD remains unclear. The objective of this study was to determine whether high-resolution computed tomography (HRCT) classification based on recent idiopathic pulmonary fibrosis guideline and specific CT findings can obtain new knowledge of prognostic factors in all MPO-ANCA-positive patients with ILD including both idiopathic ILD and MPA-ILD. METHODS: We analyzed 101 consecutive MPO-ANCA-positive patients with respiratory disease. We assessed the diagnostic accuracy of CT findings, HRCT pattern, and specific radiological signs. Prognostic predictors were determined using Cox regression models. RESULTS: Subjects with chronic ILD included 22 patients with MPA-ILD and 39 patients with ILD but without MPA. A quarter of the patients were radiological indeterminate for usual interstitial pneumonia (UIP) pattern, which resulted in a better prognosis than that for UIP pattern. "Increased attenuation around honeycomb and traction bronchiectasis" and "anterior upper lobe honeycomb-like lesion" were found to be highly frequent radiological findings (39% and 30%, respectively). In addition, the latter finding was a significant negative prognostic factor. CONCLUSIONS: Radiological indeterminate for UIP was a useful HRCT classification in MPO-ANCA-positive patients with ILD. In addition, anterior upper lobe honeycomb-like lesion was found to be specific radiological finding that was a significant prognostic factor. The present results might aid in the assessment of appropriate strategies of diagnosis in these patients.
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Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anticitoplasma de Neutrófilos , Doença Crônica , Feminino , Humanos , Fibrose Pulmonar Idiopática , Japão/epidemiologia , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Peroxidase , PrognósticoRESUMO
BACKGROUND: Interstitial lung disease (ILD) is the most common and important pulmonary manifestation of rheumatoid arthritis (RA). A radiological honeycomb pattern has been described in diverse forms of ILD that can impact survival. However, the clinical course and sequential radiological changes in the formation of the honeycomb pattern in patients with RA-ILD is not fully understood. METHODS: We evaluated the sequential changes in computed tomography findings in 40 patients with chronic forms of RA-ILD without the honeycomb pattern at initial diagnosis. We classified the patients into the Non-honeycomb group and Honeycomb group, and then analyzed the characteristics and prognosis of the two groups. The term "honeycomb formation" indicated a positive finding of honeycombing on any available follow-up CT. RESULTS: Our RA-ILD cohort included patients with probable usual interstitial pneumonia (UIP) (35%), nonspecific interstitial pneumonia (NSIP) (20%), and mixed NSIP/UIP (45%). Among all RA-ILD patients, 16 (40%) showed honeycomb formation on follow-up CT (median time between initial and last follow-up CT was 4.7 years). Patient characteristics and prognosis were not significantly different between the Non-honeycomb and Honeycomb groups. However, Kaplan-Meier survival curve for the time from the date of honeycomb formation to death showed a poor median survival time of 3.2 years. CONCLUSIONS: A certain number of patients with RA-ILD developed a honeycomb pattern during long-term follow-up, regardless of whether they had UIP or NSIP. Prognosis in the patients with characteristics of both progressive ILD and honeycomb formation could be poor. Although radiological findings over the disease course and clinical disease behavior in RA-ILD are heterogenous, clinicians should be alert to the possibility of progressive disease and poor prognosis in patients with RA-ILD who form a honeycomb pattern during follow-up observation.
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Artrite Reumatoide/diagnóstico por imagem , Pneumonias Intersticiais Idiopáticas/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Idoso , Artrite Reumatoide/complicações , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/complicações , Pneumonias Intersticiais Idiopáticas/mortalidade , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Aspiration pneumonia is a serious problem among elderly patients; it is caused by many risk factors including dysphagia, poor oral hygiene, malnutrition, and sedative medications. The aim of this study was to define a convenient procedure to objectively evaluate the risk of aspiration pneumonia in the clinical setting. METHODS: This prospective study included an aspiration pneumonia (AP) group, a community-acquired pneumonia (CAP) group, and a control (Con) group (patients hospitalized for lung cancer chemotherapy). We used the Oral Health Assessment Tool (OHAT), which assesses oral hygiene, and evaluated performance status, body mass index, serum albumin levels, substance P values in plasma, and oral bacterial counts. RESULTS: The oral health as assessed by the OHAT of the aspiration pneumonia group was significantly impaired compared with that of the CAP group and the control (5.13 ± 0.18, 4.40 ± 0.26, 3.90 ± 0.22, respectively; p < 0.05). The oral bacterial count in the aspiration pneumonia group (7.20 ± 0.11) was significantly higher than that in the CAP group (6.89 ± 0.12), consistent with the OHAT scores. Oral bacterial count was significantly reduced by oral care. CONCLUSIONS: OHAT and oral bacterial counts can be a tool to assess the requirement of taking oral care and other preventive procedures in patients at high risk of aspiration pneumonia.
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Bactérias/isolamento & purificação , Biomarcadores/sangue , Avaliação Geriátrica/métodos , Mucosa Bucal/microbiologia , Pneumonia Aspirativa/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Estudos de Casos e Controles , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Masculino , Microbiota/fisiologia , Pessoa de Meia-Idade , Higiene Bucal , Projetos Piloto , Pneumonia Aspirativa/sangue , Pneumonia Aspirativa/microbiologia , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: Nintedanib is a tyrosine kinase inhibitor that efficiently slows the progression of idiopathic pulmonary fibrosis (IPF) and has an acceptable tolerability profile. In contrast, immune checkpoint inhibitors (ICIs) such as programmed death 1 and programmed death ligand 1 inhibitors have shown clinical activity and marked efficacy in the treatment of non-small cell lung cancer. However, it is unclear whether nintedanib reduces the risk of ICI-induced pneumonitis in IPF. CASE PRESENTATION: A 78-year-old man with squamous cell lung carcinoma in IPF underwent second-line treatment with pembrolizumab. He was diagnosed as having pembrolizumab-induced pneumonitis after two cycles. He was administered prednisolone (PSL) and then improved immediately. Thereafter, his lung cancer lesion enlarged despite treatment with TS-1. Atezolizumab was then administered as 4th-line chemotherapy, but he immediately developed atezolizumab-induced pneumonitis after 1 cycle. The re-escalated dosage of PSL improved the pneumonitis, and then nintedanib was started as additional therapy. Under careful observation with nintedanib, atezolizumab was re-administered on day 1 of an every-21-day cycle. After three cycles, it remained stable without exacerbation of drug-induced pneumonitis. CONCLUSION: This case indicates the possibility that the addition of nintedanib to ICI therapy might prevent drug-induced pneumonitis or acute exacerbation of IPF. However, whether anti-fibrotic agents such as nintedanib are actually effective in preventing ICI-induced pneumonitis in ILD remains unknown and additional research is greatly needed to identify effective therapies for ILD combined with lung cancer.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Pneumonia/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/complicações , Progressão da Doença , Humanos , Fibrose Pulmonar Idiopática/complicações , Neoplasias Pulmonares/complicações , Masculino , Pneumonia/induzido quimicamente , Retratamento , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tomografia Computadorizada por Raios XAssuntos
Brônquios/patologia , Bronquite/patologia , Doença Relacionada a Imunoglobulina G4/patologia , Biópsia , Brônquios/imunologia , Bronquite/imunologia , Bronquite/fisiopatologia , Broncoscopia , Tosse/fisiopatologia , Criocirurgia , Dispneia/fisiopatologia , Humanos , Imunoglobulina G/imunologia , Doença Relacionada a Imunoglobulina G4/imunologia , Doença Relacionada a Imunoglobulina G4/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doenças Parotídeas/imunologia , Doenças Parotídeas/patologia , Plasmócitos/imunologia , Plasmócitos/patologia , Doenças da Glândula Submandibular/imunologia , Doenças da Glândula Submandibular/patologiaRESUMO
BACKGROUND: Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal accumulation of surfactants in the alveoli. Most cases are classified as autoimmune PAP (APAP) because they are associated with autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). However, GM-CSF autoantibody levels are unlikely to correlate with the disease severity or prognosis of APAP. METHODS: We collected clinical records and measured 38 serum cytokine concentrations for consecutive patients with APAP. After exclusion of 21 cytokines because of undetectable levels, 17 cytokine levels were compared between low and high disease severity scores (DSSs). We also compared whole lung lavage (WLL)-free survival with cut-off values defined by receiver operating characteristic (ROC) curves of cytokine levels and WLL administration at 11 months. RESULTS: Nineteen patients with APAP were enrolled in the study. Five were classified as DSS 1 or 2, while the others were classified as DSS 4 or 5. Comparison between DSS 1-2 and 4-5 revealed that the concentrations of IP-10 and GRO increased in the latter groups (p < 0.05). Fifteen patients underwent WLL. Comparison between those who underwent WLL within 11 months and the others showed that IP-10 and TNF-α were tended to be elevated in the former group (p = 0.082 and 0.057, respectively). The cut-off values of IP-10, 308.8 pg/mL and TNF-α, 19.1 pg/mL, defined by the ROC curves, significantly separated WLL-free survivals with log-rank analyses (p = 0.005). CONCLUSIONS: The concentrations of IP-10 and GRO may reflect the DSSs of APAP. A combination of IP-10 and TNF-α levels could be a biomarker to predict WLL-free survival.
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Doenças Autoimunes , Citocinas , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Proteinose Alveolar Pulmonar , Índice de Gravidade de Doença , Humanos , Proteinose Alveolar Pulmonar/imunologia , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/sangue , Proteinose Alveolar Pulmonar/terapia , Prognóstico , Citocinas/sangue , Masculino , Feminino , Doenças Autoimunes/imunologia , Doenças Autoimunes/sangue , Doenças Autoimunes/diagnóstico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Pessoa de Meia-Idade , Adulto , Autoanticorpos/sangue , Quimiocina CXCL10/sangue , Idoso , Fator de Necrose Tumoral alfa/sangue , Biomarcadores/sangue , Lavagem Broncoalveolar , Adulto JovemRESUMO
BACKGROUND: Nintedanib is generally safe and well tolerated and can improve prognosis in patients with various interstitial lung diseases (ILDs). Appropriate management of adverse events of nintedanib is important to ensure its long-term persistent use. Weight loss is a routinely assessed adverse event in clinical practice. This study aimed to elucidate whether body weight change in the first year of nintedanib therapy can indicate prognosis and predict tolerability in patients with ILD. METHODS: We analysed 245 consecutive ILD patients treated with nintedanib. We calculated the slope of body weight change using baseline weight and that recorded closest after the first year and then categorized percent change in body weight at this time. Significant weight loss was defined as that ≥5%. RESULTS: Subjects included 67 patients with idiopathic pulmonary fibrosis (IPF) and 76 with non-IPF progressive fibrosing-ILD including fibrotic hypersensitivity pneumonitis (n = 16), unclassifiable (n = 35), connective tissue disease-ILD (n = 21), and nonspecific interstitial pneumonia (n = 4). Older age, low body weight at initial examination, significant weight loss, and lower %FVC were significant predictors of discontinuation of nintedanib. Patients with weight loss ≥5% over the first year showed worse survival than those with weight loss <5% regardless of whether IPF existed or BMI indicated obesity. CONCLUSIONS: Careful monitoring of body weight change might suggest useful information for predicting long-term use of nintedanib and mortality risk in ILD patients treated with nintedanib. Appropriate body weight management is needed to prevent adverse events of nintedanib itself.
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Indóis , Doenças Pulmonares Intersticiais , Redução de Peso , Humanos , Indóis/efeitos adversos , Indóis/administração & dosagem , Indóis/uso terapêutico , Prognóstico , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Tempo , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/fisiopatologia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Although transbronchial lung cryobiopsy (TBLC) is widely used in diagnostic algorithms for various interstitial lung diseases (ILDs), its real-world utility in the therapeutic decision-making strategy for ILD patients remains unclear, in particular, when judging the time to start antifibrotic agents. METHODS: We analyzed medical records of 40 consecutive patients with idiopathic or fibrotic hypersensitivity pneumonitis who underwent TBLC. A TBLC-based usual interstitial pneumonia (UIP) score was used to assess three morphologic descriptors: patchy fibrosis, fibroblastic foci, and honeycombing. RESULTS: In our 40 patients with ILD, the most frequent radiological feature was indeterminate for UIP (45.0%). Final diagnosis included idiopathic pulmonary fibrosis (22.5%), fibrotic nonspecific interstitial pneumonia (5.0%), fibrotic hypersensitivity pneumonitis (35.0%), and unclassifiable ILD (37.5%). Linear mixed-effects analysis showed that declines in the slopes of %FVC and %DLCO in patients with TBLC-based UIP "Score ≥ 2" were significantly steeper than those of patients with "Score ≤ 1." During follow-up of patients with Score ≥ 2 (n = 24), more than half of them (n = 17) received an antifibrotic agent, with most patients (n = 13) receiving early administration of the antifibrotic agent within 6 months after the TBLC procedure. CONCLUSIONS: TBLC-based UIP Score ≥ 2 indicated the increased possibility of a progressive fibrosis course that may prove helpful in predicting progressive pulmonary fibrosis/progressive fibrosing ILD even if disease is temporarily stabilized due to anti-inflammatory agents. Patients may benefit from early introduction of antifibrotic agents by treating clinicians.
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Progressão da Doença , Doenças Pulmonares Intersticiais , Pulmão , Humanos , Feminino , Masculino , Idoso , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Pessoa de Meia-Idade , Biópsia/métodos , Estudos Retrospectivos , Pulmão/patologia , Pulmão/diagnóstico por imagem , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/diagnóstico , Antifibróticos/uso terapêutico , Antifibróticos/administração & dosagem , Criocirurgia/métodos , Broncoscopia/métodos , Alveolite Alérgica Extrínseca/patologia , Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Para-tracheal or para-carinal air cysts (PACs) are often asymptomatic and usually detected incidentally by methods such as computed tomography. Their clinical significance is unclear in patients with pleuroparenchymal fibroelastosis (PPFE). METHODS: We evaluated the clinical significance of PACs in PPFE and their relationship with pneumomediastinum or pneumothorax. RESULTS: In total, 50 patients had PPFE and 34 (68%) had PACs. Most PACs were para-carinal (n = 30). A para-tracheal air cyst was detected in only nine patients, which included five patients having both para-carinal and para-tracheal air cysts. Overall median survival was 24.7 months. Survival was not significantly different between the patients with [PACs(+)] and without PACs (P = 0.268). A high frequency (64%) of the complication of pneumomediastinum or pneumothorax occurred in the overall population during follow-up. Pneumomediastinum/pneumothorax occurred significantly more frequently in patients with PACs(+) than in those without (76.5% vs. 37.5%; P = 0.012). PACs(+) was the only significant risk factor for pneumomediastinum/pneumothorax. CONCLUSIONS: Our data showed that PACs commonly occur in patients with PPFE, and most PACs were para-carinal air cysts. Additionally, PACs(+) was a significant risk factor for pneumomediastinum/pneumothorax; therefore, clinicians should be more aware of these complications during follow-up examination, particular in PACs(+) patients with PPFE.
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Cistos , Enfisema Mediastínico , Pneumotórax , Humanos , Pneumotórax/diagnóstico por imagem , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Enfisema Mediastínico/diagnóstico por imagem , Enfisema Mediastínico/complicações , Relevância Clínica , Tomografia Computadorizada por Raios X , Cistos/complicações , Cistos/diagnóstico por imagemRESUMO
BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) inhalation may alleviate pulmonary inflammation caused by viral pneumonia. To investigate this, we evaluated its efficacy on COVID-19 pneumonia. METHODS: This double-blind, randomised, placebo-controlled study (ClinicalTrials.gov: NCT04642950) evaluated patients in the first half of 2021 at seven Japanese hospitals. Hospitalised patients with COVID-19 pneumonia with moderate hypoxaemia inhaled sargramostim or placebo for 5 days. The primary endpoint was days to achieve a ≥ 2-category improvement from baseline on a modified 7-category ordinal scale. Secondary endpoints included degree of oxygenation, defined by amount of oxygen supply, and serum CCL17 level. RESULTS: Seventy-five patients were randomly assigned in a 2:1 ratio to receive sargramostim or placebo, of which 47 and 23 were analysed, respectively. No difference was observed between groups regarding the primary endpoint (8.0 and 7.0 days for sargramostim and placebo, respectively) or in the secondary endpoints, except for CCL17. A post hoc sub-analysis indicated that endpoint assessments were influenced by concomitant corticosteroid therapy. When the cumulative corticosteroid dose was ≤500 mg during Days 1-5, recovery and oxygenation were faster in the sargramostim group than for placebo. Bolus dose corticosteroids were associated with temporarily impaired oxygenation and delayed clinical recovery. The increase in serum CCL17, a candidate prognostic factor, reflected improvement with sargramostim inhalation. The number of adverse events was similar between groups. Two serious adverse events were observed in the sargramostim group without causal relation. CONCLUSIONS: Inhaled sargramostim was likely to be effective for COVID-19 pneumonia unless the concomitant corticosteroid dose was high.
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COVID-19 , Humanos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Corticosteroides/uso terapêutico , Esteroides , Método Duplo-Cego , Resultado do TratamentoRESUMO
OBJECTIVE: This study was performed to evaluate the radiological features of and therapeutic responses to pulmonary disease caused by nontuberculous mycobacteria (NTM) in the setting of biological therapy for rheumatoid arthritis (RA). METHODS: We conducted a retrospective chart review of 13 patients from multiple centers who had developed pulmonary NTM disease during biological therapy for RA, including infliximab, etanercept, adalimumab, and tocilizumab. RESULTS: Most cases were asymptomatic or resulted in only common-cold-like symptoms. Abnormalities in computed tomography (CT) imaging were protean and frequently overlapped. The most predominant pattern was nodular/bronchiectatic disease (six cases), followed by alveolar infiltrate (three cases), cavitary disease (two cases), and pulmonary nodules (two cases). In most cases, pulmonary NTM disease had spread from a preexisting lesion; in particular, bronchial/bronchiolar abnormalities. In three cases, one or more nodular lesions with or without calcification were a focus of disease. Following the discontinuation of biological agents, most patients responded to anti-NTM therapy. Two patients showed no exacerbation in the absence of any anti-NTM therapy. In one patient, restarting tocilizumab therapy while continuing to receive adequate anti-NTM therapy produced a favorable outcome. In two other patients with a previous history of pulmonary NTM disease, introducing biological therapy led to recurrence, but anti-NTM therapy was effective in these patients. CONCLUSION: CT abnormalities of pulmonary NTM disease in RA patients receiving biological therapy were variable, but were not unique to this clinical setting. NTM disease can spread from preexisting structural abnormalities, even if they are minute. Contrary to our expectations, the therapeutic outcomes of pulmonary NTM disease were favorable in these patients.
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Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/induzido quimicamente , Adalimumab , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Etanercepte , Feminino , Humanos , Imunoglobulina G/efeitos adversos , Infliximab , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico por imagem , Radiografia Torácica , Receptores do Fator de Necrose Tumoral , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Objectives The association of anti-tumor necrosis factor therapy with opportunistic infections in rheumatoid arthritis (RA) patients has been reported. The goal of this study was to clarify the clinical characteristics and the risk factors of RA patients who developed Pneumocystis jirovecii pneumonia (PCP) during etanercept therapy. Methods We conducted a multicenter, case-control study in which 15 RA patients who developed PCP were compared with 74 RA patients who did not develop PCP during etanercept therapy. Results PCP developed within 26 weeks following the first injection of etanercept in 86.7% of the patients. All PCP patients presented with a rapid and severe clinical course and the overall mortality was 6.7%. Independent risk factors were identified using multivariate analysis and included age ≥ 65 years [hazard ratio (HR) 3.35, p = 0.037], coexisting lung disease (HR 4.48, p = 0.009), and concomitant methotrexate treatment (HR 4.68, p = 0.005). In patients having a larger number of risk factors, the cumulative probability of developing PCP was significantly higher (p < 0.001 for patients with two or more risk factors vs. those with no risk factor, and p = 0.001 for patients with one risk factor vs. those with no risk factor). Conclusion Physicians must consider the possibility of PCP developing during etanercept therapy in RA patients, particularly if one or more risk factors are present.
RESUMO
OBJECTIVES: The association of anti-tumor necrosis factor therapy with opportunistic infections in rheumatoid arthritis (RA) patients has been reported. The goal of this study was to clarify the clinical characteristics and the risk factors of RA patients who developed Pneumocystis jirovecii pneumonia (PCP) during etanercept therapy. METHODS: We conducted a multicenter, case-control study in which 15 RA patients who developed PCP were compared with 74 RA patients who did not develop PCP during etanercept therapy. RESULTS: PCP developed within 26 weeks following the first injection of etanercept in 86.7% of the patients. All PCP patients presented with a rapid and severe clinical course and the overall mortality was 6.7%. Independent risk factors were identified using multivariate analysis and included age ≥65 years [hazard ratio (HR) 3.35, p = 0.037], coexisting lung disease (HR 4.48, p = 0.009), and concomitant methotrexate treatment (HR 4.68, p = 0.005). In patients having a larger number of risk factors, the cumulative probability of developing PCP was significantly higher (p < 0.001 for patients with two or more risk factors vs. those with no risk factor, and p = 0.001 for patients with one risk factor vs. those with no risk factor). CONCLUSION: Physicians must consider the possibility of PCP developing during etanercept therapy in RA patients, particularly if one or more risk factors are present.
Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Imunoglobulina G/efeitos adversos , Infecções Oportunistas/induzido quimicamente , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/microbiologia , Adulto , Idoso , Antifúngicos/uso terapêutico , Antirreumáticos/uso terapêutico , Estudos de Casos e Controles , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/tratamento farmacológico , Pneumonia por Pneumocystis/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Estudos RetrospectivosRESUMO
Uveitis has many etiologies, but tuberculous uveitis is rare. We herein report 2 cases of uveitis due to tuberculosis infection. The first case was a 28-year-old man who was showed abnormal shadows in the chest radiographic examination performed in search of the etiology of uveitis. Computed tomography (CT) of the chest revealed hilar and mediastinal lymphadenopathy, small nodules, and consolidation, with a small cavity in the right upper lobe. An ulcerated nodule in the truncus intermedius and stenosis of the right middle lobe bronchus were found on bronchoscopy. The biopsy of the nodule in the truncus intermedius showed a small granuloma containing giant cells, consistent with mycobacterial infection. The culture of bronchial washings from the right upper lobe grew Mycobacterium tuberculosis. Diagnosis of pulmonary tuberculosis, tuberculous lymphadenitis, bronchial tuberculosis, and tuberculous uveitis was made. The patient was treated with antituberculosis drugs and his disease, including uveitis, improved. The second case was a 36-year-old man who presented with right hemiparesis, dysarthria, and visual loss of the left eye. He was diagnosed with neuro-Sweet disease causing optic neuritis and visual loss. His chest CT showed a nodule with centrilobular opacities in the left lower lobe that suggested mycobacterial infection. PCR of the bronchial washing from the left lower lobe was positive for M.tuberculosis and the diagnosis of pulmonary tuberculosis was established. Treatment with antituberculosis drugs and corticosteroids was initiated and his pulmonary lesion improved. However, bilateral tuberculous uveitis developed 15 days after initiation of the treatment. The uveitis gradually deteriorated thereafter despite continuation of antituberculosis therapy. Photocoagulation finally halted the disease progression. In both patients with uveitis presented here, chest radiographs and CT scans were important in determining the etiology of the uveitis. It is difficult to find the etiology of uveitis, and general examinations including the lungs are helpful to pinpoint tuberculosis as the etiology of uveitis. As tuberculous uveitis is sometimes asymptomatic and resistant to treatment, ophthalmological examination is recommended for patients with pulmonary tuberculosis.
Assuntos
Tuberculose Ocular/etiologia , Tuberculose Pulmonar/complicações , Uveíte/etiologia , Adulto , Humanos , MasculinoRESUMO
BACKGROUND: Secondary spontaneous pneumothorax (SSP) in interstitial lung disease (ILD) may influence prognosis of any ILD, and SSP onset predicts poor outcome in idiopathic pulmonary fibrosis (IPF). Recently, progressive fibrosing ILD (PF-ILD) has rapidly acquired importance. OBJECTIVE: We hypothesized that PF-ILD would strongly influence the prognosis of patients with any ILD complicated with SSP. METHODS: We retrospectively surveyed and collected data from patients hospitalized for SSP from January 2016 to June 2020. PF-ILD was defined as the following occurring within 24 months before SSP develops: relative decline in %forced vital capacity (FVC) ≥10% or two of the following: relative decline in %FVC between 5% and 10%, worsening respiratory symptoms, or increased extent of fibrosis on high-resolution computed tomography. RESULTS: We analyzed 32 patients hospitalized for SSP in ILD. This study comprised 18 patients with PF-ILD and 14 patients with non-PF-ILD. PF-ILD patients had lower body mass index (BMI) and %FVC. No significant differences in survival regarding follow-up period from the time of ILD diagnosis and hospitalization for SSP were observed between the PF-ILD and non-PF-ILD patients. Older age and lower BMI were significant predictors of mortality by multivariate Cox regression analysis. ROC analysis showed BMI ≤17.8 kg/m2 to reliably predict poor prognosis. CONCLUSIONS: Regardless of whether patients have PF-ILD, older age and lower BMI in patients with ILD places them at higher risk of developing SSP, and prognosis is poor if SSP develops. Therefore, clinical management of physique is important to improve the prognosis of ILD patients.
RESUMO
Epithelioid hemangioendothelioma (EHE) affects many organs, particularly lung and liver, and typically presents as multiple lesions. Treatment for EHE is not yet standardized, but surgery is appropriate when lesions are resectable. In our patient, radiography revealed multiple bilateral pulmonary nodules, and CT showed several liver tumors. The liver masses and those in the right lung were removed during the initial surgery; pathology of hepatic specimens confirmed the diagnosis of EHE. During the second operation, the left lung nodules were excised, and all were EHEs. Surgical removal of multiorgan multinodular EHE is a viable treatment option, especially for young patients.