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Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Biópsia/métodos , Tomografia Computadorizada por Raios X , Pulmão/patologia , Pulmão/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Progressão da Doença , Doença AgudaRESUMO
Drug-induced lung disease (DILD) encompasses a broad, highly heterogeneous group of conditions that may occur as a result of exposure to numerous agents, such as antineoplastic drugs, conventional or biological disease-modifying antirheumatic drugs, antiarrhythmics, and antibiotics. Between 3% and 5% of prevalent cases of interstitial lung diseases are reported as DILDs. The pathogenesis of lung injury in DILD is variable, multifactorial, and often unknown. Acute presentation is the most common, can occur from days to months after the start of treatment, and ranges from asymptomatic to acute respiratory failure. The CT patterns are varied and include ground-glass opacities, organizing pneumonia, and diffuse alveolar damage. Notably, there are no clinical manifestations or CT patterns specific to DILD, which makes the diagnosis quite challenging and necessitates a high index of suspicion, as well as the exclusion of alternative causes such as infection, cardiac-related pulmonary edema, exacerbation of a preexisting ILD, and neoplastic lung involvement. Discontinuation of the offending medication constitutes the cornerstone of treatment, and corticosteroid treatment is usually necessary after the onset of clinical manifestations. The prognosis varies widely, with high mortality rates in severe cases. A history of medications related to pulmonary toxicity in patients with new-onset respiratory symptoms should prompt consideration of DILD as a potential underlying cause.
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Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Tomografia Computadorizada por Raios X , Pneumopatias/induzido quimicamente , Fatores de Risco , PrognósticoRESUMO
In lung disease, persistence of KRT8-expressing aberrant basaloid cells in the alveolar epithelium is associated with impaired tissue regeneration and pathological tissue remodeling. We analyzed single cell RNA sequencing datasets of human interstitial lung disease and found the profibrotic Interleukin-11 (IL11) cytokine to be highly and specifically expressed in aberrant KRT8+ basaloid cells. IL11 is similarly expressed by KRT8+ alveolar epithelial cells lining fibrotic lesions in a mouse model of interstitial lung disease. Stimulation of alveolar epithelial cells with IL11 causes epithelial-to-mesenchymal transition and promotes a KRT8-high state, which stalls the beneficial differentiation of alveolar type 2 (AT2)-to-AT1 cells. Inhibition of IL11-signaling in AT2 cells in vivo prevents the accumulation of KRT8+ cells, enhances AT1 cell differentiation and blocks fibrogenesis, which is replicated by anti-IL11 therapy. These data show that IL11 inhibits reparative AT2-to-AT1 differentiation in the damaged lung to limit endogenous alveolar regeneration, resulting in fibrotic lung disease.
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Células Epiteliais Alveolares , Diferenciação Celular , Interleucina-11 , Regeneração , Interleucina-11/metabolismo , Interleucina-11/genética , Animais , Regeneração/genética , Humanos , Camundongos , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/metabolismo , Transição Epitelial-Mesenquimal/genética , Modelos Animais de Doenças , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/genética , Doenças Pulmonares Intersticiais/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Transdução de Sinais , FemininoRESUMO
OBJECTIVE: Interstitial lung diseases (ILDs) are diverse pulmonary disorders marked by diffuse lung inflammation and fibrosis. The variability in characteristics and treatment approaches complicates diagnosis and management. In advanced cases requiring transplantation, determining indications and selecting suitable candidates presents additional challenges. METHODS: Of all patients with non-IPF ILD between December 2016 to December 2022 were analyzed retrospectively. Patients were categorized into two groups: transplanted patients and deceased patients on the waiting list. Clinical data and survival outcomes were compared between groups. RESULTS: Of the 43 patients, 20 underwent lung transplantation while 23 died awaiting transplantation. Waiting list mortality was 53.4%, with median waiting times similar between groups (3 months for transplant patients and 6 months for those on the waiting list). There were no significant differences between groups in age, gender, height, BMI, 6-minute walk test (6MWT), or forced vital capacity (FVC). The prevalence of pulmonary hypertension (PH) was 76.7% in right heart catheterizations, similar in both groups. One single and 19 bilateral lung transplants were performed. Overall, 13 of the 20 patients survived to discharge from the hospital. One-year mortality was 7/20 (35%). The median follow-up was 34 months, with a 1-year conditional survival of 90.9% at 3 years and 70.7% at 5 years. CONCLUSIONS: This study underscores the importance of further research into non-IPF ILDs. Lung transplantation remains a viable option that can significantly enhance both the quality and longevity of life for patients with advanced ILD.
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Doenças Pulmonares Intersticiais , Transplante de Pulmão , Listas de Espera , Humanos , Feminino , Masculino , Doenças Pulmonares Intersticiais/cirurgia , Doenças Pulmonares Intersticiais/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Listas de Espera/mortalidade , Adulto , Idoso , Hipertensão Pulmonar/cirurgia , Hipertensão Pulmonar/mortalidade , Capacidade VitalRESUMO
OBJECTIVE: Interstitial lung disease (ILD) resulting from connective tissue disease (CTD) greatly undermines people's health. Cyclophosphamide (CYC) is a widely used agent in treating CTD-ILD. We compared the efficacy and safety of oral and intravenous CYC in CTD-ILD treatment. METHODS: The retrospectively enrolled CTD-ILD patients were divided into the oral and intravenous CYC groups. The chest high-resolution computed tomography examination, forced vital capacity (FVC), lung carbon monoxide diffusion capacity (Dlco) determinations, and 6 min walk test (6MWT) were performed pre-treatment and at the 3rd, 6th, and 12th months posttreatment. Radiographic ILD severity was assessed using the Warrick score. Krebs Von den Lungen-6, surfactant protein A (SP-A), SP-D, and erythrocyte sedimentation rate (ESR) before and at the 12th month post-treatment were determined. CYC cumulative dose and occurrence of adverse reactions during treatment were recorded. RESULTS: CYC cumulative dose in the intravenous CYC group was reduced. Compared with oral CYC treatment, intravenous CYC caused decreased Warrick score and increased FVC and 6MWT at the 6th month, and elevated DLco at the 3rd and 6th months posttreatment. SP-A, SP-D and ESR levels in both groups were reduced 12 months posttreatment, with a more evident decrease in the intravenous CYC group. Intravenous CYC had lower total adverse reaction incidence. CONCLUSION: Compared with oral CYC, intravenous CYC decreases Warrick score and increases FVC and 6MWT at 6 months posttreatment, and reduces SP-A, SP-D, and ESR levels after 12 months of treatment, which shows low CYC cumulative dose and adverse reaction incidence in treating CTD-ILD.
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Administração Intravenosa , Doenças do Tecido Conjuntivo , Ciclofosfamida , Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/fisiopatologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Feminino , Masculino , Administração Oral , Estudos Retrospectivos , Pessoa de Meia-Idade , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/tratamento farmacológico , Doenças do Tecido Conjuntivo/complicações , Resultado do Tratamento , Adulto , Fatores de Tempo , Imunossupressores/efeitos adversos , Imunossupressores/administração & dosagem , Capacidade Vital , Recuperação de Função Fisiológica , Idoso , Capacidade de Difusão Pulmonar , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Sedimentação Sanguínea , Tolerância ao Exercício/efeitos dos fármacos , Teste de Caminhada , Proteína D Associada a Surfactante Pulmonar/sangue , Mucina-1/sangueRESUMO
BACKGROUND/AIMS: To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. RESULTS: The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. CONCLUSION: Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.
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Abatacepte , Antirreumáticos , Artrite Reumatoide , Doenças Pulmonares Intersticiais , Humanos , Abatacepte/uso terapêutico , Abatacepte/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Idoso , Resultado do Tratamento , Progressão da Doença , Fatores de Tempo , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Fatores de Risco , Adulto , República da Coreia , Tomografia Computadorizada por Raios XAssuntos
Doenças Pulmonares Intersticiais , Ácido Micofenólico , Rituximab , Humanos , Ácido Micofenólico/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Rituximab/uso terapêutico , Feminino , Seguimentos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Idoso , Imunossupressores/uso terapêuticoRESUMO
BACKGROUND: Acute exacerbation (AE) refers to rapidly progressive respiratory deterioration in the clinical course of interstitial lung disease (ILD). Progressive pulmonary fibrosis (PPF) is the chronic progressive phenotype of ILD. No study has investigated the relationship between AE and PPF in ILD. OBJECTIVES: We aimed to determine the association between AE and PPF in ILD patients. DESIGN: A retrospective cohort study. METHODS: A total of 414 patients hospitalised for ILD were included in our study. The clinical presentations, radiographic features and laboratory findings of the patients were reviewed. RESULTS: AE was present in 120 (29.0%) ILD patients and was associated with a higher risk of death than non-AE patients in the whole cohort (HR 2.893; 95% CI, 1.847-4.529; p < 0.001). However, the significant difference disappeared when stratified by PPF (HR 1.192; 95% CI, 0.633-2.247; p = 0.586) and non-PPF (HR 1.113; 95% CI, 0.384-3.223; p = 0.844). In addition, the adverse effect of PPF on prognosis remained consistent in both AE and non-AE patients. Multivariable logistic regression analysis showed that compared with non-PPF patients, only age was a risk factor for PPF in AE-ILD, while the risk factors for PPF in the non-AE group were age, definite usual interstitial pneumonia and mediastinal lymph node enlargement. CONCLUSION: In the context of ILD, both AE and PPF were found to be associated with poor prognosis. However, the adverse effect of AE on prognosis disappeared when PPF was considered as a stratification feature, whereas the adverse effect of PPF on prognosis persisted in both AE and non-AE individuals. Therefore, it is important to investigate effective strategies to prevent disease progression after AE. Increased recognition and attention to PPF and early antifibrotic therapy at the appropriate time is also warranted.
Association between acute exacerbation and progressive pulmonary fibrosis in interstitial lung diseaseWhy was the study done? Acute exacerbation (AE) is an acute respiratory worsening of interstitial lung disease (ILD). Progressive pulmonary fibrosis (PPF) is a chronic progressive-fibrosing form of ILD. The relationship between AE and PPF in ILD remained unclear. We aimed to determine the association between AE and PPF in ILD patients.What did the researchers do? The researchers studied 414 patients with ILD to see how AE and PPF affect the outcome of ILD and explored the risk factors for PPF in ILD.What did the researchers find? AE was present in 120 (29.0%) ILD patients and was associated with higher risk of death than non-AE patients in the whole cohort. However, the significant difference disappeared when stratified by PPF and non-PPF. In addition, the adverse effect of PPF on prognosis remained consistent in both AE and non-AE patients. In AE-ILD patients, age was the only risk factor for PPF. In the non-AE group, age, definite usual interstitial pneumonia and mediastinal lymph node enlargement were risk factors for PPF.What do the findings mean? The findings suggest that it is important to investigate effective strategies to prevent disease progression after AE. Increased recognition and attention to PPF and early antifibrotic therapy at the appropriate time is also necessary.
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Progressão da Doença , Doenças Pulmonares Intersticiais , Fibrose Pulmonar , Humanos , Estudos Retrospectivos , Masculino , Feminino , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/diagnóstico , Idoso , Pessoa de Meia-Idade , Fibrose Pulmonar/fisiopatologia , Fibrose Pulmonar/mortalidade , Fatores de Risco , Prognóstico , Fatores de Tempo , Idoso de 80 Anos ou mais , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagemRESUMO
Interstitial lung abnormalities (ILAs) are immune checkpoint inhibitor (ICI)-related pneumonitis (ICI-P) risk factors. However, the relationship between imaging patterns and immunotherapy outcomes, and treatment strategies remain unclear in patients with non-small cell lung cancer (NSCLC) and ILAs. We retrospectively evaluated patients with ILAs-complicated NSCLC who received ICI therapy. ILAs were subcategorized as non-subpleural, subpleural non-fibrotic, and subpleural fibrotic (SF) based on the 2020 position paper by the Fleischner Society. We investigated ICI-P incidence, ICI-P risk factors, lung cancer prognosis, and ILAs radiological progression. Of the 481 ICI-treated patients, 79 (16.4%) had ILAs (45 non-SF and 34 SF). The ICI-P cumulative incidence (hazard ratio, 4.57; 95% confidence interval [CI], 1.90-10.98; p = 0.001) and any grade and grade ≥ 3 ICI-P incidences were higher in patients with SF-ILAs than in those with non-SF-ILAs (all grades: 7/45 [15.6%)] vs. 18/34 [52.9%]; p < 0.001; grade ≥ 3: 1/45 [2.2%] vs. 10/34 [29.4%]; p = 0.001). According to multivariate analysis, SF-ILAs independently predicted ICI-P (odds ratio, 5.35; 95% CI 1.62-17.61; p = 0.006). Patients with SF-ILAs had shorter progression-free and overall survival and higher ICI-P-related respiratory failure death rates than those with non-SF-ILAs. Approximately 2.5 times more patients with SF-ILAs showed progression by the 2-year follow-up than those with non-SF-ILAs. SF-ILAs is an independent strong predictor of ICI-P development in patients with NSCLC, may increase ICI-P severity, worsen prognosis, and accelerate ILAs progression. ILAs subcategorization is an important treatment strategy for patients with lung cancer treated with ICIs.
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Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/complicações , Masculino , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/complicações , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso de 80 Anos ou mais , Resultado do Tratamento , AdultoRESUMO
Background It is increasingly recognized that interstitial lung abnormalities (ILAs) detected at CT have potential clinical implications, but automated identification of ILAs has not yet been fully established. Purpose To develop and test automated ILA probability prediction models using machine learning techniques on CT images. Materials and Methods This secondary analysis of a retrospective study included CT scans from patients in the Boston Lung Cancer Study collected between February 2004 and June 2017. Visual assessment of ILAs by two radiologists and a pulmonologist served as the ground truth. Automated ILA probability prediction models were developed that used a stepwise approach involving section inference and case inference models. The section inference model produced an ILA probability for each CT section, and the case inference model integrated these probabilities to generate the case-level ILA probability. For indeterminate sections and cases, both two- and three-label methods were evaluated. For the case inference model, we tested three machine learning classifiers (support vector machine [SVM], random forest [RF], and convolutional neural network [CNN]). Receiver operating characteristic analysis was performed to calculate the area under the receiver operating characteristic curve (AUC). Results A total of 1382 CT scans (mean patient age, 67 years ± 11 [SD]; 759 women) were included. Of the 1382 CT scans, 104 (8%) were assessed as having ILA, 492 (36%) as indeterminate for ILA, and 786 (57%) as without ILA according to ground-truth labeling. The cohort was divided into a training set (n = 96; ILA, n = 48), a validation set (n = 24; ILA, n = 12), and a test set (n = 1262; ILA, n = 44). Among the models evaluated (two- and three-label section inference models; two- and three-label SVM, RF, and CNN case inference models), the model using the three-label method in the section inference model and the two-label method and RF in the case inference model achieved the highest AUC, at 0.87. Conclusion The model demonstrated substantial performance in estimating ILA probability, indicating its potential utility in clinical settings. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Zagurovskaya in this issue.
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Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Aprendizado de Máquina , Interpretação de Imagem Radiográfica Assistida por Computador , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Estudos Retrospectivos , Feminino , Masculino , Neoplasias Pulmonares/diagnóstico por imagem , Idoso , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Boston , Pulmão/diagnóstico por imagem , ProbabilidadeRESUMO
BACKGROUND: Although crackles on chest auscultation represent a fundamental component of the diagnostic suspect for fibrotic interstitial lung disease (ILD), their reliability has not been properly studied. We assessed the agreement among respiratory physicians on the presence and changes over time of audible crackles collected in a prospective longitudinal cohort of patients with fibrotic ILD. METHODS: Lung sounds were digitally recorded at baseline and after 12 months at eight anatomical sites. Nine respiratory physicians blindly assessed randomized couples of recordings obtained from the same anatomical site at different timepoints. The physicians indicated the presence of crackles in individual recordings and which recording from each couple eventually had more intense crackles. Fleiss' kappa coefficient was used to measure inter- and intra-rater agreement. RESULTS: Fifty-two patients, mostly with a diagnosis of IPF (n = 40, 76.9%) were prospectively enrolled between October 2019 and May 2021. The final acoustic dataset included 702 single recordings, corresponding to 351 couples of recordings from baseline and 12-months timepoints. Kappa coefficient was 0.57 (95% CI 0.55-0.58) for the presence of crackles and 0.42 (95% CI 0.41-0.43) for acoustic change. Intra-rater agreement, measured for three respiratory physicians on three repeated assessments, ranged from good to excellent for the presence of crackles (κ = 0.87, κ = 0.86, κ = 0.79), and from moderate to good for acoustic change (κ = 0.75, κ = 0.76, κ = 0.57). CONCLUSIONS: Agreement between respiratory physicians for the presence of crackles and acoustic change was acceptable, suggesting that crackles represent a reliable acoustic finding in patients with fibrotic ILD. Their role as a lung-derived indicator of disease progression merits further studies.
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Doenças Pulmonares Intersticiais , Sons Respiratórios , Humanos , Masculino , Estudos Prospectivos , Feminino , Estudos Longitudinais , Pessoa de Meia-Idade , Idoso , Reprodutibilidade dos Testes , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/fisiopatologia , Sons Respiratórios/fisiopatologia , Sons Respiratórios/diagnóstico , Auscultação/métodosRESUMO
Pulmonary high-grade neuroendocrine carcinomas (HGNECs) have poor prognoses and require multimodal treatment, and interstitial lung disease (ILD) restricts sufficient treatment of patients with lung cancer. We aimed to clarify ILD's prognostic impact on pulmonary HGNEC, which has previously gone unreported. We retrospectively analyzed 53 patients with HGNEC who underwent resections at our department between 2006 and 2021 and evaluated the clinicopathological prognostic features, including ILD. The patients' mean age was 70 years; 46 (87%) were male, and all were smokers. Large-cell neuroendocrine and small-cell lung carcinomas were diagnosed in 36 (68%) and 17 (32%) patients, respectively. The pathological stages were stage I, II, and III in 31 (58%), 11 (21%), and 11 (21%) patients, respectively. Nine patients (17%) had ILD, which was a significant overall survival prognostic factor in a multivariate Cox proportional hazards regression analysis (p = 0.048), along with lymph node metastasis (p = 0.004) and non-administration of platinum-based adjuvant chemotherapy (p = 0.003). The 5 year survival rate of the ILD patients was 0%, significantly worse than that of patients without ILD (58.7%; p = 0.003). Patients with HGNEC and ILD had a poor prognosis owing to adjuvant therapy's limited availability for recurrence and the development of acute exacerbations associated with ILD.
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Carcinoma Neuroendócrino , Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/mortalidade , Idoso , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/complicações , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Prognóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Gradação de Tumores , Estadiamento de Neoplasias , Taxa de SobrevidaRESUMO
BACKGROUND: PARP inhibitors (PARPi) are used in the treatment of ovarian, breast, pancreatic, and prostate cancers. Pneumonitis has been identified as a potential side effect, with a higher meta-analysis-assessed risk for olaparib versus other PARPi. Olaparib-induced interstitial lung disease (O-ILD) was first described within the Japanese population, with few information available for Caucasian patients. METHODS: We performed a retrospective study by pooling data from the French and Belgian pharmacovigilance databases from 2018 to 2022. Patients with O-ILD were included following a central review by: 1) pharmacologists using the French drug causality assessment method; 2) senior pneumologists or radiologists, using the Fleischner Society's recommendations. RESULTS: Five patients were identified and analysed. All were females, with ovarian or breast cancer. Median age at O-ILD diagnosis was 71 (38-72) years old, with no smoking history. Median delay between treatment initiation and symptom occurrence was 12 (6-33) weeks. Pneumonitis severity assessed using the Common Terminology Criteria for Adverse Events V5 was Grade 3 (n = 4) or 2 (n = 1). CT-scan review (n = 3) described hypersensitivity pneumonitis reaction as a common pattern. Bronchioalveolar lavage (n = 4) revealed lymphocytic alveolitis. Treatments relied on olaparib discontinuation (n = 5) and glucocorticoid intake (n = 4), with no fatal issue. Safe re-challenge with PARPi occurred in two patients. Forty additional O-ILD cases were identified in the WHO VigiBase database, including one fatal case. CONCLUSIONS: PARPi-ILD is a rare but potentially life-threatening disease, presenting as a hypersensitivity pneumonitis pattern within 3 months of PARPi initiation. Treatment primarily relies on medication discontinuation. Re-challenging with another PARPi could be considered. CLINICAL TRIAL NUMBER: CEPRO #2023-010.
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Doenças Pulmonares Intersticiais , Farmacovigilância , Ftalazinas , Piperazinas , Inibidores de Poli(ADP-Ribose) Polimerases , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Ftalazinas/efeitos adversos , Ftalazinas/uso terapêutico , Feminino , Piperazinas/efeitos adversos , Piperazinas/uso terapêutico , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Adulto , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tomografia Computadorizada por Raios X , Neoplasias Ovarianas/tratamento farmacológico , França , BélgicaRESUMO
BACKGROUND: The R-Scale-PF was proposed to evaluate the health-related quality of life (HRQoL) in patients with idiopathic pulmonary fibrosis (IPF). We generated a German version of the R-Scale-PF (GR-Scale), representing the first translation of the questionnaire into another language and assessed HRQoL longitudinally in various interstitial lung diseases (ILDs) using the R-Scale-PF scoring system at a specialized ILD centre. METHODS: We have translated the questionnaire in accordance with the WHO translation guidelines and applied it to 80 ILD patients of our department, with follow-ups after 3-6 months, assessing its internal consistency, floor and ceiling effects, concurrent validity, known-groups validity, and its responsiveness to changes over time. RESULTS: At baseline, all 80 patients completed the GR-Scale. In 70 patients (87.5%), follow-up data could be obtained after 4.43 ± 1.2 months. The GR-Scale demonstrated acceptable internal consistency (Cronbach's α 0.749) and slight floor effects. Concurrent validity analysis showed weak but significant correlations with forced vital capacity (FVC; r=-0.282 p = 0.011) and diffusion capacity for carbon monoxide (DLco; r=-0.254 p = 0.025). In the follow-up analysis, moderate correlations were found with FVC (r=-0.41 p < 0.001) and DLco (r=-0.445 p < 0.001). No significant difference in the total score was found between patients with IPF (n = 10) and with non-IPF ILDs (n = 70). The GR-Scale successfully discriminated between groups of varying disease severity based on lung function parameters and the need for long-term oxygen therapy (LTOT). Furthermore, it was able to distinguish between patients showing improvement, stability or decline of lung function parameters. CONCLUSION: Our prospective observational pilot study suggests that the GR-Scales is a simple and quick tool to measure HRQoL in patients with ILDs, thus providing an important additional information for the clinical assessment of ILD patients. TRIAL REGISTRATION: Our study was retrospectively registered in the German Clinical Trial Register (DRKS) on 02.11.2022 (DRKS-ID: DRKS00030599).
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Doenças Pulmonares Intersticiais , Qualidade de Vida , Humanos , Masculino , Feminino , Idoso , Doenças Pulmonares Intersticiais/fisiopatologia , Pessoa de Meia-Idade , Inquéritos e Questionários , Capacidade Vital , Reprodutibilidade dos Testes , Fibrose Pulmonar Idiopática/fisiopatologia , Fibrose Pulmonar Idiopática/psicologia , Alemanha , TraduçõesRESUMO
Introduction: This study aimed to identify useful clinical indicators for predicting the relapse of interstitial lung disease (ILD) complicated with anti-aminoacyl-tRNA synthetase (ARS) antibodies (anti-ARS-ILD), being treated with prednisolone and calcineurin inhibitors. Methods: Fifty patients with anti-ARS-ILD were enrolled between October 2014 and August 2022. All patients were treated with prednisolone and calcineurin inhibitors as remission induction therapy and followed up for over a year with these combination therapies. We examined patients who experienced ILD relapse after immunosuppressive treatment. We explored the risk factors for predicting ILD relapse in these patients by comparing demographic, clinical, laboratory, and radiological findings and treatments between the relapsed and non-relapsed groups on admission. Results: Of the 50 patients, 19 (38%) relapsed during a median follow-up of 4.8 years. Univariate and multivariate Cox regression analyses identified the presence of acute/subacute (A/S)-ILD, higher serum aldolase (ALD) and surfactant protein-D (SP-D) levels, and lower %forced vital capacity (FVC) as risk factors for relapse in patients with anti-ARS-ILD. Using the receiver operating curve analysis, ALD ≥6.3 U/L, SP-D ≥207 ng/mL, and %FVC ≤76.8% were determined as the cut-off levels for indicating a poor prognosis. The 5-year relapse rate was significantly higher in patients with A/S-ILD, serum ALD≥6.3 U/L, serum SP-D ≥207 ng/mL, or %FVC of ≤76.8% than in those without these parameters. (P=0.009, 0.0005, 0.0007, 0.0004, respectively) Serum ALD levels were significantly correlated with the disease activity indicators of anti-ARS-ILD. Conclusion: The presence of A/S-ILD, higher serum ALD and SP-D levels, and lower %FVC are useful indicators for predicting anti-ARS-ILD relapse.
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Aminoacil-tRNA Sintetases , Doenças Pulmonares Intersticiais , Recidiva , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Aminoacil-tRNA Sintetases/imunologia , Prognóstico , Idoso , Autoanticorpos/sangue , Quimioterapia Combinada , Inibidores de Calcineurina/uso terapêutico , Prednisolona/uso terapêutico , Fatores de Risco , Imunossupressores/uso terapêutico , Biomarcadores/sangue , AdultoRESUMO
Background: Common Variable Immunodeficiency Disorders (CVID) encompass a spectrum of immunodeficiency characterised by recurrent infections and diverse non-infectious complications (NICs). This study aimed to describe the clinical features and variation in NICs in CVID with and without interstitial lung disease (ILD) from a large UK national registry population. Methods: Retrospective, cross-sectional data from a UK multicentre database (previously known as UKPIN), categorising patients into those with CVID-ILD and those with NICs related to CVID but without pulmonary involvement (CVID-EP; EP= extra-pulmonary involvement only). Results: 129 patients were included. Chronic lung diseases, especially CVID-ILD, are prominent complications in complex CVID, occurring in 62% of the cohort. Bronchiectasis was common (64% of the cohort) and associated with greater pulmonary function impairment in patients with CVID-ILD compared to those without bronchiectasis. Lymphadenopathy and the absence of gastrointestinal diseases were significant predictors of ILD in complex CVID. Although the presence of liver disease did not differ significantly between the groups, nearly half of the CVID-ILD patients were found to have liver disease. Patients with CVID-ILD were more likely to receive immunosuppressive treatments such as rituximab and mycophenolate mofetil than the CVID-EP group, indicating greater need for treatment and risk of complications. Conclusion: This study highlights the significant burden of CVID-ILD within the CVID population with NICs only. The lungs emerged as the most frequently affected organ, with ILD and bronchiectasis both highly prevalent. These findings emphasise the necessity of a comprehensive and multidisciplinary approach in managing CVID patients, considering their susceptibility to various comorbidities and complications.
Assuntos
Imunodeficiência de Variável Comum , Doenças Pulmonares Intersticiais , Humanos , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/epidemiologia , Feminino , Masculino , Reino Unido/epidemiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Estudos Transversais , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/epidemiologia , Bronquiectasia/epidemiologia , Idoso , Adulto Jovem , Sistema de RegistrosRESUMO
BACKGROUND: Clinical amyopathic dermatomyositis is characterized by cutaneous symptoms but lacks muscle symptoms. Anti-melanoma differentiation-associated gene 5 antibodies are frequently found in Japanese patients with clinical amyopathic dermatomyositis. Patients with rapidly progressive interstitial lung disease with positive anti-melanoma differentiation-associated gene 5 antibodies have poor prognoses, and majority of them are treated with combination immunosuppressive therapy; however, the best treatment is yet to be determined. CASE PRESENTATION: A 52-year-old Asian male patient presented with a chief complaint of dyspnea on exertion. He had a typical skin rash and rapidly progressive interstitial pneumonia. Additionally, anti-melanoma differentiation-associated gene 5 antibodies were detected; therefore, he was diagnosed with dermatomyositis-associated interstitial pneumonia. Respiratory failure worsened despite administering steroid pulse therapy, tacrolimus, and cyclophosphamide. Consequently, plasma exchange was performed on day 13 of admission. After a slight improvement, the patient's respiratory failure worsened. Thus, cyclophosphamide was replaced by tofacitinib on day 28. Although respiratory failure improved and the progression of interstitial pneumonia seemed under control, ßD-glucan level increased and Aspergillus antigen was detected on day 49. Micafungin and voriconazole were administered, but the patient succumbed to worsening respiratory failure on day 61. The pathological autopsy revealed multiple nodular lesions with cavity formation in both lungs and the presence of Aspergillus with severe neutrophilic infiltration and necrosis, which supported the diagnosis of invasive pulmonary aspergillosis. CONCLUSION: The patient with anti-melanoma differentiation-associated gene 5 antibody-related rapidly progressive interstitial lung disease, whose disease was difficult to control after the administration of triple immunosuppressive therapy (steroids, tacrolimus, and cyclophosphamide), showed good response with tofacitinib. Unfortunately, the patient died of invasive pulmonary aspergillosis owing to severe immunosuppression; thus, the signs of complications should be promptly detected.
Assuntos
Dermatomiosite , Helicase IFIH1 Induzida por Interferon , Doenças Pulmonares Intersticiais , Piperidinas , Pirimidinas , Humanos , Dermatomiosite/tratamento farmacológico , Dermatomiosite/complicações , Dermatomiosite/imunologia , Masculino , Doenças Pulmonares Intersticiais/tratamento farmacológico , Pessoa de Meia-Idade , Pirimidinas/uso terapêutico , Helicase IFIH1 Induzida por Interferon/imunologia , Piperidinas/uso terapêutico , Piperidinas/administração & dosagem , Autoanticorpos/sangue , Imunossupressores/uso terapêutico , Resultado do Tratamento , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
As the clinical course of systemic sclerosis (SSc) varies widely, prognostic indicators have been sought to predict the outcomes of individual patients. Racial differences in SSc render it necessary to validate prognostic indicators in different patient cohorts. In this study, we aimed to assess clinical and laboratory parameters in Japanese patients with early-stage SSc with diffuse cutaneous involvement and/or interstitial lung disease, and identify predictive factors for disease progression. We performed multivariate analyses of baseline clinical information to estimate symptoms 4 years later in Japanese patients with diffuse cutaneous SSc and/or SSc with interstitial lung disease. Patients were enrolled in the study within 5 years of disease onset at 10 Japanese SSc centers. Over 12 years, 115 patients followed up for 4 years were included in this study. The modified Rodnan skin score (mRSS) at 4 years correlated with the baseline mRSS and finger-to-palm distance, defined as the average length from the distal tip of the fourth finger to the distal palmar crease. The percentage predicted vital capacity (%VC) in year 4 positively and negatively correlated with initial %VC and the presence of anti-topoisomerase I antibodies, respectively. The Health Assessment Questionnaire Disability Index (HAQ-DI) at 4 years was positively and negatively associated with baseline HAQ-DI and %VC, respectively. The occurrence of digital ulcers within 4 years was associated with the initial presence of digital ulcers, finger-to-palm distance, and the presence of digital pitting scars and anti-topoisomerase I antibodies. This study identified several factors that may predict the progression of early-stage SSc in Japanese patients. Finger-to-palm distance may be a useful tool for predicting the progression of skin thickening and the development of digital ulcers in the early stages of severe SSc, but larger, long-term prospective studies are needed to confirm our findings.
Assuntos
Progressão da Doença , Doenças Pulmonares Intersticiais , Índice de Gravidade de Doença , Humanos , Masculino , Feminino , Japão/epidemiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Adulto , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/etiologia , Prognóstico , Capacidade Vital , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/sangue , DNA Topoisomerases Tipo I/imunologia , Pele/patologia , Idade de Início , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/etiologia , Úlcera Cutânea/patologia , Seguimentos , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/complicações , Esclerodermia Difusa/imunologia , Esclerodermia Difusa/patologia , Avaliação da Deficiência , População do Leste AsiáticoRESUMO
OBJECTIVE: Quantitative chest computed tomography (qCT) methods are new tools that objectively measure parenchymal abnormalities and vascular features on CT images in patients with interstitial lung disease (ILD). We aimed to investigate whether the qCT measures are predictors of 5-year mortality in patients with systemic sclerosis (SSc). METHODS: Patients diagnosed with SSc were retrospectively selected from 2011 to 2022. Patients should have had volumetric high-resolution CTs (HRCTs) and pulmonary function tests (PFTs) performed at baseline and at 24 months of follow-up. The following parameters were evaluated in HRCTs using Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER): ground glass opacities, reticular pattern, honeycombing, and pulmonary vascular volume. Factors associated with death were evaluated by KaplanâMeier survival curves and multivariate analysis models. Semiquantitative analysis of the HRCTs images was also performed. RESULTS: Seventy-one patients were included (mean age, 54.2 years). Eleven patients (15.49%) died during the follow-up, and all patients had ILD. As shown by KaplanâMeier curves, survival was worse among patients with an ILD extent (ground glass opacities + reticular pattern + honeycombing) ≥ 6.32%, a reticular pattern ≥ 1.41% and a forced vital capacity (FVC) < 70% at baseline. The independent predictors of mortality by multivariate analysis were a higher reticular pattern (Exp 2.70, 95%CI 1.26-5.82) on qCT at baseline, younger age (Exp 0.906, 95%CI 0.826-0.995), and absolute FVC decline ≥ 5% at follow-up (Exp 15.01, 95%CI 1.90-118.5), but not baseline FVC. Patients with extensive disease (>20% extension) by semiquantitative analysis according to Goh's staging system had higher disease extension on qCT at baseline and follow-up. CONCLUSION: This study showed that the reticular pattern assessed by baseline qCT may be a useful tool in the clinical practice for assessing lung damage and predicting mortality in SSc.
Assuntos
Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Tomografia Computadorizada por Raios X , Humanos , Escleroderma Sistêmico/mortalidade , Escleroderma Sistêmico/diagnóstico por imagem , Escleroderma Sistêmico/complicações , Pessoa de Meia-Idade , Feminino , Masculino , Tomografia Computadorizada por Raios X/métodos , Estudos Longitudinais , Estudos Retrospectivos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/mortalidade , Idoso , Adulto , Estimativa de Kaplan-Meier , Testes de Função Respiratória , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/fisiopatologia , PrognósticoRESUMO
High-resolution computed tomography (HRCT) is important for diagnosing interstitial lung disease (ILD) in inflammatory rheumatic disease (IRD) patients. However, visual ILD assessment via HRCT often has high inter-reader variability. Artificial intelligence (AI)-based techniques for quantitative image analysis promise more accurate diagnostic and prognostic information. This study evaluated the reliability of artificial intelligence-based quantification of pulmonary HRCT (AIqpHRCT) in IRD-ILD patients and verified IRD-ILD quantification using AIqpHRCT in the clinical setting. Reproducibility of AIqpHRCT was verified for each typical HRCT pattern (ground-glass opacity [GGO], non-specific interstitial pneumonia [NSIP], usual interstitial pneumonia [UIP], granuloma). Additional, 50 HRCT datasets from 50 IRD-ILD patients using AIqpHRCT were analysed and correlated with clinical data and pulmonary lung function parameters. AIqpHRCT presented 100% agreement (coefficient of variation = 0.00%, intraclass correlation coefficient = 1.000) regarding the detection of the different HRCT pattern. Furthermore, AIqpHRCT data showed an increase of ILD from 10.7 ± 28.3% (median = 1.3%) in GGO to 18.9 ± 12.4% (median = 18.0%) in UIP pattern. The extent of fibrosis negatively correlated with FVC (ρ=-0.501), TLC (ρ=-0.622), and DLCO (ρ=-0.693) (p < 0.001). GGO measured by AIqpHRCT also significant negatively correlated with DLCO (ρ=-0.699), TLC (ρ=-0.580) and FVC (ρ=-0.423). For the first time, the study demonstrates that AIpqHRCT provides a highly reliable method for quantifying lung parenchymal changes in HRCT images of IRD-ILD patients. Further, the AIqpHRCT method revealed significant correlations between the extent of ILD and lung function parameters. This highlights the potential of AIpqHRCT in enhancing the accuracy of ILD diagnosis and prognosis in clinical settings, ultimately improving patient management and outcomes.