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Idiopathic pulmonary fibrosis (IPF) is a rare, chronic, and progressive interstitial lung disease with an average survival of approximately 3 years. The evolution of IPF is unpredictable, with some patients presenting a relatively stable condition with limited progression over time, whereas others deteriorate rapidly. In addition to IPF, other interstitial lung diseases can lead to pulmonary fibrosis, and up to a third have a progressive phenotype with the same prognosis as IPF. Clinical, biological, and radiological risk factors of progression were identified, but no specific biomarkers of fibrogenesis are currently available. A recent interest in the fibroblast activation protein alpha (FAPα) has emerged. FAPα is a transmembrane serine protease with extracellular activity. It can also be found in a soluble form, also named anti-plasmin cleaving enzyme (APCE). FAPα is specifically expressed by activated fibroblasts, and quinoline-based specific inhibitors (FAPI) were developed, allowing us to visualize its distribution in vivo by imaging techniques. In this review, we discuss the use of FAPα as a useful biomarker for the progression of lung fibrosis, by both its assessment in human fluids and/or its detection by imaging techniques and immunohistochemistry.
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Although pulmonary complications are frequent in patients suffering from hematological diseases, secondary pulmonary alveolar proteinosis is a very rare complication of myelofibrosis. We describe the case of a 65-year-old male patient treated by Ruxolitinib for myelofibrosis who developed a secondary pulmonary alveolar proteinosis complicated by a Mycobacterium avium infection. We believe that this respiratory complication might be related to the myelofibrosis and to the initiation of the Ruxolitinib according to its temporal relationship. Pulmonologists should be aware that respiratory symptoms in myelofibrosis patients taking Ruxolitinib may be related to pulmonary alveolar proteinosis.
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RATIONALE: Endoscopic lung volume reduction improves lung function, quality of life and exercise capacity in severe emphysema patients. However, its effect on the diaphragm function is not well understood. We hypothesised that endoscopic lung volume reduction increases its strength by modifying its shape. OBJECTIVES: To investigate changes in both diaphragm shape and strength induced by the insertion of endobronchial valves. METHODS: In 19 patients, both the diaphragm shape and strength were investigated respectively by 3D Slicer software applied on CT scans acquired at functional residual capacity and by transdiaphragmatic pressure measurements by bilateral magnetic stimulation of the phrenic nerves before and 3 months after unilateral valves insertion. MEASUREMENTS AND MAIN RESULTS: After lung volume reduction (median (IQR), 434 mL (-597 to -156], p<0.0001), diaphragm strength increased (transdiaphragmatic pressure: 3 cmH2O (2.3 to 4.2), p<0.0001). On the treated side, this increase was associated with an increase in the coronal (16 mm (13 to 24), p<0.0001) and sagittal (26 mm (21 to 30), p<0.0001) lengths as well as in the area of the zone of apposition (62 cm2 (3 to 100), p<0.0001) with a decrease in the coronal (8 mm (-12 to -4), p<0.0001) and sagittal (9 mm (-18 to -2), p=0.0029) radii of curvature. CONCLUSIONS: Endoscopic lung volume reduction modifies the diaphragm shape by increasing its length and its zone of apposition and by decreasing its radius of curvature on the treated side, resulting in an increase in its strength. TRIAL REGISTRATION NUMBER: NCT05799352.
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Diafragma , Pneumonectomia , Enfisema Pulmonar , Tomografia Computadorizada por Raios X , Humanos , Diafragma/diagnóstico por imagem , Masculino , Pneumonectomia/métodos , Feminino , Pessoa de Meia-Idade , Idoso , Enfisema Pulmonar/cirurgia , Enfisema Pulmonar/fisiopatologia , Enfisema Pulmonar/diagnóstico por imagem , Broncoscopia/métodos , Força Muscular/fisiologia , Capacidade Residual Funcional/fisiologiaRESUMO
Chemerin is an atypical chemokine first described as a chemoattractant agent for monocytes, natural killer cells, plasmacytoid and myeloid dendritic cells, through interaction with its main receptor, the G protein-coupled receptor chemokine-like receptor 1 (CMKLR1). Chemerin has been studied in various lung disease models, showing both pro- and anti-inflammatory properties. Given the incidence and burden of inflammatory lung diseases from diverse origins (infectious, autoimmune, age-related, etc.), chemerin has emerged as an interesting therapeutical target due to its immunomodulatory role. However, as highlighted by this review, further research efforts to elucidate the mechanisms governing chemerin's dual pro- and anti-inflammatory characteristics are urgently needed. Moreover, although a growing body of evidence suggests chemerin as a potential biomarker for the diagnosis and/or prognosis of inflammatory lung diseases, this review underscores the necessity for standardizing both sampling types and measurement techniques before drawing definitive conclusions.
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Quimiocinas , Fatores Quimiotáticos , Pneumopatias , Humanos , Anti-Inflamatórios , Quimiocinas/metabolismo , Células Dendríticas , Pneumopatias/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Real-life data on suspected familial fibrosis, defined as the occurrence of the disease in a patient younger than 50 and/or having at least one relative affected by pulmonary fibrosis remain scarce. METHODS: The Belgian and Luxembourg IPF registry (PROOF-Next) is a multicentric prospective longitudinal and observational study set in Belgium and Luxembourg. We compared characteristics and clinical course of patients with suspected familial pulmonary fibrosis (FPF) and sporadic IPF. RESULTS: We included 618 patients in the analysis, of whom 76 (12%) fulfilled criteria for FPF. They were significantly younger than sIPF (median age (range) 65 (43-87), vs. 72 (51-98), p = 0.0001). Male gender proportion and smoking status did not differ between groups, but the number of pack-year among current and former smokers was lower in FPF (20 vs. 25, p = 0.02). Besides, 87% of FPF and 76% of sIPF were treated with antifibrotic (p = 0.047). Baseline pulmonary function tests were similar in both groups, as well as median time before progression and transplant-free survival. Finally, genetic testing, performed in a minority, led to the identification of 10 telomerase-related gene variants. CONCLUSION: Although younger and exposed to less tobacco, patients with FPF show an equally aggressive progression as observed in sporadic IPF patients. These results warrant early referral of FPF patients to expert centres for optimal management.
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Fibrose Pulmonar Idiopática , Humanos , Masculino , Estudos Prospectivos , Fibrose Pulmonar Idiopática/epidemiologia , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/tratamento farmacológico , Testes de Função Respiratória , Sistema de Registros , Progressão da DoençaRESUMO
BACKGROUND: Fibroblast activation protein-α (FAPα) is a marker of activated fibroblasts that can be selectively targeted by an inhibitor (FAPI) and visualised by PET/CT imaging. We evaluated whether the measurement of FAPα in bronchoalveolar lavage fluids (BALF) and the uptake of FAPI by PET/CT could be used as biomarkers of fibrogenesis. METHODS: The dynamics of lung uptake of 18F-labeled FAPI ([18F]FAPI-74) was assessed in the bleomycin mouse model at various time points and using different concentrations of bleomycin by PET/CT. FAPα was measured in BALFs from these bleomycin-treated and control mice. FAPα levels were also assessed in BALFs from controls and patients with idiopathic pulmonary fibrosis (IPF). RESULTS: Bleomycin-treated mice presented a significantly higher uptake of [18F]FAPI-74 during lung fibrinogenesis (days 10 and 16 after instillation) compared to control mice. No significant difference was observed at initial inflammatory phase (3 days) and when fibrosis was already established (28 days). [18F]FAPI-74 tracer was unable to show a dose-response to bleomycin treatment. On the other hand, BALF FAPα levels were steeply higher in bleomycin-treated mice at day 10 and a significant dose-response effect was observed. Moreover, FAPα levels were strongly correlated with lung fibrosis as measured by the modified Aschroft histological analysis, hydroxyproline and the percentage of weight loss. Importantly, higher levels of FAPα were observed in IPF patients where the disease was progressing as compared to stable patients and controls. Moreover, patients with FAPα BALF levels higher than 192.5 pg/mL presented a higher risk of progression, transplantation or death compared to patients with lower levels. CONCLUSIONS: Our preclinical data highlight a specific increase of [18F]FAPI-74 lung uptake during the fibrotic phase of the bleomycin murine model. The measurement of FAPα in BALF appears to be a promising marker of the fibrotic activity in preclinical models of lung fibrosis and in IPF patients. Further studies are required to confirm the role of FAPα in BALF as biomarker of IPF activity and assess the relationship between FAPα levels in BALF and [18F]FAPI-74 uptake on PET/CT in patients with fibrotic lung disease.
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Fibrose Pulmonar Idiopática , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Camundongos , Animais , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose , Líquido da Lavagem Broncoalveolar , Bleomicina/efeitos adversosRESUMO
BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease, predisposing to an increased risk of infection. A complete picture of these infections is lacking. RESEARCH QUESTION: Describe the characteristics and clinical outcomes of patients diagnosed with aPAP, and to identify risk factors associated with opportunistic infections. METHODS: We conducted a retrospective cohort including all patients diagnosed with aPAP between 2008 and 2018 in France and Belgium. Data were collected using a standardised questionnaire including demographics, comorbidities, imaging features, outcomes and microbiological data. RESULTS: We included 104 patients, 2/3 were men and median age at diagnosis was 45 years. With a median follow-up of 3.4 years (IQR 1.7-6.6 years), 60 patients (58%), developed at least one infection, including 23 (22%) with opportunistic infections. Nocardia spp was the main pathogen identified (n=10). Thirty-five (34%) patients were hospitalised due to infection. In univariate analysis, male gender was associated with opportunistic infections (p=0.04, OR=3.88; 95% CI (1.02 to 22.06)). Anti-granulocyte macrophage colony-stimulating factor antibody titre at diagnosis was significantly higher among patients who developed nocardiosis (1058 (316-1591) vs 580 (200-1190), p=0.01). Nine patients had died (9%), but only one death was related to infection. INTERPRETATION: Patients with aPAP often presented with opportunistic infections, especially nocardiosis, which highlights the importance of systematic search for slow-growing bacteria in bronchoalveolar lavage or whole lung lavage.
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Doenças Autoimunes , Nocardiose , Infecções Oportunistas , Proteinose Alveolar Pulmonar , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Doenças Autoimunes/complicações , Nocardiose/diagnóstico , Nocardiose/epidemiologia , AutoanticorposRESUMO
BACKGROUND: With the increasing use of low dose CT scans, numerous pulmonary nodules are detected. As majority of them are benign, development of efficient non-surgical diagnostic intervention is mandatory. Electromagnetic navigation bronchoscopy (ENB) has been developed to reach difficult to access lesions. The aim of the present study was to compare the diagnostic yield of ENB procedures performed in a classical endoscopy suite or in a hybrid room equipped by a cone beam CT (CBCT). METHODS: A monocentric randomized study was performed in the Erasme Hospital between January 2020 and December 2021. Lung nodules of maximum 30 mm of diameter were eligible. In both arms (endoscopy or CBCT suites), ENB, fluoroscopic guidance and a radial endobronchial ultrasound were used to reach the lesion. Then six trans-bronchial biopsies (TBB) and one trans-bronchial lung cryobiopsy (TBLC) were performed. Primary outcomes were the diagnostic yield and diagnostic accuracy of the procedure. RESULTS: Forty-nine patients were randomized (24 in the endoscopy and 25 in the CBCT arms). The lesion size was 15,9 ± 4,6 mm and 16,6 ± 6,0 mm respectively (mean ± SD, p = NS). The diagnostic yield of ENB performed under CBCT guidance was 80% compared to 42% when performed in the endoscopy suite under standard fluoroscopic guidance (p < 0,05). Similarly, the diagnostic accuracy in the CBCT group was 87% compared to 54% for the endoscopy group (p < 0,05). Duration of the procedure in the CBCT and endoscopy arms was 80 ± 23 and 61 ± 13 min respectively (mean ± SD, p < 0,01). Performing TBLC in addition to TBB increased the diagnostic yield by 14% (17 and 12,5% in CBCT and endoscopy suites respectively, p = NS). CONCLUSION: This study highlighted the additional value to perform ENB procedure under CBCT guidance for small size (less than 2 cm of diameter) pulmonary nodules. TRIAL REGISTRATION: Clinical trial registration number: NCT05257382.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Humanos , Broncoscopia/métodos , Neoplasias Pulmonares/patologia , Bélgica , Fenômenos Eletromagnéticos , Nódulos Pulmonares Múltiplos/patologia , Tomografia Computadorizada de Feixe CônicoRESUMO
Endoscopic lung volume reduction using unidirectional endobronchial valves is a new technique in the treatment of patients with severe emphysema. However, the movements of the thoracic structures after endobronchial valves insertion are still unpredictable We report the unusual outcome of six patients after valves insertion in the left upper lobe. They all developed a complete atelectasis of the target lobe, a pneumothorax and sequential genuine bullae in the treated left lung of unknown etiology. The chest CT scan prior to the valves insertion was unremarkable. Three patients developed an air-liquid level in the bullae the day before a bacterial infection of their left lower lobe. The three other patients had an uneventful spontaneous resolution of their bullae at long-term follow-up. Therefore, a conservative attitude should be followed in this particular setting.
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Enfisema , Pneumotórax , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Vesícula/diagnóstico por imagem , Vesícula/etiologia , Vesícula/cirurgia , Broncoscopia/efeitos adversos , Enfisema/complicações , Seguimentos , Humanos , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Pneumotórax/cirurgia , Doença Pulmonar Obstrutiva Crônica/complicações , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/cirurgia , Resultado do TratamentoRESUMO
Background: Chemerin is an extracellular protein with chemotactic activities and its expression is increased in various diseases such as metabolic syndrome and inflammatory conditions. Its role in lung pathology has not yet been extensively studied but both known pro- and anti-inflammatory properties have been observed. The aim of our study was to evaluate the involvement of the chemerin/ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic value. Methods: Blood samples from confirmed COVID-19 patients were collected at day 1, 5 and 14 from admission to Erasme Hospital (Brussels - Belgium). Chemerin concentrations and inflammatory biomarkers were analyzed in the plasma. Blood cells subtypes and their expression of ChemR23 were determined by flow cytometry. The expression of chemerin and ChemR23 was evaluated on lung tissue from autopsied COVID-19 patients by immunohistochemistry (IHC). Results: 21 healthy controls (HC) and 88 COVID-19 patients, including 40 in intensive care unit (ICU) were included. Plasma chemerin concentration were significantly higher in ICU patients than in HC at all time-points analyzed (p<0.0001). Moreover, they were higher in deceased patients compared to survivors (p<0.05). Logistic univariate regression and multivariate analysis demonstrated that chemerin level at day 14 of admission was an independent risk factor for death. Accordingly, chemerin levels correlated with inflammatory biomarkers such as C-reactive protein and tumor necrosis factor α. Finally, IHC analysis revealed a strong expression of ChemR23 on smooth muscle cells and chemerin on myofibroblasts in advanced acute respiratory distress syndrome (ARDS). Discussion: Increased plasma chemerin levels are a marker of severity and may predict death of COVID-19 patients. However, multicentric studies are needed, before chemerin can be considered as a biomarker of severity and death used in daily clinical practice. Further studies are also necessary to identify the precise mechanisms of the chemerin/ChemR23 system in ARDS secondary to viral pneumonia.
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COVID-19 , Síndrome do Desconforto Respiratório , Quimiocinas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Receptores de Quimiocinas , Fatores de RiscoRESUMO
The new pandemic virus SARS-CoV-2 is characterized by uncontrolled hyper-inflammation in severe cases. As the IL-22/IL-22R1 axis was reported to be involved in inflammation during viral infections, we characterized the expression of IL-22 receptor1, IL-22 and IL-22 binding protein in COVID-19 patients. Blood samples were collected from 19 non-severe and 14 severe patients on the day they presented (D0), at D14, and six months later, and from 6 non-infected controls. The IL-22R1 expression was characterized by flow cytometry. Results were related to HLA-DR expression of myeloid cells, to plasma concentrations of different cytokines and chemokines and NK cells and T lymphocytes functions characterized by their IFN-γ, IL-22, IL-17A, granzyme B and perforin content. The numbers of IL-22R1+ classical, intermediate, and non-classical monocytes and the proportions of IL-22R1+ plasmacytoid DC (pDC), myeloid DC1 and DC2 (mDC1, mDC2) were higher in patients than controls at D0. The proportions of IL-22R1+ classical and intermediate monocytes, and pDC and mDC2 remained high for six months. High proportions of IL-22R1+ non-classical monocytes and mDC2 displayed HLA-DRhigh expression and were thus activated. Multivariate analysis for all IL-22R1+ myeloid cells discriminated the severity of the disease (AUC=0.9023). However, correlation analysis between IL-22R1+ cell subsets and plasma chemokine concentrations suggested pro-inflammatory effects of some subsets and protective effects of others. The numbers of IL-22R1+ classical monocytes and pDC were positively correlated with pro-inflammatory chemokines MCP-1 and IP-10 in severe infections, whereas IL-22R1+ intermediate monocytes were negatively correlated with IL-6, IFN-α and CRP in non-severe infections. Moreover, in the absence of in vitro stimulation, NK and CD4+ T cells produced IFN-γ and IL-22, and CD4+ and CD8+ T cells produced IL-17A. CD4+ T lymphocytes also expressed IL-22R1, the density of its expression defining two different functional subsets. In conclusion, we provide the first evidence that SARS-CoV-2 infection is characterized by an abnormal expression of IL22R1 on blood myeloid cells and CD4+ T lymphocytes. Our results suggest that the involvement of the IL-22R1/IL-22 axis could be protective at the beginning of SARS-CoV-2 infection but could shift to a detrimental response over time.
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COVID-19 , Linfócitos T CD8-Positivos , Quimiocinas/metabolismo , Antígenos HLA-DR/metabolismo , Humanos , Inflamação/metabolismo , Interleucina-17/metabolismo , Receptores de Interleucina , SARS-CoV-2RESUMO
INTRODUCTION: The PROOF registry is a prospective, observational study that aimed to monitor disease progression in a real-world cohort of patients with idiopathic pulmonary fibrosis (IPF). Here, longitudinal quality-of-life (QoL) outcomes, healthcare resource use (HCRU), and the association between QoL and mortality in patients enrolled in the PROOF registry are presented. METHODS: QoL outcomes (St. George's Respiratory Questionnaire [SGRQ], EuroQoL-5 dimensions-5 levels Health Questionnaire [EQ-5D-5L], EuroQoL-5 dimensions Health Questionnaire [EQ-5D] visual analogue scale [VAS] and cough VAS) and HCRU were collected for all patients. Associations between baseline QoL and mortality were assessed using univariate and multivariate analyses. During multivariate analyses, individual QoL measures were adjusted for the following covariates: age, sex, percent predicted forced vital capacity, percent predicted diffusing capacity of the lungs for carbon monoxide, smoking status, and supplementary oxygen use at registry inclusion. RESULTS: In total, 277 patients were enrolled in the PROOF registry. During the follow-up period, worsening in cough VAS score, SGRQ symptom score, and SGRQ activity score was observed, while EQ-5D VAS, SGRQ total score, and SGRQ impact score remained stable. During univariate analyses, EQ-5D VAS and all SGRQ sub-scores and total score at baseline were associated with mortality; however, during multivariate analyses, only the SGRQ total score, SGRQ impact score, and SGRQ symptom score at baseline were associated with mortality. During the follow-up period, 261 (94.2%) patients required an outpatient consultation (IPF- or non-IPF-related) and there were 182 hospitalizations in total, most of which were respiratory related (66.5%). CONCLUSIONS: The PROOF registry provided valuable, real-world data on the association between baseline QoL and mortality, and longitudinal HCRU and QoL outcomes in patients with IPF over 24 months and identified that SGRQ may be an independent prognostic factor in IPF.
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BACKGROUND: Our aims were to explore the feasibility, safety, and efficacy of peroperative transbronchial lung cryobiopsy (TBLC) guided by electromagnetic navigation bronchoscopy (ENB) and ENB-guided methylene blue marking of presumably non-palpable pulmonary nodules, and to assess its impact on video-assisted thoracoscopic surgery (VATS) and postoperative lung function. METHODS: This approach was applied to 16 consecutive patients (Group A, mean age 64 years) who were compared retrospectively to a historical group of 49 patients (Group B, mean age 62 years) with similar nodules resected without guidance. The usefulness of dye marking was graded. The success rates of both ENB-guided TBLC and nodule localization through dye marking were computed. The type of resection, volume of resected parenchyma, duration of procedures, and postoperative lung function were compared between groups. Unpaired t-test, chi-square test, unpaired Wilcoxon test, and exact Fisher test were used when appropriate. RESULTS: Malignancy was pathologically proven in all patients. TBLC revealed malignancy in 9 patients in Group A. The success rate of ENB-guided dye marking was 94%. Lobectomy was less frequently performed in Group A than in Group B (p = 0.022). Forced expiratory volume in 1 s and total lung capacity were significantly less reduced in Group A than in Group B (p = 0.006 and p = 0.019, respectively). Combined procedure was longer than surgery alone (p<0.001), but its surgical part was shorter than VATS without guidance (p < 0.001). CONCLUSION: Peroperative ENB-guided TBLC with methylene blue marking of non-palpable lung nodules is feasible. A sparing lung parenchyma procedure could be achieved thanks to the ENB-guided dye marking before VATS.
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Neoplasias Pulmonares , Lesões Pré-Cancerosas , Broncoscopia/métodos , Fenômenos Eletromagnéticos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Azul de Metileno , Pessoa de Meia-Idade , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/métodosRESUMO
The most common idiopathic interstitial lung disease (ILD) is idiopathic pulmonary fibrosis (IPF). It can be identified by the presence of usual interstitial pneumonia (UIP) via high-resolution computed tomography (HRCT) or with the use of a lung biopsy. We hypothesized that a CT-based approach using handcrafted radiomics might be able to identify IPF patients with a radiological or histological UIP pattern from those with an ILD or normal lungs. A total of 328 patients from one center and two databases participated in this study. Each participant had their lungs automatically contoured and sectorized. The best radiomic features were selected for the random forest classifier and performance was assessed using the area under the receiver operator characteristics curve (AUC). A significant difference in the volume of the trachea was seen between a normal state, IPF, and non-IPF ILD. Between normal and fibrotic lungs, the AUC of the classification model was 1.0 in validation. When classifying between IPF with a typical HRCT UIP pattern and non-IPF ILD the AUC was 0.96 in validation. When classifying between IPF with UIP (radiological or biopsy-proved) and non-IPF ILD, an AUC of 0.66 was achieved in the testing dataset. Classification between normal, IPF/UIP, and other ILDs using radiomics could help discriminate between different types of ILDs via HRCT, which are hardly recognizable with visual assessments. Radiomic features could become a valuable tool for computer-aided decision-making in imaging, and reduce the need for unnecessary biopsies.
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BACKGROUND AND OBJECTIVE: Poly(A)-specific ribonuclease (PARN) mutations have been associated with familial pulmonary fibrosis. This study aims to describe the phenotype of patients with interstitial lung disease (ILD) and heterozygous PARN mutations. METHODS: We performed a retrospective, observational, non-interventional study of patients with an ILD diagnosis and a pathogenic heterozygous PARN mutation followed up in a centre of the OrphaLung network. RESULTS: We included 31 patients (29 from 16 kindreds and two sporadic patients). The median age at ILD diagnosis was 59 years (range 54 to 63). In total, 23 (74%) patients had a smoking history and/or fibrogenic exposure. The pulmonary phenotypes were heterogenous, but the most frequent diagnosis was idiopathic pulmonary fibrosis (n = 12, 39%). Haematological abnormalities were identified in three patients and liver disease in two. In total, 21 patients received a specific treatment for ILD: steroids (n = 13), antifibrotic agents (n = 11), immunosuppressants (n = 5) and N-acetyl cysteine (n = 2). The median forced vital capacity decline for the whole sample was 256 ml/year (range -363 to -148). After a median follow-up of 32 months (range 18 to 66), 10 patients had died and six had undergone lung transplantation. The median transplantation-free survival was 54 months (95% CI 29 to ∞). Extra-pulmonary features were less frequent with PARN mutation than telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC) mutation. CONCLUSION: IPF is common among individuals with PARN mutation, but other ILD subtypes may be observed.
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Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Exorribonucleases , Humanos , Fibrose Pulmonar Idiopática/genética , Doenças Pulmonares Intersticiais/genética , Mutação/genética , Estudos RetrospectivosRESUMO
BACKGROUND: The surgical lung biopsy (SLB) is the recommended sampling technique when the pathological analysis of the lung is required in the work-up of an interstitial lung disease (ILD) but trans-bronchial lung cryobiopsy (TBLC) is increasingly recognized as an alternative approach. As TBLCs have lower mortality and morbidity risks than SLB, this study aimed to investigate the safety of TBLCs in patients at higher risk of complications and for whom SLB was not considered as an alternative. METHOD: This prospective study was conducted in two hospitals in which TBLCs were performed in patients with body mass index (BMI) > 35, and/or older than 75 years, and/or with severely impaired lung function (FVC < 50% or DLCO < 30%), and/or systolic pulmonary artery pressure > 45 mmHg, and/or a clinically significant cardiac disease. Patients with any of these risk factors constituted the high-risk group. Clinical outcomes were compared with those obtained in patients without these risk factors (low-risk group). RESULTS: Ninety-six patients were included between April 2015 and April 2020, respectively 38 and 58 in the high-risk or the low-risk group. No statistically significant difference was observed between both groups in terms of severity and rate of bleeding, pneumothorax, or duration of hospital stay (p value ranging from 0.419 to 0.914). CONCLUSION: This preliminary study on a limited number of patients suggests that TBLC appears safe in those in whom lung biopsy is at high-risk of complications according to their age, BMI, lung impairment, and cardiac comorbidities.
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Doenças Pulmonares Intersticiais/patologia , Pulmão/patologia , Idoso , Biópsia/efeitos adversos , Biópsia/métodos , Brônquios , Criocirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Fatores de RiscoRESUMO
Erythrodermic psoriasis is an uncommon and severe variant of psoriasis which may be associated with rare and severe complications such as acute respiratory distress syndrome. Early recognition of this life-threatening condition can allow prompt appropriate treatment. We report the case of a 69-year-old man with a long history of psoriasis who developed acute respiratory distress during a disease flare-up. There was no relevant past history (except for mild emphysema), known allergy, or recent treatment. Chest X-ray revealed new bilateral infiltrates, confirmed at chest computed tomography scan. Repeated cultures on aspirate of the bronchoalveolar lavage remained negative for viruses, bacteria, and parasites. Cardiac ultrasound was normal and high-dose corticosteroid therapy was initiated. Within a few days his clinical and radiological status improved significantly.
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BACKGROUND: Surfactant protein D (SP-D) and pulmonary club cell protein 16 (CC-16) are called "pneumoproteins" and are involved in host defense against oxidative stress, inflammation, and viral outbreak. This study aimed to determine the predictive value of these pneumoproteins on the incidence of acute respiratory distress syndrome (ARDS) or death in patients with coronavirus disease-2019 (COVID-19). METHODS: This retrospective study included 87 patients admitted to an emergency department. Blood samples were collected on three time points (days 1, 5, and 14 from hospital admission). SP-D and CC-16 serum levels were determined, and univariate and multivariate analyses considering confounding variables (age, body mass index, tobacco use, dyspnea, hypertension, diabetes mellitus, neutrophil-to-lymphocyte ratio) were performed. RESULTS: Based on the multivariate analysis, SP-D level on D1 was positively and slightly correlated with subsequent development of ARDS, independent of body mass index, dyspnea, and diabetes mellitus. CC-16 level on D1 was modestly and positively correlated with fatal outcome. A rise in SP-D between D1 and D5 and D1 and D14 had a strong negative association with incidence of ARDS. These associations were independent of tobacco use and neutrophil-to-lymphocyte ratio. CONCLUSIONS: Overall, our data reveal that increase in SP-D levels is a good prognostic factor for patients with COVID-19, and that initial CC-16 levels correlated with slightly higher risk of death. SP-D and CC-16 may prove useful to predict outcomes in patients with COVID-19.