Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
1.
Thorax ; 79(8): 711-717, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38914469

RESUMO

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.


Assuntos
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/fisiologia
2.
Respirology ; 29(4): 304-311, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38123492

RESUMO

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.


Assuntos
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 Doença
3.
Thorax ; 79(1): 68-74, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37758458

RESUMO

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.


Assuntos
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 , Autoanticorpos
4.
Respir Res ; 24(1): 254, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880678

RESUMO

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.


Assuntos
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 adversos
5.
BMC Pulm Med ; 23(1): 185, 2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37245012

RESUMO

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.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Humanos , Broncoscopia/métodos , Neoplasias Pulmonares/patologia , Bélgica , Fenômenos Eletromagnéticos , Nódulos Pulmonares Múltiplos/patologia , Tomografia Computadorizada de Feixe Cônico
6.
Respirology ; 27(3): 226-235, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34981600

RESUMO

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.


Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Exorribonucleases , Humanos , Fibrose Pulmonar Idiopática/genética , Doenças Pulmonares Intersticiais/genética , Mutação/genética , Estudos Retrospectivos
7.
BMC Pulm Med ; 21(1): 135, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902504

RESUMO

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.


Assuntos
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 Risco
8.
Respir Res ; 21(1): 231, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887582

RESUMO

BACKGROUND: Although increasing data supports the use of transbronchial lung cryobiopsies (TBLCs) for the diagnosis of diffuse parenchymal lung diseases (DPLDs), its role as an alternative to surgical lung biopsy (SLB) is still under debate. The aim of this study was to assess the benefit of additional SLBs performed in selected patients after TBLCs. METHOD: We conducted a multicentric Belgian prospective trial in which SLBs were performed after TBLCs when the pathological diagnosis was uncertain or if a nonspecific interstitial pneumonia (NSIP) pattern was observed hypothesizing that SLB could provide additional information and that a co-existent UIP pattern could be missed. RESULTS: Eighty-one patients with TBLCs performed for a DPLD were included in the study between April 2015 and December 2019. A specific histological diagnosis was obtained in 52 patients (64%) whereas no pathological diagnosis following TBLCs was obtained in 13 patients (16%) and a pattern suggestive of a NSIP was observed in 16 patients (20%). Fourteen out of these 29 patients had SLBs after TBLCs. SLBs showed a UIP pattern in 11 (79%), a pattern suggestive of a hypersensitivity pneumonitis in two (14%) and a NSIP pattern in one patient (7%). Among the 16 patients with pathological NSIP following TBLCs, six underwent a SLBs showing a UIP in five and confirming a NSIP in one patient only. A retrospective pathological analysis of patients having both procedures showed a lower diagnostic confidence and agreement among pathologists for TBLCs compared to SLBs. Major factors underlying the added value of SLBs were the bigger size of the sample as well as the subpleural localization of the biopsies. CONCLUSIONS: TBLCs are useful in the setting of DPLDs with a good diagnostic yield. However, our study suggests that SLB provides critical additional information in case TBLCs are inconclusive or show a pattern suggestive of a NSIP, questioning the accuracy of TBLC to adequately identify this histological pattern.


Assuntos
Broncoscopia/métodos , Criocirurgia/métodos , Pneumonias Intersticiais Idiopáticas/patologia , Pulmão/patologia , Pulmão/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Biópsia/métodos , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
9.
Respiration ; 99(1): 73-82, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31830755

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease that is, by definition, progressive. Progression of IPF is reflected by a decline in lung function, worsening of dyspnea and exercise capacity, and deterioration in health-related quality of life. In the short term, the course of disease for an individual patient is impossible to predict. A period of relative stability in forced vital capacity (FVC) does not mean that FVC will remain stable in the near future. Frequent monitoring using multiple assessments, not limited to pulmonary function tests, is important to evaluate disease progression in individual patients and ensure that patients are offered appropriate care. Optimal management of IPF requires a multidimensional approach, including both pharmacological therapy to slow decline in lung function and supportive care to preserve patients' quality of life.


Assuntos
Fibrose Pulmonar Idiopática/terapia , Indóis/uso terapêutico , Oxigenoterapia , Guias de Prática Clínica como Assunto , Inibidores de Proteínas Quinases/uso terapêutico , Piridonas/uso terapêutico , Gerenciamento Clínico , Progressão da Doença , Dispneia/fisiopatologia , Dispneia/terapia , Tolerância ao Exercício , Humanos , Fibrose Pulmonar Idiopática/fisiopatologia , Educação de Pacientes como Assunto , Assistência Centrada no Paciente , Capacidade de Difusão Pulmonar , Qualidade de Vida , Testes de Função Respiratória , Assistência Terminal , Capacidade Vital , Teste de Caminhada
10.
Respir Res ; 20(1): 10, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30646908

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by a progressive and irreversible respiratory failure. Non-invasive markers of disease activity are essential for prognosis and evaluation of early response to anti-fibrotic treatments. OBJECTIVES: The aims of this study were to determine whether fluorodeoxyglucose ([18F]-FDG) lung uptake is reduced after initiation of pirfenidone or nintedanib and to assess its possible use as a prognostic factor. METHODS: [18F]-FDG PET/CT was performed in IPF patients and in a murine model of pulmonary fibrosis. PET/CTs were performed at day 8 and day 15 post-instillation of bleomycin in pirfenidone- or vehicule-treated mice. In IPF patients, PET-CT was performed before and 3 months after the initiation of pirfenidone or nintedanib. RESULTS: In bleomycin-treated mice, pirfenidone significantly reduced the [18F]-FDG uptake compared to vehicule-treated mice at day 15 (p < 0.001), whereas no difference was observed at day 8 after bleomycin administration. In IPF patients, [18F]-FDG lung uptake before and after 3 months of treatment by nintedanib (n = 11) or pirfenidone (n = 14) showed no significant difference regardless the antifibrotic treatment. Moreover, no difference was noticed between patients with progressive or non-progressive disease at one year of follow up. CONCLUSIONS: Pirfenidone significantly reduces the lung [18F]-FDG uptake during the fibrotic phase in a mouse model of IPF. However, these preclinical data were not confirmed in IPF patients 3 months after the initiation of antifibrotic therapy. [18F]-FDG seems therefore not useful in clinical practice to assess the early response of IPF patients to nintedanib or pirfenidone.


Assuntos
Fluordesoxiglucose F18 , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/tratamento farmacológico , Indóis/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Piridonas/uso terapêutico , Idoso , Animais , Antineoplásicos/uso terapêutico , Feminino , Fibrose , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Respir Res ; 20(1): 231, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651324

RESUMO

BACKGROUND: The PROOF registry is an observational study initiated in October 2013 with the aim to monitor disease progression in a real-world population of patients with idiopathic pulmonary fibrosis (IPF). Here, we present longitudinal clinical outcomes from the PROOF registry. METHODS: Patients with IPF were enrolled across eight centers in Belgium and Luxembourg. For all patients, clinical outcomes data were collected, including mortality, lung transplant, acute exacerbations, and pulmonary hypertension. For patients treated with pirfenidone at any time during follow-up (2013-2017), for any duration of treatment (the pirfenidone-treated population): pirfenidone treatment patterns were collected; changes in pulmonary function (forced vital capacity [FVC] and carbon monoxide diffusing capacity [DLco]) were reviewed up to 24 months post-inclusion; and time-to-event analyses from the time of registry inclusion were performed. RESULTS: The PROOF registry enrolled a total of 277 patients. During follow-up, 23.1% of patients died, 5.1% received a lung transplant, 5.4% experienced an acute exacerbation, and 6.1% had comorbid pulmonary hypertension. In the pirfenidone-treated population (N = 233, 84.1%), 12.9% of patients had a temporary dose discontinuation and 31.8% had a temporary dose reduction; 4.3% of patients permanently discontinued pirfenidone due to an adverse drug reaction. Mean percent predicted FVC was 81.2% (standard deviation [SD] 19.0) at Month 0 and 78.3% (SD 25.0) at Month 24, and mean percent predicted DLco was 47.0% (SD 13.2) and 45.0% (SD 16.5), respectively. Rates of ≥ 10% absolute decline in percent predicted FVC and ≥ 15% absolute decline in percent predicted DLco over 24 months were 31.0% and 23.2%, respectively. Mean times from registry inclusion to categorical absolute decline in percent predicted FVC and percent predicted DLco were 20.1 (standard error [SE] 0.6) months and 23.4 (SE 0.5) months, respectively; mean time from registry inclusion to death was 31.0 (SE 0.9) months. CONCLUSIONS: The PROOF registry is a source of European data characterizing longitudinal clinical outcomes of patients with IPF. Over 12 months of follow-up, pulmonary function remained largely stable in patients with IPF who received pirfenidone for any duration of treatment. Pulmonary function remained similar at 24 months of follow-up, although patient numbers were lower. TRIAL REGISTRATION: PROOF is registered with the relevant authorities in Belgium and Luxembourg, with registration to Comité National d'Éthique et de Recherche (CNER) N201309/03-12 September 2013 and a notification to Comité National de Protection des Données (CNDP) for Luxembourg.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Progressão da Doença , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/mortalidade , Piridonas/uso terapêutico , Sistema de Registros , Idoso , Bélgica/epidemiologia , Feminino , Seguimentos , Humanos , Fibrose Pulmonar Idiopática/fisiopatologia , Estudos Longitudinais , Luxemburgo/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Testes de Função Respiratória/mortalidade , Testes de Função Respiratória/tendências , Resultado do Tratamento
12.
Transpl Infect Dis ; 20(1)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29120502

RESUMO

Invasive fungal infections are a major cause of mortality among solid organ transplant recipients. Scopulariopsis species and their teleomorph Microascus are molds found in soil and decaying organic matter. We report here the case of a woman who underwent bilateral lung transplantation for severe emphysema. On day 25 after transplantation, endobronchial green-black lesions were detected during routine endoscopy. Endobronchial swabs, biopsies, and bronchoalveolar lavage samples were positive for Microascus cirrosus. This fungal infection developed despite voriconazole given for previous persistent invasive aspergillosis. Treatment consisted of a combination of antifungal medication (voriconazole, terbinafine, amphotericin B, and caspofungin) and endoscopic resection of necrosed bronchial mucosa. A favorable clinical outcome was achieved after 7 weeks of treatment. Seven cases of Scopulariopsis/Microascus infection have been previously described in solid organ transplant recipients. Only two survived after treatment with an antifungal combination therapy including echinocandins, posaconazole, and terbinafine. In immunocompromised patients, infection by Microascus species is a rare but life-threatening event because of innate resistance to most common antifungal drugs. Our patient was successfully cured by combined therapy including intravenous voriconazole and caspofungin, oral terbinafine, and inhaled voriconazole and amphotericin B administered for 7 weeks in association with iterative endoscopic debridement to reduce fungal inoculum.


Assuntos
Antifúngicos/uso terapêutico , Brônquios/patologia , Bronquite/microbiologia , Transplante de Pulmão/efeitos adversos , Micoses/tratamento farmacológico , Anfotericina B/uso terapêutico , Ascomicetos/isolamento & purificação , Brônquios/efeitos dos fármacos , Brônquios/microbiologia , Endoscopia , Feminino , Humanos , Hospedeiro Imunocomprometido , Pessoa de Meia-Idade , Micoses/etiologia , Micoses/fisiopatologia , Necrose/microbiologia , Transplantados , Resultado do Tratamento , Triazóis/uso terapêutico
16.
Front Med (Lausanne) ; 11: 1393778, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39364020

RESUMO

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.

17.
Cells ; 13(2)2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38247862

RESUMO

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.


Assuntos
Quimiocinas , Fatores Quimiotáticos , Pneumopatias , Humanos , Anti-Inflamatórios , Quimiocinas/metabolismo , Células Dendríticas , Pneumopatias/metabolismo
18.
Respir Med Case Rep ; 51: 102090, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39206099

RESUMO

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.

19.
PLoS Pathog ; 7(11): e1002358, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22072972

RESUMO

Viral diseases of the respiratory tract, which include influenza pandemic, children acute bronchiolitis, and viral pneumonia of the elderly, represent major health problems. Plasmacytoid dendritic cells play an important role in anti-viral immunity, and these cells were recently shown to express ChemR23, the receptor for the chemoattractant protein chemerin, which is expressed by epithelial cells in the lung. Our aim was to determine the role played by the chemerin/ChemR23 system in the physiopathology of viral pneumonia, using the pneumonia virus of mice (PVM) as a model. Wild-type and ChemR23 knock-out mice were infected by PVM and followed for functional and inflammatory parameters. ChemR23(-/-) mice displayed higher mortality/morbidity, alteration of lung function, delayed viral clearance and increased neutrophilic infiltration. We demonstrated in these mice a lower recruitment of plasmacytoid dendritic cells and a reduction in type I interferon production. The role of plasmacytoid dendritic cells was further addressed by performing depletion and adoptive transfer experiments as well as by the generation of chimeric mice, demonstrating two opposite effects of the chemerin/ChemR23 system. First, the ChemR23-dependent recruitment of plasmacytoid dendritic cells contributes to adaptive immune responses and viral clearance, but also enhances the inflammatory response. Second, increased morbidity/mortality in ChemR23(-/-) mice is not due to defective plasmacytoid dendritic cells recruitment, but rather to the loss of an anti-inflammatory pathway involving ChemR23 expressed by non-leukocytic cells. The chemerin/ChemR23 system plays important roles in the physiopathology of viral pneumonia, and might therefore be considered as a therapeutic target for anti-viral and anti-inflammatory therapies.


Assuntos
Fatores Quimiotáticos/metabolismo , Células Dendríticas/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Vírus da Pneumonia Murina/imunologia , Pneumonia Viral/imunologia , Infecções por Pneumovirus/imunologia , Receptores Acoplados a Proteínas G/imunologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Quimiocinas , Fatores Quimiotáticos/biossíntese , Células Dendríticas/metabolismo , Mediadores da Inflamação , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Interferon Tipo I/biossíntese , Interferon Tipo I/deficiência , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Vírus da Pneumonia Murina/metabolismo , Vírus da Pneumonia Murina/patogenicidade , Pneumonia Viral/metabolismo , Infecções por Pneumovirus/metabolismo , Receptores de Quimiocinas , Receptores Acoplados a Proteínas G/biossíntese , Receptores Acoplados a Proteínas G/genética , Carga Viral
20.
J Immunol ; 186(9): 5457-67, 2011 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-21430224

RESUMO

Chronic obstructive pulmonary disease is mainly triggered by cigarette smoke (CS) and progresses even after smoking cessation. CS induces an exaggerated influx of inflammatory cells to the bronchoalveolar space and lung parenchyma, likely resulting from a complex interplay between chemoattractants and their respective receptors. In a murine CS model of chronic obstructive pulmonary disease, we studied the importance of chemokine-like receptor ChemR23 for the induction and resolution of inflammation in CS-exposed lungs. Subacute and chronic CS exposure increased protein levels of the ChemR23 ligand and chemoattractant, chemerin, in bronchoalveolar lavage (BAL) fluid of wild-type (WT) mice. Moreover, the proinflammatory chemokines CXCL1, CCL2, and CCL20 were increased in the airways of CS-exposed WT mice, accompanied by a massive accumulation of inflammatory neutrophils and monocytes, CD11b(hi)CD103(-) and CD11b(lo)CD103(+) dendritic cells (DCs), and CD4(+) and CD8(+) T cells. The lung parenchyma of WT mice was infiltrated with inflammatory neutrophils, CD11b(hi)CD103(-) DCs, and activated CD4(+) T cells after CS exposure. CS-induced inflammation was severely attenuated in BAL fluid and lungs of ChemR23 knockout mice with regard to the induction of inflammatory chemokines and the recruitment of inflammatory cells. Neutrophils and CD8(+) T cells persisted in the airways of WT mice, as did the airway-derived conventional DCs in the mediastinal lymph nodes, for at least 14 d after smoking cessation. In the BAL fluid of CS-exposed ChemR23 knockout mice, there was a remarkable delayed accumulation of T cells 14 d after the final exposure. Our data support a role for ChemR23 in directing innate and adaptive immune cells to CS-exposed lungs.


Assuntos
Doença Pulmonar Obstrutiva Crônica/imunologia , Receptores Acoplados a Proteínas G/imunologia , Fumaça/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Separação Celular , Quimiocinas/biossíntese , Quimiocinas/imunologia , Fatores Quimiotáticos/biossíntese , Fatores Quimiotáticos/imunologia , Células Dendríticas/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Imuno-Histoquímica , Inflamação/imunologia , Inflamação/patologia , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Receptores de Quimiocinas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Nicotiana
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA