Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.767
Filtrar
2.
Rev Mal Respir ; 40(1): 38-46, 2023 Jan.
Artigo em Francês | MEDLINE | ID: mdl-36564324

RESUMO

Interstitial lung diseases in children of genetic origin. Interstitial lung disease (ILD) in children (chILD) encompasses a heterogeneous group of rare respiratory disorders, most of which are chronic and severe. In more and more of these cases, a genetic cause has been identified. As of now, the main mutations have been localized in the genes encoding the surfactant proteins (SP)-C (SFTPC), SP-B (SFTPB), their transporter ATP-binding cassette, family 1, member 3 (ABCA3), transcription factor NK2 homeobox 1 (NKX2-1) and, more rarely, SP-A1 (SFTPA1) or SP-A2 (SFTPA2). Pediatric pulmonary alveolar proteinosis (PAP) is associated with mutations in CSF2RA, CSF2RB, and MARS; more recently, mutations in STING1 and COPA have been associated with specific auto-inflammatory disorders including ILD manifestations. The relationships between the molecular abnormalities and the phenotypic expressions generally remain poorly understood. In the coming years, it is expected that newly identified molecular defects will help to more accurately predict disease courses and to produce individualized targeted therapies.


Assuntos
Doenças Pulmonares Intersticiais , Proteinose Alveolar Pulmonar , Criança , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/genética , Doenças Pulmonares Intersticiais/terapia , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/genética , Proteinose Alveolar Pulmonar/terapia , Fenótipo , Mutação , Pulmão
3.
Part Fibre Toxicol ; 19(1): 69, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36539793

RESUMO

BACKGROUND: Many studies have shown that occupational exposure to indium and its compounds could induce lung disease. Although animal toxicological studies and human epidemiological studies suggest indium exposure may cause lung injury, inflammation, pulmonary fibrosis, emphysema, pulmonary alveolar proteinosis, and even lung cancer, related data collected from humans is currently limited and confined to single workplaces, and the early effects of exposure on the lungs are not well understood. OBJECTIVES: This study combined population studies and animal experiments to examine the links of indium with pulmonary injury, as well as its mechanism of action. A cross-sectional epidemiological study of indium-exposed workers from China was conducted to evaluate associations between occupational indium exposure and serum biomarkers of early effect. This study also compares and analyzes the causal perspectives of changes in human serum biomarkers induced by indium compound exposure and indium exposure-related rat lung pathobiology, and discusses possible avenues for their recognition and prevention. METHODS: This is a study of 57 exposed (at least 6 h per day for one year) workers from an indium ingot production plant, and 63 controls. Indium concentration in serum, urine, and airborne as exposure indices were measured by inductively coupled plasma-mass spectrometry. Sixteen serum biomarkers of pulmonary injury, inflammation, and oxidative stress were measured using ELISA. The associations between serum indium and 16 serum biomarkers were analyzed to explore the mechanism of action of indium on pulmonary injury in indium-exposed workers. Animal experiments were conducted to measure inflammatory factors levels in bronchoalveolar lavage fluid (BALF) and lung tissue protein expressions in rats. Four different forms of indium compound-exposed rat models were established (intratracheal instillation twice per week, 8 week exposure, 8 week recovery). Model I: 0, 1.2, 3, and 6 mg/kg bw indium tin oxide group; Model II: 0, 1.2, 3, and 6 mg/kg bw indium oxide (In2O3) group; Model III: 0, 0.523, 1.046, and 2.614 mg/kg bw indium sulfate (In2(SO4)3) group; Model IV: 0, 0.065, 0.65, and 1.3 mg/kg bw indium trichloride (InCl3) group. Lung pathological changes were assessed by hematoxylin & eosin, periodic acid Schiff, and Masson's staining, transmission electron microscopy, and the protein changes were determined by immunohistochemistry. RESULTS: In the production workshop, the airborne indium concentration was 78.4 µg/m3. The levels of serum indium and urine indium in indium-exposed workers were 39.3 µg/L and 11.0 ng/g creatinine. Increased lung damage markers, oxidative stress markers, and inflammation markers were found in indium-exposed workers. Serum indium levels were statistically and positively associated with the serum levels of SP-A, IL-1ß, IL-6 in indium-exposed workers. Among them, SP-A showed a duration-response pattern. The results of animal experiments showed that, with an increase in dosage, indium exposure significantly increased the levels of serum indium and lung indium, as well as the BALF levels of IL­1ß, IL­6, IL­10, and TNF­α and up-regulated the protein expression of SP-A, SP-D, KL-6, GM-CSF, NF-κB p65, and HO-1 in all rat models groups. TEM revealed that In2(SO4)3 and InCl3 are soluble and that no particles were found in lung tissue, in contrast to the non-soluble compounds (ITO and In2O3). No PAS-staining positive substance was found in the lung tissue of In2(SO4)3 and InCl3 exposure groups, whereas ITO and In2O3 rat models supported findings of pulmonary alveolar proteinosis and interstitial fibrosis seen in human indium lung disease. ITO and InCl3 can accelerate interstitial fibrosis. Findings from our in vivo studies demonstrated that intra-alveolar accumulation of surfactant (immunohistochemistry) and characteristic cholesterol clefts granulomas of indium lung disease (PAS staining) were triggered by a specific form of indium (ITO and In2O3). CONCLUSIONS: In indium-exposed workers, biomarker findings indicated lung damage, oxidative stress and an inflammatory response. In rat models of the four forms of indium encountered in a workplace, the biomarkers response to all compounds overall corresponded to that in humans. In addition, pulmonary alveolar proteinosis was found following exposure to indium tin oxide and indium oxide in the rat models, and interstitial fibrosis was found following exposure to indium tin oxide and indium trichloride, supporting previous report of human disease. Serum SP-A levels were positively associated with indium exposure and may be considered a potential biomarker of exposure and effect in exposed workers.


Assuntos
Lesão Pulmonar , Proteinose Alveolar Pulmonar , Fibrose Pulmonar , Humanos , Ratos , Animais , Proteinose Alveolar Pulmonar/induzido quimicamente , Proteinose Alveolar Pulmonar/patologia , Índio/toxicidade , Índio/química , Estudos Transversais , Roedores , Interleucina-6 , Inflamação , Biomarcadores
4.
Vnitr Lek ; 68(8): 525-531, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36575071

RESUMO

Interstitial lung diseases (ILDs) are not just a matter of scarring or inflammation in the lung tissue. The lungs can also serve as a repository for products that can be produced in excessive amounts in the human body as a result of disease. Geneticaly based dysfunctions of lysosomal enzymes, which leads to an unefficient degradation and transport of various macromolecules from lysosomes, are considered to be storage diseases sensu stricto. ILDs were described in patients with Gaucher disease, Niemann-Pick disease and Fabry disease. In a broader context, however, the accumulation of various substances in the lung tissue is also encountered in cases of pediatric pulmonary interstitial glycogenosis (PIG), alveolar lipoproteinosis or pulmonary amyloidosis. The cause of PIG is not clear. The disease was first described in 2002 and a lung tissue sample is required to establish this diagnosis. Even though PIG usually goes well in childhood and the patients difficulties spontaneously subside over time, the long-term prognosis of the patients is unknown. Alveolar lipoproteinoses can be acquired (e.g. after massive exposure to silica dust), autoimmune, but also genetically determined. Unlike lysosomal storage diseases, in the case of pulmonary alveolar lipoproteinosis, accumulation of abnormal macromolecules occurs only in the lungs of affected individuals. Similarly, amyloidosis is not a single disease, but a group of diseases with different etiopathogenesis, as a result of which amyloid - a group of different proteins with a distinctvive conformation, which can be deposited in various organs, including the lungs - is formed. The diagnosis of pulmonary alveolar lipoproteinosis is based on the typical appearance and biochemical composition of the fluid obtained by bronchoalveolar lavage, the diagnosis of amyloidosis is histological.


Assuntos
Amiloidose , Proteinose Lipoide de Urbach e Wiethe , Proteinose Alveolar Pulmonar , Humanos , Criança , Proteinose Lipoide de Urbach e Wiethe/patologia , Pulmão/metabolismo , Pulmão/patologia , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/metabolismo , Proteinose Alveolar Pulmonar/patologia , Alvéolos Pulmonares/patologia
5.
Nat Commun ; 13(1): 7272, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36433992

RESUMO

Alveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming. Nkrp1b-/- mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM of Nkrp1b-/- mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.


Assuntos
Proteinose Alveolar Pulmonar , Surfactantes Pulmonares , Camundongos , Animais , Macrófagos Alveolares/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Proteinose Alveolar Pulmonar/metabolismo , Surfactantes Pulmonares/metabolismo , Morte Celular
6.
Biomed Res Int ; 2022: 1589660, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330458

RESUMO

Background: Pulmonary alveolar proteinosis (PAP) is a rare disorder which is characterized by the accumulation of excessive surfactant lipids and proteins in alveolar macrophages and alveoli. Oral statin therapy has been reported to be a novel therapy for PAP with hypercholesterolemia. We aimed to evaluate the safety and efficacy of oral statin therapy for PAP without hypercholesterolemia. Methods: In a prospective real-world observational study, 47 PAP patients without hypercholesterolemia were screened. Oral statin was initiated as therapy for these PAP patients with 12 months of follow-up. Results: Forty PAP patients completed the study. 26 (65%) of 40 PAP patients responded to statin therapy according to the study criteria. Partial pressure of arterial oxygen (PaO2) and percentage of diffusion capacity predicted (DLCO%) significantly increased while disease severity score (DSS) and radiographic abnormalities decreased after 12 months of statin therapy (all p < 0.05). The factors associated with response were higher levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody and baseline total cholesterol/high-density lipoprotein cholesterol (TC/HDL) (p = 0.015 and p = 0.035, respectively). The area under the receiver operating characteristic curve (AUROC) of dose of atorvastatin for predicting the response to statin therapy for PAP was 0.859 (95% CI: 0.738-0.979, p < 0.001). The cutoff dose of atorvastatin was 67.5 mg daily with their corresponding specificity (64.3%) and sensitivity (96.2%). No severe side effects were observed during the study. Conclusions: In PAP patients without hypercholesterolemia, statin therapy resulted in improvements in arterial blood gas (ABG) measurement, pulmonary function, and radiographic assessment.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Proteinose Alveolar Pulmonar , Humanos , Proteinose Alveolar Pulmonar/tratamento farmacológico , Proteinose Alveolar Pulmonar/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Estudos Prospectivos , Atorvastatina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Macrófagos Alveolares/metabolismo , HDL-Colesterol/metabolismo
7.
Rev Mal Respir ; 39(9): 795-800, 2022 Nov.
Artigo em Francês | MEDLINE | ID: mdl-36273938

RESUMO

INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar accumulation of lipoproteinaceous material, caused by a macrophagic clearance disorder. We present a case of PAP in a patient taking the immunosuppressant drug mycophenolate mofetil (MMF) in the context of invasive pulmonary aspergillosis, of which we discuss the pathophysiology and treatment as reported in the literature. CASE REPORT: A 43-year-old man with cardiomyopathy received a heart transplant and was treated by MMF, tacrolimus and corticosteroids. Three months after the transplant, he presented with acute oxygen-dependent respiratory failure. The diagnosis of PAP seemed likely on the CT scan and was confirmed by bronchoalveolar lavage, as was the diagnostic of invasive pulmonary aspergillosis (IPA). However, GM-CSF autoantibodies were not found. As there existed a suspicion of MMF imputability, the treatment was discontinued and an antifungal treatment was started. The patient was reassessed one month after discontinuation of MMF and found to have clinically and radiologically improved. Four other cases of MMF-induced PAP have been reported in the literature. CONCLUSIONS: MMF and IPA could be predisposing cofactors for the occurrence of secondary PAP.


Assuntos
Aspergilose Pulmonar Invasiva , Proteinose Alveolar Pulmonar , Masculino , Humanos , Adulto , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/etiologia , Proteinose Alveolar Pulmonar/terapia , Aspergilose Pulmonar Invasiva/complicações , Lavagem Broncoalveolar , Autoanticorpos , Tomografia Computadorizada por Raios X/efeitos adversos
8.
J Coll Physicians Surg Pak ; 32(8): S183-S185, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36210689

RESUMO

Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. It is essential to gain a better understanding of the signs to clinically diagnose PAP and include PAP among the differential diagnoses of interstitial pulmonary diseases or other diseases with similar manifestations. We describe a 2.5-year patient with atopy who presented with pulmonary infiltration, recurrent wheezing, and cough despite steroid and salbutamol administration via inhalation. High-resolution computed tomography revealed crazy-paving patterns in both lungs, suggesting PAP. An open lung biopsy revealed intra-alveolar granular amphophilic material, which was strongly positive on periodic acid-Schiff staining. The results of pulmonary-associated surfactant protein B and C gene analyses were normal. However, granulocyte-macrophage colony-stimulating factor receptor beta-protein was not detected in leucocytes, and a novel mutation was identified in the CSF2RB gene. The patient was diagnosed with PAP and treated with whole-lung lavage. Key Words: Pulmonary alveolar proteinosis, Child, Atopy, Wheezing.


Assuntos
Proteinose Alveolar Pulmonar , Albuterol , Lavagem Broncoalveolar/métodos , Criança , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Humanos , Mutação , Ácido Periódico , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/genética , Proteinose Alveolar Pulmonar/patologia , Doenças Raras , Sons Respiratórios , Tensoativos
9.
Respir Res ; 23(1): 280, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36221098

RESUMO

BACKGROUND: Anti GM-CSF autoantibodies (aAb) have been related to acquired pulmonary alveolar proteinosis (PAP) and described in cases of severe infections such as cryptococcosis and nocardiosis in previously healthy subjects. Whether there are different anti-GM-CSF autoantibodies corresponding to these phenotypes is unclear. Therefore, we examined anti-GM-CSF autoantibodies to determine whether amount or neutralizing activity could distinguish between groups. METHODS: Plasma samples gathered in the National Institute of Health from patients with anti GM-CSF aAb and either PAP (n = 15), cryptococcal meningitis (n = 15), severe nocardiosis (n = 5) or overlapping phenotypes (n = 6) were compared. The relative amount of aAb was assessed using a particle-based approach, reported as a mouse monoclonal anti-human GM-CSF as standard curve and expressed in an arbitrary Mouse Monoclonal Antibody Unit (MMAU). The neutralizing activity of the plasma was assessed by inhibition of GM-CSF-induced intracellular phospho-STAT5 (pSTAT5) in monocytes. RESULTS: Anti-GM-CSF aAb relative amounts were higher in PAP patients compared to those with cryptococcosis (mean 495 ± 464 MMAU vs 197 ± 159 MMAU, p = 0.02); there was no difference with patients with nocardiosis (430 ± 493 MMAU) nor between the two types of infections. The dilution of plasma resulting in 50% inhibition of GM-CSF-induced pSTAT5 (approximate IC50) did not vary appreciably across groups of patients (1.6 ± 3.1%, 3.9 ± 6% and 1.8 ± 2.2% in PAP patients, cryptococcosis and nocardiosis patients, respectively). Nor was the concentration of GM-CSF necessary to induce 50% of maximal GM-CSF-induced pSTAT5 in the presence of 10 MMAU of anti-GM-CSF aAb (EC50). When studying longitudinal samples from patients with PAP or disseminated nocardiosis, the neutralizing effect of anti-GM-CSF aAb was relatively constant over time despite targeted treatments and variations in aAb levels. CONCLUSIONS: Despite different clinical manifestations, anti-GM-CSF antibodies were similar across PAP, cryptococcosis and nocardiosis. Underlying host genetics and functional analyses may help further differentiate the biology of these conditions.


Assuntos
Criptococose , Meningite Criptocócica , Nocardiose , Proteinose Alveolar Pulmonar , Animais , Anticorpos Monoclonais , Autoanticorpos , Camundongos , Proteinose Alveolar Pulmonar/diagnóstico , Fator de Transcrição STAT5
10.
BMC Pulm Med ; 22(1): 365, 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36153570

RESUMO

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare clinical syndrome involving the accumulation of lipid-rich proteinaceous material in the alveoli. There is a paucity of published studies on this condition. To better characterize the demographics, complication rates, mortality, and healthcare costs of patients hospitalized for PAP in the United States, a secondary analysis on the Hospital Cost and Utilization Project's Nationwide Inpatient Sample (NIS) was performed on patients admitted from 2012 to 2014 with a diagnosis of pulmonary alveolar proteinosis. METHODS: Using the NIS database, a secondary analysis was performed on 500 admissions with the diagnosis "pulmonary alveolar proteinosis." The clinical variables and outcome measures extracted were: patient demographics, hospital costs, length of stay, frequency of admissions, and inpatient mortality rate. RESULTS: Among a weighted estimate of 500 hospital admissions from 2012 to 2014, the number of PAP admissions averaged 4.7 per million. The population was predominantly male (55%) with a mean age of 41.45 (CI 38.3-44.5) from all socioeconomic levels. Inpatient mortality was calculated to be 5%, which may result from the fact that the majority of admitted patients had few or no comorbid conditions (CCI 0.72). The most common procedure performed during admission was a bronchoalveolar lavage. Mean length of stay was 6.2 days (CI 3.9-8.5) and average cost of admission was $29,932.20 (CI 13,739-46,124). Of note, 50% of these admissions were considered "elective." CONCLUSIONS: Demographics of patients with PAP who have been hospitalized in the United States are similar to previously reported demographics from prior patient cohorts, specifically a male predominance and a mean age in the 40 s. The inpatient mortality rate of 5% we found is consistent with prior studies demonstrating good disease-specific survival rates. Notably, the cost per admission and overall annual cost associated with PAP hospitalization was calculated to be $29932.20 and $5 million respectively. This reflects the high economic cost associated with hospitalization of PAP patients, and provokes thought about ways to make treatment more cost-effective.


Assuntos
Proteinose Alveolar Pulmonar , Adulto , Feminino , Hospitalização , Hospitais , Humanos , Pacientes Internados , Lipídeos , Masculino , Proteinose Alveolar Pulmonar/epidemiologia , Proteinose Alveolar Pulmonar/terapia , Estados Unidos/epidemiologia
11.
Ecotoxicol Environ Saf ; 241: 113812, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36068741

RESUMO

Indium-tin oxide (ITO) was previously found to have a toxic effect on lung tissues, and oxidative stress and the inflammatory response are two important mechanisms of ITO­induced lung injury. N-acetylcysteine (NAC) has been found to exhibit antioxidant and anti­inflammatory properties. The current study aimed to evaluate the possible protective effects of NAC against ITO nanoparticle (Nano-ITO)-induced pulmonary alveolar proteinosis (PAP) in adult male Sprague-Dawley rats, especially via modulation of nuclear factor-kappa B (NF-κB) signaling. For this purpose, 50 rats were randomly allocated into five groups (10 rats each) as follows: (1) control group; (2) saline group; (3) NAC (200 mg/kg) group; (4) PAP model group receiving a repeated intratracheal dose of Nano-ITO (6 mg/kg); and (5) PAP model+NF-κB inhibitor (NAC) group pre-treated intraperitoneally with NAC (200 mg/kg) twice per week before the administration of an intratracheal dose of Nano-ITO (6 mg/kg). Rats were then euthanized under anesthesia, and their lungs were removed for histopathological and biochemical investigations. A 6 mg/kg dose of Nano-ITO markedly altered the levels of some oxidative stress biomarkers. The histological examination of Nano-ITO-exposed rats demonstrated diffused alveolar damage that involved PAP, cholesterol crystals, alveolar fibrosis, pulmonary fibrosis, and alveolar emphysema. The immunohistochemical results of Nano-ITO-exposed rats revealed strongly positive NF-κB p65 and inhibitory kappa B kinase (IKK)-ß and weakly positive inhibitor of kappa-B subunit alpha (IκB-α) staining reactivity in the nuclei of cells lining the epithelium of the bronchioles and alveoli. Moreover, Nano-ITO activated the NF-κB pathway. However, pre-treatment with NAC significantly attenuated Nano-ITO-evoked alterations in the previously mentioned parameters, highlighting their antioxidant, anti-inflammatory, and anti-apoptotic potential. The results indicated that the degree of pulmonary fibrosis and proteinosis in the NAC­treated group was improved compared with that in the Nano-ITO-induced PAP model group. The level of malondialdehyde was also decreased overall in the NAC-treated group compared with that in the Nano-ITO-induced model group, indicating that the pulmonary fibrosis degree and oxidation levels were decreased. The present study also demonstrated that NAC increased the activity of antioxidant enzyme superoxide dismutase and total antioxidant capacity, indicating that it could alleviate oxidative stress in the lung tissue of Nano-ITO­exposed rats. In addition, NAC reduced the production of pro­inflammatory cytokines interleukin (IL)­1ß, IL­6, and tumor necrosis factor (TNF)­α, and increased the levels of anti­inflammatory factor IL­10. The current study demonstrated that NAC can effectively attenuate Nano-ITO­induced lung injury by reducing oxidative damage and the inflammatory response.


Assuntos
Lesão Pulmonar , Nanopartículas , Proteinose Alveolar Pulmonar , Fibrose Pulmonar , Acetilcisteína/metabolismo , Acetilcisteína/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Índio/toxicidade , Pulmão , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo , Masculino , NF-kappa B/metabolismo , Nanopartículas/toxicidade , Proteinose Alveolar Pulmonar/induzido quimicamente , Proteinose Alveolar Pulmonar/metabolismo , Proteinose Alveolar Pulmonar/patologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Compostos de Estanho , Fator de Necrose Tumoral alfa/metabolismo
12.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(9): 865-871, 2022 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-36097923

RESUMO

Autoimmune pulmonary alveolar proteinosis (aPAP) is the most common(around 90%) type of pulmonary alveolar proteinosis, characterized by the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody. Accumulating evidence has demonstrated the effectiveness of inhaled recombinant human GM-CSF for aPAP. Such a therapy has not been approved in China yet and has been classified off-label and unusual route of administration. Our expert consensus group evaluated the current knowledge with the methods of grading of recommendation assessment, development and evaluation (GRADE). The current evidence-based consensus statement covers the suitable population for inhaled GM-CSF therapy, details of prescription, usage during pregnancy and lactation, adverse effects and other suggestions in clinical usage. This consensus statement provides a clinical practice guideline of inhaled GM-CSF for aPAP in China and hopefully will accelerate basic and clinical research of aPAP.


Assuntos
Proteinose Alveolar Pulmonar , Acetaminofen/uso terapêutico , Administração por Inalação , Doenças Autoimunes , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Proteinose Alveolar Pulmonar/tratamento farmacológico
14.
Front Immunol ; 13: 931153, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928826

RESUMO

Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disorder characterized by surfactant accumulation in the small airways due to defective clearance by alveolar macrophages, resulting in impaired gas exchange. Whole lung lavage is the current standard of care treatment for PAP. Lung transplantation is an accepted treatment option when whole lung lavage or other experimental treatment options are ineffective, or in case of extensive pulmonary fibrosis secondary to PAP. A disadvantage of lung transplantation is recurrence of PAP in the transplanted lungs, especially in hereditary PAP. The hereditary form of PAP is an ultra-rare condition caused by genetic mutations in genes encoding for the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, and intrinsically affects bone marrow derived-monocytes, which differentiate into macrophages in the lung. Consequently, these macrophages typically display disrupted GM-CSF receptor-signaling, causing defective surfactant clearance. Bone marrow/hematopoietic stem cell transplantation may potentially reverse the lung disease in hereditary PAP. In patients with hereditary PAP undergoing lung transplantation, post-lung transplant recurrence of PAP may theoretically be averted by subsequent hematopoietic stem cell transplantation, which results in a graft-versus-disease (PAP) effect, and thus could improve long-term outcome. We describe the successful long-term post-transplant outcome of a unique case of end-stage respiratory failure due to hereditary PAP-induced pulmonary fibrosis, successfully treated by bilateral lung transplantation and subsequent allogeneic hematopoietic stem cell transplantation. Our report supports treatment with serial lung and hematopoietic stem cell transplantation to improve quality of life and prolong survival, without PAP recurrence, in selected patients with end-stage hereditary PAP.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Pulmão , Proteinose Alveolar Pulmonar , Fibrose Pulmonar , Surfactantes Pulmonares , Humanos , Proteinose Alveolar Pulmonar/tratamento farmacológico , Proteinose Alveolar Pulmonar/terapia , Surfactantes Pulmonares/uso terapêutico , Qualidade de Vida , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Tensoativos/uso terapêutico
15.
J Clin Immunol ; 42(8): 1730-1741, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35947322

RESUMO

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are a predisposing factor for pulmonary alveolar proteinosis (PAP) and Cryptococcus gattii cryptococcosis. This study aimed to investigate clinical manifestations in anti-GM-CSF Ab-positive patients with C. gattii cryptococcosis and analyze the properties of anti-GM-CSF Abs derived from these patients and patients with PAP. METHODS: Thirty-nine patients diagnosed with cryptococcosis (caused by C. neoformans or C. gattii) and 6 with PAP were enrolled in the present study. Clinical information was obtained from medical records. Blood samples were collected for analysis of autoantibody properties. We also explored the National Health Insurance Research Database (NHIRD) of Taiwan to investigate the epidemiology of cryptococcosis and PAP. RESULTS: High titers of neutralizing anti-GM-CSF Abs were identified in 15 patients with cryptococcosis (15/39, 38.5%). Most anti-GM-CSF Ab-positive cryptococcosis cases had central nervous system (CNS) involvement (14/15, 93.3%). Eleven out of 14 (78.6%) anti-GM-CSF Ab-positive CNS cryptococcosis patients were confirmed to be infected with C. gattii, and PAP did not occur synchronously or metachronously in a single patient from our cohort. Exploration of an association between HLA and anti-GM-CSF Ab positivity or differential properties of autoantibodies from cryptococcosis patients and PAP yielded no significant results. CONCLUSION: Anti-GM-CSF Abs can cause two diseases, C. gattii cryptococcosis and PAP, which seldom occur in the same subject. Current biological evidence regarding the properties of anti-GM-CSF Abs cannot provide clues regarding decisive mechanisms. Further analysis, including more extensive cohort studies and investigations into detailed properties, is mandatory to better understand the pathogenesis of anti-GM-CSF Abs.


Assuntos
Criptococose , Proteinose Alveolar Pulmonar , Humanos , Autoanticorpos , Criptococose/diagnóstico , Criptococose/epidemiologia , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/etiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia
16.
Medicina (Kaunas) ; 58(8)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35893099

RESUMO

Pulmonary Alveolar Proteinosis (PAP) is a rare, usually autoimmune, disease, where surfactant accumulates within alveoli due to decreased clearance, causing dyspnea and hypoxemia. The disease is even more rare in pregnancy; nevertheless, it has been reported in pregnant women and can even appear for the first time during pregnancy as an asthma-like illness. Therefore, awareness is important. Similarly to many autoimmune diseases, it can worsen during pregnancy and postpartum, causing maternal and fetal/neonatal complications. This paper offers a narrative literature review of PAP and pregnancy, while illustrating a case of a pregnant patient with known PAP who developed preeclampsia in the third trimester but had an overall fortunate maternal and neonatal outcome.


Assuntos
Doenças Autoimunes , Proteinose Alveolar Pulmonar , Surfactantes Pulmonares , Doenças Autoimunes/complicações , Dispneia/etiologia , Feminino , Humanos , Recém-Nascido , Pulmão , Gravidez , Proteinose Alveolar Pulmonar/complicações , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/terapia
17.
J Int Med Res ; 50(7): 3000605221113785, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35899929

RESUMO

Pulmonary alveolar proteinosis (PAP) is a rare respiratory system disorder. Patients with PAP are at risk for a wide variety of secondary infections. This current case report describes a patient with PAP complicated by tuberculosis. A 48-year-old male patient with multiple follow-up chest computed tomography scans that showed predominant diffuse ground glass opacity in both lung fields, presented a few years later with new calcified lesions and pleural effusion. At this point, the associated auxiliary examination indicated the possibility of PAP combined with tuberculosis infection. The patient achieved complete remission after anti-tuberculosis treatment. PAP is an easily overlooked clinical syndrome due to its low prevalence and lack of specific clinical manifestations, especially when combined with other pulmonary lesions. Therefore, clinicians should consider this rare disease in patients presenting with pulmonary disease and plan for its co-morbidity with other secondary outcomes, such as opportunistic infections, which are a common and life-threatening complication in patients with PAP. This case indicates the possibility that anti-tuberculosis therapy can improve alveolar proteinosis in patients with PAP and secondary Mycobacterium tuberculosis infection.


Assuntos
Proteinose Alveolar Pulmonar , Tuberculose , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Proteinose Alveolar Pulmonar/tratamento farmacológico , Indução de Remissão , Tomografia Computadorizada por Raios X/efeitos adversos
19.
Chest ; 161(6): e371-e376, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35680318

RESUMO

CASE PRESENTATION: A 34-year-old man presented to our institution with lightheadedness and dyspnea on exertion. His medical history included chronic pancreatitis, juvenile rheumatoid arthritis (JRA), gastroesophageal reflux disease, hypertension, lumbar degenerative disc disease, seizure disorder, anterior uveitis, and multiple vertebral fractures. In addition, he was a cigarette smoker with a 10-pack-year smoking history.


Assuntos
Tontura , Proteinose Alveolar Pulmonar , Adulto , Dispneia/diagnóstico , Dispneia/etiologia , Humanos , Masculino
20.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(7): 667-670, 2022 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-35768374

RESUMO

Objective: To observe the efficacy of lung transplantation for pulmonary alveolar proteinosis (PAP) patients and to improve the understanding of the therapy. Methods: The clinical data of a patient with autoimmune PAP treated with sequential homogenous bilateral lung transplantation were described and the literatures were reviewed. Results: This 55-year-old female patient was diagnosed with autoimmune PAP and had been treated with whole lung lavage for 19 times, but only achieved short-term symptomatic relief after each operation. Inhalation of granulocyte macrophage colony stimulating factor occurred allergic reactions. Lung transplantation was performed on February 15, 2022, and a significant improvement in oxygenation and clinical symptoms were observed. The patient remained stable during follow-up. Conclusion: Treatment with lung transplantation is safe and effective for end-stage patients with PAP in the early phase, but the long-term effect remains to be observed.


Assuntos
Transplante de Pulmão , Proteinose Alveolar Pulmonar , Administração por Inalação , Lavagem Broncoalveolar , Feminino , Humanos , Pulmão , Pessoa de Meia-Idade , Proteinose Alveolar Pulmonar/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...