RESUMEN
Tissue-resident macrophages are of vital importance as they preserve tissue homeostasis in all mammalian organs. Nevertheless, appropriate cell culture models are still limited. Here, we propose a novel culture model to study and expand murine primary alveolar macrophages (AMs), the tissue-resident macrophages of the lung, in vitro over several months. By providing a combination of granulocyte-macrophage colony-stimulating factor, TGFß, and the PPARγ activator rosiglitazone, we maintain and expand mouse ex vivo cultured AMs (mexAMs) over several months. MexAMs maintain typical morphologic features and stably express primary AM surface markers throughout in vitro culture. They respond to microbial ligands and exhibit an AM-like transcriptional profile, including the expression of AM-specific transcription factors. Furthermore, when transferred into AM-deficient mice, mexAMs efficiently engraft in the lung and fulfill key macrophage functions, leading to a significantly reduced surfactant load in those mice. Altogether, mexAMs provide a novel, simple, and versatile tool to study AM behavior in homeostasis and disease settings.
Asunto(s)
Macrófagos Alveolares/metabolismo , Animales , Animales Recién Nacidos , Células Cultivadas , Modelos Animales de Enfermedad , Hígado/metabolismo , Pulmón/patología , Pulmón/fisiopatología , Macrófagos Alveolares/patología , Ratones Endogámicos C57BL , Fenotipo , Proteinosis Alveolar Pulmonar/metabolismo , Proteinosis Alveolar Pulmonar/patología , Proteinosis Alveolar Pulmonar/fisiopatología , Transcripción GenéticaRESUMEN
CASE PRESENTATION: A 30-year-old woman was referred with increasing shortness of breath and cough in the setting of GATA2 deficiency. She initially presented 9 years previously with recurrent episodes of pneumonia and sinusitis. Genetic testing revealed a heterozygous GATA2 mutation (c.988C>T). She has since had multiple infections that have included necrotizing fasciitis of the right thumb, recurrent pilonidal infections (which required 23 procedures), esophageal candidiasis, and human papillomavirus-positive high-grade squamous intraepithelial lesion of the cervix. Serial bone marrow biopsy specimens showed persistent hypocellularity (20% to 60%) with intermittent erythroid atypia and variable detection of trisomy 8, which were concerning for evolving myelodysplastic syndrome. One year before the current admission, she was diagnosed with disseminated Mycobacterium avium complex and was treated with rifabutin, ethambutol, and azithromycin. She was taking voriconazole, acyclovir, and trimethoprim-sulfamethoxazole prophylaxis.
Asunto(s)
Tos/fisiopatología , Disnea/fisiopatología , Deficiencia GATA2/fisiopatología , Proteinosis Alveolar Pulmonar/diagnóstico , Adulto , Biopsia , Lavado Broncoalveolar , Femenino , Deficiencia GATA2/complicaciones , Deficiencia GATA2/terapia , Trasplante de Células Madre Hematopoyéticas , Humanos , Síndromes de Inmunodeficiencia/fisiopatología , Pulmón/patología , Proteinosis Alveolar Pulmonar/etiología , Proteinosis Alveolar Pulmonar/patología , Proteinosis Alveolar Pulmonar/fisiopatología , Toracoscopía , Tomografía Computarizada por Rayos XAsunto(s)
Líquido del Lavado Bronquioalveolar/citología , Trasplante de Células Madre Hematopoyéticas , Inmunosupresores , Pulmón , Macrófagos Alveolares , Proteinosis Alveolar Pulmonar , Biopsia , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Leucemia Mieloide/sangre , Leucemia Mieloide/terapia , Pulmón/diagnóstico por imagen , Pulmón/patología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/terapia , Manejo de Atención al Paciente , Reacción del Ácido Peryódico de Schiff/métodos , Proteinosis Alveolar Pulmonar/diagnóstico , Proteinosis Alveolar Pulmonar/etiología , Proteinosis Alveolar Pulmonar/fisiopatología , Proteinosis Alveolar Pulmonar/terapia , Pruebas de Función Respiratoria/métodos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Trasplante AutólogoAsunto(s)
Lavado Broncoalveolar/métodos , Disnea , Pulmón/diagnóstico por imagen , Pruebas en el Punto de Atención , Proteinosis Alveolar Pulmonar , Ultrasonografía/métodos , Adulto , Broncoscopía/métodos , Disnea/diagnóstico , Disnea/etiología , Femenino , Humanos , Proteinosis Alveolar Pulmonar/diagnóstico , Proteinosis Alveolar Pulmonar/fisiopatología , Proteinosis Alveolar Pulmonar/terapia , Radiografía Torácica/métodos , Pruebas de Función Respiratoria/métodos , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: GATA2 deficiency is a genetic disorder of hematopoiesis, lymphatics, and immunity caused by autosomal dominant or sporadic mutations in GATA2. The disease has a broad phenotype encompassing immunodeficiency, myelodysplasia, leukemia, and vascular or lymphatic dysfunction as well as prominent pulmonary manifestations. RESEARCH QUESTION: What are the pulmonary manifestations of GATA2 deficiency? STUDY DESIGN AND METHODS: A retrospective review was conducted of clinical medical records, diagnostic imaging, pulmonary pathologic specimens, and tests of pulmonary function. RESULTS: Of 124 patients (95 probands and 29 ascertained), the lung was affected in 56%. In addition to chronic infections, pulmonary alveolar proteinosis (11 probands) and pulmonary arterial hypertension (nine probands) were present. Thoracic CT imaging found small nodules in 54% (54 probands and 12 relatives), reticular infiltrates in 40% (45 probands and four relatives), paraseptal emphysema in 25% (30 probands and one relative), ground-glass opacities in 35% (41 probands and two relatives), consolidation in 21% (23 probands and two relatives), and a typical crazy-paving pattern in 7% (eight probands and no relatives). Nontuberculous mycobacteria were the most frequent organisms associated with chronic infection. Allogeneic hematopoietic stem cell transplantation successfully reversed myelodysplasia and immune deficiency and also improved pulmonary hypertension and pulmonary alveolar proteinosis in most patients. INTERPRETATION: GATA2 deficiency has prominent pulmonary manifestations. These clinical observations confirm the essential role of hematopoietic cells in many aspects of pulmonary function, including infections, alveolar proteinosis, and pulmonary hypertension, many of which precede the formal diagnosis, and many of which respond to stem cell transplantation.
Asunto(s)
Deficiencia GATA2/fisiopatología , Nódulos Pulmonares Múltiples/fisiopatología , Proteinosis Alveolar Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/fisiopatología , Enfisema Pulmonar/fisiopatología , Infecciones del Sistema Respiratorio/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Deficiencia GATA2/diagnóstico por imagen , Deficiencia GATA2/terapia , Trasplante de Células Madre Hematopoyéticas , Humanos , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Infecciones por Mycobacterium no Tuberculosas/fisiopatología , Enfisema Pulmonar/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP. METHODS: In a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 µg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo2) at week 24. RESULTS: In total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo2 data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point - the change from baseline in the A-aDo2 at week 24 - improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (-12.8 mm Hg vs. -6.6 mm Hg; estimated treatment difference, -6.2 mm Hg; P = 0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George's Respiratory Questionnaire total score at week 24 (-12.4 points vs. -5.1 points; estimated treatment difference, -7.4 points; P = 0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group. CONCLUSIONS: In patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.).
Asunto(s)
Enfermedades Autoinmunes/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Proteinosis Alveolar Pulmonar/tratamiento farmacológico , Administración por Inhalación , Adulto , Enfermedades Autoinmunes/fisiopatología , Enfermedades Autoinmunes/terapia , Lavado Broncoalveolar , Método Doble Ciego , Esquema de Medicación , Tolerancia al Ejercicio , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos adversos , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Proteinosis Alveolar Pulmonar/fisiopatología , Proteinosis Alveolar Pulmonar/terapia , Intercambio Gaseoso Pulmonar , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Prueba de PasoRESUMEN
BACKGROUND: Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of surfactant proteins within the alveolar spaces. Autoimmune PAP (APAP) caused by elevated levels of GM-CSF autoantibodies (GM-Ab) is very rarely associated with systemic autoimmune disease. Here we report a case of APAP manifested during immunosuppressive treatment for polymyositis with interstitial lung disease. CASE PRESENTATION: A 52-year-old woman treated at our hospital because of polymyositis with interstitial pneumonia had maintained remission by immunosuppressive treatment for 15 years. She had progressive dyspnea subsequently over several months with her chest CT showing ground-glass opacities (GGO) in bilateral geographic distribution. Her bronchoalveolar lavage fluid with cloudy appearance revealed medium-sized foamy macrophages and PAS-positive amorphous eosinophilic materials by cytological examination. We diagnosed her as APAP due to an increased serum GM-CSF autoantibody level. Attenuating immunosuppression failed to lead GGO improvement, but whole lung lavage (WLL) was effective in her condition. CONCLUSIONS: PAP should be considered as one of the differential diseases when the newly interstitial shadow was observed during immunosuppressive treatment. WLL should be regarded as the treatment option for APAP concurred in connective tissue disease (CTD).
Asunto(s)
Autoanticuerpos/sangre , Enfermedades Autoinmunes/diagnóstico , Enfermedades Pulmonares Intersticiales/complicaciones , Polimiositis/complicaciones , Proteinosis Alveolar Pulmonar/diagnóstico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/fisiopatología , Líquido del Lavado Bronquioalveolar/citología , Disnea/etiología , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Humanos , Inmunosupresores/efectos adversos , Pulmón/fisiopatología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Persona de Mediana Edad , Polimiositis/tratamiento farmacológico , Proteinosis Alveolar Pulmonar/inmunología , Proteinosis Alveolar Pulmonar/fisiopatología , Proteinosis Alveolar Pulmonar/terapia , Tomografía Computarizada por Rayos XRESUMEN
Inborn errors of metabolism (IEMs) whilst individually rare, as a group constitute a field which is increasingly demands on pulmonologists. With the advent of new therapies such as enzyme replacement and gene therapy, early diagnosis and treatment of these conditions can impact on long term outcome, making their timely recognition and appropriate investigation increasingly important. Conversely, with improved treatment, survival of these patients is increasing, with the emergence of previously unknown respiratory phenotypes. It is thus important that pulmonologists are aware of and appropriately monitor and manage these complications. This review aims to highlight the respiratory manifestations which can occur. It isdivided into conditions resulting primarily in obstructive airway and lung disease, restrictive lung disease such as interstitial lung disease or pulmonary alveolar proteinosis and pulmonary hypertension, whilst acknowledging that some diseases have the potential to cause all three. The review focuses on general phenotypes of IEMs, their known respiratory complications and the basic metabolic investigations which should be performed where an IEM is suspected.
Asunto(s)
Errores Innatos del Metabolismo/fisiopatología , Enfermedades Respiratorias/fisiopatología , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/metabolismo , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Obstructivas/etiología , Enfermedades Pulmonares Obstructivas/metabolismo , Enfermedades Pulmonares Obstructivas/fisiopatología , Errores Innatos del Metabolismo/complicaciones , Errores Innatos del Metabolismo/metabolismo , Proteinosis Alveolar Pulmonar/etiología , Proteinosis Alveolar Pulmonar/metabolismo , Proteinosis Alveolar Pulmonar/fisiopatología , Enfermedades Respiratorias/etiología , Enfermedades Respiratorias/metabolismoRESUMEN
We herein report a case of autoimmune pulmonary alveolar proteinosis (PAP) diagnosed after one-time exposure to silica powder. Owing to the misuse of a silica-containing fire extinguisher and the inhalation of large amounts of its powder, the patient experienced prolonged cough and visited our hospital. The findings of chest computed tomography and surgical lung biopsy specimens led to the diagnosis of PAP. Interestingly, the presence of anti-GM-CSF antibody was detected; therefore, both autoimmune characteristics and exposure to large amounts of silica may have caused the development of PAP in this patient. This case provides important insight into the mechanisms leading to the onset of PAP.
Asunto(s)
Enfermedades Autoinmunes/fisiopatología , Exposición a Riesgos Ambientales/efectos adversos , Material Particulado/efectos adversos , Proteinosis Alveolar Pulmonar/inducido químicamente , Proteinosis Alveolar Pulmonar/diagnóstico , Dióxido de Silicio/efectos adversos , Administración por Inhalación , Anciano , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/diagnóstico , Femenino , Sistemas de Extinción de Incendios , Humanos , Proteinosis Alveolar Pulmonar/fisiopatologíaRESUMEN
OBJECTIVE: Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by the alveolar accumulation of surfactant, which is composed of proteins and lipids. PAP is caused by a deficit of macrophage activity, for which the main treatment is whole-lung lavage (WLL). We report the experience at a referral center for PAP in Brazil. METHODS: This was a retrospective study involving patients with PAP followed between 2002 and 2016. We analyzed information regarding clinical history, diagnostic methods, treatments, and outcomes, as well as data on lung function, survival, and complications. RESULTS: We evaluated 12 patients (8 of whom were women). The mean age was 41 ± 15 years. Most of the patients were diagnosed by means of BAL and transbronchial biopsy. The mean number of WLLs performed per patient was 2.8 ± 2.5. One third of the patients never underwent WLL. Four patients (33.3%) had associated infections (cryptococcosis, in 2; nocardiosis, in 1; and tuberculosis, in 1), and 2 (16.6%) died: 1 due to lepidic adenocarcinoma and 1 due to complications during anesthesia prior to WLL. When we compared baseline data with those obtained at the end of the follow-up period, there were no significant differences in the functional data, although there was a trend toward an increase in SpO2. The median follow-up period was 45 months (range, 1-184 months). The 5-year survival rate was 82%. CONCLUSIONS: To our knowledge, this is the largest case series of patients with PAP ever conducted in Brazil. The survival rate was similar to that found at other centers. For symptomatic, hypoxemic patients, the treatment of choice is still WLL. Precautions should be taken in order to avoid complications, especially opportunistic infections.
Asunto(s)
Lavado Broncoalveolar/métodos , Proteinosis Alveolar Pulmonar/terapia , Adulto , Brasil , Femenino , Volumen Espiratorio Forzado , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Proteinosis Alveolar Pulmonar/diagnóstico por imagen , Proteinosis Alveolar Pulmonar/fisiopatología , Estudios Retrospectivos , Espirometría , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Capacidad VitalRESUMEN
ABSTRACT Objective: Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by the alveolar accumulation of surfactant, which is composed of proteins and lipids. PAP is caused by a deficit of macrophage activity, for which the main treatment is whole-lung lavage (WLL). We report the experience at a referral center for PAP in Brazil. Methods: This was a retrospective study involving patients with PAP followed between 2002 and 2016. We analyzed information regarding clinical history, diagnostic methods, treatments, and outcomes, as well as data on lung function, survival, and complications. Results: We evaluated 12 patients (8 of whom were women). The mean age was 41 ± 15 years. Most of the patients were diagnosed by means of BAL and transbronchial biopsy. The mean number of WLLs performed per patient was 2.8 ± 2.5. One third of the patients never underwent WLL. Four patients (33.3%) had associated infections (cryptococcosis, in 2; nocardiosis, in 1; and tuberculosis, in 1), and 2 (16.6%) died: 1 due to lepidic adenocarcinoma and 1 due to complications during anesthesia prior to WLL. When we compared baseline data with those obtained at the end of the follow-up period, there were no significant differences in the functional data, although there was a trend toward an increase in SpO2. The median follow-up period was 45 months (range, 1-184 months). The 5-year survival rate was 82%. Conclusions: To our knowledge, this is the largest case series of patients with PAP ever conducted in Brazil. The survival rate was similar to that found at other centers. For symptomatic, hypoxemic patients, the treatment of choice is still WLL. Precautions should be taken in order to avoid complications, especially opportunistic infections.
RESUMO Objetivo: A proteinose alveolar pulmonar (PAP) é uma doença rara, caracterizada pelo acúmulo alveolar de substância surfactante, composta por proteínas e lipídios. É causada por um déficit de atividade macrofágica, cujo principal tratamento é a lavagem pulmonar total (LPT). Relatamos a seguir a experiência de um centro de referência brasileiro em PAP. Métodos: Estudo retrospectivo com a avaliação de pacientes com PAP acompanhados entre 2002 e 2016. Informações sobre história clínica, métodos diagnósticos, tratamentos realizados e desfechos, incluindo dados de função pulmonar, sobrevida e presença de complicações, foram analisados. Resultados: Foram incluídos 12 pacientes (8 mulheres), com média de idade de 41 ± 15 anos. A maioria dos pacientes foi diagnosticada por LBA e biópsia transbrônquica. A média do número de LPT realizadas por paciente foi de 2,8 ± 2,5. Um terço dos pacientes não foi submetido à LPT. Quatro pacientes (33,3%) apresentaram infecções associadas (criptococose, em 2; nocardiose, em 1; e tuberculose, em 1) e houve 2 óbitos (16,6%): 1 por adenocarcinoma lepídico e 1 por complicações na indução anestésica pré-LPT. Não houve diferença significativa entre os dados funcionais; porém houve uma tendência de aumento da SpO2 ao se comparar os dados iniciais aos do final do seguimento. A mediana de seguimento foi de 45 meses (1-184 meses), com taxa de sobrevida em 5 anos de 82%. Conclusões: Pelo que sabemos, esta é a maior série de casos de PAP no Brasil. A taxa de sobrevida foi semelhante à encontrada em outros centros. A LPT ainda é o tratamento de escolha para pacientes sintomáticos e hipoxêmicos. Deve-se atentar para complicações, especialmente infecções oportunistas.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Proteinosis Alveolar Pulmonar/terapia , Lavado Broncoalveolar/métodos , Proteinosis Alveolar Pulmonar/fisiopatología , Proteinosis Alveolar Pulmonar/diagnóstico por imagen , Espirometría , Factores de Tiempo , Brasil , Tomografía Computarizada por Rayos X , Capacidad Vital , Volumen Espiratorio Forzado , Estudios Retrospectivos , Resultado del Tratamiento , Estimación de Kaplan-MeierRESUMEN
Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease that results from the accumulation of lipoproteinaceous material in the alveoli and alveolar macrophages due to abnormal surfactant homoeostasis. Identification of the granulocyte-macrophage colony-stimulating factor (GM-CSF) as an indispensable mediator of macrophage maturation and surfactant catabolism was the key discovery leading to the current understanding of the pathogenesis of most forms of PAP. Impaired GM-CSF bioavailability due to anti-GM-CSF autoimmunity is the cause of approximately 90% of adult PAP cases. Abnormal macrophage function due to endogenous or exogenous triggers, GM-CSF receptor defects, and other genetic abnormalities of surfactant production account for the remainder of causes. The usual physiological consequence of PAP is impairment of gas exchange, which can lead to dyspnoea, hypoxaemia, or even respiratory failure and death. Pulmonary fibrosis occurs occasionally in patients with PAP. For patients with moderate to severe disease, whole lung lavage is still the first-line treatment of choice. Supplemental GM-CSF is also useful, but details about indications, choice of agent, and dosing remain unclear. Other therapies, including rituximab, plasmapheresis, and lung transplantation have been described but should be reserved for refractory cases.
Asunto(s)
Proteinosis Alveolar Pulmonar/fisiopatología , Proteinosis Alveolar Pulmonar/terapia , Lavado Broncoalveolar/métodos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Humanos , Alveolos Pulmonares/fisiopatologíaRESUMEN
BACKGROUND: Secondary pulmonary alveolar proteinosis (sPAP) is an extremely rare disease. The clinical features of sPAP patients remain to be summarizeds. METHODS: Patients pathologically diagnosed with PAP and with negative results for anti-granulocyte macrophage colony stimulating factor (GM-CSF) autoantibodies from Peking Union Medical College Hospital between January 2000 and July 2016 were retrospectively studied. The PubMed database was also searched for literature to collect published cases. RESULTS: In our center, nine patients were diagnosed as sPAP with a median age of 37 years. Hematological disorders, including myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), and pulmonary tuberculosis (TB) infection were the underlying diseases. Cases secondary to MDS had very poor prognosis as all of them survived less than 2 years after their diagnosis, while those secondary to TB had favorable prognosis. Only 33.3% of cases showed interlobular septal thickening in our sPAP group. Through literature review, 164 sPAP cases were collected. The age at diagnosis was 45.0 ± 14.8 years old and the gender radio was 1.20:1 (M:F). 61.9% of cases were diagnosed by bronchoscopy. MDS and CML were common underlying diseases in 34.1% and 15.2% of patients, respectively. Patients with sPAP secondary to hematological diseases had a short survival time and half of them died within 14.95 months after diagnosis. CONCLUSIONS: MDS and TB infection were the most frequent underlying causes of sPAP in this single-center research in China, with cases secondary to MDS having a poor survival rate. sPAP was more likely to be secondary to hematological disorders, especially MDS and CML and had a fairly poor prognosis in published cases. sPAP should be suspected in PAP patients whose CT scan presents only ground-glass opacities without interlobular septal thickening.
Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Síndromes Mielodisplásicos/complicaciones , Proteinosis Alveolar Pulmonar/etiología , Tuberculosis Pulmonar/complicaciones , Adulto , Broncoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteinosis Alveolar Pulmonar/diagnóstico por imagen , Proteinosis Alveolar Pulmonar/fisiopatología , Pruebas de Función Respiratoria , Estudios Retrospectivos , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Adulto JovenAsunto(s)
Huésped Inmunocomprometido/fisiología , Proteinosis Alveolar Pulmonar/diagnóstico , Broncoscopía/métodos , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/inmunología , Masculino , Persona de Mediana Edad , Proteinosis Alveolar Pulmonar/diagnóstico por imagen , Proteinosis Alveolar Pulmonar/fisiopatología , RecurrenciaRESUMEN
INTRODUCTION: Pulmonary alveolar proteinosis is a rare, diffuse interstitial lung disease, characterized by alveolar obstruction due to the accumulation of pulmonary surfactant. CLINICAL PRESENTATION: A 30-year-old male with progressively worsening dyspnea and non-productive cough for one year. He was a sugar cane plantation worker and had prior recurrent respiratory infections. Physical exam revealed cyanosis, and bilateral coarse and fine rales. Chest computed tomography showed diffuse crazy paving pattern. Bronchoscopy with bronchoalveolar lavage yielded a foamy, thick whitish material. Cytology revealed lymphocytes and acellular proteinaceous eosinophilic material. Transbronchial biopsy confirmed the diagnosis of pulmonary alveolar proteinosis. Patient met criteria for whole lung lavage, responding favorably to this therapy. CONCLUSION: Pulmonary alveolar proteinosis is a rare lung disease and important to consider due to the diagnostic and therapeutic challenge it represents.
INTRODUCCIÓN: La proteinosis alveolar pulmonar es una enfermedad intersticial difusa poco frecuente, en la cual se produce obstrucción alveolar, debido al acúmulo de surfactante pulmonar. REPORTE DEL CASO: Varón de 30 años de edad, presentó disnea progresiva y tos seca de un año de evolución. Antecedente personal: estibador de caña de azúcar. Presentó infecciones respiratorias recurrentes. Al examen físico se encontró cianosis, crepitantes difusos bilaterales y subcrepitantes en bases pulmonares. En la tomografía torácica con contraste se encontró un patrón de "empedrado loco". Se realizó videobroncoscopia con lavado broncoalveolar, aspirando material lechoso, espumoso y mucoso. Por citología se encontró linfocitos y material eosinofílico proteináceo acelular. El estudio anatomopatológico de la biopsia transbronquial reveló proteinosis alveolar pulmonar. El paciente reunió los criterios para tratamiento con lavado broncoalveolar total. Luego de este procedimiento, evolucionó favorablemente. CONCLUSIÓN: La proteinosis alveolar pulmonar constituye una enfermedad importante a considerar, por el desafío diagnóstico y terapéutico que representa.
Asunto(s)
Lavado Broncoalveolar/métodos , Disnea/etiología , Proteinosis Alveolar Pulmonar/diagnóstico , Adulto , Biopsia , Broncoscopía/métodos , Tos/etiología , Humanos , Masculino , Proteinosis Alveolar Pulmonar/diagnóstico por imagen , Proteinosis Alveolar Pulmonar/fisiopatología , Enfermedades Raras/diagnóstico , Enfermedades Raras/diagnóstico por imagen , Enfermedades Raras/fisiopatología , Tomografía Computarizada por Rayos XRESUMEN
Pulmonary alveolar proteinosis is a broad group of rare diseases that are defined by the occupation of a lung's gas-exchange area by pulmonary surfactants that are not properly removed. The clinical and radiologic phenotypes among them are very similar. The age of manifestation plays a central role in the differential diagnosis of the almost 100 conditions and provides an efficient path to the correct diagnosis. The diagnostic approach is tailored to identify genetic or autoimmune causes, exposure to environmental agents, and associations with numerous other diseases. Whole-lung lavages are the cornerstone of treatment, and children in particular depend on the expertise to perform such therapeutic lavages. Other treatment options and long-term survival are related to the condition causing the proteinosis.
Asunto(s)
Proteinosis Alveolar Pulmonar/diagnóstico , Biopsia , Lavado Broncoalveolar/métodos , Broncoscopía , Niño , Diagnóstico Diferencial , Humanos , Aumento de la Imagen , Pulmón/patología , Proteinosis Alveolar Pulmonar/patología , Proteinosis Alveolar Pulmonar/fisiopatología , Proteinosis Alveolar Pulmonar/terapia , Intercambio Gaseoso Pulmonar/fisiología , Surfactantes Pulmonares/metabolismo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND AND OBJECTIVE: Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar filling. YKL-40, a chitinase-like protein produced by macrophages and epithelial cells, is increased in patients with interstitial lung diseases. We aimed to evaluate the role of YKL-40 as a biomarker for PAP. METHODS: A total of 34 patients with autoimmune PAP and 50 healthy controls were studied. YKL-40 was measured by ELISA in serum and bronchoalveolar lavage fluid (BALF). Chitinase coding gene polymorphisms (CHI3L1-329 and -131) were detected by PCR and pyrosequencing. Correlations between serum YKL-40 levels and disease outcome were analysed. RESULTS: Baseline serum and BALF levels of YKL-40 were higher in PAP patients than in controls (286 ± 27 ng/mL vs 42 ± 4 ng/mL, P < 0.0001; 323 ± 36 ng/mL vs 3 ± 1 ng/mL, P < 0.0001, respectively). Serum YKL-40 levels correlated with diffusing capacity of the lung for carbon monoxide (DLCO ) at baseline (P = 0.002) and over time (P < 0.0001). Patients with disease progression had higher baseline serum YKL-40 levels than those who remained stable or improved (P < 0.0001). A baseline cut-off level of 300 ng/mL was predictive of disease progression (HR (hazard ratio): 7.875, P = 0.001). The presence of the G allele was associated with higher serum and BALF levels of YKL-40. CONCLUSION: YKL-40 is elevated in serum and BALF of PAP patients, and may be of clinical utility to predict outcome in PAP.
Asunto(s)
Proteína 1 Similar a Quitinasa-3/sangre , Progresión de la Enfermedad , Proteinosis Alveolar Pulmonar/sangre , Adulto , Biomarcadores/sangre , Líquido del Lavado Bronquioalveolar/química , Proteína 1 Similar a Quitinasa-3/análisis , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Proteinosis Alveolar Pulmonar/fisiopatología , Estudios RetrospectivosRESUMEN
BACKGROUND: The congenital form of pulmonary alveolar proteinosis due to colony stimulating factor 2 receptor alpha gene mutations is a rare disease with only a few cases reported worldwide. In this study we report a new case of pulmonary alveolar proteinosis with a novel variant in colony stimulating factor 2 receptor alpha gene. CASE PRESENTATION: A 5-year-old Saudi boy presented with a history of progressive dyspnea over 6 months; he was diagnosed as having pulmonary alveolar proteinosis. A molecular study revealed a novel variation in colony stimulating factor 2 receptor alpha gene. His clinical condition showed significant improvement after whole lung lavage. CONCLUSIONS: This case has the typical presentation of congenital pulmonary alveolar proteinosis due to colony stimulating factor 2 receptor alpha defect with a novel variant in this gene likely to be pathogenic.
Asunto(s)
Lavado Broncoalveolar , Disnea/fisiopatología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Mutación , Proteinosis Alveolar Pulmonar/congénito , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Preescolar , Progresión de la Enfermedad , Disnea/etiología , Disnea/terapia , Marcadores Genéticos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/fisiología , Humanos , Masculino , Linaje , Proteinosis Alveolar Pulmonar/genética , Proteinosis Alveolar Pulmonar/fisiopatología , Proteinosis Alveolar Pulmonar/terapia , Hermanos , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was to investigate whether ultra-low-dose chest computed tomography (CT) can be used for visual assessment of CT features in patients with pulmonary alveolar proteinosis (PAP) and to evaluate the relationship between the quantitative analysis of the ultra-low-dose CT scans and the pulmonary function tests (PFTs). METHODS: Thirty-eight patients (mean [SD] age, 44.47 [12.28] years; 29 males, 9 females) with PAP were enrolled and subjected to two scans each with low-dose CT (reference parameters: 120 kV and 50 mAs) and ultra-low-dose CT (reference parameters, 80 kV, 25 mAs). Images were reconstructed via filtered back projection (FBP) for low-dose CT and iterative reconstruction (IR) for ultra-low-dose CT. All patients underwent PFT. The Visual analysis for ground glass opacity (GGO) is performed. The quantitative CT and PFT results were analyzed by canonical correlations. RESULTS: The mean body mass index (BMI) was 25.37±3.26 kg/m2. The effective radiation doses were 2.30±0.46 and 0.24±0.05 mSv for low-dose and ultra-low-dose CT, respectively. The size-specific dose estimates were 5.81±0.81 and 0.62±0.09 mSv for low-dose and ultra-low-dose CT. GGOs and interlobular septal thickening were observed bilaterally in all patients. The average visual GGO score was lower in the upper field (2.67±1.24) but higher in the middle and lower fields (3.08±1.32 and 3.08±0.97, respectively). The average score for the whole lung was 2.94±1.19. There is a significant correlation between PFTs and quantitative of ultra-low-dose CT (canonical loading = 0.78). CONCLUSIONS: Ultra-low-dose CT has the potential to quantify the lung parenchyma changes of PAP. This technique could provide a sensitive and objective assessment of PAP and has good relation with PFTs. In addition, the radiation dose of ultra-low-dose CT was very low.