RESUMO
OBJECTIVES: We aimed to reveal the incidence of lateonset noninfectious pulmonary complications and bronchiolitis obliterans syndrome and risk factors involved in development. MATERIALS AND METHODS: In this cross-sectional study, we retrospectively investigated 745 patients who underwent allogeneic hematopoietic stem cell transplantation in our hospital between January 2000 and December 2020. We evaluated demographic characteristics, comorbidities, and hematopoietic stem cell transplantation characteristics to determine possible risk factors affecting development of lateonset noninfectious pulmonary complications and bronchiolitis obliterans syndrome. RESULTS: Of 745 patients, 8.9% (n = 66) had late-onset noninfectious pulmonary complications. Complications included 38 patients with bronchiolitis obliterans syndrome, 13 with venous thromboembolism, 8 with cryptogenic organizing pneumonia, 5 with pneumothorax, 4 with interstitial lung disease-restrictive graft-versus-host disease, 5 with bronchiectasis, 2 with pneumomediastinum, and 1 with pleural effusion. Patients with and without complications were not significantly differentin terms of smoking history, hematopoietic stem cell transplantation characteristics, and conditioning regimens. Patients with complications had higher busulfan and lower antithymocyte globulin use than those without complications (both P<.05). Patients with complications more commonly had hematopoietic stem cell transplantation from related donors and chronic graft-versus-host disease (P < .05). Patients with bronchiolitis obliterans syndrome had more frequent use of busulfan (P <.05) but less frequent use of total body irradiation (P <.05) and antithymocyte globulin (P <.05) than those without this syndrome. Rate of hematopoietic stem cell transplantation from a related donor (P < .05) and frequency of chronic graftversus-host disease (P < .001) were significantly higher in patients with bronchiolitis obliterans syndrome, presented with bronchiectasis (78.6%), air trapping (67.9%), bronchial wallthickening (53.6%), and mosaic attenuation (39.3%) in thorax computed tomography. Pretransplant spirometry did not predict bronchiolitis obliterans syndrome development. CONCLUSIONS: Determining risk factors for late-onset noninfectious pulmonary complications is needed to aid in prevention and follow-up.
Assuntos
Bronquiolite Obliterante , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Masculino , Feminino , Fatores de Risco , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Fatores de Tempo , Incidência , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/diagnóstico , Resultado do Tratamento , Adulto Jovem , Pneumopatias/etiologia , Pneumopatias/diagnóstico , Pneumopatias/epidemiologia , Medição de Risco , Adolescente , Turquia/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologiaRESUMO
BACKGROUND: Post-infectious bronchiolitis obliterans (PIBO) is the most common sequelae in children with adenovirus pneumonia (ADVP). However, there are few studies on the risk factors for PIBO occurrence. This study aims to investigate the risk factors for PIBO in pediatric patients with severe ADVP, especially after invasive mechanical ventilation (IMV), as well as to build a nomogram prediction model. METHODS: The clinical data, laboratory and imaging features, and treatment of 863 children with ADVP under 3 years old who were admitted to our hospital from January to December 2019 were retrospectively analyzed. Among them, 66 children with severe ADVP received IMV treatment. The situation and the influencing factors of PIBO in children with severe ADVP were explored, and a nomogram prediction model was constructed. RESULTS: Among the 863 cases of ADVP, 46 cases (5.33%) developed PIBO. Duration of fever, IMV, complications, and neutrophil percentage were independent risk factors for PIBO in children with ADVP. Among the 66 patients with ADVP who underwent IMV, 33 patients (50.0%) developed PIBO. Gender, duration of fever, adenovirus (ADV) load, and mixed fungal coinfections were independent risk factors for PIBO. In the nomogram prediction model analysis, the area under the curve (AUC) was 0.857; in addition, HosmerâLemeshow (H-L) detection reflected good alignment (χ2 = 68.75, P < 0.01). CONCLUSIONS: A nomogram prediction model, which can be utilized to predict PIBO occurrence in pediatric patients with ADVP after IMV at an early time period, was successfully built.
Assuntos
Infecções por Adenoviridae , Bronquiolite Obliterante , Pneumonia Viral , Criança , Humanos , Pré-Escolar , Estudos Retrospectivos , Nomogramas , Respiração Artificial/efeitos adversos , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/epidemiologia , Infecções por Adenoviridae/complicações , Infecções por Adenoviridae/diagnóstico , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , AdenoviridaeRESUMO
Pulmonary chronic graft-versus-host-disease (cGVHD), or bronchiolitis obliterans syndrome (BOS), is a highly morbid complication of hematopoietic cell transplantation (HCT). The clinical significance of a single instance of pulmonary decline not meeting the criteria for BOS is unclear. We conducted a retrospective analysis in a cohort of patients who had an initial post-HCT decline in the absolute value of forced expiratory volume in 1 second (FEV1) of ≥10% or mid-expiratory flow rate of ≥25% but not meeting the criteria for BOS (pre-BOS). We examined the impact of clinical variables in patients with pre-BOS on the risk for subsequent BOS. Pre-BOS developed in 1325 of 3170 patients (42%), of whom 72 (5%) later developed BOS. Eighty-four patients developed BOS without detection of pre-BOS by routine screening. Among patients with pre-BOS, after adjusting for other significant variables, airflow obstruction (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.1 to 3.7; P = .02), percent-predicted FEV1 on decline (HR, .98; 95% CI, .97 to 1.0; P = .02), active cGVHD (HR, 7.7; 95% CI, 3.1 to 19.3; P < .001), peripheral blood stem cell source (HR, 3.8; 95% CI, 1.7 to 8.6; P = .001), and myeloablative conditioning (HR, 2.0; 95% CI, 1.1 to 3.5; P = .02) were associated with subsequent BOS. The absence of airflow obstruction and cGVHD had a negative predictive value of 100% at 6 months for subsequent BOS, but the positive predictive value of both factors was low (cGVHD, 3%; any obstruction, 4%; combined, 6%). Several clinical factors at the time of pre-BOS, particularly active cGVHD and airflow obstruction, increase the risk for subsequent BOS. These factors merit consideration to be included in screening practices to improve the detection of BOS, with the caveat that the predictive utility of these factors is limited by the overall low incidence of BOS among patients with pre-BOS.
Assuntos
Síndrome de Bronquiolite Obliterante , Bronquiolite Obliterante , Transplante de Células-Tronco Hematopoéticas , Doença Pulmonar Obstrutiva Crônica , Humanos , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/etiologia , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fatores de Risco , Doença Pulmonar Obstrutiva Crônica/complicaçõesRESUMO
The prevalence of lung transplants has increased over the years, albeit with a low survival rate amongst all solid organ transplants, including liver and heart transplantation. Microaspiration is one of the primary mechanisms that has been implicated in the pathogenesis of lung injury following lung transplants. Of late, esophageal dysfunction such as gastroesophageal reflux and esophageal hypercontractility is often noted post-lung transplant. However, reflux is associated with chronic allograft lung injury such as bronchiolitis obliterans syndrome, which is one of the predictors for long-term survival in this specialized population. Its role in acute lung injury post-lung transplant is still being explored. This review critically examines the salient points which provide the current understanding of the characteristics, pathophysiology, and implications of esophageal dysfunction following lung transplant.
Assuntos
Bronquiolite Obliterante , Doenças do Esôfago , Refluxo Gastroesofágico , Lesão Pulmonar , Transplante de Pulmão , Humanos , Lesão Pulmonar/complicações , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/epidemiologia , Refluxo Gastroesofágico/complicações , Transplante de Pulmão/efeitos adversosRESUMO
BACKGROUND: Aspiration has been associated with graft dysfunction after lung transplantation, leading some to advocate for selective use of fundoplication despite minimal data supporting this practice. METHODS: We performed a multicenter retrospective study at 4 academic lung transplant centers to determine the association of gastroesophageal reflux disease and fundoplication with bronchiolitis obliterans syndrome and survival using Cox multivariable regression. RESULTS: Of 542 patients, 136 (25.1%) underwent fundoplication; 99 (18%) were found to have reflux disease without undergoing fundoplication. Blanking the first year after transplantation, fundoplication was not associated with a benefit regarding freedom from bronchiolitis obliterans syndrome (hazard ratio [HR], 0.93; 95% CI, 0.58-1.49) or death (HR, 0.97; 95% CI, 0.47-1.99) compared with reflux disease without fundoplication. However, a time-dependent adjusted analysis found a slight decrease in mortality (HR, 0.59; 95% CI, 0.28-1.23; P = .157), bronchiolitis obliterans syndrome (HR, 0.68; 95% CI, 0.42-1.11; P = .126), and combined bronchiolitis obliterans syndrome or death (HR, 0.66; 95% CI, 0.42-1.04; P = .073) in the fundoplication group compared with the gastroesophageal reflux disease group. CONCLUSIONS: Although a statistically significant benefit from fundoplication was not determined because of limited sample size, follow-up, and potential for selection bias, a randomized, prospective study is still warranted.
Assuntos
Síndrome de Bronquiolite Obliterante , Bronquiolite Obliterante , Refluxo Gastroesofágico , Transplante de Pulmão , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/etiologia , Refluxo Gastroesofágico/cirurgia , Transplante de Pulmão/efeitos adversosRESUMO
Background: Haploidentical donor stem cell transplantation (HID-SCT) based on antithymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis had achieved a similar incidence of chronic graft-versus-host disease (cGVHD) with human leukocyte antigen (HLA)-matched sibling donor stem cell transplantation (MSD-SCT). However, bronchiolitis obliterans syndrome (BOS), which serves as pulmonary cGVHD, was rarely compared between HID and MSD transplantation. Methods: One thousand four hundred five patients with hematologic malignancies who underwent allogeneic SCT were enrolled in this retrospective study. Based on donor type, we divided the patients into three groups: HID, MSD, and match unrelated donor (MUD) groups. The cumulative incidences and risk factors of BOS were analyzed. Results: The 5-year cumulative incidence of BOS was 7.2% in the whole population. HID transplantation had a lower 5-year cumulative incidence of BOS than MSD transplantation (4.1% vs. 10.0%, p < 0.001) and a similar incidence with MUD transplantation (4.1% vs. 6.2%, p = 0.224). The 5-year cumulative incidence of BOS was lower in the ATG group than that in the non-ATG group in both the whole and MSD populations (4.6% vs. 11.2%, p < 0.001, and 4.1% vs. 11.2%, p = 0.042, respectively). The 5-year incidence of BOS in mixed grafts [peripheral blood stem cell (PBSC) plus bone marrow] group was also lower than that in the PBSC group (4.2% vs. 9.1, p = 0.001). Multivariate analysis showed that HID, ATG, and mixed grafts were protective factors for BOS [odds ratio (OR) 0.3, 95% CI 0.2-0.6, p < 0.001; OR 0.3, 95% CI 0.2-0.7, p = 0.001; OR 0.3, 95% CI 0.1-0.8, p = 0.013], and acute graft-versus-host disease (aGVHD) and cGVHD were independent risk factors for BOS (OR 2.1, 95% 1.1-4.3, p = 0.035; OR 10.1, 95% CI 4.0-25.0, p < 0.001). Conclusions: HID transplantation had a lower incidence of BOS than MSD transplantation, which might be associated with ATG and mixed grafts.
Assuntos
Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Incidência , Irmãos , Condicionamento Pré-Transplante , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/etiologia , Antígenos HLA , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/etiologia , Doadores não Relacionados , Antígenos de Histocompatibilidade Classe IIRESUMO
BACKGROUND: Bronchiolitis obliterans syndrome (BOS)-chronic graft-versus-host disease (cGVHD) affecting the lungs-is an uncommon complication of allogeneic hematopoietic cell transplant (HCT). The epidemiology and complications of lower respiratory tract infections (LRTIs) and community-acquired respiratory viruses (CARVs) in these patients are poorly understood. OBJECTIVES: We aim to characterize the epidemiology of LRTIs in patients with BOS complicating HCT. We also aim to explore the association of LRTIs and CARV detection on lung function in BOS patients. STUDY DESIGN: Adult patients with BOS at Stanford Health Care between January 2010 and December 2019 were included in this retrospective cohort study. LRTI diagnosis was based on combined clinical, microbiologic, and radiographic criteria, using consensus criteria where available. RESULTS: Fifty-five patients with BOS were included. BOS was diagnosed at a median of 19.2 (IQR 12.5-24.7) months after HCT, and patients were followed for a median of 29.3 (IQR 9.9-53.2) months from BOS diagnosis. Twenty-two (40%) patients died after BOS diagnosis; 17 patients died from complications of cGVHD (including respiratory failure and infection) and 5 died from relapsed disease. Thirty-four (61.8%) patients developed at least one LRTI. Viral LRTIs were most common, occurring in 29 (52.7%) patients, primarily due to rhinovirus. Bacterial LRTIs-excluding Nocardia and non-tuberculous mycobacteria (NTM)-were the second most common, occurring in 21 (38.2%) patients, mostly due to Pseudomonas aeruginosa. Fungal LRTIs, NTM, and nocardiosis occurred in 14 (25.5%), 10 (18.2%), and 4 (7.3%) patients, respectively. Median time to development of the first LRTI after BOS diagnosis was 15.3 (4.7-44.7) months. Twenty-six (76.5%) of the 34 patients who developed LRTIs had infections due to more than one type of organism-fungi, viruses, Nocardia, NTM, and other bacteria-over the observation period. Patients with at least one LRTI had significantly lower forced expiratory volume in one second percent predicted (FEV1%) (37% vs. 53%, p = 0.0096) and diffusing capacity of carbon monoxide (DLCO) (45.5% predicted vs. 69% predicted, p = 0.0001). Patients with at least one LRTI trended toward lower overall survival (OS) (p = 0.0899) and higher non-relapse mortality (NRM) (p = 0.2707). Patients with a CARV detected or LRTI diagnosed after BOS-compared to those without any CARV detected or LRTI diagnosed-were more likely to have a sustained drop in FEV1% from baseline of at least 10% (21 [61.8%] versus 7 [33.3%]) and a sustained drop in FEV1% of at least 30% (12 [36.4%] versus 2 [9.5%]). CONCLUSIONS: LRTIs are common in BOS and associated with lower FEV1%, lower DLCO, and a trend toward decreased OS and higher NRM. Patients with LRTIs or CARVs (even absent lower respiratory tract involvement) were more likely to have substantial declines in FEV1% over time than those without. The array of organisms-including P. aeruginosa, mold, Nocardia, NTM, and CARVs-seen in BOS reflects the unique pathophysiology of this form of cGVHD, involving both systemic immunodeficiency and structural lung disease. These patterns of LRTIs and their outcomes can be used to guide clinical decisions and inform future research.
Assuntos
Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Infecções Respiratórias , Adulto , Bronquiolite Obliterante/epidemiologia , Monóxido de Carbono , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Infecções Respiratórias/epidemiologia , Estudos Retrospectivos , Rhinovirus , SíndromeRESUMO
PURPOSE: Bronchiolitis obliterans syndrome (BOS) is a major cause of morbidity and mortality in lung transplantation and allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Clinical guidelines recommend lung function monitoring to aid early identification of BOS, but real-world rates of pulmonary function testing (PFT) have not been studied. The purpose of this study was to quantify PFT rates in lung transplantation and allo-HSCT recipients. METHODS: This longitudinal retrospective study used US data from the IQVIA PharMetrics Plus commercial claims database (January 1, 2006-September 30, 2018) and the Medicare Limited Data Set (January 1, 2010-December 31, 2018). Study recipients had no evidence of transplantation 12 months before transplantation, which was identified by using diagnosis and procedure codes. PFTs were identified by using procedure codes. Outcomes were percentage of recipients who received ≥1 PFT in each follow-up year, including spirometry, lung diffusion capacity, lung function volume test, and plethysmography, including the average number of total and specific tests per recipient. FINDINGS: The study identified 367 commercially insured and 1776 Medicare recipients who underwent lung transplantation; 92% and 86% received ≥1 lung function test in the first year after transplantation, respectively. Among recipients observable 3 years after transplant, 85% and 83% received ≥1 PFT. Among 2187 commercially insured and 1864 Medicare recipients who underwent allo-HSCT, 44% and 36% received ≥1 lung function test in the first posttransplant year. In the third year after transplant, only 31% and 26% of observable allo-HSCT recipients underwent any PFT. IMPLICATIONS: Morbidity and mortality from BOS remain high in lung transplant and allo-HSCT recipients, but lung function testing in the first posttransplant year is not universal, with substantially lower rates among allo-HSCT recipients. Furthermore, testing rates in all cohorts declined over time. Increased and sustained monitoring could lead to earlier detection of BOS and earlier intervention and treatment.
Assuntos
Bronquiolite Obliterante , Transplante de Células-Tronco Hematopoéticas , Transplante de Pulmão , Idoso , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pulmão , Transplante de Pulmão/efeitos adversos , Medicare , Estudos Retrospectivos , Síndrome , Estados UnidosRESUMO
BACKGROUND: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for pulmonary adverse events. Data on late-onset noninfectious pulmonary complications in long-term adult survivors of allo-HSCT are limited and incomplete. OBJECTIVES: This study aimed (1) to determine occurrence and degree of pulmonary sequelae in adult survivors of allo-HSCT and (2) to identify associations between pulmonary function, high-resolution CT (HRCT), and clinical characteristics. METHOD: In a nationwide, single-center cross-sectional study, 103 survivors (aged median [range] 35 [17-58] years, 53% females) were examined 17 (6-32) years after allo-HSCT and compared with healthy controls (n = 105). Methods included pulmonary function tests and HRCT. RESULTS: Chronic graft-versus-host disease was diagnosed in 33% of survivors, including 12% with bronchiolitis obliterans syndrome (BOS). Mean lung volumes (TLC, FVC, and FEV1) and gas diffusing capacity were >80% of predicted for the survivors as a group, but significantly lower than in healthy controls. Pathological HRCT findings were detected in 48% of the survivors (71% airways disease, 35% interstitial lung disease, and 24% apical subpleural interstitial thickening). Air trapping (%) on HRCT correlated with % predicted FEV1, p < 0.001. In a multiple logistic regression model, both BOS and pathological findings on HRCT were associated with chemotherapy prior to allo-HSCT, p < 0.05. CONCLUSIONS: Long-term allo-HSCT survivors had significantly lower pulmonary function than age- and gender-matched healthy controls and nearly half had pathological findings on HRCT. Longitudinal data will determine if pulmonary sequelae will remain stable or progress. We recommend lifelong monitoring of pulmonary function in allo-HSCT survivors. HRCT provides additional information, but is not suited for surveillance.
Assuntos
Bronquiolite Obliterante , Transplante de Células-Tronco Hematopoéticas , Adulto , Idoso , Bronquiolite Obliterante/diagnóstico por imagem , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/etiologia , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , SobreviventesRESUMO
OBJECTIVES: To determine the demographic and clinical characteristics, underlying comorbidities, and outcomes of children with coronavirus disease 2019 (COVID-19) infection. METHODS: In this retrospective study, we reported 62 pediatric patients (age <14 years) with confirmed COVID-19 between March 2 and July 1, 2020, at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. RESULTS: Comorbid conditions, including cardiac, neurological, respiratory, and malignant disorders, were reported in 9 patients (14.5%). The most prominent presenting complaints were fever (80.6%) and cough (48.4%). Most of our patients (80.6%) had mild disease, 11.3% had moderate disease, and 8.1% exhibited severe and critical illness. Twenty-one patients (33.9%) were hospitalized, with 4 patients (6.5%) admitted to the pediatric intensive care unit, and 3 (4.8%) patients died. CONCLUSION: All pediatric age groups are susceptible to COVID-19, with no gender difference. COVID-19 infection may result in critical illness and even mortality in subsets of pediatric patients.
Assuntos
COVID-19/fisiopatologia , Dor Abdominal/fisiopatologia , Adolescente , Asma/epidemiologia , Atrofia , Encéfalo/patologia , Bronquiolite Obliterante/epidemiologia , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/terapia , Criança , Pré-Escolar , Comorbidade , Tosse/fisiopatologia , Diarreia/fisiopatologia , Dispneia/fisiopatologia , Feminino , Febre/fisiopatologia , Cardiopatias Congênitas/epidemiologia , Mortalidade Hospitalar , Hospitalização , Humanos , Hidrocefalia/epidemiologia , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Faringite/fisiopatologia , Respiração Artificial , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Rinorreia/fisiopatologia , SARS-CoV-2 , Arábia Saudita/epidemiologia , Índice de Gravidade de Doença , Vômito/fisiopatologiaRESUMO
BACKGROUND AND OBJECTIVE: Bronchiolitis obliterans (BO) is a rare but serious condition. The natural history and outcomes remain poorly understood. In this clinical review, we aimed to describe the clinical characteristics and outcomes of children diagnosed with BO in Hong Kong (HK). METHODS: This was a retrospective study of pediatric patients with BO under the care of six respiratory units in HK from January 1996 to December 2015. Information was retrieved from medical records. RESULTS: Fifty-six patients were included with a male predominance (67.9%). The median age at diagnosis was 1.98 years (interquartile range [IQR]: 0.84-4.99 years). Postinfectious BO (PIBO) was the commonest cause (64.3%) followed by posthematopoietic stem-cell transplant (21.4%). Adenovirus (63.2%) was the commonest causative pathogen among PIBO. The median follow-up duration was 9.7 years (IQR: 2.9-14.3 years). Twenty-five patients (44.6%) could achieve symptom-free recovery at the time of follow-up. Five (8.9%) and three (5.4%) were oxygen or ventilator dependent, respectively. There were two deaths, both had posttransplant BO. Patients who developed BO after transplant had significantly worse lung function than those with PIBO. There were no risk factors significantly associated with worse clinical outcomes (oxygen/ventilator dependence or death) by logistic regression. Among patients with PIBO, coinfection at presentation was significantly associated with persistent symptoms at follow-up (p = .028). CONCLUSIONS: The most common cause of childhood BO in HK is postinfectious and coinfection at presentation was associated with persistent symptoms at follow-up. Further studies are needed to better elucidate disease progression, treatment options and long term outcomes.
Assuntos
Bronquiolite Obliterante/epidemiologia , Infecções por Adenoviridae , Adolescente , Bronquiolite Obliterante/fisiopatologia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Hong Kong/epidemiologia , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
RATIONALE: Bronchiolitis obliterans syndrome (BOS) is a severe, chronic inflammation of the airways leading to an obstruction of the bronchioles. So far, there are only a few studies looking at the long-term development of pulmonary impairment in children with BOS. OBJECTIVE: The objective of this study was to investigate the incidence and long-term outcome of BOS in children who underwent allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Medical charts of 526 children undergoing HSCT in Frankfurt/Main, Germany between 2000 and 2017 were analyzed retrospectively and as a result, 14 patients with BOS were identified. A total of 271 lung functions (spirometry and body plethysmography), 26 lung clearance indices (LCI), and 46 chest high-resolution computed tomography (HRCT) of these 14 patients with BOS were evaluated. RESULTS: Fourteen patients suffered from BOS after HSCT (2.7%), whereby three distinctive patterns of lung function impairment were observed: three out of 14 patients showed a progressive lung function decline; two died and one received a lung transplant. In five out of 14 patients with BOS persisted with a severe obstructive and secondarily restrictive pattern in lung function (forced vital capacity [FVC] < 60%, forced expiratory volume in 1 second [FEV1] < 50%, and FEV1/FVC < 0.7) and increased LCI (11.67-20.9), six out of 14 patients recovered completely after moderate lung function impairment and signs of BOS on HRCT. Long-term FVC in absolute numbers was increased indicating that the children still have lung growth. CONCLUSION: Our results showed that the incidence of BOS in children is low. BOS was associated with high mortality and may lead to persistent obstructive lung disease; although, lung growth continued to exist.
Assuntos
Bronquiolite Obliterante/diagnóstico , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/fisiopatologia , Criança , Pré-Escolar , Feminino , Volume Expiratório Forçado , Humanos , Incidência , Lactente , Pulmão/fisiopatologia , Masculino , Testes de Função Respiratória , Estudos Retrospectivos , Síndrome , Adulto JovemRESUMO
Objectives. Lung transplantation remains the only available treatment option for many end-stage lung diseases. We evaluated our long-term lung transplantation results and the impact of chronic lung allograft dysfunction (CLAD). Design. Adult de novo lung transplants (2003-2015, n=175) in a nationwide single transplant center were retrospectively analyzed. Kaplan-Meier survival and Cox regression analysis were used to evaluate the effect of CLAD. Results. Recipient and graft 1-, 5- and 10-year survival estimates were 94%, 79% and 64%, and 93%, 75% and 59%, respectively. CLAD affected 43% of patients at a median of 2.3 years after transplantation, and impaired recipient (p = .03) and graft survival (p = .001) with the most advanced CLAD stage, and restrictive CLAD phenotype, resulting in worst graft survival. CLAD was the primary cause of death in 54% of all patients, and in 80% of patients with an established CLAD diagnosis. CLAD, high-risk cytomegalovirus serostatus, and recipient preoperative sensitization increased graft loss hazard ratio. CLAD was the only significant investigated risk factor for graft loss in multivariate regression analysis. Conclusions. Although very favourable lung transplant patient long-term survival was achieved, CLAD significantly impaired recipient and graft survival. Identification of risk factors and therapeutic options for CLAD may further improve lung transplantation results.
Assuntos
Bronquiolite Obliterante/epidemiologia , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Transplante de Pulmão/efeitos adversos , Adulto , Idoso , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/mortalidade , Doença Crônica , Feminino , Finlândia/epidemiologia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/mortalidade , Humanos , Incidência , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Bronchiolitis obliterans (BO) is a rare, chronic form of obstructive lung disease, often initiated with injury of the bronchiolar epithelium followed by an inflammatory response and progressive fibrosis of small airways resulting in nonuniform luminal obliteration or narrowing. The term BO comprises a group of diseases with different underlying etiologies, courses, and characteristics. Among the better recognized inciting stimuli leading to BO are airway pathogens such as adenovirus and mycoplasma, which, in a small percentage of infected children, will result in progressive fixed airflow obstruction, an entity referred to as postinfectious bronchiolitis obliterans (PIBO). The present knowledge on BO in general is reasonably well developed, in part because of the relatively high incidence in patients who have undergone lung transplantation or bone marrow transplant recipients who have had graft-versus-host disease in the posttransplant period. The cellular and molecular pathways involved in PIBO, while assumed to be similar, have not been adequately elucidated. Since 2016, an international consortium of experts with an interest in PIBO assembles on a regular basis in Geisenheim, Germany, to discuss key areas in PIBO which include diagnostic workup, treatment strategies, and research fields.
Assuntos
Bronquiolite Obliterante , Técnicas de Diagnóstico do Sistema Respiratório , Administração dos Cuidados ao Paciente/métodos , Infecções Respiratórias/complicações , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/terapia , Criança , Humanos , Infecções Respiratórias/microbiologiaRESUMO
The contribution of T-cells after lung transplant (LTx) remains controversial with no current consensus of their role concerning chronic lung allograft dysfunction. Using flow cytometry to assess T-cell subsets of bronchoalveolar lavage fluid (BALF) in 16 cystic fibrosis (CF) LTx recipients, we identified a decline in CD4+ T-cell frequency and an increase in CD8+ T-cell frequency in patients who developed severe bronchiolitis obliterans syndrome (BOS) (N = 10) when comparing baseline (6 months post-LTx) and follow-up (most recent bronchoscopy-clinical or surveillance per protocol). Comparing BOS to No BOS cohorts, significant differences were found in CD4+ T-cell frequency [17.4 (12.5, 28.2) vs 46.6 (44.4, 48.4), p = 0.003] and CD8+ T-cell frequency [65.6 (62.8, 75.3) vs 39.2 (32.2, 43.3), p = 0.014], respectively. The mean difference of the CD4:CD8 ratio was 0.87 units lower (95% CI - 1.44 to - 0.30, p = 0.006) than patients without BOS, while the median difference of the CD4:CD8 ratio was 0.92 units lower (95% CI - 1.83 to - 0.009, p = 0.048). Therefore, our results suggest that T-cell profiles measured through flow cytometry of BALF in the CF LTx population are associated with the development of severe BOS. Further work is needed in larger patient populations to validate our findings and to determine if this is useful for recipients who underwent LTx for other indications.
Assuntos
Bronquiolite Obliterante/imunologia , Fibrose Cística/cirurgia , Transplante de Pulmão , Complicações Pós-Operatórias/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Bronquiolite Obliterante/epidemiologia , Líquido da Lavagem Broncoalveolar/citologia , Complexo CD3/imunologia , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Casos e Controles , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunofenotipagem , Imunossupressores/uso terapêutico , Masculino , Complicações Pós-Operatórias/epidemiologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVE: To investigate the natural history of fibrotic lung disease in recipients of a single lung transplant for scleroderma-associated interstitial lung disease (ILD). METHODS: Global ILD (including ground glass, nodular opacities and fibrosis) was categorized into severity quintiles on first and last post-transplant CT scans, and percent fibrosis by manual contouring was also determined, in nine single lung transplant recipients. Quantitative mean lung densities and volumes for the native and allograft lungs were also acquired. RESULTS: In the native lung, global ILD severity quintile worsened in two cases and percent fibrosis worsened in four cases (range 5-28%). In the lung allograft, one case each developed mild, moderate and severe ILD; of these, new fibrotic ILD (involving <10% of lung) occurred in two cases and acute cellular rejection occurred in one. The average change in native lung density over time was +2.2 Hounsfield Units per year and lung volume +1.4 ml per year, whereas the allograft lung density changed by -5.5 Hounsfield Units per year and total volume +27 ml per year (P = 0.011 and P = 0.039 for native vs allograft density and volume comparisons, respectively). CONCLUSIONS: While the course of ILD in the native and transplanted lungs varied in this series, these cases illustrate that disease progression is common in the native lung, suggesting that either the immune process continues to target autoantigens or ongoing fibrotic pathways are active in the native lung. Mild lung disease may occur in the allograft after several years due to either allograft rejection or recurrent mild ILD.
Assuntos
Aloenxertos/diagnóstico por imagem , Rejeição de Enxerto/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Transplante de Pulmão/métodos , Pulmão/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico por imagem , Escleroderma Sistêmico/diagnóstico por imagem , Adulto , Bronquiolite Obliterante/diagnóstico por imagem , Bronquiolite Obliterante/epidemiologia , Progressão da Doença , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Estudos Longitudinais , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/cirurgia , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/cirurgia , Recidiva , Escleroderma Sistêmico/complicações , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Evidence from animal studies and small case series suggests that primary graft dysfunction occurs less often following combined organ transplantation than following isolated organ transplantation. In this large-scale national registry study, we aimed to investigate whether survival and the rates of bronchiolitis obliterans syndrome (BOS) and coronary allograft vasculopathy (CAV) are affected by simultaneous heart and/or lung transplantation (HLTx). METHODS: Clinical data from the United Network of Organ Sharing database were retrospectively reviewed to identify transplant-naive patients who had undergone heart and/or lung transplantation between 1987 and 2016. The comparisons were conducted for isolated vs combined organ transplant. The outcomes included all-cause mortality, as well as the incidence of BOS and CAV RESULTS: Of the 98,310 patients reviewed, 63,976, 1,189, and 33,145 had received isolated heart transplantation (iHTx) (65%), HLTx (1%), and isolated lung transplantation (iLTx) (34%), respectively. In the early post-operative period, the mortality rates were higher after HLTx than after iHTx or iLTx (on crude and propensity score-matched analyses). However, the adjusted hazard risk for mortality associated with HLTx was significantly lower relative to the iLTx-associated risk beyond 3 years postoperatively, and similar relative to the iHTx-associated risk beyond 7 years postoperatively. On both crude and adjusted analyses, the incidence of BOS and CAV was significantly lower after HLTx than after iHTx or iLTx (p < 0.001 for all comparisons). CONCLUSIONS: Combined (rather than single) organ transplantation may provide immunoprotective benefits enhancing long-term survival and attenuating the risk of BOS and CAV.
Assuntos
Bronquiolite Obliterante/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Transplante de Coração-Pulmão , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Doença da Artéria Coronariana/etiologia , Feminino , Transplante de Coração-Pulmão/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Síndrome , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Lung transplantation has become a standard of care for a select group of patients with advanced lung diseases. Lung transplantation has undergone rapid growth in the last few years in Saudi Arabia. OBJECTIVE: Describe five years of experience with lung transplantation. DESIGN: Retrospective, descriptive. SETTINGS: Major tertiary care hospital. PATIENTS: All patients who underwent lung transplant surgery between 2010 to 2015. MAIN OUTCOME MEASURES: Indications for lung transplant demographics, body mass index, blood group, type of transplant surgery, morbidity rate using the Clavien-Dindo classification, rate of early- and late-onset bronchiolitis obliterans syndrome (BOS), bronchiolitis obliterans-free survival, 30- and 90-day mortality rate, and survival (30 days, 90 days, 1-year, 3-years and 5-years) for lung transplant recipients. The duration of mechanical ventilation, colonization by bacteria and need for lung volume reduction surgery for lung donors. SAMPLE SIZE: 80, 45% women and 55% men. RESULTS: The most common indication for lung transplant in Saudi Arabia is pulmonary fibrosis (45%), followed by non-cystic fibrosis bronchiectasis (25%) and cystic fibrosis-related bronchiectasis (20%). Only 45% of our lung transplant recipients had a normal BMI (18-28 kg/m2). The most frequent blood group was A (40%), followed by blood group O (32.5%). Most (85%) lung transplants were bilateral while 15% were single lung transplants. Postoperative complications developed in 64 patients, 34 (42.5%) had minor grade 1 complications, while 13 (16.5%) had severe complications leading to death (grade V). Early onset BOS developed in 6 (7.5%) patients while 16 (20%) had late onset BOS. The BOS-free survival rate was 72.5%. The mean duration of mechanical ventilation in lung donors was 9 days and most were infected by bacteria. The majority of recipients required lung volume reduction. The 30-day mortality rate was 12.5% and the 90-day mortality rate was 17.5%. Survival rates at our center were 87.5% at 30 days, 82.5% at 90 days, 81.2% at 1 year, 67.9% at 2 years and 62.1% at 5 years. CONCLUSIONS: Lung transplantation has become an invaluable approach for the treatment of end-stage respiratory disease. Our 5-year experience has shown exciting promises for lung transplantation in Saudi Arabia. LIMITATIONS: Retrospective design, single center experience. CONFLICT OF INTEREST: None.
Assuntos
Bronquiolite Obliterante/epidemiologia , Pneumopatias/cirurgia , Transplante de Pulmão/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Arábia Saudita , Taxa de Sobrevida , Fatores de Tempo , Transplantados/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a major limitation in the long-term survival of lung transplant recipients (LTRs). However, the risk factors in the development of BOS remain undetermined. We conducted an international cohort study of LTRs to assess whether Aspergillus colonization with large or small conidia is a risk factor for the development of BOS. METHODS: Consecutive LTRs from January 2005 to December 2008 were evaluated. Rates of BOS and associated risk factors were recorded at 4 years. International Society of Heart and Lung Transplantation criteria were used to define fungal and other infections. A Cox proportional-hazards-model was constructed to assess the association between Aspergillus colonization and the development of BOS controlling for confounders. RESULTS: A total of 747 LTRs were included. The cumulative incidence of BOS at 4 years after transplant was 33% (250 of 747). Additionally, 22% of LTRs experienced Aspergillus colonization after transplantation. Aspergillus colonization with either large (hazard ratio [HR]â¯=â¯0.6, 95% confidence interval [CI]â¯=â¯0.3-1.2, pâ¯=â¯0.12) or small conidia (HRâ¯=â¯0.9, 95% CIâ¯=â¯0.6-1.4, pâ¯=â¯0.74) was not associated with the development of BOS. Factors associated with increased risk of development of BOS were the male gender (HRâ¯=â¯1.4, 95% CIâ¯=â¯1.1-1.8, pâ¯=â¯0.02) and episodes of acute rejection (1-2 episodes, HRâ¯=â¯1.5, 95% CIâ¯=â¯1.1-2.1, pâ¯=â¯0.014; 3-4 episodes, HRâ¯=â¯1.6, 95% CIâ¯=â¯1.0-2.6, pâ¯=â¯0.036; >4 episodes, HRâ¯=â¯2.2, 95% CIâ¯=â¯1.1-4.3, pâ¯=â¯0.02), whereas tacrolimus use was associated with reduced risk of BOS (HRâ¯=â¯0.6, 95% CIâ¯=â¯0.5-0.9, pâ¯=â¯0.007). CONCLUSIONS: We conclude from this large multicenter cohort of lung transplant patients, that Aspergillus colonization with large or small conidia did not show an association with the development of BOS.
Assuntos
Aspergillus/isolamento & purificação , Bronquiolite Obliterante/microbiologia , Transplante de Pulmão , Complicações Pós-Operatórias/microbiologia , Adolescente , Adulto , Bronquiolite Obliterante/epidemiologia , Estudos de Coortes , Feminino , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Bronchiectasis is a chronic pulmonary disease characterized by progressive and irreversible bronchial dilatation. The aim of the present study was to investigate the etiologies and clinical features of bronchiectasis in Korean children. METHODS: We performed a retrospective review of the medical records for children diagnosed with bronchiectasis between 2000 and 2017â¯at 28 secondary or tertiary hospitals in South Korea. RESULTS: A total of 387 cases were enrolled. The mean age at diagnosis was 9.2⯱â¯5.1 years and 53.5% of the patients were boys. The most common underlying cause of bronchiectasis was preexisting respiratory infection (55.3%), post-infectious bronchiolitis obliterans (14.3%), pulmonary tuberculosis (12.3%), and heart diseases (5.6%). Common initial presenting symptoms included chronic cough (68.0%), recurrent pneumonia (36.4%), fever (31.1%), and dyspnea (19.7%). The most predominantly involved lesions were left lower lobe (53.9%), right lower lobe (47.1%) and right middle lobe (40.2%). No significant difference was observed in the distribution of these involved lesions by etiology. The forced expiratory volume in 1â¯s (FEV1) levels were lowest in cases with interstitial lung disease-associated bronchiectasis, followed by those with recurrent aspiration and primary immunodeficiency. CONCLUSIONS: Bronchiectasis should be strongly considered in children with chronic cough and recurrent pneumonia. Long-term follow-up studies on pediatric bronchiectasis are needed to further clarify the prognosis and reduce the disease burden in these patients.