Late-Onset Noninfectious Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation: Single-Center Experience.

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.

Detection of Bronchiolitis Obliterans Syndrome after Pediatric Hematopoietic Stem Cell Transplantation: An Official American Thoracic Society Clinical Practice Guideline.

Background: Many children undergo allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignant and nonmalignant conditions. Unfortunately, pulmonary complications occur frequently post-HSCT, with bronchiolitis obliterans syndrome (BOS) being the most common noninfectious pulmonary complication. Current international guidelines contain conflicting recommendations regarding post-HSCT surveillance for BOS, and a recent NIH workshop highlighted the need for a standardized approach to post-HSCT monitoring. As such, this guideline provides an evidence-based approach to detection of post-HSCT BOS in children. Methods: A multinational, multidisciplinary panel of experts identified six questions regarding surveillance for, and evaluation of, post-HSCT BOS in children. A systematic review of the literature was undertaken to answer each question. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations addressing the role of screening pulmonary function testing and diagnostic tests in children with suspected post-HSCT BOS were made. Following a Delphi process, new diagnostic criteria for pediatric post-HSCT BOS were also proposed. Conclusions: This document provides an evidence-based approach to the detection of post-HSCT BOS in children while also highlighting considerations for the implementation of each recommendation. Further, the document describes important areas for future research.

Nuances in the interpretation and utility of donor-derived cell-free DNA in lung transplantation following allogeneic hematopoietic stem cell transplantation - Case report.

Respiratory complications following allogeneic HSCT can lead to severe morbidity and mortality. Lung transplantation (LT) is a potential treatment for select patients with late-onset non-infectious pulmonary complications post-HSCT. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive biomarker for monitoring the health of allografts following LT. However, its utility in a multi-genome setting of LT after HSCT has not yet been clinically validated. Here we describe a case of a 75-year-old, male patient who underwent single-lung transplantation for BOS related to chronic GVHD and presented with persistently elevated dd-cfDNA levels. In a surveillance biopsy, the patient was diagnosed with mild acute cellular rejection at three months. The patient's lung function remained stable, and the reported dd-cfDNA levels decreased after the rejection episode but remained elevated above levels that would be considered quiescent for LT alone. In this unique setting, as 3 different genomes contributed to the dd-cfDNA% reported value, valuable insight was obtained by performing further analysis to separate the specific SNPs to identify the contribution of recipient, lung-donor, and HSCT-donor cfDNA. This study highlights the potential utility of dd-cfDNA in the multi-genome setting of lung transplant post-HSCT, nuances that need to be considered while interpreting the results, and its value in monitoring lung rejection.

[Paraneoplastic pemphigus with underlying Castleman's disease in a 16-year-old girl]. / Morbus Castleman-assoziierter paraneoplastischer Pemphigus bei einer 16-jährigen Patientin.

Paraneoplastic pemphigus is a rare, life-threatening autoimmune disease that is clinically characterized by mostly extensive and refractory mucosal erosions and polymorphous skin lesions. We report here on a 16-year-old girl with isolated oral erosions, in whom mucosal pemphigoid was initially suspected and after treatment with prednisolone and dapsone marked improvement was achieved. However, a few months later the patient developed massive respiratory insufficiency as a result of bronchiolitis obliterans, so that a lung transplant was planned. As part of the preparatory diagnostic workup, unicentric, abdominally localized Castleman's disease was diagnosed, which ultimately led to the diagnosis of paraneoplastic pemphigus as evidenced by envoplakin autoantibodies. Tumor resection and subsequent lung transplantation achieved good results with sustained mucocutaneous remission.

A review of the therapeutic potential of the cysteinyl leukotriene antagonist Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic-stem cell transplantation and its possible mechanisms.

Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in these patients is the development of bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms have been recognized for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving the TH-1 and TH-2 cells, NF-kappa B, TGF-b, several cytokines and chemokines, and cysteinyl leukotrienes (CysLT). Montelukast is a highly selective CysLT receptor antagonist that has been demonstrated to exert anti-inflammatory and anti-fibrotic effects in abundant experiments. One area of interest for the use of montelukast is lung transplants or GVHD-associated BOS. Herein, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS, and finally, the possible relationship between CysLTs antagonism and BOS improvement will be discussed.

A review of the therapeutic potential and possible mechanism of Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic stem cell transplantationLung and bone marrow transplantation are therapeutic modalities in chronic diseases of the lungs and the blood, respectively. One of the complications in these patients is the development of Bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving many immune components have been recognized. Cysteinyl leukotrienes are products of plasma membrane phospholipids that increase smooth muscle contraction, microvascular permeability, and airway mucus secretion. Montelukast is a highly selective cysteinyl leukotriene receptor blocker demonstrated to exert anti-inflammatory and anti-fibrotic effects. One area of interest for the use of montelukast is in lung transplant- or GVHD-associated BOS. In this article, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS. Finally, the possible relationship between cysteinyl leukotriene inhibition and BOS improvement will be discussed.

IL-27 Levels in Bronchoalveolar Lavage Fluid in Children with Post-infectious Bronchiolitis Obliterans.

Background: Pulmonary neutrophils may play a crucial role in the development of bronchiolitis obliterans (BO) following measles virus infection. IL-27 could potentially have a negative regulatory effect on the release of reactive oxygen species and cytotoxic granules in neutrophils. Objective: To investigate the levels of IL-27 in the bronchoalveolar lavage fluid (BALF) of children with post-infectious bronchiolitis obliterans (PIBO) and analyze the relationship between IL-27 levels and neutrophil proportions. Methods: A total of 24 children with PIBO were recruited for the experimental group, while 23 children with bronchial foreign bodies were included in the control group. Bronchoscopic alveolar lavage was performed in both groups. The levels of IL-27 in BALF were measured using enzyme-linked immunosorbent assay (ELISA). The proportions of neutrophils in BALF were determined by smear staining. The relationship between the levels of IL-27 in BALF and the neutrophil proportions was analyzed by the Pearson test. Results: The levels of IL-27 in BALF were significantly lower in children with PIBO compared to children with bronchial foreign bodies (p<0.05). Additionally, the proportions of neutrophils in BALF were significantly higher in children with PIBO compared to children with bronchial foreign bodies (p<0.05). The levels of IL-27 were negatively correlated with the neutrophil proportions in BALF in children with PIBO (p<0.05), but not in children with bronchial foreign bodies (p>0.05). Conclusion: The present study suggests that a decrease in IL-27 may be associated with an increase in neutrophils in BALF and may contribute to the pathogenesis of PIBO.

Detection of Bronchiolitis Obliterans Syndrome Using Nitrogen Multiple Breath Washout in Children Posthemopoietic Stem Cell Transplant.

Bronchiolitis obliterans syndrome (BOS) is a severe complication following hemopoietic stem cell transplantation (HSCT) and is often undetected until there is significant deterioration in pulmonary function. Lung clearance index (LCI2.5) derived from the nitrogen multiple breath washout (N2MBW) test may be more feasible and sensitive than spirometry, which is currently used for surveillance and detection of BOS. We aimed to examine the feasibility of performing surveillance N2MBW in children post-HSCT, and in an exploratory analysis, determine if LCI2.5 led to earlier detection of BOS when compared to spirometric indices. Participants aged 5 to 17 years were recruited prior to receiving HSCT into a prospective, single-center, feasibility study at the Royal Children's Hospital, Melbourne. N2MBW and spirometry were performed within the month prior to transplant and repeated at 3, 6, 9, and 12 months post-transplant. Data were also collected on the presence of graft-versus-host (GVHD) disease in any organ, including the lungs. Twenty-one (12 male) children with a mean age of 13.4 (range 9.2 to 17.1) years at recruitment participated in this study. Prior to HSCT, all participants had normal LCI2.5, while 16 (76%) demonstrated normal forced expiratory volume in 1 second (FEV1). Ninety-nine percent of N2MBW tests were technically acceptable, compared with 66% of spirometry tests. Three participants developed BOS, while 2 participants died of other respiratory complications. At 6 and 12 months post-transplant, the BOS group had increases in LCI2.5 ranging from 3 to 5 units and mean reductions in FEV1 % predicted of 40% to 53% relative to pre HSCT values, respectively. In those who developed BOS, post-HSCT LCI2.5 values were significantly worse when compared with the no BOS group (P < .001). Relative changes in LCI2.5 and FEV1 were both predictive of BOS at 6 months post HSCT. This study demonstrates that N2MBW is a more feasible test compared with spirometry in children post HSCT. However, in an exploratory analysis, LCI2.5 did not lead to earlier detection of BOS, when compared to spirometry.

Risk factors and prediction models for bronchiolitis obliterans after severe adenoviral pneumonia.

Severe adenoviral pneumonia (SAP) can cause post-infectious bronchiolitis obliterans (PIBO) in children. We aimed to investigate the relevant risk factors for PIBO and develop a predictive nomogram for PIBO in children with SAP. This prospective study analysed the clinical data of hospitalised children with SAP and categorised them into the PIBO and non-PIBO groups. Least absolute shrinkage and selection operator (LASSO) regressions were applied to variables that exhibited significant intergroup differences. Logistic regression was adopted to analyse the risk factors for PIBO. Additionally, a nomogram was constructed, and its effectiveness was assessed using calibration curves, C-index, and decision curve analysis. A total of 148 hospitalised children with SAP were collected in this study. Among them, 112 achieved favourable recovery, whereas 36 developed PIBO. Multivariable regression after variable selection via LASSO revealed that aged < 1 year (OR, 2.38, 95% CI, 0.82-6.77), admission to PICU (OR, 24.40, 95% CI, 7.16-105.00), long duration of fever (OR, 1.16, 95% CI, 1.04-1.31), and bilateral lung infection (OR, 8.78, 95% CI, 1.32-195.00) were major risk factors for PIBO. The nomogram model included the four risk factors: The C-index of the model was 0.85 (95% CI, 0.71-0.99), and the area under the curve was 0.85 (95% CI, 0.78-0.92). The model showed good calibration with the Hosmer-Lemeshow test (χ2 = 8.52, P = 0.38) and was useful in clinical settings with decision curve analysis. CONCLUSION: Age < 1 year, PICU admission, long fever duration, and bilateral lung infection are independent risk factors for PIBO in children with SAP. The nomogram model may aid clinicians in the early diagnosis and intervention of PIBO. WHAT IS KNOWN: • Adenoviruses are the most common pathogens associated with PIBO. • Wheezing, tachypnoea, hypoxemia, and mechanical ventilation are the risk factors for PIBO. WHAT IS NEW: • Age < 1 year, admission to PICU, long duration of fever days, and bilateral lung infection are independent risk factors for PIBO in children with SAP. • A prediction model presented as a nomogram may help clinicians in the early diagnosis and intervention of PIBO.

Características y seguimiento de 38 casos de bronquiolitis obliterante post-infecciosa en Bogotá­Colombia / Characteristics and follow up of 38 Post-Infectious Bronchiolitis Obliterans cases in Bogota­Colombia

Post-infectious bronchiolitis obliterans (PIBO) is a chronic obstructive bronchial disease that develops after a viral respiratory infection, acquired before 2 years of age. In Bogotá, Colombia our group published in 2017 the description and follow-up of 21 cases of this pathology. The purpose of this publication is to describe the evolution of 38 children with PIBO living in Bogotá, Colombia at 2640 m above sea level, with an average of 6.5 years of follow-up. The estimated prevalence of PIBO in the population group in the group studied here was at least 1 case per 10,526 children under 15 years of age. The highest frequency of oxygen dependence and pulmonary hypertension are highlighted in this group of children living at high altitude…

La bronquiolitis obliterante post-infecciosa (BOPI) es una enfermedad bronquial obstructiva crónica, que se desarrolla luego de una infección respiratoria viral, adquirida antes de los 2 años de vida. En Bogotá, Colombia nuestro grupo hizo en al año 2017 la descripción y seguimiento de 21 casos de esta patología. La presente publicación tiene como objetivo describir la evolución de 38 niños con BOPI que viven en la ciudad de Bogotá a 2640 m sobre el nivel del mar, con un segumiento de 6.5 años en promedio. Se calcula que la prevalencia de la enfermedad en el grupo poblacional de donde se refieren estos casos, es de al menos 1 caso por 10.526 menores de 15 años. Se destacan la mayor frecuencia de oxigeno dependencia e hipertensión pulmonar en este grupo de niños que viven a gran altura.

Función pulmonar en bronquiolitis obliterante postinfecciosa / Pulmonary function in post-infectious bronchiolitis obliterans

Bronchiolitis obliterans is a rare and severe chronic lung disease resulting from a lower respiratory tract injury. It may occur after a bone marrow or lung transplantation, infectious diseases, or less frequently after inhaling toxic substances or connective tissue diseases. Pathogenesis and molecular biology, as well as the best treatment of bronchiolitis obliterans, remain the subject of ongoing research. This review discusses our current knowledge of lung function of post-infectious bronchiolitis obliterans.

La bronquiolitis obliterante es una enfermedad pulmonar crónica rara y grave que resulta de una lesión del tracto respiratorio inferior. Puede ocurrir después de un trasplante de médula ósea o pulmón, enfermedades infecciosas, o menos frecuentemente después de inhalar sustancias tóxicas o después de enfermedades del tejido conectivo. La patogénesis y la biología molecular, así como el mejor tratamiento de la bronquiolitis obliterante, siguen siendo objeto de investigación. Esta revisión analiza nuestro conocimiento actual sobre la función pulmonar de los pacientes con bronquiolitis obliterante secundaria a infecciones.

Bronquiolite obliterante: perfil clínico e radiológico de crianças acompanhadas em ambulatório de referência / Bronchiolitis obliterans: clinical and radiological profile of children followed-up in a reference outpatient clinic / Bronquiolitis obliterante: perfil clínico y radiológico de 35 niños acompañados en ambulatorio de referencia

OBJETIVO: Descrever as características clínico-radiológicas dos pacientes com bronquiolite obliterante. MÉTODOS: Estudo descritivo e retrospectivo. Foram coletados dados de pacientes diagnosticados com bronquiolite obliterante entre 2004 e 2008 no Ambulatório de Pneumologia Pediátrica do Hospital Infantil Albert Sabin, no Ceará. O diagnóstico foi baseado em critérios clínicos e tomográficos. Foram avaliados história prévia, quadro clínico por ocasião do diagnóstico, exames complementares e evolução. RESULTADOS: Foram identificados 35 pacientes com bronquiolite obliterante. Houve predominância do sexo masculino (3:1). A média de idade no início dos sintomas foi de 7,5 meses e, por ocasião do diagnóstico, 21,8 meses. Os achados clínicos mais frequentes foram estertores/sibilos, taquipneia, dispneia e deformidade torácica. A etiologia pós-infecciosa destacou-se como a principal causa de bronquiolite obliterante. As alterações encontradas com maior frequência à radiografia e à tomografia computadorizada de alta resolução de tórax foram espessamento peribrônquico e padrão de perfusão em mosaico, respectivamente. O tratamento instituído aos pacientes foi variável e individualizado. A maioria deles evoluiu com melhora clínica durante o seguimento, apesar da persistência da sintomatologia respiratória. CONCLUSÕES: A presente casuística de bronquiolite obliterante mostrou predominância de pacientes do sexo masculino e de etiologia pós-infecciosa, corroborando os dados da literatura. Os achados tomográficos mais encontrados foram semelhantes aos descritos em trabalhos anteriores (perfusão em mosaico, espessamento peribrônquico e bronquiectasias). Ainda faltam evidências acerca do tratamento para esta doença. O diagnóstico de bronquiolite obliterante foi tardio, necessitando da suspeição clínica por parte dos pediatras frente a lactentes chiadores graves e perenes.

OBJECTIVES: To describe the clinical and radiological characteristics of patients with bronchiolitis obliterans. METHODS: This is a retrospective and descriptive study. Data were collected from patients diagnosed with bronchiolitis obliterans between 2004 and 2008 in the Pediatric Pulmonology Clinic of Hospital Infantil Albert Sabin, in Ceará, Northeast Brazil. Such diagnosis was based on clinical and tomographic criteria. Previous history, clinical findings at the diagnosis, complementary exams, and follow-up data were evaluated. RESULTS: 35 children diagnosed with bronchiolitis obliterans were identified. There was a predominance of male patients (3:1). The mean age at the onset of symptoms was 7.5 months, and bronchiolitis obliterans was diagnosed at a mean age of 21.8 months. The most common clinical findings were crackles/wheezing, tachypnea, dyspnea, and chest deformity. Post-infectious etiology was the main cause of bronchiolitis obliterans. Predominant findings at chest X-ray and high resolution computed tomography were peri-bronchial thickening and mosaic pattern, respectively. The treatment was variable and individualized. The majority of patients improved during follow-up, despite the persistence of respiratory symptoms. CONCLUSIONS: In this study, the predominance of male patients and post-infectious etiology was noted, corroborating scientific literature. The most common tomographic findings were similar to those described in previous studies (mosaic pattern, peri-bronchial thickening, and bronchiectasis). Evidence about the treatment of this disease is still lacking. The diagnosis was delayed, which indicates that clinical suspicion of bronchiolitis obliterans is necessary in children with persistent and severe wheezing.

OBJETIVO: Describir las características clínico-radiológicas de los pacientes con bronquiolitis obliterante acompañados en el Ambulatorio de Pneumología Pediátrica del Hospital Infantil Albert Sabin en la provincia de Ceará (Brasil). MÉTODOS: Estudio descriptivo y retrospectivo. Se recogieron datos de pacientes diagnosticados con bronquiolitis obliterante entre 2004 y 2008. El diagnóstico se basó en criterios clínicos y tomográficos. Se evaluaron la historia previa, el cuadro clínico en el momento del diagnóstico, exámenes complementares y evolución. RESULTADOS: Se identificaron 35 pacientes diagnosticados con bronquiolitis obliterante. Hubo predominancia de los pacientes del sexo masculino (3:1). El promedio de edad en el inicio de los síntomas fue de 7,5 meses y, en el momento del diagnóstico, 21,8 meses. Los hallazgos clínicos más frecuentes fueron ruidos respiratorios/silbidos, taquipnea, disnea y deformidad torácica. La etiología post-infecciosa se destacó como la principal causa de bronquiolitis obliterante. Las alteraciones encontradas con más frecuencia a la radiografía y a la tomografía computadorizada de alta resolución del tórax fueron espesamiento peribrónquico y estándar de perfusión en mosaico, respectivamente. El tratamiento instituido a los pacientes fue variable e individualizado. La mayoría evolucionó con mejora clínica durante el seguimiento, a pesar de la persistencia de la sintomatología respiratoria en grados variables. CONCLUSIONES: La presente casuística de bronquiolitis obliterante mostró predominancia de pacientes del sexo masculino y de etiología post-infecciosa, corroborando los datos de la literatura. Los hallazgos tomográficos más encontrados fueron semejantes a los descriptos en trabajos anteriores (perfusión en mosaico, espesamiento brónquico y bronquiectasias). Todavía faltan evidencias sobre el tratamiento para esta enfermedad. El diagnóstico de bronquiolitis obliterante fue tardío, siendo necesaria la sospecha clínica por parte de los pediatras frente a lactantes silbadores graves y perennes.

Bronquiolite obliterante pós-infecciosa em crianças / Post-infectious bronchiolitis obliterans in children

OBJETIVOS: Revisar os trabalhos publicados sobre os principais aspectos da bronquiolite obliterante pós-infecciosa, relacionados com sua história, etiologia, epidemiologia, fatores de risco, patogenia, alterações histológicas, manifestações clínicas, exames complementares, critérios diagnósticos, diagnóstico diferencial, tratamento e prognóstico. FONTES DOS DADOS: Realizou-se uma revisão não sistemática nas bases de dados MEDLINE e LILACS, selecionando-se 66 referências mais relevantes. SÍNTESE DOS DADOS: Na bronquiolite obliterante pós-infecciosa ocorre lesão do epitélio respiratório, e a gravidade clínica está relacionada aos diferentes graus de lesão e ao processo inflamatório. O diagnóstico baseia-se no quadro clínico, na exclusão dos principais diagnósticos diferenciais e no auxílio dos exames complementares. A tomografia computadorizada de alta resolução, principalmente com imagens em inspiração e expiração, possibilta a avaliação das pequenas vias aéreas. As provas de função pulmonar caracterizam-se por padrão obstrutivo fixo com redução acentuada do FEF25-75 por cento. O tratamento não está bem estabelecido, e o uso de corticoides tem sido preconizado em forma de pulsoterapia ou por via inalatória em elevadas doses, no entanto, os dados da literatura a respeito de sua eficácia ainda são escassos. O prognóstico a longo prazo é variável, podendo haver melhora clínica ou evolução para insuficiência respiratória crônica e óbito. CONCLUSÃO: A bronquiolite obliterante pós-infecciosa é uma doença que cursa com elevada morbidade e deve ser abordada por equipe multidisciplinar com acompanhamento em longo prazo.

OBJECTIVES: To review publications about the main features of post-infectious bronchiolitis obliterans and its history, etiology, epidemiology, risk factors, pathogenesis, histological findings, clinical presentation, complementary tests, diagnostic criteria, differential diagnosis, treatment and prognosis. SOURCES: Non-systematic review of MEDLINE and LILACS databases and selection of 66 most relevant studies. SUMMARY OF THE FINDINGS: In the post-infectious bronchiolitis obliterans there is an insult to respiratory epithelial cells, and its clinical severity is associated with the degree of lesion and inflammation. Diagnosis is made according to clinical signs and symptoms, by exclusion of main differential diagnoses and with the aid of complementary tests. High resolution CT, particularly images obtained during inspiration and expiration, provide information for the evaluation of the small airways. Pulmonary function tests show fixed airway obstructions and marked decrease of FEF25-75 percent. Treatment has not been definitely established, and corticoids have been administered as pulse therapy or by inhalation of high doses of steroids. However, data about its efficacy are scarce in the literature. Long-term prognosis is variable, and there might be either clinical improvement or deterioration into respiratory insufficiency and death. CONCLUSION: Post-infectious bronchiolitis obliterans is a disease with a high morbidity rate; it should be treated by a multidisciplinary team, and patients should be followed up for a long period of time.

Diagnóstico e conduta na bronquiolite obliterante pós-infecciosa / Diagnosis and management of post-infectious bronchiolitis obliterans

A broquiolite obliterante pós-infecciosa é uma das doenças obstrutiva crônica das vias aéreas inferiores caracterizada pela persistência de obstrução crônica de pequenas vias aéreas após quadro infeccioso agudo. A suspeita do diagnóstico deve ser lembrada a partir da persistência de por mais de quatro semanas, de tosse, estertores, taquidispnéia, e sibilos após o quadro de infecção de vias aéreas inferiores, como a bronquiolite aguda, especialmente em lactentes. A doença segue um curso variável, mas apresenta, em geral, bom prognóstico, pois não se trará de uma doença progressiva. O tratamento inclui o uso de antibióticos, broncodilatadores e corticóides nas exacerbações, mas deve ser adequado de acordo com cada paciente, dependendo dos achados radiológicos e de função pulmonar.

Bronquiolite obliterante pós-infeccciosa: importância do diagnóstico precoce e da abordagem pediátrica / Post infectious bronchiolitis obliterans: importance of early diagnosis and pediatric management

A Bronquiolite obliterante pós-infecciosa (BOPI) é caracterizada por obstrução crônica do fluxo aéreo associada à lesão inflamatória das pequenas vias aéreas, que se manifesta clinicamente pela persistência de sintomas como taquipnéia, sibilância, tosse e hipoxemia por mais de 2 meses após um episodio de bronquiolite viral aguda (BVA) e/ou pneumonia viral. A BOPI não é tão rara, já que 10% dos lactentes podem ter BVA e1% deles podem evoluir para BOPI. Descrevemos o caso de um paciente com história típica, mas com diagnóstico tardio e elevada morbidade. Os resultados dos exames laboratoriais e de imagem são aqui apresentados. A evolução desse caso ratifica a importância de investigação apropriada da criança com doença obstrutiva crônica. Para se reduzir a potencial morbidade e melhorar a qualidade de vida dos pacientes com BOPI, são necessários a suspeita e o diagnóstico mais precoce por parte do pediatra e o acompanhamento multidisciplinar...

Post-infectious Bronquiolitis Obliterans (PIBO) is characterized by chronic airflowobstruction associate to inflammatory injury of small airways, clinically suspected by the persistence of symptoms such as tachypnea, wheezing, cough and hypoxaemia for morethan 2 months after an episode of acute viral bronquiolitis (AVB) and/or viral pneumonia.PIBO is not so rare, since 10% of infants may have AVB and 1% of them may developBOPI. We describe the case of a patient with a typical history of PIBO, but with delayed diagnosis and high morbidity. Results of the laboratorial exams and image are presented in this study. The evolution of this case emphasizes the importance of appropriate investigation of chronic obstructive illness in children. It is necessary to stimulate early suspicionand diagnosis by pediatricians and follow-up by a multidisciplinary team, in order to decrease potential morbidity and improve quality of life of these patients...

Bronquiolitis obliterante posinfecciosa / Postinfectious bronchiolitis obliterans

La bronquiolitis obliterante es una enfermedad pulmonar crónica infrecuente y grave producto de una lesión del tracto respiratorio inferior.Puede ocurrir luego de un trasplante de médula ósea o de pulmón, de enfermedades infecciosas o, menos frecuentemente, luego de inhalaciones tóxicas o enfermedades del tejido conectivo. La patología, patogenia y biología molecular, como así también el mejor tratamiento para la bronquiolitisobliterante son áreas aún en investigación. Esta revisión discute el estado actual del conocimiento en las diferentes áreas de la bronquiolitis obliterante secundaria a una lesión infecciosa.

Bronchiolitis obliterans is an uncommon and severe form of chronic obstructive lung disease that results from an insult tothe lower respiratory tract. The bronchiolitis obliterans was described as a complication of graft versus host disease in bone marrow or lung transplant recipients. Bronchiolitis obliterans is most commonly seen in children after severe viral lower respiratory tract infections. The understanding of pathology, pathogenesis and molecular pathology, as well as the best treatment in bronchiolitis obliterans remain the subject of ongoing investigations. This review discusses our current knowledge on the different areas of bronchiolitisobliterans associated to infectious disease.

Guía clínica para el diagnóstico y cuidado de niños/adolescentes con bronquiolitis obliterante post-infecciosa, 2009 / Clinical guide for diagnosis and care of children and adolescents with post-infectious bronchiolitis obliterans, 2009

Bronchiolitis obliterans in children is an infrequent clinical syndrome, characterized by chronic airflow obstruction associated to inflammatory changes and different degrees of fibrosis in the small airways. Etiologies are varied but the most frequent one is the association with viral infections, mainly adenovirus. There is no consensus regarding diagnostic criteria, but a spectrum of persistent symptoms together with a mosaic pattern, bronchiectasis and persistent atelectasis is considered useful. Pulmonary biopsy has been questioned because of its low yield, invasiveness and complications. No specific treatment is available, therefore its treatment is supportive. Probably the best strategy is the aggressive use of antibiotics, constant kinesic and nutritional support and early pulmonary rehabilitation. This clinical guide represents a multidisciplinary effort, based on current evidence, to provide practical tools for the diagnosis and care of children and adolescents affected by post-infectious bronchiolitis obliterans.

La bronquiolitis obliterante (BO) es un síndrome clínico poco frecuente en niños, caracterizado por la obstrucción crónica al flujo de aire asociado a cambios inflamatorios y distintos grados de fibrosis en la vía aérea pequeña. Si bien existen muchas etiologías, la causa más frecuente se asocia a infecciones respiratorias virales, principalmente adenovirus. No existe un consenso para establecer su diagnóstico; sin embargo, se considera un espectro de síntomas persistentes asociados a un patrón en mosaico, bronquiectasias y atelectasias persistentes. El papel de la biopsia pulmonar ha sido cuestionado por su bajo rendimiento, invasividad y complicaciones. No existe un tratamiento específico por lo que el manejo es soporte. Probablemente la mejor estrategia constituya el empleo de antibióticos en forma agresiva, soporte kinésico y nutricional constante y una precoz rehabilitación pulmonar. Estas guías clínicas representan un esfuerzo multidisciplinario, basado en evidencias actuales para brindar herramientas prácticas para el diagnóstico y cuidado de niños y adolescentes con BO post infecciosa.