Role of CMV chemokine receptor M33 in airway graft rejection in a mouse transplant model.

BACKGROUND: Cytomegalovirus (CMV) infection is a risk factor for bronchiolitis obliterans (BO), one form of chronic lung allograft dysfunction (CLAD). The viral chemokine receptor M33 is essential for successful spread of murine CMV to host salivary glands. In the present study we investigated the impact of M33 on chronic airway rejection. METHODS: MHC I-mismatched tracheas of C·B10-H2b/LilMcdJ mice were transplanted into BALB/c (H2d) recipients and infected at different dates with wild type (WT) or M33-deleted (delM33) MCMV representing clinical settings of viral recipient (R)-donor (D)-serostatus: (D-/R+) or (D+/R-). Grafts were recovered for gene expression and histological / immunofluorescence analysis, respectively. RESULTS: Evaluations showed significantly increased signs of chronic rejection in WT-infected mice compared to uninfected allografts seen in lower epithelium/lamina propria-ratio (ELR) (ELR 0.46 ± 0.07 [WT post] vs. ELR 0.66 ± 0.10 [non-inf.]; p < 0.05). The rejection in delM33-infected groups was significantly reduced vs. WT-infected groups (0.67 ± 0.04 [delM33 post]; vs. WT post p < 0.05). Furthermore, decreased rejection was observed in WT pre-infected compared to post-infected groups (0.56 ± 0.08 [WT pre]; vs. WT post p < 0.05). CD8+ T cell infiltration was significantly higher in WT-post compared to the delM33 infected or non-infected allografts. CONCLUSIONS: These data support the role of the CMV in accelerating CLAD. The deletion of chemokine receptor M33 leads to attenuated rejection.

Severe adenovirus pneumonia with hemophagocytic syndrome and respiratory failure.

We report the case of an 18-month-old infant with severe serotype 3 adenovirus pneumonia, exceptionally associated with hemophagocytic syndrome. Treatment included cidofovir and mechanical ventilation for 13 days. The child developed chronic respiratory insufficiency due to bronchiectasis and bronchiolitis obliterans.

Infection with a respiratory virus before hematopoietic cell transplantation is associated with alloimmune-mediated lung syndromes.

BACKGROUND: Alloimmune-mediated lung syndromes (allo-LSs) are life-threatening complications after hematopoietic cell transplantation (HCT). Respiratory virus (RV) has been suggested to play a role in the pathogenesis. OBJECTIVE: We studied the relation between RV DNA/RNA detection in the upper/lower airways before HCT and the occurrence of allo-LSs. METHODS: We retrospectively analyzed all HCT recipients between 2004 and 2014, in whom real-time PCR for RV was performed in nasopharyngeal aspirates (NPAs) and bronchoalveolar lavage (BAL) fluid before HCT. The main outcome of interest was the presence of an allo-LS, which was defined as idiopathic pneumonia syndrome or bronchiolitis obliterans syndrome. Other outcomes were overall survival and treatment-related mortality. We used Cox proportional hazard models, logistic regression models, and Fine-Gray competing risk regression for analyses. RESULTS: One hundred seventy-nine children (median age, 6.8 years) were included. RVs were found in 61% (41% in BAL fluid/NPAs and 20% in NPAs only). Rhinovirus was the most frequently detected RV (42%). Allo-LSs occurred in 13%. RV positivity in BAL fluid was a predictor for allo-LSs (hazard ratio, 3.8; 95% CI, 1.4-10.7; P = .01), whereas RV positivity in NPAs only was not. No other predictors were found. Grade II to IV acute graft-versus-host disease related to steroid treatment shows a trend toward a protective effect (odds ratio, 0.16; 95% CI, 0.0-1.3; P = .08). Allo-LSs significantly increased treatment-related mortality (52% ± 10% in allo-LSs and 20% ± 4% in non-allo-LSs, P = .007). CONCLUSIONS: These results show that pre-HCT BAL fluid RV positivity was a predictor for allo-LSs. Screening for RVs before HCT might identify patients at risk for allo-LSs. This could have implications for prevention and treatment and might subsequently influence the outcomes of HCT.

Rehabilitación respiratoria en niños y adolescentes con bronquiolitis obliterante post infecciosa / Pulmonary rehabilitation in children and adolescents with post-infectious bronchiolitis obliterans

Post-infectious bronchiolitis obliterans (PIBO) is a lung disease characterized by chronic airflow limitation associated with small airway fibrosis and obliteration, caused by viral infection in the first years of life. According to the current clinical guidelines in our country, the bases of its treatment involve pharmacological and non-pharmacological strategies. Among non-pharmacological strategies, pulmonary rehabilitation (PR) is the standout, which consists of diagnostic and therapeutic management designed to evaluate and reverse function deterioration, and aimed at improving the quality of life and the prognosis of these patients.The objective of this review is to describe and discuss the components associated with pulmonary rehabilitation of PIBO patients, emphasizing the properties and attributes of the evaluation methods and the main treatment strategies that contribute to improving these patients' functionality

La bronquiolitis obliterante post infecciosa (BOPI) es una enfermedad pulmonar caracterizada por limitación crónica al flujo de aire asociado a fibrosis y obliteración de la vía aérea pequeña, que se produce como consecuencia de un cuadro infeccioso de origen viral durante los primeros años de vida. De acuerdo a la guía clínica vigente en nuestro país, las bases de su tratamiento se sustentan en estrategias farmacológicas y no farmacológicas. Entre las estrategias no farmacológicas destaca la rehabilitación respiratoria (RR), que se estructura a partir de la ejecución de protocolos de intervención con fines diagnósticos y terapéuticos, dirigidos a evaluar y revertir el deterioro funcional, teniendo como propósito central el mejorar la calidad de vida y el pronóstico de estos pacientes. El objetivo de la presente revisión es describir y discutir los componentes asociados a la rehabilitación pulmonar de los pacientes con BOPI, haciendo énfasis en las propiedades y atributos de los métodos de evaluación y en las principales estrategias de tratamiento que contribuyen a mejorar la funcionalidad de estos pacientes

Evaluating bronchodilator response in pediatric patients with post-infectious bronchiolitis obliterans: use of different criteria for identifying airway reversibility.

OBJECTIVE: Post-infectious bronchiolitis obliterans (PIBO) is a clinical entity that has been classified as constrictive, fixed obstruction of the lumen by fibrotic tissue. However, recent studies using impulse oscillometry have reported bronchodilator responses in PIBO patients. The objective of this study was to evaluate bronchodilator responses in pediatric PIBO patients, comparing different criteria to define the response. METHODS: We evaluated pediatric patients diagnosed with PIBO and treated at one of two pediatric pulmonology outpatient clinics in the city of Porto Alegre, Brazil. Spirometric parameters were measured in accordance with international recommendations. RESULTS: We included a total of 72 pediatric PIBO patients. The mean pre- and post-bronchodilator values were clearly lower than the reference values for all parameters, especially FEF25-75%. There were post-bronchodilator improvements. When measured as mean percent increases, FEV1 and FEF25-75%, improved by 11% and 20%, respectively. However, when the absolute values were calculated, the mean FEV1 and FEF25-75% both increased by only 0.1 L. We found that age at viral aggression, a family history of asthma, and allergy had no significant effects on bronchodilator responses. CONCLUSIONS: Pediatric patients with PIBO have peripheral airway obstruction that is responsive to treatment but is not completely reversible with a bronchodilator. The concept of PIBO as fixed, irreversible obstruction does not seem to apply to this population. Our data suggest that airway obstruction is variable in PIBO patients, a finding that could have major clinical implications. OBJETIVO: A bronquiolite obliterante pós-infecciosa (BOPI) é uma entidade clínica que tem sido classificada como obstrução fixa e constritiva do lúmen por tecido fibrótico. Entretanto, estudos recentes utilizando oscilometria de impulso relataram resposta ao broncodilatador em pacientes com BOPI. O objetivo deste estudo foi avaliar a resposta broncodilatadora em pacientes pediátricos com BOPI, comparando critérios diferentes para a definição da resposta. MÉTODOS: Foram avaliados pacientes pediátricos com diagnóstico de BOPI tratados em um de dois ambulatórios de pneumologia pediátrica na cidade de Porto Alegre (RS). Parâmetros espirométricos foram medidos de acordo com recomendações internacionais. RESULTADOS: Foram incluídos 72 pacientes pediátricos com BOPI no estudo. As médias dos valores pré- e pós-broncodilatador foram claramente inferiores aos valores de referência para todos os parâmetros, especialmente FEF25-75%. Houve uma melhora pós-broncodilatador. Quando medidos como aumentos percentuais médios, VEF1 e FEF25-75% melhoraram em 11% e 20%, respectivamente. Entretanto, quando os valores absolutos foram calculados, as médias de VEF1 e FEF25-75% aumentaram somente em 0,1 l. Verificamos que a idade da agressão viral, história familiar de asma e alergia não tiveram efeitos significativos na resposta ao broncodilatador. CONCLUSÕES: Pacientes pediátricos com BOPI têm uma obstrução das vias aéreas periféricas que responde ao tratamento, mas não uma reversão completa com o broncodilatador. O conceito de BOPI como obstrução fixa e irreversível parece não se aplicar a essa população. Nossos dados sugerem que a obstrução de vias aéreas em pacientes com BOPI é variável, e esse achado pode ter importantes implicações clínicas.

Evaluating bronchodilator response in pediatric patients with post-infectious bronchiolitis obliterans: use of different criteria for identifying airway reversibility / Avaliação da resposta ao broncodilatador em pacientes pediátricos com bronquiolite obliterante pós-infecciosa: uso de diferentes critérios de identificação de reversibilidade das vias aéreas

ABSTRACT Objective: Post-infectious bronchiolitis obliterans (PIBO) is a clinical entity that has been classified as constrictive, fixed obstruction of the lumen by fibrotic tissue. However, recent studies using impulse oscillometry have reported bronchodilator responses in PIBO patients. The objective of this study was to evaluate bronchodilator responses in pediatric PIBO patients, comparing different criteria to define the response. Methods: We evaluated pediatric patients diagnosed with PIBO and treated at one of two pediatric pulmonology outpatient clinics in the city of Porto Alegre, Brazil. Spirometric parameters were measured in accordance with international recommendations. Results: We included a total of 72 pediatric PIBO patients. The mean pre- and post-bronchodilator values were clearly lower than the reference values for all parameters, especially FEF25-75%. There were post-bronchodilator improvements. When measured as mean percent increases, FEV1 and FEF25-75%, improved by 11% and 20%, respectively. However, when the absolute values were calculated, the mean FEV1 and FEF25-75% both increased by only 0.1 L. We found that age at viral aggression, a family history of asthma, and allergy had no significant effects on bronchodilator responses. Conclusions: Pediatric patients with PIBO have peripheral airway obstruction that is responsive to treatment but is not completely reversible with a bronchodilator. The concept of PIBO as fixed, irreversible obstruction does not seem to apply to this population. Our data suggest that airway obstruction is variable in PIBO patients, a finding that could have major clinical implications.

RESUMO Objetivo: A bronquiolite obliterante pós-infecciosa (BOPI) é uma entidade clínica que tem sido classificada como obstrução fixa e constritiva do lúmen por tecido fibrótico. Entretanto, estudos recentes utilizando oscilometria de impulso relataram resposta ao broncodilatador em pacientes com BOPI. O objetivo deste estudo foi avaliar a resposta broncodilatadora em pacientes pediátricos com BOPI, comparando critérios diferentes para a definição da resposta. Métodos: Foram avaliados pacientes pediátricos com diagnóstico de BOPI tratados em um de dois ambulatórios de pneumologia pediátrica na cidade de Porto Alegre (RS). Parâmetros espirométricos foram medidos de acordo com recomendações internacionais. Resultados: Foram incluídos 72 pacientes pediátricos com BOPI no estudo. As médias dos valores pré- e pós-broncodilatador foram claramente inferiores aos valores de referência para todos os parâmetros, especialmente FEF25-75%. Houve uma melhora pós-broncodilatador. Quando medidos como aumentos percentuais médios, VEF1 e FEF25-75% melhoraram em 11% e 20%, respectivamente. Entretanto, quando os valores absolutos foram calculados, as médias de VEF1 e FEF25-75% aumentaram somente em 0,1 l. Verificamos que a idade da agressão viral, história familiar de asma e alergia não tiveram efeitos significativos na resposta ao broncodilatador. Conclusões: Pacientes pediátricos com BOPI têm uma obstrução das vias aéreas periféricas que responde ao tratamento, mas não uma reversão completa com o broncodilatador. O conceito de BOPI como obstrução fixa e irreversível parece não se aplicar a essa população. Nossos dados sugerem que a obstrução de vias aéreas em pacientes com BOPI é variável, e esse achado pode ter importantes implicações clínicas.

[A case of bronchiolitis obliterans secondary to human metapneumovirus bronchiolitis]. / Insan metapnömovirus bronsiyolitine ikincil gelisen bronsiyolitis obliterans olgusu.

Human metapneumovirus (hMPV), formerly classified in Paramyxoviridae family is now moved into Pneumoviridae, which was described as a novel family. It causes upper and lower respiratory tract infections (LRTIs) usually in children younger than five years old. The recent epidemiological studies indicated that hMPV is the second most frequently detected virus in LRTIs of young children, following the respiratory syncytial virus (RSV). Bronchiolitis obliterans (BO) is a chronic obstructive lung disease characterized by fibrosis of the distal respiratory airways. It is usually a result of an inflammatory process triggered by a LRTI related to adenovirus, RSV, Mycoplasma pneumoniae, measles virus, Legionella pneumophila, influenza virus or Bordetella pertussis as a causative agent. In this report, a case of hMPV bronchiolitis complicated with BO has been reported to point out the complications and severity of the clinical progress belongs to this virus. A three-month-old female patient has admitted to our pediatric intensive care unit with the diagnosis of acute bronchiolitis and respiratory failure. She was born at term, weighing 2950 gram and had been hospitalized in newborn intensive care unit for 11 days with the diagnosis of transient tachypnea of the newborn and neonatal sepsis. On auscultation, there were bilateral crepitant rales, wheezing and prolonged expirium. Her oxygen saturation was 97-98% while respiratory support was given with a non-rebreathing reservoir mask. Complete blood count, procalcitonin and C-reactive protein levels were in normal ranges. The chest radiography yielded right middle lobe atalectasia, left paracardiac infiltration and bilateral air trapping. A nasopharyngeal swab sample was analyzed by a commercial multiplex real-time reverse transcriptase-polymerase chain reaction (Thermo Fisher Scientific®, USA) developed for the detection of 15 respiratory viruses. Her sample yielded positive result for only hMPV. On the 4th day of hospitalization, the patient was intubated because of respiratory failure and carbon dioxide retention. She was extubated on the 19th day but could not tolerate. In the thorax computed tomography (CT), bilateral hyperinflation, patchy infiltration, mosaic perfusion and atelectasis especially bilateral posterior areas were detected. Bronchoscopy was normal except mild bronchomalacia in right middle lobe bronchus. The patient was diagnosed as BO secondary to hMPV bronchiolitis, according to the clinical, virological, bronchoscopic and thorax CT results. On the 76th day of admission, she was discharged with respiratory support with home ventilation via a tracheostomy cannula and medical treatments of oral metilprednisolone, nebulized salbutamol and budesonide. In conclusion, hMPV should not be undervalued especially in infants with severe LRTI that can be complicated with BO.

Severe acute measles pneumonitis: virus isolation in bronchoalveolar lavage fluid.

In the past few years, several endemic outbreaks of measles have been recognised, not only in children but also in adults, with severe and, occasionally, even fatal complications, possibly due to delayed diagnosis of the disease in adult medicine and decreasing vaccination rates. Furthermore, the treatment consists of supportive measures only. We present a case of severe measles pneumonitis in a 42-year-old man, a travel returnee, proven by direct virus isolation with PCR from bronchoalveolar lavage fluid. CT findings and pulmonary function testing revealed features of obstructive bronchiolitis; the patient was successfully treated with corticosteroids. He fully recovered, and lung function measurement returned to normal values. We conclude that acute measles can present as obstructive bronchiolitis and may be successfully treated with corticosteroids.

Pulmonary function of a paediatric cohort of patients with postinfectious bronchiolitis obliterans. A long term follow-up.

BACKGROUND: Postinfectious bronchiolitis obliterans (BO) is a chronic respiratory disease that usually follows a severe adenovirus infection. OBJECTIVE: To determine the evolution of pulmonary function and clinical outcome of children with postinfectious BO during childhood. METHODS: The study included patients diagnosed with postinfectious BO in whom at least two spirometries were performed within a minimum interval of 3 months. RESULTS: 46 met the inclusion criteria. The mean (±SD) follow-up period was 12.5 (±3.5) years. 197 spirometries and 41 plethysmographies were performed. Initial (9±3 years old) lung function was as follows (z score, mean±SD): forced vital capacity (FVC) -3.8±1; forced expiratory volume in 1 s (FEV1) -4.4±1; FEV1/FVC -2.2±1; forced expiratory flow (FEF)(25-75) -3.7±1; total lung capacity (TLC) 120±26%; residual volume (RV) 309±108%; and RV/TLC 55±13. During childhood, FVC and FEV1 increased by a mean of 11%/year (95% CI 9.3% to 12.6%; p<0.0001) and 9%/year (95% CI 7.7% to 10.2%; p<0.0001), and the FEV1/FVC ratio decreased by 1.9%/year (95% CI 1% to 2.8; p<0.001). The z score for FVC, FEV1 and FEV1/FVC decreased by 0.07 z score/year (95% CI 0.1 to 0.01; p<0.05), 0.09 z score/year (95% CI 0.1 to 0.05; p<0.01) and 0.04 z score/year (95% CI 0.09 to 0.001; p<0.02), respectively. During the follow-up period, 69% of patients required at least one hospital readmission and five required mechanical ventilation. Nine patients developed a thoracic deformity, and seven whose bronchiectasis did not respond to clinical treatment underwent a lobectomy. CONCLUSIONS: After a 12 year follow-up period, pulmonary function remained severely impaired, showing an obstructive pattern with air trapping that slowly improved during childhood. An unequal growth of lung parenchyma over the airways suggests dysinaptic growth. Patients required frequent readmission due to recurrent respiratory infections, and hypoxaemia improved slowly over time.

Bronchiolitis obliterans caused by CMV in a previously healthy Asian infant.

Cytomegalovirus (CMV) is currently the most common cause of congenital infection and the leading infectious cause of brain damage and hearing loss in children. Perinatal CMV infection rarely causes clinical manifestations in normal individuals and usually follows a benign course in immunocompetent infants. However, ~15-25% of infected preterm infants may develop pneumonia, hepatitis or sepsis-like illness, bradycardia, hepatosplenomegaly, distended bowel, anemia, or thrombocytopenia. Bronchiolitis obliterans (BO) is a rare, fibrosing form of chronic obstructive lung disease that follows severe insults to the lower respiratory tract and results in narrowing and/or complete obliteration of the small airways. In non-transplant children, the most common form of BO is a severe lower respiratory tract infection, especially of adenovirus. We experienced a case of a 37-day-old male who was diagnosed as BO on chest computed tomography (CT) after CMV pneumonia. To our best knowledge, this is the first case of BO caused by CMV pneumonia in a healthy infant.

Post-infectious bronchiolitis obliterans in children: a review of 42 cases.

BACKGROUND: This study aimed to describe the clinical characteristics, radiological features and outcomes of 42 children with post-infectious bronchiolitis obliterans (PIBO). METHODS: Forty-two children diagnosed with PIBO were prospectively studied at the First Hospital of Jilin University in northern China between January, 2008 and January, 2013. Their clinical characteristics, lung high resolution computed tomography (HRCT) findings and pulmonary function tests were reported. RESULTS: In children with PIBO, adenovirus was the most common etiologic agent (21/42), followed by Mycoplasma pneumoniae (M. pneumoniae). All of the patients presented with repeated wheezing and tachypnea. In addition, 22 patients required intensive management, while six patients required home oxygen therapy. HRCT findings were consistent with the PIBO diagnosis in all of the patients. Pulmonary function testing was useful in evaluating therapeutic responses. Systemic steroids combined with azithromycin were effective for PIBO treatment. CONCLUSIONS: Severe adenovirus bronchiolitis and M. pneumoniae infections have a higher risk of development for PIBO. HRCT and pulmonary function testing are useful in the diagnosis of PIBO. The degree of airway obstruction did not differ significantly between adenovirus and M. pneumoniae. A combination of steroids and azithromycin offers some benefit in treating these patients.

Lower incidence of CMV infection and acute rejections with valganciclovir prophylaxis in lung transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS). Finding a strategy to prevent CMV infection is an important issue. METHODS: We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed. RESULTS: For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival.For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%). CONCLUSIONS: A lower incidence of CMV infection/disease and acute rejections was observed with valganciclovir (3 months) when compared to oral ganciclovir (3 months). The long-term impact of CMV infection/disease was significant for BOS-free survival and survival.

The impact of viral respiratory tract infections on long-term morbidity and mortality following lung transplantation: a retrospective cohort study using a multiplex PCR panel.

BACKGROUND: The major factor affecting morbidity and mortality after lung transplantation (LTX) is bronchiolitis obliterans syndrome. Earlier studies have suggested a connection between the presence of viral agents and morbidity in this patient group, but data are somewhat conflicting. The objective of this study was to investigate the development of bronchiolitis obliterans syndrome and graft loss after LTX in relation to the presence of respiratory viruses during the first year after LTX. METHOD: The study is a retrospective cohort study of 39 LTX recipients 11Y13 years after surgery. Patients were operated between January 1, 1998 and December 31, 2000 at Sahlgrenska University Hospital. The presence of virus in bronchoalveolar lavage (BAL) fluids from patients during the first year after surgery was analyzed retrospectively using a multiplex polymerase chain reaction test capable of detecting 15 respiratory agents. The time to BOS or graft loss was analyzed in relation to the positive findings in BAL during the first year after LTX. RESULTS: Patients with one or more viruses detected in BAL during the first year after transplantation demonstrated a significantly faster development of BOS (P=0.005) compared with patients with no virus detected. No significant difference in graft survival was found. CONCLUSION: Our results suggest that the long-term prognosis after LTX may be negatively affected by viral respiratory tract infections during the first year after LTX.

Función pulmonar y calidad de vida en niños y adolescentes con bronquiolitis obliterante por adenovirus / Pulmonary function and quality of life in children and adolescents with bronchiolitis obliterans post-adenoviral infection

Introduction: Adenovirus infection is an important cause of pneumonia in Chilean children. Postinfectious Bronchiolitis Obliterans (PIBO) is the most important complication. There are few studies assessing pulmonary function and quality of life in PIBO patients. Objective: The aim of this study is to assess the pulmonary function and the quality of life of patients with PIBO and the correlation between both variables. Methods: 14 children with PIBO in follow up at the pediatric pulmonology outpatient clinic of a public children hospital were included in this study. Study period: April 2009 - April 2010. Pulmonary function was assessed in a medical visit by spirometry, flow/volume curve and intrathoracic gas volume measurement. The following indices were analyzed FVC, FEV1, FEV25-75, FEV1/FVC, RV, TLC, RV and RV/TLC. A survey of a self-administered Quality of Life (PedsQL, version 4.0, Spanish for Chile) was applied at the visit to investigate their global, physical and psychosocial quality of life. The Pearson linear correlation between quality of life and the pulmonary function test parameters was assessed, in the statistical analysis ap value < 0.05 was considered significant. Results: The mean age of our patients was 12.4 (range: 9-19 years-old). The functional alterations were characteristics of an obstructive respiratory disorder in 64.3 percent of the patients. Average pulmonary function test indices showed decreases in FEV1 (75 percent), FEV25-75 (48.8 percent), FEV1/FVC (67.6 percent) with normal value of FVC (93,7 percent) as well as pronounced increases in RV (333.5 percent), TLC (156 percent) and RV/TLC (51.8 percent). Mean change of FEV1 and FEV25-75post-bronchodilator was 11.3 percent and 26.4 percent respectively. Only 14.3 percent of our patients showed normal pulmonary function. The quality of life parameters were in average 58.2 percent of overall quality of life, 58.6 percent of physical quality of life and 57.9 percent of psychosocial ...

Introducción: La infección por adenovirus es una causa importante de neumonía en niños chilenos. La bronquiolitis obliterante (BOPI) es la complicación más importante. Existen pocos estudios donde evalúen la función pulmonar y la calidad de vida de los pacientes con BOPI. Objetivo: Evaluar la función pulmonar y la calidad de vida de los pacientes con BOPI y la correlación entre ambas variables. Métodos: Se incluyeron 14 niños con BOPI en el policlínico de la unidad de broncopulmonar de un hospital público de niños. Período de estudio: abril de 2009-abril de 2010. La función pulmonar se evaluó en una visita médica por espirometría, curva flujo / volumen y la determinación de volumen de gas intratorácico. Los índices analizados fueron los siguientes CVF, VEF1, FEV25-75, VEF1/CVF, VR,CPT, VR y VR / CPT. En la misma visita se realizó una encuesta auto-administrada de Calidad de Vida (PedsQL, versión 4.0, español de Chile) para investigar la calidad de vida global, física y psi-cosocial. Se aplicó la correlación lineal de Pearson entre calidad de vida y los parámetros de función pulmonar. Se consideró estadísticamente significativo unp <0,05. Resultados: La edad media de nuestros pacientes fue de 12,4 (rango: 9-19 años). La alteración funcional característica fue la obstructiva en el 64,3 por ciento de los pacientes. El promedio de los índices de pruebas de función pulmonar mostraron una disminución en VEF1 (75 por ciento), FEV25-75 (48,8 por ciento), VEF1/CVF (67,6 por ciento) con un valor normal de la CVF (93,7 por ciento), así como aumentos pronunciados en VR (333,5 por ciento), CPT (156 por ciento) y VR/CPT (51,8 por ciento). La media del cambio del VEF1 y FEV25-75post-broncodilatador fue 11,3 por ciento y 26,4 por ciento respectivamente. Sólo el 14,3 por ciento mostró una función pulmonar normal. Los parámetros de calidad de vida fueron en promedio 58,2 por ciento de calidad de vida general, 58,6 por ciento de calidad de vida física y el 57,9 por ciento...

Cytomegalovirus replication within the lung allograft is associated with bronchiolitis obliterans syndrome.

Early studies reported cytomegalovirus (CMV) pneumonitis as a risk factor for development of bronchiolitis obliterans syndrome (BOS) following lung transplantation. While improvements in antiviral prophylaxis have resulted in a decreased incidence of CMV pneumonitis, molecular diagnostic techniques allow diagnosis of subclinical CMV replication in the allograft. We hypothesized that this subclinical CMV replication was associated with development of BOS. We retrospectively evaluated 192 lung transplant recipients (LTR) from a single center between 2001 and 2009. Quantitative (PCR) analysis of CMV viral load and histological evidence of CMV pneumonitis and acute cellular rejection was determined on 1749 bronchoalveolar lavage (BAL) specimens and 1536 transbronchial biopsies. CMV was detected in the BAL of 41% of LTR and was significantly associated with the development of BOS (HR 1.8 [1.1-2.8], p = 0.02). This association persisted when CMV was considered more accurately as a time-dependent variable (HR 2.1 [1.3-3.3], p = 0.003) and after adjustment for significant covariates in a multivariate model. CMV replication in the lung allograft is common following lung transplantation and is associated with increased risk of BOS. As antiviral prophylaxis adequately suppresses CMV longer prophylactic strategies may improve long-term outcome in lung transplantation.

Respiratory viruses in lung transplant recipients: a critical review and pooled analysis of clinical studies.

Lung transplant recipients present an increased risk for severe complications associated with respiratory infections. We conducted a review of the literature examining the clinical relationship between viral respiratory infection and graft complications. Thirty-four studies describing the clinical impact of influenza, respiratory syncytial virus, parainfluenza, human metapneumovirus, rhinovirus, enterovirus, coronavirus, bocavirus or adenovirus were identified. The detection rate of respiratory viral infection ranged from 1.4% to 60%. Viruses were detected five times more frequently when respiratory symptoms were present [odds ratio (OR) = 4.97; 95% CI = 2.11-11.68]. Based on available observations, we could not observe an association between respiratory viral infection and acute rejection (OR = 1.35; 95% CI = 0.41-4.43). We found a pooled incidence of 18% (9/50) of bronchiolitis obliterans syndrome (BOS) in virus-positive cases compared to 11.6% (37/319) in virus-negative cases; however, limited number of BOS events did not allow to confirm the association. Our review confirms a causal relationship between respiratory viruses and respiratory symptoms, but cannot confirm a link between respiratory viruses and acute lung rejection. This is related in part to the heterogeneity and limitations of available studies. The link with BOS needs also to be reassessed in appropriate prospective studies.

Prolonged mechanical support in children with severe adenoviral infections: a case series and review of the literature.

Adenovirus infections occur primarily in infants and children less than 5 years of age, accounting for 2% to 5% of respiratory illnesses in the pediatric population and 4% to 10% of childhood pneumonias. Although the majority of children with adenovirus disease develop mild upper respiratory tract disease, more severe disease may occur with involvement of the lower respiratory tract characterized by pneumonitis and/or small airways disease. The authors present a case series of 3 high-risk children with severe lower respiratory tract adenoviral infections. These cases demonstrate the potential for the development of severe respiratory involvement from adenovirus in infants and children with comorbid conditions and illustrate that there may be a rapid progression of the disease as well as the need, in selected circumstances, for prolonged mechanical support. We review the role of adenovirus in lower respiratory tract infections in infants and children, its potential to result in life-threatening complications in pediatric patients with comorbid conditions, and the potential life-saving role of mechanical ventilation and extracorporeal life support (ECLS) in these children.