Trasplante pulmonar en niños. Aspectos específicos

Lung transplantation has become in recent years a therapeutic option for infantswith terminal lung disease with similar results to transplantation in adults.In Spain, since 1996 114 children lung transplants have been performed; this corresponds to3.9% of the total transplant number.The most common indication in children is cystic fibrosis, which represents between 70-80% of the transplants performed in adolescents. In infants common indications areinterstitial lung disease and pulmonary hypertension.In most children a sequential double lung transplant is performed, generally with the help ofextracorporeal circulation. Lung transplantation in children presents special challenges in monitoring and follow-up, especially in infants, given the difficulty in assessing lung function and performing transbronchial biopsies.There are some more specific complications in children like postransplant lymphoproliferative syndrome or a greater severity of respiratory virus infections .After lung transplantation children usually experiment a very important improvement in their quality of life. Eighty eight per cent of children have no limitations in their activity after 3 years of transplantation.According to the registry of the International Society for Heart & Lung Transplantation (ISHLT) survival at 5 years of transplantation is 54% and at 10 years is around 35%.     

Special considerations in pediatric lung transplantation

More than 1300 lung or heart-lung transplants have been performed in children to date, resulting in many years of improved quality of life. Increasing experience has demonstrated that this therapy is unique and differs from adult lung transplantation in terms of indications, complications, pharmacokinetics, and monitoring. Unlike adult lung transplant recipients, cystic fibrosis and pulmonary vascular disease are very common indications. Complications such as graft dysfunction and bronchiolitis obliterans occur similarly in children as in adults, but others such as posttransplant lymphoproliferative disorders, growth retardation, respiratory tract infections, and medical nonadherence appear to be more common in pediatric lung transplant recipients. In addition, infants and adolescents are two very distinct populations that require special attention. Although the new lung allocation system grants some preference to children, donor shortage remains a limiting factor. Living donor lobar transplantation is an alternative for select candidates. Survival rates are similar between adult and pediatric transplant recipients. Support for collaborative studies is critical if we are to improve long-term outcomes for our young patients.     

α1-Antitrypsinmangel aus pädiatrischer Sicht

α₁-Antitrypsin (AAT) deficiency is one of the most frequent inherited diseases. The development of clinical symptoms of liver and lung disease in individuals with severe AAT deficiency is highly variable. Gene/environmental interactions, environmental influences, and polymorphisms of modifier genes may be of importance from fetal life onwards. Clinically overt liver disease affects mainly but not exclusively young children and is rather rare. Pulmonary symptoms affect adults and are more frequent. Existing data do not support the assumption that AAT deficiency is associated with a higher asthma prevalence in children and adolescents. However, schoolchildren with low levels of AAT are at risk of developing pronounced decrements in pulmonary function, particularly if they are exposed to environmental tobacco smoke. Early diagnosis of lung involvement would be helpful to prevent further damage and potentially improve long-term outcome.     

The pulmonary manifestations of childhood onset systemic lupus erythematosus

Pleuropulmonary disease in childhood onset SLE is common. It may be insidious or present as a life threatening event. North American Indian children in our population appear to be at high risk for severe lung disease. Pulmonary symptoms are present in the majority of children at some time during their disease course and pulmonary function studies are abnormal in the majority of patients. The pulmonary manifestations and frequency of occurrence in childhood appear to be similar to that described in adult onset SLE. Although pulmonary function studies do not correlate well with pulmonary symptoms, these studies provide objective quantification of the type and severity of the functional lesion. Serial tests may be helpful in monitoring disease activity in childhood SLE.     

Comparison of primary plexogenic arteriopathy in adults and children. A morphometric study in 40 patients.

Pulmonary vascular changes were studied in histological sections from 15 children and 25 adults with primary plexogenic arteriopathy. The severity of medial hypertrophy and degree of vasoconstriction were measured in histological sections and there was a close correlation between these two variables in both children and adults. More advanced arterial changes, expressed as an index of pulmonary vascular disease, were more common in adults, and their severity correlated positively with the degree of medial hypertrophy. No such correlation was found in children. There were similar numbers of plexiform lesions per square centimetre in children and adults, so that the differences in the indices of pulmonary vascular disease were mainly due to the intimal changes. Concentric laminar intimal fibrosis was more severe in adults. It is suggested that intensive spastic vasoconstriction results in the development of fibrinoid necrosis and subsequently of plexiform lesions and that this may happen irrespective of the presence of severe intimal fibrosis. This suggests that children with primary plexogenic arteriopathy in whom plexiform lesions have not yet developed are more likely to respond to vasodilator treatment than are adults in whom irreversible changes associated with intimal fibrosis have developed.     

Comparison of primary plexogenic arteriopathy in adults and children. A morphometric study in 40 patients

Pulmonary vascular changes were studied in histological sections from 15 children and 25 adults with primary plexogenic arteriopathy. The severity of medial hypertrophy and degree of vasoconstriction were measured in histological sections and there was a close correlation between these two variables in both children and adults. More advanced arterial changes, expressed as an index of pulmonary vascular disease, were more common in adults, and their severity correlated positively with the degree of medial hypertrophy. No such correlation was found in children. There were similar numbers of plexiform lesions per square centimetre in children and adults, so that the differences in the indices of pulmonary vascular disease were mainly due to the intimal changes. Concentric laminar intimal fibrosis was more severe in adults. It is suggested that intensive spastic vasoconstriction results in the development of fibrinoid necrosis and subsequently of plexiform lesions and that this may happen irrespective of the presence of severe intimal fibrosis. This suggests that children with primary plexogenic arteriopathy in whom plexiform lesions have not yet developed are more likely to respond to vasodilator treatment than are adults in whom irreversible changes associated with intimal fibrosis have developed.     

Indications and outcomes in adult lung transplantation

Lung transplantation (LTx) is a treatment option for end-stage lung disease that would be otherwise fatal for specific patient populations. The most common indications for LTx in adults remain to be chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, alpha-1 antitrypsin deficiency, and idiopathic pulmonary arterial hypertension. Recent trends include performing re-transplantation while more patients over the age of 65 years are undergoing LTx. Even with these tendencies, slight improvements in survival have occurred. This article briefly reviews recent developments in adults undergoing LTx.     

A comparison of the clinical characteristics of children and adults with severe asthma

OBJECTIVES: This study sought to better define the clinical characteristics of severe asthma in both children and adults, and to evaluate the effect of asthma duration on multiple parameters of disease severity. DESIGN: Retrospective analysis of prospectively collected data on 275 patients (125 children) with severe asthma who were admitted to a tertiary asthma referral center. METHODS: Demographics, lung function (ie, spirometry and body box plethysmography), glucocorticoid (GC) pharmacokinetic studies, and lymphocyte stimulation assays were performed on all patients. RESULTS:Children were as likely to require therapy with high-dose inhaled GCs and long-term therapy with oral GCs, and to have had a prior intubation, yet they had significantly less airflow limitation (mean [+/- SEM] FEV(1), 74.0 +/- 2.1% predicted vs 57.1 +/- 1.8% predicted, respectively; p < 0.0001), less resistance to airflow (mean airway resistance, 140.3 +/- 8.5% predicted vs 311 +/- 18% predicted, respectively; p < 0.0001), and larger lung volumes (mean total lung capacity, 116.4 +/- 1.6% predicted vs 105.3 +/- 1.8% predicted, respectively; p < 0.0001) compared to adults. Children were more likely to be male and to display greater responsiveness to GCs in vitro. Lung function impairment was associated with asthma duration in children and in adults with onset of asthma in childhood, while there was no relationship between disease severity and asthma duration among those with adult-onset asthma. Despite significant differences in disease duration, patients with adult-onset asthma had equally compromised lung function compared to adults with long-standing asthma. CONCLUSIONS: Children with severe asthma tended to be male, to have less severe airflow obstruction, and to display greater responsiveness to GCs in vitro compared to adults. Symptoms and episodic acute declines in lung function may precede chronic airflow limitation in this group of children. As such, it may be more relevant to follow the deterioration in lung function over time in children. Finally, disease severity in children and adults whose onset of asthma occurred in childhood was related to disease duration, but not in patients with onset of asthma in adulthood.     

Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin.

Our ultimate goal in treating patients is to improve their quality of life and to increase survival. The optimal treatment for primary pulmonary hypertension will continue to change as our understanding of its causes improves and as progress is made in lung transplantation. There is no one best treatment for all patients. Optimal medical and surgical treatment must be tailored to the individual with changes in therapeutic regimens based on serial evaluations. Quality of life and survival have improved with current treatments and the future should offer additional therapies-inhaled nitric oxide, endothelin receptor blockers, and other modulators of the pulmonary vascular bed-to improve further the treatment of this disease. In conclusion, although primary pulmonary hypertension, if untreated, is most often a rapidly progressive and fatal disease, recent advances in the treatment have significantly improved the outcome for patients. Although transplantation is often considered the only definitive treatment for patients with primary pulmonary hypertension, medical treatment seems to be an effective long term palliation to successful transplantation as well as a possible alternative treatment to transplantation in selected children and adults. Quality of life and cost analyses, as well as longer follow up studies are needed to determine the best treatment for patients with primary pulmonary hypertension.     

Chronic viral hepatitis in childhood

In endemic areas infection with hepatitis B virus is a common cause of chronic liver disease in childhood. High levels of viral replication and mild ALT abnormalities are the rule in children infected perinatally and many of them are likely to maintain viral replication through their youth. Conversely about 90% of children infected later in life clear HBeAg and achieve sustained remission of liver disease before reaching adulthood. The eventual outcome of infection and disease in these patients remains unpredictable as reactivation of liver damage and viral replication may occur after several years of sustained remission. Cirrhosis is a rare and early complication of chronic HBV infection in children, and a risk factor for hepatocellular carcinoma. IFN therapy can accelerate HBV DNA clearance, improving the spontaneous anti-HBe seroconversion rate in Caucasian children by two to three times.Hepatitis delta is the most severe form of chronic viral hepatitis in childhood. Cirrhosis can be diagnosed in up to 26% of patients at presentation, and few cases respond to IFN therapy.Hepatitis C is relatively rare in children. Before the discovery of HCV blood transfusions were the most common source of infection. Hepatitis C is usually a mild, asymptomatic disease in otherwise healthy children, but has a poor propensity to spontaneous remission over the years. For this reason, and based on the experience in adults, IFN treatment is now being evaluated.     

Rational approach to the treatment for heterozygous familial hypercholesterolemia in childhood and adolescence: a review

Atherosclerosis represents a disease that begins in childhood and in which LDL cholesterol plays a pivotal role for the development of the pathology. Children and adolescents with high cholesterol levels are more likely than their peers to present cholesterol elevation as adults. The identification of genetic dyslipidemias associated with premature cardiovascular disease is crucial during childhood to delay or prevent the atherosclerotic process. Guidelines for the diagnosis and treatment of hypercholesterolemia during pediatric age are available from the National Cholesterol Education Program. A heart-healthy diet should begin at the age of 2 yr and a large number of studies have demonstrated no adverse effects on nutritional status, growth, pubertal development, and psychological aspects in children and adolescents limiting total and saturated fat intake. Pharmacotherapy should be considered in children over 10 yr of age when LDL cholesterol concentrations remain very high despite severe dietary therapy, especially when multiple risk factors are present. The only lipid-lowering drugs recommended up to now for childhood and adolescence are resins reported to be effective and well tolerated, although compliance is very poor because of unpalatability. The use of statins is increasing and seems to be effective and safe in children, even if studies enrolled a small number of patients and evaluated efficacy and safety for short-term periods. Recently, an interesting drug represented by ezetimibe has been found that may provide cholesterol-lowering additive to that reached with statin treatment. This review provides an update on recent advances in the diagnosis, therapy, and follow-up of familial hypercholesterolemia during pediatric age and adolescence.     

儿童青少年代谢综合征诊治进展

代谢综合征(MS),包括胰岛素抵抗、肥胖、高血压、高脂血症等,是成人动脉粥样硬化性心脏病及2型糖尿病的一系列潜在危险因素。新近研究发现儿童及青少年时期已出现一系列MS的表现,且相关危险因素的存在与其成年后MS的发生密切相关,在儿童及青少年期即开始重视防治MS是控制MS及相关心血管并发症的重要手段,必须引起高度重视。     

Dyslipoproteinemia and premature atherosclerosis in pediatric systemic lupus erythematosus

While modern treatments for systemic lupus erythematosus (SLE) have resulted in greatly improved long term outcome in children and adults, complications of atherosclerosis have become a major cause of morbidity and mortality. Although children and adolescents with SLE rarely experience adverse cardiovascular events before adulthood, dyslipoproteinemia and early evidence of premature atherosclerosis is present much earlier. Accelerated atherogenesis in SLE is multifactorial, most likely reflecting vascular, immune, and inflammatory changes along with medication effects. The long term complications of cardiovascular disease in childhood lupus present a particularly important target for intervention because of the potential return on investment by significantly lengthening life and improving quality of life over many decades. An ongoing multi-center, randomized, controlled trial, Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE), testing the efficacy of statins in preventing premature atherosclerosis in children and adolescents with SLE will guide future therapeutic intervention.     

Pulmonary Langerhans' cell histiocytosis

Pulmonary Langerhans' cell histiocytosis (PLCH) is an uncommon but important cause of interstitial lung disease, and it occurs predominantly in adult cigarette smokers. PLCH belongs to the spectrum of Langerhans' cell histiocytosis (LCH), diseases characterized by uncontrolled proliferation and infiltration of various organs by Langerhans' cells. Other clinical entities within this spectrum of LCH are seen in adults and children and vary in severity from mild disease that requires no therapy to severe disseminated forms with extensive organ involvement and high mortality. Organ systems involved by LCH may include skin, bone, pituitary gland, lymph nodes, and lungs. Although LCH is approximately three times more common in children than adults, pulmonary involvement is much more common in adults with LCH, in whom it frequently occurs as the sole organ involved with disease. This article summarizes recent advances and current understanding of PLCH.     

Outcomes of adults with cystic fibrosis infected with antibiotic-resistant Pseudomonas aeruginosa

BACKGROUND: Although Pseudomonas aeruginosa is the most common bacterial infection in adults with cystic fibrosis and frequently develops resistance to multiple classes of antibiotics, it has not been determined whether patients with multiple antibiotic-resistant Pseudomonas aeruginosa have worse clinical outcomes than patients with more susceptible strains. OBJECTIVES: This study assessed the impact of multiply-resistant P. aeruginosa on lung function, hospitalizations, antibiotic use, lung transplantation and survival in adults with cystic fibrosis. METHODS: In a cohort study at a university-based adult cystic fibrosis program, 75 consecutive adult cystic fibrosis patients who had P. aeruginosa isolated from sputum cultures were studied over a 4-year period. Outcomes included decline in FEV1, clinic visits, hospitalizations, courses and days of intravenous antibiotics, and lung transplantation. Multiple linear and Poisson regression for repeated measures were used to assess the outcomes. RESULTS: In comparison to patients with susceptible strains, patients with resistant P. aeruginosa had more severe baseline lung disease, more rapid decline in FEV1 (160 ml/year, p = 0.003) and were significantly more likely to undergo lung transplantation (17.6 vs. 0%, p = 0.005). CONCLUSIONS: Infection with multiple-antibiotic-resistant P. aeruginosa is associated with accelerated progression of cystic fibrosis, and has important implications for infection control strategies, antibiotic use and lung transplantation.     

Pediatric lung transplantation: indications and outcomes

Lung transplantation (LTx) is a treatment option for infants and children with untreatable and otherwise fatal pulmonary diseases. To date, over 1,800 lung transplants have been performed, most frequently in children over the age of five years. The most common indications for transplantation in children overall are cystic fibrosis (CF) and idiopathic pulmonary hypertension (PH). The surfactant protein deficiencies, other interstitial lung diseases (ILDs), and congenital heart disease are important indications among young children and infants. Re-transplantation is an option for selected recipients with chronic allograft rejection. Overall survival following pediatric LTx is similar to that encountered in adult patients, with recent registry data indicating a median survival of 4.9 years. Other outcomes such as the incidence of bronchiolitis obliterans (BO) and the presence of key post-transplant co-morbid conditions are also similar to the experience in adult lung transplant recipients.     

Severe pulmonary disease in association with Crohn's disease in a 13-year-old girl

Pulmonary manifestations of Crohn's disease are infrequent in adults and even less common in children. Our literature search found only a few cases of Crohn's disease causing pulmonary manifestations in children. We report on the case of a 13-year-old girl in whom severe pulmonary disease was found four years after the onset of Crohn's disease. Open lung biopsy uncovered bronchiolitis obliterans and granulomatous lung disease. Aggressive treatment has yielded gradual improvement. This case emphasizes the importance of recognizing the association, the differential diagnosis, and treatment implications.     

Respiratory syncytial virus infections in pediatric liver transplant recipients.

Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in infants and young children. The charts of 17 children found to have RSV among 493 children who underwent liver transplantation between February 1985 and February 1991 were reviewed. The median age at diagnosis was 20 months. Median time of diagnosis was 24 days after transplantation. Thirteen patients developed nosocomial infections while convalescing from their transplant. Common symptoms included tachypnea, cough, fever, and congestion. Acute radiographic changes were seen in 12 patients. Two deaths were associated with progressive pulmonary disease and occurred in children with infection early in the postoperative period who were intubated before the onset of symptoms. RSV in children after liver transplantation has a clinical spectrum similar to that in normal children. Early onset of infection (less than 20 days) after transplantation and preexisting lung disease may predict more severe disease.     

Childhood antecedents of adult respiratory disease

Abstract This review examines the relations between early childhood lower respiratory symptoms and adult respiratory disease. The problems associated with investigating potential associations between respiratory disease in children and adults are discussed. Some studies have limitations because they are retrospective and early childhood respiratory symptoms have not been accurately diagnosed. Therefore, in this review, particular attention is paid to longitudinal studies (some from birth) that have used strict diagnostic criteria for respiratory episodes. These studies provide unique insights into the risk factors for the development of childhood respiratory problems and for persistence of symptoms into adulthood. Although cross-sectional studies have indicated that early childhood respiratory disease is more frequent in adults with respiratory disease, evidence from longitudinal studies suggests that respiratory symptoms such as wheezing, are transient in the majority of infants and result from developmentally small airways. These longitudinal investigations have also indicated that persistence of symptoms into later childhood is associated with atopy. The important role of cigarette-smoke exposure as a risk factor for abnormal pulmonary development, persistence of respiratory disease and reduction in lung function is discussed. The discovery of genetic markers associated with respiratory syndromes such as asthma, should facilitate studies that investigate the childhood antecedents of adult respiratory disease. Future longitudinal studies using genetic markers, will allow relations between specific genotypes and phenotypic outcomes to be examined.