Surfactant dysfunction.

Mutations in genes encoding proteins needed for normal surfactant function and metabolism cause acute lung disease in newborns and chronic lung disease in older children and adults. While rare these disorders are associated with considerable pulmonary morbidity and mortality. The identification of genes responsible for surfactant dysfunction provides clues for candidate genes contributing to more common respiratory conditions, including neonatal respiratory distress syndrome and lung diseases associated with aging or environmental insults. While clinical, imaging and histopathology features of these disorders overlap, certain features are distinctive for surfactant dysfunction. Natural histories differ depending upon the genes involved and a specific diagnosis is important to provide accurate information concerning prognosis and mode of inheritance. Diagnosis of surfactant dysfunction can be made by biopsy, but identification of the specific gene involved requires molecular genetic testing, which is non-invasive. Currently there are no effective medical treatments for surfactant dysfunction. Development of therapies is a priority for research, which may benefit patients with other lung diseases.

Evaluation and management of pulmonary disease in ataxia-telangiectasia.

SUMMARY: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ATM gene, resulting in faulty repair of breakages in double-stranded DNA. The clinical phenotype is complex and is characterized by neurologic abnormalities, immunodeficiencies, susceptibility to malignancies, recurrent sinopulmonary infections, and cutaneous abnormalities. Lung disease is common in patients with A-T and often progresses with age and neurological decline. Diseases of the respiratory system cause significant morbidity and are a frequent cause of death in the A-T population. Lung disease in this population is thought to exhibit features of one or more of the following phenotypes: recurrent sinopulmonary infections with bronchiectasis, interstitial lung disease, and lung disease associated with neurological abnormalities. Here, we review available evidence and present expert opinion on the diagnosis, evaluation, and management of lung disease in A-T, as discussed in a recent multidisciplinary workshop. Although more data are emerging on this unique population, many recommendations are made based on similarities to other more well-studied diseases. Gaps in current knowledge and areas for future research in the field of pulmonary disease in A-T are also outlined.

Lung function and late pulmonary complications among survivors of hematopoietic stem cell transplantation during childhood.

Hematopoietic stem cell transplantation (HSCT) is used to treat an expanding array of malignant and non-malignant disorders. Pulmonary complications represent a significant source of morbidity and mortality in HSCT recipients. Young children, whose lungs are still developing and growing, may be especially susceptible to the insults of irradiation, drug toxicities, and recurrent infections associated with immunosuppression. Late pulmonary complications, those occurring more than three months after transplantation, are often noninfectious and present with nonspecific symptomatology. Pulmonary function testing (PFT) is a mainstay of monitoring pulmonary health in HSCT recipients. The pulmonologist should be familiar with common patterns seen on PFT in recipients of HSCT during childhood. In this review, we describe the findings in studies which have examined lung function over time in patients who underwent HSCT during childhood. We discuss patterns of PFT abnormalities, associated noninfectious syndromes and their clinical implications, as well as directions for future research.

Pulmonary dysfunction in pediatric hematopoietic stem cell transplant patients: non-infectious and long-term complications.

Pulmonary complications are among the most frequently encountered sequelae of pediatric hematopoietic stem cell transplantation (HSCT). Non-infectious complications are becoming increasingly more common in this unique population. This review addresses the diagnosis and management of non-infectious manifestations of lung disease in pediatric HSCT patients and briefly discusses the long-term pulmonary function of childhood HSCT survivors.

Pulmonary dysfunction in pediatric hematopoietic stem cell transplant patients: overview, diagnostic considerations, and infectious complications.

Pulmonary complications are among the most common and serious sequelae seen in hematopoietic stem cell transplantation (HSCT) recipients. This two-part review addresses the incidence and impact of pulmonary complications in pediatric HSCT patients. In this first part we review the available data for the use of diagnostic modalities in this population, including flexible bronchoscopy with bronchoalveolar lavage (BAL) and open lung biopsy (OLB). We also review the many infectious pulmonary complications that may occur in pediatric HSCT recipients, utilizing the traditional chronologic divisions of neutropenic phase (0-30 days following HSCT), early phase (30-100 days), and late phase (>100 days).