Leland L. Fan

Treatment of Pulmonary Hemangiomatosis with Recombinant Interferon Alfa-2a

A subsea pipeline hub is connected to the hub of an adjacent spool piece connected to an in-place manifold of a subsea structure used in the production of oil and/or gas. The pipeline hub is positioned relative to the opposing spool hub and a remotely operated pipeline connecting tool is lowered from the waters surface to the subsea structure using guidelines and structural guidance for alignment of the pipeline hub with the spool piece hub. The spool piece hub is then drawn to the pipeline hub and the hubs are clamped together by operation of the connecting tool. The seal in the connection can be tested by means of the connecting tool. The spool piece may be retrieved and replaced by the connecting tool if maintenance is needed. Connecting tool operations are powered by hydraulic fluid and controlled from the surface. The pipeline hub may be lowered vertically and pivoted into its position adjacent the spool piece or may be pulled into that position.

Clinical, radiological and pathological features of ABCA3 mutations in children

Background: Mutations in the ABCA3 gene can result in fatal surfactant deficiency in term newborn infants and chronic interstitial lung disease in older children. Previous studies on ABCA3 mutations have focused primarily on the genetic abnormalities and reported limited clinical information about the resultant disease. A study was undertaken to analyse systematically the clinical presentation, pulmonary function, diagnostic imaging, pathological features and outcomes of children with ABCA3 mutations. Methods: The records of nine children with ABCA3 mutations evaluated at Texas Children’s Hospital between 1992 and 2005 were reviewed and their current clinical status updated. Previous diagnostic imaging studies and lung biopsy specimens were re-examined. The results of DNA analyses were confirmed. Results: Age at symptom onset ranged from birth to 4 years. Cough, crackles, failure to thrive and clubbing were frequent findings. Mean lung function was low but tended to remain static. CT scans commonly revealed ground-glass opacification, septal thickening, parenchymal cysts and pectus excavatum. Histopathological patterns included pulmonary alveolar proteinosis, desquamative interstitial pneumonitis and non-specific interstitial pneumonitis, and varied with age. Dense abnormalities of lamellar bodies, characteristic of ABCA3 mutations, were seen by electron microscopy in all adequate specimens. Outcomes varied with the age at which the severity of lung disease warranted open lung biopsy, and some patients have had prolonged survival without lung transplantation. Conclusions: The presentation and course of interstitial lung disease due to ABCA3 mutations are variable, and open lung biopsy and genetic testing are warranted early in the evaluation of children with a consistent clinical picture.

Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRα gene in the X chromosome pseudoautosomal region 1

Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. The importance of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of PAP has been confirmed in humans and mice, wherein GM-CSF signaling is required for pulmonary alveolar macrophage catabolism of surfactant. PAP is caused by disruption of GM-CSF signaling in these cells, and is usually caused by neutralizing autoantibodies to GM-CSF or is secondary to other underlying diseases. Rarely, genetic defects in surfactant proteins or the common β chain for the GM-CSF receptor (GM-CSFR) are causal. Using a combination of cellular, molecular, and genomic approaches, we provide the first evidence that PAP can result from a genetic deficiency of the GM-CSFR α chain, encoded in the X-chromosome pseudoautosomal region 1.

Clinical spectrum of chronic interstitial lung disease in children

To describe the clinical spectrum of interstitial lung disease in children, we reviewed our experience with 48 patients during a 12-year period. Most patients initially had typical findings of restrictive lung disease and hypoxemia. Growth failure or pulmonary hypertension or both were found in more than one third. Specific diagnosis, made in 35 patients (70%), most often required invasive studies, particularly open lung biopsy. Although the diagnostic yield from open lung biopsy was high, the diagnosis of many patients remained uncertain. Many different disorders were encountered. The response to corticosteroids, bronchodilators, and chloroquine was inconsistent. Six patients died, five within 1 year after the initial evaluation. The spectrum of pediatric interstitial lung disease includes a large, heterogeneous group of rare disorders associated with high morbidity and mortality rates.

Isolation of Stachybotrys from the lung of a child with pulmonary hemosiderosis.

Recently, Stachybotrys atra, a toxigenic fungus, has been implicated as a potential cause of pulmonary hemorrhage/hemosiderosis in infants living in water-damaged homes. Although epidemiologic evidence supports this association, neither the organism nor its toxic products has ever been recovered from humans. We report the first case in whichStachybotrys was isolated from the bronchoalveolar lavage fluid of a child with pulmonary hemorrhage.Stachybotrys was also recovered from his water-damaged home. The patient recovered completely after his immediate removal from the environment and subsequent cleaning of his home. This case provides further evidence that this fungus is capable of causing pulmonary hemorrhage in children.

Bronchiolitis obliterans in children.

Purpose of review In this review, we discuss recent advances in our understanding of the etiology, pathology and pathogenesis, clinical presentation, diagnosis, treatment, and outcome of bronchiolitis obliterans in the nontransplant, pediatric population. Recent findings The diagnosis of bronchiolitis obliterans in children can be made with confidence based on clinical presentation, particularly with a history of adenovirus bronchiolitis or pneumonia, fixed obstructive lung disease on pulmonary function testing, and characteristic changes of mosaic perfusion, vascular attenuation, and central bronchiectasis on chest high-resolution computed tomography, thus avoiding the need for lung biopsy in most patients. Patients with postinfectious bronchiolitis obliterans generally have chronic, nonprogressive disease; in contrast, patients with bronchiolitis obliterans from Stevens–Johnson syndrome often have progressive disease that may require lung transplantation. Summary Bronchiolitis obliterans is a rare form of chronic obstructive lung disease that follows a severe insult to the lower respiratory tract, resulting in fibrosis of the small airways. In the nontransplant pediatric population, adenovirus infection is the most common cause. Treatment is largely supportive and prognosis is mainly related to the underlying cause and to the severity of the initial insult.

The safety and efficacy of thoracoscopic lung biopsy for diagnosis and treatment in infants and children

Thoracoscopic techniques were used to perform lung biopsies and limited resections in 36 consecutively treated cases. Biopsies were performed for interstitial lung disease in 27 cases, presumed metastatic lesions in 5, and cavitary lesions in 4. Histological diagnosis was obtained in 35 of the 36 cases, and therapy was directly affected by the results in 30 of 36 cases. There were no postoperative complications, and the average hospital stay for patients admitted the morning of surgery was less than 2 days. Limited thoracoscopic resection provides a safe and effective means for diagnosing and treating parenchymal disease of the lung.

Diagnostic value of transbronchial, thoracoscopic, and open lung biopsy in immunocompetent children with chronic interstitial lung disease

OBJECTIVES To evaluate the diagnostic value of transbronchial biopsy (TBB), video-assisted thoracoscopy (VAT), and open lung biopsy (OLB) in immunocompetent children with chronic, diffuse infiltrates; to identify factors that may predict diagnosis in children requiring biopsy; to determine whether age, number of biopsies, or type of procedure are associated with diagnostic yield in children undergoing transthoracic biopsy; and to compare morbidity of VAT with that of OLB. STUDY DESIGN As part of a prospective, descriptive study to define the clinical spectrum of pediatric interstitial lung disease, 30 immunocompetent children required TBB, VAT, and/or OLB for diagnosis of diffuse infiltrates. We reviewed and analyzed the following clinical variables: age; preoperative diagnosis; type of procedure; number of lobes undergoing biopsies; durations of surgery, chest tube insertion, and hospitalization; tissue diagnosis; and complications. RESULTS Specific diagnoses were made in 50%, 60%, and 53% of patients undergoing TBB, VAT, and OLB, respectively. A variety of rare disorders was found, and tissue diagnosis confirmed the preoperative diagnosis in 25% of all procedures. For patients who underwent transthoracic biopsy, patient age of greater than 24 months was significantly associated with increased diagnostic yield, but the number of lobes biopsied and type of procedure were not. VAT was associated with shorter operating time, chest tube placement, and hospitalization when compared with OLB. The complications of VAT and OLB were comparable. CONCLUSION Lung biopsy is an important tool for the diagnosis of interstitial lung disease in immunocompetent children, but the diagnosis of many children, particularly those aged 2 years or younger, remains uncertain.

Successful Treatment of Bronchiolitis Obliterans in a Bone Marrow Transplant Patient With Tumor Necrosis Factor-α Blockade

Bronchiolitis obliterans (BO) in children is a rare, inflammatory/fibrosing process involving the small airways that often results in progressive, irreversible obstructive pulmonary disease. Because treatment has focused mainly on supportive care and generally unsuccessful immunosuppression, children with BO experience significant morbidity and mortality. We report a case of biopsy-proven BO after bone marrow transplantation in a child who, after failed corticosteroid therapy, was treated with infliximab, a monoclonal antibody with binding specificity for human tumor necrosis factor-α. With initiation of treatment, her pulmonary symptoms and radiographic and spirometric evidence of BO resolved. Nine months later, she remains asymptomatic and shows no evidence of pulmonary decompensation. This case illustrates a successful treatment of BO with selective tumor necrosis factor-α blockade.

Neuroendocrine Cell Hyperplasia of Infancy: Diagnosis With High-Resolution CT

OBJECTIVE Neuroendocrine cell hyperplasia of infancy is a form of childhood interstitial lung disease originally reported as persistent tachypnea of infancy. Reports of small series of cases and anecdotal experience have suggested that this disorder may have a consistent CT pattern. The purpose of this study was to review the CT findings in children with neuroendocrine cell hyperplasia of infancy to determine the findings at high-resolution CT, the diagnostic accuracy of CT compared with biopsy, and interrater reliability. MATERIALS AND METHODS Images from 23 CT examinations of children with biopsy-proven neuroendocrine cell hyperplasia of infancy and six CT examinations of children with other childhood interstitial lung diseases were reviewed by two pediatric radiologists with special expertise in thoracic imaging. Identifying digital data were removed, and images were reviewed without clinical data. A CT assessment form was completed for each patient. RESULTS Ground-glass opacification was the most common finding in patients with neuroendocrine cell hyperplasia of infancy. The right middle lobe and lingula were most commonly involved. Air trapping with a mosaic pattern was the second most common finding. Interrater reliability was very good with a kappa value of 0.93. The sensitivity and specificity of CT in the diagnosis of neuroendocrine cell hyperplasia of infancy were at least 78% and 100%. CONCLUSION Neuroendocrine cell hyperplasia of infancy can have a characteristic appearance on high-resolution CT scans, the imaging findings being useful in differentiating neuroendocrine cell hyperplasia of infancy from other types of childhood interstitial lung disease. The appearance aids radiologists in suggesting a specific diagnosis but does not exclude this diagnosis; in 17-22% of cases, the readers in this study did not suggest the diagnosis of neuroendocrine cell hyperplasia of infancy when it was present.