Interstitial Lung Disease In Infants Research Articles

Rare interstitial lung diseases in infants

The diagnosis of interstitial lung disease in infants (chILD) is challenging due to the fact that the differential range encompasses more than 200 variants of nosologies with an overall estimated prevalence of 1.6–46 per 100,000 according to several studies. Thus, chILDs are 10 times less common than in adults. The chILD disease spectrum differs significantly from that seen in older children and adults. Interest in the topic of chILD has increased over the past 20 years, as evidenced by the published results of numerous studies and reviews. Also, multidisciplinary groups and respiratory societies have been established, such as the American Thoracic Society (ATS), the European Research Collaboration for Children’s Interstitial Lung Disease (ERS CRC chILD-EU), the French National Reference Center for Rare Respiratory Diseases in Children (RESPIRARE), etc. This article discusses recent advances in the study and diagnosis of chILD, with a special focus on rare and ultra-rare types of chILD. In addition, the stages of the diagnostic search and the increasing role of computed tomography are discussed.

Congenital alveolar dysplasia and alveolar capillary dysplasia with misalignment of the pulmonary veins: clinical and anatomical comparisons

Congenital alveolar dysplasia (СAD) and alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) are rare genetically determined interstitial lung diseases in infants that manifest in the first hours to days after birth, have fatal outcome and are usually diagnosed at autopsy.The aim of this work was to consider the clinical manifestations and pathomorphologic picture of CAD and ACD/MPV based on clinical observations of newborns who were on a ventilator, received therapy for high pulmonary hypertension and extracorporeal membrane oxygenation (ECMO). The clinical characteristics and medical history of the patients are described. The results of lifetime imaging methods, autopsy examinations with light microscopy and the use of routine staining methods of micro-preparations as well as immunohistochemical methods are considered. Morphologic changes in the lungs characteristic of CAD and ACD/MPV are described in detail in the analysis of histologic examination data.Conclusion. The pathoanatomical examination data are of crucial importance for the diagnosis of CAD and ACD/MPV, which must be suspected in newborns with respiratory insufficiency and severe pulmonary hypertension when ventilation, inhalation of nitric oxide and ECMO are ineffective.

Gene Therapeutics for Surfactant Dysfunction Disorders: Targeting the Alveolar Type 2 Epithelial Cell.

Genetic disorders of surfactant dysfunction result in significant morbidity and mortality, among infants, children, and adults. Available medical interventions are limited, nonspecific, and generally ineffective. As such, the need for effective therapies remains. Pathogenic variants in the SFTPB, SFTPC, and ABCA3 genes, each of which encode proteins essential for proper pulmonary surfactant production and function, result in interstitial lung disease in infants, children, and adults, and lead to morbidity and early mortality. Expression of these genes is predominantly limited to the alveolar type 2 (AT2) epithelial cells present in the distal airspaces of the lungs, thus providing an unequivocal cellular origin of disease pathogenesis. While several treatment strategies are under development, a gene-based therapeutic holds great promise as a definitive therapy. Importantly for clinical translation, the genes associated with surfactant dysfunction are both well characterized and amenable to a gene-therapeutic-based strategy. This review focuses on the pathophysiology associated with these genetic disorders of surfactant dysfunction, and also provides an overview of the current state of gene-based therapeutics designed to target and transduce the AT2 cells.

An Infant with Interstitial Lung Disease

Interstitial lung disease in infants, unlike older children and adults, has diverse etiology, including infective, metabolic, autoimmune, genetic, malignant and idiopathic causes. Clinical recognition of the interstitial pattern of lung involvement is important as the etiology and management is entirely different from that of recurrent or chronic lung parenchymal pathologies. We discuss the clinical and pathological findings of an infant with interstitial pneumonia, who succumbed to hospital-acquired sepsis.

Pulmonary surfactant protein adenosine triphosphate-binding-cassette-A3 gene composite mutations in infant congenital interstitial lung disease: report of a case and review of literature

6 cases died, and 6 cases survived, including 4 cases with pulmonary function disturbance to different degrees; 12 cases had ABCA3 gene mutations, 9 cases had composite ABCA3 gene mutations, in 11 cases the mutation occured in the exon of coding region, in 1 case in the intron, 9 cases had heterozygous mutations, 3 cases had homozygous mutations. Conclusion: The main phenotypes of ABCA3 mutation associated with ILD were full term neonatal respiratory distress syndrome or progressive tachypnea or dyspnea unexplained in infants. The chest HRCT showed two diffuse pulmonary interstitial changes. ABCA3 mutation mainly was multi-site composite mutations and heterozygous mutations in the exon of coding region.

Natural history of five children with surfactant protein C mutations and interstitial lung disease

Interstitial lung diseases in infants and children are uncommon and may be caused by specific inborn errors of surfactant metabolism. Five children with open lung biopsy diagnosed interstitial lung disease were followed (mean of 27.2 years) and evaluated for surfactant protein gene mutations. Four of the children were originally diagnosed as desquamative interstitial pneumonitis and one as chronic interstitial pneumonitis. All had good response to chloroquine or hydroxychloroquine treatment for periods of 7-38 months. Lung function tests, incremental exercise tests, and rentgenological studies were performed in the children. Surfactant protein gene mutations were searched in all the patients and in part of their families. Three of the patients, aged now 32, 29, and 37 years, feel well and have normal lung function, while two of the patients, both females, aged 28 and 37 years, conduct normal activities of daily living, have healthy children but have clinical, physiological and rentgenological evidence of restrictive lung disease. All five patients were found to have surfactant protein C gene (SFTPC) mutations, three of them with the most common mutation (p.I73T) and the other two with new mutations of surfactant protein C gene (p.I38F and p.V39L). We conclude that detection of surfactant protein mutations should be attempted in all children presenting with interstitial lung disease. Furthermore, treatment with hydroxychloroquine should be considered in children with SFTPC mutations. Prospective evaluation of hydroxychloroquine therapy in a greater number of patients is needed.

Interstitial lung disease in infants: new classification system, imaging technique, clinical presentation and imaging findings

Interstitial lung disease (ILD) is defined as a rare, heterogeneous group of parenchymal lung conditions that develop primarily because of underlying developmental or genetic disorders. Affected infants typically present with clinical syndromes characterized by dyspnea, tachypnea, crackles and hypoxemia. Until recently, the understanding of ILD in infants has been limited largely owing to a lack of evidence-based information of underlying pathogenesis, natural history, imaging findings and histopathological features. However, ILD in infants is now better understood and managed because of (1) advances in imaging methods that result in rapid and accurate detection, (2) improved thoracoscopic techniques for lung biopsy, (3) a consensus regarding the pathological criteria for these particular lung conditions and (4) a new classification system based on the underlying etiology of ILD. This article reviews the new classification system, imaging technique, clinical presentation and imaging findings of ILD in infants. Specialized knowledge of this new classification system in conjunction with recognition of characteristic imaging findings of ILD in infants has great potential for early and accurate diagnosis, which in turn can lead to optimal patient management.

Death of a Severe Underweight Infant with Pulmonary Interstitial Glycogenosis

Pulmonary interstitial glycogenosis (PIG) is a very rare interstitial lung disease in infants. It is poorly understood, but its pathological features are distinct; they include uniform alveolar septal thickening, caused by a group of oval to spindle-shaped cells containing abundant glycogen, without apparent inflammation or fibrosis. PIG is usual- ly associated with a good prognosis. However, in the present report, we describe the case of a 5-month-old male infant who died due to PIG; he was severely underweight and not administered proper treatment or care. The pathology of PIG was determined following a medico-legal autopsy.

Round Table Discussion: Children's Interstitial Lung Disease

Robin R. Deterding: We have the opportunity today to talk about children’s interstitial lung disease (chILD) with experts in that fi eld. My hope is that we can have a lively discussion about what we know is important in chILD and what we see coming on the horizon. I would like to begin our discussion with a question: Why is it important to recognize that chILD differs from i nterstitial lung disease (ILD) in adults? Lisa, would you like to give your thoughts about this? Lisa R. Young: I think this is an extremely important question, about which we have learned a lot in the past sev-eral years. A major reason for the importance of distinguish-ing chILD from adult ILD has to do with what patients read and think about with respect to these 2 diagnoses. A family that turns to the Internet in the belief that it has a member affected by ILD can become very quickly frightened, for ex-ample, in reading about the prognosis in idiopathic pulmo-nary fi brosis (IPF), a common form of ILD in adults but one that does not occur in children. Robin R. Deterding: Alan, what are your thoughts as a radiologist? Alan S. Brody: I agree with Lisa, and I think that some things that look like but are not the same as adult IPF may be a problem for the radiologist as well as for the clinician who does not deal with chILD, as well as for the families of patients. The 2 conditions should not be treated in the same way; they do not have the same prognosis. We did not know that years ago, but today it is very clear, as Lisa observed, that IPF, the most common adult form of ILD, does not occur in children, and if someone gives a child that diagnosis, we can tell the family right away that it is not correct, that there is more work to do to understand their child’s ILD. The prognosis of chILD is very variable and often much better than adult IPF. Lisa R. Young: We’re also learning that the etiology of chILD is often very different from the types of ILD seen in adults, and we think that understanding the eti-ology of the childhood disorder is a key step toward its treatment. James S. Hagood: I agree. For adults and physicians car-ing for adults with ILD, by far the largest category of disease is IPF, which does not appear to occur in children. And while many secondary forms of ILD and pulmonary fi brosis may be similar to what we see in older children and adolescents with rheumatic disease or hypersensitivity pneumonitis in terms of specifi c causes, the prognosis and management may differ in children. Robin R. Deterding: All of these are excellent observa-tions. The only thing I would add is that ILD in infants and children may improve or transform into a different type of lung disease, that may be similar to or different than adult ILD, as they grow older. It is very diffi cult to know what may happen until we can correctly classify these various condi-tions and follow them over time. I would like to discuss the presentations of ILD in chil-dren. What are your experiences with this, and when might you think you are dealing with a child with ILD? Lisa R. Young: The children I see generally have 2 dif-ferent categories of ILD. One of them has a very dramatic presentation, such as respiratory failure, and this generally presents in neonates at birth. I fi nd it can be more diffi cult to identify ILD in older children, which may be insidious in onset. Children may present with progressive exercise intol-erance marked only by a gradual slowing and falling behind their friends or siblings in their physical activities. In babies, the symptoms of this may include trouble with feeding, and may look like refl ux or other feeding problems, but may in-stead be related to their diffi culty with breathing. Alan S. Brody: As a radiologist, most of the children sent to me are referred, and for a number of reasons, but there is almost always some concern about the presence of lung

Interstitial lung diseases in infants and children

Interstitial lung disease (ILD) in infants and children represents a heterogeneous group of respiratory disorders that are mostly chronic and associated with high morbidity and mortality. Typical features of ILD include dyspnoea, the presence of diffuse infiltrates on chest radiographs and abnormal pulmonary function tests with evidence of a restrictive ventilatory defect (in older children) and/or impaired gas exchange. ILD is difficult to diagnose, as no classification scheme is entirely satisfactory. Recently, it has been proposed to categorise paediatric ILD as either primary pulmonary disorders or systemic disorders with pulmonary involvement. However, this classification leaves the difficult problem of which clinical conditions should be included or excluded in infants and children. The present article reviews interstitial lung disease in infants and children, placing emphasis on current concepts of pathophysiological mechanisms and approaches to treatment.

Diffuse interstitial lung disease in infants

Pediatric PulmonologyVolume 32, Issue S23 p. 74-76 Article Diffuse interstitial lung disease in infants Dr. Claire Langston, Corresponding Author Dr. Claire Langston Department of Pathology, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TexasDepartment of Pathology, Texas Children's Hospital, 6621 Fannin St., Houston, TX, USASearch for more papers by this authorLeland L. Fan, Leland L. Fan Pediatric Pulmonology Section, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TexasSearch for more papers by this author Dr. Claire Langston, Corresponding Author Dr. Claire Langston Department of Pathology, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TexasDepartment of Pathology, Texas Children's Hospital, 6621 Fannin St., Houston, TX, USASearch for more papers by this authorLeland L. Fan, Leland L. Fan Pediatric Pulmonology Section, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TexasSearch for more papers by this author First published: 29 November 2005 https://doi.org/10.1002/ppul.1950322331Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume32, IssueS23Supplement: Fourth International Congress on Pediatric Pulmonology Nice, France, February 22–24, 20002001Pages 74-76 RelatedInformation

Diffuse interstitial lung disease in infants

Diffuse interstitial lung disease in infants

The value of classifying interstitial pneumonitis in childhood according to defined histological patterns.

Interstitial pneumonitis in children is very rare and most cases have been classified according to their counterparts in adults, although the term 'chronic pneumonitis of infancy' has recently been proposed for a particular pattern of interstitial lung disease in infants. We reviewed our paediatric cases of interstitial pneumonitis, first, to look at the spectrum of histological patterns found in this age group and, second, to determine whether the classification of such cases in childhood is both appropriate and worthwhile. Twenty-five of 38 open lung biopsies showed an overlapping spectrum of interstitial pneumonitis, including three cases that fulfilled the histological criteria for chronic pneumonitis of infancy. There were 11 cases of reactive pulmonary lymphoid hyperplasia (either lymphoid interstitial pneumonitis or follicular bronchiolitis), five of which were associated with abnormalities of the immune system. Four cases were classified as desquamative interstitial pneumonitis and the remaining seven cases were classified as nonspecific interstitial pneumonitis. There were no cases with the histological features of usual interstitial pneumonitis. Most patients responded to steroids but tended to have a residual deficit in lung function. Mortality appeared to be associated with presentation at a young age. Classification of interstitial pneumonitis according to their adult counterparts is appropriate for this younger age group and can provide valuable information for the clinician. The term 'chronic pneumonitis of infancy' refers to a specific histological pattern, but whether it represents a separate disease or a reflection of pulmonary immaturity remains to be proven.