- Email: [email protected]
Chronic lung disease of prematurity: long-term respiratory outcome
S2
Oral Presentations / Paediatric Respiratory Reviews 12S1 (2011) S1–S66
and INH prophylaxis. BCG is ineffective for primary prevention of pulmonary TB and is not recommended in HIV-infected infants due to the high risk of disseminated BCG and associated mortality. The risk of TB in HIV-infected children may be greatly reduced by the use of HAART and by the use of INH preventive treatment. II.2 Chronic lung disease of prematurity: long-term respiratory outcome E. Baraldi. Department of Pediatrics, University of Padova, Italy Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that develops as a consequence of perinatal/neonatal lung injury, and it is one of the most important sequelae of premature birth. The diagnosis of BPD is currently based on the need for supplemental oxygen for at least 28 days after birth, and its severity is graded according to the respiratory support required at 36 postmenstrual weeks. BPD almost always occurs in neonates who are delivered at a gestational age of less than 30 weeks and who have a birth weight of less than 1500 g. These are about 1.5% of all newborns and BPD develops in about 20% of them. Today BPD is mainly a developmental disorder in which the immature lung fails to reach its full structural complexity. Longitudinal studies on children with BPD identified, at all ages, increased rates of chronic coughing and wheezing, a greater need to use inhaled asthma medications and a significant airflow obstruction. Children who have survived BPD and children with asthma share some clinical and functional characteristics, but available evidence suggests that the two obstructive lung diseases do not have the same underlying airway inflammation. Spirometric values reflecting airflow, such as FEV1 , are consistently lower in survivors of BPD into adolescence and young adulthood than in controls born at term rising the concern that the chronic lung disease after premature birth may predispose to the development of a chronic obstructive pulmonary disease (COPD)-like phenotype with aging. This is an open question that only follow-up and lung function studies extended to middle-age and beyond will answer. Unfortunately, no pathologic data are available elucidating which structural and pathophysiological alterations underlie the clinical and functional pulmonary abnormalities seen at long-term in some subjects delivered prematurely. A relevant question is whether the long-term pulmonary consequences of prematurity and BPD essentially depend on a non-progressive reduction of the airway caliber, due to a stabilized, non-progressive structural damage of the airways, or instead also reflect an active airway disease. Chronic lung disease of prematurity can no longer be considered only a pediatric disease and also family doctors and chest physicians should be aware of this “new” Chronic Obstructive Pulmonary Disease. References Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163: 1723–9. Baraldi E, Filippone M. Chronic lung disease after premature birth. New Eng J Med 2007; 357: 1946–1955. Kinsella JP, Greenough A, Abman SH. Bronchopulmonary dysplasia. Lancet 2006; 367: 1421–31. Filippone M, Bonetto G, Cherubin E, Carraro S, Baraldi E. Childhood course of lung function in survivors of bronchopulmonary dysplasia. JAMA 2009, 302:1418–20.
II.3 Diagnosis and management of ciliopathies A. Bush. Department of Paediatric Respirology, Imperial School of Medicine at National Heart and Lung Institute; and Royal Brompton Hospital, UK Correspondence: Correspondence: A. Bush. Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. Tel.: +44 207 351 8232; fax: +44 207 351 8763. E-mail: [email protected]
Introduction: If Nitric oxide (NO) was the molecule of the 1990s, cilia are the organelles of the 21st century. There has been an explosion of knowledge in the understanding of the disparate functions of cilia, and of disease caused by their dysfunction. This presentation will discuss the spectrum of ciliopathy, but focus mainly on the diagnosis and management of primary ciliary dyskinesia (PCD). Most of the other ciliopathies are the province of non-respiratory paediatricians. There are three groups of mammalian cilia: • Primary cilia: (which are NOT abnormal in PCD) have 9 outer doublets, no central pair, and are probably non-motile. There is only one per cell, they are found on many cell types, and probably function as chemo-, osmo- and phototransduction sensors • Nodal cilia: These are primary in structure, but motile with a circular, rotator beat. They are found in the embryonic node and determine organ situs • Motile cilia: These have the classic 9+2 structure, and are responsible for propelling mucus along epithelial surfaces (or propelling single cell organisms through liquid). There are around 200/respiratory epithelial cell. Ciliary assembly includes complex intraflagellar transport, including retrograde recycling of proteins. The process involves at least eight Bardet-Biedl-Syndrome (BBS) proteins. Ciliary signal transduction involves the hedgehog signaling pathway, and canoniocal and noncanonical Wnt pathways. The extended spectrum of ciliopathy: Syndromic Manifestations: Mutations in more than 40 genes have been associated with ciliopathy. Many are complex, overlapping genetic disorders, and each syndrome may be related to many different underlying mutations, some of which have been identified as part of the ciliosome [1]. The more important are listed below. • Joubert syndrome (JBTS): is characterized by hypotonia, ataxia, psychomotor delay, irregular breathing pattern, oculomotor apraxia with cerebellar and brainstem abnormalities • Meckel-Gruber syndrome (MKS): overlaps with JBTS. Features include posterior fossa defects, cystic dysplastic kidneys, hepatic duct proliferation and polydactyly. • Senior-Loken syndrome (SLS): is characterized mainly retinal disease (retinitis pigmentosa (RP) and congenital blindness, and renal disease (nephronophthisis, polycystic disease and cystic renal dysplasia) • Orofacial digital syndrome (OFD): is characterized by oral cavity, facial and digital malformations, cystic kidney disease and central nervous system abnormalities • Leber’s congenital amaurosis (LCA): this early presenting syndrome is characterized by poor visual function, often with nystagmus and reduced or absent papillary responses, photophobia, keratoconus and hyperopia. • Bardet-Biedl-Syndrome (BBS): This syndrome includes rodcone dystrophy, polydactyly, obesity, learning disabilities, hypogonadism and renal disease (renal dysplasia, cystic tubular disease, nephronophthisis, focal glomerular sclerosis), and detrusor instability. Among the many secondary features are speech disorders, developmental delay and behavioural disorders, strabismus, cataracts and astigmatism, brachydactyky or syndactyly, ataxia and poor coordination, hypertonia,
Oral Presentations / Paediatric Respiratory Reviews 12S1 (2011) S1–S66
and INH prophylaxis. BCG is ineffective for primary prevention of pulmonary TB and is not recommended in HIV-infected infants due to the high risk of disseminated BCG and associated mortality. The risk of TB in HIV-infected children may be greatly reduced by the use of HAART and by the use of INH preventive treatment. II.2 Chronic lung disease of prematurity: long-term respiratory outcome E. Baraldi. Department of Pediatrics, University of Padova, Italy Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that develops as a consequence of perinatal/neonatal lung injury, and it is one of the most important sequelae of premature birth. The diagnosis of BPD is currently based on the need for supplemental oxygen for at least 28 days after birth, and its severity is graded according to the respiratory support required at 36 postmenstrual weeks. BPD almost always occurs in neonates who are delivered at a gestational age of less than 30 weeks and who have a birth weight of less than 1500 g. These are about 1.5% of all newborns and BPD develops in about 20% of them. Today BPD is mainly a developmental disorder in which the immature lung fails to reach its full structural complexity. Longitudinal studies on children with BPD identified, at all ages, increased rates of chronic coughing and wheezing, a greater need to use inhaled asthma medications and a significant airflow obstruction. Children who have survived BPD and children with asthma share some clinical and functional characteristics, but available evidence suggests that the two obstructive lung diseases do not have the same underlying airway inflammation. Spirometric values reflecting airflow, such as FEV1 , are consistently lower in survivors of BPD into adolescence and young adulthood than in controls born at term rising the concern that the chronic lung disease after premature birth may predispose to the development of a chronic obstructive pulmonary disease (COPD)-like phenotype with aging. This is an open question that only follow-up and lung function studies extended to middle-age and beyond will answer. Unfortunately, no pathologic data are available elucidating which structural and pathophysiological alterations underlie the clinical and functional pulmonary abnormalities seen at long-term in some subjects delivered prematurely. A relevant question is whether the long-term pulmonary consequences of prematurity and BPD essentially depend on a non-progressive reduction of the airway caliber, due to a stabilized, non-progressive structural damage of the airways, or instead also reflect an active airway disease. Chronic lung disease of prematurity can no longer be considered only a pediatric disease and also family doctors and chest physicians should be aware of this “new” Chronic Obstructive Pulmonary Disease. References Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163: 1723–9. Baraldi E, Filippone M. Chronic lung disease after premature birth. New Eng J Med 2007; 357: 1946–1955. Kinsella JP, Greenough A, Abman SH. Bronchopulmonary dysplasia. Lancet 2006; 367: 1421–31. Filippone M, Bonetto G, Cherubin E, Carraro S, Baraldi E. Childhood course of lung function in survivors of bronchopulmonary dysplasia. JAMA 2009, 302:1418–20.
II.3 Diagnosis and management of ciliopathies A. Bush. Department of Paediatric Respirology, Imperial School of Medicine at National Heart and Lung Institute; and Royal Brompton Hospital, UK Correspondence: Correspondence: A. Bush. Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. Tel.: +44 207 351 8232; fax: +44 207 351 8763. E-mail: [email protected]
Introduction: If Nitric oxide (NO) was the molecule of the 1990s, cilia are the organelles of the 21st century. There has been an explosion of knowledge in the understanding of the disparate functions of cilia, and of disease caused by their dysfunction. This presentation will discuss the spectrum of ciliopathy, but focus mainly on the diagnosis and management of primary ciliary dyskinesia (PCD). Most of the other ciliopathies are the province of non-respiratory paediatricians. There are three groups of mammalian cilia: • Primary cilia: (which are NOT abnormal in PCD) have 9 outer doublets, no central pair, and are probably non-motile. There is only one per cell, they are found on many cell types, and probably function as chemo-, osmo- and phototransduction sensors • Nodal cilia: These are primary in structure, but motile with a circular, rotator beat. They are found in the embryonic node and determine organ situs • Motile cilia: These have the classic 9+2 structure, and are responsible for propelling mucus along epithelial surfaces (or propelling single cell organisms through liquid). There are around 200/respiratory epithelial cell. Ciliary assembly includes complex intraflagellar transport, including retrograde recycling of proteins. The process involves at least eight Bardet-Biedl-Syndrome (BBS) proteins. Ciliary signal transduction involves the hedgehog signaling pathway, and canoniocal and noncanonical Wnt pathways. The extended spectrum of ciliopathy: Syndromic Manifestations: Mutations in more than 40 genes have been associated with ciliopathy. Many are complex, overlapping genetic disorders, and each syndrome may be related to many different underlying mutations, some of which have been identified as part of the ciliosome [1]. The more important are listed below. • Joubert syndrome (JBTS): is characterized by hypotonia, ataxia, psychomotor delay, irregular breathing pattern, oculomotor apraxia with cerebellar and brainstem abnormalities • Meckel-Gruber syndrome (MKS): overlaps with JBTS. Features include posterior fossa defects, cystic dysplastic kidneys, hepatic duct proliferation and polydactyly. • Senior-Loken syndrome (SLS): is characterized mainly retinal disease (retinitis pigmentosa (RP) and congenital blindness, and renal disease (nephronophthisis, polycystic disease and cystic renal dysplasia) • Orofacial digital syndrome (OFD): is characterized by oral cavity, facial and digital malformations, cystic kidney disease and central nervous system abnormalities • Leber’s congenital amaurosis (LCA): this early presenting syndrome is characterized by poor visual function, often with nystagmus and reduced or absent papillary responses, photophobia, keratoconus and hyperopia. • Bardet-Biedl-Syndrome (BBS): This syndrome includes rodcone dystrophy, polydactyly, obesity, learning disabilities, hypogonadism and renal disease (renal dysplasia, cystic tubular disease, nephronophthisis, focal glomerular sclerosis), and detrusor instability. Among the many secondary features are speech disorders, developmental delay and behavioural disorders, strabismus, cataracts and astigmatism, brachydactyky or syndactyly, ataxia and poor coordination, hypertonia,