Children’s Interstitial and Diffuse Lung Diseases (ChILD) in 2020
Abstract
:1. Introduction
2. Classification
3. Clinical Manifestation
4. Diagnosis
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- respiratory symptoms (cough, rapid breathing, or exercise intolerance);
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- respiratory signs (resting tachypnoea, auscultation with pathological sounds even if child has no acute infection, retractions, digital clubbing, respiratory failure, failure to thrive);
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- hypoxemia;
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- diffuse abnormalities on chest imaging.
5. Follow-Up and Prognosis
6. Therapeutic Approach
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Cunningham, S.; Jaffe, A.; Young, L.R. Children’s interstitial and diffuse lung disease. Lancet Child Adolesc. Health 2019, 3, 568–577. [Google Scholar] [CrossRef]
- Nathan, N.; Berdah, L.; Borensztajn, K.; Clement, A. Chronic interstitial lung diseases in children: Diagnosis approaches. Expert Rev. Respir. Med. 2018, 12, 1051–1060. [Google Scholar] [CrossRef] [PubMed]
- Hime, N.J.; Zurynski, Y.; Fitzgerald, D.; Selvadurai, H.; Phu, A.; Deverell, M.; Elliott, E.J.; Jaffe, A. Childhood interstitial lung disease: A systematic review. Pediatric Pulmonol. 2015, 50, 1383–1392. [Google Scholar] [CrossRef] [PubMed]
- Clement, A.; ERS Task Force. Task force on chronic interstitial lung disease in immunocompetent children. Eur. Respir. J. 2004, 24, 686–697. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Deutsch, G.H.; Young, L.R.; Deterding, R.R.; Fan, L.L.; Dell, S.D.; Bean, J.A.; Brody, A.S.; Nogee, L.M.; Trapnell, B.C.; Langston, C.; et al. Diffuse lung disease in young children: Application of a novel classification scheme. Am. J. Respir. Crit. Care Med. 2007, 176, 1120–1128. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Clement, A.; Nathan, N.; Epaud, R.; Fauroux, B.; Corvol, H. Interstitial lung diseases in children. Orphanet J. Rare Dis. 2010, 5, 22. [Google Scholar] [CrossRef] [PubMed]
- Rice, A.; Tran-Dang, M.-A.; Bush, A.; Nicholson, A.G. Diffuse lung disease in infancy and childhood: Expanding the chILD classification. Histopathology 2013, 63, 743–755. [Google Scholar] [CrossRef]
- Kurland, G.; Deterding, R.R.; Hagood, J.S.; Young, L.R.; Brody, A.S.; Castile, R.G.; Dell, S.; Fan, L.L.; Hamvas, A.; Hilman, B.C.; et al. An official American Thoracic Society clinical practice guideline: Classification, evaluation, and management of childhood interstitial lung disease in infancy. Am. J. Respir. Crit. Care Med. 2013, 188, 376–394. [Google Scholar] [CrossRef] [Green Version]
- Griese, M.; Irnstetter, A.; Hengst, M.; Burmester, H.; Nagel, F.; Ripper, J.; Feilcke, M.; Pawlita, I.; Gothe, F.; Kappler, M.; et al. Categorizing diffuse parenchymal lung disease in children. Orphanet J. Rare Dis. 2015, 10, 122. [Google Scholar] [CrossRef] [Green Version]
- Casey, A.M.; Deterding, R.R.; Young, L.R.; Fishman, M.P.; Fiorino, E.K.; Liptzin, D.R. Overview of the ChILD Research Network: A roadmap for progress and success in defining rare diseases. Pediatric Pulmonol. 2020, 55, 1819–1827. [Google Scholar] [CrossRef]
- Bush, A.; Cunningham, S.; de Blic, J.; Barbato, A.; Clement, A.; Epaud, R.; Hengst, M.; Kiper, N.; Nicholson, A.G.; Wetzke, M.; et al. European protocols for the diagnosis and initial treatment of interstitial lung disease in children. Thorax 2015, 70, 1078–1084. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Clement, A.; de Blic, J.; Epaud, R.; Galeron, L.; Nathan, N.; Hadchouel, A.; Barbato, A.; Snijders, D.; Kiper, N.; Cunningham, S.; et al. Management of children with interstitial lung diseases: The difficult issue of acute exacerbations. Eur. Respir. J. 2016, 48, 1559–1563. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Spagnolo, P.; Bush, A. Interstitial Lung Disease in Children Younger Than 2 Years. Pediatrics 2016, 137. [Google Scholar] [CrossRef] [Green Version]
- Copley, S.J.; Bush, A. HRCT of paediatric lung disease. Paediatr. Respir. Rev. 2000, 1, 141–147. [Google Scholar] [PubMed]
- Klusmann, M.; Owens, C. HRCT in paediatric diffuse interstitial lung disease—A review for 2009. Pediatric Radiol. 2009, 39 (Suppl. 3), 471–481. [Google Scholar] [CrossRef] [PubMed]
- Vrielynck, S.; Mamou-Mani, T.; Emond, S.; Scheinmann, P.; Brunelle, F.; de Blic, J. Diagnostic value of high-resolution CT in the evaluation of chronic infiltrative lung disease in children. AJR Am. J. Roentgenol. 2008, 191, 914–920. [Google Scholar] [CrossRef] [PubMed]
- Brody, A.S.; Guillerman, R.P.; Hay, T.C.; Wagner, B.D.; Young, L.R.; Deutsch, G.H.; Fan, L.L.; Deterding, R.R. Neuroendocrine cell hyperplasia of infancy: Diagnosis with high-resolution CT. AJR Am. J. Roentgenol. 2010, 194, 238–244. [Google Scholar] [CrossRef] [Green Version]
- Saddi, V.; Beggs, S.; Bennetts, B.; Harrison, J.; Hime, N.; Kapur, N.; Lipsett, J.; Nogee, L.M.; Phu, A.; Suresh, S.; et al. Childhood interstitial lung diseases in immunocompetent children in Australia and New Zealand: A decade’s experience. Orphanet J. Rare Dis. 2017, 12, 133. [Google Scholar] [CrossRef] [Green Version]
- Midulla, F.; de Blic, J.; Barbato, A.; Bush, A.; Eber, E.; Kotecha, S.; Haxby, E.; Moretti, C.; Pohunek, P.; Ratjen, F.E. Flexible endoscopy of paediatric airways. Eur. Respir. J. 2003, 22, 698–708. [Google Scholar] [CrossRef]
- Faro, A.; Wood, R.E.; Schechter, M.S.; Leong, A.B.; Wittkugel, E.; Abode, K.; Chmiel, J.F.; Daines, C.; Davis, S.; Eber, E.; et al. Official American Thoracic Society technical standards: Flexible airway endoscopy in children. Am. J. Respir. Crit. Care Med. 2015, 191, 1066–1080. [Google Scholar] [CrossRef]
- Hafezi, N.; Heimberger, M.A.; Lewellen, K.A.; Maatman, T.; Montgomery, G.S.; Markel, T.A. Lung biopsy in children’s interstitial and diffuse lung disease: Does it alter management? Pediatric Pulmonol. 2020, 55, 1050–1060. [Google Scholar] [CrossRef] [PubMed]
- Langston, C.; Patterson, K.; Dishop, M.K.; chILD Pathology Co-operative Group; Askin, F.; Baker, P.; Chou, P.; Cool, C.; Coventry, S.; Cutz, E.; et al. A protocol for the handling of tissue obtained by operative lung biopsy: Recommendations of the chILD pathology co-operative group. Pediatric Dev. Pathol. 2006, 9, 173–180. [Google Scholar] [CrossRef] [PubMed]
- Cunningham, S.; Graham, C.; MacLean, M.; Aurora, P.; Ashworth, M.; Barbato, A.; Calder, A.; Carlens, J.; Clement, A.; Hengst, M.; et al. One-year outcomes in a multicentre cohort study of incident rare diffuse parenchymal lung disease in children (ChILD). Thorax 2020, 75, 172–175. [Google Scholar] [CrossRef] [PubMed]
- Bush, A.; Griese, M.; Seidl, E.; Kerem, E.; Reu, S.; Nicholson, A.G. Early onset children’s interstitial lung diseases: Discrete entities or manifestations of pulmonary dysmaturity? Paediatr. Respir. Rev. 2019, 30, 65–71. [Google Scholar] [CrossRef] [PubMed]
- Slot, E.; Edel, G.; Cutz, E.; van Heijst, A.; Post, M.; Schnater, M.; Wijnen, R.; Tibboel, D.; Rottier, R.; de Klein, A. Alveolar capillary dysplasia with misalignment of the pulmonary veins: Clinical, histological, and genetic aspects. Pulm. Circ. 2018, 8. [Google Scholar] [CrossRef] [Green Version]
- Nevel, R.J.; Garnett, E.T.; Schaudies, D.A.; Young, L.R. Growth trajectories and oxygen use in neuroendocrine cell hyperplasia of infancy. Pediatric Pulmonol. 2018, 53, 656–663. [Google Scholar] [CrossRef]
- Gomes, V.C.C.; Silva, M.C.C.; Maia Filho, J.H.; Daltro, P.; Ramos, S.G.; Brody, A.S.; Marchiori, E. Diagnostic criteria and follow-up in neuroendocrine cell hyperplasia of infancy: A case series. J. Bras. Pneumol. 2013, 39, 569–578. [Google Scholar] [CrossRef] [Green Version]
- Liptzin, D.R.; Baker, C.D.; Darst, J.R.; Weinman, J.P.; Dishop, M.K.; Galambos, C.; Brinton, J.T.; Deterding, R.R. Pulmonary interstitial glycogenosis: Diagnostic evaluation and clinical course. Pediatric Pulmonol. 2018, 53, 1651–1658. [Google Scholar] [CrossRef]
- Chakraborty, M.; Kotecha, S. Pulmonary surfactant in newborn infants and children. Breathe 2013, 9, 476–488. [Google Scholar] [CrossRef] [Green Version]
- Kazzi, B.; Lederer, D.; Arteaga-Solis, E.; Saqi, A.; Chung, W.K. Recurrent diffuse lung disease due to surfactant protein C deficiency. Respir. Med. Case Rep. 2018, 25, 91–95. [Google Scholar] [CrossRef]
- Kröner, C.; Wittmann, T.; Reu, S.; Teusch, V.; Klemme, M.; Rauch, D.; Hengst, M.; Kappler, M.; Cobanoglu, N.; Sismanlar, T.; et al. Lung disease caused by ABCA3 mutations. Thorax 2017, 72, 213–220. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Manali, E.D.; Legendre, M.; Nathan, N.; Kannengiesser, C.; Coulomb-L’Hermine, A.; Tsiligiannis, T.; Tomos, P.; Griese, M.; Borie, R.; Clement, A.; et al. Bi-allelic missense ABCA3 mutations in a patient with childhood ILD who reached adulthood. ERJ Open Res. 2019, 5, 00066–02019. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Deterding, R.R.; DeBoer, E.M.; Cidon, M.J.; Robinson, T.E.; Warburton, D.; Deutsch, G.H.; Young, L.R. Approaching Clinical Trials in Childhood Interstitial Lung Disease and Pediatric Pulmonary Fibrosis. Am. J. Respir. Crit. Care Med. 2019, 200, 1219–1227. [Google Scholar] [CrossRef] [PubMed]
- Witt, S.; Szentes, B.; Bush, A.; Cunningham, S.; Kiper, N.; Lange, J.; Leidl, R.; Terheggen-Lagro, S.; Schwerk, N.; Snijders, D.; et al. Medication for childhood interstitial lung diseases differs internationally. Eur. Respir. J. 2018, 52 (Suppl. 62). Available online: https://erj.ersjournals.com/content/52/suppl_62/PA634 (accessed on 26 October 2020).
- Avital, A.; Hevroni, A.; Godfrey, S.; Cohen, S.; Maayan, C.; Nusair, S.; Nogee, L.M.; Springer, C. Natural history of five children with surfactant protein C mutations and interstitial lung disease. Pediatric Pulmonol. 2014, 49, 1097–1105. [Google Scholar] [CrossRef]
- Williamson, M.; Wallis, C. Ten-year follow up of hydroxychloroquine treatment for ABCA3 deficiency. Pediatric Pulmonol. 2014, 49, 299–301. [Google Scholar] [CrossRef]
- Griese, M.; Köhler, M.; Witt, S.; Sebah, D.; Kappler, M.; Wetzke, M.; Schwerk, N.; Emiralioglu, N.; Kiper, N.; Kronfeld, K.; et al. Prospective evaluation of hydroxychloroquine in pediatric interstitial lung diseases: Study protocol for an investigator-initiated, randomized controlled, parallel-group clinical trial. Trials 2020, 21, 307. [Google Scholar] [CrossRef] [Green Version]
- Hetzel, M.; Suzuki, T.; Hashtchin, A.R.; Arumugam, P.; Carey, B.; Schwabbauer, M.; Kuhn, A.; Meyer, J.; Schambach, A.; Van Der Loo, J.; et al. Function and Safety of Lentivirus-Mediated Gene Transfer for CSF2RA-Deficiency. Hum. Gene Ther. Methods. 2017, 28, 318–329. [Google Scholar] [CrossRef]
- Aneja, M.K.; Rudolph, C. Gene therapy of surfactant protein B deficiency. Curr. Opin. Mol. Ther. 2006, 8, 432–438. [Google Scholar]
- Mucci, A.; Lopez-Rodriguez, E.; Hetzel, M.; Liu, S.; Suzuki, T.; Happle, C.; Ackermann, M.; Kempf, H.; Hillje, R.; Kunkiel, J.; et al. iPSC-Derived Macrophages Effectively Treat Pulmonary Alveolar Proteinosis in Csf2rb-Deficient Mice. Stem Cell Rep. 2018, 11, 696–710. [Google Scholar] [CrossRef] [Green Version]
- Nathan, N.; Sileo, C.; Thouvenin, G.; Berdah, L.; Delestrain, C.; Manali, E.; Papiris, S.; Léger, P.L.; Ducou le Pointe, H.; Coulomb l’Hermine, A.; et al. Pulmonary Fibrosis in Children. J. Clin. Med. 2019, 8, 1312. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ingelheim, B. A Double Blind, Randomised, Placebo-controlled Trial to Evaluate the Dose-exposure and Safety of Nintedanib Per os on Top of Standard of Care for 24 Weeks, Followed by Open Label Treatment With Nintedanib of Variable Duration, in Children and Adolescents (6 to 17 Year-old) With Clinically Significant Fibrosing Interstitial Lung Disease. clinicaltrials.gov; 2020 November. Report No.: NCT04093024. Available online: https://clinicaltrials.gov/ct2/show/NCT04093024 (accessed on 9 November 2020).
DISORDERS MORE PREVALENT IN INFANCY |
Diffuse developmental disorders:
|
Growth abnormalities:
|
Specific conditions of undefined aetiology:
|
Surfactant protein disorders |
DISORDERS RELATED TO SYSTEMIC DISEASE PROCESSES |
Disorders related to systemic disease:
|
Disorders of the normal host (presumed immune intact):
|
Host disorders (immunocompromised):
|
Disorders masquerading as ILD:
|
Lymphoproliferative disease:
|
Small airways disease:
|
Interstitial pneumonias unrelated to surfactant protein disorder:
|
Other patterns of diffuse lung disease:
|
Genetic Mutation | Inheritance | chILD |
---|---|---|
ABCA3 (ATP-binding cassette-family A-member 3) | Autosomal recessive | Surfactant protein disorder |
COPA (coatomer associated protein subunit alpha) | Autosomal dominant | General disorder, involving lung, joint, kidney |
CSF2RA (colony stimulating factor 2 receptor α) | X-linked | Pulmonary alveolar proteinosis |
CSF2RB (colony stimulating factor 2 receptor β) | Autosomal recessive | Pulmonary alveolar proteinosis |
FLNA (Filamin A) | X-linked recessive | General disorder, involving lung, cardiovascular system, osteo-articular system, coagulation |
FOXF1 (forkhead box F1) | Autosomal dominant | Diffuse developmental disorders, such as alveolar capillary dysplasia withmisalignment of the pulmonary veins |
GATA2 (GATA Binding Protein 2) | Autosomal dominant | Immunodeficiency 21 with pulmonary alveolar proteinosis |
MARS (metionil-transfer RNA sintetasi) | Autosomal recessive | Pulmonary alveolar proteinosis |
NKX2-1 (NK2 homeobox 1) | Autosomal dominant | Brain lung thyroid syndrome, characterized by congenital hypothyroidism, hypotonia, chorea, interstitial lung disease |
NSMCE3 (Non-structural maintenance of chromosomes element 3 homolog) | Autosomal recessive | Immunodeficiency |
OAS1 (oligoadenylate synthetase 1) | Autosomal dominant | Pulmonary alveolar proteinosis with hypogammaglobulinemia and splenomegaly |
SFTPB (Surfactant protein B deficiency) | Autosomal recessive | Surfactant protein disorder |
SFTPC (Surfactant protein C mutation) | Autosomal dominant | Surfactant protein disorder |
SLC7A7 (solute carrier family 7 member 7) | Autosomal recessive | Pulmonary alveolar proteinosis with lysinuric protein intolerance |
TBX4 (T-box transcription factor 4) | Autosomal dominant | Acinar dysplasia |
TMEM173 (transmembrane protein 173) | Autosomal dominant | Lung fibrosis with general inflammation |
chILD | Clinical Presentation and Prognosis | |
---|---|---|
Diffuse developmental disorders | Acinar dysplasia | Cyanosis at birth, survival only for few hours [24] |
Congenital alveolar dysplasia | Variable clinical presentation and prognosis [24] | |
Alveolar capillary dysplasia | Onset in first 24 h of life, death within days/weeks after presentation [25]. Less frequently onset during the first months of life [24]. | |
Growth abnormalities | Alveolar hypoplasia | Variable clinical presentation and prognosis |
Bronchodysplasia | Variable clinical presentation and prognosis | |
Related to chromosomal disorders | Variable clinical presentation and prognosis, related to the specific chromosomopathy | |
Related to congenital heart disease | Variable clinical presentation and prognosis, related to the specific congenital heart disease | |
Specific conditions of undefined aetiology | Neuroendocrine cell hyperplasia of infancy | Onset during the first months of life, variable symptoms thereafter; no deaths and no need of lung transplant described [26,27] |
Pulmonary interstitial glycogenosis | Onset immediately after birth. Good prognosis without severe comorbidities, but respiratory symptoms can persist into adolescence [28] | |
Surfactant protein disorder | SPFTB mutations | Neonatal onset with poor prognosis, even if rarely patients can survive longer [29] |
SPFTC mutations | Variable clinical presentation and prognosis [30] | |
ABCA3 mutations | Neonatal onset with poor prognosis (or, less frequently, presentation at an older age and longer survival) [31,32] |
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Ferraro, V.A.; Zanconato, S.; Zamunaro, A.; Carraro, S. Children’s Interstitial and Diffuse Lung Diseases (ChILD) in 2020. Children 2020, 7, 280. https://doi.org/10.3390/children7120280
Ferraro VA, Zanconato S, Zamunaro A, Carraro S. Children’s Interstitial and Diffuse Lung Diseases (ChILD) in 2020. Children. 2020; 7(12):280. https://doi.org/10.3390/children7120280
Chicago/Turabian StyleFerraro, Valentina Agnese, Stefania Zanconato, Andrea Zamunaro, and Silvia Carraro. 2020. "Children’s Interstitial and Diffuse Lung Diseases (ChILD) in 2020" Children 7, no. 12: 280. https://doi.org/10.3390/children7120280