Editorial
Childhood Interstitial Lung Diseases (chILD) Recognition: When Epidemiology Increases a Rare Disease Incidence
Reconocimiento de la enfermedad pulmonar intersticial en niños (chILD): cuando la epidemiología aumenta la incidencia de una enfermedad rara
Nadia Nathan
Sorbonne Université, Pediatric Pulmonology Department and Reference Center for Rare Lung Disease RespiRare, Laboratory of Childhood Genetic Diseases, Assistance Publique Hôpitaux de Paris and Inserm UMR S933, Armand Trousseau Hospital, Paris 75012, France
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Soriano, José Ramón Villagrasa, Julio Ancochea" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Joan B." "apellidos" => "Soriano" ] 1 => array:2 [ "nombre" => "José Ramón" "apellidos" => "Villagrasa" ] 2 => array:2 [ "nombre" => "Julio" "apellidos" => "Ancochea" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289621004178?idApp=UINPBA00003Z" "url" => "/03002896/0000005800000003/v2_202210210711/S0300289621004178/v2_202210210711/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Childhood Interstitial Lung Diseases (chILD) Recognition: When Epidemiology Increases a Rare Disease Incidence" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "217" "paginaFinal" => "218" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Nadia Nathan" "autores" => array:1 [ 0 => array:3 [ "nombre" => "Nadia" "apellidos" => "Nathan" "email" => array:1 [ 0 => "nadia.nathan@aphp.fr" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Sorbonne Université, Pediatric Pulmonology Department and Reference Center for Rare Lung Disease RespiRare, Laboratory of Childhood Genetic Diseases, Assistance Publique Hôpitaux de Paris and Inserm UMR S933, Armand Trousseau Hospital, Paris 75012, France" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Reconocimiento de la enfermedad pulmonar intersticial en niños (chILD): cuando la epidemiología aumenta la incidencia de una enfermedad rara" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Rare diseases have always been a challenge for clinicians and researchers: how could it be possible to study and understand a disease when each center sees so few patients? During the last decade, rare diseases networks have importantly increased the connections between the centers, at a national but also at an international level, allowing to collect the cases and to initiate large epidemiologic studies as the one provided by Torrent-Vernetta et al. in the previous issue of this journal.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Childhood interstitial lung diseases (chILD) is even more a challenge than other rare lung diseases, as it is an umbrella term for a multiplicity of exceptional disorders. Even if they share a common designation of their radiologic patterns under the name “interstitial signs”, the etiologies of chILD and consequently their clinical presentation, management and prognosis are highly variable, from newborns to teenagers, from pauci-symptomatic to fatal diseases and from supportive care to lung transplantation.</p><p id="par0015" class="elsevierStylePara elsevierViewall">This heterogeneity is illustrated by the complexity of chILDs classification. A couple years ago, chILD were classified according to their histologic aspect, as in adult ILD. However, it became quickly obvious that the pathologic pattern of a congenital alveolar dysplasia, or even of a surfactant disorder did not fit inside the items used in adults such as usual interstitial pneumonia/non-specific interstitial pneumonia/desquamative interstitial pneumonia classification. Thus, pediatric classifications have been proposed over time to include specific pediatric ILD conditions. Almost all of them distinguished two age groups: chILD of infancy (or <2 years-old) and chILD of children older than 2 years-old. To date, many classifications have been proposed by pathologists or clinicians, but the most used classifications are still those provided in the US and in Europe by Kurland et al. in 2013 and Griese et al. in 2015.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">These efforts in classifying the diseases constituted the first necessary step of a chILD recognition and of a better understanding of each entity's pathophysiology. Progressively, this led to the descriptions of the first national chILD epidemiological studies (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">In Europe, networks for chILD have been set up since 2013, allowing close collaborations between expert clinicians and researchers of the involved countries, and promoting joints efforts to “put the orphanage out of business”.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> More than 25 countries including non-European countries are currently participating in this chILD-EU network, within various programs that were funded between 2013 and 2021 by the European Union. Today, the “Clinical Research Collaboration for chILDEU” funded by the ERS since 2016 and the European Rare diseases Network (ERN)-lung represent important organizations for the chILD networks.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Between 2013 and 2019 the “chILD better together – European management Plateform for Childhood Interstitial Lung Disease” funded by the FP7 program has allowed to create the kids lung register, first multi-country register for chILD that included in 2021 more than 750 patients with reviewed chILD conditions from 179 centers all over Europe.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">5</span></a> However, collecting all the incidental cases of chILD is very difficult and chILD's incidence and prevalence remain highly underestimated, due to the lack of systematized reporting process and the high neonatal mortality.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The article provided by Torrent-Vernetta et al. constitutes a new major stone to the chILD building.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">1</span></a> Since the beginning of the chILD networks, Spain has been an active European member and Spanish authors has largely contributed to describing and better understanding rare chILD. With an elegant prospective methodology on a 2-years period, the major strength of this study is its national recruitment that is very close to a complete population screening. A number of chILD diagnoses is reported herein in 381 patients aged 0–18 years. Interestingly, this very exhaustive study evaluates the chILD's incidence as 8.18 cases/million of children per year, which is much higher than previously suggested (1.32/million in Germany). The prevalence follows the same trend with a prevalence of 46.53 cases/million of children that is also much higher than previously reported (3.6/million in UK and Ireland, 1.5 cases/million in Australasia).<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">5–7</span></a> This increased prevalence may be due to a better collection of the cases, but also to an improvement in chILD management over time. The authors also confirm an infant predominance at disease onset (60% of the cases) despite the absence of recorded case of diffuse developmental disorder during the study period.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Importantly, this study also highlights that at least 12% of chILD are related to a genetic disease with identified mutations in surfactant related genes, multisystemic and auto-inflammatory disorders genes, storage diseases genes and congenital immunodeficiency genes. This large panel of molecular etiologies of chILD points out the importance of a genetic screening as part of the initial diagnosis work-up.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> Molecular panels using next generation sequencing technics or whole exome sequencing are now available in many countries and it is possible that in the coming years, it could replace lung biopsy as gold standard for the diagnosis of chILD.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Epidemiologic studies on chILD are reported – and mostly red - by pediatricians. However, with the improvement of chILD management, most of these children will reach adulthood and will be followed in adult pulmonology departments. Adult pulmonologists are not yet prepared to receive these new patients with unknown diseases evolving since a very young age, with specific cares and potential long-term side effects of the treatments.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">9</span></a> A better collaboration between pediatricians and adult pulmonologists is a crucial step for ensuring a smooth transition of care between the teams, for the patients, but also for the parents and the caregivers.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">10</span></a> The recently launched ERS statement on Transition of pediatric patients with ILD to the adult care (Task Force number TF-2021-14) includes pediatricians and adults to better prepare the patients to their adult ILD care.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Finally yet importantly, our next goal is providing personalized medicine to children with rare lung diseases. This usually needs to be able to identify the patients in their respective centers. With this challenging aim, the article provided by Torrent-Vernetta et al. should encourage all countries to collect chILD cases and to report them, eventually with longitudinal data, in order to create easily accessible data for each etiology of chILD.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Country/areas \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of patients \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Period of time \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comments \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Reference \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UK and Ireland \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dinwiddie et al. Ped Pulm 2002.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BPOLD registry \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Laverty et al. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 14 | 1 | 15 |
| 2024 October | 75 | 36 | 111 |
| 2024 September | 86 | 37 | 123 |
| 2024 August | 92 | 43 | 135 |
| 2024 July | 89 | 38 | 127 |
| 2024 June | 82 | 30 | 112 |
| 2024 May | 68 | 43 | 111 |
| 2024 April | 59 | 34 | 93 |
| 2024 March | 47 | 27 | 74 |
| 2024 February | 45 | 28 | 73 |
| 2024 January | 43 | 23 | 66 |
| 2023 December | 55 | 23 | 78 |
| 2023 November | 84 | 24 | 108 |
| 2023 October | 91 | 39 | 130 |
| 2023 September | 87 | 42 | 129 |
| 2023 August | 76 | 46 | 122 |
| 2023 July | 67 | 39 | 106 |
| 2023 June | 53 | 28 | 81 |
| 2023 May | 66 | 48 | 114 |
| 2023 April | 63 | 45 | 108 |
| 2023 March | 134 | 61 | 195 |
| 2023 February | 79 | 23 | 102 |
| 2023 January | 52 | 45 | 97 |
| 2022 December | 86 | 36 | 122 |
| 2022 November | 95 | 56 | 151 |
| 2022 October | 68 | 48 | 116 |
| 2022 September | 67 | 40 | 107 |
| 2022 August | 80 | 43 | 123 |
| 2022 July | 87 | 59 | 146 |
| 2022 June | 73 | 72 | 145 |
| 2022 May | 88 | 45 | 133 |
| 2022 April | 371 | 107 | 478 |
| 2022 March | 139 | 43 | 182 |
| 2022 February | 2 | 2 | 4 |
Show all
