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Characteristics of disorders associated with genetic mutations of surfactant protein C

Identifieur interne : 001648 ( Main/Exploration ); précédent : 001647; suivant : 001649

Characteristics of disorders associated with genetic mutations of surfactant protein C

Auteurs : Guillaume Thouvenin [France] ; Rola Abou Taam [France] ; Florence Flamein [France] ; Loïc Guillot [France] ; Muriel Le Bourgeois [France] ; Philippe Reix [France] ; Mickael Fayon [France] ; François Counil [France] ; Ulrika Depontbriand [France] ; Delphine Feldmann [France] ; Hubert Ducou-Le Pointe [France] ; Jacques De Blic [France] ; Annick Clement [France] ; Ralph Epaud [France]

Source :

RBID : ISTEX:9FAD17A85849C5EF44A5232B0F25376E4361956E

Descripteurs français

English descriptors

Abstract

Study objectives To present diagnosis and treatment modalities of children with interstitial lung disease associated with frequent or rare surfactant protein C gene (SFTPC) mutation. Patients Twenty-two children with chronic lung disease associated with SFTPC mutation in a heterozygous form. Results Mutations located in the BRICHOS domain (‘BRICHOS domain’ group) were identified in six children, whereas 16 children carried mutations located outside the BRICHOS domain (‘non-BRICHOS domain’ group). The median age of onset was 3 (0–24) months. Four patients had neonatal respiratory distress, and symptom onset was associated with acute bronchiolitis in nine patients. Cough, tachypnoea and failure to thrive were initially noticed in all the children. Physical examination at presentation revealed tachypnoea (n=22), clubbing (n=1) and crackles (n=5). Low oxygen saturation (<95%) was observed in 18 patients. The predominant findings on initial high-resolution CT (HRCT) scans were basal-predominant ground-glass opacity (n=21) and cystic spaces (n=3). Bronchoalveolar lavage fluid (BALF) cell counts showed 379±56×103 cells/ml with increased neutrophil percentage (18±4%) independent of the mutation status. The median follow-up was 3.2 (1–18.3) years. Eighteen patients were treated by monthly methylprednisolone pulses associated with oral prednisolone (n=16), hydroxychloroquine (n=11) and/or azithromycin (n=4). Fifteen patients benefited from enteral nutrition. Conclusion Initial diagnosis is based on clinical presentation, radiological features and BALF analysis, but the definitive diagnosis requires genetic analysis. Although progressive improvement was seen in most patients, the development of new therapeutic strategies with minimal side effects is needed.

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DOI: 10.1136/adc.2009.171553


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Le document en format XML

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<term>Pneumopathies interstitielles</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Lung Diseases, Interstitial</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Pneumopathies interstitielles</term>
</keywords>
<keywords scheme="MESH" qualifier="therapy" xml:lang="en">
<term>Lung Diseases, Interstitial</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr">
<term>Glucocorticoïdes</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Agent surface</term>
<term>Association</term>
<term>Caractéristiques</term>
<term>Coagulopathie</term>
<term>Enfant</term>
<term>Génétique</term>
<term>Pédiatrie</term>
<term>Santé publique</term>
<term>Surfactant pulmonaire</term>
</keywords>
<keywords scheme="Teeft" xml:lang="en">
<term>Acute bronchiolitis</term>
<term>Adenomatoid malformation</term>
<term>Age of Onset</term>
<term>Alveolar type</term>
<term>Armand trousseau</term>
<term>Azithromycin</term>
<term>Balf</term>
<term>Balf analysis</term>
<term>Biol</term>
<term>Brichos</term>
<term>Brichos domain</term>
<term>Brichos domain group</term>
<term>Bril formation</term>
<term>Bronchoalveolar</term>
<term>Bronchoalveolar lavage</term>
<term>Bronchoscopy</term>
<term>Centre hospitalier universitaire</term>
<term>Clinical presentation</term>
<term>Common mutation</term>
<term>Constant ndings</term>
<term>Control scan</term>
<term>Different treatments</term>
<term>Diffuse lung disease</term>
<term>Domain</term>
<term>Domain brichos domain</term>
<term>Domain group</term>
<term>Enteral nutrition</term>
<term>Exercise intolerance</term>
<term>Female</term>
<term>Gastrointestinal symptoms</term>
<term>General anaesthesia</term>
<term>Genetic mutations</term>
<term>Hrct</term>
<term>Hrct scan</term>
<term>Humans</term>
<term>Hydroxychloroquine</term>
<term>Infant</term>
<term>Infant, Newborn</term>
<term>Interstitial lung disease</term>
<term>Lung biopsy</term>
<term>Lung disease</term>
<term>Lung disorders</term>
<term>Lung surfactant protein</term>
<term>Male</term>
<term>Methylprednisolone</term>
<term>Methylprednisolone pulse</term>
<term>Mutation</term>
<term>Mutation status</term>
<term>Ndings</term>
<term>Neutrophil percentage</term>
<term>Nogee</term>
<term>Nonbrichos domain</term>
<term>Nutritional support</term>
<term>Oral steroids</term>
<term>Oxygen Inhalation Therapy</term>
<term>Oxygen saturation</term>
<term>Patients patients</term>
<term>Physical examination</term>
<term>Physiol</term>
<term>Physiol lung cell</term>
<term>Present study</term>
<term>Radiological features</term>
<term>Recombinant antihuman</term>
<term>Respir</term>
<term>Respir cell</term>
<term>Respir crit care</term>
<term>Respiratory distress</term>
<term>Respiratory symptoms</term>
<term>Sftpc</term>
<term>Sftpc disorders</term>
<term>Sftpc mutation</term>
<term>Sftpc mutations</term>
<term>Sporadic cases</term>
<term>Steroid</term>
<term>Supplemental oxygen</term>
<term>Surfactant</term>
<term>Surfactant homeostasis</term>
<term>Surfactant protein</term>
<term>Surfactant proteins</term>
<term>Symptom onset</term>
<term>Tachypnoea</term>
<term>Tomography, X-Ray Computed</term>
<term>Treatment Outcome</term>
<term>Treatment modalities</term>
<term>Viral infection</term>
<term>Viral infection prophylaxis</term>
<term>Western blot analysis</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Bronchoscopie</term>
<term>Femelle</term>
<term>Humains</term>
<term>Liquide de lavage bronchoalvéolaire</term>
<term>Mutation</term>
<term>Mâle</term>
<term>Nourrisson</term>
<term>Nouveau-né</term>
<term>Oxygénothérapie</term>
<term>Pneumopathies interstitielles</term>
<term>Résultat thérapeutique</term>
<term>Tomodensitométrie</term>
<term>Âge de début</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Association</term>
<term>Enfant</term>
<term>Génétique</term>
<term>Pédiatrie</term>
<term>Santé publique</term>
</keywords>
</textClass>
<langUsage>
<language ident="en">en</language>
</langUsage>
</profileDesc>
</teiHeader>
<front>
<div type="abstract">Study objectives To present diagnosis and treatment modalities of children with interstitial lung disease associated with frequent or rare surfactant protein C gene (SFTPC) mutation. Patients Twenty-two children with chronic lung disease associated with SFTPC mutation in a heterozygous form. Results Mutations located in the BRICHOS domain (‘BRICHOS domain’ group) were identified in six children, whereas 16 children carried mutations located outside the BRICHOS domain (‘non-BRICHOS domain’ group). The median age of onset was 3 (0–24) months. Four patients had neonatal respiratory distress, and symptom onset was associated with acute bronchiolitis in nine patients. Cough, tachypnoea and failure to thrive were initially noticed in all the children. Physical examination at presentation revealed tachypnoea (n=22), clubbing (n=1) and crackles (n=5). Low oxygen saturation (<95%) was observed in 18 patients. The predominant findings on initial high-resolution CT (HRCT) scans were basal-predominant ground-glass opacity (n=21) and cystic spaces (n=3). Bronchoalveolar lavage fluid (BALF) cell counts showed 379±56×103 cells/ml with increased neutrophil percentage (18±4%) independent of the mutation status. The median follow-up was 3.2 (1–18.3) years. Eighteen patients were treated by monthly methylprednisolone pulses associated with oral prednisolone (n=16), hydroxychloroquine (n=11) and/or azithromycin (n=4). Fifteen patients benefited from enteral nutrition. Conclusion Initial diagnosis is based on clinical presentation, radiological features and BALF analysis, but the definitive diagnosis requires genetic analysis. Although progressive improvement was seen in most patients, the development of new therapeutic strategies with minimal side effects is needed.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>France</li>
</country>
<region>
<li>Aquitaine</li>
<li>Auvergne-Rhône-Alpes</li>
<li>Languedoc-Roussillon</li>
<li>Nouvelle-Aquitaine</li>
<li>Occitanie (région administrative)</li>
<li>Pays de la Loire</li>
<li>Rhône-Alpes</li>
<li>Île-de-France</li>
</region>
<settlement>
<li>Bordeaux</li>
<li>Lyon</li>
<li>Montpellier</li>
<li>Nantes</li>
<li>Paris</li>
</settlement>
<orgName>
<li>Université Paris-Descartes</li>
</orgName>
</list>
<tree>
<country name="France">
<region name="Île-de-France">
<name sortKey="Thouvenin, Guillaume" sort="Thouvenin, Guillaume" uniqKey="Thouvenin G" first="Guillaume" last="Thouvenin">Guillaume Thouvenin</name>
</region>
<name sortKey="Clement, Annick" sort="Clement, Annick" uniqKey="Clement A" first="Annick" last="Clement">Annick Clement</name>
<name sortKey="Clement, Annick" sort="Clement, Annick" uniqKey="Clement A" first="Annick" last="Clement">Annick Clement</name>
<name sortKey="Clement, Annick" sort="Clement, Annick" uniqKey="Clement A" first="Annick" last="Clement">Annick Clement</name>
<name sortKey="Counil, Francois" sort="Counil, Francois" uniqKey="Counil F" first="François" last="Counil">François Counil</name>
<name sortKey="De Blic, Jacques" sort="De Blic, Jacques" uniqKey="De Blic J" first="Jacques" last="De Blic">Jacques De Blic</name>
<name sortKey="De Blic, Jacques" sort="De Blic, Jacques" uniqKey="De Blic J" first="Jacques" last="De Blic">Jacques De Blic</name>
<name sortKey="Depontbriand, Ulrika" sort="Depontbriand, Ulrika" uniqKey="Depontbriand U" first="Ulrika" last="Depontbriand">Ulrika Depontbriand</name>
<name sortKey="Epaud, Ralph" sort="Epaud, Ralph" uniqKey="Epaud R" first="Ralph" last="Epaud">Ralph Epaud</name>
<name sortKey="Epaud, Ralph" sort="Epaud, Ralph" uniqKey="Epaud R" first="Ralph" last="Epaud">Ralph Epaud</name>
<name sortKey="Epaud, Ralph" sort="Epaud, Ralph" uniqKey="Epaud R" first="Ralph" last="Epaud">Ralph Epaud</name>
<name sortKey="Fayon, Mickael" sort="Fayon, Mickael" uniqKey="Fayon M" first="Mickael" last="Fayon">Mickael Fayon</name>
<name sortKey="Feldmann, Delphine" sort="Feldmann, Delphine" uniqKey="Feldmann D" first="Delphine" last="Feldmann">Delphine Feldmann</name>
<name sortKey="Flamein, Florence" sort="Flamein, Florence" uniqKey="Flamein F" first="Florence" last="Flamein">Florence Flamein</name>
<name sortKey="Flamein, Florence" sort="Flamein, Florence" uniqKey="Flamein F" first="Florence" last="Flamein">Florence Flamein</name>
<name sortKey="Guillot, Loic" sort="Guillot, Loic" uniqKey="Guillot L" first="Loïc" last="Guillot">Loïc Guillot</name>
<name sortKey="Guillot, Loic" sort="Guillot, Loic" uniqKey="Guillot L" first="Loïc" last="Guillot">Loïc Guillot</name>
<name sortKey="Le Bourgeois, Muriel" sort="Le Bourgeois, Muriel" uniqKey="Le Bourgeois M" first="Muriel" last="Le Bourgeois">Muriel Le Bourgeois</name>
<name sortKey="Le Bourgeois, Muriel" sort="Le Bourgeois, Muriel" uniqKey="Le Bourgeois M" first="Muriel" last="Le Bourgeois">Muriel Le Bourgeois</name>
<name sortKey="Pointe, Hubert Ducou Le" sort="Pointe, Hubert Ducou Le" uniqKey="Pointe H" first="Hubert Ducou-Le" last="Pointe">Hubert Ducou-Le Pointe</name>
<name sortKey="Reix, Philippe" sort="Reix, Philippe" uniqKey="Reix P" first="Philippe" last="Reix">Philippe Reix</name>
<name sortKey="Taam, Rola Abou" sort="Taam, Rola Abou" uniqKey="Taam R" first="Rola Abou" last="Taam">Rola Abou Taam</name>
<name sortKey="Taam, Rola Abou" sort="Taam, Rola Abou" uniqKey="Taam R" first="Rola Abou" last="Taam">Rola Abou Taam</name>
<name sortKey="Thouvenin, Guillaume" sort="Thouvenin, Guillaume" uniqKey="Thouvenin G" first="Guillaume" last="Thouvenin">Guillaume Thouvenin</name>
<name sortKey="Thouvenin, Guillaume" sort="Thouvenin, Guillaume" uniqKey="Thouvenin G" first="Guillaume" last="Thouvenin">Guillaume Thouvenin</name>
</country>
</tree>
</affiliations>
</record>

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