title: Pulmonary manifestations in adult patients with chronic granulomatous disease.
abstract: Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by failure of superoxide production in phagocytic cells. The disease is characterised by recurrent infections and inflammatory events, frequently affecting the lungs. Improvement of life expectancy now allows most patients to reach adulthood. We aimed to describe the pattern of pulmonary manifestations occurring during adulthood in CGD patients. This was a retrospective study of the French national cohort of adult patients (≥16 years old) with CGD. Medical data were obtained for 67 adult patients. Pulmonary manifestations affected two-thirds of adult patients. Their incidence was significantly higher than in childhood (mean annual rate 0.22 versus 0.07, p=0.01). Infectious risk persisted despite anti-infectious prophylaxis. Invasive fungal infections were frequent (0.11 per year per patient) and asymptomatic in 37% of the cases. They often required lung biopsy for diagnosis (10 out of 30). Noninfectious respiratory events concerned 28% of adult patients, frequently associated with a concomitant fungal infection (40%). They were more frequent in patients with the X-linked form of CGD. Immune-modulator therapies were required in most cases (70%). Respiratory manifestations are major complications of CGD in adulthood. Noninfectious pulmonary manifestations are as deleterious as infectious pneumonia. A specific respiratory monitoring is necessary.
authors.affiliation: Service de Pneumologie, Hôpital Foch, Suresnes, France UPRES EA 220, Suresnes, France Faculté des Sciences de la Santé Simone Veil, Université Versailles-Saint-Quentin-en-Yvelines, Versailles, France h.salvator@hopital-foch.com.
authors.forename: Hélène
authors.initials: H
authors.lastname: Salvator
authors.affiliation: CEREDIH, Centre de Référence des Déficits Immunitaires Héréditaires, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France Service d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France INSERM UMR 1163, Paris, France.
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.affiliation: Service de Pneumologie, Hôpital Foch, Suresnes, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Catherinot
authors.affiliation: Service de Pneumologie, Hôpital Foch, Suresnes, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rivaud
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker Pasteur, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Pilmis
authors.affiliation: Service de Pneumologie A, Centre de Compétence Maladies Rares Pulmonaires, DHU FIRE, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France INSERM UMR 1152, Paris, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Borie
authors.affiliation: Service de Pneumologie A, Centre de Compétence Maladies Rares Pulmonaires, DHU FIRE, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France INSERM UMR 1152, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Crestani
authors.affiliation: Service de Pneumologie, Hôpital Foch, Suresnes, France UPRES EA 220, Suresnes, France Faculté des Sciences de la Santé Simone Veil, Université Versailles-Saint-Quentin-en-Yvelines, Versailles, France.
authors.forename: Colas
authors.initials: C
authors.lastname: Tcherakian
authors.affiliation: CEREDIH, Centre de Référence des Déficits Immunitaires Héréditaires, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France INSERM UMR 1163, Paris, France Service d'Hématologie Adulte, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.affiliation: Service de Médecine Interne, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dunogue
authors.affiliation: UF Dysfonctionnements Immunitaires, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France INSERM UMR 1149, Paris, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Gougerot-Pocidalo
authors.affiliation: UF Dysfonctionnements Immunitaires, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France INSERM UMR 1149, Paris, France.
authors.forename: Margarita
authors.initials: M
authors.lastname: Hurtado-Nedelec
authors.affiliation: Délégation pour la Recherche Clinique et l'Innovation, Hôpital Foch, Suresnes, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dreyfus
authors.affiliation: Service de Médecine Interne, Hospices Civils de Lyon, Groupe Hospitalier Sud, Université de Lyon, Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durieu
authors.affiliation: Service d'Hématologie et Oncologie pédiatrique, Centre Hospitalier Universitaire de Nancy, Nancy, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Fouyssac
authors.affiliation: CEREDIH, Centre de Référence des Déficits Immunitaires Héréditaires, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France INSERM UMR 1163, Paris, France Service d'Hématologie Adulte, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: CEREDIH, Centre de Référence des Déficits Immunitaires Héréditaires, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France INSERM UMR 1163, Paris, France Service des Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker Pasteur, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.affiliation: CEREDIH, Centre de Référence des Déficits Immunitaires Héréditaires, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France Service d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France INSERM UMR 1163, Paris, France Collège de France, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Service de Pneumologie, Hôpital Foch, Suresnes, France UPRES EA 220, Suresnes, France Faculté des Sciences de la Santé Simone Veil, Université Versailles-Saint-Quentin-en-Yvelines, Versailles, France.
authors.forename: Louis-Jean
authors.initials: LJ
authors.lastname: Couderc
mesh_terms: D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use; D058070:Asymptomatic Diseases; D001706:Biopsy; D015331:Cohort Studies; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D008168:Lung / Q000473:pathology*; D008171:Lung Diseases / Q000209:etiology; D008172:Lung Diseases, Fungal / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics; D018410:Pneumonia, Bacterial / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human; C527764:NCF2 protein, human; C060505:neutrophil cytosolic factor 1