title: Interstitial lung disease with multiple microgranulomas in chronic granulomatous disease.
abstract: BACKGROUND
  Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that is characterized by susceptibility to bacterial and fungal infections. CGD patients also suffer from immune regulatory disorders, such as CGD-associated bowel inflammation with granuloma, which could be caused by excessive inflammation without demonstrable infection.
  
  
  OBJECTIVE
  We investigated the clinical manifestation of interstitial lung disease (ILD) resulting from excessive inflammation in X-linked CGD patients.
  
  
  METHODS
  Pulmonary CT images and testing of serum KL-6 levels were performed to assess ILD in the patients. For this study, patients with pulmonary lesions due to demonstrable infections were excluded from among ILD patients.
  
  
  RESULTS
  Among 33 CGD patients, four developed ILD; they had increased reticulo-nodular opacities on CT images and elevated serum KL-6 levels. Histopathological examinations revealed multiple homogeneous microgranulomas in the lesions of inflammatory cell infiltration. Mononuclear cells obtained from their pulmonary lesions produced higher amounts of inflammatory cytokines than the peripheral blood mononuclear cells of CGD patients, suggesting that the only infiltrating cells in the pulmonary lesions were activated and produced large amounts of inflammatory cytokines in ILD patients. Interestingly, an anti-inflammatory drug, such as a corticosteroid or thalidomide, but not anti-bacterial or anti-fungal drugs, improved CT image findings and reduced their KL-6 levels.
  
  
  CONCLUSIONS
  CGD patients' daily exposures to inhaled antigens may induce excessive reactions with the production of inflammatory cytokines leading to the development of ILD with multiple microgranulomas, which could be due to an inadequate production of reactive oxygen species in CGD.
authors.affiliation: Department of Human Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan, kawai-t@ncchd.go.jp.
authors.forename: Toshinao
authors.initials: T
authors.lastname: Kawai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Midori
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nakazawa
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Goto
authors.forename: Toru
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Masataka
authors.initials: M
authors.lastname: Higuchi
authors.forename: Takanobu
authors.initials: T
authors.lastname: Maekawa
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Tamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagasaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hojo
authors.forename: Masafumi
authors.initials: M
authors.lastname: Onodera
mesh_terms: D017668:Age of Onset; D002648:Child; D006105:Granulomatous Disease, Chronic / Q000150:complications*; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000150:complications* / Q000473:pathology; D008297:Male; D018396:Mucin-1 / Q000097:blood; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1