T W Hoffman1, C H M van Moorsel2,3, K M Kazemier2,3,4, D H Biesma5, J C Grutters2,3, D A van Kessel2,3. 1. Department of Pulmonology, St. Antonius Hospital, Koekoekslaan 1, 3435CM, Nieuwegein, The Netherlands. t.hoffman@antoniusziekenhuis.nl. 2. Department of Pulmonology, St. Antonius Hospital, Koekoekslaan 1, 3435CM, Nieuwegein, The Netherlands. 3. Division of Heart and Lungs, University Medical Centre, Utrecht, The Netherlands. 4. Centre for Translational Immunology, University Medical Centre, Utrecht, The Netherlands. 5. Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, The Netherlands.
Abstract
PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease, in which inflammation is thought to only play a secondary role. Several factors associated with acute exacerbations of IPF (AE-IPF) have been identified, including infections. This study investigated whether humoral immunodeficiency or increased inflammatory markers at diagnosis were associated with AE-IPF and survival. METHODS: Four-hundred-and-nine patients diagnosed with IPF between 2011 and 2017 were retrospectively included. Immune status investigations at diagnosis included measurement of serum immunoglobulins (available in 38%), leukocyte and lymphocyte subsets in blood and bronchoalveolar lavage (BAL) fluid (available in 58%), as well as response to pneumococcal vaccination (available in 64%). RESULTS: Serum immunoglobulins or IgG subclass levels were below the lower limit of normal in 6%. The response to pneumococcal vaccination was severely impaired in 1%. Thirteen percent of patients developed an AE-IPF (4.7% per year). AE-IPF were associated with elevated lymphocytes in BAL fluid at diagnosis (p = 0.03). Higher serum IgA and IgG at diagnosis were associated with worse survival (p = 0.01; and p = 0.04), as were an increased BAL lymphocyte percentage (p = 0.005), and higher blood leukocytes and neutrophils (p = 0.01; and p = 0.0005). In a multivariate model, only BAL lymphocyte count retained statistical significance (p = 0.007). CONCLUSION: The prevalence of humoral immunodeficiencies was low in patients with IPF and not associated with AE-IPF or survival. Elevated lymphocytes in BAL were associated with the development of AE-IPF and worse survival. Higher serum immunoglobulins and immune cells in blood were also associated with worse survival. The local immune response in the lungs may be a target for future therapies.
PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease, in which inflammation is thought to only play a secondary role. Several factors associated with acute exacerbations of IPF (AE-IPF) have been identified, including infections. This study investigated whether humoral immunodeficiency or increased inflammatory markers at diagnosis were associated with AE-IPF and survival. METHODS: Four-hundred-and-nine patients diagnosed with IPF between 2011 and 2017 were retrospectively included. Immune status investigations at diagnosis included measurement of serum immunoglobulins (available in 38%), leukocyte and lymphocyte subsets in blood and bronchoalveolar lavage (BAL) fluid (available in 58%), as well as response to pneumococcal vaccination (available in 64%). RESULTS: Serum immunoglobulins or IgG subclass levels were below the lower limit of normal in 6%. The response to pneumococcal vaccination was severely impaired in 1%. Thirteen percent of patients developed an AE-IPF (4.7% per year). AE-IPF were associated with elevated lymphocytes in BAL fluid at diagnosis (p = 0.03). Higher serum IgA and IgG at diagnosis were associated with worse survival (p = 0.01; and p = 0.04), as were an increased BAL lymphocyte percentage (p = 0.005), and higher blood leukocytes and neutrophils (p = 0.01; and p = 0.0005). In a multivariate model, only BAL lymphocyte count retained statistical significance (p = 0.007). CONCLUSION: The prevalence of humoral immunodeficiencies was low in patients with IPF and not associated with AE-IPF or survival. Elevated lymphocytes in BAL were associated with the development of AE-IPF and worse survival. Higher serum immunoglobulins and immune cells in blood were also associated with worse survival. The local immune response in the lungs may be a target for future therapies.
Authors: L Ten Klooster; C H M van Moorsel; J M Kwakkel-van Erp; H van Velzen-Blad; J C Grutters Journal: Clin Exp Immunol Date: 2015-06-08 Impact factor: 4.330
Authors: David A Lynch; Nicola Sverzellati; William D Travis; Kevin K Brown; Thomas V Colby; Jeffrey R Galvin; Jonathan G Goldin; David M Hansell; Yoshikazu Inoue; Takeshi Johkoh; Andrew G Nicholson; Shandra L Knight; Suhail Raoof; Luca Richeldi; Christopher J Ryerson; Jay H Ryu; Athol U Wells Journal: Lancet Respir Med Date: 2017-11-15 Impact factor: 30.700
Authors: Ganesh Raghu; Kevin J Anstrom; Talmadge E King; Joseph A Lasky; Fernando J Martinez Journal: N Engl J Med Date: 2012-05-20 Impact factor: 91.245
Authors: Christa L Wagner; Vidya Sagar Hanumanthu; C Conover Talbot; Roshini S Abraham; David Hamm; Dustin L Gable; Christopher G Kanakry; Carolyn D Applegate; Janet Siliciano; J Brooks Jackson; Stephen Desiderio; Jonathan K Alder; Leo Luznik; Mary Armanios Journal: J Clin Invest Date: 2018-10-22 Impact factor: 14.808
Authors: Peter Heukels; Jennifer A C van Hulst; Menno van Nimwegen; Carian E Boorsma; Barbro N Melgert; Jan H von der Thusen; Bernt van den Blink; Rogier A S Hoek; Jelle R Miedema; Stefan F H Neys; Odilia B J Corneth; Rudi W Hendriks; Marlies S Wijsenbeek; Mirjam Kool Journal: Respir Res Date: 2019-10-24