The Role of Infection in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Abstract

Background Acute exacerbation of IPF (AE-IPF) is associated with high mortality. We studied changes in pathogen involvement during AE-IPF and explored a possible role of infection in AE-IPF. Objectives Our purpose is to investigate the role of infection in AE-IPF. Methods Overall, we recruited 170 IPF patients (48 AE-IPF, 122 stable) and 70 controls at Shanghai Pulmonary Hospital. Specific IgM against microbial pathogens and pathogens in sputum were assessed. RNA sequences of pathogens in nasopharyngeal swab of IPF patients were detected by PathChip. A panel of serum parameters reflecting immune function were assessed. Results Antiviral/bacterial IgM was higher in IPF vs. controls and in AE-IPF vs. stable IPF. Thirty-eight different bacterial strains were detected in IPF patient sputum. Bacteria-positive results were found in 9/48 (18.8%) of AE-IPF and in 26/122 (21.3%) stable IPF. Fifty-seven different viruses were detected in nasopharyngeal swabs of IPF patients. Virus-positive nasopharyngeal swabs were found in 18/30 (60%) of tested AE-IPF and in 13/30 (43.3%) of stable IPF. AE-IPF showed increased inflammatory cytokines (IL-6, IFN-γ, MIG, IL-17, and IL-9) vs. stable IPF and controls. Mortality of AE-IPF in one year (39.5%) was higher compared to stable IPF (28.7%).Conclusions. IPF patients had different colonization with pathogens in sputum and nasopharyngeal swabs; they also displayed abnormally activated immune response, which was exacerbated during AE-IPF.

“A Chain Only as Strong as Its Weakest Link”: An Up-to-Date Literature Review on the Bidirectional Interaction of Pulmonary Fibrosis and COVID-19

“… 31 Influenza A immune response was prominently related to the development of AE-IPF. 32 AE-IPF has also been reported after influenza A vaccination. 33 Moreover, enhanced fibrotic response, epithelial apoptosis, and fibrogenesis was described in the fibrotic lung infected with influenza A.…”

“… 9 IPF seems to be the most common ILD 10 and often misdiagnosed, 11 categorized as “life-threatening”, “under-diagnosed”, or “too little studied”—only to emphasize that it is an irreversible and progressive respiratory disease, with a rough incidence of 23.4/100 000, 12 and a median survival of 2–3 years after diagnosis. 13 , 14 The complicated and time-consuming diagnostic, 15 together with the few treatment options, make IPF comparable to many forms of cancer (in terms of survival and death rates). 16 …”

The contribution of infection and the respiratory microbiome in acute exacerbations of idiopathic pulmonary fibrosis

“…Having excluded infection clinically, a cohort of 37 IPF patients experiencing an exacerbation underwent surgical lung biopsy and over one-third exhibited evidence of viral infection based on immunohistochemistry or microarray [28]. More recently, viral sequences were profiled in nasopharyngeal swabs of 30 stable IPF and 30 AE-IPF patients which revealed higher virus-positive rates in the AE-IPF cohort (60%) compared to stable disease (43%) [29]. HHV was the most prominent virus in the AE-IPF group as well as influenza A [29].…”

“…More recently, viral sequences were profiled in nasopharyngeal swabs of 30 stable IPF and 30 AE-IPF patients which revealed higher virus-positive rates in the AE-IPF cohort (60%) compared to stable disease (43%) [29]. HHV was the most prominent virus in the AE-IPF group as well as influenza A [29]. As AE-IPF have been reported following influenza A vaccination, its presence suggests that cold-associated infection may potentially trigger these events [31].…”

“…More recently, WENG et al [29] have employed molecular techniques to examine sputum cultures of 170 patients experiencing an exacerbation. They detected 38 different bacterial strains with gram-negative bacteria accounting for 89% of pathogens: Klebsiella pneumonia (26%), Mycobacterium tuberculosis (21%), and Acinetobacter baumannii (10%) dominated the sputum samples [29]. Together these studies demonstrate that alterations in the respiratory microbiome occur during acute exacerbations but they do not provide any functional or mechanistic insights.…”