Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an often deadly complication of IPF. No focussed international guidelines for the management of AE-IPF exist. The aim of this international survey was to assess the global variability in prevention, diagnostic and treatment strategies for AE-IPF.Pulmonologists with ILD expertise were invited to participate in a survey designed by an international expert panel.509 pulmonologists from 66 countries responded. Significant geographical variability in approaches to manage AE-IPF was found. Common preventive measures included antifibrotic drugs and vaccination. Diagnostic differences were most pronounced regarding use of Krebs von den Lungen-6 and viral testing, while high-resolution computed tomography, brain natriuretic peptide and D-dimer are generally applied. High-dose steroids are widely administered (94%); the use of other immunosuppressant and treatment strategies is highly variable. Very few (4%) responders never use immunosuppression. Antifibrotic treatments are initiated during AE-IPF by 67%. Invasive ventilation or extracorporeal membrane oxygenation are mainly used as a bridge to transplantation. Most physicians educate patients comprehensively on the severity of AE-IPF (82%) and consider palliative care (64%).Approaches to the prevention, diagnosis and treatment of AE-IPF vary worldwide. Global trials and guidelines to improve the prognosis of AE-IPF are needed.

BackgroundInterstitial lung diseases (ILDs) are associated with a high burden of disease. However, data on the prognostic impact of comorbidities and comorbidity-related pharmaceutical treatments in patients with various ILDs remain sparse.MethodsUsing longitudinal claims data from a German Statutory Health Insurance Fund, we assessed comorbidity in ILD subtypes and associated drug treatments. Baseline comorbidity was assessed via the Elixhauser Comorbidity Index that was amended by ILD-relevant conditions. Drug treatment was assessed on the substance level using the ATC-codes of drugs prescribed at the time of ILD diagnosis. Subsequently, the comorbid conditions (main analysis) and pharmaceutical substances (secondary analysis) with a meaningful association to survival were identified for the complete ILD cohort and within the subtype strata. For this, we applied multivariate Cox models using a LASSO selection process and visualized the findings within comorbidomes.ResultsIn the 36,821 patients with ILDs, chronic obstructive pulmonary disease (COPD), arterial hypertension, and ischaemic heart disease (IHD) were the most prevalent comorbidities. The majority of patients with cardiovascular diseases received pharmaceutical treatment, while, in other relevant comorbidities, treatment quotas were low (COPD 46%, gastro-oesophageal reflux disease 65%). Comorbidities had a clinically meaningful detrimental effect on survival that tended to be more pronounced in the case of untreated conditions (e.g. hazard ratios for treated IHD 0.97 vs. 1.33 for untreated IHD). Moreover, comorbidity impact varied substantially between distinct subtypes.ConclusionsOur analyses suggest that comorbid conditions and their treatment profile significantly affect mortality in various ILDs. Therefore, comprehensive comorbidity assessment and management remains important in any ILD.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0769-0) contains supplementary material, which is available to authorized users.

Chronic diseases of the respiratory tract, such as cystic fibrosis, are associated with mucosal and systemic hypoxia. Innate immune functions of airway epithelial cells are required to prevent and control infections of the lung parenchyma. The transcription factor hypoxia-inducible factor 1a (HIF-1a) regulates cellular adaptation to low oxygen conditions. Here, we show that hypoxia and HIF-1a regulate innate immune mechanisms of cultured human bronchial epithelial cells (HBECs). Exposure of primary HBECs to hypoxia or the prolyl hydroxylase inhibitor dimethyloxaloylglycine (DMOG) resulted in a significantly decreased expression of inflammatory mediators (IL-6, IFN-g-induced protein 10) in response to ligands for TLRs (flagellin, polyI:C) and Pseudomonas aeruginosa, whereas the expression of inflammatory mediators was not affected by hypoxia or DMOG in the absence of microbial factors. Small interfering RNA-mediated knockdown of HIF-1a in HBECs and in the bronchial epithelial cell line Calu-3 resulted in increased expression of inflammatory mediators. The inflammatory response was decreased in lungs of mice stimulated with inactivated P. aeruginosa under hypoxia. These data suggest that hypoxia suppresses the innate immune response of airway epithelial cells via HIF-1a.

Background: Interstitial lung diseases (ILDs) are associated with a high burden of disease. However, data on the prognostic impact of comorbidities and comorbidity-related pharmaceutical treatments in patients with various ILDs remain sparse. Methods: Using longitudinal claims data from a German Statutory Health Insurance Fund, we assessed comorbidity in ILD subtypes and associated drug treatments. Baseline comorbidity was assessed via the Elixhauser Comorbidity Index that was amended by ILD-relevant conditions. Drug treatment was assessed on the substance level using the ATC-codes of drugs prescribed at the time of ILD diagnosis. Subsequently, the comorbid conditions (main analysis) and pharmaceutical substances (secondary analysis) with a meaningful association to survival were identified for the complete ILD cohort and within the subtype strata. For this, we applied multivariate Cox models using a LASSO selection process and visualized the findings within comorbidomes. Results: In the 36,821 patients with ILDs, chronic obstructive pulmonary disease (COPD), arterial hypertension, and ischaemic heart disease (IHD) were the most prevalent comorbidities. The majority of patients with cardiovascular diseases received pharmaceutical treatment, while, in other relevant comorbidities, treatment quotas were low (COPD 46%, gastro-oesophageal reflux disease 65%). Comorbidities had a clinically meaningful detrimental effect on survival that tended to be more pronounced in the case of untreated conditions (e.g. hazard ratios for treated IHD 0.97 vs. 1.33 for untreated IHD). Moreover, comorbidity impact varied substantially between distinct subtypes. Conclusions: Our analyses suggest that comorbid conditions and their treatment profile significantly affect mortality in various ILDs. Therefore, comprehensive comorbidity assessment and management remains important in any ILD.