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Background Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis, nomogram model for its prognosis and acute exacerbation was constructed. Methods Two hundred and sixty eight patients with IPF were grouped with different severity according to fibrosis area, serum Club cell secretory protein 16(CC16) was compared between these groups. All patients were randomly divided into training and testing sets. COX regression and LASSO algorithm were used to screen featured characteristics. Then nomogram models were constructed, ROC curve, calibration curve and decision curve analysis(DCA) were conducted to evaluate the performance of model. Expression of CC16 were detected in fibrotic human lung tissues, bronchoalveolar lavage fluid (BALF) and Bleomycin(BLM)-treated mouse lung tissues and serums. Results Serum CC16 gradually increased with the severity of fibrosis, and was especially high in AE-IPF group. CC16 and diffusion capacity for carbon monoxide (DLCO) were screened as characteristic variables to construct nomogram model for IPF prognosis. The survival was significantly lower in high-risk group scored by the model. The area under ROC curves(AUCs) for 1-year and 2-year mortality prediction were 0.866 and 0.916, respectively. This model performed better than gender-age-physiology (GAP) index for predicting 2-year and 3-year mortality. Another nomogram model for acute exacerbation of IPF based on CC16, Krebs von den Lungen-6(KL-6) and DLCO was developed, the AUC was 0.815. Expression of CC16 obviously up-regulated in fibrotic lung tissues, BALF and BLM-treated mice lung tissues and serums. Conclusions The nomogram model based on CC16 performed good predictive ability for prognosis and acute exacerbation of IPF.

Objective To develop and validate a diagnosis model to inform risk stratified decisions for idiopathic pulmonary fibrosis patients experiencing acute exacerbations (AE-IPF). Methods In this retrospective cohort study performed from 1 January 2016 to 31 December 2022, we used data from the West China Hospital of Sichuan University for model development and validation. Blood test results and the underlying diseases of patients were collected through the HIS system and LIS system. An algorithm for filtering candidate variables based on least absolute shrinkage and selection operator (LASSO) regression. Logistic regression was performed to develop the risk model. Multiple imputation handled missing predictor data. Model performance was assessed through calibration and diagnostic odds ratio. Results 311 and 133 participants were included in the development and validation cohorts, respectively. 3 candidate predictors (29 parameters) were included. A logistic regression analysis revealed that dyspnea, percentage of CD4 +   T-lymphocytes, and percentage of monocytes are independent risk factors for AE-IPF. Nomographic model was constructed using these independent risk factors, and the C-index was 0.69. For internal validation, the C-index was 0.69, and that indicated good accuracy. Diagnostic odds ratio was 5.40. Meanwhile, in mild, moderate, and severe subgroups, AE positivity rates were 0.37, 0.47, and 0.81, respectively. The diagnostic model can classify patients with AE-IPF into different risk classes based on dyspnea, percentage of CD4 +   T-lymphocytes, and percentage of monocytes. Conclusion A diagnosis model was developed and validated that used information collected from HIS system and LIS system and may be used to risk stratify idiopathic pulmonary fibrosis patients experiencing acute exacerbations.

Glucocorticoid (GC) hormone has been commonly used to treat systemic inflammation and immune disorders. However, the side effects associated with long-term use of high-dose GC hormone limit its clinical application seriously. GC hormone that can specifically target the lung might decrease the effective dosage and thus reduce GC-associated side effects. In this study, we successfully prepared human lung-targeting liposomal methylprednisolone crosslinked with nanobody (MPS-NSSLs-SPANb). Our findings indicate that MPS-NSSLs-SPANb may reduce the effective therapeutic dosage of MPS, achieve better efficacy, and reduce GC-associated side effects. In addition, MPS-NSSLs-SPANb showed higher efficacy and lower toxicity than conventional MPS.

Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are the leading cause of mortality among patients with IPF. There is still a lack of effective treatments for AE-IPF, resulting in a hospitalization mortality rate as high as 70%–80%. To reveal the complicated mechanism of AE-IPF, more attention has been paid to its disturbed immune environment, as patients with IPF exhibit deficiencies in pathogen defense due to local immune dysregulation. During the development of AE-IPF, the classical stimulatory signals in adaptive immunity are inhibited, while the nonclassical immune reactions (Th17) are activated, attracting numerous neutrophils and monocytes to lung tissues. However, there is limited information about the specific changes in the immune response of AE-IPF. We summarized the immune mechanisms of AE-IPF in this review.

Background At present, there is short of effective treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). The treatment of IPF with traditional Chinese medicine (TCM) has some advantages. However, the evidence is unclear whether TCM can be recommended as an effective therapy to treat AE-IPF. The purpose of the study is to explore the efficacy and safety of TCM for patients with AE-IPF. Methods A randomized, double-blind, placebo-controlled, exploratory clinical trial will be performed. A total of 80 patients diagnosed with AE-IPF will be randomized into the intervention or control group. In addition to conventional treatment, the intervention group will be treated with Kangxianhuanji granule, and the control group will be given a placebo granule. The administration frequency is 10 g each time and two times daily. After 4 weeks of treatment, the patients were followed up for 12 weeks. The primary outcomes are treatment failure rate and all-cause mortality. Secondary outcome measures will include the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, Modified British Medical Research Council (mMRC) score, the St George’s Respiratory Questionnaire idiopathic pulmonary fibrosis (SGRQ-I) score, and arterial blood gas analysis. Discussion TCM may be beneficial in IPF. However, it has never been evaluated in patients with AE-IPF, who are incredibly prone to respiratory failure and have a high mortality rate. It is the first clinical trial to explore the efficacy and safety of TCM in the treatment of AE-IPF. This result will provide a basis for further study, which provides a high-quality evidence for the treatment of AE-IPF with TCM. Trial registration Chinese Clinical Trial Registry ChiCTR1900026289 . Registered on 29 September 2019.