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: Both a probable usual interstitial pneumonia (UIP) pattern (p-UIP) and a definite UIP pattern (d-UIP) on high-resolution computed tomography (HRCT) are sufficient to establish a diagnosis of idiopathic pulmonary fibrosis (IPF) without the need for a surgical lung biopsy, according to the 2022 IPF guidelines. However, it remains unknown whether patients with p-UIP and d-UIP have similar disease behaviors and clinical courses. Material and Methods: We retrospectively collected clinical data of patients with IPF and divided the patients into two groups according to their HRCT patterns: a p-UIP group and a d-UIP group. The baseline characteristics, survival rates, and pulmonary function tests were compared between the two groups. The risk factors for mortality were determined by Cox regression in p-UIP and d-UIP separately. Results: There were 304 patients in the p-UIP group and 480 patients in the d-UIP group. Patients in the d-UIP group were more likely to have smoking histories (p < 0.001) and had lower baseline FVC% (74% vs. 77%, p = 0.021) and DLCO% (50% vs. 58%, p < 0.001). Survival rates were higher in p-UIP compared with d-UIP (p = 0.004). There were no differences in changes in FVC% or DLCO% between the two groups. Baseline DLCO% was the only independent risk factor for mortality in p-UIP. Baseline FVC% was independently associated with mortality in d-UIP. Symptom of cough was a risk factor for disease progression (OR = 1.2, p = 0.002) in p-UIP, while symptom of dyspnea might be associated with disease progression in d-UIP (OR = 2.7, p = 0.065). Male patients (OR = 1.88, p = 0.002) with a smoking history (OR = 1.16, p = 0.002) were at higher risk of developing d-UIP. Conclusions: We observed the different disease trajectories between p-UIP and d-UIP. P-UIP on HRCT might identify a subgroup of IPF patients who are in the early stage with a better prognosis.

Background: In patients with fibrotic interstitial lung disease (ILD), a progressive pulmonary fibrosis (PPF) typically demonstrates worsening respiratory symptoms, lung function decline and continuing fibrosis. The goal of this study was to compare the three different diagnostic criteria of PPF. Methods: Except for idiopathic pulmonary fibrosis (IPF), all consecutive adult patients with fibrotic ILD were retrospectively examined for the three predefined diagnostic criteria of PPF. The three criteria assessed the disease progression in preceding 6 (0.5-year), 12 (1-year) and 24 (2-year) months respectively. The clinical characteristics, decline in predicted percent of forced vital capacity (FVC%) and survival of three groups were compared, followed by determination of risk factors for mortality. Results: We identified 246 patients by 0.5-year standard, 154 patients by 1-year standard and 281 patients by 2-year standard. Among them, 95% of patients in 1-year group were also included in 2-year group. The average 1-year decline in FVC% was −1.0%, −2.7%, and −4.1% for 0.5-, 1-, and 2-year group respectively. The 4-year survival rate was 74% in 0.5-year group, 66% in 1-year group, and 62% in 2-year group. In multivariate Cox model, only baseline predicted percent diffusing capacity of the lungs for carbon monoxide (DL_CO%) <50% was correlated with mortality, with a hazard ratio of 3.4 (95% CI: 1.1–10.6, P=0.03). Conclusions: In the current situations, both the 1- and 2-year criterion are the reasonable choice to define PPF both in researches and clinical practice, and DLCO% is an independent predictor for mortality of PPF.

Background and objective: In patients with fibrotic interstitial lung disease (ILD), a progressive fibrosing phenotype (PPF) typically demonstrates worsening respiratory symptoms, lung function decline and continuing fibrosis. The goal of this study was to compare the three different diagnostic criteria of PPF. Methods: Except for idiopathic pulmonary fibrosis, all consecutive adult patients with fibrotic ILD were retrospectively examined for the three predefined diagnostic criteria of PPF. The three criteria assess the disease progression in preceding 6 (half-year), 12 (one-year) and 24 (two-year) months respectively. The clinical characteristics, decline in predicted percent of forced vital capacity (FVC%) and survival of the three groups were compared, followed by determination of risk factors for mortality. Results: We identified 246 patients by half-year standard, 154 patients by one-year standard and 281 patients by two-year standard. Among them, 95% of patients in one-year group were also included in two-year group. The average one-year decline in FVC% was -1.0%, -2.7%, and -4.1% for half-year, one-year and two-year group respectively. The 4-year survival rate was 74% in half-year group, 66% in one-year group and 62% in two-year group. In multivariate Cox model, only baseline DLCO%<50% was correlated with mortality, with a hazard ratio of 3.4 (95% CI 1.1-10.6, P=0.03). Conclusion: In the current situations, both the one-year and two-year criterion are the reasonable choice to define PPF both in researches and clinical practice, and DLCO% is an independent predictor for mortality of PPF.