Exacerbation Of Idiopathic Pulmonary Fibrosis Research Articles

Clinical manifestations and prognostic factors analysis of patients hospitalised with acute exacerbation of idiopathic pulmonary fibrosis and other interstitial lung diseases

BackgroundAcute exacerbation (AE) is a life-threatening condition taking place not only in idiopathic pulmonary fibrosis (IPF) but also in interstitial lung diseases (ILD) other than IPF (non-IPF ILD). This study...

The Impact of Chronic Comorbidities on Outcomes in Acute Exacerbations of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a chronic progressive lung disease of unknown cause with a high associated mortality. We aimed to compare the impact of chronic medical conditions on hospital outcomes of patients with acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). This was a retrospective cohort study using the NIS database from 2016 to 2018. We included patients aged 60 and older hospitalized in academic medical centers with the diagnoses of IPF and acute respiratory failure. We examined factors associated with hospital mortality and length of stay (LOS) using survey-weighted multivariate logistic and negative binomial regression. Out of 4975 patients with AE-IPF, 665 (13.4%) did not survive hospitalization. There was no difference in the mean age between survivors and non-survivors. Patients were more likely to be male, predominantly white, and have Medicare coverage. Most non-survivors were from households with higher median income. Hospital LOS was longer among non-survivors than survivors (9.4 days vs. 9.8 days; p < 0.001). After multivariate-logistic regression, diabetes was found to be protective (aOR 0.62, 95% CI 0.50-0.77; p < 0.0001) while chronic kidney disease (CKD) conferred a significantly higher risk of death after AE-IPF (aOR 6.85, 95% CI 1.90-24.7; p = 0.00). Our multivariate adjusted negative binomial regression model for LOS identified obesity (IRR 0.85, 95% CI 0.76-0.94; p ≤ 0.00) and hypothyroidism (IRR 0.90, 95% CI 0.83-0.98; p = 0.02) to be associated with shorter hospital LOS. Our results suggest that CKD is a significant contributor to hospital mortality in AE-IPF, and diabetes mellitus may be protective. Obesity and hypothyroidism are linked with shorter hospital LOS among patients hospitalized with AE-IPF in US academic medical centers.

The Prevalence of COVID-19 Infection in Patients Presented with Acute Exacerbation of Asthma, COPD and Idiopathic Pulmonary Fibrosis at the Emergency Department of Al-Shaab Teaching Hospital from July 2021 to November 2021

Background: The ongoing global pandemic of COVID-19 has raised concerns about its impact on patients with pre-existing respiratory conditions. Understanding the association between COVID-19 and chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) is crucial for early detection and appropriate management. Studying the prevalence rates of COVID-19 in this specific patient population will contribute to the existing knowledge and inform healthcare strategies for better patient care. The objective of this study is to assess the prevalence of COVID-19 infection in patients who presented with acute exacerbation of asthma, COPD and IPF. Method: This cross-sectional descriptive hospital-based study was conducted at Al-Shaab Teaching Hospital in Sudan and included adult Sudanese patients with exacerbation of asthma, COPD, or IPF who presented in the ER from February 2021 to July 2021. A representative sample of 345 patients was selected using a convenience, non-randomized sampling technique. Data were collected using a structured questionnaire and analyzed using SPSS version 26. Ethical clearance and approval were obtained for the study. Results: The study included 175 (50.7%) patients with asthma, 116 (33.6%) with IPF and 54 (15.7%) with COPD. The overall prevalence of COVID-19 among the patients was 58 (16.8%). Among the three groups, the highest prevalence of COVID-19 was observed in 22 (40.7%) patients with COPD, followed by 16 (13.8%) patients with IPF and 20 (11.4%) asthmatic patients (p value &lt; 0.05). In the asthmatic patients, the most common age groups affected were 25-34 years and 35-44 years, while in COPD and IPF patients, the prevalence was higher among patients aged 55 years and above (p value &lt; 0.05). Additionally, the prevalence of COVID-19 in COPD and IPF patients was significantly higher among males than females (p value &lt; 0.05). Conclusion: The prevalence of COVID-19 among patients with pre-existing respiratory conditions, such as asthma, COPD and IPF, is considerable, with the highest prevalence observed in patients with COPD. Furthermore, this study found that age and gender are associated factors with the prevalence of COVID-19 in these patient populations. These findings contribute to our understanding of the association between COVID-19 and chronic lung diseases, providing valuable information for early detection and appropriate management. The results of this study can inform healthcare strategies and contribute to better patient care in this specific patient population.

Retrospective analysis of patients hospitalized with acute exacerbation of idiopathic pulmonary fibrosis

Retrospective analysis of patients hospitalized with acute exacerbation of idiopathic pulmonary fibrosis

Prognostic factors associated with mortality in acute exacerbations of idiopathic pulmonary fibrosis: A systematic review and meta-analysis

BackgroundAcute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) increases mortality risk, but which factors increase mortality is unknown. We aimed to perform a prognostic review of factors associated with mortality in patients with IPF. Study designand methods: We searched MEDLINE, EMBASE, and CINAHL for studies that reported on the association between any prognostic factor and AE-IPF. We assessed risk of bias using the QUIPS tool. We conduced pairwise meta-analyses using REML heterogeneity estimator, and GRADE approach to assess the certainty of the evidence. ResultsWe included 35 studies in our analysis. We found that long-term supplemental oxygen at baseline (aHR 2.52 [95 % CI 1.68 to 3.80]; moderate certainty) and a diagnosis of IPF compared to non-IPF ILD (aHR 2.19 [95 % CI 1.22 to 3.92]; moderate certainty) is associated with a higher risk of death in patients with AE-IPF. A diffuse pattern on high resolution computed tomography (HRCT) compared to a non-diffuse pattern (aHR 2.61 [95 % CI 1.32 to 2.90]; moderate certainty) is associated with a higher risk of death in patients with AE-IPF. We found that using corticosteroids prior to hospital admission (aHR 2.19 [95 % CI 1.26 to 3.82]; moderate certainty) and those with increased neutrophils (by % increase) in bronchoalveolar lavage (BAL) during the exacerbation is associated with a higher risk of death (aHR 1.02 [1.01 to 1.04]; moderate certainty). InterpretationOur results have implications for healthcare providers in making treatment decisions and prognosticating the clinical trajectory of patients, for researchers to design future interventions to improve patient trajectory, and for guideline developers in making decisions about resource allocation.

Safety and efficacy of CT-guided percutaneous microwave ablation for stage I non-small cell lung cancer in patients with comorbid idiopathic pulmonary fibrosis.

To evaluate the safety and efficacy of microwave ablation (MWA) for stage I non-small cell lung cancer (NSCLC) in patients with idiopathic pulmonary fibrosis (IPF). A retrospective single-center cohort study was conducted in patients with clinical stage I NSCLC who underwent CT-guided MWA from Nov 2016 to Oct 2021. The patients were divided into the IPF group and the non-IPF group. The primary endpoints were 90-day adverse events and hospital length of stay (HLOS). The secondary endpoints included overall survival (OS) and progression-free survival (PFS). A total of 107 patients (27 with IPF and 80 without IPF) were finally included for analysis. No procedure-related acute exacerbation of IPF or death occurred post-MWA. The rates of adverse events were similar between the groups (48.6% vs. 47.7%; p = 0.998). The incidence of grade 3 adverse events in the IPF group was higher than that in the non-IPF group without a significant difference (13.5% vs. 4.6%; p = 0.123). Median HLOS was 5days in both groups without a significant difference (p = 0.078). The 1-year and 3-year OS were 85.2%/51.6% in the IPF group, and 97.5%/86.4% in the non-IPF group. The survival of patients with IPF was significantly poorer than the survival of patients without IPF (p < 0.001). There was no significant difference for PFS (p = 0.271). MWA was feasible in the treatment of stage I NSCLC in patients with IPF. IPF had an adverse effect on the survival of stage I NSCLC treated with MWA. CT-guided microwave ablation is a well-tolerated and effective potential alternative treatment for stage I non-small cell lung cancer in patients with idiopathic pulmonary fibrosis. • Microwave ablation for stage I non-small cell lung cancer was well-tolerated without procedure-related acute exacerbation of idiopathic pulmonary fibrosis and death in patients with idiopathic pulmonary fibrosis. • No differences were observed in the incidence of adverse events between patients with idiopathic pulmonary fibrosis and those without idiopathic pulmonary fibrosis after microwave ablation (48.6% vs. 47.7%; p = 0.998). • The 1-year and 3-year overall survival rates (85.2%/51.6%) in the idiopathic pulmonary fibrosis group were worse than those in the non- idiopathic pulmonary fibrosis group (97.5%/86.4%) (p < 0.001).

Serum heme oxygenase-1 as a prognostic biomarker in patients with acute exacerbation of interstitial lung disease

Serum heme oxygenase (HO)-1 level has been reported as a clinically reliable diagnostic biomarker for acute exacerbation of interstitial lung disease (ILD); however, its utility for predicting mortality among these patients is unclear. Serum HO-1 levels of patients newly diagnosed with acute exacerbation of ILD were measured at the time of initiating steroid pulse therapy. The relationship between serum HO-1 and various other serum biomarkers, change in HRCT findings, and disease prognosis at 12 weeks after diagnosis of acute exacerbation was evaluated in 51 patients, of whom 17 (33%) had idiopathic pulmonary fibrosis (IPF). Serum HO-1 was higher in patients with acute exacerbation of IPF than in patients with acute exacerbation of other ILDs. Serum HO-1 levels were higher in patients who died within these 12 weeks than in survivors. Among age, sex, comorbidities, IPF diagnosis, HRCT findings, and blood biomarkers, serum HO-1 was a primary predictor of 12-week mortality. In 41 patients who underwent repeat HRCT, serum HO-1 was higher in patients with honeycomb progression than in those without. Serum HO-1 measurement could be useful for evaluating disease mortality and morbidity of patients with acute exacerbation of ILDs.

Pulse versus non-pulse corticosteroid therapy in patients with acute exacerbation of idiopathic pulmonary fibrosis.

Corticosteroids are commonly used for the treatment of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF); however, the optimal initial dose of corticosteroids remains uncertain due to a lack of sufficient evidence. We evaluated whether the administration of a pulse dose of corticosteroids resulted in improved survival outcomes compared with conventional non-pulse dose of corticosteroids. We retrospectively analysed 238 patients with AE-IPF treated with corticosteroids at a tertiary referral hospital between January 2013 and December 2021. Based on whether a pulse dose of corticosteroids (methylprednisolone of ≥250 mg/day or equivalent) was administered within 7 days of hospitalization for AE-IPF, the patients were divided into the pulse and non-pulse regimen groups. The survival outcomes were compared between the two groups using multivariable regression and propensity score-matched analyses. Among the 238 patients, 59 patients received pulse dose of corticosteroids, whereas 179 patients received conventional non-pulse dose of corticosteroids. After adjusting for the confounding factors related to the baseline clinical and radiographic severity, compared with the conventional non-pulse regimen, the pulse regimen of corticosteroids did not reduce the risk of mortality at the 3-month (aHR 0.84, 95% CI 0.45-1.38) or 12-month (aHR 0.96, 95% CI 0.60-1.25) follow-ups. Propensity score-matched analysis revealed similar results. The survival outcomes of patients with AE-IPF who received a pulse dose of corticosteroids did not differ from those of patients who received conventional non-pulse dose of corticosteroids. Further prospective studies are required to establish the optimal initial dose of corticosteroids for the treatment of AE-IPF.

Neutrophil-to-Lymphocyte Ratio in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Background: This study aimed to clarify the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). Methods: Eighty-six patients diagnosed with AE-IPF were included in this single-center retrospective study. The NLR was calculated by dividing the peripheral neutrophil count by the peripheral lymphocyte count. The cut-off values of the NLR for predicting 90-day survival were determined using receiver operating characteristic curve analysis. Oxygenation deterioration on days 4 and 8 relative to that on day 1 was clinically defined. The prognostic value of NLR was evaluated using Cox proportional hazard regression analysis. Results: The cut-off value of day-1, day-4, and day-8 NLRs for predicting 90-day survival was 12.13, 14.90, and 10.56, respectively. A higher day-1 NLR was a significant predictor of a poor prognosis in univariate and multivariate analyses. Survival was significantly better in patients without oxygenation deterioration on days 4 and 8 than in those with deterioration. Day-4 and day-8 NLR could predict 90-day survival in patients without oxygenation deterioration. Conclusions: Day-1 NLR was a useful predictor of 90-day survival in AE-IPF. Further, monitoring day-4 and day-8 NLRs and evaluating oxygenation deterioration may be useful for managing AE-IPF.

Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: An exploratory randomized controlled trial

BackgroundAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an important occurrence in the natural history of idiopathic pulmonary fibrosis (IPF), associated with high hospitalization rates, high mortality and poor prognosis. At present, there is no effective treatment for AE-IPF. Chinese herbal medicine has some advantages in treating IPF, but its utility in AE-IPF is unclear. ObjectiveThe treatment of AE-IPF with Kangxian Huanji Granule (KXHJ), a compound Chinese herbal medicine, lacks an evidence-based justification. This study explores the efficacy and safety of KXHJ in patients with AE-IPF. Design, setting, participants and interventionsWe designed a randomized, double-blind, placebo-controlled, exploratory clinical trial. A total of 80 participants diagnosed with AE-IPF were randomly assigned to receive KXHJ or a matching placebo; the treatment included a 10 g dose, administered twice daily for 4 weeks, in addition to conventional treatment. Participants were followed up for 12 weeks after the treatment. Main outcome measuresThe primary endpoints were treatment failure rate and all-cause mortality. Secondary endpoints included the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, the modified British Medical Research Council (mMRC) score, and the St George’s Respiratory Questionnaire for IPF (SGRQ-I) score. ResultsThe rate of treatment failure at 4 weeks was lower in the intervention group compared to the control group (risk ratio [RR]: 0.22; 95% confidence interval [CI]: 0.051 to 0.965, P = 0.023). There was no significant difference in all-cause mortality at 16 weeks (RR: 0.75; 95% CI: 0.179 to 3.138; P > 0.999) or in the acute exacerbation rate during the 12-week follow-up period (RR: 0.69; 95% CI: 0.334 to 1.434; P = 0.317). The intervention group had a shorter length of hospitalization than the control group (mean difference [MD]: –3.30 days; 95% CI, –6.300 to –0.300; P = 0.032). Significant differences in the mean change from baseline in the mMRC (between-group difference: –0.67; 95% CI: –0.89 to –0.44; P < 0.001) and SGRQ-I score (between-group difference: –10.36; 95% CI: –16.483 to –4.228; P = 0.001) were observed after 4 weeks, and also in the mMRC (between-group difference: –0.67; 95% CI: –0.91 to –0.43; P < 0.001) and SGRQ-I (between-group difference: –10.28; 95% CI, –15.838 to –4.718; P < 0.001) at 16 weeks. The difference in the adverse events was not significant. ConclusionKXHJ appears to be effective and safe for AE-IPF and can be considered a complementary treatment in patients with AE-IPF. As a preliminary exploratory study, our results provide a basis for further clinical research. Trial registrationChinese Clinical Trial Registry (ChiCTR1900026289).Please cite this article as: Li JS, Zhang HL, Guo W, Wang L, Zhang D, Zhao LM, Zhou M. Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: an exploratory randomized controlled trial. J Integr Med. 2023; Epub ahead of print.

Polymyxin B-immobilised fibre column treatment for acute exacerbation of idiopathic pulmonary fibrosis patients with mechanical ventilation: a nationwide observational study

BackgroundThe prognosis for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is poor, and there is no established treatment. Hence, we aimed to investigate the effectiveness of a polymyxin B-immobilised fibre column (PMX) for the treatment of AE-IPF.MethodsData were retrospectively collected from the Japanese Diagnosis Procedure Combination database from 1 July 2010 to 31 March 2018. We identified adult patients with idiopathic pulmonary fibrosis who received high-dose methylprednisolone (mPSL) therapy and mechanical ventilation upon admission. Eligible patients (n = 5616) were divided into those receiving PMX treatment combined with high-dose mPSL (PMX group, n = 199) and high-dose mPSL alone (mPSL alone group, n = 5417). To compare outcomes between the two groups, we applied a stabilised inverse probability of treatment weighting (IPTW) using propensity scores. The primary outcome was in-hospital mortality, and the secondary outcomes were 14- and 28-day mortality and length of hospital stay.ResultsThe in-hospital mortality rates of the PMX and mPSL alone groups were 79.9% and 76.4%, respectively. The results did not significantly differ between the two groups after performing a stabilised IPTW. The odds ratio of the PMX group compared with the mPSL alone group was 1.56 (95% confidence interval 0.80–3.06; p = 0.19). The 14- and 28-day mortality and length of hospital stay (secondary outcomes) also did not significantly differ between the two groups.ConclusionsIn AE-IPF patients using mechanical ventilation, the treatment outcome was not significantly better for PMX combined with high-dose mPSL than for high-dose mPSL alone.

Myeloid Heterogeneity Mediates Acute Exacerbations of Pulmonary Fibrosis.

Epidemiological evidence indicates that exposure to particulate matter is linked to the development of idiopathic pulmonary fibrosis (IPF) and increases the incidence of acute exacerbations of IPF. In addition to accelerating the rate of lung function decline, exposure to fine particulate matter (particulate matter smaller than 2.5 μm [PM2.5]) is a risk factor for increased mortality in subjects with IPF. In this article, we show that exposure to PM2.5 mediates monocyte recruitment and fibrotic progression in mice with established fibrosis. In mice with established fibrosis, bronchoalveolar lavage cells showed monocyte/macrophage heterogeneity after exposure to PM2.5. These cells had a significant inflammatory and anti-inflammatory signature. The mixed heterogeneity of cells contributed to the proinflammatory and anti-inflammatory response. Although monocyte-derived macrophages were recruited to the lung in bleomycin-injured mice treated with PM2.5, recruitment of monocytes expressing Ly6Chi to the lung promoted progression of fibrosis, reduced lung aeration on computed tomography, and impacted lung compliance. Ly6Chi monocytes isolated from PM2.5-exposed fibrotic mice showed enhanced expression of proinflammatory markers compared with fibrotic mice exposed to vehicle. Moreover, IPF bronchoalveolar lavage cells treated ex vivo with PM2.5 showed an exaggerated inflammatory response. Targeting Ly6Chi monocyte recruitment inhibited fibrotic progression in mice. Moreover, the adoptive transfer of Ly6Chi monocytes exacerbated established fibrosis. These observations suggest that enhanced recruitment of Ly6Chi monocytes with a proinflammatory phenotype mediates acute exacerbations of pulmonary fibrosis, and targeting these cells may provide a potential novel therapeutic target to protect against acute exacerbations of IPF.

Design of a phase III, double-blind, randomised, placebo-controlled trial of BI 1015550 in patients with idiopathic pulmonary fibrosis (FIBRONEER-IPF)

IntroductionThere is an unmet need for new treatments for idiopathic pulmonary fibrosis (IPF). The oral preferential phosphodiesterase 4B inhibitor, BI 1015550, prevented a decline in forced vital capacity (FVC) in...

Identifying oxidative stress-related biomarkers in idiopathic pulmonary fibrosis in the context of predictive, preventive, and personalized medicine using integrative omics approaches and machine-learning strategies.

Idiopathic pulmonary fibrosis (IPF) is a rare interstitial lung disease with a poor prognosis that currently lacks effective treatment methods. Preventing the acute exacerbation of IPF, identifying the molecular subtypes of patients, providing personalized treatment, and developing individualized drugs are guidelines for predictive, preventive, and personalized medicine (PPPM/3PM) to promote the development of IPF. Oxidative stress (OS) is an important pathological process of IPF. However, the relationship between the expression levels of oxidative stress-related genes (OSRGs) and clinical indices in patients with IPF is unclear; therefore, it is still a challenge to identify potential beneficiaries of antioxidant therapy. Because PPPM aims to recognize and manage diseases by integrating multiple methods, patient stratification and analysis based on OSRGs and identifying biomarkers can help achieve the above goals. Transcriptome data from 250 IPF patients were divided into training and validation sets. Core OSRGs were identified in the training set and subsequently clustered to identify oxidative stress-related subtypes. The oxidative stress scores, clinical characteristics, and expression levels of senescence-associated secretory phenotypes (SASPs) of different subtypes were compared to identify patients who were sensitive to antioxidant therapy to conduct differential gene functional enrichment analysis and predict potential therapeutic drugs. Diagnostic markers between subtypes were obtained by integrating multiple machine learning methods, their expression levels were tested in rat models with different degrees of pulmonary fibrosis and validation sets, and nomogram models were constructed. CIBERSORT, single-cell RNA sequencing, and immunofluorescence staining were used to explore the effects of OSRGs on the immune microenvironment. Core OSRGs classified IPF into two subtypes. Patients classified into subtypes with low oxidative stress levels had better clinical scores, less severe fibrosis, and lower expression of SASP-related molecules. A reliable nomogram model based on five diagnostic markers was constructed, and these markers' expression stability was verified in animal experiments. The number of neutrophils in the immune microenvironment was significantly different between the two subtypes and was closely related to the degree of fibrosis. Within the framework of PPPM, this work comprehensively explored the role of OSRGs and their mediated cellular senescence and immune processes in the progress of IPF and assessed their capabilities aspredictors of high oxidative stress and disease progression,targets of the vicious loop between regulated pulmonary fibrosis and OS for targeted secondary and tertiary prevention, andreferences for personalized antioxidant and antifibrotic therapies. The online version contains supplementary material available at 10.1007/s13167-023-00334-4.

Economic Burden of Idiopathic Pulmonary Fibrosis in Spain: A Prospective Real-World Data Study (OASIS Study).

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease associated with dyspnoea, cough and impaired quality of life affecting around 7500 patients in Spain. Our aim was to estimate the economic impact of IPF according to forced vital capacity (FVC) % predicted level in adult patients. We conducted a prospective, observational, multicentric study of patients with confirmed IPF in Spain. Total annual IPF-related costs were estimated per patient, and categorised according to the FVC% predicted value (FVC < 50%, FVC 50-80%, FVC > 80%) and total sample. Incurred direct health- and non-health-related costs and indirect costs were calculated considering the IPF-related healthcare resource use and the corresponding unitarian costs. Results were updated to 2023 euros. Two hundred and four consecutivepatients with IPF were included: 77% male, average age (standard deviation) 70.8 (7.6) years. At baseline, FVC% was < 50%, 50-80% and > 80% of predicted value in 10.8%, 74.5% and 14.7% of patients, respectively. The final cost-evaluable population included 180 subjects. The mean (standard deviation) total annual IPF-related cost was €26,997 (17,555), with statistically significant differences (p = 0.0002) between groups: €44,412 (33,389) for the FVC < 50%, €25,803 (14,688) for the FVC 50-80% and €23,242 (13,642) for the FVC > 80%. Annual direct health costs had the greatest weight and included pharmacological treatments [€22,324 (13,773)] and hospitalisation days [€1659 (7362)]. 14 patients had ≥ 1 acute exacerbation of IPF during the study; mean total cost of an acute exacerbation of IPF was €10,372. According to the multivariate analysis, an impaired lung function (FVC < 50%) and use of antifibrotic treatment were determinants of cost (p < 0.0001 both). We observed a significantly higher annual IPF-related cost at a lower level of predicted FVC%, the direct cost having the greatest weight to the total costs. Maintaining patients at early disease stages by slowing IPF progression is relevant to reduce the economic impact of IPF. EU PAS register number EUPAS19387 (1 June, 2017).

A Real-World Prognosis in Idiopathic Pulmonary Fibrosis: A Special Reference to the Role of Antifibrotic Agents for the Elderly.

Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of idiopathic interstitial pneumonia, and its prevalence increases with age. In the era of pre-antifibrotic agents, the median survival time of Japanese patients with IPF is 35 months, with a 5-year survival rate in western countries ranging from 20% to 40%. The prevalence of IPF is highest in elderly patients aged ≥75 years; however, the efficacy and safety of long-term use of pirfenidone and/or nintedanib are not fully understood. This study aimed to determine the efficacy and safety of the sole use of antifibrotic agents (pirfenidone or nintendanib) for IPF in the elderly. We retrospectively reviewed patients with IPF who were diagnosed and treated with either pirfenidone or nintedanib in our hospital between 2008 and 2019. We excluded patients with the subsequent use of both antifibrotic agents. We examined the survival probability and frequency of acute exacerbation, with focus on long-term use (≥1 year), elderly patients (≥75 years of age), and disease severity. We identified 91 patients with IPF (male to female ratio: 63 to 28, age 42 to 90 years). The numbers of patients with disease severity classified by JRS (I/II/III/IV) and GAP stage (I/II/III) were (38/6/17/20) and (39/36/6), respectively. The survival probabilities were comparable between the elderly (n = 46) and non-elderly groups (n = 45, p = 0.877). After the initiation of antifibrotic agents, the cumulative incidence ratio of acute exacerbation of IPF was significantly lower in the early stage (GAP stage I, n = 20) than in the progressive stage of disease (GAP stages II and III, n = 20, p = 0.028). A similar trend was noted in the JRS disease severity classification (I, II vs. III, IV) (n = 27 vs. n = 13, p = 0.072). In the long-term treatment (≥1 year) group (n = 40), the survival probabilities at 2 and 5 years after treatment initiation were 89.0% and 52.4%, respectively, which did not reach the median survival rate. Even in elderly patients (≥75 years of age), antifibrotic agents demonstrated positive effects on survival probability and the frequency of acute exacerbation. These positive effects would be improved for earlier JRS/GAP stages or long-term use.

Survie en vie réelle des patients ayant une fibrose pulmonaire idiopathique sous traitement anti-fibrosant

Idiopathic pulmonary fibrosis (IPF) is an irreversible fibrosing disease with median survival at diagnosis of 2-5years. That said, pirfenidone and nintedanib slow down the gradual decline in respiratory function. Clinical trials have shown that while they are not curative, these drugs reduce mortality and increase survival time compared to placebo. This objective of this work was to compare the real-life survival of patients with IPF diagnosed at the Tours University Hospital depending on whether or not they took anti-fibrotic medication. This is a monocentric retrospective study involving 176patients diagnosed with IPF starting from 1997. Out of these 176patients, 100 were treated with anti-fibrotic agents and 76 did not receive any anti-fibrotic treatment. Survival significantly increased in the group with anti-fibrotic medication, with median survival of 59months [46-87] versus 39months [29-65] (P=0.022). Predictive factors for death were neoplasia, IPF exacerbation and decreased DLCO. Our study corroborates the beneficial result observed in clinical trials by showing longer survival in patients using anti-fibrotic agents.

Skeletal muscle atrophy and short-term mortality in patients with acute exacerbation of idiopathic pulmonary fibrosis: an observational cohort study

BackgroundSkeletal muscle atrophy, a common complication of idiopathic pulmonary fibrosis (IPF), and its presence upon diagnosis can indicate a poor prognosis. Patients with IPF frequently experience acute exacerbations (AE), which is associated with a high mortality rate. However, the association between skeletal muscle atrophy and short-term mortality remains unknown. MethodsWe performed a retrospective, multicenter cohort study of patients admitted for AE-IPF in Japan. The cross-sectional areas of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA) were analyzed via single-slice computed tomography (CT). The primary outcome was 90-day mortality. Survival probability was estimated using the Kaplan–Meier method, and the log-rank test was used between the low and high groups of ESMCSA and PMCSA. We used multivariable Cox proportional-hazards models to evaluate the association between ESMCSA and PMCSA and prognosis. ResultsOf the 212 patients included, 94 (44%) died during the observation period. The low ESMCSA group (<25.6 cm2) had a significantly worse prognosis than that of the high ESMCSA group (≥25.6 cm2) (hazard ratio (HR) [95% confidence interval (CI)]: 1.52 [1.00–2.33], P = 0.049). Multivariable analyses showed that all-cause mortality was associated with low ESMCSA (model 1, adjusted HR [95% CI]: 1.59 [0.98–2.60]; model 2, 1.55 [0.95–2.56], and model 3, 1.67 [1.00–2.78], respectively). The adjusted HR of low PMCSA (<20.4 cm2) vs. high PMCSA (≥20.4 cm2) was 1.39 (95% CI: 0.88–2.20). ConclusionsLow ESMCSA on CT images is associated with a high 90-day mortality rate in patients with AE-IPF.

Hospital-level variation in practices and outcomes for patients with severe acute exacerbations of idiopathic pulmonary fibrosis: a retrospective multicentre cohort study

BackgroundIn the absence of evidence-based strategies to improve patient outcomes, the management of patients with severe idiopathic pulmonary fibrosis (IPF) exacerbations may vary widely across centres. We assessed between-hospital variation...

Idiopathic Pulmonary Fibrosis and Post-COVID-19 Lung Fibrosis: Links and Risks.

Idiopathic pulmonary fibrosis (IPF) is considered the paradigmatic example of chronic progressive fibrosing disease; IPF does not result from a primary immunopathogenic mechanism, but immune cells play a complex role in orchestrating the fibrosing response. These cells are activated by pathogen-associated or danger-associated molecular patterns generating pro-fibrotic pathways or downregulating anti-fibrotic agents. Post-COVID pulmonary fibrosis (PCPF) is an emerging clinical entity, following SARS-CoV-2 infection; it shares many clinical, pathological, and immune features with IPF. Similarities between IPF and PCPF can be found in intra- and extracellular physiopathological pro-fibrotic processes, genetic signatures, as well as in the response to antifibrotic treatments. Moreover, SARS-CoV-2 infection can be a cause of acute exacerbation of IPF (AE-IPF), which can negatively impact on IPF patients' prognosis. In this narrative review, we explore the pathophysiological aspects of IPF, with particular attention given to the intracellular signaling involved in the generation of fibrosis in IPF and during the SARS-CoV-2 infection, and the similarities between IPF and PCPF. Finally, we focus on COVID-19 and IPF in clinical practice.