Inpatient data were extracted from the Japanese Diagnosis Procedure Combination database, the details of which have been reported elsewhere [17]. More than 1000 hospitals, representing approximately 50% of all discharges from acute care hospitals in Japan. We collected data that included sex and age; hospitalisation and discharge dates; weight and height; severity of dyspnoea based on the Hugh–Jones dyspnoea scale [18]; level of consciousness upon admission; smoking index; activities of daily living; frequency of hospitalisation; intensive care unit (ICU) admission during hospitalisation; main diagnoses, pre-existing comorbidities upon admission and complications after admission as recoded by the attending physicians based on the International Classification of Diseases, 10th revision (ICD-10) codes accompanied by text in Japanese; procedures and their dates; dates and doses of drugs administered during hospitalisation; and discharge status.

This study used data collected from 1 July 2010 to 31 March 2018. The inclusion criteria were patients aged ≥ 15 years, those diagnosed with interstitial pneumonia (ICD-10 codes J84.1, J84.8 and J84.9), those who underwent computed tomography scan within 1 day after admission and those who received treatment with intravenous mPSL at a dose of 500–1000 mg/day for 3 days, which was started within 4 days after admission [19, 20]. Patients with IPF were selected as follows. Firstly, we excluded patients with any of the following diagnoses of idiopathic interstitial pneumonias other than IPF recorded in Japanese text: idiopathic nonspecific interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, cryptogenic organising pneumonia, acute interstitial pneumonia, desquamative interstitial pneumonia, lymphoid interstitial pneumonia, idiopathic pleuroparenchymal fibroelastosis and unclassifiable idiopathic interstitial pneumonia. Secondly, we excluded patients with secondary interstitial lung diseases identified using ICD-10 codes (hypersensitivity pneumonitis [J67], connective tissue disease associated with interstitial lung disease [M05, M06 and M30–35], sarcoidosis [D86], amyloidosis [E85], drug-induced lung disease [J70], radiation pneumonitis [J70], Pneumocystis jirovecii pneumonia [B59], pneumoconiosis [J60–65], pulmonary alveolar proteinosis [J84.0)] eosinophilic pneumonia [J82], Langerhans cell histiocytosis [C96] and lymphangioleiomyomatosis [D21.9]); those receiving medications, including carperitide and tolvaptan for acute heart failure, within 1 day after admission; and those who received intra-aortic balloon pumping during hospitalisation [19, 20]. The remaining patients were assumed to have AE-IPF. Then, we also excluded patients with missing data about the level of consciousness, age and treatment year; patients who died within 6 days after admission to prevent immortal time bias; patients with sepsis (ICD-10 codes A40 and A41) and those without mechanical ventilation. In this study, we included only AE-IPF patients with mechanical ventilation under intubation and we did not count the use of non-invasive positive pressure ventilation as an inclusion criterion. Eligible patients were divided into two groups: those who received PMX treatment for ≥ 1 day, which was started within 6 days after admission, combined with high-dose mPSL (PMX group) and those who received high-dose mPSL alone (mPSL alone group).

The characteristics of patients evaluated in this study were sex, age, treatment year, body mass index, Hugh–Jones dyspnoea scale scores upon admission, level of consciousness upon admission, Charlson Comorbidity Index, smoking index, activities of daily living scale (Barthel Index) upon admission, history of previous hospitalisation (0, 1–2 or ≥ 3), type of hospital (academic or non-academic hospital), ICU admission and comorbidities. The Charlson Comorbidity Index scores were calculated according to the previous study (Additional file 1) [21]. The Charlson Comorbidity Index scores were classified into four categories (0, 1, 2 and ≥ 3). Further, we examined data on procedures and treatments, including haemodialysis, high-flow nasal cannula oxygen therapy and use of antibiotics and medications for IPF within 3 days after admission. We identified the use of hydrocortisone, as well as noradrenaline, as a treatment for shock, because shock is a complication indicating the severity in patients with AE-IPF. The Japan Coma Scale was used to evaluate the level of consciousness upon admission [22, 23], which is widely used in Japan and well correlated with the Glasgow Coma Scale score [24]. The ICD-10 codes were used to identify the following comorbidities (Additional file 2: Table S1) bronchial asthma, chronic obstructive pulmonary disease, pneumonia, pulmonary embolism, bronchiectasis, pneumothorax, lung and other types of cancer, disseminated intravascular coagulation, chronic heart failure, acute coronary syndrome, diabetes mellitus, stroke, renal failure, liver dysfunction, gastroesophageal reflux disease and urinary tract infection.

The primary outcome was all-cause in-hospital mortality. The secondary outcomes were 14- and 28-day mortality and length of hospital stay.

Dichotomous and categorical variables were presented as numbers with percentages and continuous variables as the median and interquartile range (IQR). To account for differences in baseline characteristics between the two groups, we conducted stabilised inverse probability of treatment weighting (IPTW) analyses using propensity scores. Stabilised IPTW uses propensity scores and adjusts for measured potential confounders while preserving sample size [25]. To control covariate imbalance, the specific stabilised weights were generated using propensity scores, which can predict the probability of receiving PMX treatment combined with high-dose mPSL therapy. To estimate the propensity score, a logistic regression model for receiving high-dose mPSL alone therapy was used with the following independent variables: sex, age, treatment year, body mass index, Hugh–Jones dyspnoea scale score, level of consciousness upon admission, Charlson Comorbidity Index, smoking index, Barthel Index upon admission, frequency of hospitalisation, type of hospital, ICU hospitalisation within 3 days after admission, comorbidities and procedures (haemodialysis and high-flow nasal cannula oxygen therapy), antibiotics (ampicillin/sulbactam, tazobactam/piperacillin, third-generation cephalosporin, fourth-generation cephalosporin, carbapenem, fluoroquinolone and anti-methicillin-resistant Staphylococcus aureus drug) and drugs (noradrenaline, hydrocortisone, cyclophosphamide, tacrolimus, pirfenidone, nintedanib and furosemide). A standardised mean difference was used to assess covariate balance. A value of < 20% indicated an acceptable balancing of covariates between the two groups. Stabilised IPTW analyses can preserve sample size and appropriately estimate average treatment effects over the marginal distribution of measured covariates in a study cohort.

We used generalised linear models with cluster-robust standard errors, treating each hospital as a cluster, to compare the primary and secondary outcomes. Logistic regression analyses of in-hospital mortality and 14- and 28-day mortality were performed. Then, odds ratios and their 95% confidence intervals (CIs) were calculated. The lengths of hospital stay between the two groups were compared via Poisson regression analysis, and the incidence rate ratios and their 95% CIs were calculated. To address competing outcomes, the lengths of hospital stay was evaluated among the survivors alone and all patients.

We performed sensitivity analysis 1 for patients who received PMX treatment and/or high-dose mPSL therapy at an earlier stage after admission. We included patients diagnosed with interstitial pneumonia who received treatment with intravenous mPSL at a dose of 500–1000 mg/day for 3 days, which was started within 2 days after admission. Then, we divided the patients into two groups: those who received PMX treatment for ≥ 1 day, which was started within 4 days after admission, combined with high-dose mPSL (PMX_S1 group) and those who received high-dose mPSL alone (mPSL alone_S1 group). We excluded patients who died within 4 days after admission. Other inclusion and exclusion criteria were the same as in the main analysis. Furthermore, we conducted sensitivity analysis 2 which included only patients aged 51 years or older, because IPF develops predominantly in the elderly. We used the same inclusion and exclusion criteria as in the main analysis except for age, and divided patients into two groups: those who received PMX treatment combined with high-dose mPSL (PMX_S2 group) and those who received high-dose mPSL alone (mPSL alone_S2 group). We examined the same outcomes in sensitivity analysis 1 and 2 as in the main analysis.

A two-tailed significance level of 0.05 was used in all statistical analyses. STATA/MP version 16 software (STATA Corp., College Station, TX, USA) was used to perform all tests.