Demographic and pathological features of enrolled LC patients and LC-ILD patients.

Altogether, 13,085 pathologically diagnosed LC patients were enrolled in this study. There were 5316 LC patients in the 2014–2017 group, 3035 of whom were male (57.1%). The median age was 61 (range 13–95, IQR 53–67) years, and 2869 patients received surgery (54.0%). In the 2018–2021 group, there were 7769 LC patients, 3640 of whom were male (46.9%), which was less than that in 2014–2017 group (46.9% vs. 57.1%, χ2 = 131.1, p < 0.001). The median age was 61 (range 15–94, IQR 53–67) years, and 5473 patients received surgery (54.0%).

The pathological patterns of LC in the 2014–2017 group vs. the 2018–2021 group were recorded as follows: adenocarcinoma 3597/67.7% vs. 6218/80.0%, SCC 839/15.8% vs. 822/10.6%, SCLC 545/10.3% vs. 497/6.4%, NSCNEN 97/1.8% vs. 76/1.0%, and other NSCLCs 238/4.5% vs. 156/2.0%.

Among the 13,085 LC patients, 509 patients (3.89%) had 551 cases of ILD. There were more LC-ILD patients in the 2018–2021 group than in the 2014–2017 group (401/5.16% vs. 108/2.03%, χ2 = 82.7, p < 0.001) (Fig. 2). Among 509 LC-ILD patients, 420 patients were male (82.5%), 399 patients had a smoking history (78.4%), and 231 patients had emphysema (52.8%). There were more male (84.3% vs. 75.9%, p = 0.04) and older (66 vs. 64 years, p = 0.01) LC-ILD patients in the 2018–2021 group than in the 2014–2017 group. There were less LC and LC-ILD patients who were admitted in 2020 because the monitor strategy of COVID-19 in China. In Beijing, the COVID-19 patients were treated in designated hospital. LC-ILD patients with COVID-19 were not enrolled in our study.

Fig. 2

Prevalence of ILD in LC inpatients from 2014 to 2021

The underlying causes of ILD for enrolled LC-ILD patients

The detailed study flow is shown in Fig. 3. There were 360 IIP patients in the 509 enrolled LC-ILD patients. Among them, 92 patients had IPF. Twelve IPF patients were prescribed treatment for ILD, with 7 patients receiving N-acetylcysteine, 3 receiving nintedanib, and 2 receiving pirfenidone. Among the non-IPF IIP patients, 27 patients received ILD treatment, with 13 patients taking glucocorticoids, 12 taking N-acetylcysteine, 1 taking nintedanib, and 1 taking pirfenidone. As for LC treatment in the 360 IIP patients, 275 patients had chemotherapy, 66 patients took TKI, 121 patients had immunotherapy (with 80 patients taking immunotherapy as a first-line treatment), 59 patients had radiation therapy, and 8 patients received palliative therapy only. Some of the patients had complications with LC treatment-associated ILDs, with 13 cases suffering from radiation pneumonitis, 13 cases suffering from CIP, and 2 cases suffering from TKI-associated ILD.

Fig. 3

Flow chart of study. a Among the 50 cases of radiation pneumonitis, 15 case had pre-existing ILD (13 cases of IIP, 1 case of SSc-ILD, and 1 case of IgG4-RD-ILD), and 11 cases were combined with CIP. b Among the 73 cases of CIP, 13 case had pre-existing IIP, and 11 cases were combined with radiation pneumonitis. c Among the 11 cases of TKI-associated ILD, 3 cases had pre-existing ILD (2 cases of IIP, and 1 case of RA-ILD)

Fifty-five CTD-ILD patients were enrolled in the study, and 28 patients were male (50.9%). The mean age was 62.4 ± 9.1 years at the diagnosis of LC. There were 16 cases of rheumatoid arthritis (one of whom later developed TKI-associated ILD), 11 cases of systemic sclerosis (one later developed radiation pneumonitis), 10 cases of inflammatory myopathy, 5 cases of primary Sjögren’s syndrome, 5 cases of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, 5 cases of undifferentiated connective tissue disease, 1 case of mixed connective tissue disease, 1 case of systemic lupus erythematosus, and 1 case of IgG4-related disease (who later developed radiation pneumonitis). Most of these patients received treatment for CTD-ILD, with 43 patients taking glucocorticoids and/or immunosuppressants and 2 patients taking pirfenidone. Concerning LC treatment, 33 patients received chemotherapy, 12 patients took TKI, 5 patients had immunotherapy, 7 patients had radiation therapy, and 2 patients only received palliative therapy.

There were 134 cases of LC treatment-associated ILD among 509 patients/551 cases of LC-ILD, including CIP (73 cases), radiation pneumonitis (50 cases), and TKI-associated ILD (11 cases, with 2 cases related to gefitinib, 2 related to almonertinib, 2 related to icotinib, 1 related to osimertinib, 1 related to brigatinib, 1 related to crizotinib, 1 related to furmonertinib, and 1 related to anlotinib). Eight patients (72.7%) with TKI-associated ILD received systemic glucocorticoid treatment. Thirty-seven cases (74%) of radiation pneumonitis were treated with glucocorticoids.

CIP cases have been admitted to our hospital since 2018, and 73 cases were included in this study (8 cases in 2018, 14 cases in 2019, 16 cases in 2020, and 35 cases in 2021). Eleven CIP cases were complicated by radiation pneumonitis, and 13 CIP cases had preexisting IIPs before the administration of immunotherapy. The LC pathological patterns of CIP cases included adenocarcinoma (32 cases), SCC (31 cases), SCLC (7 cases), and other NSCLCs (3 cases).

The LC characteristics of enrolled LC-ILD patients

The LC pathological patterns of 509 LC-ILD patients are presented in Fig. 4 and Table 1: adenocarcinoma 204/40.1% (2.1% of all adenocarcinoma cases), SCC 160/31.4% (9.6% of all SCC cases), SCLC 113/22.2% (10.8% of all SCLC cases), NSCNEN 13/2.6% (7.5% of all NSCNEN cases), and other NSCLCs 19/3.7% (4.8% of all other NSCLC cases).

Fig. 4

LC pathological patterns of 509 LC-ILD patients

Table 1 LC pathological patterns of LC-ILD patients in 2014–2017 and 2018–2021Different characteristics of LC-ILD between 2014–2017 and 2018–2021

A comparison of the clinical and pathological characteristics of LC-ILD patients in the 2014–2017 group and 2018–2021 group is presented in Table 2. Compared with the 2014–2017 group, patients in 2018–2021 had a higher male percentage (84.3% vs. 75.9%, p = 0.04), older age (median age 66 years vs. 64 years, p = 0.01), fewer IPF cases (15.2% vs. 28.7%, p = 0.001), fewer cases who had surgical resection (15.7% vs. 34.3%, p < 0.001), and fewer cases suffering from acute exacerbation of ILD after surgical resection (6.3% vs. 10.8%, p = 0.045). The differences in the distribution of both the underlying causes of ILD (p < 0.001) and the chronological sequences of ILD and LC diagnosis (p = 0.003) between the two groups were also statistically significant. No LC-ILD patients who were enrolled in our study were suffered from COVID-19. There were no significant differences of the underlying causes of ILD and the pathological patterns of LC between the 2018–2019 group and 2020–2021 group (Table 3). However, the patients were older in 2020–2021 group than in 2018–2019 group, and more LC-ILD patients were arranged with surgical resection in 2018–2019 group than in 2020–2021 group.

Table 2 Different characters of LC-ILD between 2014-2017group and 2018-2021groupTable 3 Different characters of LC-ILD between 2018–2019 group and 2020–2021 groupCauses of death in LC-ILD patients

Forty LC-IIP patients died during the follow-up: 20 patients died of lung cancer progression, 12 patients died of uncontrolled ILD, 5 patients died of severe pulmonary infection, 2 patients died of severe arrhythmia, and one patient died of immune-related myocarditis. Two LC-CTD-ILD patients died during the follow-up: one patient died of lung cancer progression, and the other died of ILD associated with anti-melanoma differentiation-associated gene 5-positive dermatomyositis.