Can acute exacerbations occurring late after surgery with interstitial lung diseases be predicted?

The incidence of acute exacerbation (AE) 31 days after surgery in lung cancer (LC) patients with interstitial lung disease (ILD) has not yet been elucidated. This study aimed to identify the AE incidence rate, mortality rate, and risk factors in patients with late-stage LC with ILD.

We conducted a retrospective study on 410 patients with ILD on preoperative computed tomography among 3939 patients with LC who underwent their first surgery between August 2008 and July 2019. We divided the patients into Group A (early AE; 18cases), Group B (late AE; 40 cases), and Group C (no AE; 352 cases).

There were no significant differences in the clinical background between Groups A and B. The AE incidence rates were 0.56 case per person-years at ≤ 30 days, 0.24 at 90 days, 0.14 at 180 days, 0.10 at 1 year, 0.078 at 2 years, 0.086 at 3 years, 0.064 at 4 years, and 0.059 at 5 years after surgery. The mortality rates of the first AE were 10/18 (56%), 3/5 (60%), 7/13 (54%), and 7/22 (32%) at onset ≤ 30 days, 31-90 days, 91-365 days, and 366-1825 days after surgery, respectively. Multivariate Cox proportional analysis showed that adjuvant chemotherapy and a usual IP (UIP) pattern on CT + KL-6 ≥ 1000 (hazard ratio 3.647, 2.631) were predictors of late AEs.

Patients with adjuvant chemotherapy and a usual IP (UIP) pattern on CT + KL-6 ≥ 1000 are likely to develop later AEs. Therefore, early intervention with antifibrotic therapy is recommended.