[A multicenter clinical study of diffuse alveolar hemorrhage in Chinese children]

Objective: To understand the etiological diagnosis, triggers for disease recurrence and treatment status of diffuse alveolar hemorrhage (DAH) in Chinese children. Methods: A retrospective cohort study was conducted. Clinical data, including baseline information, laboratory findings, chest imaging findings and treatment regimens were collected from 567 children with DAH admitted to 21 hospitals in China from 2002 to 2021. Cases with immune-related etiologies or undetermined etiological diagnosis were included and divided into two groups based on glucocorticoids treatment duration: ≥3 months group and <3 months group. The study period from January 2002 to December 2021 was divided into two time intervals: 2002-2011 and 2012-2021. The two groups were compared in terms of etiological diagnosis rate, initial and overall immunosuppressant use rate, disease recurrence rate and mortality rate. All group comparisons were performed using the χ² test. Results: Among the 567 children with DAH, 333 were male and 234 were female. The age at onset was 4.0 (2.1, 6.5) years and the follow-up duration was 4.4 (2.4, 7.2) years. A definite etiological diagnosis was established in 107 cases (18.9%), while 460 cases (81.1%) remained without a definite etiological diagnosis. Among the 494 cases (including idiopathic pulmonary hemosiderosis and those with undetermined etiological diagnosis), 389 cases (78.7%) were initially treated with glucocorticoids alone and 45 cases (9.1%) with a combination of glucocorticoids and immunosuppressants. Throughout the treatment, immunosuppressants were used in 132 cases (26.7%). Among the 549 cases (including immune-related cases and those with undetermined etiological diagnosis), 303 cases (55.2%) experienced recurrent exacerbation of the disease. The common triggers included respiratory infection in 193 cases (35.2%), glucocorticoid dose reduction in 103 cases (18.8%) and non-adherence to medication in 66 cases (12.0%). Eight cases were lost to follow-up. The mortality rate was 8.7% (47/541), with causes of death including end-stage lung disease with severe infection in 32 cases (5.9%), severe pulmonary hemorrhage in 12 cases (2.2%) and unknown cause in 3 cases (0.5%). Among those receiving glucocorticoids therapy, 373 cases were in the ≥3 months group and 125 cases in the <3 months group. The mortality rate in the ≥3 months group was lower than that in the <3 months group (P<0.01). There were 92 cases in the 2002-2012 group and 457 cases in the 2012-2021 group. The utilization rates of immunosuppressants in both initial treatment and the entire treatment course for children with immune-related and those with undetermined etiological diagnosis were higher in the 2012-2021 group than in the 2002-2012 group (both P<0.01). Conclusions: In China, pediatric DAH has complex etiologies and a definitive etiological diagnosis remains difficult to establish in some cases. Recurrent exacerbation is common and mainly due to the respiratory infection, glucocorticoids dose reduction and non-adherence to medication. Glucocorticoids remain the primary treatment, with combined use of immunosuppressants in some cases.