Cyclophosphamide for interstitial lung disease-associated acute respiratory failure: mortality, clinical response and radiological characteristics

BMC Pulm Med. 2021 Jul 28;21(1):249. doi: 10.1186/s12890-021-01615-2.

Abstract

Background: Treatment for interstitial lung disease (ILD) patients with acute respiratory failure (ARF) is challenging, and literature to guide such treatment is scarce. The reported in-hospital mortality rates of ILD patients with ARF are high (62-66%). Cyclophosphamide is considered a second-line treatment in steroid-refractory ILD-associated ARF. The first aim of this study was to evaluate the in-hospital mortality in patients with ILD-associated ARF treated with cyclophosphamide. The second aim was to compare computed tomographic (CT) patterns and physiological and ventilator parameters between survivors and non-survivors.

Methods: Retrospective analysis of patients with ILD-associated ARF treated with cyclophosphamide between February 2016 and October 2017. Patients were categorized into three subgroups: connective tissue disease (CTD)-associated ILD, other ILD or vasculitis. In-hospital mortality was evaluated in the whole cohort and in these subgroups. Clinical response was determined using physiological and ventilator parameters: Sequential Organ Failure Assessment Score (SOFA), PaO2/FiO2 (P/F) ratio and dynamic compliance (Cdyn) before and after cyclophosphamide treatment. The following CT features were quantified: ground-glass opacification (GGO) proportion, reticulation proportion, overall extent of parenchymal disease and fibrosis coarseness score.

Results: Fifteen patients were included. The overall in-hospital mortality rate was 40%. In-hospital mortality rates for CTD-associated ILD, other ILD and vasculitis were 20, 57, and 33%, respectively. The GGO proportion (71% vs 45%) was higher in non-survivors. There were no significant differences in the SOFA score, P/F ratio or Cdyn between survivors and non-survivors. However, in survivors the P/F ratio increased from 129 to 220 mmHg and Cdyn from 75 to 92 mL/cmH2O 3 days after cyclophosphamide treatment. In non-survivors the P/F ratio hardly changed (113-114 mmHg) and Cdyn even decreased (27-20 mL/cmH2O).

Conclusion: In this study, we found a mortality rate of 40% in patients treated with cyclophosphamide for ILD-associated ARF. Connective tissue disease-associated ILD and vasculitis were associated with a lower risk of death. In non-survivors, the CT GGO proportion was significantly higher. The P/F ratio and Cdyn in survivors increased after 3 days of cyclophosphamide treatment.

Keywords: Acute respiratory failure; Cyclophosphamide; Ground-glass opacification; Interstitial lung disease.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Connective Tissue Diseases / drug therapy*
  • Connective Tissue Diseases / physiopathology
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / adverse effects
  • Female
  • Hospital Mortality
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Lung Compliance
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / physiopathology
  • Male
  • Middle Aged
  • Netherlands
  • Pulmonary Diffusing Capacity / physiology
  • Pulmonary Gas Exchange
  • Respiratory Distress Syndrome / drug therapy*
  • Respiratory Distress Syndrome / physiopathology
  • Retrospective Studies
  • Severity of Illness Index
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide