Causes of acute respiratory failure in the immunocompromised host

A wide spectrum of heterogeneous conditions can render a patient immunocompromised. Recent years have seen an increase in the number of immunocompromised patients given the earlier detection of conditions that require immunosuppressive therapies, changes in immunosuppressive regimens leading to increased survival or novel therapeutic advancements in oncologic care. Acute respiratory failure (ARF) is the leading cause of critical illness and mortality in this population. This review highlights the spectrum of causes of ARF in immunocompromised patients with a particular focus on acute toxicities of novel oncologic treatments.

Recent years have seen improved survival amongst critically ill immunocompromised patients with ARF. This is likely attributable to patient selection of immunosuppressive therapy, improved noninvasive microbiologic diagnostic techniques, improved antimicrobial prophylaxis, treatment, stewardship, and advancements in supportive care including intensive care. Infectious complications remain the leading cause of ARF in this population. However, one of the greatest challenges physicians continue to face is accurate identification of the cause of ARF, given the vast (and increasing) noninfectious causes of ARF across these patients. Emerging therapies, such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR T-cell) have contributed to this problem. Finally, undetermined ARF is reported in approximately 13% of immunocompromised and is associated with a worse prognosis.

Infectious complications are still the leading cause of ARF in immunocompromised patients. However, noninfectious complications, derived from the underlying disease or treatment, should be always considered, including novel therapies, such as ICIs and CAR T cells. Further research should focus in improving the diagnostic rate in this subgroup.