Lowering Mortality In Patients With Idiopathic Pulmonary Fibrosis

A rare disease of unknown etiology, idiopathic pulmonary fibrosis (IPF) is characterized by progressive, irreversible scarring of the lung interstitium leading to a reduction in respiratory function and early mortality. In the course of the disease, patients with IPF may experience acute exacerbation (AE-IPF), which may lead to acute respiratory failure (ARF). By increasing the alveolar-arterial oxygen tension difference (PA-aO₂), impaired alveolar-end capillary diffusion to O₂, and ventilation-perfusion (VA/Q) mismatching represent the most common mechanism of severe, refractory hypoxaemia during an exacerbation episode.

Conventional oxygen therapy and invasive ventilator assistance are considered the standards of care for the treatment of blood gas abnormalities in critically ill patients with exacerbated IPF; nevertheless, the correction of hypoxemia still represents a challenge for physicians in the ICU. Patients’ outcomes frequently remain poor, with the majority dying within the first month and nearly all others within a year.

Recently developed strategies to improve oxygenation for the management of ARF in adult patients include high-flow nasal cannula (HFNC) oxygen therapy. HFNC is a supportive therapy technique that delivers heated, humidified inspired gas at a high flow rate and a precise fraction of inspired oxygen (FiO₂) through small pliable nasal prongs (see Picture). Several mechanisms have been reported to contribute to oxygenation improvement, which is one of the main potential benefits of using HFNC therapy as an alternative to standard oxygen therapy.

Delivering high inspiratory flow, HFNC may provide a better matching of gas flow in individuals with ARF, limiting the entrainment of room air during inspiration and ensuring higher FiO₂ (Image). Using high flows creates a small continuous positive airway pressure: a flow-dependent generation of positive end-expiratory pressure (PEEP) has been measured in healthy volunteers, with a median pressure of 7.4 cm H₂O at 60L/min. As a result, PEEP may reduce VA/Q mismatching and improve PaO₂ by preventing lung collapse. The continuous administration of a very high flow of gas directly in the nasopharinx washes CO₂, avoiding the rebreathing of the previous exhaled gas. Although dead space has not been measured in previous research, an experimental study has shown that fresh gas administered by HFNC at 30 L/min flushes the dead space in the nasal cavity and increases the FiO₂.

HFNC oxygen therapy is being increasingly used to correct severe, refractory hypoxemia in patients with respiratory distress due to a variety of causes, in particular exacerbation of Chronic Obstructive Pulmonary Disease (COPD).

For a study published in Therapeutic Advances in Respiratory Disease, my colleagues and I conducted a retrospective cohort study to assess the effect of a new treatment algorithm incorporating HFNC on the short-term outcomes of patients with AE-IPF. To this aim, patients with AE-IPF who developed ARF and were admitted to our respiratory ICU (RICU) were considered. Of participants, about 53% failed to respond satisfactorily to conventional oxygen therapy and required HFNC oxygen therapy. The overall RICU mortality rate of our study group was 47.1%. Considering that the short-term mortality of this specific patient population reported by other studies has been exceedingly high, reaching approximately 90% prior to 2007 and touching 70% according to more recent studies, the algorithm including HFNC seems to have had a positive effect on short-term prognosis, although survival remained low after patients were discharged. In particular, HFNC appears to have played an important role in reversing hypoxemia in 40% of our patients who were unable to achieve sufficient oxygenation while they were using standard, non-rebreathing face masks.

Despite a number of limitations, our study provides useful information for physicians entrusted with the care of exacerbated IPF patients:

• Use of a treatment algorithm incorporating HFNC can be associated with a short-term mortality lower than 50% in the event of ARF.
• HFNC should be provided to patients who are not responding to conventional oxygen therapy, as it seems to improve oxygenation in a relevant number of cases.