Inhalation therapies in acute respiratory distress syndrome

Abstract

The defining features of acute respiratory distress syndrome (ARDS) are an excessive inflammatory respiratory response associated with high morbidity and mortality. Treatment consists mainly of measures to avoid worsening lung injury and cannot reverse the underlying pathophysiological process. New pharmacological agents have shown promising results in preclinical studies; however, they have not been successfully translated to patients with ARDS. The lack of effective therapeutic interventions has resulted in a recent interest in strategies to prevent ARDS with treatments delivering medications directly to the lungs by inhalation and nebulization, hopefully minimizing systemic adverse events. We analyzed the effect of different aerosolized drugs such as bronchodilators, corticosteroids, pulmonary vasodilators, anticoagulants, mucolytics and surfactant. New therapeutic strategies and ongoing trials using carbon monoxide (CO) and AP301 peptide are also briefly reviewed.

Future Trends in Nebulized Therapies for Pulmonary Disease

“…Adaptable nebulizer technology is ideal for combination in aerosol delivery systems where the objective is to augment lung dose by controlling, and possibly calculating and adapting to, a patient's breathing patterns. The role of nebulizers in treating respiratory disease, and symptoms of disease is the subject of numerous recent reviews, including in acute respiratory distress syndrome (ARDS) [2,3], chronic obstructive pulmonary disorder (COPD) [4,5], cystic fibrosis (CF) [6,7], ventilator-associated pneumonia (VAP) [8,9], dyspnea [10], and acute asthma [11], among others.…”

Identification of three classes of acute respiratory distress syndrome using latent class analysis

“…Clinical outcomes may be greatly improved if ARDS is promptly identified at an early stage and treated properly. Despite strenuous efforts being made to improve the clinical outcomes of ARDS ( Steinberg et al, 2006 ; Mansur et al, 2015 ; Zhang, Chen & Ni, 2015 ; Kacmarek et al, 2016 ; Artigas et al, 2017 ), the mortality rate remains unacceptably high ( Frenzel et al, 2011 ; Dalhoff et al, 2012 ; Bellani et al, 2016 ; Wang et al, 2016 ). The recent LUNG SAFE study reports a hospital mortality of 40%, with an increase across the severity in the Berlin definition ( Bellani et al, 2016 ).…”

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“…94,95 In addition to the traditional intravenous and subcutaneous administration of heparin, inhaled UFH and LMWH have been proposed and used in the context of pulmonary inflammation and ARDS, although optimal dosing and formulation is still under investigation. [96][97][98][99] Poor prognosis is associated with COVID-19 patients who display systemic inflammation in conjunction with coagulopathy, as manifested by increased D-dimers and fibrin degradation products (FDPs). 74 It has also been demonstrated that critically ill COVID-19 patients treated with anticoagulants, including UFH and LMWH, have a better prognosis as shown by increased survival and decreased need for mechanical ventilation.…”