Rationale Cigarette smoke exposure is associated with an increased risk of the acute respiratory distress syndrome (ARDS); however, the mechanisms underlying this relationship remain largely unknown. Objective To assess pathways of lung injury and inflammation in smokers and non-smokers with and without lipopolysaccharide (LPS) inhalation using established biomarkers. Methods We measured plasma and bronchoalveolar lavage (BAL) biomarkers of inflammation and lung injury in smokers and non-smokers in two distinct cohorts of healthy volunteers, one unstimulated (n=20) and one undergoing 50 μg LPS inhalation (n=30). Measurements and main results After LPS inhalation, cigarette smokers had increased alveolar-capillary membrane permeability as measured by BAL total protein, compared with non-smokers (median 274 vs 208 μg/mL, p=0.04). Smokers had exaggerated inflammation compared with non-smokers, with increased BAL interleukin-1β (p=0.002), neutrophils (p=0.02), plasma interleukin-8 (p=0.003), and plasma matrix metalloproteinase-8 (p=0.006). Alveolar epithelial injury after LPS was more severe in smokers than non-smokers, with increased plasma (p=0.04) and decreased BAL (p=0.02) surfactant protein D. Finally, smokers had decreased BAL vascular endothelial growth factor (VEGF) (p<0.0001) with increased soluble VEGF receptor-1 (p=0.0001). Conclusions Cigarette smoke exposure may predispose to ARDS through an abnormal response to a ‘second hit,’ with increased alveolar-capillary membrane permeability, exaggerated inflammation, increased epithelial injury and endothelial dysfunction. LPS inhalation may serve as a useful experimental model for evaluation of the acute pulmonary effects of existing and new tobacco products.

The estimation of extra-vascular lung water (EVLW) is an essential component in the assessment of critically ill patients. EVLW is independently associated with mortality and its manipulation has been shown to improve outcome. Accurate assessment of lung water is possible with CT and MR imaging but these are impractical for real-time measurement in sick patients and have been superseded by single thermal dilution techniques. While useful, single thermo-dilution requires repeated calibration and is prone to error, suggesting a need for other monitoring methods. Traditionally the lung was not thought amenable to ultrasound examination owing to the high acoustic impedance of air; however, the identification of artefacts in diseased lung has led to increased use of ultrasound as a point of care investigation for both diagnosis and to monitor response to interventions. Following the initial description of B-lines in association with increased lung water, accumulating evidence has shown that they are a useful and responsive measure of the presence and dynamic changes in EVLW. Animal models have confirmed a correlation with lung gravimetry and the utility of B-lines has been demonstrated in many clinical situations and correlated against other established measures of EVLW. With increasing availability and expertise the role of ultrasound in estimating EVLW should be embedded in clinical practice and incorporated into clinical algorithms to aid decision making. This review looks at the evidence for ultrasound as a valid, easy to use, non-invasive point of care investigation to assess EVLW.

Background: Mechanical ventilation for acute respiratory failure is one of the most common indications for admission to intensive care units (ICUs). Airway mucus clearance is impaired in these patients medication, impaired mucociliary motility, increased mucus production etc. and mucoactive agents have the potential to improve outcomes. However, studies to date have provided inconclusive results. Despite this uncertainty, mucoactives are used in adult ICUs, although the extent of use and perceptions about place in therapy are not known. Aims and Objectives: We aim to describe the use of mucoactive agents in mechanically ventilated patients in UK adult critical care units. Specifically, our objectives are to describe clinicians perceptions about the use of mucoactive agents, understand the indications and anticipated benefits, and describe the prevalence and type of mucoactive agents in use. Methods: We conducted three surveys. Firstly, a practitioner-level survey aimed at nurses, physiotherapists and doctors to elucidate individual practitioners perceptions about the use of mucoactive agents. Secondly, a critical care unit-level survey aimed at pharmacists to understand how these perceptions translate into practice. Thirdly, a point prevalence survey to describe the extent of prescribing and range of products in use. The practitioner-level survey was disseminated through the UK Intensive Care Society for completion by a multi-professional membership. The unit-level and point prevalence surveys were disseminated cthrough the UK Clinical Pharmacy Association for completion by pharmacists. Results: The individual practitioners survey ranked ‘thick secretions’ as the main reason for commencing mucoactive agents determined using clinical assessment. The highest ranked perceived benefit for patient centred outcomes was the duration of ventilation. Of these respondents, 79% stated that further research was important and 87% expressed support for a clinical trial. The unit-level survey found that mucoactive agents were used in 83% of units. The most highly ranked indication was again ‘thick secretions’ and the most highly ranked expected patient centred clinical benefit being improved gas exchange and reduced ventilation time. Only five critical care units provided guidelines to direct the use of mucoactive agents (4%). In the point prevalence survey, 411/993 (41%) of mechanically ventilated patients received at least one mucoactive agent. The most commonly administered mucoactives were inhaled sodium chloride 0.9% (235/993, 24%), systemic carbocisteine (161/993, 16%) and inhaled hypertonic sodium cloride (127/993, 13%). Conclusions: Mucoactive agents are used extensively in mechanically ventilated adult patients in UK ICUs to manage ‘thick secretions’, with a key aim to reduce the duration of ventilation. There is widespread support for clinical trials to determine the optimal use of mucoactive agent therapy in this patient population.

Background: Acute type two respiratory failure (AT2RF) is characterized by high carbon dioxide levels (PaCO2 >6kPa). Non-invasive ventilation (NIV), the current standard of care, has a high failure rate. High flow nasal therapy (HFNT) has potential additional benefits such as CO2 clearance, the ability to communicate and comfort. The primary aim of this systematic review is to determine whether HFNT in AT2RF improves 1) PaCO2, 2) clinical and patient-centred outcomes and 3) to assess potential harms. Methods: We searched EMBASE, MEDLINE and CENTRAL (January 1999-January 2021). Randomised controlled trials (RCTs) and cohort studies comparing HFNT with low flow nasal oxygen (LFO) or NIV were included. Two authors independently assessed studies for eligibility, data extraction and risk of bias. We used Cochrane risk of bias tool for RCTs and Ottawa-Newcastle scale for cohort studies. Results: From 727 publications reviewed, four RCTs and one cohort study (n=425) were included. In three trials of HFNT vs NIV, comparing PaCO2 (kPa) at last follow-up time point, there was a significant reduction at four hours (1 RCT; HFNT median 6.7, IQR 5.6 – 7.7 vs NIV median 7.6, IQR 6.3 – 9.3) and no significant difference at 24-hours or five days. Comparing HFNT with LFO, there was no significant difference at 30-minutes. There was no difference in intubation or mortality. Conclusions: This review identified a small number of studies with low to very low certainty of evidence. A reduction of PaCO2 at an early time point of four hours post-intervention was demonstrated in one small RCT. Significant limitations of the included studies were lack of adequately powered outcomes and clinically relevant time-points and small sample size. Accordingly, systematic review cannot recommend the use of HFNT as the initial management strategy for AT2RF and trials adequately powered to detect clinical and patient-relevant outcomes are urgently warranted.

(1) Background: High-flow nasal therapy (HFNT) has shown several benefits in addressing respiratory failure. However, the quality of evidence and the guidance for safe practice are lacking. This survey aimed to understand HFNT practice and the needs of the clinical community to support safe practice. (2) Method: A survey questionnaire was developed and distributed to relevant healthcare professionals through national networks in the UK, USA and Canada; responses were collected between October 2020 and April 2021. (3) Results: In the UK and Canada, HFNT was used in 95% of hospitals, with the highest use being in the emergency department. HNFT was widely used outside of a critical care setting. HFNT was mostly used to treat acute type 1 respiratory failure (98%), followed by acute type 2 respiratory failure and chronic respiratory failure. Guideline development was felt to be important (96%) and urgent (81%). Auditing of practice was lacking in 71% of hospitals. In the USA, HFNT was broadly similar to UK and Canadian practice. (4) Conclusions: The survey results reveal several key points: (a) HFNT is used in clinical conditions with limited evidence; (b) there is a lack of auditing; (c) it is used in wards that may not have the appropriate skill mix; and (d) there is a lack of guidance for HFNT use.