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This article, published in the journal Thorax, explores the effects of non-invasive ventilation (NIV) on sleep in chronic hypercapnic respiratory failure. It discusses the impact of chronic respiratory diseases on sleep quality and the potential role of NIV in improving health-related quality of life. The article also highlights the physiological changes that occur during sleep in patients with conditions such as chronic obstructive pulmonary disease (COPD), obesity-related respiratory failure (ORRF), and neuromuscular disorders (NMD). It emphasizes the importance of monitoring sleep quality in patients using long-term NIV and the need for further research to fully understand the effects of NIV on sleep quality. The document provides a list of references that cover studies on the relationship between sleep quality and various respiratory conditions, including COPD, obesity-related hypoventilation syndrome, and neuromuscular diseases. These references offer valuable information for researchers and healthcare professionals working with these patient populations. [Extracted from the article]

BackgroundOrganophosphate pesticides are heavily used in agriculture, and adverse associations with respiratory health in occupational settings have been reported. However, most of the evidence comes from studies where there were no biomarkers of exposure and no objective outcome measurement. Non-occupational chronic effects among residents living in agricultural communities are less well described.ObjectiveTo evaluate associations between early-life organophosphate exposure and lung function of children living in an agricultural community.MethodsParticipants were 279 children from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal birth cohort. The area under the curve for organophosphate exposure was determined by urinary diethyl and dimethyl dialkylphosphate metabolites of organophosphate pesticides, which were measured five times during childhood (6-60 months). Spirometry was performed at age 7 years. Regression models controlled for maternal smoking during pregnancy, season of birth, particulate matter concentrations with aerodynamic diameter ≤2.5 μm (PM2.5), breast feeding duration, mould and pets at home, distance of home from a highway, food insecurity, maternal education, season of spirometry, sex, height and technician.ResultsChildhood diethyl, dimethyl and total dialkylphosphate concentrations were associated with significant decreases in lung function at age 7. Specifically, we found lower FEV1, (L/s) (ß=-0.16, 95% CI -0.30 to -0.02, p=0.03) and FVC (L) (ß=-0.17, 95% CI -0.34 to 0.01, p=0.06) per 10-fold increase of total dialkylphosphate levels.ConclusionsEarly-life organophosphate exposure as assessed by dialkylphosphate concentrations was adversely associated with 7-year-old children's lung function.

Introduction: High-flow nasal cannula (HFNC) provides benefits to patients undergoing flexible bronchoscopy (FOB). We compared the effects of HFNC versus standard therapy (ST) on gas exchange, lung volume and diaphragm function in patients undergoing FOB for bronchoalveolar lavage (BAL).Methods: 36 outpatients were randomised to ST or HFNC. Arterial blood gases, episodes of severe desaturation, changes of end-expiratory lung impedance (ΔEELI), diaphragm ultrasound were recorded. Measurements were done at baseline (T0), after bronchoscope insertion (T1), at the end of the procedure (T2) and 10 min afterwards (T3).Results: Arterial partial oxygen pressure (PaO2) was not different between T0 (10.8 (95% CI 8.7 to 12.0) kPa and T2 (11.1 (95% CI 10.4 to 12.0) kPa) with HFNC, while decreased from 11.1 (95% CI 10.5 to 12.1) to 9.1 (95% CI 8.4 to 9.8) kPa with ST. At T2, PaO2 was significantly higher with HFNC than with ST (p<0.001). Also, with HFNC, compared with ST, fewer desaturations occurred (11% vs 56%; p<0.01). ΔEELI was no different at the different time points with HFNC, while with ST there was a significant decrease at T1 (-170 (95% CI -382 to -32) mL, p=0.003), T2 (-211 (95% CI -425 to -148) mL, p<0.001) and T3 (-213 (95% CI -398 to -81) mL, p<0.001), as opposed to T0. EELI was lower with ST than HFNC at T1 (p=0.006), T2 (p=0.001) and T3 (p=0.002). Diaphragm displacement was no different between groups (p=0.748), while the thickening fraction significantly increased at T1 and T2 with ST only (p<0.01).Conclusions: During FOB for BAL, HFNC improves gas exchange, avoiding loss of end-expiratory lung volume and preventing increase of diaphragm activation.Trial Registration Number: NCT04016480. [ABSTRACT FROM AUTHOR]

Purpose: To assess the association between respiratory muscle weakness (RMW) at intensive care unit (ICU) discharge and 5-year mortality and morbidity, independent from confounders including peripheral muscle strength.Methods: Secondary analysis of the prospective 5-year follow-up of the EPaNIC cohort (ClinicalTrials.gov: NCT00512122), limited to 366 patients screened for respiratory and peripheral muscle strength in the ICU with maximal inspiratory pressure (MIP) after removal of the artificial airway, and the Medical Research Council sum score. RMW was defined as an absolute value of MIP <30 cmH2O. Associations between RMW at (or closest to) ICU discharge and all-cause 5-year mortality, and key measures of 5-year physical function, comprising respiratory muscle strength (MIP), hand-grip strength (HGF), 6 min walk distance (6MWD) and physical function of the SF-36 quality-of-life questionnaire (PF-SF-36), were assessed with Cox proportional hazards and linear regression models, adjusted for confounders including peripheral muscle strength.Results: RMW was present in 136/366 (37.2%) patients at ICU discharge. RMW was not independently associated with 5-year mortality (HR with 95% CI 1.273 (0.751 to 1.943), p=0.352). Among 156five-year survivors, those with, as compared with those without RMW demonstrated worse physical function (MIP (absolute value, cmH2O): 62(42-77) vs 94(78-109), p<0.001; HGF (%pred): 67(44-87) vs 96(68-110), p<0.001; 6MWD (%pred): 87(74-102) vs 99 (80-111), p=0.009; PF-SF-36 (score): 55 (30-80) vs 80 (55-95), p<0.001). Associations between RMW and morbidity endpoints remained significant after adjustment for confounders (effect size with 95% CI: MIP: -23.858 (-32.097 to -15.027), p=0.001; HGF: -18.591 (-30.941 to -5.744), p=0.001; 6MWD (transformed): -1587.007 (-3073.763 to -179.253), p=0.034; PF-SF-36 (transformed): 1.176 (0.144-2.270), p=0.036).Conclusions: RMW at ICU discharge is independently associated with 5-year morbidity but not 5-year mortality. [ABSTRACT FROM AUTHOR]

Background: Identifying subtypes of acute respiratory failure survivors may facilitate patient selection for post-intensive care unit (ICU) follow-up clinics and trials.Methods: We conducted a single-centre prospective cohort study of 185 acute respiratory failure survivors, aged ≥ 65 years. We applied latent class modelling to identify frailty subtypes using frailty phenotype and cognitive impairment measurements made during the week before hospital discharge. We used Fine-Gray competing risks survival regression to test associations between frailty subtypes and recovery, defined as returning to a basic Activities of Daily Living disability count less than or equal to the pre-hospitalisation count within 6 months. We characterised subtypes by pre-ICU frailty (Clinical Frailty Scale score ≥ 5), the post-ICU frailty phenotype, and serum inflammatory cytokines, hormones and exosome proteomics during the week before hospital discharge.Results: We identified five frailty subtypes. The recovery rate decreased 49% across each subtype independent of age, sex, pre-existing disability, comorbidity and Acute Physiology and Chronic Health Evaluation II score (recovery rate ratio: 0.51, 95% CI 0.41 to 0.63). Post-ICU frailty phenotype prevalence increased across subtypes, but pre-ICU frailty prevalence did not. In the subtype with the slowest recovery, all had cognitive impairment. The three subtypes with the slowest recovery had higher interleukin-6 levels (p=0.03) and a higher prevalence of ≥ 2 deficiencies in insulin growth factor-1, dehydroepiandrostersone-sulfate, or free-testosterone (p=0.02). Exosome proteomics revealed impaired innate immunity in subtypes with slower recovery.Conclusions: Frailty subtypes varied by prehospitalisation frailty and cognitive impairment at hospital discharge. Subtypes with the slowest recovery were similarly characterised by greater systemic inflammation and more anabolic hormone deficiencies at hospital discharge. [ABSTRACT FROM AUTHOR]

Introduction: Although home non-invasive ventilation (NIV) is increasingly used to manage patients with chronic ventilatory failure, there are limited data on the long-term outcome of these patients. Our aim was to report on home NIV populations and the long-term outcome from two European centres.Methods: Cohort analysis including all patients established on home NIV from two European centres between 2008 and 2014.Results: Home NIV was initiated in 1746 patients to treat chronic ventilatory failure caused by (1) obesity hypoventilation syndrome±obstructive sleep apnoea (OHS±OSA) (29.5%); (2) neuromuscular disease (NMD) (22.7%); and (3) obstructive airway diseases (OAD) (19.1%). Overall cohort median survival following NIV initiation was 6.6 years. Median survival varied by underlying aetiology of respiratory failure: rapidly progressive NMD 1.1 years, OAD 2.7 years, OHS±OSA >7 years and slowly progressive NMD >7 years. Multivariate analysis demonstrated higher mortality in patients with rapidly progressive NMD (HR 4.78, 95% CI 3.38 to 6.75), COPD (HR 2.25, 95% CI 1.64 to 3.10), age >60 years at initiation of home NIV (HR 2.41, 95% CI 1.92 to 3.02) and NIV initiation following an acute admission (HR 1.38, 95% CI 1.13 to 1.68). Factors associated with lower mortality were NIV adherence >4 hours per day (HR 0.64, 95% CI 0.51 to 0.79), OSA (HR 0.51, 95% CI 0.31 to 0.84) and female gender (HR 0.79, 95% CI 0.65 to 0.96).Conclusion: The mortality rate following initiation of home NIV is high but varies significantly according to underlying aetiology of respiratory failure. In patients with chronic respiratory failure, initiation of home NIV following an acute admission and low levels of NIV adherence are poor prognostic features and may be amenable to intervention. [ABSTRACT FROM AUTHOR]

The use of extracorporeal membrane oxygenation for high-risk rigid bronchoscopy has been reported in few urgent cases. We report our experience with this approach which was planned electively in five cases on 202 procedures (2.5%). It was proposed because of the potential inability to ventilate the lungs using conventional techniques due to extensive tracheobronchial lesions or the risk of major intraoperative bleeding related to disease characteristics. There were no intraoperative complications and postoperative course was favourable in all patients. With a maximum follow-up of 3 years and 7 months, all patients are alive with no tracheostomy despite major morbidities. [ABSTRACT FROM AUTHOR]

Purpose: Acute respiratory failure (ARF) is a common cause of admission to intensive care units (ICUs). Mucoactive agents are medications that promote mucus clearance and are frequently administered in patients with ARF, despite a lack of evidence to underpin clinical decision making. The aim of this systematic review was to determine if the use of mucoactive agents in patients with ARF improves clinical outcomes.Methods: We searched electronic and grey literature (January 2020). Two reviewers independently screened, selected, extracted data and quality assessed studies. We included trials of adults receiving ventilatory support for ARF and involving at least one mucoactive agent compared with placebo or standard care. Outcomes included duration of mechanical ventilation. Meta-analysis was undertaken using random-effects modelling and certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation.Results: Thirteen randomised controlled trials were included (1712 patients), investigating four different mucoactive agents. Mucoactive agents showed no effect on duration of mechanical ventilation (seven trials, mean difference (MD) -1.34, 95% CI -2.97 to 0.29, I2=82%, very low certainty) or mortality, hospital stay and ventilator-free days. There was an effect on reducing ICU length of stay in the mucoactive agent groups (10 trials, MD -3.22, 95% CI -5.49 to -0.96, I2=89%, very low certainty).Conclusion: Our findings do not support the use of mucoactive agents in critically ill patients with ARF. The existing evidence is of low quality. High-quality randomised controlled trials are needed to determine the role of specific mucoactive agents in critically ill patients with ARF.Prospero Registration Number: CRD42018095408. [ABSTRACT FROM AUTHOR]

Introduction: Chronic non-invasive ventilation (NIV) has become evidence-based care for stable hypercapnic COPD patients. While the number of patients increases, home initiation of NIV would greatly alleviate the healthcare burden. We hypothesise that home initiation of NIV with the use of telemedicine in stable hypercapnic COPD is non-inferior to in-hospital NIV initiation.Methods: Sixty-seven stable hypercapnic COPD patients were randomised to initiation of NIV in the hospital or at home using telemedicine. Primary outcome was daytime arterial carbon dioxide pressure (PaCO2) reduction after 6 months NIV, with a non-inferiority margin of 0.4 kPa. Secondary outcomes were health-related quality of life (HRQoL) and costs.Results: Home NIV initiation was non-inferior to in-hospital initiation (adjusted mean difference in PaCO2 change home vs in-hospital: 0.04 kPa (95% CI -0.31 to 0.38 kPa), with both groups showing a PaCO2 reduction at 6 months compared with baseline (home: from 7.3±0.9 to 6.4±0.8 kPa (p<0.001) and in-hospital: from 7.4±1.0 to 6.4±0.6 kPa (p<0.001)). In both groups, HRQoL improved without a difference in change between groups (Clinical COPD Questionnaire total score-adjusted mean difference 0.0 (95% CI -0.4 to 0.5)). Furthermore, home NIV initiation was significantly cheaper (home: median €3768 (IQR €3546-€4163) vs in-hospital: median €8537 (IQR €7540-€9175); p<0.001).Discussion: This is the first study showing that home initiation of chronic NIV in stable hypercapnic COPD patients, with the use of telemedicine, is non-inferior to in-hospital initiation, safe and reduces costs by over 50%.Trial Registration Number: NCT02652559. [ABSTRACT FROM AUTHOR]

An application (app) for the Severe Respiratory Insufficiency Questionnaire (SRI) has been designed and developed for mobile devices. In a randomised controlled trial comprising 60 patients with chronic respiratory failure, the app was compared with the classic paper SRI. Thereby, it was shown that the SRI app is a practical tool that is well accepted. Missing values can be completely avoided by using the SRI app. Finally, reliability, convergent and discriminant validities were established. Accordingly, for the individual SRI subscales, Cronbach's alpha ranged between 0.56 and 0.81 (app) and between 0.54 and 0.83 (paper), respectively. The multilingual SRI app is accessible free of charge for non-profit research purposes. [ABSTRACT FROM AUTHOR]

Neural respiratory drive (NRD), as reflected by change in parasternal muscle electromyogram (EMGpara), predicts clinical deterioration and safe discharge in patients admitted to hospital with an acute exacerbation of COPD (AECOPD). The clinical utility of NRD to predict the long-term outcome of patients following hospital admission with an AECOPD is unknown. We undertook a post hoc analysis of a previously published prospective observational cohort study measuring NRD in 120 patients with AECOPD. Sixty-nine (57.5%) patients died during follow-up (median 3.6 years). Respiratory failure was the most common cause of death (n=29; 42%). In multivariate analysis, factors independently associated with an increased mortality included NRD (HR 2.14, 95% CI 1.29 to 3.54, p=0.003), age (HR 2.03, 95% CI 1.23 to 3.34, p=0.006), PaCO2 at admission (HR 1.83, 95% CI 1.06 to 3.06, p=0.022) and long-term oxygen use (HR 2.98, 95% CI 1.47 to 6.03, p=0.002). NRD at hospital discharge could be measured in order to assess efficacy of interventions targeted to optimise COPD and reduce mortality following an AECOPD. Original clinicaltrial.gov number: NCT01361451. [ABSTRACT FROM AUTHOR]

The CIRO Academy in Horn (the Netherlands) organised a 2-day meeting to present and discuss the studies published in 2017 pertaining to key priority areas of respiratory and critical care medicine. This review summarises studies focussing on pulmonary rehabilitation and exercise training, physical activity, chronic respiratory failure and palliative respiratory care published in 2017. [ABSTRACT FROM AUTHOR]

Background: Patients who are sick enough to be admitted to an intensive care unit (ICU) commonly experience symptoms of psychological distress after discharge, yet few effective therapies have been applied to meet their needs.Methods: Pilot randomised clinical trial with 3-month follow-up conducted at two academic medical centres. Adult (≥18 years) ICU patients treated for cardiorespiratory failure were randomised after discharge home to 1 of 3 month-long interventions: a self-directed mobile app-based mindfulness programme; a therapist-led telephone-based mindfulness programme; or a web-based critical illness education programme.Results: Among 80 patients allocated to mobile mindfulness (n=31), telephone mindfulness (n=31) or education (n=18), 66 (83%) completed the study. For the primary outcomes, target benchmarks were exceeded by observed rates for all participants for feasibility (consent 74%, randomisation 91%, retention 83%), acceptability (mean Client Satisfaction Questionnaire 27.6 (SD 3.8)) and usability (mean Systems Usability Score 89.1 (SD 11.5)). For secondary outcomes, mean values (and 95% CIs) reflected clinically significant group-based changes on the Patient Health Questionnaire depression scale (mobile (-4.8 (-6.6, -2.9)), telephone (-3.9 (-5.6, -2.2)), education (-3.0 (-5.3, 0.8)); the Generalized Anxiety Disorder scale (mobile -2.1 (-3.7, -0.5), telephone -1.6 (-3.0, -0.1), education -0.6 (-2.5, 1.3)); the Post-Traumatic Stress Scale (mobile -2.6 (-6.3, 1.2), telephone -2.2 (-5.6, 1.2), education -3.5 (-8.0, 1.0)); and the Patient Health Questionnaire physical symptom scale (mobile -5.3 (-7.0, -3.7), telephone -3.7 (-5.2, 2.2), education -4.8 (-6.8, 2.7)).Conclusions: Among ICU patients, a mobile mindfulness app initiated after hospital discharge demonstrated evidence of feasibility, acceptability and usability and had a similar impact on psychological distress and physical symptoms as a therapist-led programme. A larger trial is warranted to formally test the efficacy of this approach.Trial Registration Number: Results, NCT02701361. [ABSTRACT FROM AUTHOR]

This observational study aims to assess the outcome and safety of O2-therapy by high-flow nasal cannula (HFNC) in 28 consecutive patients with severe hypoxemic acute respiratory failure (hARF) consequent to SARS-CoV-2 infection, unresponsive to conventional O2-therapy. Nineteen patients had a positive response. Nine patients required escalation of treatment to non-invasive ventilation (five subsequently intubated). None of the staff had a positive swab testing during the study period and the following 14 days. Severity of hypoxemia and C reactive protein level were correlated with HFNC failure. These data suggest HFNC to be a safe treatment for less severe patients with SARS-CoV-2 hARF and efficacy will need to be assessed as part of a clinical trial. [ABSTRACT FROM AUTHOR]

Severity of hypoxaemia can be assessed using the partial pressure of arterial oxygen to fraction of inspired oxygen ratio (FiO2). However, in patients breathing through non-rebreather reservoir bag oxygen mask, accuracy of bedside FiO2 estimation methods remains to be tested. In a post-hoc analysis of a multicentre clinical trial, three FiO2 estimation methods were compared with FiO2 measured with a portable oxygen analyser introduced in the oxygen mask. Among 262 patients analysed, mean (SD) measured FiO2 was 65% (13). The 3%-formula (21% + oxygen flow rate in L/min × 3) was the most accurate method to estimate FiO2 Other methods overestimated FiO2 and hypoxaemia severity, so they should be avoided. [ABSTRACT FROM AUTHOR]

Background: Efficiency of randomised clinical trials of acute respiratory distress syndrome (ARDS) depends on the fraction of deaths attributable to ARDS (AF ARDS ) to which interventions are targeted. Estimates of AF ARDS in subpopulations of ARDS could improve design of ARDS trials., Methods: We performed a matched case-control study using the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE cohort. Primary outcome was intensive care unit mortality. We used nearest neighbour propensity score matching without replacement to match ARDS to non-ARDS populations. We derived two separate AF ARDS estimates by matching patients with ARDS to patients with non-acute hypoxaemic respiratory failure (non-AHRF) and to patients with AHRF with unilateral infiltrates only (AHRF-UL). We also estimated AF ARDS in subgroups based on severity of hypoxaemia, number of lung quadrants involved and hyperinflammatory versus hypoinflammatory phenotypes. Additionally, we derived AF AHRF estimates by matching patients with AHRF to non-AHRF controls, and AF AHRF-UL estimates by matching patients with AHRF-UL to non-AHRF controls., Results: Estimated AF ARDS was 20.9% (95% CI 10.5% to 31.4%) when compared with AHRF-UL controls and 38.0% (95% CI 34.4% to 41.6%) compared with non-AHRF controls. Within subgroups, estimates for AF ARDS compared with AHRF-UL controls were highest in patients with severe hypoxaemia (41.1% (95% CI 25.2% to 57.1%)), in those with four quadrant involvement on chest radiography (28.9% (95% CI 13.4% to 44.3%)) and in the hyperinflammatory subphenotype (26.8% (95% CI 6.9% to 46.7%)). Estimated AF AHRF was 33.8% (95% CI 30.5% to 37.1%) compared with non-AHRF controls. Estimated AF AHRF-UL was 21.3% (95% CI 312.8% to 29.7%) compared with non-AHRF controls., Conclusions: Overall AF ARDS mean values were between 20.9% and 38.0%, with higher AF ARDS seen with severe hypoxaemia, four quadrant involvement on chest radiography and hyperinflammatory ARDS., Competing Interests: Competing interests: CS is funded by UKRI (MR/S035753/1 and MR/X005070/1) and the National Institute for Health and Care Research (NIHR133788). Work in her research group is supported by GlaxoSmithKline, the Wellcome Trust and the Cambridge NIHR Biomedical Research Centre, and she has received consultancy fees from AbbVie, Sanofi and GlaxoSmithKline. CSC is funded by National Institutes of Health R35-HL140026 and reports grant funding from Roche-Genentech and Quantum Leap Healthcare collaborative, in addition to the National Institutes of Health, and consulting fees from Vasomune, Gen1e Life Sciences, Cellenkos and Janssen. EF reports personal fees from ALung Technologies, Aerogen, Baxter, GE Healthcare, Inspira and Vasomune outside the submitted work. JGL is funded by a Future Research Leaders Award (16-FRL-3845) from Science Foundation Ireland and reports receiving consulting fees from Baxter and from GlaxoSmithKline. RS reports no conflicts. MS-H is funded by a clinician scientist fellowship from the National Institute for Health Research (CS-2016-16-011) and reports receiving grants from the NIHR, MRC, EME, HTA, Huo Foundation and highlights industry support for TRAITS research programme (a Chief Scientists Office, Scotland funded time critical precision medicine in adult critically ill patients (TRAITS Programme))., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Few studies have assessed the impact of home ventilation in patients with myotonic dystrophy type 1 (DM1) and no specific recommendations are available. We assessed the survival associated with category of home ventilation adherence of patients with DM1 followed up at a home ventilation unit using a Cox proportional hazards model. 218 patients were included; those who refused or delayed their acceptance of non-invasive ventilation were at higher risk for severe events (invasive ventilation or death) (P=0.03). Risk of death was associated with orthopnoea (HR 2.37; 95% CI 1.17 to 4.80; P<0.02) and adherence category (100 to 90% vs >75%: HR 3.26; 95% CI 1.32 to 8.04; P<0.03). Failure to use home ventilation as prescribed may be associated with increased mortality in patients with DM1. [ABSTRACT FROM AUTHOR]

Background: Acute hypoxic respiratory failure (AHRF) is associated with significant acute mortality. It is unclear whether later mortality is predominantly driven by pre-existing comorbid disease, the acute inciting event or is the result of AHRF itself.Methods: Observational cohort study of elderly US Health and Retirement Study (HRS) participants in fee-for-service Medicare (1998-2012). Patients hospitalised with AHRF were matched 1:1 to otherwise similar adults who were not currently hospitalised and separately to patients hospitalised with acute inciting events (pneumonia, non-pulmonary infection, aspiration, trauma, pancreatitis) that may result in AHRF, here termed at-risk hospitalisations. The primary outcome was late mortality-death in the 31 days to 2 years following hospital admission.Results: Among 15 075 HRS participants, we identified 1268 AHRF and 13 117 at-risk hospitalisations. AHRF hospitalisations were matched to 1157 non-hospitalised adults and 1017 at-risk hospitalisations. Among patients who survived at least 30 days, AHRF was associated with a 24.4% (95%CI 19.9% to 28.9%, p<0.001) absolute increase in late mortality relative to adults not currently hospitalised and a 6.7% (95%CI 1.7% to 11.7%, p=0.01) increase relative to adults hospitalised with acute inciting event(s) alone. At-risk hospitalisation explained 71.2% of the increased odds of late mortality, whereas the development of AHRF itself explained 28.8%. Risk for death was equivalent to at-risk hospitalisation beyond 90 days, but remained elevated for more than 1 year compared with non-hospitalised controls.Conclusions: In this national sample of older Americans, approximately one in four survivors with AHRF had a late death not explained by pre-AHRF health status. More than 70% of this increased risk was associated with hospitalisation for acute inciting events, while 30% was associated with hypoxemic respiratory failure. [ABSTRACT FROM AUTHOR]

Background: There is heterogeneity among the outcomes evaluated in studies of survivors of acute respiratory failure (ARF).Aim: To evaluate the importance of specific outcome domains to acute respiratory distress syndrome (ARDS) survivors, their family members and clinical researchers.Methods: Nineteen outcome domains were identified from the National Institutes of Health's Patient Reported Outcomes Measurement Information System; WHO's International Classification of Functioning, Disability, and Health; Society of Critical Care Medicine's Post-Intensive Care Syndrome (PICS); as well as patient, clinician and researcher input. We surveyed ARDS survivors, family members and critical care researchers, 279 respondents in total, using a 5-point scale (strongly disagree, disagree, neutral, agree and strongly agree) to rate the importance of measuring each domain in studies of ARF survivors' postdischarge outcomes.Measurements and Main Results: At least 80% of patients and family members supported (ie, rated 'agree' or 'strongly agree') that 15 of the 19 domains should be measured in all future studies. Among researchers, 6 of 19 domains were supported, with researchers less supportive for all domains, except survival (95% vs 72% support). Overall, four domains were supported by all groups: physical function, cognitive function, return to work or prior activities and mental health.Conclusion: Patient, family and researcher groups supported inclusion of outcome domains that fit within the PICS framework. Patients and family members also supported many additional domains, emphasising the importance of including patients/family, along with researchers, in consensus processes to select core outcome domains for future research studies. [ABSTRACT FROM AUTHOR]

Rationale: In the last decade, due to expansion of greenhouses and irrigated farms, the use of pesticides in Ethiopia has increased 6-13-fold leading to potential health risks.Objective: To investigate if occupational exposure to pesticides is associated with respiratory health effects in farmers and farm workers from commercial farming systems.Methods: We performed two cross-sectional surveys comprising different farming systems. In the first survey we studied respiratory symptoms among 1104 subjects of which 601 were occupationally exposed to pesticides (ie, 256 pesticide applicators, 345 re-entry workers) and 503 unexposed individuals. The second survey, carried out 2 years later in the same farming regions, additionally included lung function measurement and comprised a total of 387 study subjects of which 206 were occupationally exposed to pesticides (142 applicators and 64 re-entry workers) and 180 unexposed individuals.Results: We observed increased risks for chronic cough and shortness of breath (OR=3.15, 95% CI 1.56 to 6.36 and OR=6.67, 95% CI 2.60 to 17.58) among the exposed subjects as compared with unexposed individuals in the first survey. These results were corroborated in the second survey where we also observed reductions in FEV1 (140 mL), forced expiratory flow 25%-75% (550 mL/s) and risk of FEV1/FVC ratio <0.8 (OR=4.31, 95% CI 2.11 to 8.81) among pesticide exposed workers.Conclusions: These findings indicate an increased risk of adverse respiratory health among workers exposed to pesticides. As those effects occurred in young workers (mean age 27 years) and within a relative short duration of exposure (4 years) implementation of stringent occupational health measures are warranted. [ABSTRACT FROM AUTHOR]

Background: Most patients with amyotrophic lateral sclerosis (ALS) are treated with mechanical insufflation-exsufflation (MI-E) in order to improve cough. This method often fails in ALS with bulbar involvement, allegedly due to upper-airway malfunction. We have studied this phenomenon in detail with laryngoscopy to unravel information that could lead to better treatment.Methods: We conducted a cross-sectional study of 20 patients with ALS and 20 healthy age-matched and sex-matched volunteers. We used video-recorded flexible transnasal fibre-optic laryngoscopy during MI-E undertaken according to a standardised protocol, applying pressures of ±20 to ±50 cm H2O. Laryngeal movements were assessed from video files. ALS type and characteristics of upper and lower motor neuron symptoms were determined.Results: At the supraglottic level, all patients with ALS and bulbar symptoms (n=14) adducted their laryngeal structures during insufflation. At the glottic level, initial abduction followed by subsequent adduction was observed in all patients with ALS during insufflation and exsufflation. Hypopharyngeal constriction during exsufflation was observed in all subjects, most prominently in patients with ALS and bulbar symptoms. Healthy subjects and patients with ALS and no bulbar symptoms (n=6) coordinated their cough well during MI-E.Conclusions: Laryngoscopy during ongoing MI-E in patients with ALS and bulbar symptoms revealed laryngeal adduction especially during insufflation but also during exsufflation, thereby severely compromising the size of the laryngeal inlet in some patients. Individually customised settings can prevent this and thereby improve and extend the use of non-invasive MI-E. [ABSTRACT FROM AUTHOR]

The article presents the British Thoracic Society/Intensive Care Society (BTS/ICS) guideline with recommendations and practice points in managing ventilation to adults with acute hypercapnic respiratory failure including the modes of mechanical ventilation, use of tracheostomy, and cystic fibrosis.

Design: Randomised crossover trial with 6 months of standard best practice clinical care (control group) and 6 months with the addition of telemonitoring.Participants: 68 patients with chronic lung disease (38 with COPD; 30 with chronic respiratory failure due to other causes), who had a hospital admission for an exacerbation within 6 months of randomisation and either used long-term oxygen therapy or had an arterial oxygen saturation (SpO2) of <90% on air during the previous admission. Individuals received telemonitoring (second-generation system) via broadband link to a hospital-based care team.Outcome Measures: Primary outcome measure was time to first hospital admission for an acute exacerbation. Secondary outcome measures were hospital admissions, general practitioner (GP) consultations and home visits by nurses, quality of life measured by EuroQol-5D and hospital anxiety and depression (HAD) scale, and self-efficacy score (Stanford).Results: Median (IQR) number of days to first admission showed no difference between the two groups—77 (114) telemonitoring, 77.5 (61) control ( p=0.189). Hospital admission rate at 6 months increased (0.63 telemonitoring vs 0.32 control p=0.026). Home visits increased during telemonitoring; GP consultations were unchanged. Self-efficacy fell, while HAD depression score improved marginally during telemonitoring.Conclusions: Telemonitoring added to standard care did not alter time to next acute hospital admission, increased hospital admissions and home visits overall, and did not improve quality of life in chronic respiratory patients.Trial Registration Number: NCT02180919 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

This cross-sectional study evaluated health-related quality of life (HRQoL) in patients with slowly progressive neuromuscular disorders dependent on mechanical ventilation (MV; ≥16 hours/day). 119 participants, with 9 years (25th-75th percentiles: 4-15 years) of MV dependence, were included. MV was applied via a tracheostomy in 80 participants (67.2%) and non-invasive interfaces in 39 participants (32.8%), including 28 participants (71.8%) with daytime mouthpiece ventilation. HRQoL was rated good or excellent by 81 participants (68.1%), independently from age, diagnosis or respiratory autonomy. On multivariate analysis, time since MV initiation, independence from family member(s), residence in a rural area, ability to go outdoors with MV and tracheostomy were associated with better HRQoL., Competing Interests: Competing interests: MD reports grants from Fondation de France, AFM Téléthon and Fondation Garches, during the conduct of the study; personal fees from Air Liquide Medical Systems, Breas Medical AB, ResMed SAS and GSK; and non-financial support from L3 Medical, outside the submitted work. Other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Lymphangioleiomyomatosis (LAM) is a rare lung disease of women, causing cystic remodelling of the lung and progressive respiratory failure. The cellular composition, microenvironment and cellular interactions within the LAM lesion remain unclear. To facilitate data sharing and collaborative LAM research, we performed an integrative analysis of single-cell data compiled from lung, uterus and kidney of patients with LAM from three research centres and developed an LAM Cell Atlas (LCA) Web-Portal. The LCA offers a variety of interactive options for investigators to search, visualise and reanalyse comprehensive single-cell multiomics data sets to reveal dysregulated genetic programmes at transcriptomic, epigenomic and cell-cell connectome levels., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Patient-ventilator asynchrony (PVA) can adversely affect the successful initiation of non-invasive home mechanical ventilation (HMV). The aim of this observational study was to quantify the prevalence of PVA during initiation of HMV and to determine the relationship between PVA and nocturnal gas exchange.Method: Type and frequency of PVA were measured by surface parasternal intercostal muscle electromyography, thoracoabdominal plethysmography and mask pressure during initiation of HMV. Severe PVA was defined, as previously, as asynchrony affecting ≥10% of breaths.Results: 28 patients (18 male) were enrolled aged 61±15 years and with a body mass index of 35±9 kg/m(2). Underlying diagnoses were neuromuscular disease with or without chest wall disease (n=6), obesity related chronic respiratory failure (n=12) and COPD (n=10). PVA was observed in all patients with 79% of patients demonstrating severe PVA. Triggering asynchrony was most frequent, observed in 24% (IQR: 11-36%) of breaths, with ineffective efforts accounting for 16% (IQR: 4-24%). PVA types were similar between disease groups, with the exception of auto-triggering, which was higher in patients with COPD (12% (IQR: 6-26%)). There was no correlation observed between PVA and time spent with oxygen saturations ≤90%, mean oxygen saturations or transcutaneous carbon dioxide levels during overnight ventilation.Conclusions: Severe PVA was identified in the majority of patients, irrespective of pathophysiological disease state. This was not associated with ineffective ventilation as evidenced by gas exchange. [ABSTRACT FROM AUTHOR]

IntroductionAutomatic titration modes of non-invasive ventilation, including average volume assured pressure support (AVAPS), are hybrid technologies that target a set volume by automated adjustment of pressure support (PS). These automated modes could offer potential advantages over fixed level PS, in particular, in patients who are super obese.MethodsConsecutive patients with obesity hypoventilation syndrome were enrolled in a two-centre prospective single-blind randomised controlled trial of AVAPS versus fixed-level PS using a strict protocolised setup.MeasurementsThe primary outcome was change in daytime arterial PCO2(PaCO2) at 3 months. Body composition, physical activity (7-day actigraphy) and health-related quality of life (severe respiratory insufficiency questionnaire, SRI) were secondary outcome measures.Results50 patients (body mass index 50±7 kg/m2; 55±11 years; 53% men) were enrolled with a mean PaCO2of 6.9±0.8 kPa and SRI of 53±17. 46 patients (23 AVAPS and 23 PS) completed the trial. At 3 months, improvements in PaCO2were observed in both groups (AVAPS 0.6 kPa, 95% CI 0.2 to 1.1, p<0.01 vs PS 0.6 kPa, 95% CI 0.1 to 1.1, p=0.02) but no between-group difference (−0.1 kPa, 95% CI −0.7 to 0.6, p=0.87). SRI also improved in both groups (AVAPS 11, 95% CI 6 to 17, p<0.001 vs PS 7, 95% CI 1 to 12, p=0.02; between groups 5, 95% CI −3 to 12, p=0.21). Secondary analysis of both groups combined showed improvements in daytime physical activity that correlated with reduction in fat mass (r=0.48; p=0.01).ConclusionThe study demonstrated no differences between automated AVAPS mode and fixed-level PS mode using a strict protocolised setup in patients who were super obese. The data suggest that the management of sleep-disordered breathing may enhance daytime activity and promote weight loss in super-obese patients. Trial registration details available at http://www.controlled-trials.com/ISRCTN63940700 [ABSTRACT FROM AUTHOR]

Background Respiratory failure is a life-threatening and unpredictable complication of systemic sclerosis (SSc). A study was undertaken to assess the value of alveolar nitric oxide (NO) in predicting the risk of lung function deterioration leading to respiratory failure or death in patients with SSc. Methods 105 patients with SSc were enrolled in this prospective cohort and were followed longitudinally over a 3-year period during which the risk of occurrence of deleterious events was analysed according to alveolar concentration (CANO), conducting airway output (J' awNO) and fractional concentration (FENO0.05) of exhaled NO measured at inclusion. Comparison was made between each NO parameter to predict the occurrence of deleterious events, defined as a 10% decrease in total lung capacity or forced vital capacity from baseline, or death. Results The area under the receiver operating Results The area under the receiver operating characteristic curve of CANO to predict the occurrence of the combined events was 0.84 (95% CI 0.76 to 0.92; p<0.001), which was significantly higher than those of J' awNO and FENO0.05 (p<0.001). A cut-off of CANO of 5.3 ppb had a sensitivity of 88% and a specificity of 62% for the prediction of the occurrence of combined events during follow-up, and was validated in an independent cohort of patients with SSc. Combined events occurred more frequently in patients whose CANO was >5.3 ppb. The adjusted HR for patients with CANO >5.3 ppb was 6.06 (95% CI 2.36 to 15.53; p<0.001). CANO accurately predicted the occurrence of combined events irrespective of forced vital capacity values or the presence of interstitial lung disease at baseline. Conclusions Increased CANO accurately identifies patients with SSc with a high risk of developing lung function deterioration and may help to initiate early appropriate treatment. INSET: Key messages. [ABSTRACT FROM AUTHOR]

The article offers information on randomised controlled trial in malnourished patients with chronic respiratory failure CRF to analyze the effects of 3 months home rehabilitation on body functioning and composition. It concludes that multimodal nutritional rehabilitation is needed to improve body composition, increased exercise tolerance and quality of life in women and survival in compliant patients and proposes inclusion of the suggestions in the treatment of malnourished patients with CRF.

Pulmonary disease is the most important cause of morbidity and mortality in cystic fibrosis (CF). Most patients with CF die from respiratory failure with extensive airway destruction. Airway remodelling, defined as structural airway wall changes, begins early in life in CF but the sequence of remodelling events in the disease process is poorly understood. Airway remodelling in CF has traditionally been thought to be solely the consequence of repeated cycles of inflammation and infection. However, new evidence obtained from developmental, physiological and histopathological studies suggests that there might instead be multiple mechanisms leading to airway remodelling in CF including (1) changes related to infection and inflammation; (2) changes specific to CF as a result of CF transmembrane conductance regulator (CFTR) dysfunction in the airway wall, independent of infection and inflammation; and (3) protective responses to (1) and/or (2). Recent advances in bronchoscopic techniques have allowed airway mucosal (endobronchial) biopsies to be taken in children and even infants. Endobronchial biopsy studies may provide insight into the role and relative contribution of the different mechanisms of airway remodelling in CF, with the main limitation that they assess only changes in proximal large airways and not in peripheral small airways from where CF disease is thought to originate. Findings from biopsy studies could encourage the development of novel therapeutic strategies targeting structural changes in addition to infection and inflammation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mechanical ventilation (MV) is a life-saving intervention in acute respiratory failure without any alternative. However, even protective ventilation strategies applying minimal mechanical stress may evoke ventilator-induced lung injury (VILI). Adjuvant pharmacological strategies in addition to lung-protective ventilation to attenuate VILI are lacking. Adrenomedullin exhibited endothelial barrier-stabilising properties in vitro and in vivo. METHODS: In untreated mice (female C57/Bl6 mice, 11–15 weeks old) and animals treated with adrenomedullin, lung permeability, local and systemic inflammation and markers of distal organ function were assessed following 2 or 6 h of mechanical ventilation with 100% oxygen and protective or moderately injurious ventilator settings, respectively. RESULTS: Adrenomedullin dramatically reduced lung permeability in VILI in mice, leading to improved oxygenation. Adrenomedullin treatment reduced myosin light chain phosphorylation, attenuated the accumulation of leucocytes in the lung and prevented the increase in lactate and creatinine levels in mice ventilated with high tidal volumes. Moreover, adrenomedullin protected against VILI even when treatment was initiated 2 h after the beginning of mechanical ventilation in a 6 h VILI mouse model. CONCLUSION: Adjuvant treatment with adrenomedullin may be a promising new pharmacological approach to attenuate VILI. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study was to investigate factors affecting clinical outcomes of adults hospitalised with severe seasonal influenza. METHODS: A prospective, observational cohort study was conducted over 24 months (2007–2008) in two acute, general hospitals. Consecutive, hospitalised adult patients were recruited and followed once their laboratory diagnosis of influenza A/B was established (based on viral antigen detection and virus isolation from nasopharyngeal aspirates collected per protocol). Outcomes studied included in-hospital death, length of stay and duration of oxygen therapy. Factors affecting outcomes were analysed using multivariate Cox proportional hazards models. Sequencing analysis on the neuraminidase gene was performed for available H1N1 isolates. RESULTS: 754 patients were studied (influenza A, n=539; >75% H3N2). Their mean age was 70±18 years; co-morbidities and serious complications were common (61–77%). Supplemental oxygen and ventilatory support was required in 401 (53.2%) and 41 (5.4%) patients, respectively. 39 (5.2%) patients died; pneumonia, respiratory failure and sepsis were the causes. 395 (52%) patients received antiviral (oseltamivir) treatment. Omission of antiviral treatment was associated with delayed presentation or negative antigen detection results. The mortality rate was 4.56 and 7.42 per 1000 patient-days in the treated and untreated patients, respectively; among those with co-morbidities, it was 5.62 and 11.64 per 1000 patient-days, respectively. In multivariate analysis, antiviral use was associated with reduced risk of death (adjusted HR (aHR) 0.27 (95% CI 0.13 to 0.55); p<0.001). Improved survival was observed with treatment started within 4 days from onset. Earlier hospital discharge (aHR 1.28 (95% CI 1.04 to 1.57); p=0.019) and faster discontinuation of oxygen therapy (aHR 1.30 (95% CI 1.01 to 1.69); p=0.043) was associated with early treatment within 2 days. Few (n=15) H1N1 isolates in this cohort had the H275Y mutation. CONCLUSIONS: Antiviral treatment for severe influenza is associated with reduced mortality and improved clinical outcomes. [ABSTRACT FROM AUTHOR]