Chest最新文献

Background: Pulmonary rehabilitation (PR) is a beneficial intervention for people with interstitial lung disease (ILD), however the effect of PR on survival is unclear. This study compared the survival outcomes in people with ILD who were allocated to PR versus those who were allocated to control in two published randomised controlled trials (RCTs).

Research question: Does participation in PR impact survival among people with ILD?

Study design and methods: The combined data from the two previous RCTs of PR in ILD were included. Time from start of PR until date of death, lung transplantation or censoring was calculated. Kaplan-Meir and Cox proportional hazard regression analysis were used to assess the impact of PR on survival. Baseline variables of age at time of PR, gender, FVC, 6-minute walk distance (6MWD), exertional nadir SpO₂ and diagnosis of idiopathic pulmonary fibrosis (IPF) were included as covariates.

Results: Of the 182 participants with ILD (87 IPF, 109 males, mean (SD) age 69(10), FVC%pred 76(19), TLCO%pred 48(16)), death occurred in 62%, 6% were transplanted, 20% were alive and 12% were lost to follow-up. Median survival for those who completed PR was 6.1 years (95% CI 4.4 to 7.9) compared to 4.7 years (95%CI 3.4 to 6.0) for those in the control group, however this was not significantly different (log rank p=0.7). After adjusting for baseline variables, at 5 years, completion of PR was associated a 44% lower risk of mortality (HR 0.56 (0.36-0.88), p=0.01). At 10 years, no difference in survival was observed between the PR and control group.

Interpretation: Participation in PR among people with ILD may impact survival at 5 years. Along with clinical improvements following PR, the potential for a survival benefit further strengthens the importance of PR in the standard care of people with ILD.

Background: Airway management is a critical component of the care of patients experiencing cardiac arrest, but data from randomized trials on the use of video vs direct laryngoscopy for intubation in the setting of cardiac arrest are limited. Current AHA guidelines recommend placement of an endotracheal tube either during CPR or shortly after return of spontaneous circulation but do not provide guidance around intubation methods, including the choice of laryngoscope.

Research question: Does use of video laryngoscopy improve the incidence of successful intubation on the first attempt, compared to use of direct laryngoscopy, among adults undergoing tracheal intubation after experiencing cardiac arrest?

Study design and methods: This secondary analysis of the Direct versus Video Laryngoscope (DEVICE) trial compared video laryngoscopy versus direct laryngoscopy in the subgroup of patients who were intubated following cardiac arrest. The primary outcome was the incidence of successful intubation on the first attempt. Additional outcomes included the duration of laryngoscopy.

Results: Among the 1,417 patients in the DEVICE trial, 113 (7.9%) had experienced cardiac arrest prior to intubation, of whom 48 were randomized to the video laryngoscopy group and 65 to the direct laryngoscopy group. Successful intubation on the first attempt occurred in 40 of 48 patients (83.3%) in the video laryngoscopy group and 42 of 65 patients (64.6%) in the direct laryngoscopy group (absolute risk difference, 18.7 percentage points; 95% confidence interval [CI], 1.2 to 36.2; P = 0.03). The mean duration of laryngoscopy was 48.0 seconds (standard deviation [SD], 37.3 seconds) in the video laryngoscope group and 98.0 seconds (SD, 122.4) in the direct laryngoscopy group (mean difference, -50.0; 95% CI, -86.8 to -13.3, P = 0.004).

Interpretation: Among adults undergoing tracheal intubation after experiencing cardiac arrest, use of video laryngoscopy was associated with increased incidence of successful intubation on the first attempt and shortened duration of laryngoscopy, compared to use of direct laryngoscopy.

Background: Delirium is a common and serious syndrome of acute brain dysfunction associated with negative outcomes. Melatonin may have a role in delirium prevention for critically ill adults based on data from non-critically ill patient populations. Our objective was to assess the feasibility of a multi-centre, randomized, placebo-controlled trial testing the hypothesis that low-dose melatonin prevents delirium in critically ill adults.

Methods: We conducted this three-arm feasibility trial in three tertiary academic ICUs. Included participants were ≥18 years old, confirmed free from delirium at enrollment, and anticipated >48 hours intensive care unit (ICU) stay. We randomized participants to nightly melatonin 0.5mg or 2mg or placebo. Feasibility outcomes were protocol adherence and recruitment rates. Our primary feasibility target was ≥85% (±5% margin of error) of drug doses administered as per protocol. Secondary objectives were to explore adverse drug effects, melatonin pharmacokinetics, and clinical outcomes.

Results: We screened 2259 patients, excluding 1863 (82.5%), resulting in 396 eligible patients, of whom 71 consented; recruitment rate 0.8 patients/month/site. Median (IQR) age was 60.5 (48,67) years; median admission SOFA score 7 (3,10). Percentage drug administration protocol adherence per patient was median 100% (IQR 92.3%, 100%) or mean 88.7% (SD 24.4). There were 25 protocol violations with no differences between groups. Fourteen (20%) patients developed delirium during the study period; 25 (36%) experienced sub-syndromal delirium; no differences between study groups. No serious adverse effects were detected.

Conclusion: Our trial protocol comparing two low doses of melatonin and placebo for delirium prevention in critically ill adults demonstrated feasibility for protocol adherence. However, trial eligibility rates were modest primarily due to delirium being present or the inability to screen. Consent rates were also low. This finding suggests that conducting delirium prevention trials that require delirium to be absent on enrolment is particularly challenging in the ICU.

Background: Changes in body composition, including loss of muscle mass and obesity, adversely affect lung function.

Research question: What is the relationship between lung function, visceral adiposity, and skeletal muscle mass, considering myosteatosis measured using CT scans in middle-aged Korean adults?

Study design and methods: We reviewed 15,827 participants (9,237 men and 6,590 women) with a mean (SD) age of 52.5 (8.3) years who underwent comprehensive health examinations, including abdominal CT imaging and spirometry. Selected CT scans were segmented automatically to quantify total abdominal muscle area (TAMA), visceral fat area (VFA), and subcutaneous fat area. Muscle quality was assessed by categorizing TAMA into 3 regions based on CT scan density: good-quality muscle (normal-attenuation muscle area [NAMA]), fatty muscle (low attenuation muscle area), and intermuscular and intramuscular fat areas. Low lung function was defined as FVC % predicted and FEV₁ < 80% predicted. Standardized residuals for CT scan-derived measurements, adjusted for age and BMI using linear regression, were calculated and stratified into quartiles for lung function comparison. Multivariate logistic regression was used to analyze associations between low lung function and variables.

Results: NAMA was correlated positively with FVC and FEV₁, whereas VFA was correlated negatively with both. In men, low FVC and FEV₁ were associated significantly with lower NAMA and higher VFA. Among women with obesity (BMI ≥ 25 kg/m²), low FVC and FEV₁ were associated significantly with higher VFA and lower NAMA (FVC only); among women without obesity, low FVC and FEV₁ were associated negatively with NAMA.

Interpretation: Lung function was associated significantly with visceral adiposity and skeletal muscle quality, which differed according to sex and BMI. Improving lung function may require tailored management, including reducing visceral fat, enhancing skeletal muscle quality based on CT scan-body composition analysis, or both.

Topic importance: Accurate assessment of a patient's volume status is crucial in many conditions, informing decisions on fluid prescribing, vasoactive agents, and decongestive therapies. Determining a patient's volume status is challenging, due to limitations in examination and investigations and the complexities of fluid homeostasis in disease states. Point-of-care ultrasound (POCUS) is useful in assessing hemodynamic parameters related to volume status, fluid responsiveness, and fluid tolerance. It requires understanding several physiologic concepts to accurately interpret and integrate POCUS findings into volume-related clinical decision-making.

Review findings: The following concepts serve as a scaffold for a comprehensive volume status assessment: central venous pressure, right heart function, left heart assessment, extravascular volume, and venous congestion. POCUS allows us access to these hemodynamic and structural data points as an extension and refinement of the physical exam. Often, multiple POCUS applications are employed, and findings must be integrated with the rest of the clinical evaluation. We illustrate this using three common scenarios: hypotension, hypoxia, and acute kidney injury. Clinicians must be aware of the strengths and weaknesses of findings in different physiologic states, and potential pitfalls of image acquisition and interpretation. Further studies are necessary to determine the benefits and clinical outcomes of a POCUS-directed volume status assessment.

Summary: Volume status assessment is ubiquitous, yet challenging to perform. This review summarizes foundational physiologic concepts relevant to volume status evaluation, and highlights how multiorgan POCUS informs on hemodynamic parameters that can be combined with the conventional clinical assessment to make fluid-related decisions.

Background: Adaptation of the right ventricle is a key determinant of outcomes in pulmonary arterial hypertension (PAH). Despite a compelling rationale to develop targeted therapies for the right ventricle in PAH, no such treatments exist. H₂-receptor antagonism is a potential myocardial-focused paradigm in heart failure.

Research question: Do H₂-receptor antagonists improve outcomes in participants with PAH?

Study design and methods: We conducted a 24-week, single-center, 1:1 randomized, double-blind, placebo-controlled trial of the H₂-receptor antagonist famotidine in patients with a diagnosis of PAH. The primary outcome was change in six-minute walk distance (6MWD) at 24 weeks. Secondary endpoints included B-type natriuretic peptide levels, NYHA functional class, right ventricular parameters, health-related quality of life, and escalation in PAH-focused care.

Results: From May 2019 to July 2023, 80 participants were randomized with 79 receiving study drug. There was no significant difference in the primary outcome of 6MWD at 24 weeks, with an increase of 4.7 meters seen in the placebo arm versus a decrease of 17.0 meters in the famotidine arm (p = 0.24). There were also no differences in secondary endpoints at 24 weeks. Study drug was well tolerated, and safety profiles were similar between arms. Adherence and study conduct was good overall. Participants with methamphetamine-associated PAH were similar in all aspects to the study participants more broadly.

Interpretation: The results of this trial do not support the routine use of famotidine 20 mg daily as an adjunct therapy for the treatment of PAH. The REHAB-PH trial argues against the practice of avoiding participants with methamphetamine-associated PAH in randomized clinical trials of novel therapies.

Clinical trials registration: The trial was registered at clinicaltrials.gov (NCT03554291).

Background: Central airway obstruction (CAO), seen in a variety of malignant and nonmalignant airway disorders, is associated with a poor prognosis. The management of CAO is dependent on provider training and local resources, which may make the clinical approach and outcomes highly variable. We reviewed the current literature and provided evidence-based recommendations for the management of CAO.

Methods: A multidisciplinary expert panel developed key questions using the Patient, Intervention, Comparator, and Outcomes format and conducted a systematic literature search using MEDLINE (PubMed) and the Cochrane Library. The panel screened references for inclusion and used vetted evaluation tools to assess the quality of included studies and extract data, and graded the level of evidence supporting each recommendation. A modified Delphi technique was used to reach consensus on recommendations.

Results: A total of 9,688 abstracts were reviewed, 150 full-text articles were assessed, and 31 studies were included in the analysis. One good practice statement and 10 graded recommendations were developed. The overall certainty of evidence was very low.

Conclusions: Therapeutic bronchoscopy can improve the symptoms, quality of life, and survival of patients with malignant and nonmalignant CAO. Multi-modality therapeutic options, including rigid bronchoscopy with general anesthesia, tumor/tissue debridement, ablation, dilation, and stent placement, should be utilized when appropriate. Therapeutic options and outcomes are dependent on the underlying etiology of CAO. A multidisciplinary approach and shared decision-making with the patient are strongly encouraged.

Background: Complex pleural space infections often require treatment with multiple doses of intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease, with treatment failure frequently necessitating surgery. Pleural infections are rich in neutrophils, and neutrophil elastase degrades plasminogen, the target substrate of tPA, that is required to generate fibrinolysis. We hypothesized that pleural fluid from patients with pleural space infection would show high elastase activity, evidence of inflammatory plasminogen degradation, and low fibrinolytic potential in response to tPA that could be rescued with plasminogen supplementation.

Research question: Does neutrophil elastase degradation of plasminogen contribute to intrapleural fibrinolytic failure?

Study design and methods: We obtained infected pleural fluid and circulating plasma from hospitalized adults (n = 10) with institutional review board approval from a randomized trial evaluating intrapleural fibrinolytics vs surgery for initial management of pleural space infection. Samples were collected before the intervention and on days 1, 2, and 3 after the intervention. Activity assays, enzyme-linked immunosorbent assays, and Western blot analysis were performed, and turbidimetric measurements of fibrinolysis were obtained from pleural fluid with and without exogenous plasminogen supplementation. Results are reported as median (interquartile range) or number (percentage) as appropriate, with an α value of .05.

Results: Pleural fluid elastase activity was more than fourfold higher (P = .02) and plasminogen antigen levels were more than threefold lower (P = .04) than their corresponding plasma values. Pleural fluid Western blot analysis demonstrated abundant plasminogen degradation fragments consistent with elastase degradation patterns. We found that plasminogen activator inhibitor 1 (PAI-1), the native tPA inhibitor, showed high antigen levels before the intervention, but the overwhelming majority of this PAI-1 (82%) was not active (P = .003), and all PAI-1 activity was lost by day 2 after the intervention in patients receiving intrapleural tPA and deoxyribonuclease. Finally, using turbidity clot lysis assays, we found that the pleural fluid of 9 of 10 patients was unable to generate a significant fibrinolytic response when challenged with tPA and that plasminogen supplementation rescued fibrinolysis in all patients.

Interpretation: Our findings suggest that inflammatory plasminogen deficiency, not high PAI-1 activity, is a significant contributor to intrapleural fibrinolytic failure.

Trial registry: ClinicalTrials.gov; No.: NCT03583931; URL: www.

Clinicaltrials: gov.