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Background: Lower respiratory tract infections are common in patients receiving invasive mechanical ventilation in an Intensive Care Unit (ICU) after an acute brain injury and may have deleterious consequences.

Research question: In adults with acute brain injury receiving invasive mechanical ventilation in an ICU, is the administration of prophylactic parenteral antibiotics, compared to placebo or usual care, associated with reduced mortality?

Study design and methods: We conducted a systematic review and meta-analysis. We searched for randomised clinical trials (RCTs) in electronic databases, as well as unpublished trials. The primary outcome was hospital mortality, secondary outcomes included the incidence of ventilator associated pneumonia, ICU length of stay, and duration of mechanical ventilation. We used a random effects model to estimate the pooled risk ratio (RR) with corresponding 95% confidence intervals (CI) for binary outcomes and the mean difference (MD) with 95% CI for continuous outcomes. Certainty of evidence was evaluated using GRADE methods.

Results: There were 1728 reports of studies screened, with 7 RCTs recruiting 835 participants included. No trials were adjudicated as having a high risk of bias. The pooled estimated risk ratio (RR) for mortality associated with the use of prophylactic antibiotics was 0.91 (95% CI 0.70 to 1.17, p=0.39, low certainty). The pooled estimated RR for ventilator associated pneumonia was 0.56 (95% CI 0.35 to 0.89, low certainty). The pooled estimated duration of mechanical ventilation for those allocated to prophylactic antibiotics compared to control (mean difference (MD) -2.0 days, 95% CI -6.1 to 2.1, very low certainty) and duration of ICU admission (MD -2.2 days, 95% CI -5.4 to 1.1 days, very low certainty) were similar.

Interpretation: Current evidence from randomised clinical trials does not provide definitive evidence regarding the effect of prophylactic antibiotics on mortality in patients receiving invasive mechanical ventilation in the ICU.

Background: Serum anti-glycopeptidolipid (GPL) core immunoglobuin A (IgA) antibody test has been proposed as a diagnostic tool for Mycobacterium avium complex pulmonary diseases. Cross-reactivity with other non-tuberculous mycobacteria (NTM), including M. abscessus, indicates that it may have a role as a broader screening test for NTM pulmonary disease (NTM-PD). NTM-PD is believed to be underdiagnosed in patients with bronchiectasis.

Research question: Can the serum anti-GPL core IgA antibody test be used to screen for NTM-PD in bronchiectasis?

Study design and methods: Patients from the prospective European Bronchiectasis Registry (EMBARC-BRIDGE; NCT03791086) were enrolled. Patients from the United Kingdom, Italy, Spain, Belgium, the Netherlands, and Germany were included. A control cohort of patients without any underlying lung disease was also recruited. The levels of serum IgA antibodies against the GPL core were measured using an enzyme immunoassay kit, and receiver operating characteristics curve analysis was conducted to evaluate the accuracy of the antibody level in screening for NTM-PD.

Results: 282 patients were enrolled (151 [53.6%] female, median age 68 years). Median (quartile 1-3) anti-GPL-core IgA antibody levels were 0.2 (0.1-0.3) U/mL in patients without NTM isolation and NTM-PD (n=238), 0.3 (0.2-0.4) U/mL in NTM isolation that were incompatible with the diagnosis of NTM-PD (n=18) and 1.5 (0.4-6.2) U/mL in NTM-PD (n=26) (P=0.0001). Antibody levels showed excellent accuracy in identifying patients with NTM-PD (area under the curve 0.886, 95% CI 0.800-0.973) in bronchiectasis cohort and also showed excellent discrimination of patients with NTM-PD from those with NTM isolation who did not meet the diagnostic criteria for NTM-PD (0.816, 95% CI 0.687-0.945).

Interpretation: The anti-GPL-core IgA antibody demonstrated excellent efficacy in screening for NTM-PD in a large bronchiectasis cohort.

A 72-year-old gentleman with metastatic pancreatic cancer was admitted to the ICU with increased oxygen demand and confusion, likely related to pulmonary metastases. In the presence of his son, the healthcare agent, and the team, the patient requested to be do-not-attempt-resuscitation and do-not-intubate (DNR/DNI) before losing decision-making capacity. When the patient's brother and another son heard of the code status change, they insisted on a return to Full Code. Although the youngest son (the healthcare agent) was present for the patient's request to be DNR/DNI, he declined to represent the patient's wishes and agreed with a return to Full Code. Numerous discussions over subsequent days revolved around the attempt to honor the patient's wishes in the setting of the surrogate's unwillingness or inability to make decisions in alignment with his father's wishes. This case reviews and analyzes the ethical options available to the clinical team in responding to requests for potentially inappropriate treatment at a patient's end of life, and explores the roles of relational autonomy, beneficence vs nonmaleficence, and holding the balance of clinicians' and ethicists' professional, legal, and ethical responsibilities.

Background: Evaluating expiratory airway function in infants is challenging, as the gold standard, the raised-volume rapid thoraco-abdominal compression technique is technically difficult and has a high failure rate.

Research question: Are measurements obtained during passive expiration from total lung capacity correlated with forced expiration measurements obtained by the raised-volume technique in infants?

Study design and methods: This observational retrospective analysis included infants born ≥ 36 weeks gestation who underwent pulmonary function testing using the raised-volume rapid thoraco-abdominal compression technique at Hadassah Medical Centre between January 2011 and December 2019. Technically acceptable forced and passive flow-volume curve measurements were included in the analysis.

Results: Out of 296 eligible infants, 276 (93%) had technically acceptable passive flow-volume curves while 226 (76%) had acceptable forced curves (p<0.001). The success rate of producing an acceptable curve was 70% for the passive curves and 39% for forced curves (p < 0.001). The Spearman correlation coefficients of vital capacity, expiratory volumes at 0.5 second, maximal expiratory flows, and expiratory flows at 50%, 75% and 85% of vital capacity were 0.92, 0.72, 0.83, 0.66, 0.67, 0.68, respectively (n= 226; p<0.001 for all). The correlation remained high regardless of the level of expiratory airway obstruction, gender or age. The mean inter-maneuver coefficients of variation were fairly low for both methods (5.2% vs 5.4%, p=NS).

Interpretation: The passive flow-volume curve offers reliable and reproducible data with high correlation to the forced flow-volume curve. Therefore, the passive flow-volume curve can serve as an alternative tool in evaluating expiratory airway function in infants.

Background: Chronic obstructive pulmonary disease (COPD) management is guided by the respiratory symptom burden, assessed using the modified Medical Research Council (mMRC) scale and/or COPD Assessment Test (CAT).

Research question: What is the ability of mMRC and CAT to detect abnormally high exertional breathlessness on incremental cardiopulmonary cycle exercise testing (CPET) in people with COPD?

Study design and methods: Analysis of people aged ≥40 years with post-bronchodilator FEV₁/FVC<0.70 and ≥10 smoking pack-years from the Canadian Cohort Obstructive Lung Disease study. Abnormal exertional breathlessness was defined as a breathlessness (Borg 0-10) intensity rating > upper limit of normal (ULN) at the symptom-limited peak of CPET using normative reference equations.

Results: We included 318 people with COPD (40% women), age 66.5±9.3 years (mean±SD), FEV₁ 79.5±19.0%predicted; 26% had abnormally low exercise capacity (V'O_2peak

Interpretation: In COPD, mMRC and CAT have low concordance with CPET and fail to identify many people with abnormally high exertional breathlessness.

Background: Recent treatment guidelines for chronic obstructive pulmonary disease (COPD) have replaced the long-acting beta₂-agonist and inhaled corticosteroid (LABA-ICS) combination with single-inhaler triple therapy that adds a long-acting muscarinic antagonist (LAMA-LABA-ICS). Yet, the corresponding trials reported numerically higher incidences of cardiovascular adverse events with triple therapy compared with LABA-ICS.

Research question: Does single-inhaler triple therapy increase the incidence of major adverse cardiovascular events, compared with LABA-ICS, in a real-world clinical practice setting?

Study design and methods: We identified a cohort of COPD patients, 40 years or older, treated during 2017-2021, from the United Kingdom's Clinical Practice Research Datalink. Among LAMA-naïve patients, initiators of single-inhaler triple therapy were matched 1:1 to LABA-ICS users on time-conditional propensity scores. They were compared on the incidence of major adverse cardiovascular events (MACE), defined as hospitalization for myocardial infarction or stroke, or all-cause-mortality, over one year.

Results: The cohort included 10,255 initiators of triple therapy and 10,255 matched users of LABA-ICS. The incidence rate of MACE was 11.3 per 100 per year with triple therapy compared with 8.7 per 100 per year for LABA-ICS. The corresponding adjusted hazard ratio (HR) of MACE with triple therapy was 1.28 (95% CI: 1.05-1.55), relative to LABA-ICS, though the increase was mainly in the first four months (HR 1.41; 95%CI: 1.14-1.74). The HR of all-cause death was 1.31 (95% CI: 1.06-1.62), while for acute myocardial infarction and stroke hospitalization it was 1.00 (95% CI: 0.56-1.79) and 1.06 (95% CI: 0.48-2.36), respectively, with triple therapy, relative to LABA-ICS.

Interpretation: In a real-world setting of COPD treatment, patients who initiated single-inhaler triple therapy had an increased incidence of MACE compared with similar patients treated with a LABA-ICS inhaler. This small increase was due to the all-cause mortality component, occurring mainly in the first four months after treatment initiation.

Background: Oronasal masks are used widely for treating OSA with CPAP. However, oronasal CPAP is associated with lower effectiveness and lower adherence than nasal CPAP.

Research question: What is the impact of oral route and lateral position in patients well adapted to oronasal CPAP? Can these patients be switched to nasal CPAP?

Study design and methods: Patients with OSA receiving oronasal CPAP underwent 2 CPAP polysomnography titrations in random order using an oronasal mask with 2 independent sealed compartments connected to 2 separate pneumotachographs. One study was performed with the nasal and oral compartments opened and the other study was performed with only the oral compartment opened. CPAP titration was carried out in the supine and lateral positions. Finally, the patients were offered a nasal mask. A third polysomnography test was performed using nasal CPAP.

Results: Twenty patients with OSA (baseline apnea-hypopnea index [AHI], 52 ± 21 events/h) adapted to oronasal CPAP were studied. Most patients (75%) were oronasal breathers with optimal CPAP. Oral CPAP was less effective to treat OSA than oronasal CPAP, evidenced by a higher residual AHI (median, 2 [interquartile range (IQR), 1-6.0] vs 12.5 [IQR, 1.8-28.3); P = .003), despite a significantly higher CPAP level (median, 10 cm H₂O [IQR, 9-10 cm H₂O] vs 11 cm H₂O [IQR, 10-12 cm H₂O]; P = .003). The residual AHI was significantly lower in the lateral position for both oronasal and oral CPAP. Finally, patients (75%) agreed to change and preferred to continue using a nasal mask, which resulted in lower CPAP and better OSA control.

Interpretation: The effectiveness of oronasal CPAP to abolish OSA is decreased significantly when patients are required to breathe exclusively through the mouth. Oronasal CPAP efficacy is significantly better in the lateral position. The transition to nasal mask results in higher CPAP effectiveness to treat OSA.

Clinical trial registry: ClinicalTrials.gov; No.: NCT05272761; URL: www.

Clinicaltrials: gov.

The advanced practice respiratory therapist (APRT) is a new health care practitioner trained to provide a scope of practice that exceeds that of the registered respiratory therapist (RRT) and is aligned with an advanced practice provider (APP) role. As part of a physician-led team, APRTs are trained to provide diagnostic and therapeutic patient care services in multiple settings across the health care spectrum, including critical care, acute and subacute inpatient care, and outpatient care such as preventative, ambulatory, and chronic care. Competency domains that must be included in accredited APRT education programs include medical knowledge, interpersonal and communication skills, patient care, professionalism, practice-based learning and improvement, and systems-based practice. Some of the individual competencies included in these domains must be incorporated into didactic coursework, some into laboratory and simulation activities, and all competencies must be incorporated into clinical coursework. Preclinical preparation of the APRT student includes coursework with other APP students and other health professions students, and courses created specifically to address the required competency domains. APRT students also complete a variety of patient simulations using standardized patients, task trainers, and patient simulators to ensure they are prepared to complete clinical education. The clinical courses include a minimum of 1200 hours of supervised practice by a licensed physician in outpatient clinics, interventional pulmonology, inpatient pulmonary services, perioperative services, and ICUs. The APRT is trained to assess patients, develop care plans, and order, evaluate, and modify care based on each patient's response, and can be incorporated as a valuable member of the cardiopulmonary patient care team.

Background: Aspergillus species cause diverse clinical manifestations in bronchiectasis including allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization (AS), and raised IgG indicating exposure to or infection with Aspergillus.

Research question: What are the prevalence and clinical significance of Aspergillus-associated conditions in individuals with bronchiectasis?

Study design and methods: Patients with bronchiectasis enrolled into the European Bronchiectasis Registry from 2015 through 2022 with laboratory testing for Aspergillus lung disease (total IgE, IgE specific to Aspergillus or Aspergillus skin test, or IgG specific to Aspergillus and blood eosinophil counts) were included for analysis. Modified International Society for Human and Anima Mycology ABPA working group criteria (2021) were used to define ABPA.

Results: Nine thousand nine hundred fifty-three patients were included. Six hundred eight patients (6.1%) were classified as having ABPA, 570 patients (5.7%) showed AS, 806 patients (8.1%) showed raised Aspergillus-specific IgG without AS, 184 patients (1.8%) showed both AS and had raised Aspergillus-specific IgG levels, and 619 patients (6.2%) demonstrated eosinophilic bronchiectasis (elevated eosinophil counts without evidence of Aspergillus lung disease). The remaining 72% showed negative Aspergillus serologic findings. Patients with ABPA, AS, or raised Aspergillus-specific IgG demonstrated more severe disease, with worse lung function and more frequent exacerbations at baseline. During long-term follow-up, patients with raised Aspergillus-specific IgG experienced higher exacerbation frequency and more severe exacerbations. AS was associated with increased exacerbations and hospitalizations only in patients not receiving inhaled corticosteroids (ICS).

Interpretation: Aspergillus lung disease is common in bronchiectasis. Raised IgG levels to Aspergillus are associated with significantly worse outcomes, whereas ABPA and AS are associated with severe disease and exacerbations with a risk that is attenuated by ICS use.