Chest最新文献

In this installment of the How I Do It series on severe asthma, we tackle the clinical conundrum of choosing the right biologic for the right patient with severe asthma. With six biologics now approved for use in this area comprising four different targeting strategies (anti-Ig E: omalizumab; anti-IL-5 and anti-IL-5-receptor: mepolizumab, reslizumab, and benralizumab; anti-IL-4-receptor: dupilumab; anti-thymic stromal lymphopoietin: tezepelumab), this question is increasingly complex. Recognizing that no head-to-head trial has compared biologics, we based our review on the expected effects of inhibiting different aspects of type 2 airway inflammation, supported whenever possible by clinical trial and real-world data. We use four variations of a case of severe uncontrolled asthma to develop concepts and considerations introduced in the previous installment ("Workup of Severe Asthma") and discuss pregnancy-related, biomarker-related, comorbidity-related, and corticosteroid dependency-related considerations when choosing a biologic. The related questions of deciding when, why, and how to switch from one biologic to another also are discussed. Overall, we consider that the choice of biologics should be based on the available clinical trial data for the desired efficacy outcomes, the biomarker profile of the patient, safety profiles (eg, when pregnancy is considered), and opportunities to target two comorbidities with one biologic. Using systemic and airway biomarkers (blood eosinophils and exhaled nitric oxide [Feno]) and other phenotypic characteristics, we suggest a framework to facilitate therapeutic decision-making. Post hoc studies and new comparative studies are needed urgently to test this framework and to determine whether it allows us to make other clinically useful predictions.

Background: Echocardiographic tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary arterial pressure (sPAP) ratio is a noninvasive surrogate for right ventricle (RV)-pulmonary arterial (PA) coupling. It has been related to outcome in patients with moderate to severe pulmonary hypertension (PH).

Research question: Is RV-PA coupling of prognostic relevance in patients with suspected PH, but only normal or mildly elevated mean pulmonary arterial pressure (mPAP), and is it associated with impaired exercise capacity and exercise hemodynamics?

Study design and methods: Patients with mPAP of < 25 mm Hg who underwent echocardiography and exercise right heart catheterization in our PH clinic were analyzed retrospectively. Mild PH was defined as mPAP of 21 to 24 mm Hg and exercise PH (EPH) was defined as a mPAP to cardiac output (CO) slope of > 3 mm Hg/L/min. Multivariate analysis was performed to identify independent predictors for clinical worsening (CW), defined by disease-related hospitalization, transplantation, or death.

Results: Two hundred thirty-seven patients (155 female with median age, 64 years [interquartile range (IQR), 54-73 years]; no PH: n = 147; mild PH: n = 90; EPH: n = 202) were included. During the observation time of 63 months (IQR, 29-104 months), 36 patients died and 126 clinical worsening events occurred. TAPSE to sPAP ratio was an age- and sex-independent predictor of mortality (hazard ratio [HR], 0.09; 95% CI, 0.01-0.62; P = .014) and clinical worsening (HR, 0.05; 95% CI, 0.35-0.78; P = .002). TAPSE to sPAP ratio also was correlated significantly to 6-min walk distance (r = 0.33; P < .001) and exercise hemodynamics (mPAP to CO slope: r_ρ = -0.56; P < .001). The best multivariate predictive model for clinical worsening in this population consisted of TAPSE to sPAP ratio (HR, 0.71; 95% CI, 0.53-0.95; P = .021), N-terminal pro-brain natriuretic peptide (HR, 1.15; 95% CI, 0.99-1.34; P = .065), and 6-min walk distance (HR, 0.998; 95% CI, 0.995-1.00; P = .042).

Interpretation: Our results indicate that in patients with suspected PH, but normal or only mildly elevated resting mPAP, TAPSE to sPAP ratio is an independent predictor of outcome. In addition, it is associated significantly with exercise capacity and exercise hemodynamics and may be a helpful tool in the prediction of future clinical worsening of this patient population.

Background: Early randomized controlled trials (RCTs) of bronchoscopic lung volume reduction (BLVR) have shown clinically meaningful benefits in lung function, dyspnea, and quality of life in patients with severe emphysema. Safety outcome data obtained after BLVR in the United States are scarce outside the RCTs.

Research question: What is the rate of inpatient complications after BLVR in the real world in the United States?

Study design and methods: We used the National Inpatient Sample database to identify in-hospital complications after BLVR from 2018 through 2020. Complications were defined as pneumothorax, COPD exacerbation, pneumonia, hemoptysis, acute respiratory failure, and valve removal. We also analyzed all-cause in-hospital mortality and length of stay (LOS).

Results: We identified 467 admissions related to BLVR procedures. The number of procedures doubled between 2019 and 2020 (from 153 to 295 procedures). The median age was 67.9 years (interquartile range, 61.1-72.8 years), 210 patients (45.0%) were female, 401 patients (85.8%) were White, and Medicare was the primary expected payer for 72.8% of patients. Most procedures were performed in urban teaching hospitals (56.9%). The rate of pneumothorax was 26.3%, that of acute respiratory failure was 19.5%, that of COPD exacerbation was 8.8%, that of pneumonia was 7.3%, and that of hemoptysis was 5.3%. Chest tube placement was required in 84 of 123 patients (68.3%) with pneumothorax. The endobronchial valve had to be removed in 69 patients (14.8%). The median LOS was 2.8 days (interquartile range, 2.3-4.5 days). The number of in-hospital deaths was fewer than 11 (< 2.3%). Overall, the subgroup who experienced in-hospital complications did not differ significantly from the others in terms of comorbidities, demographics, and hospital characteristics.

Interpretation: We found that the real-world complication rate after BLVR was similar to the published complication rates from early randomized clinical trials. In-hospital mortality was low, suggesting that aside from the commonly anticipated complications, BLVR is a safe treatment option for severe emphysema.

Background: Alongside the recognized Global Initiative for Obstructive Lung Disease (GOLD) classification, the Staging of Airflow Obstruction by Ratio (STAR) severity scheme has been proposed for categorizing COPD.

Study question: What are the agreement and utility of the GOLD and STAR classifications in patients with severe COPD entering the rehabilitation setting?

Study design and methods: Medical records were reviewed in this multicenter retrospective study, examining key functional variables and their changes in a large cohort of patients with COPD undergoing pulmonary rehabilitation.

Results: A total of 1,516 participants (33.7% female participants; median age, 72.0 years) were included in the analysis. Compared with GOLD, the use of the STAR classification resulted in a different disease severity category for 53.4% of patients. An unweighted Cohen's kappa of 0.25 and a Bangdiwala B value of 0.24 indicated a fair agreement between the 2 classifications. Higher weighted agreement measures (0.47 and 0.78, respectively) suggested that discrepancies between the classifications mainly occurred for contiguous stages. GOLD exhibited superior discrimination between stages for chronic respiratory failure, whereas STAR exhibited better performance in detecting hyperinflation. In terms of their application within pulmonary rehabilitation settings, GOLD exhibited superior performance compared with STAR in identifying the minimal clinically important difference in 6-min walking distance and modified Medical Research Council score. Accordingly, GOLD but not STAR acted as an independent predictor for achieving a minimal clinically important difference in modified Medical Research Council score (OR, 1.48; 95% CI, 1.12-1.94; P = .005) and also independently predicted changes in the Braden scale score (β = 0.154; P = .004).

Interpretation: STAR exhibited a more uniform gradation of disease severity and enhanced performance in detecting hyperinflation, but our preliminary findings do not endorse its utilization in the rehabilitation setting.