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- Bjermer, Leif, et al.
(författare)
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Reslizumab for Inadequately Controlled Asthma with Elevated Blood Eosinophil Levels : a Randomized Phase 3 Study
- 2016
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Ingår i: Chest. - : Elsevier BV. - 1931-3543 .- 0012-3692. ; 150:4, s. 789-798
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This phase 3 study further characterizes the efficacy and safety of reslizumab (a humanized anti-interleukin-5 monoclonal antibody) in patients aged 12-75 years with asthma inadequately controlled by at least a medium-dose inhaled corticosteroid, and blood eosinophils ≥400cells/μL.METHODS: Patients were randomized to receive reslizumab 0.3 or 3.0mg/kg or placebo once/every 4 weeks/16 weeks. Primary endpoint was change from baseline in pre-bronchodilator forced expiratory volume in 1 sec (FEV1) over 16 weeks. Secondary endpoints included forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF25-75%), patient-reported control of asthma symptoms, short-acting beta agonist (SABA) use, blood eosinophil levels, and safety.RESULTS: Reslizumab significantly improved FEV1 (difference vs placebo [reslizumab 0.3 and 3.0mg/kg]:115mL[95% CI 16-215; P= .0237] and 160mL[95% CI 60-259; P= .0018]). Clinically meaningful increases in FVC (130mL) and FEF25-75% (233mL/s) were observed with reslizumab 3.0mg/kg. Reslizumab improved Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) versus placebo (greater effects seen with 3.0mg/kg; P<0.05). The minimally important difference was reached for AQLQ (reslizumab 3.0mg/kg) but not ACQ. Asthma Symptom Utility Index and SABA use were improved with reslizumab. The most common adverse events were asthma worsening, headache, and nasopharyngitis; most were mild-to-moderate in severity.CONCLUSIONS: Reslizumab improved lung function, asthma control and symptoms, and quality of life, and was well tolerated in patients with inadequately controlled asthma (despite standard therapy), and elevated blood eosinophils. Overall, the 3.0mg/kg dose of reslizumab provided greater improvements in asthma outcomes (vs 0.3mg/kg), with comparable safety.
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- D'Andrea, Antonello, et al.
(författare)
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Right Ventricular Functional Reserve in Early-Stage Idiopathic Pulmonary Fibrosis : An Exercise Two-Dimensional Speckle Tracking Doppler Echocardiography Study
- 2019
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Ingår i: Chest. - : Elsevier BV. - 1931-3543 .- 0012-3692. ; 155:2, s. 297-306
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The most important determinant of long-term survival in patients with idiopathic pulmonary fibrosis is the right ventricular (RV) adaptation to the increased pulmonary vascular resistance. Our aim was to explore RV contractile reserve during stress echocardiography in early-stage IPF.METHODS: Fifty early-stage patients with IPF and 50 healthy control patients underwent rest and stress echocardiography, including RV two-dimensional speckle tracking echocardiography. At peak exertion, blood gas analysis and spirometry were also assessed.RESULTS: At rest, RV diameters were mildly increased in IPF; however, although RV conventional systolic function indexes were similar between the IPF and control groups, RV global longitudinal strain and RV lateral wall longitudinal strain (LWLS) were significantly reduced in the IPF cohort. During physical exercise, patients with IPF showed a reduced exercise tolerance with lower maximal workload (P < .01), level of oxygen saturation (P < .001), and peak heart rate (P < .01). Systolic and diastolic BP values were similar in both groups. Systolic pulmonary artery pressure (PAPs) increase (ΔPAPs) during exertion was higher in IPF vs healthy subjects (P < .0001); RV LWLS increase (ΔRV LWLS) during exercise was lower in patients with IPF vs control patients (P < .00001). By multivariable analysis, RV LWLS at rest and ΔRV LWLS were directly related to peak exertion capacity, PAPs, and blood oxygen saturation level (Spo2; P < .0001). Δ RV LWLS was directly related to diffusion lung carbon monoxide (P < .0001).CONCLUSIONS: RV myocardial dysfunction is already present at rest in early-stage IPF and worsens during exertion as detected by two-dimensional speckle-tracking echocardiography. The RV altered contractile reserve appears to be related to reduced exercise tolerability and impaired pulmonary hemodynamic.
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- Marengoni, Alessandra, et al.
(författare)
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The Relationship Between COPD and Frailty : A Systematic Review and Meta-Analysis of Observational Studies
- 2018
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Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 154:1, s. 21-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Frailty is common in seniors and is characterized by diminished physiological reserves and increased vulnerability to stressors. Frailty can change the prognosis and treatment approach of several chronic diseases, including COPD. The association between frailty and COPD has never been systematically reviewed.OBJECTIVES: The goal of this study was to conduct a systematic review and meta-analysis assessing the association of COPD with frailty and pre-frailty.METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used when reporting this review. We searched PubMed, Web of Science, and Embase from January 1, 2002, to October 6, 2017. The quality of the studies was evaluated by using the Newcastle Ottawa Scale. Two assessors independently rated each study: scores > 7 were considered a low risk of bias; 5 to 7, a moderate risk of bias; and < 5, a high risk of bias. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity (I-2) and publication bias were assessed.RESULTS: Atotal of 27 studies were selected: 23 cross-sectional, three longitudinal, and one both. The pooled prevalence of pre-frailty in individuals with COPD was 56% (95% CI, 52-60; I-2 = 80.8%); it was 19% (95% CI, 14-24; I-2 = 94.4%) for frailty. Patients with COPD had a two-fold increased odds of frailty (pooled OR, 1.97 [95% CI, 1.53-2.53]; I-2 = 0.0%). Three longitudinal studies, presenting heterogeneous aims and methods, suggested a bidirectional association between COPD and frailty.CONCLUSIONS: Frailty and pre-frailty are common in individuals with COPD. Older subjects with COPD have a two-fold increased odds of frailty. These results may have clinical implications, as they identify the need to assess frailty in individuals with COPD and to further investigate any potential negative effects associated with the co-occurrence of these conditions. Longitudinal research that examines temporal associations between COPD and frailty are needed to further clarify this relationship and to assess if treatment of COPD may prevent the onset of frailty.
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- Pincikova, Terezia, et al.
(författare)
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Severely Impaired Control of Bacterial Infections in a Patient With Cystic Fibrosis Defective in Mucosal-Associated Invariant T Cells
- 2018
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Ingår i: Chest. - : ELSEVIER SCIENCE BV. - 0012-3692 .- 1931-3543. ; 153:5, s. E93-E96
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a unique case of a patient with cystic fibrosis characterized by severely impaired control of bacterial respiratory infections. This patient's susceptibility to such infections was much worse than expected from a cystic fibrosis clinical perspective, and he died at age 22 years despite extensive efforts and massive use of antibiotics. We found that this severe condition was associated with a near-complete deficiency in circulating mucosal-associated invariant T (MAIT) cells as measured at several time points. MAIT cells are a large, recently described subset of T cells that recognize microbial riboflavin metabolites presented by the highly evolutionarily conserved MR1 molecules. The MAIT cell deficiency was specific; other T-cell subsets were intact. Even though this is only one unique case, the findings lend significant support to the emerging role of MAIT cells in mucosal immune defense and suggest that MAIT cells may significantly modify the clinical phenotype of respiratory diseases.
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| 10. |
- Sator, Lea, et al.
(författare)
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Overdiagnosis of COPD in Subjects With Unobstructed Spirometry A BOLD Analysis
- 2019
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Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 156:2, s. 277-288
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012.METHODS: A false positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC < 0.7).RESULTS: Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication.CONCLUSIONS: False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.
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