| 1. |
|
|
| 2. |
- Chen, Chengshui, et al.
(författare)
-
Preventive and Therapeutic Effects of Phosphoinositide 3-Kinase Inhibitors on Acute Lung Injury
- 2011
-
Ingår i: Chest. - : Elsevier BV. - 1931-3543 .- 0012-3692. ; 140:2, s. 391-400
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Phosphoinositide 3-kinases (PI3Ks) are involved in a number of biologic responses. Recent preclinical studies demonstrated that the PI3K-dominant signal pathway could play an important role in the development of acute lung injury, although the mechanism remains unclear. Methods: CD-1 mice were administered different PI3K inhibitors either intranasally or intragastrically once a day for 3 days before intratracheal instillation of lipopolysaccharide at 4 h and 24 h. Effects of SHBM1009 on lipopolysaccharide-induced capillary permeability, leukocyte distribution and activation, and epithelial cell function were measured. Therapeutic effects of SHBM1009 on pancreatic elastase-induced lung injury were evaluated in rats. Results: The data demonstrated that the local delivery of PI3K inhibitors played more effective roles in the prevention of endotoxin-induced lung injury than the systemic delivery. The preventive effects of PI3K inhibitors varied most likely because of chemical properties, targeting sites, and pharmacokinetics. The local PI3K inhibitors prevented both endotoxin- and elastase-induced lung injury in mice and rats, possibly through directly inhibiting or inactivating the function of airway epithelial cells, which could not produce chemoattractant factors to activate neutrophils and macrophages. Conclusions: PI3K may be a therapeutic target for lung injury, and local delivery of PI3K inhibitors may be one of the optimal approaches for the therapy. CHEST 2011; 140(2):391-400
|
|
| 3. |
- Dong, Yaa-Hui, et al.
(författare)
-
Use of Inhaled Corticosteroids in Patients With COPD and the Risk of TB and Influenza A Systematic Review and Meta-analysis of Randomized Controlled Trials
- 2014
-
Ingår i: Chest. - : Elsevier BV. - 1931-3543 .- 0012-3692. ; 145:6, s. 1286-1297
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of inhaled corticosteroids (ICSs) is associated with an increased risk of pneumonia in patients with COPD. However the risks of other respiratory infections such as TB and influenza remain unclear. Methods: Through a comprehensive literature search of MEDLINE EMBASE CINAHL Cochrane Library and ClinicalTrials.gov from inception to July 2013 we identified randomized controlled trials of ICS therapy lasting at least 6 months. We conducted meta-analyses by the Peto Mantel-Haenszel and Bayesian approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of TB and influenza. Results: Twenty-five trials (22,898 subjects) for TB and 26 trials (23,616 subjects) for influenza were included. Compared with non-ICS treatment ICS treatment was associated with a significantly higher risk of TB (Peto OR 2.29 95% CI 1.04-5.03) but not influenza (Peto OR 1.24 95% CI 0.94-1.63). Results were similar with each meta-analytic approach. Furthermore the number needed to harm to cause one additional TB event was lower for patients with COPD treated with ICSs in endemic areas than for those in nonendemic areas (909 vs 1,667 respectively). Conclusions: This study raises safety concerns about the risk of TB and influenza associated with ICS use in patients with COPD which deserve further investigation.
|
|
| 4. |
- Ekström, Magnus, et al.
(författare)
-
Increased relative mortality in women with severe oxygen-dependent COPD
- 2010
-
Ingår i: Chest. - : American College of Chest Physicians. - 0012-3692 .- 1931-3543. ; 137:1, s. 31-36
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Although the incidence of COPD is rapidly increasing in women, knowledge is lacking concerning differences in relative mortality and causes of death in women compared with men. We aimed to analyze differences in relative mortality and cause-specific mortality between men and women on long-term oxygen therapy (LTOT) for COPD. Methods: Patients starting LTOT for COPD in Sweden between January 1, 1987, and December 31, 2004, were prospectively followed until termination of LTOT or through December 31, 2004. Causes of death according to the Swedish National Causes of Death Register were compared between the study group and the general Swedish population matched for age and sex, with the relative mortality expressed as standardized mortality rates (SMRs). Results: A total of 7,646 patients, 4,033 women and 3,613 men, were followed for a median of 1.7 years (range 0-18.0). No patient was lost to follow-up. A total of 5,448 patients, 2,745 women and 2,703 men, died. Women had a higher SMR than men: overall mortality, SMR 12.0 (95%, 11.6-12.5) vs 7.4 (95% CI, 7.1-7.6); for respiratory disease, SMR 127.9 (95% CI, 122.4-133.6) vs 66.0 (95% CI, 63.1-69.0); cancer, SMR 3.5 (95% CI, 3.0-3.9) vs 2.2 (95% CI, 1.9-2.5); and cardiovascular disease, SMR 3.7 (95% CI, 3.3-4.1) vs 2.5 (95% CI, 2.3-2.7), respectively. Conclusions: In severe COPD treated with long-term oxygen, women have higher relative mortality than men both overall and for respiratory disease, as well as for cardiovascular disease and cancer.
|
|
| 5. |
- Fazio, Nicola, et al.
(författare)
-
Everolimus Plus Octreotide Long-Acting Repeatable in Patients With Advanced Lung Neuroendocrine Tumors Analysis of the Phase 3, Randomized, Placebo-Controlled RADIANT-2 Study
- 2013
-
Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 143:4, s. 955-962
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The incidence of neuroendocrine tumors (NETs) has increased approximately fivefold since the 1980s. A similar increase in the incidence of lung NETs has been reported, but therapy has not been optimized. Methods: This exploratory subanalysis evaluated the efficacy and safety of everolimus plus octreotide long-acting repeatable (LAIR) in a cohort of patients with low- to intermediate-grade advanced lung NET from the phase 3, randomized, placebo-controlled RADIANT-2 (RAD001 in Advanced Neuroendocrine Tumors) study. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate, overall survival, change from baseline in biomarker levels, and safety outcomes. Results: Patients were randomly assigned to everolimus plus octreotide LAIR (n = 33) or placebo plus octreotide LAIR (n = 11). Median PFS was 13.63 months in the everolimus plus octreotide LAIR arm compared with 5.59, months in the placebo plus octreotide LAIR arm (relative risk for progression: HR, 0.72; 95% CI, 0.31-1.68; P = .228). More patients receiving everolimus plus octreotide LAR (67%) experienced minor tumor shrinkage (not partial response as per RECIST [Response Evaluation Criteria in Solid Tumors]) than those receiving placebo plus octreotide LAIR (27%). Most frequently reported adverse events (AEs) included stomatitis, rash, diarrhea, and asthenia. This was consistent with the overall RADIANT-2 trial and the safety profile of everolimus. Conclusions: This exploratory subgroup analysis of the RADIANT-2 trial indicates that in patients with advanced lung NET, the addition of everolimus to octreotide LAIR improves median PFS by 2.4-fold compared with placebo plus octreotide LAIR. These clinically significant observations support the continued evaluation of everolimus treatment regimens in this patient population. Trial registry: ClinicalTrials.gov; No.: NCT00412061; PRL: www.clinicaltrials.gov CHEST 2013; 143(4):955-962
|
|
| 6. |
|
|
| 7. |
- Grote, Ludger, 1964, et al.
(författare)
-
Oximeter-based autonomic state indicator algorithm for cardiovascular risk assessment.
- 2011
-
Ingår i: Chest. - : Elsevier BV. - 1931-3543 .- 0012-3692. ; 139:2, s. 253-259
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiovascular (CV) risk assessment is important in clinical practice. An autonomic state indicator (ASI) algorithm based on pulse oximetry was developed and validated for CV risk assessment. Methods: One hundred forty-eight sleep clinic patients (98 men, mean age 50 ± 13 years) underwent an overnight study using a novel photoplethysmographic sensor. CV risk was classified according to the European Society of Hypertension/European Society of Cardiology (ESH/ESC) risk factor matrix. Five signal components reflecting cardiac and vascular activity (pulse wave attenuation, pulse rate acceleration, pulse propagation time, respiration-related pulse oscillation, and oxygen desaturation) extracted from 99 randomly selected subjects were used to train the classification algorithm. The capacity of the algorithm for CV risk prediction was validated in 49 additional patients. Results: Each signal component contributed independently to CV risk prediction. The sensitivity and specificity of the algorithm to distinguish high/low CV risk in the validation group were 80% and 77%, respectively. The area under the receiver operating characteristic curve for high CV risk classification was 0.84. β-Blocker treatment was identified as an important factor for classification that was not in line with the ESH/ESC reference matrix. Conclusions: Signals derived from overnight oximetry recording provide a novel potential tool for CV risk classification. Prospective studies are warranted to establish the value of the ASI algorithm for prediction of outcome in CV disease.
|
|
| 8. |
- Guida, Giuseppe, et al.
(författare)
-
Determinants of Exhaled Nitric Oxide in Chronic Rhinosinusitis
- 2010
-
Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 137:3, s. 658-664
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic rhinosinusitis (CRS) has been reported to be associated with increased values of exhaled nitric oxide (ENO), which could not be entirely explained by the association between CRS and asthma. The aim of this study was to investigate the variables associated with increased ENO in patients with CRS. Methods: This was a prospective cross-sectional descriptive study of 93 consecutive patients with CRS. The effect on ENO of age, gender, atopy, asthma, respiratory symptoms without bronchial hyperresponsiveness (BHR), and nasal polyps was evaluated by multiple regression analysis. Results: Nasal polyps (P=.01), asthma (P<.001), and respiratory symptoms without BHR (P=.01) were the only independent variables associated with increased ENO. The prevalence of asthma was significantly higher in subjects with nasal polyps (61% vs 29.4%), P=.005, whereas the prevalence of respiratory symptoms without BHR was higher in those without nasal polyps (44.1% vs 15.3%, P=.003). Respiratory symptoms without BHR were associated with significantly higher ENO and prevalence of sputum eosinophilia (eosinophils>3%) in patients with nasal polyps compared with those without nasal polyps (68.2 vs 24.0 ppb, P=.001; 60% vs 8.3%, P=.03, respectively). Conclusions: The presence of nasal polyps in patients with CRS was associated with increased asthma prevalence as well as increased ENO levels. Respiratory symptoms without BHR were associated with eosinophilic airway inflammation and increased ENO only in patients with nasal polyps. These findings suggest important clinical and biologic differences between the two types of CRS, with and without nasal polyps.
|
|
| 9. |
- Hagstad, Stig, 1978, et al.
(författare)
-
Passive Smoking Exposure Is Associated With Increased Risk of COPD in Never Smokers
- 2014
-
Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 145:6, s. 1298-1304
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Passive smoking, or environmental tobacco smoke (ETS), is a risk factor for lung cancer, cardiovascular disease, and childhood asthma, but a relationship with COPD has not been fully established. Our aim was to study ETS as a risk factor for COPD in never smokers. Methods: Data from three cross-sectional studies within the Obstructive Lung Disease in Northern Sweden (OLIN) database were pooled. Of the 2,182 lifelong never smokers, 2,118 completed structured interviews and spirometry of acceptable quality. COPD was defined according to the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria using postbronchodilator spirometry. The association of COPD with ETS in single and multiple settings was calculated by multivariate logistic regression adjusting for known risk factors for COPD. Results: COPD prevalence was associated with increased ETS exposure: 4.2% (no ETS), 8.0% (ETS ever at home), 8.3% (ETS at previous work), and 14.7% (ETS ever at home and at both previous and current work), test for trend P 5.003. Exclusion of subjects aged >= 65 years and subjects reporting asthma yielded similar results. ETS in multiple settings, such as ever at home and at both previous and current work, was strongly associated to COPD (OR, 3.80; 95% CI, 1.29-11.2). Conclusions: In this population-based sample of never smokers, ETS was independently associated with COPD. The association was stronger for ETS in multiple settings. ETS in multiple settings was, after age, the strongest risk factor for COPD and comparable to personal smoking of up to 14 cigarettes/d in comparable materials. The findings strongly advocate measures against smoking in public places.
|
|
| 10. |
- Janaudis-Ferreira, Tania, 1976-, et al.
(författare)
-
Resistance arm training in patients with chronic obstructive pulmonary disease : a randomized controlled trial
- 2011
-
Ingår i: Chest. - : American College of Chest Physicians. - 0012-3692 .- 1931-3543. ; 139:1, s. 151-158
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The study aimed to evaluate the effect of upper extremity resistance training for patients with COPD on dyspnea during activity of daily living (ADL), arm function, arm exercise capacity, muscle strength and health related quality of life (HRQL)METHODS: Patients were randomly assigned to an intervention or control group. The intervention group underwent arm resistance training. The control group performed a sham. Both groups exercised 3 times a week for 6 weeks. Dyspnea during ADL and HRQL were measured using the chronic respiratory disease questionnaire (CRDQ). Arm function and exercise capacity were measured using the 6-minute pegboard and ring test (6PBRT) and the unsupported upper limb exercise test (UULEX), respectively. Muscle strength for the biceps, triceps, anterior and middle deltoids was obtained using an isometric dynamometer.RESULTS: Thirty-six patients with COPD (66 +/- 9 yrs) participated in the study. Compared with the control group, the magnitude of change in the intervention group was greater for the 6PBRT (p = 0.03), UULEX (p = 0.01) and elbow flexion force (p = 0.01); elbow extension force (p = 0.02), shoulder flexion force (p = 0.029) and shoulder abduction force (p = 0.01). There was no between-group difference in dyspnea during ADL, HRQL or symptoms during the 6PBRT or UULEX (all p values greater than 0.08).CONCLUSIONS: Resistance based arm training improved arm function, arm exercise capacity and muscle strength in patients with COPD. No improvement in dyspnea during ADL, HRQL or symptoms was demonstrated.
|
|
