| 1. |
- Grigg, Jonathan, et al.
(författare)
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Cigarette smoke and platelet-activating factor receptor dependent adhesion of Streptococcus pneumoniae to lower airway cells
- 2012
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Ingår i: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 67:10, s. 908-913
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Tidskriftsartikel (refereegranskat)abstract
- Background Exposure to cigarette smoke (CS) is associated with increased risk of pneumococcal infection. The mechanism for this association is unknown. We recently reported that the particulate matter from urban air simulates platelet-activating factor receptor (PAFR)-dependent adhesion of pneumococci to airway cells. We therefore sought to determine whether CS stimulates pneumococcal adhesion to airway cells. Methods Human alveolar (A549), bronchial (BEAS2-B), and primary bronchial epithelial cells (HBEpC) were exposed to CS extract (CSE), and adhesion of Streptococcus pneumoniae determined. The role of PAFR in mediating adhesion was determined using a blocker (CV-3988). PAFR transcript level was assessed by quantitative real-time PCR, and PAFR expression by flow cytometry. Lung PAFR transcript level was assessed in mice exposed to CS, and bronchial epithelial PAFR expression assessed in active-smokers by immunostaining. Results In A549 cells, CSE 1% increased pneumococcal adhesion (p<0.05 vs control), PAFR transcript level (p<0.01), and PAFR expression (p<0.01). Pneumococcal adhesion to A549 cells was attenuated by CV-3988 (p<0.001). CSE 1% stimulated pneumococcal adhesion to BEAS2-B cells and HBEpC (p<0.01 vs control). CSE 1% increased PAFR expression in BEAS2-B (p<0.01), and in HBEpC (p<0.05). Lung PAFR transcript level was increased in mice exposed to CS in vivo (p<0.05 vs room air). Active smokers (n=16) had an increased percentage of bronchial epithelium with PAFR-positive cells (p<0.05 vs never smokers, n=11). Conclusion CSE stimulates PAFR-dependent pneumococcal adhesion to lower airway epithelial cells. We found evidence that CS increases bronchial PAFR in vivo.
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| 2. |
- Nyberg, Andre, Docent, 1984-, et al.
(författare)
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Effects of low-load/high-repetition resistance training on exercise capacity, health status and limb muscle adaptation in patients with severe COPD : a randomized controlled trial
- 2021
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Ingår i: Chest. - : Elsevier. - 0012-3692 .- 1931-3543. ; 159:5, s. 1821-1832
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Tidskriftsartikel (refereegranskat)abstract
- Background: Training volume is paramount in the magnitude of physiological adaptations following resistance training. However, patients with severe COPD are limited by dyspnea during traditional two-limb low-load/high-repetition resistance training (LLHR-RT), resulting in suboptimal training volumes. During a single exercise session, single-limb LLHR-RT decreases the ventilatory load and enables higher localized training volumes compared with two-limb LLHR-RT.Research Question: Does single-limb LLHR-RT lead to more profound effects compared with two-limb LLHR-RT on exercise capacity (6-min walk distance [6MWD]), health status, muscle function, and limb adaptations in patients with severe COPD?Study Design and Methods: Thirty-three patients (mean age 66 ± 7 years; FEV1 39 ± 10% predicted) were randomized to 8 weeks of single- or two-limb LLHR-RT. Exercise capacity (6MWD), health status, and muscle function were compared between groups. Quadriceps muscle biopsy specimens were collected to examine physiological responses.Results: Single-limb LLHR-RT did not further enhance 6MWD compared with two-limb LLHR-RT (difference, 14 [–12 to 39 m]. However, 73% in the single-limb group exceeded the known minimal clinically important difference of 30 m compared with 25% in the two-limb group (P = .02). Health status and muscle function improved to a similar extent in both groups. During training, single-limb LLHR-RT resulted in a clinically relevant reduction in dyspnea during training compared with two-limb LLHR-RT (–1.75; P = .01), but training volume was not significantly increased (23%; P = .179). Quadriceps muscle citrate synthase activity (19%; P = .03), hydroxyacyl-coenzyme A dehydrogenase protein levels (32%; P < .01), and capillary-to-fiber ratio (41%; P < .01) were increased compared with baseline after pooling muscle biopsy data from all participants.Interpretation: Single-limb LLHR-RT did not further increase mean 6MWD compared with two-limb LLHR-RT, but it reduced exertional dyspnea and enabled more people to reach clinically relevant improvements in 6MWD. Independent of execution strategy, LLHR-RT improved exercise capacity, health status, muscle endurance, and enabled several physiological muscle adaptations, reducing the negative consequences of limb muscle dysfunction in COPD.
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| 3. |
- Nyberg, Andre, Docent, 1984-, et al.
(författare)
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Role of progression of training volume on intramuscular adaptations in patients with chronic obstructive pulmonary disease
- 2022
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Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Quadriceps dysfunction is a common systemic manifestation of chronic obstructive pulmonary disease (COPD), for which treatment using resistance training is highly recommended. Even though training volume is suggested to be a key explanatory factor for intramuscular adaptation to resistance training in healthy older adults, knowledge is scarce on the role of progression of training volume for intramuscular adaptations in COPD.Methods: This study was a sub-analysis of a parallel-group randomized controlled trial. Thirteen patients with severe to very severe COPD (median 66 yrs, forced expiratory volume in 1 s 44% predicted) performed 8 weeks of low-load resistance training. In a post hoc analysis, they were divided into two groups according to their training volume progression. Those in whom training volume continued to increase after the first 4 weeks of training outlined the continued progression group (n = 9), while those with limited increase (<5%) or even reduction in training volume after the initial 4 weeks composed the discontinued progression group (n = 4). Fiber-type distribution and oxidative muscle protein levels, i.e., citrate synthase (CS), hydroxyacyl-coenzyme A dehydrogenase (HADH), mitochondrial transcription factor A (TfAM) as well as quadriceps endurance measures (total work from elastic band and isokinetic knee extension tests), were assessed before and after the intervention period.Results: The continued progression group sustained their training volume progression during weeks 5-8 compared to weeks 1-4 (median +25%), while the discontinued progression group did not (median -2%) (p = 0.007 between groups). Compared with baseline values, significant between-group differences in fiber type distribution and TfAM muscle protein levels (range ± 17-62%, p < 0.05) and in individual responses to change in Type I and Type IIa fiber type proportion, CS, HADH, and TfAM muscle protein levels outcomes (median 89 vs. 50%, p = 0.001) were seen in favor of the continued progression group. Moreover, only the continued progression group had a significant increase in HADH muscle protein levels (+24%, p = 0.004), elastic band (+56%, p = 0.004) and isokinetic (+7%, p = 0.004) quadriceps endurance, but the between-group differences did not reach statistical significance (range 14-29%, p = 0.330-1.000).Discussion: The novel findings of the current study were that patients with COPD who had a continued progression of training volume across the 8-weeks intervention had an increased proportion of Type I fibers, and TfAM muscle protein levels and decreased proportion of Type II fibers compared to those that did not continue to progress their training volume after the initial weeks. Additionally, HADH muscle protein levels and quadriceps endurance measurements only improved in the continued progression group, although no significant between-group differences were seen. These findings highlight the importance of continued progression of training volume during resistive training to counteract quadriceps dysfunction within the COPD population. Still, considering the small sample size and the post hoc nature of our analyses, these results should be interpreted cautiously, and further research is necessary.
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| 4. |
- Shen, Pamela, et al.
(författare)
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Cigarette smoke attenuates the nasal host response to Streptococcus pneumoniae and predisposes to invasive pneumococcal disease in mice.
- 2016
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Ingår i: Infection and Immunity. - 1098-5522. ; 84:5, s. 1536-1547
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pneumoniae is a leading cause of invasive bacterial infections, with nasal colonization an important first step for disease. While cigarette smoking is a strong risk factor for invasive pneumococcal disease, underlying mechanisms remain unknown. This is partly due to a lack of clinically relevant animal models investigating nasal pneumococcal colonization in the context of cigarette smoke exposure. We present a model of nasal pneumococcal colonization in cigarette smoke-exposed mice and document, for the first time, that cigarette smoke predisposes to invasive pneumococcal infection and mortality in an animal model. Cigarette smoke increased the risk of bacteraemia and meningitis without prior lung infection. Mechanistically, deficiency in IL-1α or PAFR, an important host receptor thought to bind and facilitate pneumococcal invasiveness, did not rescue cigarette smoke-exposed mice from invasive pneumococcal disease. Importantly, we observed cigarette smoke to attenuate nasal inflammatory mediator expression, particularly that of neutrophil recruiting chemokines, normally elicited by pneumococcal colonization. Smoking cessation during nasal pneumococcal colonization rescued nasal neutrophil recruitment and prevented invasive disease in mice. We propose that cigarette smoke predisposes to invasive pneumococcal disease by suppressing inflammatory processes of the upper respiratory tract. Given that smoking prevalence remain high worldwide, these findings are relevant to the continued efforts to reduce invasive pneumococcal disease burden.
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