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- Subramaniyam, Devipriya, et al.
(författare)
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Secretory Leukocyte Protease Inhibitor inhibits neutrophil apoptosis.
- 2011
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Ingår i: Respirology. - : Wiley. - 1440-1843 .- 1323-7799. ; Dec, s. 300-307
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Tidskriftsartikel (refereegranskat)abstract
- SUMMARY AT A GLANCE: Secretory leukocyte proteinase inhibitor (SLPI) is a major anti-elastase barrier at the epithelial surfaces of upper respiratory tract. Our findings indicate clear up-regulation of SLPI in response to endotoxin in nasal secretions. In addition, SLPI shows dose-dependent anti-apoptotic and chemotactic effects on primary human neutrophils. ABSTRACT: Background and objective: The Secretory Leukocyte Protease Inhibitor (SLPI) is a major anti-elastase barrier at the epithelial surfaces of upper respiratory tract. In addition to its anti-protease activity, SLPI has been shown to express anti-bacterial, anti-viral and anti-inflammatory properties. Methods: We measured SLPI concentration in nasal lavage fluid of healthy volunteers after challenge with endotoxin (LPS) and evaluated SLPI effects in vitro on neutrophil chemotaxis, adhesion, cytokine (IL-8) release and apoptosis. Results: SLPI concentration in nasal lavage (n = 9) 2, 6 and 24 hrs after the challenge with LPS (25 µg) increased from 32% to 238% compared to baseline (226 ± 71 ng/ml). In vitro, SLPI (20 to 80µg/ml) induced neutrophil chemotaxis (6-fold, p < 0.001) and decreased neutrophil apoptosis by 73% (p = 0.006), relative to controls. However, SLPI had no affect on IL-8 release or neutrophil adhesion to fibronectin. SLPI-positive immunoreactivity was co-localised with neutrophils in lung specimens from patients with chronic obstructive pulmonary disease. Conclusions: Our findings indicate up-regulation of SLPI in response to LPS in nasal secretions and show anti-apoptotic effects of SLPI in primary human neutrophils suggesting a new role of SLPI during neutrophilic inflammation.
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| 2. |
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| 3. |
- Lindberg, Anne, et al.
(författare)
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Fast onset of effect of budesonide/formoterol versus salmeterol/fluticasone and salbutamol in patients with chronic obstructive pulmonary disease and reversible airway obstruction.
- 2007
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Ingår i: Respirology (Carlton, Vic.). - : Wiley. - 1323-7799 .- 1440-1843. ; 12:5, s. 732-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Data on the onset of action of COPD medications are lacking. This study compared the onset of bronchodilation following different inhaled therapies in patients with moderate-to-severe COPD and reversible airway obstruction. METHODS: In this double-blind, double-dummy, crossover study, 90 patients (aged >or=40 years; FEV(1) 30-70% predicted) were randomized to a single dose (two inhalations) of budesonide/formoterol 160/4.5 microg, salmeterol/fluticasone 25/250 microg, salbutamol 100 microg or placebo (via pressurized metered-dose inhalers) on four visits. The primary end-point was change in FEV(1) 5 min after drug inhalation; secondary end-points included inspiratory capacity (IC) and perception of onset of effect. RESULTS: Budesonide/formoterol significantly improved FEV(1) at 5 min compared with placebo (P < 0.0001) and salmeterol/fluticasone (P = 0.0001). Significant differences were first observed at 3 min. Onset of effect was similar with budesonide/formoterol and salbutamol. Improvements in FEV(1) following active treatments were superior to placebo after 180 min (all P < 0.0001); both combinations were better than salbutamol at maintaining FEV(1) improvements (P
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| 4. |
- Ólafsdóttir, Inga S., et al.
(författare)
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Serum levels of matrix metalloproteinase-9, tissue inhibitors of metalloproteinase-1 and their ratio are associated with impaired lung function in the elderly : a population-based study
- 2010
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Ingår i: Respirology (Carlton South. Print). - : Wiley. - 1323-7799 .- 1440-1843. ; 15:3, s. 530-535
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMP) and their inhibitors, tissue inhibitors of metalloproteinases (TIMP), regulate homeostasis and turnover of the extra cellular matrix. The aim of this study was to investigate the associations of serum MMP-9 and TIMP-1 with lung function. METHODS: Spirometry was performed in a population-based sample of 888 subjects aged 70 years. Serum MMP-9 and TIMP-1 concentrations were measured by ELISA. RESULTS: Lower FEV(1) values were associated with higher serum levels of MMP-9 (P = 0.001) and TIMP-1 (P < 0.001), and a higher ratio of MMP-9 to TIMP-1 (P = 0.02). These associations were significant after adjustment for gender, weight, height, BMI, current smoking, pack years of smoking and the time for which samples were frozen. After stratification for gender, the associations between FEV(1) and MMP-9, TIMP-1, and their ratio, were significant in men but not in women. CONCLUSIONS: Lower FEV(1) was significantly but weakly associated with higher serum levels of MMP-9, TIMP-1 and a higher MMP-9/TIMP-1 ratio. This association was stronger in men than in women, suggesting a possible role for extracellular matrix remodelling in the development of impaired lung function. These associations may also partly explain the association between low FEV(1) and cardiovascular disease.
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| 5. |
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| 6. |
- Bailly, S., et al.
(författare)
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Clusters of sleep apnoea phenotypes: A large pan-European study from the European Sleep Apnoea Database (ESADA)
- 2021
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Ingår i: Respirology. - : Wiley. - 1323-7799 .- 1440-1843. ; 26:4, s. 378-387
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: To personalize OSA management, several studies have attempted to better capture disease heterogeneity by clustering methods. The aim of this study was to conduct a cluster analysis of 23 000 OSA patients at diagnosis using the multinational ESADA. Methods: Data from 34 centres contributing to ESADA were used. An LCA was applied to identify OSA phenotypes in this European population representing broad geographical variations. Many variables, including symptoms, comorbidities and polysomnographic data, were included. Prescribed medications were classified according to the ATC classification and this information was used for comorbidity confirmation. Results: Eight clusters were identified. Four clusters were gender-based corresponding to 54% of patients, with two clusters consisting only of men and two clusters only of women. The remaining four clusters were mainly men with various combinations of age range, BMI, AHI and comorbidities. The preferred type of OSA treatment (PAP or mandibular advancement) varied between clusters. Conclusion: Eight distinct clinical OSA phenotypes were identified in a large pan-European database highlighting the importance of gender-based phenotypes and the impact of these subtypes on treatment prescription. The impact of cluster on long-term treatment adherence and prognosis remains to be studied using the ESADA follow-up data set. © 2020 Asian Pacific Society of Respirology
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| 7. |
- Buttery, S. C., et al.
(författare)
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Contemporary perspectives in COPD: Patient burden, the role of gender and trajectories of multimorbidity
- 2021
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Ingår i: Respirology. - : Wiley. - 1323-7799 .- 1440-1843. ; 26:5, s. 419-441
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Tidskriftsartikel (refereegranskat)abstract
- An individual's experience of COPD is determined by many factors in addition to the pathological features of chronic bronchitis and emphysema and the symptoms that derive directly from them. Multimorbidity is the norm rather than the exception, so most people with COPD are living with a range of other medical problems which can decrease overall quality of life. COPD is caused by the inhalation of noxious particles or gases, in particular tobacco smoke, but also by early life disadvantage impairing lung development and by occupations where inhaled exposures are common (e.g. industrial, farming and cleaning work). Wealthy people are therefore relatively protected from developing COPD and people who do develop the condition may have reduced resources to cope. COPD is also no longer a condition that predominantly affects men. The prevalence of COPD among women has equalled that of men since 2008 in many high-income countries, due to increased exposure to tobacco, and in low-income countries due to biomass fuels. COPD is one of the leading causes of death in women in the USA, and death rates attributed to COPD in women in some countries are predicted to overtake those of men in the next decade. Many factors contribute to this phenomenon, but in addition to socioeconomic and occupational factors, there is increasing evidence of a higher susceptibility of females to smoking and pollutants. Quality of life is also more significantly impaired in women. Although most medications (bronchodilators and inhaled corticosteroids) used to treat COPD demonstrate similar trends for exacerbation prevention and lung function improvement in men and women, this is an understudied area and clinical trials frequently have a preponderance of males. A better understanding of gender-based predictors of efficacy of all therapeutic interventions is crucial for comprehensive patient care. There is an urgent need to recognize the increasing burden of COPD in women and to facilitate global improvements in disease prevention and management in this specific population. Many individuals with COPD follow a trajectory of both lung function decline and also multimorbidity. Unfavourable lung function trajectories throughout life have implications for later development of other chronic diseases. An enhanced understanding of the temporal associations underlying the development of coexisting diseases is a crucial first step in unravelling potential common disease pathways. Lessons can be learned from exploring disease trajectories of other NCD as well as multimorbidity development. Further research will be essential to explain how early life risk factors commonly influence trajectories of COPD and other diseases, how different diseases develop in relation to each other in a temporal way and how this ultimately leads to different multimorbidity patterns in COPD. This review integrates new knowledge and ideas pertaining to three broad themes (i) the overall burden of disease in COPD, (ii) an unappreciated high burden in women and (iii) the contrast of COPD trajectories and different multimorbidity patterns with trajectories of other NCD. The underlying pathology of COPD is largely irreversible, but many factors noted in the review are potentially amenable to intervention. Health and social care systems need to ensure that effective treatment is accessible to all people with the condition. Preventive strategies and treatments that alter the course of disease are crucial, particularly for patients with COPD as one of many problems.
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| 10. |
- Ekström, Magnus, et al.
(författare)
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Cardiovascular and antacid treatment and mortality in oxygen-dependent pulmonary fibrosis : A population-based longitudinal study
- 2016
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Ingår i: Respirology. - : Wiley. - 1440-1843 .- 1323-7799. ; 21:4, s. 705-711
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Severe idiopathic pulmonary fibrosis is associated with an increased risk of cardiovascular disease and gastro-oesophageal reflux, which may influence prognosis. We evaluated associations between cardiovascular and antacid medications, and mortality, in oxygen-dependent pulmonary fibrosis (PF) of unknown cause.METHODS: Prospective population-based study of adults starting long-term oxygen therapy (LTOT) for PF in Sweden 2005-2009. PF of unknown cause was defined by excluding patients with known or probable secondary PF. Time-dependent associations between medications and all-cause mortality were analysed using extended Cox regression, adjusting for potential confounders including age, sex, vital capacity, blood gases, body mass index, performance status, comorbidity and concurrent medications.RESULTS: Of 462 included patients, 329 (71%) died under observation. No patient was lost to follow-up. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) were associated with reduced adjusted mortality (HR 0.63; 0.47-0.85) and antiplatelet drugs with increased mortality (HR 1.49; 1.11-2.00), largely driven by higher mortality in women. There were no associations with mortality for antacid treatments, β-blockers, diuretics or statins.CONCLUSION: In oxygen-dependent PF, treatment with ACEI/ARB was associated with improved survival, antiplatelet drugs with decreased survival, whereas there was no association between antacid, β-blocker, diuretic or statin treatment and survival.
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