| 1. |
- Shrine, N, et al.
(författare)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Tidskriftsartikel (refereegranskat)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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| 2. |
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| 3. |
- Loth, Daan W, et al.
(författare)
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Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
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Tidskriftsartikel (refereegranskat)abstract
- Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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| 4. |
- Nijs, Jo, et al.
(författare)
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Nociplastic Pain Criteria or Recognition of Central Sensitization? Pain Phenotyping in the Past, Present and Future
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 10:15
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Tidskriftsartikel (refereegranskat)abstract
- Recently, the International Association for the Study of Pain (IASP) released clinical criteria and a grading system for nociplastic pain affecting the musculoskeletal system. These criteria replaced the 2014 clinical criteria for predominant central sensitization (CS) pain and accounted for clinicians' need to identify (early) and correctly classify patients having chronic pain according to the pain phenotype. Still, clinicians and researchers can become confused by the multitude of terms and the variety of clinical criteria available. Therefore, this paper aims at (1) providing an overview of what preceded the IASP criteria for nociplastic pain ('the past'); (2) explaining the new IASP criteria for nociplastic pain in comparison with the 2014 clinical criteria for predominant CS pain ('the present'); and (3) highlighting key areas for future implementation and research work in this area ('the future'). It is explained that the 2021 IASP clinical criteria for nociplastic pain are in line with the 2014 clinical criteria for predominant CS pain but are more robust, comprehensive, better developed and hold more potential. Therefore, the 2021 IASP clinical criteria for nociplastic pain are important steps towards precision pain medicine, yet studies examining the clinimetric and psychometric properties of the criteria are urgently needed.
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| 5. |
- Sakornsakolpat, Phuwanat, et al.
(författare)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Fabbri, L. M., et al.
(författare)
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COPD and multimorbidity: recognising and addressing a syndemic occurrence
- 2023
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Ingår i: Lancet Respiratory Medicine. - 2213-2600. ; 11:11, s. 1020-1034
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Tidskriftsartikel (refereegranskat)abstract
- Most patients with chronic obstructive pulmonary disease (COPD) have at least one additional, clinically relevant chronic disease. Those with the most severe airflow obstruction will die from respiratory failure, but most patients with COPD die from non-respiratory disorders, particularly cardiovascular diseases and cancer. As many chronic diseases have shared risk factors (eg, ageing, smoking, pollution, inactivity, and poverty), we argue that a shift from the current paradigm in which COPD is considered as a single disease with comorbidities, to one in which COPD is considered as part of a multimorbid state-with co-occurring diseases potentially sharing pathobiological mechanisms-is needed to advance disease prevention, diagnosis, and management. The term syndemics is used to describe the co-occurrence of diseases with shared mechanisms and risk factors, a novel concept that we propose helps to explain the clustering of certain morbidities in patients diagnosed with COPD. A syndemics approach to understanding COPD could have important clinical implications, in which the complex disease presentations in these patients are addressed through proactive diagnosis, assessment of severity, and integrated management of the COPD multimorbid state, with a patient-centred rather than a single-disease approach.
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| 11. |
- Hurth, A., et al.
(författare)
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Assessment of Central Sensitization in Breast Cancer Survivors: Convergent Validity and Use of the Central Sensitization Inventory (CSI) and Its Short-Form as a Clustering Tool
- 2021
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Ingår i: Clinics and Practice. - : MDPI AG. - 2039-7275 .- 2039-7283. ; 11:3, s. 607-618
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Tidskriftsartikel (refereegranskat)abstract
- The Central Sensitization Inventory (CSI) measurement properties in patients having nonspecific, noncancer pain are well-established. However, studies examining the reliability and validity of either the CSI or the Central Sensitization Inventory short-form version (CSI-9) in breast cancer survivors (BCS) are scarce. The purpose was to evaluate convergent validity and internal consistency of the CSI and CSI-9. Additionally, the relevance of a new cluster calculator using the CSI was explored. The cross-sectional multi-center study included 65 BCS and 37 healthy volunteers. Patients filled out multiple questionnaires assessing pain, number of painful areas, anxiety, depression and quality of life. The relevance of a cluster calculator was explored by known-group comparisons and boxplot description. All hypotheses were formulated before data analysis. The majority of hypotheses on the correlations between the CSI or CSI-9 and other health outcomes were confirmed (22 out of 27). The CSI and CSI-9 have excellent (alpha = 0.92) and good (alpha = 0.86) internal consistency, respectively. The CSI cluster calculator might be an interesting tool to use to have a patient's overall condition snapshot. Generally, the study findings support the construct validity and internal consistency of the CSI, which underline the use of this self-reported instrument in BCS. The CSI-9 shows promising results, but should be further evaluated.
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| 12. |
- Nijs, Jo, et al.
(författare)
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Towards precision pain medicine for pain after cancer: the Cancer Pain Phenotyping Network multidisciplinary international guidelines for pain phenotyping using nociplastic pain criteria
- 2023
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912. ; 130:5, s. 611-621
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Tidskriftsartikel (refereegranskat)abstract
- Pain after cancer remains underestimated and undertreated. Precision medicine is a recent concept that refers to the ability to classify patients into subgroups that differ in their susceptibility to, biology, or prognosis of a particular disease, or in their response to a specific treatment, and thus to tailor treatment to the individual patient characteristics. Applying this to pain after cancer, the ability to classify post-cancer pain into the three major pain phenotypes (i.e. nociceptive, neuropathic, and nociplastic pain) and tailor pain treatment accordingly, is an emerging issue. This is especially relevant because available evidence suggests that nociplastic pain is present in an important subgroup of those patients experiencing post-cancer pain. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system for nociplastic pain account for the need to identify and correctly classify patients according to the pain phenotype early in their treatment. These criteria are an important step towards precision pain medicine with great potential for the field of clinical oncology. Within this framework, the Cancer Pain Phenotyping (CANPPHE) Network, an international and interdisciplinary group of oncology clinicians and researchers from seven countries, applied the 2021 IASP clinical criteria for nociplastic pain to the growing population of those experiencing post-cancer pain. A manual is provided to allow clinicians to differentiate between predominant nociceptive, neuropathic, or nociplastic pain after cancer. A seven-step diagnostic approach is presented and illustrated using cases to enhance understanding and encourage effective implementation of this approach in clinical practice.
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| 13. |
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| 15. |
- Gagatek, Sebastian, et al.
(författare)
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Validation of Clinical COPD Phenotypes for Prognosis of Long-Term Mortality in Swedish and Dutch Cohorts
- 2022
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Ingår i: COPD. - : Informa Healthcare. - 1541-2555 .- 1541-2563. ; 19:1, s. 330-338
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable mortality risk. The aim of our investigation was to validate a simple clinical algorithm for long-term mortality previously proposed by Burgel et al. in 2017. Subjects with COPD from two cohorts, the Swedish PRAXIS study (n = 784, mean age (standard deviation (SD)) 64.0 years (7.5), 42% males) and the Rotterdam Study (n = 735, mean age (SD) 72 years (9.2), 57% males), were included. Five clinical clusters were derived from baseline data on age, body mass index, dyspnoea grade, pulmonary function and comorbidity (cardiovascular disease/diabetes). Cox models were used to study associations with 9-year mortality. The distribution of clinical clusters (1-5) was 29%/45%/8%/6%/12% in the PRAXIS study and 23%/26%/36%/0%/15% in the Rotterdam Study. The cumulative proportion of deaths at the 9-year follow-up was highest in clusters 1 (65%) and 4 (72%), and lowest in cluster 5 (10%) in the PRAXIS study. In the Rotterdam Study, cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared with cluster 5, the meta-analysed age- and sex-adjusted hazard ratio (95% confidence interval) for cluster 1 was 6.37 (3.94-10.32) and those for clusters 2 and 3 were 2.61 (1.58-4.32) and 3.06 (1.82-5.13), respectively. Burgel's clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with the best prognosis and clusters 2 and 3 with intermediate prognosis in two independent cohorts from Sweden and the Netherlands.
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| 16. |
- Jackson, Victoria E, et al.
(författare)
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Meta-analysis of exome array data identifies six novel genetic loci for lung function.
- 2018
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Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
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| 17. |
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| 18. |
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| 19. |
- Lahousse, A., et al.
(författare)
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Lifestyle and Pain following Cancer: State-of-the-Art and Future Directions
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- This review discusses chronic pain, multiple modifiable lifestyle factors, such as stress, insomnia, diet, obesity, smoking, alcohol consumption and physical activity, and the relationship between these lifestyle factors and pain after cancer. Chronic pain is known to be a common consequence of cancer treatments, which considerably impacts cancer survivors' quality of life when it remains untreated. Improvements in lifestyle behaviour are known to reduce mortality, comorbid conditions (i.e., cardiovascular diseases, other cancer, and recurrence) and cancer-related side-effects (i.e., fatigue and psychological issues). An inadequate stress response plays an important role in dysregulating the body's autonomic, endocrine, and immune responses, creating a problematic back loop with pain. Next, given the high vulnerability of cancer survivors to insomnia, addressing and treating those sleep problems should be another target in pain management due to its capacity to increase hyperalgesia. Furthermore, adherence to a healthy diet holds great anti-inflammatory potential for relieving pain after cancer. Additionally, a healthy diet might go hand in hand with weight reduction in the case of obesity. Consuming alcohol and smoking have an acute analgesic effect in the short-term, with evidence lacking in the long-term. However, this acute effect is outweighed by other harms on cancer survivors' general health. Last, informing patients about the benefits of an active lifestyle and reducing a sedentary lifestyle after cancer treatment must be emphasised when considering the proven benefits of physical activity in this population. A multimodal approach addressing all relevant lifestyle factors together seems appropriate for managing comorbid conditions, side-effects, and chronic pain after cancer. Further research is needed to evaluate whether modifiable lifestyle factors have a beneficial influence on chronic pain among cancer survivors.
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| 20. |
- Lahousse, A., et al.
(författare)
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The effect of psychologically informed practice with behavioural graded activity in cancer survivors: systematic review and meta-analysis
- 2024
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Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 18, s. 854-899
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Tidskriftsartikel (refereegranskat)abstract
- Purpose This systematic review and meta-analysis aimed to determine the effectiveness of psychologically informed practice (PIP) with behavioural graded activity (BGA) compared to (1) waitlist controls (WLC), (2) other interventions (OI), (3) PIP alone or (4) BGA alone in cancer patients and survivors (CPaS). Methods PubMed, Web of Science and Embase were screened for randomised controlled trials encompassing BGA + PIP in CPaS. Effect sizes were inventoried for outcomes regarding physical activity (PA), quality of life (QoL) and debilitating symptoms (DS), which were assessed at four time points: post-intervention (PI), follow-up F1 (1 to 3 months), F2 (4 to 6 months) and F3 (> 6 months). The quality of the evidence was classified by the GRADE approach. Results Thirty-three studies were found eligible, comprising 4330 participants. Significant effects with low heterogeneity of PIP + BGA comparing to WLC were found for anxiety (SMD - 1.29 [-1.71; - 0.86]), depression ( SMD - 0.79 [- 1.10; - 0.48]), functional impairment (SMD - 0.72 [- 0.95; - 0.50]), PA (self-reported: (SMD - 0.58 [- 0.84; - 0.32]) and objectively measured: (SMD - 0.51 [- 0.90; - 0.13])) and social impairment (SMD - 0.33 [- 0.58; - 0.08]). When comparing PIP + BGA to OI, fatigue (SMD - 0.35 [- 0.51; - 0.20]) and PA ( SMD - 0.26 [- 0.41; - 0.11]) at PI, and fatigue ( SMD - 0.34 [- 0.58; - 0.10]) at F1 were found significant with low heterogeneity. No significant effects were observed in the meta-analyses of studies comparing PIP + BGA to BGA or PIP alone. Conclusions PIP with BGA has a favourable effect on DS, PA and QoL in CPaS when compared to non-behavioural interventions such as WLC, usual care and education. However, further research is needed on `how' and `when' PIP + BGA should be provided in cancer rehabilitation.
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| 21. |
- Lahousse, A., et al.
(författare)
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The Mediating Effect of Perceived Injustice and Pain Catastrophizing in the Relationship of Pain on Fatigue and Sleep in Breast Cancer Survivors: A Cross-Sectional Study
- 2022
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Ingår i: Pain Medicine. - : Oxford University Press (OUP). - 1526-2375 .- 1526-4637. ; 23:7, s. 1299-1310
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Tidskriftsartikel (refereegranskat)abstract
- Objective Multidimensional aspects of pain have raised awareness about cognitive appraisals, such as perceived injustice (PI) and pain catastrophizing (PC). It has been demonstrated that they play an important role in patients' pain experience. However, the mediating effect of these appraisals has not been investigated in breast cancer survivors (BCS), nor have they been related to fatigue and sleep. Methods Cross-sectional data from 128 BCS were analysed by structural path analysis with the aim to examine the mediating effect of PI and PC in the relationship of pain on fatigue and sleep. Results The indirect mediating effects of PI on fatigue (CSI*PI = 0.21; P < .01 and VAS*PI = 1.19; P < .01) and sleep (CSI*PI = 0.31; P < .01 and VAS*PI = 1.74; P < .01) were found significant for both pain measures (Central Sensitization Inventory [CSI] and Visual Analogue Scale [VAS]). PC, on the other hand, only mediated the relationship between pain measured by VAS and fatigue (VAS*PC = 0.80; P = .03). Positive associations were found, indicating that higher pain levels are positively correlated with PI and PC, which go hand in hand with higher levels of fatigue and sleep problems. Conclusions PI is an important mediator in the relationship of pain on fatigue and sleep, while PC is a mediator on fatigue after cancer treatment. These findings highlight that both appraisals are understudied and open new perspectives regarding treatment strategies in BCS.
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| 22. |
- Mathioudakis, A. G., et al.
(författare)
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Current developments and future directions in COPD
- 2020
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Ingår i: European Respiratory Review. - : European Respiratory Society (ERS). - 0905-9180 .- 1600-0617. ; 29:158
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Tidskriftsartikel (refereegranskat)abstract
- The European Respiratory Society journals publish respiratory research and policy documents of the highest quality, offering a platform for the exchange and promotion of scientific knowledge. In this article, focusing on COPD, the third leading cause of death globally, we summarise novel research highlights focusing on the disease's underlying mechanisms, epidemiology and management, with the aim to inform and inspire respiratory clinicians and researchers.
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| 23. |
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| 24. |
- Nijs, Jo, et al.
(författare)
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Pain and opioid use in cancer survivors: A practical guide to account for perceived injustice
- 2021
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Ingår i: Pain Physician. - 1533-3159. ; 24:5, s. 309-317
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Tidskriftsartikel (refereegranskat)abstract
- Background: The presence of pain decreases survival rates in cancer. Pain management in clinical settings is often suboptimal and secondary to other cancer-related treatments, leaving many people undertreated. Opioid use is associated with side effects and decreased survival rate in cancer patients. Hence, there is an urgent need for considering factors such as perceived injustice that sustain post-cancer pain and trigger a behavioral pattern associated with opioid use. Injustice beliefs represent a maladaptive pattern of cognitive appraisal that may be a salient target for improving pain-related coping in these patients. Perceived injustice is associated with increased opioid prescription and prospectively predicted opioid use at 1-year follow-up, urging the need for targeted interventions to diminish perceived injustice. Objectives: Explain the importance of screening for perceived injustice in patients with pain following cancer treatment, its potential relevance for opioid abuse, and its potential impact on the management of pain following cancer. Also, prove clinicians with a clinical guide for an approach comprising of modified pain neuroscience education, motivational interviewing, and acceptance-based interventions to account for perceived injustice in patients having pain following cancer. Study Design: A narrative review, perspective and treatment manual Setting: Several universities, a university of applied science department, a university hospital, and a private clinic (i.e., transdisciplinary pain treatment center). Methods: Patients were cancer survivors with pain. Intervention included modified pain neuroscience education, motivational interviewing, and acceptance-based interventions. Measurements were taken through the Injustice Experience Questionnaire (IEQ). Results: The IEQ can be used to assess perceived injustice in a valid way. Education about pain, including discussing perceived injustice, should be the first part of the management of pain in cancer survivors. In order to obtain the often-required behavioural change towards a more adaptive lifestyle, motivational interviewing can be used. To thoroughly tackle perceived injustice in patients having pain following cancer, special emphasis should be given to the individual reasons patients identify for experiencing (continued) pain and related symptoms. Pain acceptance should also be thoroughly addressed. Limitations: Clinical trials exploring the benefits, including cost-effectiveness, of such a multimodal approach in patients with pain following cancer treatment are needed. Conclusions: In light of its potential relevance for opioid abuse and potential impact on conservative management strategies, clinicians are advised to screen for perceived injustice in patients with pain following cancer treatment. Therapeutic targeting of perceived injustice can be done through an approach comprising of modified pain neuroscience education, motivational interviewing, and acceptance-based interventions. © 2021, American Society of Interventional Pain Physicians. All rights reserved.
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| 25. |
- Tang, Wenbo, et al.
(författare)
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Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7, s. e100776-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. Methods: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. Results: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 x 10(-7)). In addition, meta-analysis using the five cohorts with >= 3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18 x 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. Conclusions: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.
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