| 1. |
- Sawalha, Sami, 1975-
(författare)
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Chronic obstructive pulmonary disease : clinical phenotyping, mortality and causes of death
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is common. The estimated prevalence is about 10% among adults, but varies largely dependent on the major risk factors age and smoking. Under-diagnosis of COPD is substantial and is related to disease severity. Thus, subjects with mild to moderate COPD are underrepresented in medical registers among health care providers as well as in national registers. Post- bronchodilator (BD) spirometry is mandatory for the diagnosis of COPD, but not sufficient to assess and manage COPD. Phenotyping based on spirometry and clinical manifestations can make it easier to apply individual assessment of subjects with COPD. COPD is a systemic disease with pulmonary and extra-pulmonary manifestations and comorbidities are common. Comorbidities most probably contribute to the observed increased mortality among subjects with COPD, however, the impact of comorbidities on mortality and causes of death among subjects with mild to moderate COPD is unclear. Furthermore, there seems to be sex-dependent differences with regard to susceptibility to risk factors, clinical manifestation and outcomes.Aim: The overall aim of this thesis was to identify and characterize clinical relevant COPD phenotypes in population-based studies, using spirometry together with clinical characteristics such as respiratory symptoms, exacerbations, and comorbidities, and their impact on mortality and further, also cause of death.Methods: This thesis is based on data from the Obstructive Lung Disease in Northern Sweden (OLIN) COPD study. The study population was recruited in the years 2002-2004, when all 993 individuals with (FEV1/VC<0.70) were identified after examinations of population-based cohorts, together with age- and sex-matched non-obstructive referents (n=in total 1,986). In this thesis, cross-sectional data from recruitment were used together with mortality data from the Swedish Tax Agency from the date of recruitment in 2002-2004 and onwards. Data on cause of death was collected from the Swedish National Board for Health and Welfare register for all deaths until 31 December 2015. Spirometry was used to identify the following spirometric groups, in paper I: Non-COPD (FEV1/VC≥0.70); COPD (pre- BD FEV1/VC<0.70); in paper II: Non- obstructive (FEV1/VC≥0.70), Pre- not post-BD obstructive (pre- not post-BD FEV1/VC<0.70); COPD (post-BD FEV1/VC<0.70); In paper III: Normal Lung Function (NLF, FEV1/VC≥0.7 & FVC≥80% predicted), COPD (post BD FEV1/VC<0.70) and Lower Limit of Normal COPD (LLN-COPD, the LLN criterion applied among those with COPD); in paper IV: NLF and COPD defined as in paper III, and Restrictive Spirometric pattern (RSP, FEV1/VC≥0.70 & FVC<80% predicted). The OLIN-COPD study and collection of data on causes of death were approved by the regional ethical committee at Umeå University.Results: Paper I: Subjects with COPD had more productive cough than non-COPD, and men more than women. Productive cough increased the risk for exacerbations in COPD and non-COPD and productive cough was associated with worse survival in both groups. In adjusted models (HR;95%CI) the increased risk for death associated with productive cough among those with COPD persisted (1.48;1.13-1.94) when compared with non-COPD without productive cough, significantly so also among men with COPD (1.63;1.17-2.26), but not among women (1.23;0.76-1.99).Paper-II: Pre-BD spirometry misclassified every fourth subject as having COPD. Subjects with pre- but not post-BD obstruction were similar to subjects with COPD regarding reported ‘any respiratory symptoms’, asthma before the age of 40, exacerbations, and comorbidities. The cumulative mortality among subjects with pre- not post-BD obstruction was similar to among subjects in the non-obstructive group, still, the survival was better than among those with COPD. The increased risk for death for COPD persisted also in an adjusted model (1.24; 1.04-1.49) when compared with the non-obstructive group, and the pattern was similar among men and women (1.27; 1.00-1.60 and1.24; 0.92-1.13).Paper III: Men with COPD had more CVD and DM compared to women, while anxiety/depression (A/D) was more common among women than men in all spirometric groups. Men had a higher cumulative mortality than women in all groups. However, CVD seemed to have a greater impact on mortality among women than men, while anxiety/depression increased the risk for death similarly in both sexes. The use of the LLN criterion did not change the observed pattern.Paper IV: CVD was the most common cause of death in all spirometric groups, NLF, RSP and COPD, followed by cancer. Those with COPD and RSP had a similar and higher cumulative mortality than those with NLF. RSP and COPD had an increased risk for CVD death and respiratory death, independent of age, sex, smoking habits and BMI-category, however, the increased risk for CVD death did not reach statistical significance in RSP. In all the groups, the risk for deaths due to cancer was similar, however, lung cancer was more common in COPD than in NLF and RSP. The pattern was fairly similar among men and women. Conclusions: Simple diagnostic procedures like history of respiratory symptoms, exacerbations, and comorbidity can, together with spirometry, contribute with important clinical classification of prognostic importance. Productive cough increased the risk for exacerbations in both COPD and non-COPD. The highest risk for exacerbations and death was observed among subjects with COPD and productive cough. It was impossible to distinguish COPD from those with pre- not post-BD obstruction based on the history of respiratory symptoms, asthma, exacerbations and comorbidities. Still, COPD was associated with an increased risk for death while pre- not post-BD obstruction had better survival than COPD but similar as non-obstructive. There were sex-dependent differences regarding comorbidities and mortality. CVD was less common among women but had a greater impact on mortality compared to among men while A/D, less common among men, increased the risk for death similarly in both sexes. CVD and cancer were the most common causes of death in all spirometric groups. RSP had a similar and higher mortality as COPD when compared with NLF. The risk for cancer-related death was similar in all groups, while the results indicated that COPD and RSP had an increased risk for CVD and respiratory death.
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| 2. |
- Irewall, Tommie, 1987-
(författare)
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Prevalence and incidence of and risk factors for asthma and exercise-induced laryngeal obstruction in elite endurance athletes
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Asthma is highly prevalent in endurance athletes, but we lack up-to-date information on the prevalence and incidence of asthma in cross-country skiers. Exercise-induced laryngeal obstruction (EILO) is an important differential diagnosis to exercise-induced asthma, and its symptoms can mimic asthma. The two conditions may co-exist, and misdiagnosis of EILO may result in unnecessary asthma treatment. The gold standard diagnostic test for EILO is continuous laryngoscopy during exercise (CLE). Aims: The aim of this thesis was to study the prevalence and incidence of asthma in endurance athletes, with a special focus on cross-country skiers. In addition, the thesis aimed to assess the prevalence of EILO in cross-country skiers and to study the intra-individual variability of laryngeal obstruction scores using the CLE test. Methods: Study 1 (papers I & II) comprised a cohort of elite endurance athletes who participated in an annual postal survey including questions regarding asthma, allergy, and exercise between 2011 and 2015. The invited athletes were Swedish elite skiers and orienteers, belonging to national teams, universities with elite sport contracts, Swedish National Elite Sport Schools, or national top ranking. The study population in paper I comprised adolescent skiers at Swedish National Elite Sport Schools (n=253) between 2011 and 2013, together with a reference population aged 16–20 years that was matched for school municipality (n=500) and invited in 2013. Paper II included all skiers and orienteers (n=666) participating in the prospective survey in 2011–2015. The incidence of physician- diagnosed asthma was defined as the number of incident cases of physician- diagnosed asthma divided by the summarized time at risk in person-years in the population without physician-diagnosed asthma at baseline. In study 2 (papers III & IV), elite skiers and competitive athletes (n=109) were screened for allergy, exercise-induced bronchoconstriction, and EILO at Östersund Hospital between 2015 and 2017. The participants answered a questionnaire regarding asthma, allergy, and exercise and underwent a CLE test, eucapnic voluntary hyperventilation (EVH) test, and skin prick test. Laryngeal obstruction was assessed at the glottic and supraglottic levels using a visual grade iv score (0–3 points). EILO was defined as ≥ 2 points at maximal effort exercise. Current asthma was defined as self-reported physician-diagnosed asthma and use of asthma medication in the last 12 months. All participants were invited to a follow-up examination off-season if the first examination was performed during the competitive season, or on-season if the first visit occurred during off-season. Paper III included 89 elite skiers that completed the first baseline visit. Paper IV included all 29 athletes that completed the baseline and follow-up testing regardless of diagnosis, treatment, and respiratory symptoms. Results: In paper I, the response rate was 96% in the skier population and 48% in the reference population. Skiers at Swedish National Elite Sport Schools had a higher prevalence of physician-diagnosed asthma than the reference population (27% vs. 19%, p=0.046). Median age at asthma onset was higher in skiers compared to in the reference population (12.0vs 8.0 years, p<0.001). Female sex, family history of asthma, nasal allergies, and being a skier were independent risk factors associated with physician-diagnosed asthma. In paper II, the response rate was 88.7% at baseline and decreased by year of follow-up. The population at risk at baseline consisted of 290 skiers and 159 orienteers, and the incidence rate (95% confidence interval [CI]) of physician- diagnosed asthma was 61.2 (45.7–80.3) per 1000 person-years. Risk factors for incident physician-diagnosed asthma were family history of asthma, being a skier, and wheezing without having a cold. In paper III, 24 (27%) of the 89 elite cross-country skiers fulfilled the study criterion for EILO. Current asthma was present in 34 (38%) skiers, whereof 10 (29%) of whom had concomitant EILO. A higher proportion of skiers with EILO and current asthma reported wheezing or shortness of breath following exercise compared to skiers with asthma only. In paper IV, the CLE score was mainly unchanged at follow-up after 3–23 months. In the 11 athletes with moderate supraglottic obstruction at first visit and receiving advice for breathing exercises, 3 (27%) had mild obstruction at follow- up. Among athletes without no or mild supraglottic obstruction at first visit, 3 (17%) had moderate laryngeal supraglottic obstruction at follow-up. Conclusions: Adolescent skiers have a high prevalence of self-reported physician-diagnosed asthma. The onset of asthma commonly occurs during early adolescence. Endurance athletes also have a high incidence of physician-diagnosed asthma v during their career, especially among skiers. Furthermore, skiers have a high prevalence of EILO, including nearly 30% of skiers with current asthma. In endurance athletes, the grade of laryngeal obstruction according to CLE was fairly stable when reassessed after 3–23 months, regardless of the grade of laryngeal obstruction, respiratory symptoms at baseline, and advice on breathing exercises after the first visit. Therefore, when assessing skiers with exercise-related respiratory symptoms, both EILO and asthma should be considered.
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| 3. |
- Nilsson, Ulf, 1974-
(författare)
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Cardiovascular aspects on chronic obstructive pulmonary disease : with focus on ischemic ECG abnormalities, QT prolongation and arterial stiffness
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Chronic Obstructive Pulmonary disease (COPD) is an under-diagnosed disease with a prevalence of approximately 10%, highly dependent on age and smoking habits. Comorbidities are common in COPD and of these, cardiovascular diseases (CVD) are the most common. COPD is the fourth leading cause of death globally, and CVD probably contribute to the high mortality. Within CVD, Ischemic Heart Disease (IHD) is the most common. It is highly clinically relevant to identify signs of ischemic heart disease, other cardiac conditions, and risk factors for CVD in COPD. Electrocardiogram (ECG) is a simple but still major diagnostic tool in clinical cardiology, including disturbances in the electric conduction system and ischemia. Due to the under-diagnosis of COPD, there is limited knowledge regarding the prevalence and prognostic impact of ECG abnormalities in COPD. Arterial stiffness is a risk factor for CVD, which has raised an increased interest, however not evaluated in population based studies of COPD.Aim: The overall aim was to describe cardiovascular aspects on COPD, with a specific focus on arterial stiffness, prevalence and prognostic impact of ischemic ECG abnormalities and prolonged QT interval, by comparing subjects with and without obstructive lung function impairment in a population-based cohort.Methods: The thesis is based on the Obstructive Lung Disease in Northern Sweden (OLIN) COPD study; a population-based longitudinal cohort study. During the years 2002-2004, all participants in clinical examinations from previously recruited large population-based cohorts were invited to re-examination including spirometry and a structured interview. All subjects with obstructive lung function impairment (n=993) were identified, together with 993 age and sex-matched referents without airway obstruction. The study population (n=1986) has been invited to annual examinations since 2005 including spirometry and structured interview. Papers I-III are based on data from 2005 when electrocardiogram (ECG) was recorded in addition to the basic program. All ECGs were Minnesota coded and QT-time was measured. Paper IV is based data from 2010 when non-invasive measurements of arterial stiffness, assessed as pulse wave velocity (PWV), was added to the program. Spirometric data were classified as normal lung function (NLF), restrictive spirometric pattern (RSP) and airway obstruction (COPD). The following spirometric criteria for COPD were used: post-bronchodilator FEV1/VC<0.70 (papers I-IV, in paper III labelled GOLD-COPD) and lower limit of normal, LLN (LLN-COPD) (paper III). Spirometric classification of COPD severity was based on FEV1 % predicted as a continuous variable or according to the Global Initiative for Obstructive Lung Disease (GOLD), divided into GOLD 1-4.Results: The prevalence of ischemic heart disease (IHD), both self-reported and assessed as probable and possible ischemic ECG abnormalities (I-ECG) according to the Whitehall criteria, was similar among subjects with NLF and COPD. The prevalence of both self-reported and probable (I-ECG) according to Whitehall increased by GOLD grade. Among those with COPD, self-reported IHD was associated with disease severity, assessed as FEV1 % predicted also after adjustment for age and sex (paper I).In both COPD and NLF, those with I-ECG had a higher cumulative mortality over 5 years than those without I-ECG (29.6 vs. 10.6%, p<0.001 and 17.1 vs. 6.3 %, p=0.001). When analysed in a multivariate model, the Mortality Risk Ratio (MRR, 95%CI) was increased for subjects with COPD and I-ECG (2.4, 1.5-3.9), and non-significantly so for NLF with I-ECG (1.65, 0.94-2.90), when compared to NLF without I-ECG. When analyzed separately among subjects with COPD, the increased risk for death associated with I-ECG persisted independent of age, sex, BMI-class, smoking habits and disease severity assessed as FEV1 % predicted (1.89, 1.20-2.99). The proportion without reported IHD was high among those with I-ECG; 72.4% in NLF and 67.3% in COPD. The pattern was similar also among them; I-ECG was associated with an increased risk for death in COPD and non-significantly so in NLF (paper II).Mean corrected QT-time (QTc) and prevalence of QTc prolongation was higher in RSP than NLF but similar in NLF and GOLD-COPD. The prevalence of borderline as well as prolonged QTc increased by GOLD grade (test for trend p=0.012 for both groups). Of those with GOLD-COPD, 52% fulfilled the LLN-criterion (LLN-COPD). When comparing LLN-COPD and NLF, the pattern was similar as when comparing NLF and GOLD-COPD. The cumulative mortality over 5 years was higher among subjects with borderline and prolonged QTc than those with normal QTc in subjects with GOLD-COPD and LLN-COPD but not in NLF and RSP (paper III).Arterial stiffness, assessed as PWV, was higher in GOLD 3-4 compared to non-COPD (10.52 vs. 9.13 m/s, p=0.042). Reported CVD and age >60 were both associated with significantly higher PWV in COPD as well as in non-COPD. In a multivariate model, GOLD 3-4 remained associated with higher PWV when compared with non-COPD, also when adjusted for sex, age group, smoking habits, blood pressure, reported CVD and pulse rate (paper IV).Conclusion: In this population-based study, the prevalence of ischemic ECG abnormalities was similar among subjects with normal lung function and COPD, but increased by disease severity among subjects with COPD. Ischemic ECG abnormalities were associated with an increased mortality among subjects with COPD, independent of common confounders and disease severity, also among those without known heart disease. Whilst the prevalence of QTc prolongation was similar in NLF, COPD and LLN-COPD, it was associated with an increased mortality only in the COPD-groups. ECG is a simple non-invasive method and seems to identify findings of prognostic importance among subjects with COPD. Central arterial stiffness, a known risk factor for cardiovascular disease, was increased among subjects with severe and very severe COPD when compared to subjects without COPD independent of common confounders.
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| 4. |
- Schyllert, Christian, 1983-
(författare)
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Social determinants in asthma : population-based studies on asthma and respiratory symptoms in relation to occupation, occupational exposure and socioeconomic status
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Asthma is one of the most common chronic obstructive airway diseases among children and adults, with a prevalence between 6-11% in European countries. It is also the most common work-related occupational respiratory disease. There are different methods to classify occupational exposure and, even though there is no clear consensus on which method is the most accurate, the single-item question on exposure to the composite measure vapour, gas, dust or fumes (VGDF) is commonly used in epidemiological research. Low socioeconomic status is associated with asthma and also behavioural factors such as smoking and over-weight, which by themselves are risk factors for asthma. Socioeconomic status is, however, truly a multifaceted concept and using only one measure does not encompass its entire effect on health-related outcomes. Asthma does also have a negative impact on the quality of life among adolescents: they report less physical fitness compared to their peers and more school absenteeism due to respiratory symptoms. Still, research on whether childhood asthma has any impact on socioeconomic status in young adulthood is scarce.Aim: The overall aim is to study social determinants of health such as socioeconomic status, occupation and occupational exposure and their relationship with asthma and respiratory symptoms among adults and further, to evaluate if asthma during childhood or adolescence is associated with social determinants in young adulthood.Method: This thesis includes four papers based on data from the Obstructive Lung Disease in Northern Sweden (OLIN) studies. Papers I-III are cross-sectional studies among adults; a structured interview from clinical examinations between 2002-04 (paper I, n=4036) and postal questionnaire surveys from 2006 (paper II, n=9992) and 2016 (paper III, n=6854) with the addition of register-based data in paper III. Paper IV is a longitudinal prospective cohort study; the first OLIN paediatric cohort followed from 7 to 19 years of age and a postal questionnaire follow-up at ages 27-28 in 2015 (n=2017). Asthma was defined as physician diagnosis (paper I) together with respiratory symptoms (paper II-IV) or use of asthma medication (paper IV). In paper IV asthma was further categorized based on age of onset and p v and adolescence. Main or longest held occupation was used to categorize occupational and socioeconomic groups. In papers III and IV additional measures of socioeconomic status were included; educational level (papers III and IV) and income (paper III). In all papers, occupational exposure to vapour and/or gas, dust and fumes (VGDF or GDF) were taken into consideration and in paper I further divided into subgroups based on a detailed questionnaire on occupational exposure.Results: In paper I we found that the association between occupational exposure to VGDF and asthma and rhinitis was driven by the component of chemicals rather than dusts. In paper II, the ISCO-based manual Swedish Standard Classification of Occupations (SSYK) and the manual Socioeconomic classification (SEI), could both identify occupational and socioeconomic groups at risk for respiratory symptoms and asthma, while the older ISCO-based manual Nordic Classification of Occupations (NYK) was not as sensitive.In paper III, behavioural risk factors for respiratory symptoms and asthma such as smoking and obesity and, occupational exposure to GDF were associated with low educational level. Interaction analyses between income level and sex revealed different patterns among women and men. Among women, low income was associated with all respiratory symptoms as well as asthma, while among men only with productive cough.In paper IV, early onset asthma was associated with lower educational level in young adulthood, especially not continuing after compulsory school. Further, those with asthma during childhood or adolescence did not seem to refrain from smoking at age 19, nor did they as young adults seem to avoid occupations with known or expected exposure to GDF.Conclusions: Increased automation in industries have decreased the number of manual workers in industries with typically dirty tasks, meaning that the interrelationships between the subgroups included in VGDF may have changed. This may also affect the meaning of occupational exposure to VGDF, at least with regard to asthma and rhinitis, and according to our findings exposure to the component of chemicals may be the most important. We also found that the use of an ISCO-based manual (SSYK) as well as socioeconomic classification based on job-title (SEI) can be useful and easily applicable tools to identify occupational and socioeconomic groups at risk for respiratory symptoms and asthma. Further, low socioeconomic status is associated with respiratory vi symptoms and asthma. It seems as these associations relies more on low income than low educational level. Low educational level as well as low income are furthermore related to known behavioural risk factors for respiratory symptoms and asthma such as obesity, smoking and, also potentially modifiable risk factors as occupational exposure to gas dust or fumes. Having a persisting asthma since childhood is associated with lower educational level as a young adult. This may, in turn, be related with behavioural risk factors as discussed above and, there were no indications that those with child or adolescent asthma refrained from smoking at age 19. Neither did they in young adulthood avoid occupations with known or expected exposure to gas, dust or fumes, such as manufacturing, construction and transportation work. To conclude, our results indicate a vicious circle with regard to the relationship between the studied social determinants of health and asthma and respiratory symptoms.
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| 5. |
- Eriksson Ström, Jonas
(författare)
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Epigenetic changes and immunological features of chronic obstructive pulmonary disease
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is a heterogenous and chronic inflammatory syndrome with the lungs as its main target organ. Clinically, COPD is characterized by airflow limitation, chronic respiratory symptoms, and many extrapulmonary comorbidities. Tobacco smoke is the main environmental risk factor, but pollutants and smoke from biomass fuel are also major contributors. Why some, but not all, smokers develop the disease is a key but largely unresolved research question. Genetic factors seem to explain 40—60% of COPD susceptibility, but what additional role epigenetic factors such as DNA methylation might play has not been thoroughly investigated.Immune cells are of vital importance in the COPD pathogenesis. Among airway lymphocytes, cytotoxic CD8+ T cells are the ones most often found to be involved in the disease, but other lymphocyte populations are not as well studied.Among patients with manifest COPD, the rate of decline in lung function differs widely. Smoking cessation decreases the rate, but beyond that, it is not well understood why some patients experience a more rapid and some a much slower disease progression. Rapid decline is associated with a poor prognosis and has been recognized as a separate phenotype of COPD. Aim: The overall aim of this thesis was to examine the immunologic and epigenetic features of COPD with a focus on the rapid decline phenotype, using flow cytometry and measurement of DNA methylation in cells from bronchoalveolar lavage (BAL) fluid together with clinical characteristics such as rate of decline in lung function, use of inhaled corticosteroids and smoking status. The studies included in this thesis were all part of the Respiratory and Cardiovascular Effects in COPD (“KOLIN”) study.Methods: The study population was the same for all studies in this thesis. Subjects were recruited from the Obstructive Lung Disease in Northern Sweden (OLIN) COPD study according to predetermined criteria. OLIN COPD also provided the longitudinal data needed for classification of rapid/non-rapid decliners (decline in forced expiratory volume in the first second [FEV1] ≥60 or ≤30 mL/year respectively). BAL fluid was analyzed for cell type composition using flow cytometry. DNA methylation in BAL cells was measured using the Illumina MethylationEPIC BeadChip. In the statistical analysis, flow cytometry data was analyzed using group-wise comparisons and multivariable regression models. DNA methylation data was analyzed for association with COPD and accelerated epigenetic aging (defined as the difference between chronological and epigenetic age) using multilinear regression models. Differentially methylated positions and regions associated with COPD were analyzed for gene association and pathway enrichment and integrated with data from previous gene expression and genome-wide association studies.Results: Paper I: in this first paper based on flow cytometry, we focused on cytotoxic lymphocytes and found that Natural Killer (NK) cells in BAL were increased in COPD while invariant Natural Killer T (iNKT) and Natural Killer T-like (NKT-like) cells increased with smoking but not with COPD. NK cells were also higher when comparing ex-smokers with and without COPD. No significant differences were found between COPD subjects with a rapid vs. a non-rapid decline in lung function.Paper II: regulatory immune cells were investigated in this second flow cytometry-based paper. We found that FoxP3+ regulatory T cells (Tregs) were significantly lower in COPD subjects with a rapid decline in lung function compared to those with a non-rapid decline. This result was significant before as well as after adjustments for inhaled corticosteroids (ICS) usage and smoking. None of the investigated regulatory immune cell populations (T helper cells, activated T helper cells, and FoxP3+ Tregs) displayed significant differences associated with either COPD or smoking.Paper III: measurements of BAL cell DNA methylation revealed epigenome-wide differential methylation in COPD; 1,155 differentially methylated positions (DMPs) and 7,097 differentially methylated regions. Functional analysis using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases identified biologically plausible pathways and gene relationships, including enrichment for transcription factor activity. No correlation was found between COPD and accelerated aging. For 79 unique DMPs, DNA methylation correlated significantly with gene expression in BAL. Thirty-nine percent of DMPs were co-located with single nucleotide polymorphisms (SNPs) associated with COPD.Conclusions: Among cytotoxic cell types, the NK cell population stood out as it 1) was increased in COPD; and 2) did not normalize in COPD subjects that had quit smoking. This indicates that NK cells might contribute to the continued disease progression in COPD even after smoking cessation.COPD subjects with a rapid decline in lung function had significantly lower levels of Fox P3+ Tregs in BAL. Further longitudinal research is needed to establish the causal direction of this relationship, but based on the evidence available to date, I deem it more plausible that a low expression of Fox P3+ Tregs would lead to a rapid decline in lung function, than the other way around.Our epigenome-wide association study (EWAS) identified widespread differential methylation in COPD, and many DMPs displayed a strong correlation with gene expression. Somewhat less than half of DMPs were located in close proximity to COPD-associated SNPs, suggesting that these might be sites where genetic factors regulate methylation status. In sum, our findings suggest strong associations between epigenetic factors and COPD. As this was the first ever published EWAS of COPD based on BAL cells, results must be validated in future studies.
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| 6. |
- Larsson, Kjell, et al.
(författare)
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Behandling med läkemedel kan reducera mortaliteten vid KOL
- 2022
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Ingår i: Läkartidningen. - : Läkartidningen Förlag. - 0023-7205 .- 1652-7518. ; 119
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Forskningsöversikt (refereegranskat)abstract
- Approximately 500 000 individuals in Sweden have chronic obstructive pulmonary disease (COPD). Co-morbid, especially cardiovascular, conditions are common in COPD and globally COPD is the third most common cause of mortality. Mortality in COPD is driven by dyspnea, exacerbations and comorbidities and is reduced by smoking cessation and lung rehabilitation. Also, pharmacological treatment, in particular inhaled corticosteroids, reduces mortality in COPD. The reduction in mortality that can be achieved by treatment with inhaled corticosteroids in combinations with long-acting bronchodilators is of the same order of magnitude as the effect on mortality by treatment of hyperlipidemia and hypertension.
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| 7. |
- Sundh, Josefin, 1972-
(författare)
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Quality of life, mortality and exacerbations in COPD
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Risk factors for poor health related quality of life (HRQL), mortality and exacerbations in Chronic Obstructive Pulmonary Disease (COPD) need to be explored.Objectives: To examine associations of comorbidity and Body Mass Index (BMI) with HRQL using the Clinical COPD Questionnaire (CCQ); to examine the prognostic qualities of the multidimensional instrument DOSE index; to examine the association of health status estimated by the CCQ with mortality; and to examine management of exacerbations and subsequent exacerbation risk.Material: Randomly selected patients from primary and secondary care, usingthe COPD cohort of the PRAXIS study. Information was collected using apatient questionnaire, record review and a clinical questionnaire. Mortalitydata wereobtained from the National Board of Health and Welfare.Methods: Multiple linear regression analysis, survival analysis and standardisedmortality ratios.Results: Heart disease, depression and underweight were associated withhigher CCQ. A higher DOSE index was associated with higher mortality. Ahigher CCQ was associated with higher mortality risk and mortality risk wasraised compared with the general population. Exacerbation management inprimary care was not optimal. An extra scheduled visit to an asthma/COPDnurse was associated with a reduced risk of subsequent exacerbations.Conclusions: The influence of comorbidity on HRQL in COPD patients is important. The DOSE index is useful as it combines important issues in COPD management with prognostic qualities. Health status estimated by CCQ is predictive of mortality. Exacerbation management in primary care COPD patients needs to be optimised, and nurse led asthma/COPD clinics may be a way to optimise resources with possible beneficial effects on exacerbation risk. These results could be used to improve COPD care and to facilitate focusing resources for those at greatest risk.
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| 8. |
- Warm, Katja, 1977-
(författare)
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The epidemiology of allergic sensitization and the relation to asthma and rhinitis
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Allergic sensitization is the most important risk factor for asthma and rhinitis among children, adolescents and young adults. Less is known about the incidence and remission of allergic sensitization, particularly in older adults. Furthermore, it is not clear if the earlier documented increase in prevalence of allergic sensitization continues. This thesis is focused on prevalence, incidence and remission of allergic sensitization to airborne allergens among adolescents and adults as well as on time trends in prevalence among adults. Furthermore, associated risk factors and the relation of allergic sensitization to asthma and rhinitis were assessed.Methods: In the study of children and adolescents, incidence, remission and prevalence of allergic sensitization were assessed in a cohort study of schoolchildren, aged 7-8 years (y) at baseline. In the studies of adults, incidence and remission of allergic sensitization were assessed in a randomly selected adult population sample in 1994 (n=664) aged 20-69 y, which was followed up in 2004 (n=555). Trends in prevalence of allergic sensitization were assessed by comparing two cross-sectional studies; the cohort from 1994 and another randomly selsected population sample examined in 2009 (n=737). The relation of allergic sensitization to asthma and rhinitis was determined in the adult cohort in 2009. Allergic sensitization was assessed by skin prick test (SPT) with ten common airborne allergens at ages 7-8, 11-12 and 19 y in the cohort of children and in the participants ≤ 60 y in the adult cohorts. Specific IgE to nine airborne allergens was analyzed in the adult cohorts in 2004 and 2009. Risk factors for allergic sensitization and variables defining respiratory disease and symptoms were assessed by questionnaires in the cohort of children and by structured interviews in the adult cohorts.Results: The 10-year cumulative incidence of allergic sensitization among the adults from 1994 to 2004 was 5%, while remission was 32%. In both adult cohorts, the prevalence of allergic sensitization was highest among young adults, aged 20-29 y, 55% and 61% and decreased significantly with increasing age. Among children and adolescents, both incidence and persistence of allergic sensitization were high, and the prevalence of allergic sensitization increased by age from 21% at age 7-8 y to 42% at age 19 y. Multisensitization at age 19 y was strongly associated with early onset of sensitization. The prevalence of sensitization to the major specific allergens birch, timothy, cat and dog as well as multisensitization (from 40% in 1994 to 56% in 2009, p=0.002) increased significantly from 1994 to 2009 among the adults. Sensitization to any allergen increased from 35% to 39%, however not significantly (p=0.13). A family history of allergic rhinitis was strongly and consistently associated with allergic sensitization in all ages. Male sex and urban living were significantly positively and birth order and furry animals at home in childhood were negatively associated with onset of sensitization before the age of 7-8 y, but not with onset of sensitization from 11-12y to 19 y. Young adult age and urban living were significant factors associated with allergic sensitization in adult age. Sensitization to any animal was significantly positively associated with current asthma (OR4.80 (95% CI 2.68-8.60)), whereas both sensitization to any pollen (OR 4.25 (2.55-7.06)) and any animal (OR 3.90 (95% CI 2.31-6.58)) were associated with current allergic rhinitis. The association between allergic sensitization and allergic rhinitis was strongest in young adult age and decreased with increasing age, while asthma was similarly associated with sensitization to any animal across all adult ages. Among asthmatics, the prevalence of allergic sensitization decreased with increasing age of asthma onset.Conclusion: Both incidence and persistence of allergic sensitization were high among children and adolescents explaining the increase in prevalence by increasing age. An inverse pattern with low incidence and high remission of allergic sensitization was seen among adults. The decrease in prevalence of allergic sensitization by increasing adult age might at least partly be explained by normal ageing and not only by an effect of year of birth (cohort effect). The significant increase in prevalence of sensitization to the specific allergens explained the significant increase in multisensitization over 15 years. A family history of allergy was the strongest and the only consistent risk factor for allergic sensitization in all ages. The prevalence of allergic sensitization decreased with increasing age of asthma onset among adult asthmatics.
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