| 1. |
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| 2. |
- Bech, Thea Wilhelmine, et al.
(författare)
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Feasibility of completing Multidimensional Dyspnea Profile and Dyspnea-12 over the telephone in patients with oxygen-dependent disease
- 2021
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Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Breathlessness is prevalent in severe disease and consists of different dimensions that can be measured using the Multidimensional Dyspnea Profile (MDP) and Dyspnea-12 (D-12). We aimed to evaluate the feasibility of MDP and D-12 over telephone interviews in oxygen-dependent patients, compared with other patient-reported outcomes (modified Medical Research Council (mMRC) and Chronic Obstructive Pulmonary Disease Assessment Test (CAT)) and with completion by hand. Methods Cross-sectional, telephone study of 50 patients with home oxygen therapy. Feasibility was assessed as completion time (self-reported by patients and measured), difficulty (self-reported) and help required to complete the instruments (staff). Completion time was compared with mMRC and CAT, and feasibility was compared with completion by hand in cardiopulmonary outpatients (n=182). Feasibility by age and gender was analysed using logistic regression. Results Of 136 patients approached, 50 (37%) participated (mean age: 72±10 years, 66% women). Completion times (in minutes) were relatively short for MDP (self-reported 6 (IQR 5-10), measured 8 (IQR 6-10)) and D-12 (self-reported 5 (IQR 3-8), measured 3 (IQR 3-4)), and slightly longer than mMRC (median 1 (IQR 1-1)) and CAT (median 3 (IQR 2-5)). Even though the majority of patients required no help, more assistance was required by older patients. Compared with patients reporting by hand, completion over the telephone required somewhat longer time and more assistance. Conclusion Many patients with severe oxygen-dependent disease were unable or unwilling to assess symptoms over the telephone. However, among those able to participate, MDP and D-12 are feasible to measure multiple dimensions of breathlessness over the telephone.
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| 3. |
- Bermúdez Barón, Nicolás, et al.
(författare)
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Among respiratory symptoms, wheeze associates most strongly with impaired lung function in adults with asthma: a long-term prospective cohort study
- 2021
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Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Asthma is a common disease and a major public health concern. Respiratory symptoms are related to its prognosis, which in turn associates with lung function. Still this association on a long-term basis is not entirely understood. Aim To study the association of the type and number of respiratory symptoms with FEV1 and FEV1 decline in women and men with asthma. Method A population-based cohort of adults with asthma was examined at study entry between 1986 and 2001 and at follow-up between 2012 and 2014, and n=977 had valid measurements of FEV1 on both occasions. Data regarding respiratory symptoms at study entry (recurrent wheeze, dyspnoea, longstanding cough and productive cough) were analysed in relation to FEV1 and annual decline in FEV1, both unadjusted and adjusted for other potentially associated factors by linear regression. Results For both sexes recurrent wheeze and dyspnoea were associated with lower FEV1 at study entry and follow-up, while productive cough was associated with lower FEV1 only at follow-up. No associations were found between the type of symptoms and annual decline in FEV1. In adjusted analyses, the association between recurrent wheeze and lower FEV1 both at study entry and follow-up remained significant among women. Also, the association between a higher number of symptoms with lower FEV1 both at study entry and follow-up were present for both sexes and remained after adjustment. Conclusions Particularly recurrent wheeze and a higher number of respiratory symptoms may predict lower lung function also in the long run among women and men with asthma.
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| 4. |
- Bertels, Xander, et al.
(författare)
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Phenotyping asthma with airflow obstruction in middle-aged and older adults : a CADSET clinical research collaboration
- 2023
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Ingår i: BMJ open respiratory research. - : BMJ Publishing Group Ltd. - 2052-4439. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The prevalence and clinical profile of asthma with airflow obstruction (AO) remain uncertain. We aimed to phenotype AO in population- and clinic-based cohorts.METHODS: This cross-sectional multicohort study included adults ≥50 years from nine CADSET cohorts with spirometry data (N=69 789). AO was defined as ever diagnosed asthma with pre-BD or post-BD FEV1/FVC <0.7 in population-based and clinic-based cohorts, respectively. Clinical characteristics and comorbidities of AO were compared with asthma without airflow obstruction (asthma-only) and chronic obstructive pulmonary disease (COPD) without asthma history (COPD-only). ORs for comorbidities adjusted for age, sex, smoking status and body mass index (BMI) were meta-analysed using a random effects model.RESULTS: The prevalence of AO was 2.1% (95% CI 2.0% to 2.2%) in population-based, 21.1% (95% CI 18.6% to 23.8%) in asthma-based and 16.9% (95% CI 15.8% to 17.9%) in COPD-based cohorts. AO patients had more often clinically relevant dyspnoea (modified Medical Research Council score ≥2) than asthma-only (+14.4 and +14.7 percentage points) and COPD-only (+24.0 and +5.0 percentage points) in population-based and clinic-based cohorts, respectively. AO patients had more often elevated blood eosinophil counts (>300 cells/µL), although only significant in population-based cohorts. Compared with asthma-only, AO patients were more often men, current smokers, with a lower BMI, had less often obesity and had more often chronic bronchitis. Compared with COPD-only, AO patients were younger, less often current smokers and had less pack-years. In the general population, AO patients had a higher risk of coronary artery disease than asthma-only and COPD-only (OR=2.09 (95% CI 1.26 to 3.47) and OR=1.89 (95% CI 1.10 to 3.24), respectively) and of depression (OR=1.41 (95% CI 1.19 to 1.67)), osteoporosis (OR=2.30 (95% CI 1.43 to 3.72)) and gastro-oesophageal reflux disease (OR=1.68 (95% CI 1.06 to 2.68)) than COPD-only, independent of age, sex, smoking status and BMI.CONCLUSIONS: AO is a relatively prevalent respiratory phenotype associated with more dyspnoea and a higher risk of coronary artery disease and elevated blood eosinophil counts in the general population compared with both asthma-only and COPD-only.
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| 5. |
- Bjornsdottir, E., et al.
(författare)
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Respiratory symptoms are more common among short sleepers independent of obesity
- 2017
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Ingår i: Bmj Open Respiratory Research. - : BMJ. - 2052-4439. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Sleep length has been associated with obesity and various adverse health outcomes. The possible association of sleep length and respiratory symptoms has not been previously described. The aim of this study was to investigate the association between sleep length and respiratory symptoms and whether such an association existed independent of obesity. Methods This is a multicentre, cross-sectional, population-based study performed in 23 centres in 10 different countries. Participants (n=5079, 52.3% males) were adults in the third follow-up of the European Community Respiratory Health Survey III. The mean +/- SD age was 54.2 +/- 7.1 (age range 39-67 years). Information was collected on general and respiratory health and sleep characteristics. Results The mean reported nighttime sleep duration was 6.9 +/- 1.0 hours. Short sleepers (<6 hours per night) were n=387 (7.6%) and long sleepers (>= 9 hours per night) were n=271 (4.3%). Short sleepers were significantly more likely to report all respiratory symptoms (wheezing, waking up with chest tightness, shortness of breath, coughing, phlegm and bronchitis) except asthma after adjusting for age, gender, body mass index (BMI), centre, marital status, exercise and smoking. Excluding BMI from the model covariates did not affect the results. Short sleep was related to 11 out of 16 respiratory and nasal symptoms among subjects with BMI >= 30 and 9 out of 16 symptoms among subjects with BMI <30. Much fewer symptoms were related to long sleep, both for subjects with BMI <30 and >= 30. Conclusions Our results show that short sleep duration is associated with many common respiratory symptoms, and this relationship is independent of obesity.
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| 6. |
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| 7. |
- Bonnert, Marianne, et al.
(författare)
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Internet-delivered cognitive-behaviour therapy for anxiety related to asthma : study protocol for a randomised controlled trial
- 2024
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Ingår i: BMJ Open Respiratory Research. - : BMJ Publishing Group Ltd. - 2052-4439. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction There is an established association between asthma and anxiety. The overlap between asthma symptoms and symptoms of anxiety may cause individuals to overestimate their asthma severity and restrict their daily activities leading to a low quality of life. There is currently weak evidence for treatments targeting anxiety related to asthma, but cognitive–behavioural therapy (CBT) has shown some promising but mixed results. The current randomised controlled trial will investigate if exposure-based internet-delivered CBT (Internet-CBT) is more effective than treatment as usual+medical education (TAU+ME) to relieve symptoms of anxiety and asthma control.Methods and analysis 90 participants will be randomised 1:1 to 8 weeks of Internet-CBT or TAU+ME. The primary outcome, the patient-reported Catastrophising Asthma Scale, will be analysed from baseline to the primary endpoint at 16 weeks using hierarchical linear mixed model of the slope over time. Secondary outcomes, such as asthma control, quality of life and forced expiratory volume in 1 s, will be analysed correspondingly.Ethics and dissemination All participants will be informed about the study and leave their consent before study entry. All results will be analysed at group level and reported through publication in a peer-reviewed scientific journal within the field. The study received ethical approval by the Swedish Ethical Review Authority in January 2020 (ID: 2019-05985; 2022-01117-02).
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| 8. |
- Cristea, Lucas, et al.
(författare)
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Breathlessness dimensions association with physical and mental quality of life : the population based VASCOL study of elderly men
- 2021
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Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 8:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Breathlessness is a multidimensional symptom prevalent in elderly affecting many aspects of life. We aimed to determine how different dimensions of breathlessness are associated with physical and mental quality of life (QoL) in elderly men.METHODS: This was a cross-sectional, population-based analysis of 672 men aged 73 years in a Swedish county. Breathlessness was assessed using Dyspnoea-12 (D-12) and Multidimensional Dyspnoea Profile (MDP), and QoL using the Short Form 12 physical and mental scores. Scores were compared as z-scores across scales and analysed using multivariable linear regression, adjusted for smoking, body mass index and the presence of respiratory and cardiovascular disease.RESULTS: Worse breathlessness was related to worse physical and mental QoL across all the D-12 and MDP dimension scores. Physical QoL was most strongly associated with perceptional breathlessness scores, D-12 total and physical scores (95% CI -0.45 to -0.30). Mental QoL was more strongly influenced by affective responses, MDP emotional response score (95% CI -0.61 to -0.48). Head-to-head comparison of the instruments confirmed that D-12 total and physical scores most influenced physical QoL, while mental QoL was mostly influenced by the emotional responses captured by the MDP.CONCLUSION: Breathlessness dimensions and QoL measures are associated differently. Physical QoL was most closely associated with sensory and perceptual breathlessness dimensions, while emotional responses were most strongly associated with mental QoL in elderly men. D-12 and MDP contribute complimentary information, where affective and emotional responses may be related to function, deconditioning and QoL.
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| 9. |
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| 10. |
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| 11. |
- Ekström, Magnus, et al.
(författare)
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Validation of the Swedish Multidimensional Dyspnea Profile (MDP) in outpatients with cardiorespiratory disease
- 2019
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Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Breathlessness is a cardinal symptom in cardiorespiratory disease. An instrument for measuring different aspects of breathlessness was recently developed, the Multidimensional Dyspnea Profile (MDP). This study aimed to validate the MDP in terms of the underlying factor structure, internal consistency, test-retest reliability and concurrent validity in Swedish outpatients with cardiorespiratory disease. Methods Outpatients with stable cardiorespiratory disease and breathlessness in daily life were recruited. Factor structure of MDP was analysed using confirmatory factor analysis; internal consistency was analysed using Cronbach's alpha; and test-retest reliability was analysed using intraclass correlation coefficients (ICCs) for patients with unchanged breathlessness between assessments (baseline, after 30-90 min and 2 weeks). Concurrent validity was evaluated using correlations with validated scales of breathlessness, anxiety, depression and health-related quality of life. Results In total, 182 outpatients with cardiorespiratory disease and breathlessness in daily life were included; 53.3% were women; main diagnoses were chronic obstructive pulmonary disease (24.7%), asthma (21.4%), heart failure (19.2%) and idiopathic pulmonary fibrosis (18.7%). The MDP total, immediate perception and emotional response scores, and individual item scores showed expected factor structure and acceptable measurement properties: internal consistency (Cronbach's alpha, range 0.80-0.93); test-retest reliability at 30-90 min and 2 weeks (ICC, range 0.67-0.91); and concurrent validity. There was no evidence of a learning effect. Findings were similar between diagnoses. Discussion MDP is a valid instrument for multidimensional measurement of breathlessness in Swedish outpatients across cardiorespiratory diseases.
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| 12. |
- Emilsson, Össur Ingi, et al.
(författare)
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Nocturnal gastro-oesophageal reflux and respiratory symptoms are increased in sleep apnoea : comparison with the general population
- 2024
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Ingår i: BMJ Open Respiratory Research. - : BMJ Publishing Group Ltd. - 2052-4439. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Aim To assess respiratory symptoms and nocturnal gastro-oesophageal reflux (nGER) among untreated obstructive sleep apnoea (OSA) patients, compared with the general population. Also, if nGER associates differently with respiratory symptoms among OSA patients.Methods 2 study cohorts were included: 822 newly diagnosed subjects with moderate–severe OSA and 738 Icelandic general population study participants. All participants answered the same questionnaires. Those reporting nGER symptoms at least once per week were defined as ‘with nGER’; those without nGER symptoms and without nGER medication were defined as ‘no nGER’; and other participants were defined as having ‘possible nGER’. Propensity score-based weights were used to minimise confounding and selection bias and facilitate causal interpretations.Results The prevalence of nGER among OSA patients was 14.1%, compared with 5.8% in the general population. This increased prevalence in OSA was not explained by differences in age, gender, body mass index, smoking, hypertension and diabetes (adjusted OR (95% CI)=3.79 (2.24 to 6.43)). OSA patients ‘with nGER’ and with ‘possible nGER’ reported more wheezing (44% and 44% vs 25%, respectively) and productive cough (47% and 42% vs 29%, respectively), compared with OSA patients with ‘no nGER’. The same pattern was seen in the general population, although with a generally lower prevalence. The effect of nGER on respiratory symptoms was similar between the two cohorts.Conclusion nGER was more often reported among untreated moderate–severe OSA patients than in the general population. Participants with nGER had more wheezing and productive cough, both among untreated OSA patients and in the general population.
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| 13. |
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| 14. |
- Hohmann, C, et al.
(författare)
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Sex-specific incidence of asthma, rhinitis and respiratory multimorbidity before and after puberty onset: individual participant meta-analysis of five birth cohorts collaborating in MeDALL
- 2019
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Ingår i: BMJ open respiratory research. - : BMJ. - 2052-4439. ; 6:1, s. e000460-
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Tidskriftsartikel (refereegranskat)abstract
- To understand the puberty-related sex shift in the prevalence of asthma and rhinitis as single entities and as respiratory multimorbidities, we investigated if there is also a sex-specific and puberty-related pattern of their incidences.MethodsWe used harmonised questionnaire data from 18 451 participants in five prospective observational European birth cohorts within the collaborative MeDALL (Mechanisms of the Development of Allergy) project. Outcome definitions for IgE-associated and non-IgE-associated asthma, rhinitis and respiratory multimorbidity (first occurrence of coexisting asthma and rhinitis) were based on questionnaires and the presence of specific antibodies (IgE) against common allergens in serum. For each outcome, we used proportional hazard models with sex–puberty interaction terms and conducted a one-stage individual participant data meta-analysis.ResultsGirls had a lower risk of incident asthma (adjusted HR 0.67, 95% CI 0.61 to 0.74), rhinitis (0.73, 0.69 to 0.78) and respiratory multimorbidity (0.58, 0.51 to 0.66) before puberty compared with boys. After puberty onset, these incidences became more balanced across the sexes (asthma 0.84, 0.64 to 1.10; rhinitis 0.90, 0.80 to 1.02; respiratory multimorbidity 0.84, 0.63 to 1.13). The incidence sex shift was slightly more distinct for non-IgE-associated respiratory diseases (asthma 0.74, 0.63 to 0.87 before vs 1.23, 0.75 to 2.00 after puberty onset; rhinitis 0.88, 0.79 to 0.98 vs 1.20, 0.98 to 1.47; respiratory multimorbidity 0.66, 0.49 to 0.88 vs 0.96, 0.54 to 1.71) than for IgE-associated respiratory diseases.DiscussionWe found an incidence ‘sex shift’ in chronic respiratory diseases from a male predominance before puberty to a more sex-balanced incidence after puberty onset, which may partly explain the previously reported sex shift in prevalence. These differences need to be considered in public health to enable effective diagnoses and timely treatment in adolescent girls.
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| 15. |
- Hussain-Alkhateeb, Laith, 1977, et al.
(författare)
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Novel non-invasive particles in exhaled air method to explore the lining fluid of small airways-a European population-based cohort study
- 2021
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Ingår i: BMJ open respiratory research. - : BMJ Publishing Group Ltd. - 2052-4439. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Respiratory tract lining fluid of small airways mainly consists of surfactant that can be investigated by collection of the particles of exhaled aerosol (PExA) method. This offers an exciting prospect to monitor small airway pathology, including subjects with asthma and smokers.AIM: To explore the influence of anthropometric factors and gender on phospholipids, surfactant protein A (SP-A) and albumin of the lining fluid of small airwaysand to examine the association with asthma and smoking. Furthermore, to examine if the surfactant components can predict lung function in terms of spirometry variables.METHOD: This study employs the population-based cohort of the European Community Respiratory Health Survey III, including participants from Gothenburg city, Sweden (n=200). The PExA method enabled quantitative description and analytical analysis of phospholipids, SP-A and albumin of the lining fluid of small airways.RESULTS: Age was a significant predictor of the phospholipids. The components PC14:0/16:0, PC16:0/18:2 (PC, phosphatidylcholine) and SP-A were higher among subjects with asthma, whereas albumin was lower. Among smokers, there were higher levels particularly of di-palmitoyl-di-phosphatidyl-choline compared with non-smokers. Most phospholipids significantly predicted the spirometry variables.CONCLUSION: This non-invasive PExA method appears to have great potential to explore the role of lipids and proteins of surfactant in respiratory disease.
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| 16. |
- Klepaker, G., et al.
(författare)
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Association of respiratory symptoms with body mass index and occupational exposure comparing sexes and subjects with and without asthma: follow-up of a Norwegian population study (the Telemark study)
- 2022
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Ingår i: Bmj Open Respiratory Research. - : BMJ. - 2052-4439. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Occupational exposure and increased body mass index (BMI) are associated with respiratory symptoms. This study investigated whether the association of a respiratory burden score with changes in BMI as well as changes in occupational exposure to vapours, gas, dust and fumes (VGDF) varied in subjects with and without asthma and in both sexes over a 5-year period. Methods In a 5-year follow-up of a population-based study, 6350 subjects completed a postal questionnaire in 2013 and 2018. A respiratory burden score based on self-reported respiratory symptoms, BMI and frequency of occupational exposure to VGDF were calculated at both times. The association between change in respiratory burden score and change in BMI or VGDF exposure was assessed using stratified regression models. Results Changes in respiratory burden score and BMI were associated with a beta-coefficient of 0.05 (95% CI 0.04 to 0.07). This association did not vary significantly by sex, with 0.05 (0.03 to 0.07) for women and 0.06 (0.04 to 0.09) for men. The association was stronger among those with asthma (0.12; 0.06 to 0.18) compared with those without asthma (0.05; 0.03 to 0.06) (p=0.011). The association of change in respiratory burden score with change in VGDF exposure gave a beta-coefficient of 0.15 (0.05 to 0.19). This association was somewhat greater for men versus women, with coefficients of 0.18 (0.12 to 0.24) and 0.13 (0.07 to 0.19), respectively (p=0.064). The estimate was similar among subjects with asthma (0.18; -0.02 to 0.38) and those without asthma (0.15; 0.11 to 0.19). Conclusions Increased BMI and exposure to VGDF were associated with increased respiratory burden scores. The change due to increased BMI was not affected by sex, but subjects with asthma had a significantly larger change than those without. Increased frequency of VGDF exposure was associated with increased respiratory burden score but without statistically significant differences with respect to sex or asthma status.
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| 17. |
- Knox-Brown, Ben, et al.
(författare)
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Isolated small airways obstruction predicts future chronic airflow obstruction : a multinational longitudinal study
- 2023
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Ingår i: BMJ open respiratory research. - : BMJ Publishing Group Ltd. - 2052-4439. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic airflow obstruction is a key characteristic of chronic obstructive pulmonary disease. We investigated whether isolated small airways obstruction is associated with chronic airflow obstruction later in life.METHODS: We used longitudinal data from 3957 participants of the multinational Burden of Obstructive Lung Disease study. We defined isolated small airways obstruction using the prebronchodilator mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FVC) (FEF25-75) if a result was less than the lower limit of normal (1/FVC). We also used the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) to define small airways obstruction. We defined chronic airflow obstruction as post-bronchodilator FEV1/FVCRESULTS: Median follow-up time was 8.3 years. Chronic airflow obstruction was more likely to develop in participants with isolated small airways obstruction at baseline (FEF25-75 less than the LLN, OR: 2.95, 95% CI 1.02 to 8.54; FEV3/FVC less than the LLN, OR: 1.94, 95% CI 1.05 to 3.62). FEF25-75 was better than the FEV3/FVC ratio to discriminate future chronic airflow obstruction (AUC: 0.764 vs 0.692). Results were similar among participants of the UK Biobank study.CONCLUSION: Measurements of small airways obstruction can be used as early markers of future obstructive lung disease.
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| 18. |
- Kochovska, Slavica, et al.
(författare)
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Persisting breathlessness and activities reduced or ceased: a population study in older men
- 2022
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Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 9:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Breathlessness is debilitating and increases in prevalence with age, with people progressively reducing their everyday activities to ‘self-manage’ it. This study aimed to evaluate the impact of breathlessness on function in terms of activities that have been reduced or ceased (‘compromised’) in older men.Methods A cross-sectional postal survey of Swedish 73-year-old man in the VAScular and Chronic Obstructive Lung disease study self-reporting on demographics, breathlessness (modified Medical Research Council (mMRC) scale, Dyspnoea-12, Multidimensional Dyspnea Scale) and its duration, anxiety/depression (Hospital Anxiety and Depression Scale), performance status (WHO Performance Status), everyday activities reduced/ceased and exertion.Results 148/828 (17.9%) respondents reported breathlessness (mMRC >2), of whom 51.9% had reduced/ceased activities compared with 9.6% who did not. Physical activity was the most common activity reduced/ceased (48.0%) followed by sexual activity (41.2%) and social activities (37.8%). Of 16.0% of respondents with mMRC 3–4 talking on the phone was affected compared with only 2.9% of respondents with mMRC 2. Worsening breathlessness was associated with increasingly sedentary lifestyles and more limited function, those reporting reduced/ceased activities had an associated increase in reporting anxiety and depression. In adjusted analyses, breathlessness was associated with increased likelihood of activities being ceased overall as well as physical and sexual activities being affected separately.Conclusion Worsening breathlessness was associated with decreasing levels of self-reported physical activity, sexual activity and function. Overall, the study showed that people with persisting breathlessness modify their lifestyle to avoid it by reducing or ceasing a range of activities, seeking to minimise their exposure to the symptom.
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| 19. |
- Kullberg, S, et al.
(författare)
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Effects of infliximab on lung and circulating natural killer cells, CD56+ T cells and B cells in sarcoidosis
- 2021
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Ingår i: BMJ open respiratory research. - : BMJ. - 2052-4439. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Tumour necrosis factor α (TNF-α) is pivotal in sarcoid granuloma formation, and inhibitors of TNF-α offer an attractive third-line treatment option in sarcoidosis. The sarcoid inflammation is characterised by an exaggerated T helper 1 response, and evidence indicates a contribution of dysregulated and/or deficient NK (natural killer) cells, CD56+ T cells and B cells.ObjectivesInsight into how TNF-α inhibitors influence these cells may provide more information on inflammatory mechanisms in sarcoidosis and improve understanding of such treatment. We therefore evaluated treatment effects of the TNF-α inhibitor infliximab on lung and peripheral blood (PB) NK, CD56+ T cells and B cells.MethodsFifteen patients were assessed with PB samples, spirometry and CT scan, and 11 of them also underwent bronchoalveolar lavage (BAL) close to start of infliximab treatment. These investigations were repeated after 6 months of treatment.ResultsTwelve out of 15 patients disclosed a clinical improvement at follow-up. Median percentage of BAL fluid (BALF) CD56+ T cells increased while a decrease was seen in PB (p<0.05 and 0.005, respectively). No significant changes were observed for NK cells. There was a trend towards increased median percentage of PB B cells (p=0.07), and a negative correlation was observed between PB and BALF B cells after treatment (p<0.05).ConclusionIn conclusion, 6 months of infliximab treatment in patients with sarcoidosis, of whom the majority benefited from the treatment, influenced immune cells in the lung and circulation differently, highlighting the importance of investigating several compartments concomitantly when evaluating treatment effects on the inflammatory activity.
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| 20. |
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| 21. |
- Lindstedt, Sandra, et al.
(författare)
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Lung transplant after 6 months on ECMO support for SARS-CoV-2-induced ARDS complicated by severe antibody-mediated rejection
- 2021
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Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 8, s. 1-4
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Tidskriftsartikel (refereegranskat)abstract
- There have been a few reports of successful lung transplantation (LTx) in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS); however, all reports were with rather short follow-up. Here we present a 62-year-old man without prior lung diseases. Following SARS-CoV-2-induced ARDS and 6 months of extracorporeal membrane oxygenation, he underwent LTx. 3 months post-transplantation he developed acute hypoxia requiring emergency intubation. Chest imaging showed acute rejection, and de novo DQ8-DSA was discovered. He was treated with a high dose of corticosteroids and plasmapheresis and was extubated 4 days later, yet the de novo DQ8-DSA remained. After sessions of plasmapheresis and rituximab, the levels of de novo DQ8-DSA remained unchanged. Nine months post-transplantation the patient died of respiratory failure. We herein discuss the decision to transplant, the transplantation itself and the postoperative course with severe antibody-mediated rejection. In addition, we evaluated the histological changes of the explanted lungs and compared these with end-stage idiopathic pulmonary fibrosis tissue, where both similarities and differences are seen. With the current case experience, one might consider close monitoring regarding DSA, and gives further support that LTx should only be considered for very carefully selected patients.
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| 22. |
- McCollum, ED, et al.
(författare)
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Defining hypoxaemia from pulse oximeter measurements of oxygen saturation in well children at low altitude in Bangladesh: an observational study
- 2021
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Ingår i: BMJ open respiratory research. - : BMJ. - 2052-4439. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- WHO defines hypoxaemia, a low peripheral arterial oxyhaemoglobin saturation (SpO2), as <90%. Although hypoxaemia is an important risk factor for mortality of children with respiratory infections, the optimal SpO2 threshold for defining hypoxaemia is uncertain in low-income and middle-income countries (LMICs). We derived a SpO2 threshold for hypoxaemia from well children in Bangladesh residing at low altitude.MethodsWe prospectively enrolled well, children aged 3–35 months participating in a pneumococcal vaccine evaluation in Sylhet district, Bangladesh between June and August 2017. Trained health workers conducting community surveillance measured the SpO2 of children using a Masimo Rad-5 pulse oximeter with a wrap sensor. We used standard summary statistics to evaluate the SpO2 distribution, including whether the distribution differed by age or sex. We considered the 2.5th, 5th and 10th percentiles of SpO2 as possible lower thresholds for hypoxaemia.ResultsOur primary analytical sample included 1470 children (mean age 18.6±9.5 months). Median SpO2 was 98% (IQR 96%–99%), and the 2.5th, 5th and 10th percentile SpO2 was 91%, 92% and 94%. No child had a SpO2 <90%. Children 3–11 months had a lower median SpO2 (97%) than 12–23 months (98%) and 24–35 months (98%) (p=0.039). The SpO2 distribution did not differ by sex (p=0.959).ConclusionA SpO2 threshold for hypoxaemia derived from the 2.5th, 5th or 10th percentile of well children is higher than <90%. If a higher threshold than <90% is adopted into LMIC care algorithms then decision-making using SpO2 must also consider the child’s clinical status to minimise misclassification of well children as hypoxaemic. Younger children in lower altitude LMICs may require a different threshold for hypoxaemia than older children. Evaluating the mortality risk of sick children using higher SpO2 thresholds for hypoxaemia is a key next step.
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| 23. |
- Mindus, Stephanie, et al.
(författare)
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Respiratory symptoms, exacerbations and sleep disturbances are more common among participants with asthma and chronic airflow limitation : an epidemiological study in Estonia, Iceland and Sweden
- 2024
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Ingår i: BMJ open respiratory research. - : BMJ Publishing Group Ltd. - 2052-4439. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic airflow limitation (CAL) is a hallmark of chronic obstructive pulmonary disease but is also present in some patients with asthma. We investigated respiratory symptoms, sleep and health status of participants with and without CAL with particular emphasis on concurrent asthma using data from adult populations in Iceland, Estonia and Sweden investigated within the Burden of Obstructive Lung Disease study.METHODS: All participants underwent spirometry with measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) before and after bronchodilation. CAL was defined as postbronchodilator FEV1/FVC below the lower limit of normal. IgE-sensitisation and serum concentrations of eosinophil-derived neurotoxin (S-EDN) were assessed in a subsample. The participants were divided into four groups: no self-reported doctor's diagnosed asthma or CAL, asthma without CAL, CAL without asthma and asthma and CAL: χ2 test and analysis of variance were used in bivariable analyses and logistic and linear regression when analysing the independent association between respiratory symptoms, exacerbations, sleep-related symptoms and health status towards CAL, adjusting for centre, age, sex, body mass index, smoking history and educational level.RESULTS: Among the 1918 participants, 190 (9.9%) had asthma without CAL, 127 (6.6%) had CAL without asthma and 50 (2.6%) had CAL with asthma. Having asthma with CAL was associated with symptoms such as wheeze (adjusted OR (aOR) 6.53 (95% CI 3.53 to 12.1), exacerbations (aOR 12.8 (95% CI 6.97 to 23.6), difficulties initiating sleep (aOR 2.82 (95% CI 1.45 to 5.48), nocturnal gastro-oesophageal reflux (aOR 3.98 (95% CI 1.79 to 8.82)) as well as lower physical health status. In these analyses, those with no asthma and no CAL were the reference group. The prevalence of IgE-sensitisation was highest in both asthma groups, which also had higher levels of S-EDN.CONCLUSION: Individuals with self-reported asthma with CAL suffer from a higher burden of respiratory and sleep-related symptoms, higher exacerbation rates and lower health status when compared with participants with asthma alone or CAL alone.
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| 24. |
- Müller, Catharina, et al.
(författare)
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Early extracellular matrix changes are associated with later development of bronchiolitis obliterans syndrome after lung transplantation
- 2017
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Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic lung allograft dysfunction in the form of bronchiolitis obliterans syndrome (BOS) is the main cause of death beyond 1-year post-lung transplantation. The disease-initiating triggers as well as the molecular changes leading to fibrotic alterations in the transplanted lung are largely unknown. The aim of this study was to identify potential early changes in the extracellular matrix (ECM) in different compartments of the transplanted lung prior to the development of BOS.METHODS: Transbronchial biopsies from a cohort of 58 lung transplantation patients at the Copenhagen University hospital between 2005 and 2006, with or without development of BOS in a 5-year follow-up, were obtained 3 and 12 months after transplantation. Biopsies were assessed for total collagen, collagen type IV and biglycan in the alveolar and small airway compartments using Masson's Trichrome staining and immunohistochemistry.RESULTS: A time-specific and compartment-specific pattern of ECM changes was detected. Alveolar total collagen (p=0.0190) and small airway biglycan (p=0.0199) increased between 3 and 12 months after transplantation in patients developing BOS, while collagen type IV (p=0.0124) increased in patients without BOS. Patients with early-onset BOS mirrored this increase. Patients developing grade 3 BOS showed distinct ECM changes already at 3 months. Patients with BOS with treated acute rejections displayed reduced alveolar total collagen (p=0.0501) and small airway biglycan (p=0.0485) at 3 months.CONCLUSIONS: Patients with future BOS displayed distinct ECM changes compared with patients without BOS. Our data indicate an involvement of alveolar and small airway compartments in post-transplantation changes in the development of BOS.
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| 25. |
- Rolandsson Enes, Sara, et al.
(författare)
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Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells
- 2014
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Ingår i: BMJ Open Respiratory Research. - : BMJ Publishing Group. - 2052-4439. ; 1:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported. This study therefore aimed to identify and characterise the ‘bona fide’ MSC in human lungs and to investigate if the MSC numbers correlate with the development of bronchiolitis obliterans syndrome in lung-transplanted patients. METHODS: Primary lung MSC were directly isolated or culture-derived from central and peripheral transbronchial biopsies of lung-transplanted patients and evaluated using a comprehensive panel of in vitro and in vivo assays. RESULTS: Primary MSC were enriched in the CD90/CD105 mononuclear cell fraction with mesenchymal progenitor frequencies of up to four colony-forming units, fibroblast/100 cells. In situ staining of lung tissues revealed that CD90/CD105 MSCs were located perivascularly. MSC were tissue-resident and exclusively donor lung-derived even in biopsies obtained from patients as long as 16 years after transplantation. Culture-derived mesenchymal stromal cells showed typical in vitro MSC properties; however, xenotransplantation into non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice showed that lung MSC readily differentiated into adipocytes and stromal tissues, but lacked significant in vivo bone formation. CONCLUSIONS: These data clearly demonstrate that primary MSC in human lung tissues are not only tissue resident but also tissue-specific. The identification and phenotypic characterisation of primary lung MSC is an important first step in identifying the role of MSC in normal lung physiology and pulmonary diseases.
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