Improved Air Quality and Asthma Incidence from School-Age to Young Adulthood: A Population-based Prospective Cohort Study.

Background The benefits of improved air quality on asthma remain understudied. Therefore, our aim was to investigate associations of changes in ambient air pollution with incident asthma from school-age until young adulthood in an area with mostly low air pollution levels. Methods Participants in the BAMSE birth cohort from Stockholm without asthma before the 8-year follow-up were included (N=2371). We estimated the association of change in individual-level air pollutant exposure (particulate matter with diameter ⩽2.5 µm (PM2.5) and, ⩽10 µm (PM10), black carbon (BC) and nitrogen oxides (NOx)) from the first year of life to the 8-year follow-up with asthma incidence from the 8-year until the 24-year follow-up. Multi-pollutant trajectories were identified using Group-Based Multivariate Trajectory model. We also used parametric g-computation to quantify the asthma incidence under different hypothetical interventions regarding air pollution levels. Results Air pollution levels at residency decreased during the period, with median reductions of 5.6% for PM2.5, 3.1% for PM10, 5.9% for BC, and 26.8% for NOx. A total of 395 incident asthma cases were identified from the 8-year until the 24-year follow-up. The odds ratio for asthma was 0.89 (95%CI: 0.80, 0.99) for each interquartile range reduction in PM2.5 (equal to 8.1% reduction). Associations appeared less clear for PM10, BC and NOx. Five multi-pollutant trajectories were identified, where the largest reduction trajectory displayed the lowest odds of asthma (OR=0.55, 95%CI: 0.31, 0.98) compared with the least reduction trajectory. If the PM2.5 exposure had not declined up to the 8-year follow-up, the hypothetical asthma incidence was estimated to have been 10.9% higher (95%CI: 0.8%, 20.8%). Conclusions Decrease in PM2.5 levels during childhood was associated with lower risk of incident asthma from school-age to young adulthood in an area with relatively low air pollution levels, suggesting broad respiratory health benefits from improved air quality. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Treatment with the SQ tree sublingual immunotherapy tablet is safe and well tolerated in real-life.

BACKGROUND: The SQ tree sublingual immunotherapy (SLIT)-tablet is authorised for treatment of allergic rhinoconjunctivitis with or without asthma in trees of the birch homologous group in 21 European countries. The primary objective of this study was to explore the safety in real-life. METHODS: In a prospective, non-interventional post-authorisation safety study (EUPAS31470), adverse events (AEs) and adverse drug reactions (ADRs) at first administration and follow-up visits, symptoms, medication use, and pollen food syndrome were recorded by physicians in 6 European countries during the first 4-6 months of treatment. RESULTS: ADRs with the SQ tree SLIT-tablet were reported in 57.7% of 1069 total patients (median age 36.0 years, 53.7% female) during the entire observation period (severity, mild-to-moderate: 70.1%, severe: 4.7%, serious: 0.7%) and in 45.9% after first administration. ADRs were not increased with pollen exposure at first administration. With coadministration of the SQ tree and grass SLIT-tablet AEs were reported in 73.8% of patients and in 52.8% with the SQ tree SLIT-tablet alone. Nasal and eye symptoms improved in 86.9% and 80.9% of patients and use of symptomatic medication in 76.0%. PFS with symptoms was reported in 43.0% of patients at baseline and in 4.3% at the individual last visit. CONCLUSIONS: The results of this non-interventional safety study with the SQ tree SLIT-tablet confirm the safety profile from placebo-controlled clinical trials and support effectiveness in real-life according to the published efficacy data. Safety was not impaired by pollen exposure at first administration or co-administration with other SLIT-tablets.

Multiarray screening identifies plasma proteins associated with Th17 cell differentiation and viral defense in coincident asthma and obesity.

BACKGROUND: The immunological mechanisms behind the clinical association between asthma and obesity in adolescence are not fully understood. This study aimed to find new plasma protein biomarkers associated specifically with coincident asthma and obesity in adolescents. METHODS: This was a cross-sectional study in children and adolescents 10-19 years old (N = 390). Relative plasma concentrations of 113 protein biomarkers related to inflammation and immune response were determined by proximity extension assay (Target 96; Olink, Uppsala, Sweden). Differences in protein concentrations between healthy controls (n = 84), subjects with asthma (n = 138), subjects with obesity (n = 107), and subjects with both asthma and obesity (AO; n = 58) were analyzed by ANCOVA, adjusting for age and sex, and in a separate model adjusting also for the sum of specific IgE antibody concentrations to a mix of food allergens (fx5) and aeroallergens (Phadiatop). Proteins elevated in the AO group but not in the obesity or asthma groups were considered specifically elevated in asthma and obesity. RESULTS: Five proteins were elevated specifically in the AO group compared to controls (here sorted from largest to smallest effect of asthma and obesity combined): CCL8, IL-33, IL-17C, FGF-23, and CLEC7A. The effects of adjusting also for specific IgE were small but IL-33, IL-17C, and FGF-23 were no longer statistically significant. CONCLUSION: We identified several new potential plasma biomarkers specifically elevated in coincident asthma and obesity in adolescents. Four of the proteins, CCL8, IL-33, IL-17C, and CLEC7A, have previously been associated with viral mucosal host defense and Th17 cell differentiation.

Pregnancy outcomes as related to in utero exposure to air pollution and greenness: The Life-GAP Project.

Background: Lower birth weight and preterm birth may increase the risk of adverse health outcomes later in life. We examined whether maternal exposure to air pollution and greenness during pregnancy is associated with offspring birth weight and preterm birth. Methods: We analyzed data on 4286 singleton births from 2358 mothers from Respiratory Health in Northern Europe, a prospective questionnaire-based cohort study (1990-2010). Mixed-effects regression models with random intercepts for mothers and centers were used to estimate the association of exposures to particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), ozone (O3), black carbon (BC), and greenness (Normalized Difference Vegetation Index in 300m-buffers [NDVI300m]) with birth outcomes, adjusting for potential confounders. Results: Median (interquartile range [IQR]) exposures to PM2.5, PM10, NO2, O3, BC, and NDVI300m during pregnancy were 8.4(5.0) µg/m3, 14.4(8.3) µg/m3, 14.0(11.0) µg/m3, 54.7(10.2) µg/m3, 0.47(0.41) µg/m3, and 0.31(0.20), respectively. IQR increases in air pollution exposures during pregnancy were associated with decreased birth weight and the strongest association was seen for PM2.5 (-49g; 95% confidence interval [CI] = -83, -16). However, O3 showed an opposite association. IQR increase in NDVI300m was associated with an increase in birth weight of 25 g (95% CI = 7, 44). Preterm birth was not associated with the exposures. Conclusion: Increased greenness and decreased air pollution may contribute to healthier pregnancies and improve overall health in the next generation. This emphasizes the need to adopt policies that target the reduction of air pollution emissions and exposure of the population.

Relationships between symptoms and lung function in asthma and/or chronic obstructive pulmonary disease in a real-life setting: the NOVEL observational longiTudinal studY.

BACKGROUND: The relationships between spirometric assessment of lung function and symptoms (including exacerbations) in patients with asthma and/or chronic obstructive pulmonary disease (COPD) in a real-life setting are uncertain. OBJECTIVES: To assess the relationships between baseline post-bronchodilator (post-BD) spirometry measures of lung function and symptoms and exacerbations in patients with a physician-assigned diagnosis of asthma and/or COPD. DESIGN: The NOVEL observational longiTudinal studY (NOVELTY) is a global, prospective, 3-year observational study. METHODS: Logistic regression analysis was used to evaluate relationships. Spirometry measures were assessed as percent predicted (%pred). Symptoms were assessed at baseline, and exacerbations were assessed at baseline and Year 1. RESULTS: A total of 11,181 patients in NOVELTY had spirometry data (asthma, n = 5903; COPD, n = 3881; asthma + COPD, n = 1397). A 10% lower post-BD %pred forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) - adjusted for age and sex - were significantly associated with dyspnea (modified Medical Research Council ⩾ grade 2), frequent breathlessness [St George's Respiratory Questionnaire (SGRQ)], frequent wheeze attacks (SGRQ), nocturnal awakening (Respiratory Symptoms Questionnaire; ⩾1 night/week), and frequent productive cough (SGRQ). Lower post-BD %pred FEV1 and, to a lesser extent, lower post-BD %pred FVC were significantly associated with ⩾1 physician-reported exacerbation at baseline or Year 1. This association was stronger in patients with COPD than in those with asthma. CONCLUSION: In a real-life setting, reduced lung function is consistently associated with symptoms in patients with asthma, COPD, or asthma + COPD. The relationship with exacerbations is stronger in COPD only than in asthma. TRAIL REGISTRATION: clinicaltrials.gov identifier: NCT02760329 (www.clinicaltrials.gov).

Relationships between symptoms and lung function in asthma and/or chronic obstructive pulmonary disease in a study performed in a real-life setting: the NOVELTY studyBackground: Asthma and chronic obstructive pulmonary disease (COPD) have many symptoms in common. To confirm diagnosis, doctors use spirometry, a test to measure the amount of air that can be breathed out from the lungs and how fast it can be blown out. The relationship between these measurements and symptoms in asthma and COPD is not well understood.Objectives: The aim of this research is to describe the characteristics, treatment, and impact of asthma and/or COPD in patients who are receiving their usual medical care.Methods: NOVELTY is a large study of around 12,000 patients across 19 countries. This analysis of NOVELTY looked at the relationships between two spirometry measurements and the symptoms of asthma and/or COPD experienced by patients. The spirometry measurements were: - forced expiratory volume in 1 second (FEV₁) ­ the amount of air that can be blown out of the lungs in 1 second- forced vital capacity (FVC) ­ the amount of air that can be forcibly breathed out from the lungs after taking the deepest breath possibleResults: The lower the FEV₁ and FVC, the more common the symptoms of breathlessness, wheeze attacks, night-time awakening, and coughing up of phlegm or mucus. These relationships were similar for FEV₁ and FVC. Lower FEV₁ was more strongly associated with worse symptoms in COPD than in asthma.Conclusion: These findings help to improve our understanding of the relationships between spirometry measures and symptoms in patients with asthma and/or COPD.

Internet-delivered cognitive-behaviour therapy for anxiety related to asthma: study protocol for a randomised controlled trial.

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). TRIAL REGISTRATION NUMBER: Registered at ClinicalTrials.gov (ID: NCT04230369).

Enhancing EQ-5D-5L Sensitivity in Capturing the Most Common Symptoms in Post-COVID-19 Patients: An Exploratory Cross-Sectional Study with a Focus on Fatigue, Memory/Concentration Problems and Dyspnea Dimensions.

This study aimed to determine whether the EQ-5D-5L tool captures the most common persistent symptoms, such as fatigue, memory/concentration problems and dyspnea, in patients with post-COVID-19 conditions while also investigating if adding these symptoms improves the explained variance of the health-related quality of life (HRQoL). In this exploratory cross-sectional study, two cohorts of Swedish patients (n = 177) with a history of COVID-19 infection answered a questionnaire covering sociodemographic characteristics and clinical factors, and their HRQoL was assessed using EQ-5D-5L with the Visual Analogue Scale (EQ-VAS). Spearman rank correlation and multiple regression analyses were employed to investigate the extent to which the most common persistent symptoms, such as fatigue, memory/concentration problems and dyspnea, were explained by the EQ-5D-5L. The explanatory power of EQ-5D-5L for EQ-VAS was also analyzed, both with and without including symptom(s). We found that the EQ-5D-5L dimensions partly captured fatigue and memory/concentration problems but performed poorly in regard to capturing dyspnea. Specifically, the EQ-5D-5L explained 55% of the variance in memory/concentration problems, 47% in regard to fatigue and only 14% in regard to dyspnea. Adding fatigue to the EQ-5D-5L increased the explained variance of the EQ-VAS by 5.7%, while adding memory/concentration problems and dyspnea had a comparatively smaller impact on the explained variance. Our study highlights the EQ-5D-5L's strength in capturing fatigue and memory/concentration problems in post-COVID-19 patients. However, it also underscores the challenges in assessing dyspnea in this group. Fatigue emerged as a notably influential symptom, significantly enhancing the EQ-5D-5L's predictive ability for these patients' EQ-VAS scores.

Interplay of clinical biomarkers in allergic asthma diagnosis and severity: A case-control study.

Given asthma's large phenotypic diversity, the study was aimed to use specific biomarkers to characterize Allergic asthma (AA) and its severity. Blood was collected from 42 healthy controls (HCs) and 96 patients with AA. Biomarkers related to blood cell number and function: total leukocyte count (TLCs), neutrophil, lymphocyte, monocyte, eosinophil, basophil, neutrophil-to-lymphocyte ratio (NLR), immunoglobulin E (IgE), tryptase and eosinophilic cationic protein (ECP) as well as remodelling biomarkers (Matrix metalloproteinase (MMP-9), (MMP-16), Fibroblast growth factor (FGF-18) and (FGF-23) and alpha-skeletal muscle actin-1 (ACTa-1) were measured. Significant differences were observed in hematological parameters with higher levels of total leukocytes, eosinophil, and basophil counts in the AA group compared to HCs. The disease group also had significantly higher levels of several serum biomarkers (IgE, TPs, ECP, MMP-9, MMP-16, FGF-18, FGF-23, and ACTa-1) compared to HC. Forced expiratory volume 1 (FEV1) and forced vital capacity (FVC) had a strong negative correlation with ECP, IgE, and ACTa-1. FEV1 was negatively correlated with MMP-16 and tryptase. Patients with AA have higher levels of several biomarkers, such as MMP-9, MMP-16, FGF-18, FGF-23, IgE, tryptase, and ACTa-1. In addition, IgE, tryptase, ACTa-1, and MMP-16 are related to lung function impairment in AA. This indicates that measuring multiple biomarkers may be of value in the future when diagnosing and monitoring AA.

Associations of long-term exposure to air pollution and greenness with incidence of chronic obstructive pulmonary disease in Northern Europe: The Life-GAP project.

BACKGROUND: Prolonged exposure to air pollution has been linked to adverse respiratory health, yet the evidence concerning its association with chronic obstructive pulmonary disease (COPD) is inconsistent. The evidence of a greenness effect on chronic respiratory diseases is limited. OBJECTIVE: This study aimed to investigate the association between long-term exposure to particulate matter (PM2.5 and PM10), black carbon (BC), nitrogen dioxide (NO2), ozone (O3) and greenness (as measured by the normalized difference vegetation index - NDVI) and incidence of self-reported chronic bronchitis or COPD (CB/COPD). METHODS: We analyzed data from 5355 adults from 7 centers participating in the Respiratory Health in Northern Europe (RHINE) study. Mean exposures to air pollution and greenness were assessed at available residential addresses in 1990, 2000 and 2010 using air dispersion models and satellite data, respectively. Poisson regression with log person-time as an offset was employed to analyze the association between air pollution, greenness, and CB/COPD incidence, adjusting for confounders. RESULTS: Overall, there were 328 incident cases of CB/COPD during 2010-2023. Despite wide statistical uncertainty, we found a trend for a positive association between NO2 exposure and CB/COPD incidence, with incidence rate ratios (IRRs) per 10 µg/m³ difference ranging between 1.13 (95% CI: 0.90-1.41) in 1990 and 1.18 (95% CI: 0.96-1.45) in 2000. O3 showed a tendency for inverse association with CB/COPD incidence (IRR from 0.84 (95% CI: 0.66-1.07) in 2000 to 0.88 (95% CI: 0.69-1.14) in 2010. No consistent association was found between PM, BC and greenness with CB/COPD incidence across different exposure time windows. CONCLUSION: Consistent with prior research, our study suggests that individuals exposed to higher concentrations of NO2 may face an elevated risk of developing COPD, although evidence remains inconclusive. Greenness was not associated with CB/COPD incidence, while O3 showed a tendency for an inverse association with the outcome.

Asthma Is Associated With Increased Sickness Absence Among Young Adults.

BACKGROUND: There is limited knowledge about how asthma affects sickness absence in young adulthood. OBJECTIVE: To examine how asthma and different asthma phenotypes affect sickness absence among young adults and potential modifying factors. A secondary aim was to estimate productivity losses related to sickness absence for asthma. METHODS: The study included 2391 participants from the Swedish population-based cohort BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology). Information on asthma, asthma phenotypes, and lifestyle factors was collected from questionnaires and clinical examinations at age approximately 24 years (2016-2019). Information on sickness absence for longer than 14 days was obtained from a national register for the years 2020 and 2021. Associations between asthma, asthma phenotypes, and sickness absence were analyzed with logistic regression models adjusted for sex, birth year, education, and overweight status. RESULTS: At age 24 years, 272 (11.4%) fulfilled the definition of asthma. Sickness absence was more common among those with asthma than among those without (15.1% vs 8.7%; P = .001; adjusted odds ratio 1.73; 95% CI, 1.19-2.51). Analyses of asthma phenotypes showed that the association tended to be stronger for persistent asthma, uncontrolled asthma, and asthma in combination with rhinitis; no consistent differences were observed across phenotypes related to allergic sensitization or inflammation. The association tended to be stronger among those with overweight than among those with normal weight. Asthma, especially uncontrolled asthma, was associated with higher productivity losses from sickness absence. CONCLUSIONS: Asthma may be associated with higher sickness absence and productivity losses. Achieving better asthma control and reducing allergic symptoms may reduce sickness absence among individuals with asthma.

A comparative study of multiple biomarkers levels in complicated versus noncomplicated type 2 diabetic patients.

The prevalence of diabetes mellitus is growing globally and the management of diabetes is a critical issue for public health. This study aimed to analyze the concentration of different biomarkers in patients with type 2 diabetes mellitus (T2DM) without complication, T2DM patients with complication (T2DM+C), and compared to healthy controls (HC). For this aim, there were 164 participants: 59 T2DM, 60 T2DM+C, and 45 HC. Venous blood was collected and the levels of Hemoglobin A1C (HbA1C), fasting blood glucose, Interleukin-31 (IL-31), IL-35, glutamic acid decarboxylase antibody (GADA), developmental locus-1 (Del-1), fibroblast growth factor-9 (FGF-9) and FGF-18) and lipid profile (total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride) were analyzed. Results showed that IL-31 was significantly higher in T2DM compared to HC (p<0.0001), and compared to T2DM+C (p<0.0001). IL-31 was significantly lower in T2DM+C than HC (p=0.009). The level of serum GADA was significantly elevated in T2DM compared to HC (p=0.0009), and T2DM+C (p=0.03). There was a significant correlation between (IL-31, IL-35, GADA, Del-1, FGF-9 and FGF-18). The duration of having diabetes was significantly longer in T2DM+C compared to T2DM (p<0.0001). However, there was no significant difference in the level of HBA1C% between T2DM+C and T2DM patients (p=0.98). In conclusion, there were significant differences in biomarker concentrations between all three groups. This indicates that the monitoring of multiple biomarkers may be of value in the controlling of T2DM in the future.

Disease burden and unmet need for acute allergic reactions - A patient perspective.

Background: Acute allergic reactions (AARs) occur shortly after exposure to an allergen, and the severity is on a continuum. Systemic corticosteroids (CS) are mainstay treatment of moderate to severe AARs, whereas those at risk of the most severe AARs (ie, anaphylaxis) are also recommended prescription of epinephrine autoinjectors. There is limited research on the impact of AARs not fulfilling the criteria for anaphylaxis. We have characterized a sample with a history of moderate to severe AARs and evaluated their self-reported disease burden (ie, daily life impact, anxiety, and treatment impediments). Methods: Survey study of adults with experience of AARs treated with CS. Participants recruited from a web-based panel and using social media were asked to complete a questionnaire related to their allergy and experience of AARs. The results were summarized for the whole sample and across subgroups with and without prescription of epinephrine. Results: The final study sample included 387 participants (80% women, mean age 41), of which 129 (33%) had at some point been prescribed epinephrine. The most common symptoms were respiratory (80%) and skin (78%) manifestations, and the mean (standard deviation, SD) self-rated severity score (scale from 0 [very mild] to 10 [very severe]) of the most recent AAR was 6.1 (2.0). More than 80% had experience of AARs interrupting daily activities and 50% of AARs that had limited work/studies or participation in leisure activities. Most of the respondents reported some degree of anxiety related to AARs and 43% had feared for their lives. Moreover, difficulties swallowing allergy medicine at an AAR was experienced by 26% and not having the medicine available when needed by 66%. Participants with prescription of epinephrine experienced more severe AARs than those without such prescription (mean [SD] severity 6.8 [2.1] vs 5.8 [1.8], p < 0.0001); however, also those without epinephrine prescription reported considerable anxiety and impact on daily life and to a similar degree as those with prescription. Conclusions: In this sample, subjects with experience of AARs treated with CS showed a considerable disease burden with anxiety and interruption on daily life, as well as problems related to access to, and swallowing of, medication. Although respondents with epinephrine prescription had more severe disease, a high disease burden was also evident among those without epinephrine. The study increases the knowledge of people with moderate to severe AARs, a patient population that has previously been underrepresented in the research literature.

FEV1 and FVC as robust risk factors for cardiovascular disease and mortality: Insights from a large population study.

INTRODUCTION: Data is limited on influence of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in a large adult population, including individuals with normal spirometry at baseline. METHODS: Using the UK Biobank cohort, a multivariable Cox regression analysis was conducted on 406,424 individuals to examine the association between FEV1 and FVC, categorized into three groups based on their percentage of predicted values (%pred) (≥80, 60-80 and < 60), and overall mortality, cardiovascular mortality, myocardial infarction, stroke, and heart failure over approximately 12.5 years. Moreover, a subgroup analysis was conducted on 295,459 individuals who had normal spirometry. RESULTS: Reduced FEV1 and FVC %pred values were associated with an elevated risk across all studied outcomes. Individuals with the lowest FEV1 and FVC %pred values (<60 %) exhibited HR of 1.83 (95 % CI 1.74-1.93) and 1.98 (95 % CI 1.76-2.22) for overall mortality, and 1.96 (95 % CI 1.83-2.1) and 2.26 (95 % CI 1.94-2.63) for cardiovascular mortality. Moreover, a graded association was observed between lower FEV1 and FVC %pred, even among never smokers and individuals with normal spirometry at baseline. DISCUSSION: Reduced FEV1 and FVC represent robust risk factors for cardiovascular disease and mortality. The fact that the increased risk was evident also at FEV1 and FVC levels exceeding 80 %pred challenges the contemporary classification of lung function categories and the notion that the entire FEV1- and FVC-range above 80 % of predicted represents a normal lung function.

Nocturnal gastro-oesophageal reflux and respiratory symptoms are increased in sleep apnoea: comparison with the general population.

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.

Association between physical activity over a 10-year period and current insomnia symptoms, sleep duration and daytime sleepiness: a European population-based study.

OBJECTIVES: To explore the relationship between physical activity over a 10-year period and current symptoms of insomnia, daytime sleepiness and estimated sleep duration in adults aged 39-67. DESIGN: Population-based, multicentre cohort study. SETTING: 21 centres in nine European countries. METHODS: Included were 4339 participants in the third follow-up to the European Community Respiratory Health Survey (ECRHS III), who answered questions on physical activity at baseline (ECRHS II) and questions on physical activity, insomnia symptoms, sleep duration and daytime sleepiness at 10-year follow-up (ECRHS III). Participants who reported that they exercised with a frequency of at least two or more times a week, for 1 hour/week or more, were classified as being physically active. Changes in activity status were categorised into four groups: persistently non-active; became inactive; became active; and persistently active. MAIN OUTCOME MEASURES: Insomnia, sleep time and daytime sleepiness in relation to physical activity. RESULTS: Altogether, 37% of participants were persistently non-active, 25% were persistently active, 20% became inactive and 18% became active from baseline to follow-up. Participants who were persistently active were less likely to report difficulties initiating sleep (OR 0.60, 95% CI 0.45-0.78), a short sleep duration of ≤6 hours/night (OR 0.71, 95% CI 0.59-0.85) and a long sleep of ≥9 hours/night (OR 0.53, 95% CI 0.33-0.84) than persistently non-active subjects after adjusting for age, sex, body mass index, smoking history and study centre. Daytime sleepiness and difficulties maintaining sleep were not related to physical activity status. CONCLUSION: Physically active people have a lower risk of some insomnia symptoms and extreme sleep durations, both long and short.

Biomarkers of chronic airflow limitation and COPD identified by mass spectrometry.

Rationale: COPD affects 300 million people worldwide and is the third leading cause of death according to World Health Organization global health estimates. Early symptoms are subtle, and so COPD is often diagnosed at an advanced stage. Thus, there is an unmet need for biomarkers that can identify individuals at early stages of the disease before clinical symptoms have manifested. To date, few biomarkers are available for clinical diagnostic use in COPD. Methods: We evaluated a panel of serum biomarkers related to inflammation and infection for their ability to discriminate between 77 subjects with chronic airflow limitation (CAL) and 142 subjects with COPD, versus 150 healthy subjects (divided into two control groups that were matched with regards to age, gender and smoking to CAL and COPD). Healthy subjects and CAL were from Burden of Obstructive Lung Disease (BOLD), a population-based study. CAL was defined by post-bronchodilatory forced expiratory volume in 1 s/forced vital capacity ratio <0.7 in the BOLD population. COPD subjects were from Tools for Identifying Exacerbations (TIE), a COPD patient cohort. Quantification of 100 biomarker candidates was done by liquid chromatography-tandem mass spectrometry. Results: Several protein-derived peptides were upregulated in CAL, compared to controls; most notably peptides representing histidine-rich glycoprotein (HRG), α1-acid glycoprotein (AGP1), α1-antitrypsin (α1AT) and fibronectin. Out of these, HRG-, AGP1- and α1AT-specific peptides were also elevated in the COPD cohort. Conclusion: HRG, AGP1 and α1AT biomarkers distinguish subjects with CAL and COPD from healthy controls. HRG and AGP1 represent novel findings.

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.

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.

Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients.

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

Polysomnographic characteristics of excessive daytime sleepiness phenotypes in obstructive sleep apnea: results from the international sleep apnea global interdisciplinary consortium.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a major symptom of obstructive sleep apnea (OSA). Traditional polysomnographic (PSG) measures only partially explain EDS in OSA. This study analyzed traditional and novel PSG characteristics of two different measures of EDS among patients with OSA. METHODS: Sleepiness was assessed using the Epworth Sleepiness Scale (>10 points defined as "risk of dozing") and a measure of general sleepiness (feeling sleepy ≥ 3 times/week defined as "feeling sleepy"). Four sleepiness phenotypes were identified: "non-sleepy," "risk of dozing only," "feeling sleepy only," and "both at risk of dozing and feeling sleepy." RESULTS: Altogether, 2083 patients with OSA (69% male) with an apnea-hypopnea index (AHI) ≥ 5 events/hour were studied; 46% were "non-sleepy," 26% at "risk of dozing only," 7% were "feeling sleepy only," and 21% reported both. The two phenotypes at "risk of dozing" had higher AHI, more severe hypoxemia (as measured by oxygen desaturation index, minimum and average oxygen saturation [SpO2], time spent < 90% SpO2, and hypoxic impacts) and they spent less time awake, had shorter sleep latency, and higher heart rate response to arousals than "non-sleepy" and "feeling sleepy only" phenotypes. While statistically significant, effect sizes were small. Sleep stages, frequency of arousals, wake after sleep onset and limb movement did not differ between sleepiness phenotypes after adjusting for confounders. CONCLUSIONS: In a large international group of patients with OSA, PSG characteristics were weakly associated with EDS. The physiological measures differed among individuals characterized as "risk of dozing" or "non-sleepy," while "feeling sleepy only" did not differ from "non-sleepy" individuals.