Post COVID-19 symptoms are common, also among young adults in the general population.

Post coronavirus disease-19 (post COVID-19) is mainly studied in clinical populations and less is known about post COVID-19 in a young general population. The aim of the study is to investigate the prevalence and symptoms of post COVID-19 and its potential risk factors in young adults. Participants from the Swedish population-based birth cohort BAMSE were included (n = 2022, mean age 26.5 years). Post COVID-19 was assessed through a questionnaire and defined as symptoms after confirmed COVID-19 (registry-based or self-reported positive test) lasting for ≥ 2 months. In total, 681 participants had had confirmed COVID-19. Among them, 112 (16.5%) fulfilled the definition of post COVID-19 (17.8% in females, 14.5% in males, p = 0.26). The most common post COVID-19 symptoms were altered smell and taste (68.8%), dyspnea (33.7%) and fatigue (30.4%). Overall, no major risk factors for post COVID-19 were identified except for being bedbound during COVID-19. However, asthma and rhinitis were associated with the post COVID-19 symptom dyspnea, migraine with altered smell and taste, and lower self-rated health with fatigue. In conclusion, post COVID-19 symptoms are common, also among young adults in the general population. Although not life-threatening, it could have a considerable impact on public health due to the high prevalence and long-term symptoms.

Exploring proteomic plasma biomarkers in eosinophilic and neutrophilic asthma.

BACKGROUND: Few biomarkers identify eosinophilic and neutrophilic asthma beyond cell concentrations in blood or sputum. Finding novel biomarkers for asthma endotypes could give insight about disease mechanisms and guide tailored treatment. Our aim was to investigate clinical characteristics and inflammation-related plasma proteins in relation to blood eosinophil and neutrophil concentrations in subjects with and without asthma. METHODS: We included 24-26-year-old subjects (n = 2063) from the Swedish population-based cohort BAMSE. Subjects with asthma (n = 239) and without asthma (n = 1824) were subdivided based on blood eosinophil and neutrophil concentrations (cut-offs 0.3 × 109 /L and 5.0 × 109 /L, respectively). We measured the levels of 92 plasma proteins using Olink Proseek Multiplex Inflammation Panel Assay. Group statistics tests were used to analyse the data, as well as adjusted multiple logistic regression models. RESULTS: Among subjects with asthma, 21.8% had eosinophilic asthma and 20.5% neutrophilic asthma. Eosinophilic asthma, but not neutrophilic asthma, was associated with a distinct clinical phenotype with, for example, higher proportions of eczema and sensitization. Most plasma proteins that associated with high eosinophil and/or neutrophil blood concentrations in subjects with asthma showed similar associations in subjects without asthma. However, out of these proteins, MMP10 levels were associated with eosinophilic asthma and were significantly higher as compared to controls with high eosinophilic concentration, while CCL4 levels associated with high neutrophil concentration only in subjects with asthma. CONCLUSIONS: Eosinophilic asthma was associated with a clear clinical phenotype. With our definitions, we identified MMP10 as a possible plasma biomarker for eosinophilic asthma and CCL4 was linked to neutrophilic asthma. These proteins should be evaluated further in clinical settings and using sputum granulocytes to define the asthma endotypes.

Lung function in young adulthood: differences between males and females with asthma.

Background: There are phenotypic differences in asthma in males and females. Differences in lung function between the sexes at the peak lung function level in young adulthood are so far not directly addressed. The aim of the present study was to assess lung function in early adulthood in males and females depending on asthma onset and remission. Methods: Participants were included from the population-based birth cohort BAMSE and classified as having: never asthma, childhood asthma in remission, adolescent onset asthma or persistent asthma. Pre- and post-bronchodilator lung function (in Z-score) and lung clearance index (LCI) were measured at age 24 years. Lung function was compared stratified for sex between the never asthma and asthma groups univariately and in multiple linear regression analyses adjusted for maternal and paternal asthma, maternal smoking during pregnancy, secondary smoking, daily smoking, early respiratory syncytial virus infection, traffic pollution, childhood allergic sensitisation, and body mass index at age 24 years. Results: All asthma phenotypes were associated with a lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) post-bronchodilation at 24 years. This was most pronounced in males with persistent asthma compared to males with never asthma (regression coefficient: -0.503; 95% CI: -0.708- -0.298). Childhood asthma (in remission or persistent) was associated with a lower FEV1. After adjustment, the associations remained significant for males. For females, the significant associations with lower FEV1 and FEV1/FVC remained only for subjects with asthma in remission. Persistent asthma was associated with higher LCI in females. Conclusions: In females, in contrast to males, the association between asthma and lower lung function was attenuated after adjustment for known risk factors.

General Stress Among Young Adults with Asthma During the COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has profoundly affected the lives of the global population. OBJECTIVE: To explore anxiety and stress in relation to COVID-19 among young adults, and the potential influence of asthma and allergic rhinitis. METHODS: This cross-sectional study included 1644 participants from the population-based birth cohort BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology), participating in a follow-up at age 24 years and a COVID-19 follow-up conducted in August-November 2020 (mean age, 25.3 years). Anxiety and concern related to COVID-19 were analyzed as general anxiety, concern of own health and health of family members, and contact with online health care providers due to concern about COVID-19. Stress was measured with the perceived stress scale. RESULTS: Around half the participants reported increased anxiety due to COVID-19, and this was more common among females (57.0%, compared with 42.6% in males; P < .001). Young adults with asthma reported more concern about their own health (adjusted odds ratio, 1.50; 95% CI, 1.12-2.02) and perceived stress (adjusted regression coefficient [adjusted ß], 1.49; 95% CI, 0.52-2.45) compared with peers without asthma, and this was more pronounced among females and those with uncontrolled asthma. Symptoms of allergic rhinitis were not associated with increased concern or anxiety in relation to COVID-19. CONCLUSIONS: Young adults with asthma experience more COVID-19-related health concerns, compared with those without asthma, especially females and participants with uncontrolled asthma This needs to be considered in the care of young people with asthma.

Lung function before and after COVID-19 in young adults: A population-based study.

Background: There is limited evidence on the long-term impact of mild-to-moderate coronavirus disease 2019 (COVID-19) on lung function among young adults. Objectives: We aimed to assess whether COVID-19 has a negative impact on lung function in young adults and whether asthma, allergic sensitization, or use of inhaled corticosteroids (ICSs) modifies a potential association. Methods: Participants from the population-based BAMSE (Barn, Allergi, Miljö, Stockholm, Epidemiologi) cohort with spirometry assessed before (2016-2019) and after onset of the COVID-19 pandemic (2020-2021) were included. Serum levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain-specific IgG, IgM, and/or IgA (determined with ELISA) defined seropositivity. Mean change in lung function (ie, change in FEV1, forced vital capacity [FVC], and FEV1/FVC ratio expressed as percent of predicted [pp]) from before to after onset of the pandemic were compared between the seronegative and seropositive participants. In seropositive participants, change in lung function was assessed in relation to allergic sensitization and self-reported ICS use. Results: Of the 853 included participants, 29% (n = 243) were seropositive. There were no differences in change in lung function between the seronegative and seropositive participants (for mean change in FEV1 pp [SD], seropositivity = 0.87% [4.79%] and seronegativity = 1.03% (4.76%) [P = .66] for difference using a t test; FVC pp (SD), seropositivity = 1.34% (4.44%) and seronegativity = 1.29% (4.27%) [P = .87]; and for FEV1/FVC pp (SD), seropositivity = -0.25% (3.13%) and seronegativity = -0.13% (3.15%) [P = .61]). Similar results were observed among participants with asthma (n = 147 [17%]). Among seropositive participants, allergic sensitization or ICS use did not influence lung function. Conclusion: We found no evidence of mild-to-moderate COVID-19 affecting lung function long term in a population-based cohort of young adults. Moreover, neither asthma nor allergic sensitization nor ICS use affected the results.

Uncontrolled asthma from childhood to young adulthood associates with airflow obstruction.

INTRODUCTION: Lung function development from childhood to young adulthood is important for lung health later in life. We investigated the association between asthma control and lung function from 8 to 24 years of age. METHODS: A total of 668 participants from the population-based BAMSE cohort study, with persistent or incidental asthma and between 8 and 24 years of age, were included. Asthma was defined as controlled or uncontrolled at each examination based on the Global Initiative for Asthma (GINA) criteria. Dynamic spirometry was performed at 8, 16 and 24 years of age. Associations between uncontrolled asthma and pre-bronchodilation forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio were evaluated with a generalised estimating equation model, as overall associations and at each examination. Unadjusted and adjusted (for sex, current asthma, allergic sensitisation, body mass index, smoking, smoke exposure, inhaled corticosteroid use) analyses were done; and were thereafter stratified by sex, elevated blood eosinophils (≥0.3×109 cells·µL-1), elevated F ENO (≥25 ppb), allergic sensitisation and ever/never smoking. RESULTS: Uncontrolled asthma was associated with a lower overall FEV1/FVC z-score from 8 to 24 years of age (adjusted regression coefficient -0.11; 95% CI (-0.20 to -0.02; p=0.016). After stratification, this association was primarily seen among females (adjusted regression coefficient -0.170; 95% CI (-0.298 to -0.044; p=0.009) and participants with elevated F ENO (regression coefficient -0.207; 95% CI -0.342 to -0.073; p=0.002), in contrast to males and participants with normal F ENO. CONCLUSION: Uncontrolled asthma is associated with airflow obstruction from childhood to young adulthood. This highlights the importance of active management of asthma during growth.

Inflammatory patterns in fixed airflow obstruction are dependent on the presence of asthma.

RATIONALE: Fixed airflow obstruction (FAO) can complicate asthma. Inflammation is a proposed underlying mechanism. OBJECTIVE: Our aim in this cross-sectional investigation was to evaluate the blood leucocyte pattern and level of exhaled nitric oxide in asthmatics and non-asthmatics with or without FAO. METHODS: A total of 11,579 individuals aged ≥20 years from the US National Health and Nutrition Examination Survey were included. They were grouped as: controls without asthma and FAO (n = 9,935), asthmatics without FAO (n = 674), asthmatics with FAO (n = 180) and non-asthmatics with FAO (n = 790). FAO was defined as post-bronchodilator FEV1/FVC < lower limit of normal. Exhaled nitric oxide ≥ 25ppb, blood eosinophil levels ≥300 cells/µL, and blood neutrophil levels ≥5100 cells/µL were defined as elevated. Stratified analyses for smoking and smoking history were performed. RESULTS: Elevated blood eosinophil levels were more common in all groups compared to the controls, with the highest prevalence in the group with asthma and fixed airflow obstruction (p<0.01). In a multiple logistic regression model adjusted for potential confounders including smoking, the asthma groups had significantly higher odds ratios for elevated B-Eos levels compared to the control group (odds ratio 1.4, (confidence interval: 1.1-1.7) for the asthma group without fixed airflow obstruction and 2.5 (1.4-4.2) for the asthma group with fixed airflow obstruction). The group with fixed airflow obstruction without asthma had higher odds ratio for elevated blood neutrophil levels compared to the controls: 1.4 (1.1-1.8). Smoking and a history of smoking were associated to elevated B-Neu levels. CONCLUSION: Fixed airflow obstruction in asthma was associated with elevated blood eosinophil levels, whereas fixed airflow obstruction without asthma was associated with elevated blood neutrophil levels.

Blood eosinophil level and lung function trajectories: cross-sectional and longitudinal studies in European cohorts.

BACKGROUND: Elevated blood eosinophils have been associated with lower lung function and are believed to be associated with accelerated lung function decline. METHOD: Blood eosinophils were measured in four cohorts: <45 years cohort within the Vlagtwedde-Vlaardingen (V&V) study, the Uppsala cohort of the European Community Respiratory Health Survey (ECRHS-Uppsala; <45 years), ≥45 years cohort within the V&V study, and the Rotterdam study (≥45 years). Blood eosinophils at baseline were classified as normal (<300 cells·µL-1) or elevated (≥300 cells·µL-1). Lung function was measured at baseline and follow-up with spirometry: forced expiratory volume in 1 s (FEV1), vital capacity (VC) and their ratio FEV1/VC. The association between blood eosinophils and lung function was tested cross-sectionally using linear regression and longitudinally using a mixed model, both adjusted for age, sex, height, pack-years smoking and smoking status. Stratified analyses were done for asthma. RESULTS: Elevated blood eosinophils were associated with lower FEV1 (regression coefficient -147 mL (95% CI -188 to -105 mL)), VC (-120 mL (-165 to -75 mL)) and FEV1/VC (-1.3% (-1.9% to -0.6%)) at baseline in the two <45 years cohorts, and with lower FEV1 (-70 mL (-112 to -27 mL)) and FEV1/VC (-1.8% (-2.6% to -1.0%)) in the two ≥45 years cohorts. Elevated blood eosinophils were associated with an accelerated decline in FEV1 (-5.5 mL·year-1 (95% CI -10.5 to -0.5 mL·year-1)) and VC (-6.4 mL·year-1 (-11.26 to -1.5 mL·year-1)) compared to normal blood eosinophils in the younger asthmatic subjects in the longitudinal studies. CONCLUSION: Elevated blood eosinophils are associated with lower lung function in the general population and with an accelerated lung function decline among asthmatic individuals.

Systemic and breath biomarkers for asthma: an update.

PURPOSE OF REVIEW: Finding suitable biomarkers to phenotype asthma, identify individuals at risk of worsening and guide treatment is highly prioritized in asthma research. We aimed to provide an analysis of currently used and upcoming biomarkers, focusing on developments published in the past 2 years. RECENT FINDINGS: Type 2 inflammation is the most studied asthma mechanism with the most biomarkers in the pipeline. Blood eosinophils and fractional exhaled nitric oxide (FeNO) are those most used clinically. Recent developments include their ability to identify individuals at higher risk of exacerbations, faster decline in lung function and more likely to benefit from anti-IL-5 and anti-IL-4/-13 treatment. Certain patterns of urinary eicosanoid excretion also relate to type 2 inflammation. Results of recent trials investigating the use of serum periostin or dipeptidyl peptidase-4 to guide anti-IL-13 therapy were somewhat disappointing. Less is known about non-type 2 inflammation but blood neutrophils and YKL-40 may be higher in patients with evidence of non-type 2 asthma. Volatile organic compounds show promise in their ability to distinguish both eosinophilic and neutrophilic asthma. SUMMARY: The ultimate panel of biomarkers for identification of activated inflammatory pathways and treatment strategies in asthma patients still lies in the future, particularly for non-type 2 asthma, but potential candidates are available.

Fixed airflow obstruction relates to eosinophil activation in asthmatics.

BACKGROUND: Some asthmatics develop irreversible chronic airflow obstruction, for example, fixed airflow obstruction (fixed-AO). This is probably a consequence of airway remodelling, but neither its relation to inflammation nor which asthma biomarkers can be clinically useful are elucidated. We hypothesized that the presence of type 2 inflammation relates to fixed-AO. OBJECTIVES: To evaluate the presence of four markers for type 2 inflammation in fixed airflow obstruction among asthmatics. METHODS: This was a cross-sectional study of 403 participants with asthma, aged 17-75 years, from three Swedish centres. Fixed airflow obstruction was defined as forced expiratory volume during the first second (FEV1 ) over forced vital capacity (FVC) being below the lower limit of normal (LLN). The following type 2 inflammation markers were assessed: exhaled nitric oxide (FeNO), serum periostin, serum eosinophil cationic protein (S-ECP), and urinary eosinophil-derived neurotoxin (U-EDN). RESULTS: Elevated U-EDN (values in the highest tertile, ≥65.95 mg/mol creatinine) was more common in subjects with fixed-AO vs. subjects without fixed-AO: 55% vs. 29%, P < 0.001. Elevated U-EDN related to increased likelihood of having fixed-AO in both all subjects and never-smoking subjects, with adjusted (adjusted for sex, age group, use of inhaled corticosteroids last week, atopy, early-onset asthma, smoking history, and packyears) odds ratios (aOR) of 2.38 (1.28-4.41) and 2.51 (1.04-6.07), respectively. In a separate analysis, having both elevated S-ECP (>20 µg/L) and U-EDN was related to having the highest likelihood of fixed-AO (aOR (95% CI) 6.06 (2.32-15.75)). Elevated serum periostin or FeNO did not relate to fixed-AO. CONCLUSIONS AND CLINICAL RELEVANCE: These findings support that type 2 inflammation, and in particular eosinophil inflammation, is found in asthma with fixed-AO. This could indicate a benefit from eosinophil-directed therapies. Further longitudinal studies are warranted to investigate causality and relation to lung function decline.