Roxana Mincheva

Background: As a surrogate for eosinophilic activation, eosinophil‐derived neurotoxin (EDN) is a potential clinical biomarker. However, EDN levels and discriminatory ability in different asthma phenotypes are unknown. We quantified serum and nasal lavage fluid (NLF) EDN levels and assessed the potential to differentiate clinically defined asthma phenotypes in an adult‐representative sample. Methods: A total of 1499 serum and 386 NLF samples from individuals with current asthma obtained from the West Sweden Asthma Study were analyzed for EDN. Eosinophilic asthma was defined as blood eosinophil count of ≥ 300 cells/mm ³ , T2‐high asthma was defined as blood eosinophil count of ≥ 300 cells/mm ³ or fractional exhaled nitric oxide (FeNO) levels of ≥ 25 ppb. Other asthma phenotypes were defined based on presence of atopy, chronic rhinosinusitis (CRS), nasal polyposis, and obesity. Results: Subjects with eosinophilic asthma had higher serum and NLF EDN levels than those with non‐eosinophilic asthma. In ROC analyses, serum EDN provided excellent discrimination between eosinophilic and non‐eosinophilic asthma (area under curve [AUC] = 0.84, 95% CI = 0.82–0.86); the corresponding AUC for NLF EDN was 0.67 (95% CI = 0.62–0.73). Serum and NLF EDN were higher in atopic asthma, T2‐high asthma, and asthma with nasal polyposis compared to their counterparts, but not in asthma with CRS. The highest absolute values of serum and NLF EDN were observed in the high eosinophil + FeNO group, followed by the high‐eosinophil‐only and high‐FeNO‐only groups. Conclusion: Both serum and NLF EDN were higher in those with eosinophilic compared to non‐eosinophilic asthma. However, only serum EDN appears to distinguish eosinophilic asthma in ROC analyses.

Background: Sex differences have been reported in the incidence, prevalence and severity of asthma. Previous findings from animal models have revealed sex‐related differences in inflammatory pathways that may contribute to asthma pathogenesis, but human studies are limited.Methods: Airway and blood samples (n = 55 and n = 85 respectively) were collected from adult females and males with asthma and healthy subjects. Type 2 innate lymphoid cells (ILC2s), T helper (Th)2 cells and their expression of IL‐33R/ST2 (ST2L) were evaluated by flow cytometry. IL‐13, thymic stromal lymphopoietin (TSLP), IL‐33 and soluble IL‐33R/ST2 (sST2) were measured by ELISA. Let‐7 miRNA expression in bronchial biopsies was determined by qPCR.Results: Females with asthma reported more exacerbations and had a higher number of airway eosinophils compared with males with asthma. Bronchial biopsy expression of Let‐7f, Let‐7g and miR‐98 tended to be higher in males with asthma compared with females and inversely correlated with asthma exacerbations. In contrast, increased levels of IL‐13, TSLP and sST2 were found in females with asthma compared with males.Conclusion: Our study demonstrates different inflammatory signatures between males and females with asthma. Let‐7 miRNAs act as immune modulators by inhibiting the production of IL‐13 and may be an important factor explaining the sex disparity seen in asthma.

Objective: Although asthma and chronic obstructive pulmonary disease (COPD) have been regarded as distinct conditions, emerging literature suggests that overlapping phenotypes, called asthma-COPD overlap (ACO), exists. The aim of this study was to describe prevalence, patient characteristics and morbidity of ACO. Methods: From a cross-sectional population sample, the West Sweden Asthma Study, subjects with suspected asthma, chronic bronchitis or COPD, and a random sample, were invited to clinical examinations. ACO was defined as doctor-diagnosed asthma, or clear clinical signs of asthma at examination, with a FEV1/FVC < 0.7. Results: Subjects were categorized as ACO (N = 181), COPD only (N = 89), asthma only (N = 651) or healthy (n = 1036) based on clinical examinations. Prevalence of ACO was 3.4% in the random sample (N = 1172) and 18.1% among asthmatics (N = 138) in the random sample. Subjects with ACO (mean age 59 years, 54% women) had an age and gender distribution in between asthma only (45 years, 63% women) and COPD only (62 years, 41% women). Ever-smoking was reported by 71%, 48% and 74% in the ACO, asthma only and COPD only groups, respectively. Subjects with ACO had worse lung function (mean FEV1% of predicted normal 76%) than asthma only (100%) and COPD only (87%) and reported more respiratory symptoms. Also respiratory related emergency visits were more common in ACO compared to asthma only and COPD only, respectively. Conclusions: ACO is present in 3.4% of the population and common among subjects with both asthma and COPD. Subjects with ACO had worse lung function and more symptoms than subjects with asthma or COPD only.

Atopic diseases including asthma, rhinitis and eczema have increased in the second half of the past century. This has been well studied among children and adolescents but with the exception of asthma to a much lesser extent in adults. The adult risk factor pattern of atopic diseases, in particular of eczema, and their relation to allergic sensitization are yet to be fully elucidated. Studies among adults that have compared the risk factor pattern for these conditions in the same material are very few. The objective of this study was to compare the risk factor patterns for asthma, rhinitis and eczema in a randomly selected adult population. A questionnaire survey on atopic diseases was dispatched by mail to 30,000 randomly selected individuals in West Sweden aged 16–75 years and 62 % participated. A subgroup of 2000 individuals was selected for clinical examinations including blood sampling for specific serum Immunoglobulin E to common airborne allergens and 1172 attended. The prevalence of current asthma was 11.8 %, current rhinitis 42.8 %, current eczema 13.5 and 2.3 % had all three conditions while 13.9 % had at least two conditions. No mutual risk factor was identified for all three conditions. Allergic sensitization was a strong risk factor for current asthma (OR 4.1 CI 2.7–6.3) and current rhinitis (OR 5.1 CI 3.8–6.9) but not so for current eczema. Obesity was a risk factor for current asthma and current rhinitis, while farm childhood decreased the risk for current asthma and current rhinitis. Occupational exposure to gas dust or fumes and female sex was associated with an increased risk of current asthma and current eczema. There are different risk factor patterns for asthma, rhinitis and eczema in adults but some risk factors are overlapping between some of the conditions. The effect of mutable risk factors should be assessed further in longitudinal studies.

Asthma is a complex disease presenting with variable symptoms which are sometimes hard to control. The purpose of the study was to describe the prevalence of asthma symptoms, use of asthma medications and allergic sensitization in subjects with asthma. We also related those indices to the level of asthma control, lung function and in particular, cough. An extensive questionnaire was sent to randomly selected adults from the West Sweden region. Clinical examinations and interview were performed in a subset. Of the participants, 744 were defined as having an ongoing asthma - reported ever having asthma or physician diagnosed asthma and one of the following – use of asthma medications, recurrent wheeze or attacks of shortness of breath with or without wheeze in the last 12 months. A respiratory disease-free control group of 847 subjects was also described. According to GINA guidelines, 40.6% of the asthmatics had partly controlled and 17.8% had uncontrolled asthma. Asthmatic subjects reported significantly more symptoms in the last 12 months than the control group – wheezing (79.4 vs 9.2%), shortness of breath (36.1 vs 2.5%), wheezing with shortness of breath (58.7 vs 1.3%). Important complaints were morning cough (42.5 vs 15.5%), cough with sputum production (36.1 vs 6.8%) and longstanding cough (32.5 vs 11.1%), which bothered two thirds of the uncontrolled and one third of partly controlled subjects. Asthma medications were used by 87.5% of the asthmatics, although around 30% of them who had insufficiently controlled disease used only short-acting beta-agonists. Asthmatics also had lower lung function, reacted to lower doses of methacholine that the controls and 13.6% of them had a FEV1/FVC ratio below 0.7. Allergic rhinitis was reported by 73.8% of the asthmatics and they were more frequently sensitized to several common allergens. Approximately 60% of asthmatics from this population-based study had insufficiently controlled asthma and persistent complaints, despite a high use of asthma medications. These self-reported symptoms were supported by clinical examination data. Increased cough frequency is an indicator of a more severe and difficult to control disease and should be considered when asthma is characterized.

Different conditions make the proximal airways susceptible to tussigenic stimuli in the chronic cough (CC) syndrome. Leukotrienes can be implicated in the inflammatory mechanism at play in it. Montelukast is a selective cysteinyl-leukotriene receptor antagonist with proven effectiveness in patients with asthma. The aim of our real-life pilot study was to use montelukast to relieve cough symptoms in patients with CC allegedly due to the two frequent causes other than asthma – upper airway cough syndrome and gastroesophageal reflux (GER).