Allergic sensitisation and type-2 inflammation is associated with new-onset and persistent allergic disease.

BACKGROUND: Allergic disease is common. The aim of this study was to look at the change in asthma and rhinitis over time and to characterise factors contributing to remission and persistence of disease. METHODS: This cohort study included 255 individuals with or without asthma and or rhinitis that participated in a population survey and a follow-up 10 years later. The participants were tested for allergic sensitisation, total IgE, multiplex allergen component analysis and type-2 inflammatory markers: exhaled nitric oxide (FE NO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). RESULTS: Of the 132 healthy individuals, 112 remained healthy, 16 developed rhinitis, 4 asthma and rhinitis over the 10 years. Out of 82 subjects with rhinitis, 26 went into remission, 53 remained unchanged and 3 developed asthma in addition to rhinitis. None of the 41 participants with asthma and rhinitis went into remission. Subjects with persistent rhinitis and asthma had higher levels of total IgE (odds ratio [OR] 95% confidence interval [CI]: 6.16 [3.05-12.5]) at baseline and after 10 years, and FE NO and ECP at baseline (OR per log unit increase, 95% CI 5.21 [1.20-22.7] and 6.32 [1.52-26.4], respectively), compared with those that remained healthy. Subjects with persistent rhinitis were more likely to be sensitised to grass pollen and had higher total IgE levels than those that went into remission. Individuals with persistent asthma were more likely to be sensitised to tree pollen and furry animals than those with only persistent rhinitis (OR 95% CI: 3.50 [1.29-9.49] and 6.73 [2.00-22.6], respectively). CONCLUSION: IgE sensitisation and total IgE levels are associated with the persistence of rhinitis and asthma. Participants with persistent allergic disease had higher levels of allergen sensitisation and type 2 inflammation markers at baseline than those who remained healthy.

Asthma and asthma-related comorbidity: effects on nocturnal oxygen saturation.

STUDY OBJECTIVES: Nocturnal symptoms are very common in asthma, which is associated with worse sleep quality. The nocturnal oxygen saturation may be decreased in asthma; however, whether this association is dependent on nocturnal asthma symptoms, lung function, coexisting obstructive sleep apnea (OSA), or other asthma-related comorbidities is unknown. The objective of this study was to examine the effects of asthma, OSA, lung function, airway symptoms, and asthma-related comorbidities on the nocturnal oxygen saturation in a cross-sectional community-based population study. METHODS: In total, 395 women and 392 men underwent overnight polysomnography, performed spirometry, and completed questionnaires on airway symptoms and asthma-related comorbidities. RESULTS: Participants with asthma (n = 88) had a lower nocturnal oxygen saturation than those without asthma (93.8% vs 94.3%, P = .01) also after adjusting for comorbidity, age, body mass index, and smoking status (coefficient -0.38; CI -0.67, -0.10; P < .01). The nocturnal oxygen saturation was lower among participants with wheezing, nocturnal chest tightness, fixed airflow limitation, gastroesophageal reflux, obesity, and OSA than in those without these conditions. The associations between lower oxygen saturation and wheezing, forced expiratory volume in 1 second, gastroesophageal reflux, and apnea-hypopnea index were significant also after adjusting for age, sex, body mass index, and smoking status. Participants with both wheezing and OSA had a significantly lower nocturnal oxygen saturation (92.5 ± 0.5%) than participants with wheezing only (94.3 ± 0.3%) and OSA only (93.6 ± 0.2% %) (P < .01). CONCLUSIONS: Participants with asthma displayed a lower mean oxygen saturation during sleep, which could not be explained only by coexisting OSA or obesity. Also, asthma symptoms and lung function were associated with lower nocturnal oxygen saturation. The lower oxygen saturation seen in asthma is hence multifactorial in origin and is a result of the combination of symptoms, lung function, and comorbidity. CITATION: Sundbom F, Janson C, Ljunggren M, Lindberg E. Asthma and asthma-related comorbidity: effects on nocturnal oxygen saturation. J Clin Sleep Med. 2022;18(11):2635-2641.

Health-related quality of life as associated with asthma control, psychological status and insomnia.

Background: Asthma is associated not only with lower health-related quality of life (HRQL) but also with psychological health and insomnia. The aim of this study was to investigate associations between HRQL, asthma symptoms, psychological status and insomnia in adults from three Nordic countries. Methods: This study comprised 2,270 subjects aged 29-55 from Sweden, Iceland and Norway. HRQL was measured with the 36-Item Short Form Health Survey (SF-36). The physical (PCS) and mental health (MCS) component scores were calculated with higher values, indicating better health status. Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Insomnia was assessed with the Basic Nordic Sleep Questionnaire. An asthma score consisting of a sum of the positive answers to five respiratory symptoms was used in the analysis. Spirometry and allergy tests were also performed. Results: High HADS and sleep disturbance scores were both related to a low PCS and MCS, respectively, after adjusting for confounders. High age and high body mass index (BMI) were associated with low scores on the PCS, whilst the opposite was found for the MCS. A higher asthma score was related to a low PCS. An interaction between the HADS and the asthma symptom score was observed for the PCS (P = 0.0002), where associations between psychological status and the PCS were more pronounced for individuals with more symptoms than for individuals without symptoms. Conclusions: In this study, we found that HRQL of life was independently related to the HADS, insomnia and asthma symptoms. Further prospective studies to identify the most efficient target for intervention in order to improve asthma control are needed.

Multimorbidity in asthma, association with allergy, inflammatory markers and symptom burden, results from the Swedish GA2 LEN study.

BACKGROUND: Asthma is common worldwide and a large part of subjects with asthma have concomitant allergic multimorbidity in the form of rhinitis and/or eczema. OBJECTIVE: The aim of this study is to investigate whether the presence of allergic multimorbidity in asthma relates to allergic sensitization, allergic and respiratory symptoms, quality of life, inflammatory markers, lung function, use of medication and background factors. METHODS: A total of 437 asthmatics from the (GA2 LEN) cross-sectional survey in Sweden were grouped depending on the presence of rhinitis and/or eczema. The impact of allergic multimorbidity was assessed in terms of allergic sensitization, allergic and respiratory symptoms, quality of life, type-2 inflammatory markers (exhaled nitric oxide, eosinophil activation markers, periostin), lung function, use of medication and background factors. RESULTS: Subjects with asthma, rhinitis and eczema were more likely to be sensitized to seasonal allergens (67% vs 32%, P < .001), food allergens (54% vs 18%, P < .001) and to have a higher degree of sensitization than subjects with only asthma (23% vs 10%, P < .001). Subjects with allergic multimorbidity more often had allergic reactions to food (28% vs 10%, P = .002), more respiratory symptoms and anxiety/depression (40% vs, 14%, P < .001) than subjects with only asthma, despite having similar levels of type 2 inflammatory markers. Individuals with allergic multimorbidity were more likely to be diagnosed with asthma before the age of 12 (48% vs 27%, P = .016) and to have maternal heredity for allergy (53% vs 33%, P = .011) than subjects with only asthma. CONCLUSION AND CLINICAL RELEVANCE: Asthmatics with allergic multimorbidity are more likely to be sensitized to seasonal aeroallergens, food allergens and they have a higher degree of sensitization compared with those with only asthma. Allergic multimorbidity is associated with respiratory and allergy symptoms, anxiety and/or depression.

Association between lung function decline and obstructive sleep apnoea: the ALEC study.

PURPOSE: To study changes in lung function among individuals with a risk of obstructive sleep apnoea (OSA), and if asthma affected this relationship. METHODS: We used data from the European Community Respiratory Health Survey II and III, a multicentre general population study. Participants answered questionnaires and performed spirometry at baseline and 10-year follow-up (n = 4,329 attended both visits). Subjects with high risk for OSA were identified from the multivariable apnoea prediction (MAP) index, calculated from BMI, age, gender, and OSA symptoms at follow-up. Asthma was defined as having doctor's diagnosed asthma at follow-up. Primary outcomes were changes in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from baseline to follow-up. RESULTS: Among 5108 participants at follow-up, 991 (19%) had a high risk of OSA based on the MAP index. Participants with high OSA risk more often had wheeze, cough, chest tightness, and breathlessness at follow-up than those with low OSA risk. Lung function declined more rapidly in subjects with high OSA risk (low vs high OSA risk [mean ± SD]: FEV1 = - 41.3 ± 24.3 ml/year vs - 50.8 ± 30.1 ml/year; FVC = - 30.5 ± 31.2 ml/year vs - 45.2 ± 36.3 ml/year). Lung function decline was primarily associated with higher BMI and OSA symptoms. OSA symptoms had a stronger association with lung function decline among asthmatics, compared to non-asthmatics. CONCLUSION: In the general population, a high probability of obstructive sleep apnoea was related to faster lung function decline in the previous decade. This was driven by a higher BMI and more OSA symptoms among these subjects. The association between OSA symptoms and lung function decline was stronger among asthmatics.

Study of atopic multimorbidity in subjects with rhinitis using multiplex allergen component analysis.

BACKGROUND: Rhinitis is a common problem within the population. Many subjects with rhinitis also have atopic multimorbidity, such as asthma and eczema. The purpose of this investigation was to compare subjects with only rhinitis to those that have rhinitis, asthma and/or eczema in relation to immunoglobulin E (IgE) sensitization, inflammatory markers, family history, lung function and body mass index (BMI). METHODS: A total of 216 adult subjects with rhinitis from the European Community Respiratory Health Survey II were investigated with multiplex component allergen analysis (103 allergen components), total IgE, C-reactive protein, eosinophilic cationic protein, fractional exhaled nitric oxide and spirometry. Rhinitis, eczema, asthma and parental allergy were questionnaire-assessed. RESULTS: Of the 216 participants with rhinitis, 89 also had asthma and/or eczema. Participants with rhinitis that also had asthma or eczema were more likely to be IgE-sensitized (3.44, odds ratio, OR: 95% CI 1.62-7.30, adjusted for sex, age, mother's allergy, total IgE and forced expiratory volume (FEV1)). The number of IgE-positive components was independently associated with atopic multimorbidity (1.11, OR: 95% Cl 1.01-1.21) adjusted for sex, age, mother's allergy, total IgE and FEV1. When analysing different types of sensitization, the strongest association with atopic multimorbidity was found in participants that were IgE-sensitized both to perennial and seasonal allergens (4.50, OR: 95% CI 1.61-12.5). Maternal allergy (2.75, OR: 95% CI 1.15-4.46), high total IgE (2.38, OR: 95% CI 1.21-4.67) and lower FEV1 (0.73, OR: 95% CI 0.58-0.93) were also independently associated with atopic multimorbidity, while no association was found with any of the other inflammatory markers. CONCLUSION: IgE polysensitization, to perennial and seasonal allergens, and levels of total IgE seem to be the main determinants of atopic multimorbidity in subjects with rhinitis. This indicates that disease-modifying treatment that targets IgE sensitization may be of value when decreasing the risk of developing atopic multimorbidity.

Prevalence of allergic sensitization to storage mites in Northern Europe.

BACKGROUND: Allergic sensitization to storage mites has mostly been related to occupational exposures like farming, grain/cattle handling, whereas for non-occupational settings, storage mite sensitization has been attributed to cross-reactivity with house dust mite (HDM) allergens. OBJECTIVE: We aimed to describe the prevalence of allergic sensitization to storage mites, co-sensitization to HDM allergens and respiratory symptoms in Denmark, Iceland, Norway and Sweden. METHODS: The population comprised of 1180 participants born 1945-1972 of the third follow-up of the population-based cohort European Community Respiratory Health Survey (ECRHS) in Aarhus, Bergen, Reykjavik and Uppsala. A clinical examination included skin prick tests (SPT) to Lepidoglyphus destructor, Tyrophagus putrescentiae, Acarus siro and common inhalant allergens, as well as standardized interviews. RESULTS: 8% were sensitized to HDM and 10% to storage mite, with some variation by study centre: Reykjavik 13%, Bergen 8% and Aarhus 7%. In Uppsala, only L destructor (3%) was measured. Storage mite sensitization was higher among men (11%) than women (8%). Among storage mite sensitized, 44% were also sensitized to HDM. Storage mite sensitization was associated with asthma and nasal allergies, but not with age, education, pet keeping or place of upbringing. CONCLUSIONS AND CLINICAL RELEVANCE: In this Northern European population-based study, allergic sensitization to storage mite was as common as HDM sensitization. Storage mite sensitization was, independently of HDM sensitization, associated with respiratory symptoms and asthma. Our findings suggest that storage mite sensitization should be evaluated with regard to inclusion into the common inhalant allergen panel in Northern Europe.

Insomnia symptoms and asthma control-Interrelations and importance of comorbidities.

BACKGROUND: Insomnia symptoms are common with asthma. The aim of the study was to analyse the associations between insomnia symptoms and asthma control, asthma severity, and asthma-related comorbidity in a community-based population. METHODS: Adults (n = 23 875, ages 18-45) from the community-based LifeGene study answered a questionnaire on insomnia symptoms, airway symptoms, asthma diagnosis, asthma medication, and asthma-related comorbidities (chronic rhinosinusitis, gastro-oesophageal reflux, anxiety, depression, or obesity). RESULTS: Of the participants, 1272 (5.3%) had asthma. The prevalence of any insomnia symptom was higher in participants with uncontrolled asthma (n = 201) than with controlled or partially controlled asthma (32.2% vs 19.9% and 20.1%, respectively, P < .01). There was no significant difference in the prevalence of insomnia symptoms between subjects with controlled asthma and subjects without asthma. Subjects with asthma and any asthma-related comorbidity reported more insomnia symptoms (29.0% vs 22.4%, P < .01) compared to asthmatics without comorbidity. Moreover, the prevalence was highest among subjects reporting both uncontrolled asthma and any asthma-related comorbidity (45.1%, P < .01). Uncontrolled asthma remained significantly associated with insomnia symptoms (OR 1.72 (1.15-2.56)) after adjusting for age, sex, BMI, smoking history, comorbidities, physical activity, and educational level, while medication level was not. Among asthma-related comorbidities, chronic rhinosinusitis (OR 1.62 (1.20-2.19)), obesity (1.87 (1.07-3.25)), and depression (OR 1.85 (1.34-2.55)) were independently associated with insomnia symptoms. CONCLUSION: Uncontrolled asthma was significantly associated with insomnia symptoms, while controlled or partially controlled asthma was not. Asthma-related comorbidity is of great importance, and asthma control seems to be more important than asthma severity for insomnia symptoms.

Sublingual grass allergen specific immunotherapy: a retrospective study of clinical outcome and discontinuation.

BACKGROUND: Sublingual immunotherapy (SLIT) is effective, tolerable, and convenient for many allergic patients. Still, real-world evidence is scarce and the aim of this study is to assess the patient reported outcome of treatment with SLIT against grass pollen allergy in a consecutive patient population. METHODS: Patients (n = 329) who were confirmed to be allergic to timothy grass and had been prescribed SLIT were consecutively enrolled in the study and completed a questionnaire online or in hard copy. RESULTS: 207 (62.9%) patients responded to the questionnaire. The female/male ratio was 105/102 with a mean age of 39 ± 11 years (range 19-70 years). 113 (55%) patients reported they had completed the full 3-year treatment period, 49 (24%) were still on treatment, and 45 (22%) had discontinued treatment prematurely. Respondents who had completed the full treatment period reported that their allergy symptoms in the most recent grass pollen season had improved to a larger extent than subjects still on treatment or discontinuing the treatment prematurely. Improvement of asthma was twice as common among patients who completed compared to discontinued treatment (42 vs. 20%). Younger age (37 ± 12 vs. 41 ± 11 years, p < 0.001) and a higher prevalence of reported oral and/or gastrointestinal side effects (49 vs. 24%, p = 0.02) characterised the group that terminated SLIT. Forgetfulness was the most commonly reported specific reason. CONCLUSION: Treatment perseverance resulted in improved patient reported outcome. Forgetfulness was the most frequently reported reason for discontinuing SLIT treatment against grass pollen allergy.

Effects of Coexisting Asthma and Obstructive Sleep Apnea on Sleep Architecture, Oxygen Saturation, and Systemic Inflammation in Women.

STUDY OBJECTIVES: Both asthma and obstructive sleep apnea (OSA) are strongly associated with poor sleep. Asthma and OSA also have several features in common, including airway obstruction, systemic inflammation, and an association with obesity. The aim was to analyze the effect of asthma, OSA, and the combination of asthma and OSA on objectively measured sleep quality and systemic inflammation. METHODS: Sleep and health in women is an ongoing community-based study in Uppsala, Sweden. Three hundred eighty-four women ages 20 to 70 years underwent overnight polysomnography and completed questionnaires on airway diseases and sleep complaints. C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor α were analyzed. RESULTS: The group with both asthma and OSA had higher CRP, higher IL-6, a longer sleeping time in stage N1 sleep and stage N2 sleep, and less time in stage R sleep than the control group with no asthma or OSA. The group with both asthma and OSA had lower mean oxygen saturation (93.4% versus 94.7%, P = .04) than the group with OSA alone. The results were consistent after adjusting for age, body mass index, and smoking status. Asthma was independently associated with lower oxygen saturation, whereas OSA was not. CONCLUSIONS: Our data indicate that coexisting asthma and OSA are associated with poorer sleep quality and more profound nocturnal hypoxemia than either of the conditions alone. The results are similar to earlier findings related to OSA and chronic obstructive pulmonary disease, but they have not previously been described for asthma.

Chronic Rhinosinusitis Impairs Sleep Quality: Results of the GA2LEN Study.

Study objectives: To analyze the prevalence of sleep problems in subjects with Chronic rhinosinusitis (CRS) and to determine whether the disease severity of CRS affects sleep quality. Methods: Questionnaires were sent to a random sample of 45 000 adults in four Swedish cities. Questions on CRS, asthma, allergic rhinitis, co-morbidities, tobacco use, educational level, and physical activity were included. CRS was defined according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) epidemiological criteria. The disease severity of CRS was defined by the number of reported CRS symptoms. Sleep quality was assessed using the Basic Nordic Sleep Questionnaire. Results: Of the 26 647 subjects, 2249 (8.4%) had CRS. Reported sleep problems were 50%-90% more common among subjects with CRS compared with those without or the total population. The prevalence of reported sleep problems increased in conjunction with the severity of CRS. After adjusting for gender, BMI, age, tobacco use, asthma, somatic diseases, physical activity level, and educational level, participants with four symptoms of CRS (compared with subjects without CRS symptoms) displayed a higher risk of snoring (adj. OR [95% CI]: 3.13 [2.22-4.41]), difficulties inducing sleep (3.98 [2.94-5.40]), difficulties maintaining sleep (3.44 [2.55-4.64]), early morning awakening (4.71 [3.47-6.38]) and excessive daytime sleepiness (4.56 [3.36-6.18]). The addition of persistent allergic rhinitis to CRS further increased the risk of sleep problems. Conclusions: Sleep problems are highly prevalent among subjects with CRS. The disease severity of CRS negatively affects sleep quality.

Effects of poor asthma control, insomnia, anxiety and depression on quality of life in young asthmatics.

OBJECTIVE: Asthma-related quality of life has previously been shown to be associated with asthma control. The aims of the present study were to further analyze this correlation, identify other variables with impact on asthma-related quality of life and investigate the covariance among these variables. METHODS: Information was retrieved from a cohort of 369 patients, aged 12-35, with physician-diagnosed asthma requiring anti-inflammatory treatment for at least 3 months per year. Questionnaire data [including the mini-Asthma Quality of Life Questionnaire (mAQLQ), asthma control test (ACT) and Hospital Anxiety and Depression Scale (HADS)], quality of sleep, lung function data and blood samples were analyzed. Linear regression models with the mAQLQ score as the dependent scalar variable were calculated. RESULTS: ACT was the single variable that had the highest explanatory value for the mAQLQ score (51.5%). High explanatory power was also observed for anxiety and depression (17.0%) and insomnia (14.1%). The population was divided into groups depending on the presence of anxiety and depression, uncontrolled asthma and insomnia. The group that reported none of these conditions had the highest mean mAQLQ score (6.3 units), whereas the group reporting all of these conditions had the lowest mAQLQ score (3.8 units). CONCLUSIONS: The ACT score was the single most important variable in predicting asthma-related quality of life. Combining the ACT score with the data on insomnia, anxiety and depression showed considerable additive effects of the conditions. Hence, we recommend the routine use of the ACT and careful attention to symptoms of insomnia, anxiety or depression in the clinical evaluation of asthma-related quality of life.