Publications by authors named "Christer Janson"

441 Publications

MAIT cell counts are associated with the risk of hospitalization in COPD.

Respir Res 2022 May 18;23(1):127. Epub 2022 May 18.

Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with chronic inflammation in the airways. Mucosal-associated invariant T (MAIT) cells are unconventional, innate-like T cells highly abundant in mucosal tissues including the lung. We hypothesized that the characteristics of MAIT cells in circulation may be prospectively associated with COPD morbidity.

Methods: COPD subjects (n = 61) from the Tools for Identifying Exacerbations (TIE) study were recruited when in stable condition. At study entry, forced expiratory volume in 1 s (FEV) was measured and peripheral blood mononuclear cells were cryopreserved for later analysis by flow cytometry. Patients were followed for 3 years to record clinically meaningful outcomes.

Results: Patients who required hospitalization at one or more occasions during the 3-year follow-up (n = 21) had lower MAIT cell counts in peripheral blood at study inclusion, compared with patients who did not get hospitalized (p = 0.036). In contrast, hospitalized and never hospitalized patients did not differ in CD8 or CD4 T cell counts (p = 0.482 and p = 0.221, respectively). Moreover, MAIT cells in hospitalized subjects showed a more activated phenotype with higher CD38 expression (p = 0.014), and there was a trend towards higher LAG-3 expression (p = 0.052). Conventional CD4 and CD8 T cells were similar between the groups. Next we performed multi-variable logistic regression analysis with hospitalizations as dependent variable, and FEV, GOLD 2017 group, and quantity or activation of MAIT and conventional T cells as independent variables. MAIT cell count, CD38 expression on MAIT cells, and LAG-3 expression on both MAIT and CD8 T cells were all independently associated with the risk of hospitalization.

Conclusions: These findings suggest that MAIT cells might reflect a novel, FEV-independent immunological dimension in the complexity of COPD. The potential implication of MAIT cells in COPD pathogenesis and MAIT cells' prognostic potential deserve further investigation.
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http://dx.doi.org/10.1186/s12931-022-02045-2DOI Listing
May 2022

The effect of the COVID-19 pandemic on severe asthma care in Europe: will care change for good?

ERJ Open Res 2022 Apr 16;8(2). Epub 2022 May 16.

Clinic for Pulmonology, University Clinical Center Kragujevac, Kragujevac, Serbia.

Background: The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care.

Methods: In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021.

Results: 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%).

Conclusions: Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.
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http://dx.doi.org/10.1183/23120541.00065-2022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994963PMC
April 2022

Changes in critical inhaler technique errors in inhaled COPD treatment - A one-year follow-up study in Sweden.

Respir Med 2022 Jun 9;197:106849. Epub 2022 Apr 9.

Department of Pharmacy, Uppsala University, Uppsala, Sweden.

Background: Critical inhaler technique errors have been associated with lower treatment efficacy in chronic obstructive pulmonary disease (COPD). We aimed to assess and follow-up critical inhaler technique errors, and to investigate their association with COPD symptoms and exacerbations.

Methods: COPD-diagnosed primary and secondary care outpatients (n = 310) demonstrated inhaler technique with inhaler devices they were currently using. Critical errors in opening, positioning and loading the inhaler device, and exhalation through dry-powder inhalers were assessed and corrected, and the assessment was repeated one year later. COPD Assessment Test, the modified Medical Research Council dyspnoea scale and history of exacerbations were collected at both visits.

Results: The proportion of patients making ≥1 critical inhaler technique error was lower at follow-up in the total population (46% vs 37%, p = 0.01) and among patients with unchanged device models (46% vs 35%, p = 0.02), but not among patients with a new inhaler device model (46% vs 41%, p = 0.56). Not positioning the device correctly was the most common critical error at both visits (30% and 22%). Seventy-four percent of the patients had unchanged COPD treatment from baseline to follow-up. Treatment escalation, de-escalation, and switch was observed in 14%, 11%, and 1% of the patients, respectively. No association was found between critical errors and COPD symptoms or exacerbations.

Conclusions: Assessment and correction of inhaler technique was associated with a decrease in critical inhaler technique errors. This effect was most pronounced in patients using the same device models throughout the follow-up period.
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http://dx.doi.org/10.1016/j.rmed.2022.106849DOI Listing
June 2022

Long-term effect of asthma on the development of obesity among adults: an international cohort study, ECRHS.

Thorax 2022 Apr 27. Epub 2022 Apr 27.

Non-Communicable Diseases and Environment Programme, ISGlobal, Barcelona, Spain.

Introduction: Obesity is a known risk factor for asthma. Although some evidence showed asthma causing obesity in children, the link between asthma and obesity has not been investigated in adults.

Methods: We used data from the European Community Respiratory Health Survey (ECRHS), a cohort study in 11 European countries and Australia in 3 waves between 1990 and 2014, at intervals of approximately 10 years. We considered two study periods: from ECRHS I () to ECRHS II (), and from ECRHS II () to ECRHS III (). We excluded obese (body mass index≥30 kg/m) individuals at visit . The relative risk (RR) of obesity at associated with asthma at was estimated by multivariable modified Poisson regression (lag) with repeated measurements. Additionally, we examined the association of atopy and asthma medication on the development of obesity.

Results: We included 7576 participants in the period ECRHS I-II (51.5% female, mean (SD) age of 34 (7) years) and 4976 in ECRHS II-III (51.3% female, 42 (8) years). 9% of participants became obese in ECRHS I-II and 15% in ECRHS II-III. The risk of developing obesity was higher among asthmatics than non-asthmatics (RR 1.22, 95% CI 1.07 to 1.38), and particularly higher among non-atopic than atopic (1.47; 1.17 to 1.86 vs 1.04; 0.86 to 1.27), those with longer disease duration (1.32; 1.10 to 1.59 in >20 years vs 1.12; 0.87 to 1.43 in ≤20 years) and those on oral corticosteroids (1.99; 1.26 to 3.15 vs 1.15; 1.03 to 1.28). Physical activity was not a mediator of this association.

Conclusion: This is the first study showing that adult asthmatics have a higher risk of developing obesity than non-asthmatics, particularly those non-atopic, of longer disease duration or on oral corticosteroids.
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http://dx.doi.org/10.1136/thoraxjnl-2021-217867DOI Listing
April 2022

Annual and Post-Exacerbation Follow-Up of Asthma Patients in Clinical Practice - A Large Population-Based Study in Sweden.

J Asthma Allergy 2022 13;15:475-486. Epub 2022 Apr 13.

Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.

Background: Symptom control has not improved in Swedish asthma patients during the last two decades. Guidelines recommend annual reviews for asthma patients treated with maintenance inhaled corticosteroids (ICS). We aimed to describe how visit patterns in an ICS-treated asthma population in Sweden were related to applicable asthma guidelines.

Methods: Swedish electronic health data for incident asthma patients, ≥18 years, with at least one ICS collection (index date) between 2006 and 2017 were included. Exacerbations were defined as hospitalizations, emergency visits, or collection of oral corticosteroids (OCS). Probability of an asthma-related regular follow-up visit and probability of a follow-up visit after an exacerbation, both within 15 months, were estimated using the cumulative incidence function, time-to-event analysis, and incident rate ratios.

Results: In 51,349 asthma patients (mean age 47.6 years, 63% females), 17,573 had a regular asthma visit in primary or secondary care within 15 months after the index, yielding an overall probability of a visit of 37.4%. Patients with a follow-up visit had higher ICS collection and lower OCS collection than patients without regular visits. Among 22,097 patients with acute exacerbations, the probability of a visit within 15 months after an exacerbation was 31.0%. The probability of having a visit increased during the study period.

Conclusion: Only one-third of ICS-treated asthma patients, regardless of asthma severity, had a regular or post-exacerbation follow-up visit within a 15-month period. The consequences of this lack of adherence to guidelines need further evaluation to secure optimal asthma management.
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http://dx.doi.org/10.2147/JAA.S357086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014309PMC
April 2022

Parental Prepuberty Overweight and Offspring Lung Function.

Nutrients 2022 Apr 4;14(7). Epub 2022 Apr 4.

Centre for International Health, Department of Global Public Health and Primary Care, University of Bergen, 5020 Bergen, Norway.

In a recent study we found that fathers' but not mothers' onset of overweight in puberty was associated with asthma in adult offspring. The potential impact on offspring's adult lung function, a key marker of general and respiratory health, has not been studied. We investigated the potential causal effects of parents' overweight on adult offspring's lung function within the paternal and maternal lines. We included 929 offspring (aged 18-54, 54% daughters) of 308 fathers and 388 mothers (aged 40-66). Counterfactual-based multi-group mediation analyses by offspring's sex (potential moderator) were used, with offspring's prepubertal overweight and/or adult height as potential mediators. Unknown confounding was addressed by simulation analyses. Fathers' overweight before puberty had a negative indirect effect, mediated through sons' height, on sons' forced expiratory volume in one second (FEV) (beta (95% CI): -144 (-272, -23) mL) and forced vital capacity (FVC) (beta (95% CI): -210 (-380, -34) mL), and a negative direct effect on sons' FVC (beta (95% CI): -262 (-501, -9) mL); statistically significant effects on FEV/FVC were not observed. Mothers' overweight before puberty had neither direct nor indirect effects on offspring's lung function. Fathers' overweight starting before puberty appears to cause lower FEV and FVC in their future sons. The effects were partly mediated through sons' adult height but not through sons' prepubertal overweight.
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http://dx.doi.org/10.3390/nu14071506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9002985PMC
April 2022

Environmental Sustainability in Respiratory Care: An Overview of the healthCARe-Based envirONmental Cost of Treatment (CARBON) Programme.

Adv Ther 2022 May 13;39(5):2270-2280. Epub 2022 Mar 13.

Hull York Medical School, Hull, UK.

Introduction: Faced with the challenges of climate change, countries are seeking to decarbonise their economies. A greater understanding of what comprises the carbon footprint of care in healthcare systems will identify potential strategies for reduction of greenhouse gas (GHG) emissions. In respiratory care, the focus has been on preventer inhalers, thereby omitting contributions from other aspects such as healthcare resource utilisation (HCRU) and reliever inhaler use. The healthCARe-Based envirONmental cost of treatment (CARBON) programme aims to provide a broader understanding of the carbon footprint associated with respiratory care.

Methods: CARBON will quantify the carbon footprint of medications and HCRU among approximately 2.5 million patients with respiratory diseases from seven ongoing studies spanning more than 40 countries. Across studies, to obtain the carbon footprint of all inhaled, oral, and injectable medications, SimaPro life cycle assessment software modelling resource and energy consumption data, in addition to Ecoinvent data sets and certified published studies, will be used. The carbon footprint of HCRU in the United Kingdom will be estimated by applying the methodology and data obtained from the Sustainable Healthcare Coalition Care Pathway Guidance.

Planned Outcomes: In asthma, CARBON studies will quantify GHG emissions associated with well-controlled versus not well-controlled asthma, the contribution of short-acting β-agonist (SABA) reliever inhalers (and their potential overuse) to the carbon footprint of care, and how implementation of treatment guidelines can drive improved outcomes and footprint reduction. In chronic obstructive pulmonary disease (COPD), CARBON studies will assess the impact of exacerbation history on GHG emissions associated with HCRU and SABA use in subsequent years and estimate the carbon footprint associated with all aspects of COPD care.

Conclusion: CARBON aims to show that the principle of evidence-led care focused on improvement of clinical outcomes has the potential to benefit patients and the environment.
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http://dx.doi.org/10.1007/s12325-022-02076-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9056443PMC
May 2022

Eosinophilic airway diseases: basic science, clinical manifestations and future challenges.

Eur Clin Respir J 2022 2;9(1):2040707. Epub 2022 Mar 2.

Department of Respiratory Medicine, Bispebjerg Hospital and Copenhagen University, Copenhagen, Denmark.

Eosinophils have a broad range of functions, both homeostatic and pathological, mediated through an array of cell surface receptors and specific secretory granules that promote interactions with their microenvironment. Eosinophil development, differentiation, activation, survival and recruitment are closely regulated by a number of type 2 cytokines, including interleukin (IL)-5, the key driver of eosinophilopoiesis. Evidence shows that type 2 inflammation, driven mainly by interleukin (IL)-4, IL-5 and IL-13, plays an important role in the pathophysiology of eosinophilic airway diseases, including asthma, chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Several biologic therapies have been developed to suppress type 2 inflammation, namely mepolizumab, reslizumab, benralizumab, dupilumab, omalizumab and tezepelumab. While these therapies have been associated with clinical benefits in a range of eosinophilic diseases, their development has highlighted several challenges and directions for future research. These include the need for further information on disease progression and identification of treatable traits, including clinical characteristics or biomarkers that will improve the prediction of treatment response. The Nordic countries have a long tradition of collaboration using patient registries and Nordic asthma registries provide unique opportunities to address these research questions. One example of such a registry is the NORdic Dataset for aSThmA Research (NORDSTAR), a longitudinal population-based dataset containing all 3.3 million individuals with asthma from four Nordic countries (Denmark, Finland, Norway and Sweden). Large-scale, real-world registry data such as those from Nordic countries may provide important information regarding the progression of eosinophilic asthma, in addition to clinical characteristics or biomarkers that could allow targeted treatment and ensure optimal patient outcomes.
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http://dx.doi.org/10.1080/20018525.2022.2040707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8896196PMC
March 2022

Risk Factors for the Absence of Diagnosis of Asthma Despite Disease Symptoms: Results from the Swedish GA2LEN Study.

J Asthma Allergy 2022 9;15:179-186. Epub 2022 Feb 9.

Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.

Background: Asthma is a common chronic disease presenting with airway symptoms such as wheezing, chest tightness and attacks of breathlessness. Underdiagnosis of asthma is common and correlates to negative outcomes such as a lower quality of life and reduced work capacity.

Purpose: This study aims to identify factors for not being diagnosed with asthma if presenting with asthma symptoms.

Patients And Methods: A questionnaire was sent to 45,000 subjects (age 16-74 years) in Sweden. Subjects who reported both wheeze and breathlessness and wheeze when not having a cold were defined as having asthma-related symptoms. Data on demographics, educational level, smoking, physical activity, comorbidities, symptoms and asthma were collected. Logistic regression was used to identify risk factors for not being diagnosed with asthma.

Results: Of the 25,391 who responded to the survey, 6.2% reported asthma-related symptoms. Of these, 946 had been diagnosed with asthma previously, while 632 had not. Independent risk factors for not being diagnosed with asthma were higher age (OR (95% CI) (2.17 (1.39-3.40))), male sex (1.46 (1.17-1.81)), current smoking (2.92 (2.22-3.84)), low level of education (1.43 (1.01-2.01)), low physical activity (1.36 (1.06-1.74)), and hypertension (1.50 (1.06-2.12)).

Conclusion: Men, smokers, older subjects, and those with low educational level or low physical activity are less likely to be diagnosed with asthma despite presenting asthma-related symptoms.
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http://dx.doi.org/10.2147/JAA.S350245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842640PMC
February 2022

Effects of switching from a metered dose inhaler to a dry powder inhaler on climate emissions and asthma control: post-hoc analysis.

Thorax 2022 Feb 7. Epub 2022 Feb 7.

Respiratory Therapy Area, GlaxoSmithKline R&D, Brentford, UK.

Objective: To compare the effects of switching from a pressurised metered dose inhaler (pMDI)-based to a dry powder inhaler (DPI)-based maintenance therapy versus continued usual care on greenhouse gas emissions (carbon dioxide equivalents, COe) and asthma control.

Methods: This post-hoc analysis was based on a subset of 2236 (53%) patients from the Salford Lung Study in Asthma who at baseline were using a pMDI-based controller therapy. During the study patients were randomised to fluticasone furoate/vilanterol (FF/VI) via the ELLIPTA DPI (switched from pMDI to DPI) (n=1081) or continued their usual care treatment (n=1155), and were managed in conditions close to everyday clinical practice. Annual COe (kg) was calculated for the total number of maintenance and rescue inhalers prescribed. Asthma control was assessed by the proportion of ACT responders (composite of ACT total score ≥20 and/or increase from baseline ≥3).

Results: The groups were well matched for demographic characteristics and baseline Asthma Control Test (ACT) total score (mean age: 49 years; mean ACT score: usual care, 16.6; FF/VI, 16.5). Annual COe kg per patient (maintenance plus rescue therapy) was significantly lower with FF/VI DPI treatment ('switch' group) than usual care (least squares geometric mean 108 kg (95% CI 102 to 114) vs 240 kg (95% CI 229 to 252), p<0.001). Asthma control was consistently superior over the 12 months in the FF/VI DPI group compared with usual care.

Conclusions: Patients switching from a pMDI-based to a DPI-based maintenance therapy more than halved their inhaler carbon footprint without loss of asthma control. The remaining inhaler carbon footprint could be reduced through switches from pMDI to DPI rescue medications or alternative lower-carbon footprint rescue inhalers if available. Asthma control improved in both groups, with greater control demonstrated in those initiated on FF/VI DPI.

Trial Registration Number: NCT01706198.
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http://dx.doi.org/10.1136/thoraxjnl-2021-218088DOI Listing
February 2022

Allergies and COVID-19 vaccines: An ENDA/EAACI Position paper.

Allergy 2022 Feb 2. Epub 2022 Feb 2.

Allergy Research Group, Allergy Unit, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga-IBIMA, Plaza del Hospital Civil s/n, Málaga, Spain.

Background: Anaphylaxis, which is rare, has been reported after COVID-19 vaccination, but its management is not standardized.

Method: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed.

Results: No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1-anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2-anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine; and 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left-over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable.

Conclusions: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated.
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http://dx.doi.org/10.1111/all.15241DOI Listing
February 2022

Agreement of the modified Medical Research Council and New York Heart Association scales for assessing the impact of self-rated breathlessness in cardiopulmonary disease.

ERJ Open Res 2022 Jan 24;8(1). Epub 2022 Jan 24.

Lund University, Faculty of Medicine, Dept of Clinical Sciences Lund, Respiratory Medicine and Allergology, Lund, Sweden.

Background: The functional impact of breathlessness is assessed using the modified Medical Research Council (mMRC) scale for chronic respiratory disease and with the New York Heart Association Functional Classification (NYHA) scale for heart failure. We evaluated agreement between the scales and their concurrent validity with other clinically relevant patient-reported outcomes in cardiorespiratory disease.

Methods: Outpatients with stable chronic respiratory disease or heart failure were recruited. Agreement between the mMRC and NYHA scales was analysed using Cramér's V and Kendall's tau B tests. Concurrent validity was evaluated using correlations with clinically relevant measures of breathlessness, anxiety, depression, and health-related quality of life. Analyses were conducted for all participants and separately in chronic obstructive pulmonary disease (COPD) and heart failure.

Results: In a total of 182 participants with cardiorespiratory disease, the agreement between the mMRC and NYHA scales was moderate (Cramér's V: 0.46; Kendall's tau B: 0.57) with similar results for COPD (Cramér's V: 0.46; Kendall's tau B: 0.66) and heart failure (Cramér's V: 0.46; Kendall's tau B: 0.67). In the total population, the scales correlated in similar ways to other patient-reported outcomes.

Conclusion: In outpatients with cardiorespiratory disease, the mMRC and NYHA scales show moderate to strong correlations and similar associations with other patient-reported outcomes. This supports that the scales are comparable when assessing the impact of breathlessness on function and patient-reported outcomes.
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http://dx.doi.org/10.1183/23120541.00460-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784890PMC
January 2022

[Pharmacological treatment reduces mortality in COPD].

Lakartidningen 2022 01 12;119. Epub 2022 Jan 12.

professor, överläkare, lung-, allergi- och sömnforskning, institutionen för medicins-ka vetenskaper; båda Uppsala universitet.

Approximately 500 000 individuals in Sweden have chronic obstructive pulmonary disease (COPD). Co-morbid, especially cardiovascular, conditions are common in COPD and globally COPD is the third most common cause of mortality. Mortality in COPD is driven by dyspnea, exacerbations and comorbidities and is reduced by smoking cessation and lung rehabilitation. Also, pharmacological treatment, in particular inhaled corticosteroids, reduces mortality in COPD. The reduction in mortality that can be achieved by treatment with inhaled corticosteroids in combinations with long-acting bronchodilators is of the same order of magnitude as the effect on mortality by treatment of hyperlipidemia and hypertension.
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January 2022

Neutrophil-to-lymphocyte ratio, blood eosinophils and COPD exacerbations: a cohort study.

ERJ Open Res 2021 Oct 27;7(4). Epub 2021 Dec 27.

Dept of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.

Background: Blood neutrophil-to-lymphocyte ratio (NLR) and blood eosinophils (B-Eos) are emerging biomarkers in COPD. This study examined whether they could predict acute exacerbations of COPD (AECOPDs), and determined their longitudinal stability.

Methods: In this closed cohort study, Swedish subjects with spirometry-verified COPD attended three yearly visits in a stable phase of the disease. Blood cell counts, spirometry and questionnaire-assessed AECOPD-history (worsening of COPD leading to an unscheduled visit and/or use of antibiotics and/or oral corticosteroids) were collected at each visit.

Results: Of 466 included subjects 57% were female. Baseline mean±sd forced expiratory volume in 1 s was 58±17% predicted. High NLR (≥3.0) was more common in subjects with previous AECOPDs than in those without (33.5% 20.4%, p=0.002). In two-level mixed-effects logistic regression models adjusted for confounders, NLR as a continuous variable (OR 1.20, 95% CI 1.04-1.38) and B-Eos ≥300 cells·µL (OR 1.54, 95% CI 1.06-2.24) were associated with future AECOPDs. In 386 subjects with blood cell data available at all three visits, the intraclass correlation coefficient for NLR was 0.61 (95% CI 0.56-0.66) and for B-Eos 0.69 (95% CI 0.64-0.73). NLR was persistently ≥3.0 in 10.6% and B-Eos was persistently ≥300 cells·µL in 15.3%.

Conclusions: Stable phase NLR and B-Eos were associated with future AECOPDs. NLR on its own is probably not useful to predict AECOPDs but might be included in a risk scoring index. A minority of subjects with COPD had persistently elevated stable-phase NLR or B-Eos, and the biomarkers showed fair longitudinal reliability.
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http://dx.doi.org/10.1183/23120541.00471-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8711083PMC
October 2021

COPD - do the right thing.

BMC Fam Pract 2021 12 11;22(1):244. Epub 2021 Dec 11.

Integrative Toxicology, National Institute of Environmental Medicine, IMM, Karolinska Institutet, Stockholm, Sweden.

A gap exists between guidelines and real-world clinical practice for the management and treatment of chronic obstructive pulmonary disease (COPD). Although this has narrowed in the last decade, there is room for improvement in detection rates, treatment choices and disease monitoring. In practical terms, primary care practitioners need to become aware of the huge impact of COPD on patients, have non-judgemental views of smoking and of COPD as a chronic disease, use a holistic consultation approach and actively motivate patients to adhere to treatment.This article is based on discussions at a virtual meeting of leading Nordic experts in COPD (the authors) who were developing an educational programme for COPD primary care in the Nordic region. The article aims to describe the diagnosis and lifelong management cycle of COPD, with a strong focus on providing a hands-on, practical approach for medical professionals to optimise patient outcomes in COPD primary care.
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http://dx.doi.org/10.1186/s12875-021-01583-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666021PMC
December 2021

Different components of excessive daytime sleepiness and the change with positive airway pressure treatment in patients with obstructive sleep apnea: Results from the Icelandic Sleep Apnea Cohort (ISAC).

J Sleep Res 2022 Jun 3;31(3):e13528. Epub 2021 Dec 3.

Division of Sleep Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Excessive daytime sleepiness includes both an inability to stay awake during the day and a general feeling of sleepiness. We describe different dimensions of daytime sleepiness in adults with moderate-severe obstructive sleep apnea (OSA) before and after 2 years of positive airway pressure (PAP) treatment. Using the Epworth Sleepiness Scale (score >10 defined as "risk of dozing") and Basic Nordic Sleep Questionnaire (feeling sleepy ≥3 times/week defined as "feeling sleepy"), participants were categorised into sleepiness phenotypes labelled non-sleepy, risk of dozing only, feeling sleepy only, or both symptoms. Participants repeated baseline assessments and PAP adherence was evaluated after 2 years. PAP-adherent subjects with sleepiness symptoms at both baseline and follow-up were considered persistently sleepy. Of the 810 participants, 722 (89%) returned for follow-up. At baseline, 17.7% were non-sleepy, 7.7% were at risk of dozing only, 24.7% were feeling sleepy only, and 49.9% had both symptoms. PAP adherence did not differ by baseline sleepiness phenotype. Patients with risk of dozing demonstrated greater PAP benefits for sleepiness symptoms than non-sleepy and feeling sleepy only phenotypes. Using these phenotypes, 42.3% of PAP users had persistent sleepiness; they had less severe OSA (p < 0.001), more persistent OSA symptoms and more often had symptoms of insomnia than patients in whom sleepiness resolved. Our present results, therefore, suggest that measuring the risk of dozing and the feeling of sleepiness reflect different sleepiness components and may respond differently to PAP. Patients feeling sleepy without risk of dozing may need more thorough evaluation for factors contributing to sleepiness before initiating treatment.
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http://dx.doi.org/10.1111/jsr.13528DOI Listing
June 2022

The risk of respiratory tract infections and antibiotic use in a general population and among people with asthma.

ERJ Open Res 2021 Oct 29;7(4). Epub 2021 Nov 29.

Dept of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.

Aim: The aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals.

Method: This study included 15 842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25-54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations.

Results: In the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53-3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18-4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood.

Conclusion: In this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma.
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http://dx.doi.org/10.1183/23120541.00429-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628194PMC
October 2021

Self-reported exercise-induced dyspnea and airways obstruction assessed by oscillometry and spirometry in adolescents.

Pediatr Allergy Immunol 2022 01 9;33(1):e13702. Epub 2021 Dec 9.

Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.

Background: Self-reported exercise-induced dyspnea (EID) is common among adolescents. Possible underlying pathologies are exercise-induced bronchoconstriction (EIB) and laryngeal obstruction (EILO). The forced oscillation technique (FOT) may evaluate exercise-induced changes in airway caliber.

Aim: To investigate in adolescents the relationship between EID, EIB (post-exercise fall in forced expiratory volume in 1s (FEV )≥10%), EILO, and post-exercise challenge changes in FOT parameters.

Methods: One hundred and forty-three subjects (97 with EID) of 13-15 years old underwent a standardized exercise challenge with FOT measurement and spirometry repeatedly performed between 2 and 30 min post-exercise. EILO was studied in a subset of 123 adolescents. Subjects showing greater changes than the healthy subgroup in the modulus of the inspiratory impedance were considered FOT responders.

Results: EID-nonEIB subjects presented similar post-exercise changes in all FOT parameters to nonEID-nonEIB adolescents. Changes in all FOT parameters correlated with FEV fall. 45 of 97 EID subjects responded neither by FEV nor FOT to exercise. 19 and 18 subjects responded only by FEV (onlyFEV responders) or FOT (onlyFOTresponders), respectively. Only a lower baseline forced vital capacity (FVC)%predicted and a higher FEV /FVC distinguished the onlyFEV responders from onlyFOTresponders. FOT parameters did not present specific post-exercise patterns in EILO subjects.

Conclusion: FOT can be used to identify post-exercise changes in lower airway function. However, EID has a modest relation with both FEV and FOT responses, highlighting the need for objective testing. More research is needed to understand whether onlyFEV responders and onlyFOTresponders represent different endotypes.
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http://dx.doi.org/10.1111/pai.13702DOI Listing
January 2022

The negative health effects of having a combination of snoring and insomnia.

J Clin Sleep Med 2022 Apr;18(4):973-981

Department of Medical Sciences, Respiratory, Allergy, and Sleep Research, Uppsala University, Uppsala, Sweden.

Study Objectives: Insomnia and snoring are common sleep disorders. The aim was to investigate the association of having a combination of insomnia symptoms and snoring with comorbidity and daytime sleepiness.

Methods: The study population comprised 25,901 participants (16-75 years, 54.4% women) from 4 Swedish cities, who answered a postal questionnaire that contained questions on snoring, insomnia symptoms (difficulties initiating and/or maintaining sleep and/or early morning awakening), smoking, educational level, and respiratory and nonrespiratory disorders.

Results: Snoring was reported by 4,221 (16.2%), while 9,872 (38.1%) reported ≥ 1 insomnia symptom. A total of 2,150 (8.3%) participants reported both insomnia symptoms and snoring. The association with hypertension (adjusted odds ratio [OR], 1.4; 95% confidence interval [CI], 1.2-1.6), chronic obstructive pulmonary disease (adjusted OR, 1.8; 95% CI, 1.3-2.4), asthma (adjusted OR, 1.9; 95% CI, 1.6-2.3), daytime sleepiness (adjusted OR, 7.9; 95% CI, 7.1-8.8), and the use of hypnotics (adjusted OR, 7.5; 95% CI, 6.1-9.1) was highest for the group with both insomnia symptoms and snoring.

Conclusions: Participants with both snoring and insomnia run an increased risk of hypertension, chronic obstructive pulmonary disease, asthma, daytime sleepiness, and use of hypnotics. It is important to consider snoring in patients seeking medical assistance for insomnia and, vice versa, in patients with snoring inquiring about insomnia.

Citation: Hägg SA, Ilieva E, Ljunggren M, et al. The negative health effects of having a combination of snoring and insomnia. . 2022;18(4):973-981.
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http://dx.doi.org/10.5664/jcsm.9764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8974365PMC
April 2022

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA²LEN position paper.

Allergy 2021 Nov 6. Epub 2021 Nov 6.

Section of Allergology and Clinical Immunology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.

Background: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin.

Methods: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results.

Results: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds.

Conclusion: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.
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http://dx.doi.org/10.1111/all.15167DOI Listing
November 2021

Swallowing dysfunction in patients hospitalised due to a COPD exacerbation.

ERJ Open Res 2021 Oct 25;7(4). Epub 2021 Oct 25.

Centre for Research and Development, Uppsala University/Region Gävleborg, Uppsala, Sweden.

https://bit.ly/3mFKNq1.
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http://dx.doi.org/10.1183/23120541.00515-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542964PMC
October 2021

Maternal preconception occupational exposure to cleaning products and disinfectants and offspring asthma.

J Allergy Clin Immunol 2022 01 18;149(1):422-431.e5. Epub 2021 Oct 18.

Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway; Centre for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.

Background: Emerging research suggests health effects in offspring after parental chemical exposures before conception. Many future mothers are exposed to potent chemicals at work, but potential offspring health effects are hardly investigated.

Objective: We sought to investigate childhood asthma in relation to mother's occupational exposure to cleaning products and disinfectants before conception.

Methods: The multicenter Respiratory Health In Northern Europe/Respiratory Health In Northern Europe, Spain and Australia generation study investigated asthma and wheeze starting at age less than 10 years in 3318 mother-offspring pairs. From an asthma-specific Job-Exposure Matrix and mothers' occupational history, we defined maternal occupational exposure to indoor cleaning agents (cleaning products/detergents and disinfectants) starting before conception, in the 2-year period around conception and pregnancy, or after birth. Never-employed mothers were excluded. Exposed groups include cleaners, health care workers, cooks, and so forth. Associations were analyzed using mixed-effects logistic regression and ordinary logistic regression with clustered robust SEs and adjustment for maternal education.

Results: Maternal occupational exposure to indoor cleaning starting preconception and continuing (n = 610) was associated with offspring's childhood asthma: odds ratio 1.56 (95% CI, 1.05-2.31), childhood asthma with nasal allergies: 1.77 (1.13-2.77), and childhood wheeze and/or asthma: 1.71 (95% CI, 1.19-2.44). Exposure starting around conception and pregnancy (n = 77) was associated with increased childhood wheeze and/or asthma: 2.25 (95% CI, 1.03-4.91). Exposure starting after birth was not associated with asthma outcomes (1.13 [95% CI, 0.71-1.80], 1.15 [95% CI, 0.67-1.97], 1.08 [95% CI, 0.69-1.67]).

Conclusions: Mother's occupational exposure to indoor cleaning agents starting before conception, or around conception and pregnancy, was associated with more childhood asthma and wheeze in offspring. Considering potential implications for vast numbers of women in childbearing age using cleaning agents, and their children, further research is imperative.
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http://dx.doi.org/10.1016/j.jaci.2021.08.025DOI Listing
January 2022

Respiratory symptoms, lung function, and fraction of exhaled nitric oxide before and after assignment in a desert environment-a cohort study.

Respir Med 2021 Nov-Dec;189:106643. Epub 2021 Oct 8.

Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. Electronic address:

Background: Inhalation of small particulate matter (PM 2.5) may be associated with development of respiratory disease. Increased respiratory symptoms have been reported among military staff after service in countries with recurrent desert storms.

Objective: The aim was to investigate whether an assignment in a desert environment and exposure to desert storms are associated with negative effects on respiratory health.

Methods: In two cohorts of Swedish soldiers serving in Mali as part of the United Nations stabilization forces, examination with spirometry, determination of fraction of exhaled nitric oxide (FeNO), and a questionnaire including participant characteristics, symptoms, and exposure was performed before and after service. Ambient air sampling was conducted on-site. Paired t-test was used to compare pre- and post-variables on lung function data, FeNO and symptom level.

Results: Most indoor and outdoor air measurements of dust and silica were within the Swedish occupational exposure limit for PM2.5 and silica (<0.10-2.7 mg/m and <0.002-0.40 mg/m, respectively) as well as for respirable dust and silica (0.056-0.078 mg/mand 0.0033-0.025 mg/m, respectively). In the subgroup of participants with reported exposure to desert storms during the stay in Mali, forced expiratory volume in 1 s (FEV) was significantly lower after exposure than before the mission (mean litres (SD) 4.21 ± 0.66 vs 4.33 ± 0.72, p = 0.021).

Conclusion: Exposure to a desert storm was associated with a decrease in FEV. Exposure to small particulate matter may contribute to the development of respiratory disease and thus spirometry should be performed after occupational exposure to desert storms.
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http://dx.doi.org/10.1016/j.rmed.2021.106643DOI Listing
February 2022

Reliability of external impulse oscillometry reference values for assessing respiratory health in Swedish adults.

Clin Exp Allergy 2022 02 22;52(2):355-358. Epub 2021 Oct 22.

Department of Clinical Sciences and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.

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http://dx.doi.org/10.1111/cea.14033DOI Listing
February 2022

Relationship between longitudinal changes in type-2 inflammation, immunoglobulin E sensitization, and clinical outcomes in young asthmatics.

Clin Transl Allergy 2021 Sep;11(7):e12066

Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

Background: Asthma is a heterogeneous condition where biomarkers may be of considerable advantage in diagnosis and therapy monitoring. However, the changes in asthma biomarkers and immunoglobulin E (IgE) over the course of life has not been extensively investigated.

Objective: To study longitudinal changes in type-2 inflammatory biomarkers, IgE, and clinical outcomes, and the association between these changes, in young asthmatics.

Methods: Asthmatics (age 10-35 years, n = 253) were examined at baseline and at a follow-up visit, 43 [23-65] (median [range]) months later. Subjects were analyzed using the multi-allergen tests Phadiatop and fx5 (ImmunoCAP) and grouped based on the baseline allergen-specific IgE antibody (sIgE) concentration: <0.10, 0.10-0.34, and ≥0.35 kU /L. The relationship between changes (Δ values) in type-2 biomarkers (individualized fraction of exhaled nitric oxide [FeNO%], blood eosinophil [B-Eos] count, total IgE [tIgE] and sIgE, lung function [% predicted forced expiratory volume in 1 second (FEV ) and FEV /forced vital capacity (FVC)], and Asthma Control Test [ACT]) score were determined.

Results: At follow up, FEV and FEV /FVC had decreased (93.6% vs. 95.8%, and 93.4% vs. 94.7% of predicted, respectively [p < 0.001 both]), whereas ACT score had increased (21.6 vs. 20.6, p = 0.001). A significant decline in lung function was seen in subjects with sIgE ≥ 0.10 kUA/L, but not in those with undetectable sIgE (<0.10 kU /L). Furthermore, tIgE and sIgE declined over time (p < 0.001 all) whereas FeNO% and B-Eos count were not significantly changed. In univariate analysis, significant negative correlations between ∆B-Eos count and ∆FeNO%, on one hand, and changes in lung function, on the other hand, were seen, and multivariate analysis showed an independent relationship between ΔFeNO%, and ΔFEV (p < 0.05) and ΔFEV /FVC% (p < 0.01). Sex-specific analysis showed that the independent association between ΔFeNO%, and ΔFEV remained only in females (p = 0.005), and there was a significant interaction with sex (p = 0.02).

Conclusion: In young asthmatics, IgE levels declined over 43 months, whereas FeNO and B-Eos remained unchanged. In spite of improved asthma control, an accelerated lung function decline was seen in patients with detectable sIgE at baseline, and the decline correlated with changes in type-2 biomarkers. Particularly, the increase in individualized FeNO associated independently with decline in FEV in females.
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http://dx.doi.org/10.1002/clt2.12066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083004PMC
September 2021

Importance of type and degree of IgE sensitisation for defining fractional exhaled nitric oxide reference values.

Respir Med 2021 11 21;188:106621. Epub 2021 Sep 21.

Department of Medical Sciences, Clinical Physiology, Uppsala University, Sweden. Electronic address:

Background: Fractional exhaled nitric oxide (FE) is a marker of type 2 airway inflammation used in clinical practice in asthma. However, reference values are needed to broaden the clinical use of FE and this is within the scope of a newly started Global Lung Function Initiative task force. We aim to study FE levels with special emphasis on the upper limit of normal (ULN) in relation to the type and degree of IgE sensitisation.

Methods: FE was measured in 1855 non-smoking, respiratory healthy subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Atopic subjects (n = 424), defined as being IgE-sensitised to aeroallergens (ImmunoCAP Phadiatop™, ≥0.35 PAU/l) were compared to non-atopic subjects (<0.35 PAU/l, n = 1431). Atopic subjects were further characterised according to their grade of IgE sensitisation (IgE antibody tertiles: (T1<1.16, T2 1.16-3.72 and T3 >3.72 PAU/l) and sensitisation to perennial (cat or mite) or seasonal (birch) allergens.

Results: Subjects IgE-sensitised to cat or mite had higher FE compared to non-atopic subjects (FE (ppb): median 20.0 vs. 15.0, and ULN 50.4 vs. 33.0, p < 0.001). This was seen to a lesser extent for subjects IgE-sensitised to birch only (median 18.0 vs. 15.0, and ULN 38.0 vs. 33.0, p = 0.048). Atopic subjects with a high degree of IgE sensitisation (Phadiatop: >3.72 PAU/l) had the highest FE compared to non-atopic subjects (median 20.0 vs. 15.0, and ULN 56.0 vs. 33.0, p < 0.001).

Conclusions: The type and degree of IgE sensitisation should be considered in generating FE reference values.
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http://dx.doi.org/10.1016/j.rmed.2021.106621DOI Listing
November 2021

Inhaled corticosteroids in COPD: risk and benefits.

Authors:
Christer Janson

Thorax 2022 Jun 23;77(6):530-531. Epub 2021 Sep 23.

Dep om Medical Sciences: Respiratory Medicine, Uppsala University, Uppsala, Sweden

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http://dx.doi.org/10.1136/thoraxjnl-2021-217930DOI Listing
June 2022

Cross-sectional study on exhaled nitric oxide in relation to upper airway inflammatory disorders with regard to asthma and perennial sensitization.

Clin Exp Allergy 2022 02 5;52(2):297-311. Epub 2021 Oct 5.

Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.

Background: Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitization as a major determinant.

Objective: We aimed to see whether there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitization, in a multi-centre population-based study.

Methods: A total of 741 subjects with current asthma and 4155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitization status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO were assessed in adjusted multivariate regression models and test for interaction with perennial sensitization and asthma on the relation between UAID and FeNO were made.

Results: UAID were associated with higher FeNO after adjusting for perennial sensitization, asthma and other confounders: with 4.4 (0.9-7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7-9.2) % higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitization was found in the relationship between current rhinitis and FeNO (p = .03) and between rhinoconjunctivitis and FeNO (p = .03). After stratification by asthma and perennial sensitization, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitization, with 12.1 (0.2-25.5) % higher FeNO in subjects with current rhinitis than in those without.

Conclusions & Clinical Relevance: Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitization. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the upper and lower airways and that sensitization needs to be accounted for in the relation between FeNO and rhinitis.
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http://dx.doi.org/10.1111/cea.14019DOI Listing
February 2022

ERS/EAACI statement on adherence to international adult asthma guidelines.

Eur Respir Rev 2021 Sep 15;30(161). Epub 2021 Sep 15.

Dept of Medical Science, Respiratory, Allergy and Sleep Research, Uppsala University and University Hospital, Uppsala, Sweden.

Guidelines aim to standardise and optimise asthma diagnosis and management. Nevertheless, adherence to guidelines is suboptimal and may vary across different healthcare professional (HCP) groups.Further to these concerns, this European Respiratory Society (ERS)/European Academy of Allergy and Clinical Immunology (EAACI) statement aims to: 1) evaluate the understanding of and adherence to international asthma guidelines by HCPs of different specialties an international online survey; and 2) assess strategies focused at improving implementation of guideline-recommended interventions, and compare process and clinical outcomes in patients managed by HCPs of different specialties systematic reviews.The online survey identified discrepancies between HCPs of different specialties which may be due to poor dissemination or lack of knowledge of the guidelines but also a reflection of the adaptations made in different clinical settings, based on available resources. The systematic reviews demonstrated that multifaceted quality improvement initiatives addressing multiple challenges to guidelines adherence are most effective in improving guidelines adherence. Differences in outcomes between patients managed by generalists or specialists should be further evaluated.Guidelines need to consider the heterogeneity of real-life settings for asthma management and tailor their recommendations accordingly. Continuous, multifaceted quality improvement processes are required to optimise and maintain guidelines adherence. Validated referral pathways for uncontrolled asthma or uncertain diagnosis are needed.
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http://dx.doi.org/10.1183/16000617.0132-2021DOI Listing
September 2021

IgE cross-linking induces activation of human and mouse mast cell progenitors.

J Allergy Clin Immunol 2022 Apr 4;149(4):1458-1463. Epub 2021 Sep 4.

Department of Medical Biochemistry and Microbiology, BMC, Uppsala University, Uppsala, Sweden. Electronic address:

Background: The concept of innate and adaptive effector cells that are repleted by maturing inert progenitor cell populations is changing. Mast cells develop from rare mast cell progenitors populating peripheral tissues at homeostatic conditions, or as a result of induced recruitment during inflammatory conditions.

Objective: Because FcεRI-expressing mast cell progenitors are the dominating mast cell type during acute allergic lung inflammation in vivo, we hypothesized that they are activated by IgE cross-linking.

Methods: Mouse peritoneal and human peripheral blood cells were sensitized and stimulated with antigen, or stimulated with anti-IgE, and the mast cell progenitor population analyzed for signs of activation by flow cytometry. Isolated peritoneal mast cell progenitors were studied before and after anti-IgE stimulation at single-cell level by time-lapse fluorescence microscopy. Lung mast cell progenitors were analyzed for their ability to produce IL-13 by intracellular flow cytometry in a mouse model of ovalbumin-induced allergic airway inflammation.

Results: Sensitized mouse peritoneal mast cell progenitors demonstrate increased levels of phosphorylation of tyrosines on intracellular proteins (total tyrosine phosphorylation), and spleen tyrosine kinase (Syk) phosphorylation after antigen exposure. Anti-IgE induced cell surface-associated lysomal-associated membrane protein-1 (LAMP-1) in naive mast cell progenitors, and prompted loss of fluorescence signal and altered morphology of isolated cells loaded with lysotracker. In human mast cell progenitors, anti-IgE increased total tyrosine phosphorylation, cell surface-associated LAMP-1, and CD63. Lung mast cell progenitors from mice with ovalbumin-induced allergic airway inflammation produce IL-13.

Conclusions: Mast cell progenitors become activated by IgE cross-linking and may contribute to the pathology associated with acute allergic airway inflammation.
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http://dx.doi.org/10.1016/j.jaci.2021.08.019DOI Listing
April 2022
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