Publications by authors named "Deborah Jarvis"

174 Publications

Single-Input Multi-Output U-Net for Automated 2D Foetal Brain Segmentation of MR Images.

J Imaging 2021 Oct 1;7(10). Epub 2021 Oct 1.

Academic Unit of Radiology, Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield S10 2RX, UK.

In this work, we develop the Single-Input Multi-Output U-Net (SIMOU-Net), a hybrid network for foetal brain segmentation inspired by the original U-Net fused with the holistically nested edge detection (HED) network. The SIMOU-Net is similar to the original U-Net but it has a deeper architecture and takes account of the features extracted from each side output. It acts similar to an ensemble neural network, however, instead of averaging the outputs from several independently trained models, which is computationally expensive, our approach combines outputs from a single network to reduce the variance of predications and generalization errors. Experimental results using 200 normal foetal brains consisting of over 11,500 2D images produced Dice and Jaccard coefficients of 94.2 ± 5.9% and 88.7 ± 6.9%, respectively. We further tested the proposed network on 54 abnormal cases (over 3500 images) and achieved Dice and Jaccard coefficients of 91.2 ± 6.8% and 85.7 ± 6.6%, respectively.
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http://dx.doi.org/10.3390/jimaging7100200DOI Listing
October 2021

Wheezing trajectories from childhood to adulthood in a population-based cohort.

Allergol Int 2021 Sep 29. Epub 2021 Sep 29.

Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.

Background: Wheezing may lead to asthma and reduced pulmonary function in later life. The study aims to identify wheezing trajectories and investigate their relation with pulmonary function and asthma-related outcomes at 22 years of age.

Methods: Individuals from a population-based cohort in Brazil (1993 Pelotas Birth Cohort) with post-bronchodilator pulmonary function data at 22 years (3350) were included in the study. From parentally reported (4 and 11 years) and self-reported (15, 18 and 22 years) history of wheezing in the last 12 months, we used a group-based trajectory modelling approach to derive wheezing trajectories.

Results: Four trajectories were identified: never/infrequent, transient-early, late-onset and persistent wheeze. After adjustments, wheezing trajectories remained associated with lower post-bronchodilator values of pulmonary function. Individuals in the persistent wheeze trajectory had a markedly poorer pulmonary function and also showed greater odds of asthma-related outcomes compared to other trajectories groups. Those following this trajectory had on average -109 ml (95% CI: -188; -35), -1.80 percentage points (95% CI: -2.73; -0.87) and -316 ml/s (95% CI: -482; -150) lower FEV, FEV/FVC ratio and FEF respectively; higher odds of self-reported medical diagnosis of allergy (OR 6.18; 95% CI: 3.59; 10.61) and asthma (OR 12.88; 95% CI: 8.91; 18.61) and asthma medication use (OR 9.42; 95% CI: 5.27; 16.87) compared to the never/infrequent group.

Conclusions: Wheezing trajectories, especially the persistent wheeze trajectory, were related to lower pulmonary function values and increased risk of asthma and allergy diagnosis in early adulthood.
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http://dx.doi.org/10.1016/j.alit.2021.09.002DOI Listing
September 2021

Bronchodilator response and lung function decline: Associations with exhaled nitric oxide with regard to sex and smoking status.

World Allergy Organ J 2021 May 18;14(5):100544. Epub 2021 May 18.

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

Background: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients. The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations.

Objectives: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex.

Methods: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey.

Results: Among asthmatic subjects, higher percentage declines of FEV and FEV/FVC were associated with higher FeNO levels (p = 0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p = 0.001) and females (p = 0.001) in stratified analyses.Percentage increase in FEV after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV and FeNO levels in non-smokers and women, regardless of asthma status.

Conclusions: We found a relationship between elevated FeNO and larger FEV decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects.
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http://dx.doi.org/10.1016/j.waojou.2021.100544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142084PMC
May 2021

Causal Effects of Body Mass Index on Airflow Obstruction and Forced Mid-Expiratory Flow: A Mendelian Randomization Study Taking Interactions and Age-Specific Instruments Into Consideration Toward a Life Course Perspective.

Front Public Health 2021 11;9:584955. Epub 2021 May 11.

Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.

Obesity has complex links to respiratory health. Mendelian randomization (MR) enables assessment of causality of body mass index (BMI) effects on airflow obstruction and mid-expiratory flow. In the adult SAPALDIA cohort, recruiting 9,651 population-representative samples aged 18-60 years at baseline (female 51%), BMI and the ratio of forced expiratory volume in 1 second (FEV) to forced vital capacity (FVC) as well as forced mid-expiratory flow (FEF25-75%) were measured three times over 20 follow-up years. The causal effects of BMI in childhood and adulthood on FEV1/FVC and FEF25-75% were assessed in predictive (BMI averaged over 1st and 2nd, lung function (LF) averaged over 2nd and 3rd follow-up; = 2,850) and long-term cross-sectional models (BMI and LF averaged over all follow-ups; = 2,728) by Mendelian Randomization analyses with the use of weighted BMI allele score as an instrument variable and two-stage least squares (2SLS) method. Three different BMI allele scores were applied to specifically capture the part of BMI in adulthood that likely reflects tracking of genetically determined BMI in childhood. The main causal effects were derived from models containing BMI (instrumented by BMI genetic score), age, sex, height, and packyears smoked as covariates. BMI interactions were instrumented by the product of the instrument (BMI genetic score) and the relevant concomitant variable. Causal effects of BMI on FEV1/FVC and FEF25-75% were observed in both the predictive and long-term cross-sectional models. The causal BMI- LF effects were negative and attenuated with increasing age, and stronger if instrumented by gene scores associated with childhood BMI. This non-standard MR approach interrogating causal effects of multiplicative interaction suggests that the genetically rooted part of BMI patterns in childhood may be of particular relevance for the level of small airway function and airflow obstruction later in life. The methodological relevance of the results is first to point to the importance of a life course perspective in studies on the etiological role of BMI in respiratory health, and second to point out novel methodological aspects to be considered in future MR studies on the causal effects of obesity related phenotypes.
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http://dx.doi.org/10.3389/fpubh.2021.584955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144328PMC
June 2021

The coexistence of asthma and COPD: risk factors, clinical history and lung function trajectories.

Eur Respir J 2021 Apr 16. Epub 2021 Apr 16.

Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.

Rationale: Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.

Objectives: Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history, and lung function trajectories from early adulthood to the late sixties of middle aged subjects having asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111), or none of these (n=3477).

Methods: Interview data and prebronchodilator FEV and FVC were obtained during three clinical examinations in 1991-1993, 1999-2002, and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68, according to the presence of fixed airflow obstruction (postbronchodilator FEV/FVC below the lower limit of normal), a lifetime history of asthma, and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics, and risk factors of these phenotypes were estimated.

Main Results: Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9 and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.

Conclusions: The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.
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http://dx.doi.org/10.1183/13993003.04656-2020DOI Listing
April 2021

Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach.

Eur Respir J 2021 10 21;58(4). Epub 2021 Oct 21.

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

Mechanistic research suggests that lifestyle and environmental factors impact respiratory health across generations by epigenetic changes transmitted through male germ cells. Evidence from studies on humans is very limited.We investigated multigeneration causal associations to estimate the causal effects of tobacco smoking on lung function within the paternal line. We analysed data from 383 adult offspring (age 18-47 years; 52.0% female) and their 274 fathers, who had participated in the European Community Respiratory Health Survey (ECRHS)/Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study and had provided valid measures of pre-bronchodilator lung function. Two counterfactual-based, multilevel mediation models were developed with: paternal grandmothers' smoking in pregnancy and fathers' smoking initiation in prepuberty as exposures; fathers' forced expiratory volume in 1 s (FEV) and forced vital capacity (FVC), or FEV/FVC z-scores as potential mediators (proxies of unobserved biological mechanisms that are true mediators); and offspring's FEV and FVC, or FEV/FVC z-scores as outcomes. All effects were summarised as differences (Δ) in expected z-scores related to fathers' and grandmothers' smoking history.Fathers' smoking initiation in prepuberty had a negative direct effect on both offspring's FEV (Δz-score -0.36, 95% CI -0.63- -0.10) and FVC (-0.50, 95% CI -0.80- -0.20) compared with fathers' never smoking. Paternal grandmothers' smoking in pregnancy had a negative direct effect on fathers' FEV/FVC (-0.57, 95% CI -1.09- -0.05) and a negative indirect effect on offspring's FEV/FVC (-0.12, 95% CI -0.21- -0.03) compared with grandmothers' not smoking before fathers' birth nor during fathers' childhood.Fathers' smoking in prepuberty and paternal grandmothers' smoking in pregnancy may cause lower lung function in offspring. Our results support the concept that lifestyle-related exposures during these susceptibility periods influence the health of future generations.
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http://dx.doi.org/10.1183/13993003.02791-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529197PMC
October 2021

Does the use of inhaled corticosteroids in asthma benefit lung function in the long-term? A systematic review and meta-analysis.

Eur Respir Rev 2021 Mar 19;30(159). Epub 2021 Jan 19.

Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Australia

While asthma is known to be associated with an increased risk of progressive lung function impairments and fixed airflow obstruction, there is ongoing debate on whether inhaled corticosteroids (ICS) modify these long-term risks. Searches were performed of the PubMed, Embase and CENTRAL databases up to 22 July 2019 for studies with follow-up ≥1 year that investigated the effects of maintenance ICS on changes in lung function in asthma.Inclusion criteria were met by 13 randomised controlled trials (RCTs) (n=11 678) and 11 observational studies (n=3720). Median (interquartile range) follow-up was 1.0 (1-4) and 8.4 (3-28) years, respectively. In the RCTs, predominantly in individuals with mild asthma, ICS use was associated with improved pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV) across all age groups (2.22% predicted (95% CI 1.32-3.12), n=8332), with similar estimates of strength in association for children and adults. Improvements in post-BD FEV were observed in adults (1.54% (0.87-2.21), n=3970), but not in children (0.20% (-0.49-0.90), n=3924) (subgroup difference, p=0.006). Estimates were similar between smokers and nonsmokers. There were no RCT data on incidence of fixed airflow obstruction. In the observational studies, ICS use was associated with improved pre-BD FEV in children and adults. There were limited observational data for post-BD outcomes.In patients with mild asthma, maintenance ICS are associated with modest, age-dependent improvements in long-term lung function, representing an added benefit to the broader clinical actions of ICS in asthma. There is currently insufficient evidence to determine whether treatment reduces incidence of fixed airflow obstruction in later life.
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http://dx.doi.org/10.1183/16000617.0185-2020DOI Listing
March 2021

Interactive effects of allergens and air pollution on respiratory health: A systematic review.

Sci Total Environ 2021 Feb 4;757:143924. Epub 2020 Dec 4.

National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address:

Background: Studies have demonstrated an adverse role of outdoor allergens on respiratory symptoms. It is unknown whether this effect is independent or synergistic of outdoor air pollutants.

Methods: We systematically reviewed all epidemiological studies that examined interaction effects between counts of outdoor airborne allergens (pollen, fungal spores) and air pollutants, on any respiratory health outcome in children and adults. We searched the MEDLINE, EMBASE and Scopus databases. Each study was summarized qualitatively and assessed for quality and risk of bias (International Prospective Register for Systematic Reviews, registration number CRD42020162571).

Results: Thirty-five studies were identified (15 timeseries, eight case-crossovers, 11 panels and one cohort study), of which 12 reported a significant statistical interaction between an allergen and air pollutant. Eight interactions were related to asthma outcomes, including one on lung function measures and wheeze, three to medical consultations for pollinosis and one to allergic symptoms (nasal, ocular or bronchial). There was no consensus as to which allergen or air pollutant is more likely to interact. No study investigated whether interactions are stronger in atopic individuals.

Conclusion: Despite strong evidence from small experimental studies in humans, only a third of studies identified significant allergen-pollutant interactions using common epidemiological study designs. Exposure misclassification, failure to examine subgroups at risk, inadequate statistical power or absence of population-level effects are possible explanations.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812370PMC
February 2021

Characteristics Associated with Accelerated Lung Function Decline in a Primary Care Population with Chronic Obstructive Pulmonary Disease.

Int J Chron Obstruct Pulmon Dis 2020 25;15:3079-3091. Epub 2020 Nov 25.

Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK.

Background: Estimates for lung function decline in chronic obstructive pulmonary disease (COPD) have differed by study setting and have not been described in a UK primary care population.

Purpose: To describe rates of FEV and FVC decline in COPD and investigate characteristics associated with accelerated decline.

Patients And Methods: Current/ex-smoking COPD patients (35 years+) who had at least 2 FEV or FVC measurements ≥6 months apart were included using Clinical Practice Research Datalink. Patients were followed up for a maximum of 13 years. Accelerated rate of lung function decline was defined as the fastest quartile of decline using mixed linear regression, and association with baseline characteristics was investigated using logistic regression.

Results: A total of 72,683 and 50,649 COPD patients had at least 2 FEV or FVC measurements, respectively. Median rates of FEV and FVC changes or decline were -18.1mL/year (IQR: -31.6 to -6.0) and -22.7mL/year (IQR: -39.9 to -6.7), respectively. Older age, high socioeconomic status, being underweight, high mMRC dyspnoea and frequent AECOPD or severe AECOPD were associated with an accelerated rate of FEV and FVC decline. Current smoking, mild airflow obstruction and inhaled corticosteroid treatment were additionally associated with accelerated FEV decline whilst women, sputum production and severe airflow obstruction were associated with accelerated FVC decline.

Conclusion: Rate of FEV and FVC decline was similar and showed similar heterogeneity. Whilst FEV and FVC shared associations with baseline characteristics, a few differences highlighted the importance of both lung function measures in COPD progression. We identified important characteristics that should be monitored for disease progression.
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http://dx.doi.org/10.2147/COPD.S278981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701160PMC
June 2021

Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts.

Ann Am Thorac Soc 2021 02;18(2):238-246

Occupational and Environmental Medicine, School of Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up. To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking. A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV and the FEV/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts. Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.
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http://dx.doi.org/10.1513/AnnalsATS.202002-113OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020720PMC
February 2021

Accelerated FEV decline and risk of cardiovascular disease and mortality in a primary care population of COPD patients.

Eur Respir J 2021 03 4;57(3). Epub 2021 Mar 4.

Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK.

Accelerated lung function decline has been associated with increased risk of cardiovascular disease (CVD) in a general population, but little is known about this association in chronic obstructive pulmonary disease (COPD). We investigated the association between accelerated lung function decline and CVD outcomes and mortality in a primary care COPD population.COPD patients without a history of CVD were identified in the Clinical Practice Research Datalink (CPRD)-GOLD primary care dataset (n=36 382). Accelerated decline in forced expiratory volume in 1 s (FEV) was defined using the fastest quartile of the COPD population's decline. A Cox regression was used to assess the association between baseline accelerated FEV decline and a composite CVD outcome over follow-up (myocardial infarction, ischaemic stroke, heart failure, atrial fibrillation, coronary artery disease and CVD mortality). The model was adjusted for age, sex, smoking status, body mass index, history of asthma, hypertension, diabetes, statin use, Modified Medical Research Council (mMRC) dyspnoea score, exacerbation frequency and baseline FEV % predicted.6110 COPD patients (16.8%) had a CVD event during follow-up; median length of follow-up was 3.6 years (interquartile range (IQR) 1.7-6.1 years). Median rate of FEV decline was -19.4 mL·year (IQR -40.5-1.9); 9095 patients (25%) had accelerated FEV decline (> -40.5 mL·year), 27 287 (75%) did not (≤ -40.5 mL·year). Risk of CVD and mortality was similar between patients with and without accelerated FEV decline (HR 0.98, 95% CI 0.90-1.06). Corresponding risk estimates were 0.99 (95% CI 0.83-1.20) for heart failure, 0.89 (95% CI 0.70-1.12) for myocardial infarction, 1.01 (95% CI 0.82-1.23) for stroke, 0.97 (95% CI 0.81-1.15) for atrial fibrillation, 1.02 (95% CI 0.87-1.19) for coronary artery disease and 0.94 (95% CI 0.71-1.25) for CVD mortality. Rather, risk of CVD was associated with a mMRC score ≤2 and two or more exacerbations in the year prior.CVD outcomes and mortality were associated with exacerbation frequency and severity and increased mMRC dyspnoea score but not with accelerated FEV decline.
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http://dx.doi.org/10.1183/13993003.00918-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930472PMC
March 2021

Changes in appearance of cortical formation abnormalities in the foetus detected on sequential in utero MR imaging.

Eur Radiol 2021 Mar 4;31(3):1367-1377. Epub 2020 Sep 4.

Pediatric Radiology and Neuroradiology Department, Children's Hospital V. Buzzi, Milan, Italy.

Objectives: We describe 64 foetuses with cortical formation abnormalities (CFA) who had two in utero magnetic resonance (iuMR) exams, paying particular detail to those in which the original classification of CFA category changed between the two studies. The goal was to attempt to quantify the value of third-trimester follow-up studies in CFA foetuses on second-trimester iuMR imaging.

Methods: The 64 foetuses reviewed came from a CFA cohort of 374 foetuses reported in an earlier publication, which detailed a classification for foetal CFA. A consensus panel of senior paediatric neuroradiologists reviewed both studies, described any change in the category of CFA between them, and attempted to predict the possible clinical significance of any differences based on the combined clinical experience of the panel.

Results: In 40/64 (62%) foetuses, the CFA description was the same on both studies. In 24/64 (38%) cases, there was a category change which included three foetuses without CFA on first examination, six foetuses where the difference involved change in laterality/symmetry, and in 15 cases the re-classification involved categorical change within the same group. Brain abnormalities other than CFA were present in 30/64 (47%) foetuses on the first study and in 33/64 (52%) on the second. We predicted that prognosis would have changed on the basis of the second study in 8% of cases, all indicating worse prognosis.

Conclusions: We have shown that the extra diagnostic and predicted prognostic yield justifies follow-up studies in the third trimester if a CFA is shown on the second-trimester iuMR imaging.

Key Points: • Sixty-four foetuses with cortical formation abnormalities had two iuMR studies, for the vast majority the baseline in the second trimester and the sequential in the third. • In three foetuses, the cortical formation abnormality (CFA) was not visible on the first study. In a further 21 foetuses, the categorical description of the CFA changed between the two studies. Prognosis changed in 8% of the cases following the second iuMR study, and in all cases, the prognosis was worse. • Multiple iuMR studies provide information about the natural history of CFA; the extra diagnostic and predicted prognostic yield justifies follow-up studies.
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http://dx.doi.org/10.1007/s00330-020-07125-9DOI Listing
March 2021

Characterisation of pulmonary function trajectories: results from a Brazilian cohort.

ERJ Open Res 2020 Jul 25;6(3). Epub 2020 Aug 25.

Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.

Background: Pulmonary function (PF) trajectories are determined by different exposures throughout the life course. The aim of this study was to investigate characteristics related to PF trajectories from 15 to 22 years in a Brazilian cohort.

Methods: A birth cohort study (1993 Pelotas Birth Cohort) was conducted with spirometry at 15, 18 and 22 years. PF trajectories were built based on z-score of forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and their ratio using a group-based trajectory model. Associations with exposures reported from perinatal to 22 years were described.

Results: Three trajectories, low (LT), average (AT) and high (HT) were identified in 2917 individuals. Wealthiest individuals belonged to the HT of FEV (p=0.023). Lower maternal pregestational body mass index (BMI) (22.4±0.2; p<0.001 and 22.1±0.14; p<0.001) and lower birth weight (3164.8±25.4; p=0.029 and 3132.3±19.4; p=0.005) were related to the LT of FEV and FVC. Mother's smoking exposure during pregnancy (37.7%; p=0.002), active smoking at ages 18 and 22 years (20.1% and 25.8%; p<0.001) and family history of asthma (44.8%; p<0.001) were related to the LT of FEV/FVC. Wheezing, asthma and hospitalisations due to respiratory diseases in childhood were related to the LT of both FEV and FEV/FVC. Higher BMIs were related to the HT of FEV and FVC at all ages.

Conclusions: PF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.
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http://dx.doi.org/10.1183/23120541.00065-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445117PMC
July 2020

Physical activity and lung function-Cause or consequence?

PLoS One 2020 20;15(8):e0237769. Epub 2020 Aug 20.

ISGlobal, Barcelona, Spain.

Concerns exist that the positive association of physical activity with better lung function, which has been suggested in previous longitudinal studies in smokers, is due to reverse causation. To investigate this, we applied structural equation modeling (SEM), an exploratory approach, and marginal structural modeling (MSM), an approach from the causal inference framework that corrects for reverse causation and time-dependent confounding and estimates causal effects, on data from participants in the European Community Respiratory Health Survey (ECRHS, a multicentre European cohort study initiated in 1991-1993 with ECRHS I, and with two follow-ups: ECRHS II in 1999-2003, and ECRHS III in 2010-2014). 753 subjects who reported current smoking at ECRHS II, with repeated data on lung function at ECRHS I, II and III, physical activity at ECRHS II and III, and potential confounders at ECRHS I and II, were included in the analyses. SEM showed positive associations between physical activity and lung function in both directions. MSM suggested a protective causal effect of physical activity on lung function (overall difference in mean β (95% CI), comparing active versus non-active individuals: 58 mL (21-95) for forced expiratory volume in one second and 83 mL (36-130) for forced vital capacity). Our results suggest bi-directional causation and support a true protective effect of physical activity on lung function in smokers, after accounting for reverse causation and time-dependent confounding.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237769PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446897PMC
October 2020

Seasonality of food-related anaphylaxis admissions and associations with temperature and pollen levels.

J Allergy Clin Immunol Pract 2021 01 31;9(1):518-520.e2. Epub 2020 Jul 31.

National Heart and Lung Institute, Imperial College, London, United Kingdom; MRC Centre for the Environment and Health, Imperial College London, London, United Kingdom.

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http://dx.doi.org/10.1016/j.jaip.2020.07.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794659PMC
January 2021

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

Sleep Breath 2021 Jun 6;25(2):587-596. Epub 2020 Jul 6.

Department of Sleep Medicine, Landspitali, Reykjavik, Iceland.

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.
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http://dx.doi.org/10.1007/s11325-020-02086-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195766PMC
June 2021

Describing the status of reproductive ageing simply and precisely: A reproductive ageing score based on three questions and validated with hormone levels.

PLoS One 2020 30;15(6):e0235478. Epub 2020 Jun 30.

Department of Clinical Science, University of Bergen, Bergen, Norway.

Objective: Most women live to experience menopause and will spend 4-8 years transitioning from fertile age to full menstrual stop. Biologically, reproductive ageing is a continuous process, but by convention, it is defined categorically as pre-, peri- and postmenopause; categories that are sometimes supported by measurements of sex hormones in blood samples. We aimed to develop and validate a new tool, a reproductive ageing score (RAS), that could give a simple and yet precise description of the status of reproductive ageing, without hormone measurements, to be used by health professionals and researchers.

Methods: Questionnaire data on age, menstrual regularity and menstrual frequency was provided by the large multicentre population-based RHINE cohort. A continuous reproductive ageing score was developed from these variables, using techniques of fuzzy mathematics, to generate a decimal number ranging from 0.00 (nonmenopausal) to 1.00 (postmenopausal). The RAS was then validated with sex hormone measurements (follicle stimulating hormone and 17β-estradiol) and interview-data provided by the large population-based ECRHS cohort, using receiver-operating characteristics (ROC).

Results: The RAS, developed from questionnaire data of the RHINE cohort, defined with high precision and accuracy the menopausal status as confirmed by interview and hormone data in the ECRHS cohort. The area under the ROC curve was 0.91 (95% Confidence interval (CI): 0.90-0.93) to distinguish nonmenopausal women from peri- and postmenopausal women, and 0.85 (95% CI: 0.83-0.88) to distinguish postmenopausal women from nonmenopausal and perimenopausal women.

Conclusions: The RAS provides a useful and valid tool for describing the status of reproductive ageing accurately, on a continuous scale from 0.00 to 1.00, based on simple questions and without requiring blood sampling. The score allows for a more precise differentiation than the conventional categorisation in pre-, peri- and postmenopause. This is useful for epidemiological research and clinical trials.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235478PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326235PMC
September 2020

Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study.

BMC Pulm Med 2020 Jun 16;20(1):171. Epub 2020 Jun 16.

National Heart and Lung Institute, Imperial College London, London, UK.

Background: Low lung function has been associated with increased body mass index (BMI). The aim of this study was to investigate whether the effect of BMI on lung function is mediated by DNA methylation.

Methods: We used individual data from 285,495 participants in four population-based cohorts: the European Community Respiratory Health Survey, the Northern Finland Birth Cohort 1966, the Swiss Study on Air Pollution and Lung Disease in Adults, and the UK Biobank. We carried out Mendelian randomisation (MR) analyses in two steps using a two-sample approach with SNPs as instrumental variables (IVs) in each step. In step 1 MR, we estimated the causal effect of BMI on peripheral blood DNA methylation (measured at genome-wide level) using 95 BMI-associated SNPs as IVs. In step 2 MR, we estimated the causal effect of DNA methylation on FEV, FVC, and FEV/FVC using two SNPs acting as methQTLs occurring close (in cis) to CpGs identified in the first step. These analyses were conducted after exclusion of weak IVs (F statistic < 10) and MR estimates were derived using the Wald ratio, with standard error from the delta method. Individuals whose data were used in step 1 were not included in step 2.

Results: In step 1, we found that BMI might have a small causal effect on DNA methylation levels (less than 1% change in methylation per 1 kg/m2 increase in BMI) at two CpGs (cg09046979 and cg12580248). In step 2, we found no evidence of a causal effect of DNA methylation at cg09046979 on lung function. We could not estimate the causal effect of DNA methylation at cg12580248 on lung function as we could not find publicly available data on the association of this CpG with SNPs.

Conclusions: To our knowledge, this is the first paper to report the use of a two-step MR approach to assess the role of DNA methylation in mediating the effect of a non-genetic factor on lung function. Our findings do not support a mediating effect of DNA methylation in the association of lung function with BMI.
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http://dx.doi.org/10.1186/s12890-020-01212-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298775PMC
June 2020

Cortical formation abnormalities on foetal MR imaging: a proposed classification system trialled on 356 cases from Italian and UK centres.

Eur Radiol 2020 Oct 13;30(10):5250-5260. Epub 2020 May 13.

Academic Unit of Radiology, University of Sheffield, Sheffield, UK.

Objective: To formulate a classification system for foetal cortical formation abnormalities (CFAs) based on in utero magnetic resonance (iuMR) appearances and trial it in 356 cases.

Methods: This retrospective study included all cases of foetal CFA diagnosed between 2000 and 2017 from seven centres in Italy and UK. All of the studies were reviewed by a panel of paediatric neuroradiologists experienced in iuMR with the aid of an algorithm designed to categorise the abnormalities.

Results: Consensus expert review confirmed 356 foetuses with CFA and the first level of classification distinguished bilateral CFA (229/356-64%) from unilateral CFA (127/356-36%) cases with sub-classification of the bilateral cases into asymmetric (65/356-18%) and symmetric (164/356-46%) involvement. There was a statistically significant excess of foetuses with small head size, e.g. 17% of the cohort had a bi-parietal diameter < 3rd centile. There was a small but statistically significant excess of males in the cohort. Further categorisation was made on fine anatomical structure.

Conclusions: It is often not possible to classify foetal CFA using the principles and nomenclature used in paediatric neuroradiology. We have created a classification system for foetal CFA based on the analysis of 356 cases and believe that this will assist future research designed to correlate ante-natal and post-natal imaging features and understand the clinical sequelae of CFA described in utero.

Key Points: • We describe a morphological classification system of foetal brain cortical formation abnormalities that can be used in clinical practice. • This classification system can be used in future research studies to evaluate the long-term imaging and clinical outcomes of foetal brain cortical formation abnormalities in 17- to 38-week gestational age range. • The practical value of the work is in providing a framework and language to look for imaging clues that may differentiate between different CFA in further studies.
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http://dx.doi.org/10.1007/s00330-020-06899-2DOI Listing
October 2020

Polycystic ovary syndrome and lung function: a Mendelian randomization study.

Am J Obstet Gynecol 2020 09 7;223(3):455-457. Epub 2020 Mar 7.

Department of Clinical Science, University of Bergen; Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.

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http://dx.doi.org/10.1016/j.ajog.2020.03.003DOI Listing
September 2020

Incidence trends of airflow obstruction among European adults without asthma: a 20-year cohort study.

Sci Rep 2020 02 26;10(1):3452. Epub 2020 Feb 26.

Population Health and Occupational Disease, National Heart and Lung Institute, Imperial College London, London, UK.

Investigating COPD trends may help healthcare providers to forecast future disease burden. We estimated sex- and smoking-specific incidence trends of pre-bronchodilator airflow obstruction (AO) among adults without asthma from 11 European countries within a 20-year follow-up (ECRHS and SAPALDIA cohorts). We also quantified the extent of misclassification in the definition based on pre-bronchodilator spirometry (using post-bronchodilator measurements from a subsample of subjects) and we used this information to estimate the incidence of post-bronchodilator AO (AO), which is the primary characteristic of COPD. AO incidence was 4.4 (95% CI: 3.5-5.3) male and 3.8 (3.1-4.6) female cases/1,000/year. Among ever smokers (median pack-years: 20, males; 12, females), AO incidence significantly increased with ageing in men only [incidence rate ratio (IRR), 1-year increase: 1.05 (1.03-1.07)]. A strong exposure-response relationship with smoking was found both in males [IRR, 1-pack-year increase: 1.03 (1.02-1.04)] and females [1.03 (1.02-1.05)]. The positive predictive value of AO for AO was 59.1% (52.0-66.2%) in men and 42.6% (35.1-50.1%) in women. AO incidence was 2.6 (1.7-3.4) male and 1.6 (1.0-2.2) female cases/1,000/year. AO incidence was considerable in Europe and the sex-specific ageing-related increase among ever smokers was strongly related to cumulative tobacco exposure. AO incidence is expected to be half of AO incidence.
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http://dx.doi.org/10.1038/s41598-020-60478-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044325PMC
February 2020

Body mass index and weight change are associated with adult lung function trajectories: the prospective ECRHS study.

Thorax 2020 04 25;75(4):313-320. Epub 2020 Feb 25.

Department of Public Health, Section for Environment Occupation and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark.

Background: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS).

Methods: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations.

Results: In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25-1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had -1011 mL (95% CI -1.259 to -763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (<-0.25 kg/year) exhibited an attenuation of FVC and FEV declines. We found no association between weight change profiles and FEV/FVC decline.

Conclusion: Moderate and high weight gain over 20 years was associated with accelerated lung function decline, while weight loss was related to its attenuation. Control of weight gain is important for maintaining good lung function in adult life.
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http://dx.doi.org/10.1136/thoraxjnl-2019-213880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231449PMC
April 2020

Normal appearances and dimensions of the foetal cavum septi pellucidi and vergae on in utero MR imaging.

Neuroradiology 2020 May;62(5):617-627

Academic Unit of Radiology, University of Sheffield, Floor C, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK.

Purpose: The aim of this study is to provide normative data about the appearances and dimensions of the cavum septi pellucidi and vergae (CSPV) on in utero MR (iuMR) imaging in second and third trimester foetuses.

Methods: Two hundred normal foetuses (from a low-risk pregnancy, with normal ante-natal USS findings and no intracranial abnormality of iuMR) had iuMR imaging between 18 and 37 gestational weeks (gw). The anatomical features on those studies were compared with published atlases of post-mortem foetal brains. The length, width and volume of the CSPV were measured in all foetuses.

Results: The anatomy of the CSPV and its relationship with the corpus callosum and the fornices on iuMR imaging was comparable with post-mortem data at all gestational ages studied. The length of the CSPV increased throughout pregnancy, whereas the width and volume of CSPV reached a maximum between 29 and 31 gw and then showed a reduction later in pregnancy.

Conclusion: The iuMR imaging features of the CSPV and its close anatomical relations closely correspond to post-mortem data. The CSPV was patent in all cases but we have shown that closure commences in the midpart of the third trimester and advances in a posterior to anterior direction.
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http://dx.doi.org/10.1007/s00234-020-02364-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186260PMC
May 2020

Long-term air pollution exposure is associated with increased severity of rhinitis in 2 European cohorts.

J Allergy Clin Immunol 2020 03 23;145(3):834-842.e6. Epub 2020 Jan 23.

INSERM, U1168, VIMA: Aging and Chronic Diseases, Epidemiological and Public Health Approaches, Villejuif, France; University of Versailles St-Quentin-en-Yvelines, UMR 1168, Montigny le Bretonneux, France; ISGLobal, Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Electronic address:

Background: Very few studies have examined the association between long-term outdoor air pollution and rhinitis severity in adults.

Objective: We sought to assess the cross-sectional association between individual long-term exposure to air pollution and severity of rhinitis.

Methods: Participants with rhinitis from 2 multicenter European cohorts (Epidemiological Study on the Genetics and Environment on Asthma and the European Community Respiratory Health Survey) were included. Annual exposure to NO, PM, PM, and PM (calculated by subtracting PM from PM) was estimated using land-use regression models derived from the European Study of Cohorts for Air Pollution Effects project, at the participants' residential address. The score of rhinitis severity (range, 0-12), based on intensity of disturbance due to symptoms reported by questionnaire, was categorized into low (reference), mild, moderate, and high severity. Polytomous logistic regression models with a random intercept for city were used.

Results: A total of 1408 adults with rhinitis (mean age, 52 years; 46% men, 81% from the European Community Respiratory Health Survey) were included. The median (1st quartile-3rd quartile) score of rhinitis severity was 4 (2-6). Higher exposure to PM was associated with higher rhinitis severity (adjusted odds ratio [95% CI] for a 10 μg/m increase in PM: for mild: 1.20 [0.88-1.64], moderate: 1.53 [1.07-2.19], and high severity: 1.72 [1.23-2.41]). Similar results were found for PM. Higher exposure to NO was associated with an increased severity of rhinitis, with similar adjusted odds ratios whatever the level of severity. Adjusted odds ratios were higher among participants without allergic sensitization than among those with, but interaction was found only for NO CONCLUSIONS: People with rhinitis who live in areas with higher levels of pollution are more likely to report more severe nasal symptoms. Further work is required to elucidate the mechanisms of this association.
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http://dx.doi.org/10.1016/j.jaci.2019.11.040DOI Listing
March 2020

Association of adult lung function with accelerated biological aging.

Aging (Albany NY) 2020 01 11;12(1):518-542. Epub 2020 Jan 11.

Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

Lung function, strongly associated with morbidity and mortality, decreases with age. This study examines whether poor adult lung function is associated with age accelerations (AAs). DNA methylation (DNAm) based AAs, lifespan predictors (GrimAge and plasminogen activator inhibitor 1-PAI1) and their related age-adjusted measures were estimated from peripheral blood at two time points (8-to-11 years apart) in adults from two cohorts: SAPALDIA (n=987) and ECRHS (n=509). Within each cohort and stratified by gender (except for estimators from GrimAge and PAI1), AAs were used as predictors in multivariate linear regression with cross-sectional lung function parameters, and in covariate-adjusted mixed linear regression with longitudinal change in lung function and meta-analysed.AAs were found cross-sectionally associated with lower mean FEV1 (Forced Expiratory Volume in one second) (AA-residuals:P-value=4x10; Intrinsic Epigenetic AA:P-value=2x10) in females at the follow-up time point only, and the same trend was observed for FVC (Forced Vital Capacity). Both lifespan and plasma level predictors were observed strongly associated with lung function decline and the decline was stronger in the follow-up time points (strongest association between FEV1 and DNAmAge GrimAge:P-value=1.25x10).This study suggests that DNAm based lifespan and plasma level predictors can be utilised as important factors to assess lung health in adults.
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http://dx.doi.org/10.18632/aging.102639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977706PMC
January 2020

Asthma and treatment with inhaled corticosteroids: associations with hospitalisations with pneumonia.

BMC Pulm Med 2019 Dec 19;19(1):254. Epub 2019 Dec 19.

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

Background: Pneumonia is an important cause of morbidity and mortality. COPD patients using inhaled corticosteroids (ICS) have an increased risk of pneumonia, but less is known about whether ICS treatment in asthma also increases the risk of pneumonia. The aim of this analysis was to examine risk factors for hospitalisations with pneumonia in a general population sample with special emphasis on asthma and the use of ICS in asthmatics.

Methods: In 1999 to 2000, 7340 subjects aged 28 to 54 years from three Swedish centres completed a brief health questionnaire. This was linked to information on hospitalisations with pneumonia from 2000 to 2010 and treatment with ICS from 2005 to 2010 held within the Swedish National Patient Register and the Swedish Prescribed Drug Register.

Results: Participants with asthma (n = 587) were more likely to be hospitalised with pneumonia than participants without asthma (Hazard Ratio (HR 3.35 (1.97-5.02)). Other risk factors for pneumonia were smoking (HR 1.93 (1.22-3.06)), BMI < 20 kg/m2 (HR 2.74 (1.41-5.36)) or BMI > 30 kg/m2 (HR 2.54 (1.39-4.67)). Asthmatics (n = 586) taking continuous treatment with fluticasone propionate were at an increased risk of being hospitalized with pneumonia (incidence risk ratio (IRR) 7.92 (2.32-27.0) compared to asthmatics that had not used fluticasone propionate, whereas no significant association was found with the use of budesonide (IRR 1.23 (0.36-4.20)).

Conclusion: Having asthma is associated with a three times higher risk of being hospitalised for pneumonia. This analysis also indicates that there are intraclass differences between ICS compounds with respect to pneumonia risk, with an increased risk of pneumonia related to fluticasone propionate.
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http://dx.doi.org/10.1186/s12890-019-1025-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923948PMC
December 2019

Lifetime Risk Factors for Pre- and Post-Bronchodilator Lung Function Decline. A Population-based Study.

Ann Am Thorac Soc 2020 03;17(3):302-312

Allergy and Lung Health Unit, The University of Melbourne, Melbourne, Victoria, Australia.

Interactions between early life and adult insults on lung function decline are not well understood, with most studies investigating prebronchodilator (pre-BD) FEV decline. To investigate relationships between adult risk factors and pre- and post-BD lung function decline and their potential effect modification by early life and genetic factors. Multiple regression was used to examine associations between adult exposures (asthma, smoking, occupational exposures, traffic pollution, and obesity) and decline in both pre- and post-BD spirometry (forced expiratory volume in 1 s [FEV], forced vital capacity [FVC], and FEV/FVC) between ages 45 and 53 years in the Tasmanian Longitudinal Health Study ( = 857). Effect modification of these relationships by childhood respiratory risk factors, including low childhood lung function and GST (glutathione S-transferase) gene polymorphisms, was investigated. Baseline asthma, smoking, occupational exposure to vapors/gases/dusts/fumes, and living close to traffic were associated with accelerated decline in both pre- and post-BD FEV. These factors were also associated with FEV/FVC decline. Occupational exposure to aromatic solvents was associated with pre-BD but not post-BD FEV decline. Maternal smoking accentuated the effect of personal smoking on pre- and post-BD FEV decline. Lower childhood lung function and having the GSTM1 null allele accentuated the effect of occupational exposure to vapors/gases/dusts/fumes and personal smoking on post-BD FEV decline. Incident obesity was associated with accelerated decline in FEV and more pronounced in FVC. This study provides new evidence for accentuation of individual susceptibility to adult risk factors by low childhood lung function, GSTM1 genotype, and maternal smoking.
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http://dx.doi.org/10.1513/AnnalsATS.201904-329OCDOI Listing
March 2020

Atopy Modifies the Association Between Inhaled Corticosteroid Use and Lung Function Decline in Patients with Asthma.

J Allergy Clin Immunol Pract 2020 03 5;8(3):980-988.e10. Epub 2019 Nov 5.

Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.

Background: Inhaled corticosteroids (ICSs) are the mainstay of asthma treatment, but response to medication is variable. Patients with allergic inflammation generally show a better short-term response to ICSs; however, studies on predictors of long-term response are few.

Objective: To assess whether allergic sensitization can modify the association between ICS use and lung function decline over 20 years in adult asthma.

Methods: We used data from the 3 clinical examinations of the European Community Respiratory Health Survey. We measured ICS use (no use, and use for <1.3, 1.3-8, and >8 years) and FEV decline among subjects with asthma over the 2 periods between consecutive examinations. We conducted a cohort study combining data of the 2 periods (906 observations from 745 subjects) to assess whether the association between ICS use and FEV decline was modified by allergic sensitization (IgE > 0.35 kU/L for any of house-dust mite, timothy grass, cat, or Cladosporium).

Results: FEV decline was similar for non-ICS users, as well as ICS users for less than 1.3 years, with and without allergic sensitization. However, among subjects on ICSs for a longer period, sensitization was associated with an attenuated decline (P = .006): in the group treated for more than 8 years, FEV decline was on average 27 mL/y (95% CI, 11-42) lower for subjects with sensitization compared with nonsensitized subjects.

Conclusions: Our study suggests that biomarkers of atopy can predict a more favorable long-term response to ICSs. Randomized controlled studies are needed to confirm these findings.
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http://dx.doi.org/10.1016/j.jaip.2019.10.023DOI Listing
March 2020
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