Apoetm1Unc mice have impaired alveologenesis, low lung function, and rapid loss of lung function

2008 ◽  
Vol 294 (5) ◽  
pp. L991-L997 ◽  
Author(s):  
Donald Massaro ◽  
Gloria DeCarlo Massaro
Keyword(s):  
Lung Function ◽  
Apolipoprotein E ◽  
Early Adulthood ◽  
Early Death ◽  
Forced Expiratory Volume ◽  
Early Mortality ◽  
Accelerated Ageing ◽  
Rapid Loss ◽  
Apolipoprotein E Genotypes ◽  
Never Smokers

Diminished lung function, indicated by a low forced expiratory volume in one second (FEV1), and short physical stature, predict early mortality from all causes, including cardiovascular, among smokers and never smokers. The basis for these associations is unclear, and, it is not known if there is a pulmonary morphological component to the relationship between low FEV1 and early death in a general population. Some apolipoprotein E genotypes also predict atherosclerosis and early mortality. These considerations led us to examine the Apoe tm1Unc (Apoe) mouse, in which the apolipoprotein E gene is deleted, and that develops dyslipidemia, atherosclerosis at an early age, and has a shorter life span than the founder wild-type (wt) strain. We asked if Apoe mice have a morphological or functional pulmonary phenotype. We measured the size, number, and surface area of pulmonary gas-exchange units (alveoli) and mechanical properties of the lung. Compared with wt mice, Apoe mice had: 1) diminished developmental alveologenesis, 2) increased airway resistance in early adulthood, 3) high lung volume and high dynamic and static compliance in later adulthood, 4) more rapid loss of lung recoil with age, and 5) were less long than wt mice. These findings in mice indicate the association of a low FEV1 with early death in humans may have developmental, and accelerated ageing, related pulmonary components, and that dietary, genetic, or dietary and genetic influences, on lipid metabolism may be an upstream cause of inflammation and oxidative stress, currently considered to be major risk factors for COPD.

scholarly journals Association of asthma and smoking with lung function impairment in adolescence and early adulthood: the Isle of Wight Birth Cohort Study

2019 ◽  
Vol 55 (3) ◽  
pp. 1900477 ◽  
Author(s):  
S. Hasan Arshad ◽  
Claire Hodgekiss ◽  
John W. Holloway ◽  
Ramesh Kurukulaaratchy ◽  
Wilfried Karmaus ◽  
...  
Keyword(s):  
Lung Function ◽  
Birth Cohort ◽  
Smoking Status ◽  
Early Adulthood ◽  
Adult Life ◽  
Population Based ◽  
Forced Expiratory Volume ◽  
Birth Cohort Study ◽  
Irreversible Damage ◽  
Isle Of Wight

We investigated associations of asthma and smoking with lung function and airway reversibility from childhood to early adulthood.The population-based Isle of Wight Birth Cohort (n=1456) was assessed at birth, and at 1, 2, 4, 10, 18 and 26 years. Asthma was defined as physician diagnosis plus current wheeze and/or treatment. Spirometry was conducted at 10 (n=981), 18 (n=839) and 26 years (n=547). Individuals were subdivided into nonsmokers without asthma, nonsmokers with asthma, smokers without asthma and smokers with asthma, based on asthma and smoking status at 26 years. Their lung function trajectories from 10 to 26 years were examined using longitudinal models.Nonsmokers with asthma had smaller forced expiratory volume in 1 s (FEV1), FEF25–75% (forced expiratory flow at 25–75% of forced vital capacity (FVC)) and FEV1/FVC ratio compared to nonsmokers without asthma at age 10 and 18 years, with differences reduced after bronchodilator (pre-bronchodilator FEV1 at 26 years 3.75 L versus 4.02 L, p<0.001; post-bronchodilator 4.02 L versus 4.16 L, p=0.08). This lung function deficit did not worsen after 18 years. Smokers without asthma had smaller FEF25–75% and FEV1/FVC ratio (but not FEV1) at 26 years compared to nonsmokers without asthma, with the deficit appearing after 18 years and persisting despite bronchodilator response (for FEV1/FVC ratio at 26 years 0.80 versus 0.81, p=0.002; post-bronchodilator 0.83 versus 0.85, p=0.005). Smokers with asthma had worse lung function compared to other groups.Lung function deficits associated with asthma and smoking occur early in life. They are not fully responsive to bronchodilators, indicating a risk for long-term lung health, which highlights the need to institute preventive measures in adolescence and early adult life before irreversible damage occurs.

scholarly journals Low sputum MMP-9/TIMP ratio is associated with airway narrowing in smokers with asthma

2014 ◽  
Vol 44 (4) ◽  
pp. 895-904 ◽  
Author(s):  
Rekha Chaudhuri ◽  
Charles McSharry ◽  
Jeffrey Brady ◽  
Christal Grierson ◽  
C. Martina Messow ◽  
...  
Keyword(s):  
Lung Function ◽  
Structural Changes ◽  
Symptom Control ◽  
Airflow Obstruction ◽  
Forced Expiratory Volume ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Lumen Area ◽  
Airway Narrowing ◽  
Airway Lumen ◽  
Never Smokers

Asthmatic smokers have poor symptom control and accelerated decline in lung function. A reduced ratio of matrix metalloproteinase (MMP)-9/tissue inhibitors of metalloproteinases (TIMPs) in nonsmokers with asthma has been implicated in airway remodelling. We tested the hypothesis that sputum MMP-9 activity/TIMPs ratios are reduced in smokers compared with never-smokers with asthma and are associated with reduced lung function and altered computed tomography (CT) measures of airway wall dimensions.Lung function, airway dimensions by CT, and induced sputum concentrations (and activity) of MMP-9 and TIMP-1 and -2 were measured in 81 asthmatics and 43 healthy subjects (smokers and never-smokers). Respiratory epithelial MMP9 and TIMP mRNA was quantified in 31 severe asthmatics and 32 healthy controls.Sputum MMP-9 activity/TIMP-1 and TIMP-2 ratios, and nasal epithelial MMP9/TIMP1 and MMP9/TIMP2 expression ratios were reduced in smokers with asthma compared with never-smokers with asthma. Low sputum ratios in asthmatic smokers were associated with reduced post-bronchodilator forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity ratio and segmental airway lumen area.The association of a low sputum MMP-9 activity/TIMP-1 ratio with persistent airflow obstruction and reduced CT airway lumen area in smokers with asthma may indicate that an imbalance of MMP-9 and TIMPs contributes to structural changes to the airways in this group.

scholarly journals The role of air pollution and lung function in cognitive impairment

2018 ◽  
Vol 51 (2) ◽  
pp. 1701963 ◽  
Author(s):  
Anke Hüls ◽  
Andrea Vierkötter ◽  
Dorothea Sugiri ◽  
Michael J. Abramson ◽  
Ulrich Ranft ◽  
...  
Keyword(s):  
Air Pollution ◽  
Cognitive Impairment ◽  
Lung Function ◽  
Neuropsychological Test ◽  
Forced Expiratory Volume ◽  
Z Scores ◽  
Causal Mediation Analysis ◽  
Never Smokers

Air pollution has been associated with impaired lung and cognitive function, especially impairment in visuo-construction performance (VCP). In this article, we evaluate whether the effect of air pollution on VCP is mediated by lung function.We used data from the SALIA cohort (baseline 1985–1994 and follow-up 2007–2010) including 587 women aged 55 years at baseline. Particulate matter (PM) and nitrogen dioxide (NO2) exposures at baseline were estimated via land-use regression models. Lung function was characterised by averages between baseline and follow-up. We used age- and height-controlled Global Lung Initiative (GLI) z-scores of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC. VCP was assessed at follow-up with the CERAD-Plus neuropsychological test battery and causal mediation analysis was conducted.An increase of one interquartile range in FEV1 and FVC was positively associated with VCP (β=0.18 (95% CI 0.02–0.34) and β=0.23 (95% CI 0.07–0.39), respectively). The proportion of the association between NO2 on VCP mediated by FEV1 was 6.2% and this was higher in never smokers (7.2%) and non-carriers of the APOE-ε4 allele (11.2%). However, none of the mediations were statistically significant.In conclusion, air pollution associated VCP was partially mediated by lung function. Further studies on the mechanisms underlying this pathway are required to develop new strategies to prevent air pollution induced cognitive impairment.

scholarly journals The effects of marijuana smoking on lung function in older people

2019 ◽  
Vol 54 (6) ◽  
pp. 1900826 ◽  
Author(s):  
Wan C. Tan ◽  
Jean Bourbeau ◽  
Shawn D. Aaron ◽  
James C. Hogg ◽  
François Maltais ◽  
...  
Keyword(s):  
Lung Function ◽  
Population Based ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Long Term Effects ◽  
Obstructive Pulmonary Disease ◽  
Before And After ◽  
Rate Of Decline ◽  
Never Smokers

BackgroundPrevious studies have associated marijuana exposure with increased respiratory symptoms and chronic bronchitis among long-term cannabis smokers. The long-term effects of smoked marijuana on lung function remain unclear.MethodsWe determined the association of marijuana smoking with the risk of spirometrically defined chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio <0.7) in 5291 population-based individuals and the rate of decline in FEV1 in a subset of 1285 males and females, aged ≥40 years, who self-reported use (or non-use) of marijuana and tobacco cigarettes and performed spirometry before and after inhaled bronchodilator on multiple occasions. Analysis for the decline in FEV1 was performed using random mixed effects regression models adjusted for age, sex and body mass index. Heavy tobacco smoking and marijunana smoking was defined as >20 pack-years and >20 joint-years, respectively.Results∼20% of participants had been or were current marijuana smokers with most having smoked tobacco cigarettes in addition (83%). Among heavy marijuana users, the risk of COPD was significantly increased (adjusted OR 2.45, 95% CI 1.55–3.88). Compared to never-smokers of marijuana and tobacco, heavy marijuana smokers and heavy tobacco smokers experienced a faster decline in FEV1 by 29.5 mL·year−1 (p=0.0007) and 21.1 mL·year−1 (p<0.0001), respectively. Those who smoked both substances experienced a decline of 32.31 mL·year−1 (p<0.0001).InterpretationHeavy marijuana smoking increases the risk of COPD and accelerates FEV1 decline in concomitant tobacco smokers beyond that observed with tobacco alone.

scholarly journals Serum 25-hydroxyvitamin D level, smoking and lung function in adults: the HUNT Study

2015 ◽  
Vol 46 (2) ◽  
pp. 355-363 ◽  
Author(s):  
Tricia L. Larose ◽  
Ben M. Brumpton ◽  
Arnulf Langhammer ◽  
Carlos A. Camargo ◽  
Yue Chen ◽  
...  
Keyword(s):  
Lung Function ◽  
Forced Expiratory Volume ◽  
Lung Function Decline ◽  
Cross Sectional ◽  
Hydroxyvitamin D ◽  
Impaired Lung Function ◽  
25 Hydroxyvitamin D ◽  
Hunt Study ◽  
Never Smokers

The association between serum 25-hydroxyvitamin D (25(OH)D) level and lung function changes in the general population remains unclear.We conducted cross-sectional (n=1220) and follow-up (n=869) studies to investigate the interrelationship of serum 25(OH)D, smoking and lung function changes in a random sample of adults from the Nord-Trøndelag Health (HUNT) Study, Norway.Lung function was measured using spirometry and included forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % pred and FEV1/FVC ratio. Multiple linear and logistic regression models estimated the adjusted difference in lung function measures or lung function decline, adjusted odds ratios for impaired lung function or development of impaired lung function and 95% confidence intervals.40% of adults had serum 25(OH)D levels <50 nmol·L−1. Overall, those with a serum 25(OH)D level <50 nmol·L−1 showed worse lung function and increased odds of impaired lung function compared to the ≥50 nmol·L−1 group. These associations tended to be stronger among ever-smokers, including greater decline in FEV1/FVC ratio and greater odds of the development of impaired lung function (FEV1/FVC <70% OR 2.4, 95% CI 1.2–4.9). Associations among never-smokers were null. Results from cross-sectional and follow-up studies were consistent. There were no associations between serum 25(OH)D levels and lung function or lung function changes in never-smokers, whereas significant associations were observed in ever-smokers.

scholarly journals DNA methylation at birth is associated with lung function development till age 26 years

2020 ◽  
pp. 2003505
Author(s):  
Nandini Mukherjee ◽  
Ryan Arathimos ◽  
Su Chen ◽  
Parnian Kheirkhah Rahimabad ◽  
Luhang Han ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Lung Function ◽  
Early Adulthood ◽  
Forced Expiratory Volume ◽  
Parents And Children ◽  
Forced Expiratory Flow ◽  
Heel Prick ◽  
F2 Generation ◽  
Preventative Interventions

Little is known about whether DNA methylation (DNAm) of cytosine-phosphate-guanine (CpG) sites at birth predicts patterns of lung function development. We used heel prick DNAm from the F1-generation of Isle of Wight birth cohort (IOWBC-F1) for discovery of CpGs associated with lung function trajectories (Forced Expiratory Volume, Forced Vital Capacity, their ratio, and Forced Expiratory Flow at 25–75%) over the first 26 years, stratified by sex. We replicated the findings in the Avon Longitudinal Study of Parents and Children (ALSPAC) using cord blood DNAm.Epigenome-wide screening was applied to identify CpGs associated with lung function trajectories in 396 boys, and 390 girls of IOWBC-F1. Replication in ALSPAC focused on lung function at ages 8, 15 and 24 years. Statistically significantly replicated CpGs were investigated for consistency in direction of association between cohorts, stability of DNAm over time in IOWBC-F1, relevant biological processes, and for association with gene expression (n=161) in IOWBC F2-generation (IOWBC-F2).Differential DNAm of 8 CpGs on genes GLUL, MYCN, HLX, LHX1, COBL, COL18A1, STRA6, and WNT11 involved in developmental processes, were significantly associated with lung function in the same direction in IOWBC-F1 and ALSPAC, and showed stable patterns at birth, age 10 and 18 years between high and low lung function trajectories in IOWBC-F1. CpGs on LHX1 and COL18A1 were linked to gene expression in IOWBC-F2.In two large cohorts, novel DNAm at birth were associated with patterns of lung function in adolescence and early adulthood providing possible targets for preventative interventions against adverse pulmonary function development.

scholarly journals The Impact of Tobacco Smoking on Adult Asthma Outcomes

2021 ◽  
Vol 18 (3) ◽  
pp. 992
Author(s):  
Angelica Tiotiu ◽  
Iulia Ioan ◽  
Nathalie Wirth ◽  
Rodrigo Romero-Fernandez ◽  
Francisco-Javier González-Barcala
Keyword(s):  
Lung Function ◽  
Asthma Control ◽  
Tobacco Smoking ◽  
Smoking Status ◽  
Forced Expiratory Volume ◽  
Asthmatic Patients ◽  
Asthma Outcomes ◽  
Never Smokers ◽  
Respiratory Outcomes ◽  
The Impact

Background: Tobacco smoking is associated with more severe asthma symptoms, an accelerated decline in lung function, and reduced responses to corticosteroids. Our objective was to compare asthma outcomes in terms of disease control, exacerbation rates, and lung function in a population of asthmatic patients according to their smoking status. Methods: We compared patients’ demographics, disease characteristics, and lung-function parameters in current-smokers (CS, n = 48), former-smokers (FS, n = 38), and never-smokers (NS, n = 90), and identified predictive factors for asthma control. Results: CS had a higher prevalence of family asthma/atopy, a lower rate of controlled asthma, impaired perception of dyspnea, an increased number of exacerbations, and poorer lung function compared to NS. The mean asthma control questionnaire’s (ACQ) score was higher in CS vs. NS and FS (1.9 vs. 1.2, p = 0.02). Compared to CS, FS had a lower rate of exacerbations, a better ACQ score (similar to NS), a higher prevalence of dyspnea, and greater lung-diffusion capacity. Non-smoking status, the absence of dyspnea and exacerbations, and a forced expiratory volume in one second ≥80% of predicted were associated with controlled asthma. Conclusions: CS with asthma exhibit worse clinical and functional respiratory outcomes compared to NS and FS, supporting the importance of smoking cessation in this population.

scholarly journals Epigenome-wide association study of lung function level and its change

2019 ◽  
Vol 54 (1) ◽  
pp. 1900457 ◽  
Author(s):  
Medea Imboden ◽  
Matthias Wielscher ◽  
Faisal I. Rezwan ◽  
André F.S. Amaral ◽  
Emmanuel Schaffner ◽  
...  
Keyword(s):  
Lung Function ◽  
Association Study ◽  
Adult Population ◽  
Population Based ◽  
Forced Expiratory Volume ◽  
Cross Sectional ◽  
Aryl Hydrocarbon ◽  
Inverse Variance ◽  
Never Smokers ◽  
Meta Analyses

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery–replication EWAS design, DNAme in blood and spirometry were measured twice, 6–15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10−7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10−21 and pcombined=7.22×10−50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65×10−20).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.

No effect of artificial gravity on lung function with exercise training during head-down bed rest

2015 ◽  
pp. 1-7
Author(s):  
Longxiang Su ◽  
Yinghua Guo ◽  
Yajuan Wang ◽  
Delong Wang ◽  
Changting Liu
Keyword(s):  
Lung Function ◽  
Pulse Rate ◽  
Vital Capacity ◽  
Pulmonary Ventilation ◽  
Bed Rest ◽  
Forced Expiratory Volume ◽  
Observation Time ◽  
Artificial Gravity ◽  
Postural Changes ◽  
Expiratory Flow

AbstractTo explore the effectiveness of microgravity simulated by head-down bed rest (HDBR) and artificial gravity (AG) with exercise on lung function. Twenty-four volunteers were randomly divided into control and exercise countermeasure (CM) groups for 96 h of 6° HDBR. Comparisons of pulse rate, pulse oxygen saturation (SpO2) and lung function were made between these two groups at 0, 24, 48, 72, 96 h. Compared with the sitting position, inspiratory capacity and respiratory reserve volume were significantly higher than before HDBR (0° position) (P&lt; 0.05). Vital capacity, expiratory reserve volume, forced vital capacity, forced expiratory volume in 1 s, forced inspiratory vital capacity, forced inspiratory volume in 1 s, forced expiratory flow at 25, 50 and 75%, maximal mid-expiratory flow and peak expiratory flow were all significantly lower than those before HDBR (P&lt; 0.05). Neither control nor CM groups showed significant differences in the pulse rate, SpO2, pulmonary volume and pulmonary ventilation function over the HDBR observation time. Postural changes can lead to variation in lung volume and ventilation function, but a HDBR model induced no changes in pulmonary function and therefore should not be used to study AG CMs.

scholarly journals Clinical features and management of children with primary ciliary dyskinesia in England

2020 ◽  
Vol 105 (8) ◽  
pp. 724-729 ◽  
Author(s):  
Bruna Rubbo ◽  
Sunayna Best ◽  
Robert Anthony Hirst ◽  
Amelia Shoemark ◽  
Patricia Goggin ◽  
...  
Keyword(s):  
Lung Function ◽  
Hearing Impairment ◽  
Hearing Aids ◽  
Primary Ciliary Dyskinesia ◽  
Service Evaluation ◽  
Forced Expiratory Volume ◽  
Management Service ◽  
National Data ◽  
Randomised Controlled ◽  
Ciliary Dyskinesia

ObjectiveIn England, the National Health Service commissioned a National Management Service for children with primary ciliary dyskinesia (PCD). The aims of this study were to describe the health of children seen in this Service and compare lung function to children with cystic fibrosis (CF).DesignMulti-centre service evaluation of the English National Management PCD Service.SettingFour nationally commissioned PCD centres in England.Patients333 children with PCD reviewed in the Service in 2015; lung function data were also compared with 2970 children with CF.ResultsMedian age at diagnosis for PCD was 2.6 years, significantly lower in children with situs inversus (1.0 vs 6.0 years, p<0.001). Compared with national data from the CF Registry, mean (SD) %predicted forced expiratory volume in one second (FEV1) was 76.8% in PCD (n=240) and 85.0% in CF, and FEV1 was lower in children with PCD up to the age of 15 years. Approximately half of children had some hearing impairment, with 26% requiring hearing aids. Children with a lower body mass index (BMI) had lower FEV1 (p<0.001). One-third of children had positive respiratory cultures at review, 54% of these grew Haemophilus influenzae.ConclusionsWe provide evidence that children with PCD in England have worse lung function than those with CF. Nutritional status should be considered in PCD management, as those with a lower BMI have significantly lower FEV1. Hearing impairment is common but seems to improve with age. Well-designed and powered randomised controlled trials on management of PCD are needed to inform best clinical practice.

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