scholarly journals Spirometric traits show quantile-dependent heritability, which may contribute to their gene-environment interactions with smoking and pollution

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9145 ◽  
Author(s):  
Paul T. Williams
Keyword(s):  
Quantile Regression ◽  
Population Distribution ◽  
Genetic Effect ◽  
Forced Expiratory Volume ◽  
Gene Environment ◽  
Heart Study ◽  
Significance Levels ◽  
Forced Expiratory Flow ◽  
Expiratory Flow ◽  
Regression Slopes

Background “Quantile-dependent expressivity” refers to a genetic effect that is dependent upon whether the phenotype (e.g., spirometric data) is high or low relative to its population distribution. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and the FEV1/FVC ratio are moderately heritable spirometric traits. The aim of the analyses is to test whether their heritability (h2) is constant over all quantiles of their distribution. Methods Quantile regression was applied to the mean age, sex, height and smoking-adjusted spirometric data over multiple visits in 9,993 offspring-parent pairs and 1,930 sibships from the Framingham Heart Study to obtain robust estimates of offspring-parent (βOP), offspring-midparent (βOM), and full-sib regression slopes (βFS). Nonparametric significance levels were obtained from 1,000 bootstrap samples. βOPs were used as simple indicators of quantile-specific heritability (i.e., h2 = 2βOP/(1+rspouse), where rspouse was the correlation between spouses). Results βOP ± standard error (SE) decreased by 0.0009 ± 0.0003 (P = 0.003) with every one-percent increment in the population distribution of FEV1/FVC, i.e., βOP ± SE were: 0.182 ± 0.031, 0.152 ± 0.015; 0.136 ± 0.011; 0.121 ± 0.013; and 0.099 ± 0.013 at the 10th, 25th, 50th, 75th, and 90th percentiles of the FEV1/FVC distribution, respectively. These correspond to h2 ± SEs of 0.350 ± 0.060 at the 10th, 0.292 ± 0.029 at the 25th, 0.262 ± 0.020 at the 50th, 0.234 ± 0.025 at the 75th, and 0.191 ± 0.025 at the 90th percentiles of the FEV1/FVC ratio. Maximum mid-expiratory flow (MMEF) h2 ± SEs increased 0.0025 ± 0.0007 (P = 0.0004) with every one-percent increment in its distribution, i.e.: 0.467 ± 0.046, 0.467 ± 0.033, 0.554 ± 0.038, 0.615 ± 0.042, and 0.675 ± 0.060 at the 10th, 25th, 50th, 75th, and 90th percentiles of its distribution. This was due to forced expiratory flow at 75% of FVC (FEF75%), whose quantile-specific h2 increased an average of 0.0042 ± 0.0008 for every one-percent increment in its distribution. It is speculated that previously reported gene-environment interactions may be partially attributable to quantile-specific h2, i.e., greater heritability in individuals with lower FEV1/FVC due to smoking or airborne particles exposure vs. nonsmoking, unexposed individuals. Conclusion Heritabilities of FEV1/FVC, MMEF, and FEF75% from quantile-regression of offspring-parent and sibling spirometric data suggest their quantile-dependent expressivity.

scholarly journals Quantile-specific heritability of plasma fibrinogen concentrations

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262395
Author(s):  
Paul T. Williams
Keyword(s):  
Smoking Status ◽  
Genetic Effect ◽  
Disease Status ◽  
Plasma Fibrinogen ◽  
Blood Protein ◽  
Fibrinogen Concentration ◽  
Gene Environment ◽  
Heart Study ◽  
Regression Slopes ◽  
Pollution Exposure

Background Fibrinogen is a moderately heritable blood protein showing different genetic effects by sex, race, smoking status, pollution exposure, and disease status. These interactions may be explained in part by “quantile-dependent expressivity”, where the effect size of a genetic variant depends upon whether the phenotype (e.g. plasma fibrinogen concentration) is high or low relative to its distribution. Purpose Determine whether fibrinogen heritability (h2) is quantile-specific, and whether quantile-specific h2 could account for fibrinogen gene-environment interactions. Methods Plasma fibrinogen concentrations from 5689 offspring-parent pairs and 1932 sibships from the Framingham Heart Study were analyzed. Quantile-specific heritability from offspring-parent (βOP, h2 = 2βOP/(1+rspouse)) and full-sib regression slopes (βFS, h2 = {(1+8rspouseβFS)0.05–1}/(2rspouse)) were robustly estimated by quantile regression with nonparametric significance assigned from 1000 bootstrap samples. Results Quantile-specific h2 (±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted fibrinogen distribution when estimated from βOP (Ptrend = 5.5x10-6): 0.30±0.05 at the 10th, 0.37±0.04 at the 25th, 0.48±0.05 at the 50th, 0.61±0.06 at the 75th, and 0.65±0.08 at the 90th percentile, and when estimated from βFS (Ptrend = 0.008): 0.28±0.04 at the 10th, 0.31±0.04 at the 25th, 0.36±0.03 at the 50th, 0.41±0.05 at the 75th, and 0.50±0.06 at the 90th percentile. The larger genetic effect at higher average fibrinogen concentrations may contribute to fibrinogen’s greater heritability in women than men and in Blacks than Whites, and greater increase from smoking and air pollution for the FGB -455G>A A-allele. It may also explain greater fibrinogen differences between: 1) FGB -455G>A genotypes during acute phase reactions than usual conditions, 2) GTSM1 and IL-6 -572C>G genotypes in smokers than nonsmokers, 3) FGB -148C>T genotypes in untreated than treated diabetics, and LPL PvuII genotypes in macroalbuminuric than normoalbuminuric patients. Conclusion Fibrinogen heritability is quantile specific, which may explain or contribute to its gene-environment interactions. The analyses do not disprove the traditional gene-environment interpretations of these examples, rather quantile-dependent expressivity provides an alternative explanation that warrants consideration.

scholarly journals Quantile-Dependent Expressivity of Serum Uric Acid Concentrations

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Paul T. Williams
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Effect Size ◽  
Genetic Variant ◽  
Genetic Effect ◽  
Obese Patients ◽  
Processed Meats ◽  
Gene Environment ◽  
Heart Study ◽  
Regression Slopes

Objective. “Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., serum uric acid) is high or low relative to its distribution. Analyses were performed to test whether serum uric acid heritability is quantile-specific and whether this could explain some reported gene-environment interactions. Methods. Serum uric acid concentrations were analyzed from 2151 sibships and 12,068 offspring-parent pairs from the Framingham Heart Study. Quantile-specific heritability from offspring-parent regression slopes ( β OP , h 2 = 2 β OP / 1 + r spouse ) and full-sib regression slopes ( β FS , h 2 = 1 + 8 r spouse β FS 0.5 − 1 / 2 r spouse ) was robustly estimated by quantile regression with nonparametric significance assigned from 1000 bootstrap samples. Results. Quantile-specific h 2 (±SE) increased with increasing percentiles of the offspring’s sex- and age-adjusted uric acid distribution when estimated from β OP   P trend = 0.001 : 0.34 ± 0.03 at the 10th, 0.36 ± 0.03 at the 25th, 0.41 ± 0.03 at the 50th, 0.46 ± 0.04 at the 75th, and 0.49 ± 0.05 at the 90th percentile and when estimated from β FS   P trend = 0.006 . This is consistent with the larger genetic effect size of (1) the SLC2A9 rs11722228 polymorphism in gout patients vs. controls, (2) the ABCG2 rs2231142 polymorphism in men vs. women, (3) the SLC2A9 rs13113918 polymorphism in obese patients prior to bariatric surgery vs. two-year postsurgery following 29 kg weight loss, (4) the ABCG2 rs6855911 polymorphism in obese vs. nonobese women, and (5) the LRP2 rs2544390 polymorphism in heavier drinkers vs. abstainers. Quantile-dependent expressivity may also explain the larger genetic effect size of an SLC2A9/PKD2/ABCG2 haplotype for high vs. low intakes of alcohol, chicken, or processed meats. Conclusions. Heritability of serum uric acid concentrations is quantile-specific.

scholarly journals Factors affecting spirometry reference range in growing children

2019 ◽  
Vol 35 (6) ◽  
Author(s):  
Sara Sadiq ◽  
Nadeem Ahmed Rizvi ◽  
Fahad Khalid Soleja ◽  
Muaz Abbasi
Keyword(s):  
Reference Range ◽  
Forced Expiratory Volume ◽  
P Value ◽  
Strong Positive Correlation ◽  
Linear Regression Models ◽  
Factors Affecting ◽  
Independent Variables ◽  
Creative Commons ◽  
Forced Expiratory Flow ◽  
Expiratory Flow

Objectives: To find out the association of weight, height and age with spirometry variables and to generate a regression equation by taking weight as an independent variable beside age and height among children and adolescents of Karachi. Methods: A modified form of ISSAC questionnaire was used. The spirometry variables recorded were Forced vital capacity (FVC), Forced expiratory volume in 1 second (FEV1), FEV1/FVC, Peak expiratory flow rate (PEF), Forced expiratory flow between 25% and 75% expired volume (FEF25-75). A person’s correlation coefficient among boys and girls were calculated for all spirometry variable considering age, height and weight as independent variables. The linear regression models were calculated. Results: The results reported a linear correlation of lung function variables with all three independent variables (i.e. p-value = 0.000), in which age and height manifested a strong positive correlation while weight reported a moderately significant correlation. All spirometry variables such as FVC, FEV1, PEF and FEF25-75 reported a significant coefficient of dependency and coefficient of correlation individually with age, height and weight. Conclusion: It is concluded that beside age, height and weight both also have significant correlation with lung volumes so these should be taken into account when using spirometry as a diagnostic test. doi: https://doi.org/10.12669/pjms.35.6.1212 How to cite this:Sadiq S, Rizvi NA, Soleja FK, Abbasi M. Factors affecting spirometry reference range in growing children. Pak J Med Sci. 2019;35(6):1587-1591. doi: https://doi.org/10.12669/pjms.35.6.1212 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals The Value of Spirometry in Subglottic Stenosis

2019 ◽  
Vol 98 (2) ◽  
pp. 98-101 ◽  
Author(s):  
Alhelali Abdullah ◽  
A. Alrabiah ◽  
Sayed S. Habib ◽  
Y. Aljathlany ◽  
A. Aljasser ◽  
...  
Keyword(s):  
Upper Airway ◽  
Forced Expiratory Volume ◽  
Endoscopic Examination ◽  
Subglottic Stenosis ◽  
King Saud University ◽  
Medical City ◽  
Forced Expiratory Flow ◽  
Surgery Outcomes ◽  
Expiratory Flow ◽  
Grade 3

The diagnosis of subglottic stenosis (SGS) is usually made by clinical assessment and definitively by a direct endoscopic examination. This study aimed to evaluate different spirometric values in relation to anatomical grading and severity of subglottic stenosis cases of upper airway obstruction. Cases of SGS that underwent dilatational procedures endoscopically at the otolaryngology department of the King Saud University Medical City, Riyadh, Saudi Arabia, from June 2015 to October 2017 were collected. Pulmonary function test (PFT) pre- and postoperative parameters and the grades of subglottic stenosis were extracted. We compared different spirometric values to the severity of SGS and compared the pre- and postoperative results for each patient. There were 19 cases with a valid PFT study within 7 days preoperatively in addition to a documented intraoperative grading according to the Myer-Cotton grading system; 7 (36.8%) were grade 1, 8 (42.1%) were grade 2, and 4 (21.1%) were grade 3. The actual preoperative ratio of forced expiratory volume (FEV1) in 1 second to peak expiratory flow (PEF) for all 19 patients ranged from 7.34 to 21.40 mL/L/min. We found a significant improvement in all spirometric parameters postdilatation including PEF ( P < .001), FEV1 ( P < .001), FEV1/PEF ( P = .001), forced expiratory flow (FEF) from 25%, 50%, and 75% of vital capacity, respectively, FEF25 ( P < .001), FEF50 ( P = .001), FEF75 ( P = .048), and maximum mid-expiratory flow ( P = .002). We did not find any correlation between the severity of stenosis and spirometric values. This study revealed that spirometry is a useful marker in following up patients with subglottic stenosis and is also a good indicator to determine postairway surgery outcomes. However, these markers do not correlate with anatomical grading and the severity of subglottic stenosis.

Relationship of ventilatory capacity to hyperbaric exposure in divers

1984 ◽  
Vol 56 (6) ◽  
pp. 1655-1658 ◽  
Author(s):  
I. S. Davey ◽  
J. E. Cotes ◽  
J. W. Reed
Keyword(s):  
Flow Rate ◽  
Vital Capacity ◽  
Positive Association ◽  
Forced Expiratory Volume ◽  
Elastic Tissue ◽  
Significant Positive Association ◽  
Cross Sectional ◽  
Maximal Depth ◽  
Forced Expiratory Flow ◽  
Expiratory Flow

The results of divers' annual medical examinations were used to assess the effects of diving exposure independent of age, stature, and smoking on forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). Cross-sectional analysis of records for 858 men showed a significant positive association between the maximal depth that subjects had experienced and FVC but not FEV1. There was a significant negative association for FEV1/FVC%, and this index was also positively correlated with years of diving exposure. Among a subsample of 81 men the forced expiratory flow rate at low lung volume was reduced relative to that of control subjects similarly assessed; the extent of the reduction from the reference value was significantly correlated with the diving exposure. Longitudinal analysis of results for 255 men over a minimum of 5 yr showed that the change in FVC per annum (positive or negative) was correlated with the change in maximal depth; there were no similar associations for FEV1 or FEV1/FVC%. Thus diving exposure affects the vital capacity and the forced expiratory flow rate at small lung volumes. The latter is evidence for narrowing of airways that might be secondary to diving-induced loss of lung elastic tissue; this hypothesis merits further investigation.

An assessment of forced expiratory volumes and flow rates in the detection of early ventilatory impairment in RN submariners

1985 ◽  
Vol 71 (3) ◽  
pp. 167-170
Author(s):  
R. Herrmann ◽  
G. M. Clifford ◽  
D. J. Smith ◽  
Caroline S. M. Searing
Keyword(s):  
Forced Vital Capacity ◽  
Vital Capacity ◽  
Linear Regression Analysis ◽  
Smoking Habit ◽  
Multiple Linear Regression Analysis ◽  
Forced Expiratory Volume ◽  
Single Breath ◽  
Forced Expiratory Flow ◽  
Expiratory Flow ◽  
Highly Correlated

AbstractA prospective study of an early diagnostic test of small airway dysfunction, the forced expiratory flow between 75 and 85% of the forced vital capacity, was carried out in 230 RN submariners. All the subjects were male caucasians, of whom 105 were smokers and 125 non-smokers. Measurements were performed using a single breath wedge spirometer (Vitalograph®) and forced vital capacity (FVC), forced expiratory volume in one second (FEV1), ratio of the FEV1 to the FVC (FEV1/FVC%) and the forced expiratory flow between 75 and 85% of the forced vital capacity (FEF75–85) obtained from the tracings in accordance with the recommendations of the American Thoracic Society. Multiple linear regression analysis of these four measurements together with height, age and smoking habit showed age to be the most significant factor for FEF75–85, followed by height Height was the most significant factor for FVC and FEV1 followed by age. Age was the only significant factor for FEV1/FVC%. FEF75-85 was highly correlated with FEV1/FVC% (r = 0.72) and to a lesser extent with FEV1 and FVC (r = 0.70 and 0.37 respectively). In the presence of age and height no significant effect of smoking habit on FEF75–85 could be demonstrated. However when the FEV1/FYC%, age and smoking habit were examined, there was found to be a significantly greater decrease in FEV1/FYC% with age in the smokers. It would appear that in this study FEV1/FVC% is a more sensitive index of early obstructive changes induced by smoking than measurement of flow at low lung volumes.

Wheezing in Infants with Cystic Fibrosis: Clinical Course, Pulmonary Function, and Survival Analysis

PEDIATRICS ◽  
1992 ◽  
Vol 90 (5) ◽  
pp. 703-706
Author(s):  
Joseph Reisman ◽  
Mary Corey ◽  
Gerard Canny ◽  
Henry Levison ◽  
Eitan Kerem ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pulmonary Function ◽  
Flow Rate ◽  
Forced Expiratory Volume ◽  
Common Finding ◽  
Study Cohort ◽  
Expiratory Phase ◽  
Significant Difference ◽  
Forced Expiratory Flow ◽  
Expiratory Flow

Wheezing is a common finding in infants with cystic fibrosis (CF). This study was undertaken to determine the prevalence of wheezing in infants with CF and to compare the clinical outcome of those who wheezed in infancy with that of those who did not. The study cohort included 229 CF patients born between 1965 and 1979 with CF diagnosed before 2 years of age. Fifty-seven (25%) had physician-documented wheezing during the first 2 years of life. Wheezing had resolved by the age of 2 years in 50% of the patients and by the age of 4 years in 75%. Although wheezing seemed to be linked to a family history of allergy and asthma, the frequency of the ΔF508 mutation was similar to that of the non-wheezers. There was no significant difference in survival at the age of 13 years between the two groups. At the age of 7 years, patients who had wheezed had significantly lower forced expiratory flow rate at mid-expiratory phase (85 ± 34% predicted) compared with those with no wheezing history (101 ± 34% predicted). At the age of 13 years, forced expiratory volume in 1 second values was lower in the wheezing group (69 ± 24% predicted vs 78 ± 21% predicted), as was forced expiratory flow rate at mid-expiratory phase (56 ± 33% predicted vs 69 ± 30% predicted). In conclusion, although wheezing in infants with CF seems to have diminished with age, pulmonary function abnormalities were more evident at 7 and 13 years of age in the group that wheezed than in the group that did not.

scholarly journals EVALUATION OF ADENOIDS BY ORONASAL AND NASAL SPIROMETRY

2018 ◽  
Vol 11 (10) ◽  
pp. 272 ◽  
Author(s):  
Gayatri Devi R ◽  
Sethu G
Keyword(s):  
Flow Rate ◽  
Upper Airway ◽  
Cost Effective ◽  
Forced Expiratory Volume ◽  
Adenoid Hypertrophy ◽  
Before And After ◽  
Forced Expiratory Flow ◽  
Expiratory Flow ◽  
Age Range ◽  
Peak Inspiratory Flow Rate

Objectives: The main aim of this study is to compare the oronasal and nasal spirometry among adenoid hypertrophy children before and after surgery.Methods: A total of 40 healthy and 40 adenoid hypertrophy children were recruited for this study with the age range from 6 to 15 years. All the children were examined by two measurements (1) oronasal spirometry and (2) nasal spirometry. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1), FEV 1/FVC%, forced expiratory time (FET), peak expiratory flow rate, peak inspiratory flow rate (PIFR), and forced expiratory flow (FEF)25-75, FEF25%, FEF50%, FEF75%, FIF25%, FIF50%, and FIF75% were recorded.Results: All the parameters were significantly reduced in adenoid hypertrophy by nasal spirometry when compared to oronasal spirometry. FEV1/ FVC% was insignificant from oral to nasal values among adenoid hypertrophy in both the sexes. FET can act as an indicator for upper airway obstruction which shown significantly in adenoid hypertrophy but insignificant among control and adenoidectomy. Inspiratory parameters also had shown more variation in nasal than oronasal spirometry.Conclusion: Significant differences were found in many parameters between oronasal and nasal spirometry among adenoids and adenoidectomy. Nasal spirometry is a portable one, simple, and less cost-effective and so it can be used to determine the obstruction in the nose nasopharynx region.

Effects of aerosol methacholine and histamine on airways and lung parenchyma in healthy humans

1993 ◽  
Vol 74 (6) ◽  
pp. 2681-2686 ◽  
Author(s):  
R. Pellegrino ◽  
B. Violante ◽  
E. Crimi ◽  
V. Brusasco
Keyword(s):  
Vital Capacity ◽  
Transpulmonary Pressure ◽  
Lung Parenchyma ◽  
Forced Expiratory Volume ◽  
Flow Volume ◽  
Tissue Properties ◽  
Bronchodilator Effect ◽  
Healthy Humans ◽  
Forced Expiratory Flow ◽  
Expiratory Flow

To investigate whether histamine (His) and methacholine (MCh) have different effects on airways and lung parenchyma, 11 healthy subjects were given aerosol MCh until a response plateau was obtained and then two doses of His. At the plateau, forced expiratory volume in 1 s and forced expiratory flow at 40% of vital capacity from partial flow-volume curves were reduced by 19 +/- 3 (SE) and 80 +/- 4%, respectively. Aerosol His decreased forced expiratory volume in 1 s by an additional 12 +/- 1% but left partial forced expiratory flow unchanged. The bronchodilator effect of deep inhalation, as inferred from the ratio of forced expiratory flow from maximal to that from partial flow-volume curves, increased after MCh and plateaued but decreased after His. Quasi-static transpulmonary pressure-volume area determined in seven subjects was unchanged after MCh but was increased by 57 +/- 10% after His. We conclude that adding His after the response to MCh plateaued does not increase the maximal degree of bronchoconstriction but may increase parenchymal hysteresis, thus blunting the bronchodilator effect of deep inhalation. These results suggest that His and MCh have similar effects on airway smooth muscle but different effects on lung tissue properties.

Ozone exposure decreases the effect of a deep inhalation on forced expiratory flow in normal subjects

2004 ◽  
Vol 96 (5) ◽  
pp. 1651-1657 ◽  
Author(s):  
S. K. Kjærgaard ◽  
O. F. Pedersen ◽  
M. R. Miller ◽  
T. R. Rasmussen ◽  
J. C. Hansen ◽  
...  
Keyword(s):  
Fish Oil ◽  
Normal Subjects ◽  
Lavage Fluid ◽  
Forced Expiratory Volume ◽  
Ozone Exposure ◽  
Double Blind ◽  
Forced Expiratory Flow ◽  
Clean Air ◽  
Nasal Lavage Fluid ◽  
Expiratory Flow

Sixteen healthy nonsmoking subjects (7 women), 21-49 yr old, were exposed in a climate chamber to either clean air or 300 parts/billion ozone on 4 days for 5 h each day. Before each exposure, the subjects had been pretreated with either oxidants (fish oil) or antioxidants (multivitamins). The study design was double-blind crossover with randomized allocation to the exposure regime. Full and partial flow-volume curves were recorded in the morning and before and during a histamine provocation at the end of the day. Nasal cavity volume and inflammatory markers in nasal lavage fluid were also measured. Compared with air, ozone exposure decreased peak expiratory flow, forced expiratory volume in 1 s, and forced vital capacity (FVC), with no significant effect from the pretreatment regimens. Ozone decreased the ratio of maximal to partial flow at 40% FVC by 0.08 ± 0.03 (mean ± SE, analysis of variance: P = 0.018) and at 30% FVC by 0.10 ± 0.05 ( P = 0.070). Ozone exposure did not significantly increase bronchial responsiveness, but, after treatment with fish oil, partial flows decreased more than after vitamins during the histamine test, without changing the maximal-to-partial flow ratio. The decreased effect of a deep inhalation after ozone exposure can be explained by changes in airway hysteresis relative to parenchymal hysteresis, due either to ozone-induced airway inflammation or to less deep inspiration after ozone, not significantly influenced by multivitamins or fish oil.

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