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PubMed2026

A cross-sectional study of oxidative stress pathway genotypes and their interactions with environmental pollutant levels identifies associations with gene expression and lung function.

BACKGROUND: Asthma is a heterogeneous disease influenced by genetic and environmental factors. Fine particulate matter (PM2.5) exacerbates asthma, likely through oxidative stress pathways, but whether genetic variation modifies this effect remains unclear. METHODS: We analysed data on 948 adults with asthma from the Severe Asthma Research Program (SARP), linking ZIP-code-level PM2.5 exposure with whole-genome sequencing data. We tested 4337 single nucleotide polymorphisms (SNPs) in 120 oxidative stress pathway genes for gene-environment (GxE) interactions with PM2.5 on lung function (forced expiratory volume in 1 s [FEV1] % predicted) using weighted linear regression. Gene expression data from bronchial epithelial cells (n = 170) were used to assess cis-expression quantitative trait loci (eQTLs). FINDINGS: Higher PM2.5 exposure was associated with lower FEV1% predicted (β per μg/m3 = -0.7, p = 0.01). We identified 20 SNPs across seven genes (OXSR1, PXDN, TPO, LRRK2, APP, MSRA, MSRB2) with significant GxE interactions after multiple-testing correction. Five SNPs were also eQTLs, linking PM2.5-modified gene expression to lung function. Minor alleles in OXSR1 and PXDN were associated with reduced gene expression and worsened FEV1% under high PM2.5 exposure. Conversely, TPO variants were associated with higher baseline expression and lower lung function, but under increasing PM2.5 exposure, minor allele carriers showed suppressed TPO expression and improved FEV1%. INTERPRETATION: This study identified 20 SNPs in oxidative stress pathway genes that modify the effect of PM2.5 on lung function in asthma. These findings highlight the importance of integrating environmental context in genetic studies and suggest potential therapeutic targets for pollution-sensitive asthma phenotypes. FUNDING: Supported by NIH grants.

Cross-Sectional Studies↗

PubMed1993

Clinical and radiologic features, lung function and therapeutic results in pulmonary histiocytosis X.

Clinical appearance, radiologic findings, lung function and results of corticosteroid therapy were analyzed in 42 adult cases of biopsy-proven pulmonary histiocytosis X. Symptoms were present in only 64%. Using the ILO classification 1980, the evaluation of chest radiographs revealed all categories of profusion, size and shape of nodules. The characteristic 'ring figures', i.e. thin-walled cysts, in the parenchyma were detected in 78% of conventional tomographies (n = 27) and in all patients examined by CT (n = 5). In patients with early disease, lung function tests (n = 26) including body plethysmography, pulmonary diffusing capacity and ergospirometry revealed that parameters of gas exchange are most sensitive (TL,CO 84%, KCO 72%). Bronchial reactivity to carbachol was significantly higher than in controls (n = 12). Lung perfusion scintigram showed an abnormal, but uncharacteristic pattern in 81% (n = 26). During corticosteroid therapy, no progression was observed (n = 36). 85% of patients with radiographic evidence of progressive disease improved after administration of corticosteroids (n = 14).

Adolescent↗

PubMed1999

Effect of temperature on lung function and symptoms in chronic obstructive pulmonary disease.

The present study investigated whether falls in environmental temperature increase morbidity from chronic obstructive pulmonary disease (COPD). Daily lung function and symptom data were collected over 12 months from 76 COPD patients living in East London and related to outdoor and bedroom temperature. Questionnaires were administered which asked primarily about the nature of night-time heating. A fall in outdoor or bedroom temperature was associated with increased frequency of exacerbation, and decline in lung function, irrespective of whether periods of exacerbation were excluded. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) fell markedly by a median of 45 mL (95% percentile range: -113-229 mL) and 74 mL (-454-991 mL), respectively, between the warmest and coolest week of the study. The questionnaire revealed that 10% had bedrooms <13 degrees C for 25% of the year, possibly because only 21% heated their bedrooms and 48% kept their windows open in November. Temperature-related reduction in lung function, and increase in exacerbations may contribute to the high level of cold-related morbidity from chronic obstructive pulmonary disease.

Aged↗

PubMed1997

Postnatal lung function and protein permeability after fetal or maternal corticosteroids in preterm lambs.

We evaluated postnatal lung function and intravascular albumin loss to tissues of 123-days-gestation preterm surfactant-treated and ventilated lambs 15 h after direct fetal (n = 8) or maternal (n = 9) betamethasone treatment or saline placebo (n = 9). The betamethasone-treated groups had similar increases in dynamic compliances, ventilatory efficiency indexes, and lung volumes relative to controls (P < 0.05). The losses of 125I-labeled albumin from blood, a marker of intravascular integrity, and the recoveries of 125I-albumin in muscle and brain were similar for control and betamethasone-exposed lambs. Betamethasone-treated lambs had lower recoveries of 125I-albumin in lung tissues and in alveolar washes than did controls (P < 0.01). Although blood pressures were higher for the treated groups (P < 0.05), all groups had similar blood volumes, cardiac outputs, and organ blood flows. Maternal or fetal treatment with betamethasone 15 h before preterm delivery equivalently improved postnatal lung function, reduced albumin recoveries in lungs, and increased blood pressures. However, prenatal betamethasone had no effects on the systemic intravascular losses of albumin or did not change blood volumes.

Adrenal Cortex Hormones↗

PubMed1992

Antenatal ambroxol effects on surfactant pool size and postnatal lung function in preterm ventilated rabbits.

Following maternal treatments with 50 mg/kg/day ambroxol for 2 or 3 days before delivery at 28 days gestation, preterm rabbits were ventilated to evaluate lung function. Subsequently, surfactant saturated phosphatidylcholine (SatPC) pool sizes were measured. One half of the ambroxol treated and control rabbits were given surfactant at delivery. Although surfactant improved lung function comparably for control and ambroxol treated rabbits, ambroxol treatments did not change ventilatory pressure requirements, compliances, or the recovery of intravascular labeled albumin in the lungs. Ambroxol treatments tended to increase lung volumes as evaluated by pressure-volume curves. The ambroxol treatments significantly increased lung tissue SatPC by 22%, but there were no changes in alveolar SatPC pool values. These results do not indicate a large effect of ambroxol on lung function in preterm rabbits.

Ambroxol↗

PubMed1997

Respiratory symptoms and lung function abnormalities among machine operators in automobile production.

This cross-sectional study was designed to assess differences in prevalence of respiratory symptoms and lung function between machine operators exposed to semisynthetic or soluble metal-working fluids (MWFs) and unexposed assemblers and to assess exposure-response relationships with MWF type, total aerosol, endotoxin, culturable bacteria and fungi. We evaluated 183 machine operators and 66 assemblers from one large automobile transmission plant using questionnaires, spirometry data, and cross-shift assessment of both lung function and respiratory symptoms. We found that airborne exposures to total aerosol, endotoxin, culturable bacteria and fungi were higher in machine operations than in the assembly area. There was a correlation between bulk and airborne culturable bacteria, but not between bulk and airborne culturable fungi. Machine operators had significantly more usual cough, usual phlegm, work-related chest tightness and post-shift symptoms of chest tightness, throat irritation, and cough compared with assemblers. We found exposure-response relationships between respiratory symptoms and total aerosol, as well as culturable fungi and bacteria. Associations with endotoxin were not strong or consistent, possibly because airborne levels were generally low. Cross-shift lung function decrements did not differ between machine operators and assemblers and there were no associations with MWF or specific exposures. The finding of respiratory symptoms at low levels of exposure in this study suggests the need to re-assess total aerosol thresholds. Associations between airborne fungal exposures and respiratory symptoms need further study to characterize sources of exposure other than MWF in machining operations.

Adult↗

PubMed1995

[Duration of the effect of inhaled corticosteroids on lung function and sensitivity of the respiratory tract in patients with bronchial asthma].

AIM: The effects of cessation of therapy with inhaled steroids on symptoms, lung function, and airway responsiveness in stable bronchial asthma should be examined. PATIENTS AND METHODS: During a 4-week run-in period 24 patients inhaled beclomethasone dipropionate (BDP) 2000 micrograms/d and salbutamol 800 micrograms/d. This was followed by a 6-week treatment period during which the patients obtained either placebo plus 800 micrograms salbutamol or 2000 micrograms BDP plus 800 micrograms salbutamol in a randomized double-blind design. Symptoms, lung function, and airway responsiveness to histamine were measured before and after the run-in period and at the end of each week during the treatment period. RESULTS: Airway responsiveness was assessed as the concentration of inhaled histamine which caused a 20% fall in FEV1 compared to baseline (PC20). During the run-in period, 21 of the 24 patients showed an increase of PC20 (p = 0.0005). In the placebo group, 5 patients had to cease the protocol after 1 to 4 weeks of the treatment period because of intolerable symptoms and severe worsening of lung function; PC20 on entry was significantly smaller in these patients compared to those who completed the protocol (p = 0.01). After 6 weeks, FEV1 had decreased by 8.5% (p = 0.005) and PC20 by 1.71 doubling concentrations (p = 0.0003). In the BDP group, all patients completed the study and PC20 after the treatment period was significantly higher (p = 0.04) in the BDP than in the placebo group. CONCLUSION: Our data suggest that patients on long-term inhaled steroid therapy with a high degree of bronchial hyperresponsiveness are more likely to show early deterioration of their clinical state after cessation of inhaled steroids.

Administration, Inhalation↗

PubMed1996

The effects of ambient ozone on lung function in children: a reanalysis of six summer camp studies.

Studies of children attending summer camps often have observed relationships between daily outdoor ozone (O3) concentrations and decreased lung function that are qualitatively similar to results seen in human chamber studies. The former studies, focusing on the pulmonary effects of O3 and associated pollutants on children under natural conditions of exposure, are potentially of great importance to understanding the public health impact of ambient O3. However, a thorough assessment of the results of these studies has been hampered by differences in the analysis and reporting of data across the various studies. We obtained data sets from six summer camp studies carried out by three separate investigative groups, including two New Jersey studies performed by New York University, two studies in Ontario carried out by Health and Welfare Canada, and two studies in southern California. The data consisted of sequential, daily measurements of forced expiratory volume in 1 sec (FEV1), peak expiratory flow rate (PEFR), and 1-hr O3 concentration in the hour preceding lung function measurements for each child. We analyzed the relationships between lung function and O3 using linear regression models that fit subject-specific intercepts and a single, pooled O3 slope. These models were fit for each of the six studies separately and for all studies combined. All of the study-specific slopes of FEV1 on O3 were negative (i.e., increased O3 associated with decreased FEV1); five of six were statistically significant. Analysis of the combined six-study data set yielded a slope of -0.50 ml FEV1/ppb O3 (p<0.0001). Addition of time-trend variables to the combined-data analysis diminished, but did not eliminate, the FEV1-O3 relationship. Study-specific slopes for PEFR on O3 were more variable. Combined over studies, no significant relationship was observed between PEFR and O3. However, this negative finding appeared to be partially confounded by time trends in PEFR. The results of this reanalysis provide strong evidence that children exposed to O3 under natural conditions experience decreases in FEV1 of the kind demonstrated in laboratory studies, and raise concern that other acute respiratory effects observed in those studies (e.g., pulmonary inflammation) may also occur in young people exposed to ambient O3.

Adolescent↗

PubMed1995

Lung function measurement in awake young children.

The aim of the study was to evaluate methods applicable in a clinical setting for monitoring of changes in lung function in awake young children. Impedance measurements by the impulse oscillation technique (ZIOS), respiratory resistance measurements by the interrupter technique (Rint) and transcutaneous measurements of oxygen tension (Ptc,O2) were compared with concomitant measurements of specific airway resistance (sRaw) and forced expiratory volume in one second (FEV1) by whole body plethysmography and spirometry, respectively, during methacholine challenge in 21 young children aged 4-6 yrs, with suspected asthma. Measurements with each technique were repeated after each challenge step. A special face-mask was developed with an integrated mouthpiece which ensured mouth breathing during the measurements. The order of sensitivity of the techniques to assess methacholine-induced changes in lung function was ZIOS > sRaw > Ptc,O2 > FEV1 > Rint. ZIOS was significantly more sensitive than all subsequent methods, and Ptc,O2 was significantly more sensitive than FEV1. ZIOS, sRaw and Rint, but not Ptc,O2 and FEV1, detected the subclinical increase in bronchial muscle tone in the children during baseline, which was revealed by the significantly reduced airway obstruction after inhalation of a beta 2-agonist as compared to baseline. It is concluded that ZIOS, Rint and Ptc,O2 change in parallel with sRaw and FEV1 and with a comparable sensitivity during simultanoeous measurements of the response to methacholine in young children aged 4-6 yrs. This implies that ZIOS, Rint and Ptc,O2 provide convenient indices of changes in lung function. Their combined use will be useful for monitoring airway diseases of young children.

Airway Resistance↗

PubMed2003

Effect of hypocaloric meals with different macronutrient compositions on energy metabolism and lung function in obese women.

OBJECTIVE: We investigated the effect of hypocaloric mixed diets with different proportions of carbohydrate, protein, and fat on resting metabolic rate and the thermic effect of food in obese women. METHODS: Three mixed hypocaloric diets were consumed in random order during separate periods lasting 7 d each. Between each dietary period there was a washout period of 10 d. Diet 1 had a higher proportion of energy from carbohydrate (72%), diet 2 had a higher proportion of energy from protein (43%), and diet 3 had a higher proportion of energy from fat (68%). Indirect calorimetry and lung function tests were done after the completion of each 7-d diet. Seven obese women, ages 22 to 45 y and with body mass indexes of 32 to 59 kg/m(2), participated in the study. Oxygen consumption, carbon dioxide production, resting metabolic rate, and the thermic effect of food by indirect calorimetry were measured. Lung function tests included spirometry in the seated and upright positions, arterial blood gas analysis, and maximal inspiratory and expiratory pressures. RESULTS: There were no statistically significant differences in the resting metabolic rate and the thermic effect of food resulting from the three diets. The mean resting metabolic rates (kJ/d) were 7453 +/- 1446 for diet 1, 7461 +/- 1965 for diet 2, and 7076 +/- 2048 for diet 3. The mean thermic effects of food (kcal/min) were -0.02 +/- 0.07 for diet 1, -0.01 +/- 0.25 for diet 2, and 0.05 +/- 0.13 for diet 3. Lung function tests were normal before and after the hypocaloic diets: partial pressure of oxygen (mmHg) values were 81 +/- 13, 77 +/- 8, and 78 +/- 11 for diets 1 to 3, respectively; and partial pressure of carbon dioxide (mmHg) were 37 +/- 4, 37 +/- 3, and 37 +/- 4 for diets 1 to 3, respectively. CONCLUSIONS: Obese women with normal lung function tests and consuming mixed hypocaloric diets showed no alteration in resting metabolic rate and a reduced or absent thermic effect of food independently of the macronutrient composition.

Adult↗

PubMed1994

Decline of lung function in adults with bronchial asthma.

To investigate the annual decline of lung function in subjects with self-reported asthma, we analyzed data from a longitudinal epidemiologic study. The Copenhagen City Heart Study. The study sample consisted of 10,952 subjects (4,824 men), 20 to 90 yr of age, randomly selected from the city of Copenhagen followed over a 5-yr period. The overall prevalence of asthma was 3.7% (n = 177) in men and 3.6% (n = 219) in women. Subjects who reported asthma at the first examination had, in general, lower values for lung function than did nonasthmatic subjects, which was also the case for subjects who developed asthma during follow-up (new asthma). The annual loss of FEV1 increased with age among both asthmatics and nonasthmatics. Multiple regression analysis showed a higher decline of FEV1 in subjects with new asthma. The excess decline was, on average, 39 ml/yr in men (p = 0.002) and 11 ml/yr in women (NS), respectively, compared with that in nonasthmatic subjects. In subjects with chronic asthma, the decline was not increased compared with that in nonasthmatic subjects. Separate analyses of lifelong nonsmokers revealed that the excess decline of FEV1 in subjects with new asthma was, on average, 33 ml/yr, whereas it was not significantly increased in subjects with chronic asthma. In conclusion, this study of a large sample from the general population showed that the rate of decline of FEV1 is increased in subjects with new asthma, whereas in subjects with chronic asthma the decline of FEV1 did not differ significantly from the decline in the nonasthmatic subjects.

Adult↗

PubMed2004

Effect of in utero growth retardation on lung function at follow-up of prematurely born infants.

The aim of the study was to determine if prematurely born children who had suffered intra-uterine growth retardation (IUGR) had more severe lung function abnormalities than those born an appropriate weight for gestational age (AGA). Analysis of the lung function results of 119 infants (median (range) gestational age of 30 (23-35) weeks) was undertaken. In total, 31 of the infants had suffered IUGR and were born small for gestational age (SGA). Functional residual capacity and airways resistance (Raw) were measured at a median post-natal age of 10 (6-24) months. Specific airway conductance (sGaw) was calculated from thoracic gas volume and Raw. The SGA children were born at a greater gestational age and had a lower body weight at testing than the AGA children. Raw and sGaw differed between the SGA and AGA children. Regression analysis demonstrated that lung volumes were significantly related to body weight at testing, Raw was related to IUGR, maternal smoking and bronchopulmonary dysplasia, and sGaw to maternal smoking. In conclusion, these results suggest that prematurely born infants who have suffered intra-uterine growth retardation may be at increased risk of impaired lung function at follow-up.

Birth Weight↗

PubMed1984

Relation between efficacy of sodium cromoglycate and baseline lung function in exercise- and hyperventilation-induced asthma.

The protective effect of sodium cromoglycate (SCG) against exercise- and hyperventilation-induced asthma with respect to basal lung function was investigated in young asthmatics. The subjects performed standardized exercise or isocapnic hyperventilation challenge tests breathing cold dry air; in each case the effect of SCG was compared with that of a placebo in a double-blind fashion. With exercise as the challenge in 24 subjects, there was a strong positive correlation between the protective effect of SCG and the basal level of lung function. Using hyperventilation as the challenge in 11 subjects, there was no such correlation, but excluding two known placebo responders, there was a negative correlation between the protective effect of SCG and basal lung function. There findings suggest that exercise and hyperventilation operate differently in inducing asthma.

Adolescent↗

PubMed1997

The effect of regular salbutamol on lung function and bronchial hyperresponsiveness in normal subjects and nonasthmatic atopic subjects with allergic rhinitis.

BACKGROUND: The effects of regular inhaled beta-agonist treatment on lung function remain a controversial issue. In an earlier study, the administration of regular inhaled salbutamol resulted in negative changes in FEV1 not only in asthmatics, but also in nonasthmatic atopic subjects. OBJECTIVE: The aim of this study was to confirm these findings and also to examine whether regular inhaled salbutamol would increase bronchial hyperresponsiveness in atopic or normal individuals. DESIGN: The study was a randomized, double-blind, placebo-controlled, crossover investigation. PARTICIPANTS: There were two groups: 10 normal healthy subjects (group A) and nine nonasthmatic atopic subjects (group B). INTERVENTIONS: Subjects received inhaled salbutamol or identical placebo for periods of 6 weeks, the dose being increased in stepwise fashion at 2-week intervals. MEASUREMENTS: Changes in lung function were assessed by measuring spirometric values, airways conductance, and changes in complete and partial expiratory flow volume curves. Changes in these parameters following a methacholine challenge were used to assess bronchial hyperresponsiveness. RESULTS: No statistically significant differences in lung function or bronchial hyperresponsiveness were noted to occur as the result of treatment in either group. CONCLUSION: Our results do not support the view that regular inhaled salbutamol in normal or atopic subjects without asthma causes adverse changes in the airways.

Administration, Inhalation↗

PubMed1994

Effect of antibiotic treatment on inflammatory markers and lung function in cystic fibrosis patients with Pseudomonas cepacia.

BACKGROUND: The acquisition of Pseudomonas cepacia in patients with cystic fibrosis is associated with increasing deterioration in lung function and more frequent hospital admissions. Pseudomonas cepacia is usually resistant to several antibiotics in vitro, but the response of patients colonised with the organism has not been extensively studied in vivo. METHODS: A three month prospective study was performed to investigate the response of 14 Ps cepacia positive patients and 10 Ps cepacia negative patients to a two week course of intravenous antibiotics. All those who were Ps cepacia negative and six of the 14 Ps cepacia positive patients had Ps aeruginosa in their sputum which was sensitive to the prescribed therapy. The inflammatory markers C-reactive protein, white blood cell count, serum lactoferrin, neutrophil elastase/alpha 1-antitrypsin complex, and tumour necrosis factor alpha were measured at the start and end of each antibiotic course. RESULTS: The median (range) % improvement in baseline FEV1 and FVC following treatment in the group as a whole was 15.2% (-23.5% to 156.3%) and 23.9% (-36.8% to 232.7%) respectively. There was no statistical difference in improvement in lung function, body weight, or inflammatory markers between individuals who were Ps cepacia positive and those who were Ps cepacia negative. CONCLUSIONS: Patients who are Ps cepacia positive appear to respond as well to intravenous antibiotics as those who are Ps cepacia negative, despite having lower lung function and a bacterium in their sputum which is resistant in vitro to the antibiotics used.

Adult↗

PubMedDate not supplied

Sitting height, fat-free mass and body fat as reference variables for lung function in healthy British children: comparison with stature.

The ventilatory capacity, total lung capacity and transfer factor with their respective subdivisions have been measured on 254 healthy British boy and girl twins aged 8-16 yrs. The logarithmic regression relationships of lung function on stature have been compared with those on sitting height and on stature plus indices of body muscle and fat. The regressions on stature and on sitting height describe the results with similar precision, but stature is marginally better; either index may be used as the reference variable. For the description of inspiratory capacity and of all indices which include this volume (e.g. vital capacity, total lung capacity and transfer factor), additional precision is secured by adding to the regression equation on stature a term for fat-free mass or body mass divided by the square of the stature; for the description of functional residual capacity, the inclusion of a term for % body fat similarly reduces the variance about the regression equation. The difference in lung function between boys and girls is smaller when the function is related to stature than to sitting height. It is further reduced when fat-free mass/sature and % body fat are also included in the prediction equations. The equations may be used to obtain reference values for indices of lung function in similar subjects.

Adipose Tissue↗

PubMed2001

Increased incidence of myocardial infarction and stroke in hypertensive men with reduced lung function.

BACKGROUND AND OBJECTIVE: Although hypertension is associated with increased cardiovascular risk, many individuals remain free from disease. This study is aimed to investigate whether this variation in individual susceptibility is associated with lung function. DESIGN: Population-based prospective cohort study. PARTICIPANTS: 'Men born in 1914', Malmö, Sweden. Subjects (n = 639) were examined and considered free from prevalent cardiovascular disease at age 55 years. MAIN OUTCOME MEASURES: Mortality, fatal and non-fatal stroke and cardiac events (fatal or non-fatal myocardial infarction) during 28-years follow-up. RESULTS: Of the men, 467 had normal blood pressure and 172 (27%) had hypertension (> or = 160/95 mmHg or treatment for hypertension). Hypertensive men with height-adjusted forced expiratory volume during 1 s (FEV1.0) below median had significantly higher rates of stroke (13.4 versus 5.8/1,000 person-years), cardiac events (27.1 versus 12.8/1,000 person-years) and all cause mortality (52.5 versus 28.6/1,000 person-years) than hypertensive men with high FEV1.0. These differences remained statistically significant after adjustment for potential confounders. Men with normal blood pressure and FEV1.0 below median had higher rates of stroke (5.4 versus 4.2/1,000 person-years), cardiac events (13.3 versus 11.6/1,000 person-years) and all cause mortality (29.9 versus 21.2/1,000 person-years) than men with normal blood pressure and high FEV1.0. After adjustments for potential confounders, FEV1.0 was significantly associated with mortality among men with normal blood pressure, whereas the associations with stroke and cardiac events did not reach significance. CONCLUSION: The incidence of cardiovascular disease and death associated with hypertension is increased among men with reduced lung function. The synergistic interaction between hypertension and lung function was independent of smoking and other potential confounders.

Cohort Studies↗

PubMed1994

Dust-related decline in lung function among animal feed workers.

The study describes results of the first part of a follow-up study among 50 animal feed and grain elevator workers. The initial results suggest that the change in lung function over a 5 year period is related to the dust exposure. Workers in the high exposure category showed a greater decline in lung function than workers in the low exposure category. The decline in lung function was strongest for workers who were low exposed at the beginning of the study and who became high exposed during the follow-up period.

Adult↗