The structural basis of airways hyperresponsiveness in asthma.

We hypothesized that structural airway remodeling contributes to airways hyperresponsiveness (AHR) in asthma. Small, medium, and large airways were analyzed by computed tomography in 21 asthmatic volunteers under baseline conditions (FEV1 = 64% predicted) and after maximum response to albuterol (FEV1 = 76% predicted). The difference in pulmonary function between baseline and albuterol was an estimate of AHR to the baseline smooth muscle tone (BSMT). BSMT caused an increase in residual volume (RV) that was threefold greater than the decrease in forced vital capacity (FVC) because of a simultaneous increase in total lung capacity (TLC). The decrease in FVC with BSMT was the major determinant of the baseline FEV1 (P < 0.0001). The increase in RV correlated inversely with the relaxed luminal diameter of the medium airways (P = 0.009) and directly with the wall thickness of the large airways (P = 0.001). The effect of BSMT on functional residual capacity (FRC) controlled the change in TLC relative to the change in RV. When the FRC increased with RV, TLC increased and FVC was preserved. When the relaxed large airways were critically narrowed, FRC and TLC did not increase and FVC fell. With critical large airways narrowing, the FRC was already elevated from dynamic hyperinflation before BSMT and did not increase further with BSMT. FEV1/FVC in the absence of BSMT correlated directly with large airway luminal diameter and inversely with the fall in FVC with BSMT. These findings suggest that dynamic hyperinflation caused by narrowing of large airways is a major determinant of AHR in asthma.     

Vitamin supplementation does not protect against symptoms in ozone-responsive subjects

Vitamin supplements have been reported to reduce the magnitude of symptoms in subjects exposed to oxidant air pollution. To confirm whether supplementation with vitamins C and E could reduce lung function decrements, airway inflammation, and epithelial injury in subjects sensitive to ozone, a double-blinded, crossover control study was performed. Fourteen ozone-responsive subjects were randomly exposed to both air and ozone (0.2 ppm for 2 h) after 7 days of either placebo treatment or supplementation with vitamin C (500 mg/day) and E (100 mg/day). Lung function was assessed pre- and immediately postexposure and blood samples were taken at set intervals. Inflammatory, tissue injury, and antioxidant responses were examined in lavage fluid obtained by bronchoscopy 6 h postexposure. Exposure to ozone resulted in significant (P < 0.01) decrements in FEV1 with no protection observed following vitamin supplementation (-8.5%) versus placebo (-7.3%) treatment. Similarly, ozone-induced neutrophilia were of a similar magnitude after both treatments (P < 0.05). This lack of protection was observed despite elevated plasma vitamin C (+60.1%) and vitamin E (+51.4%) concentrations following supplementation, and increased vitamin C concentrations in the airways after supplementation following ozone exposure. These data do not therefore support the contention that acute ozone-induced symptoms can be attenuated through the use of dietary antioxidants in well-nourished individuals.     

Ozone inhalation effects consequent to continuous exercise in females: comparison to males

Exposure to ozone (O3) at ambient photochemical smog alert levels has been shown to cause alteration in pulmonary function and exercise response in humans, but there is a paucity of data on females. The initial purpose of the present investigation was to study the effects of O3 inhalation on pulmonary function and selected exercise respiratory metabolism and breathing pattern responses in young adult females. Six female subjects exercised continuously on a bicycle ergometer for 1 h on 10 occasions at one of three intensities, while exposed to 0.0, 0.20, 0.30, or 0.40 ppm O3. Forced expiratory volume and flow rates and residual volume (RV) were measured before and immediately following each protocol. During exercise, expired minute ventilation (VE), respiratory frequency (fR), tidal volume, O2 uptake (VO2), and heart rate (HR) were measured every 10 min. O3 dose-dependent decrements were observed for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), and forced expiratory flow rate during the middle half of FVC, coupled with an increase in RV and altered exercise ventilatory pattern. There was also an increased VE but no significant O3 effect on VO2 or HR. Comparison of the females' responses to those of a group of young adult males (previously studied) at the same total O3 effective dose (i.e., expressed as the simple product of O3 concentration, VE, and exposure time) revealed significantly greater effects on FVC, FEV1.0, and fR for the females. With VE reduced for females as a function of exercise intensity at the same percent of maximum VO2, these differences were considerably attenuated, although not negated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ozone inhalation effects in females varying widely in lung size: comparison with males

It has been suggested that lung size accounts for observed gender differences in responsiveness to the same total inhaled dose of O3. To test the hypothesis that lung size is a determinant of magnitude of response within a gender, two groups of 14 healthy young adult females differing significantly in forced vital capacity [FVC; i.e., small-lung group mean = 3.74 liters (range 3.2-4.0) and large-lung group mean = 5.11 liters (range 4.5-6.2] were exposed for 1 h to filtered air (FA) and to 0.18 and 0.30 ppm O3. On each occasion, subjects exercised continuously on a cycle ergometer at a work rate that elicited a mean minute ventilation of approximately 47 l/min. For the small-lung group [mean total lung capacity (TLC) = 4.52 liters] exercise O2 uptake was 67% of maximal O2 uptake (VO2max), and that for the large-lung group (TLC 6.37 liters) was 61% of VO2max. Statistical analysis revealed significant decrements for both groups in FVC, forced expiratory volume in 1 s (FEV1.0), and forced expiratory flow rate in the middle half of FVC on exposure to 0.18 and 0.30 ppm O3. Exercise respiratory frequency increased, and tidal volume decreased significantly in both groups in response to 0.18 and 0.30 ppm O3 exposure. On exposure to 0.30 ppm O3, the number of individual subjective symptoms reported and their severity were significantly greater for both groups than those reported for the FA and 0.18 ppm O3 exposures. Both groups evidenced similar percent changes in pulmonary function and exercise ventilation response, and in subjective symptom response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary function in men after oxygen breathing at 3.0 ATA for 3.5 h.

As a pulmonary component of Predictive Studies V, designed to determine O2 tolerance of multiple organs and systems in humans at 3.0-1.5 ATA, pulmonary function was evaluated at 1.0 ATA in 13 healthy men before and after O2 exposure at 3.0 ATA for 3.5 h. Measurements included flow-volume loops, spirometry, and airway resistance (Raw) (n = 12); CO diffusing capacity (n = 11); closing volumes (n = 6); and air vs. HeO2 forced vital capacity maneuvers (n = 5). Chest discomfort, cough, and dyspnea were experienced during exposure in mild degree by most subjects. Mean forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25-75% of vital capacity (FEF25-75) were significantly reduced postexposure by 5.9 and 11.8%, respectively, whereas forced vital capacity was not significantly changed. The average difference in maximum midexpiratory flow rates at 50% vital capacity on air and HeO2 was significantly reduced postexposure by 18%. Raw and CO diffusing capacity were not changed postexposure. The relatively large change in FEF25-75 compared with FEV1, the reduction in density dependence of flow, and the normal Raw postexposure are all consistent with flow limitation in peripheral airways as a major cause of the observed reduction in expiratory flow. Postexposure pulmonary function changes in one subject who convulsed at 3.0 h of exposure are compared with corresponding average changes in 12 subjects who did not convulse.     

Ozone-induced changes in pulmonary function and bronchial responsiveness in asthmatics

To compare the responses of asthmatic and normal subjects to high effective doses of ozone, nine asthmatic and nine normal subjects underwent two randomly assigned 2-h exposures to filtered, purified air and 0.4 ppm ozone with alternating 15-min periods of rest and exercise on a cycle ergometer (minute ventilation = 30 l.min-1.m-2). Before and after each exposure, pulmonary function and bronchial responsiveness to methacholine were measured and symptoms were recorded. Ozone exposure was associated with a statistically significant decrease in forced vital capacity (FVC), forced expired volume in 1 s (FEV1), percent FEV1 (FEV1%), and forced expired flow at 25-75% FVC (FEF25-75) in both normal and asthmatic subjects. However, comparing the response of asthmatic and normal subjects to ozone revealed a significantly greater percent decrease in FEV1, FEV1%, and FEF25-75 in the asthmatic subjects. The effect of ozone on FVC and symptom scores did not differ between the two groups. In both normal and asthmatic subjects, exposure to ozone was accompanied by a significant increase in bronchial responsiveness. We conclude that exposure to a high effective ozone dose produces 1) increased bronchial responsiveness in both normal and asthmatic subjects, 2) greater airways obstruction in asthmatic than in normal subjects, and 3) similar symptoms and changes in lung volumes in the two groups.     

Effects of exercise training on airway closure in asthmatics

We previously reported that responsiveness to methacholine (Mch) in the absence of deep inspiration (DI) decreased in healthy subjects after a short course of exercise training. We assessed whether a similar beneficial effect of exercise on airway responsiveness could occur in asthmatics. Nine patients (male/female: 3/6; mean age ± SD: 24 ± 2 yr) with mild untreated asthma [forced expiratory volume in 1 s (FEV(1)): 100 ± 7.4% pred; FEV(1)/vital capacity (VC): 90 ± 6.5%] underwent a series of single-dose Mch bronchoprovocations in the absence of DI in the course of a 10-wk training rowing program (6 h/wk of submaximal and maximal exercise), at baseline (week 0), and at week 5 and 10. The single-dose Mch was established as the dose able to induce ≥15% reduction in inspiratory vital capacity (IVC) and was administered to each subject at every challenge occasion. Five asthmatics (male/female: 1/4; mean age ± SD: 26 ± 3 yr) with similar baseline lung function (FEV(1): 102 ± 7.0% predicted; FEV(1)/VC: 83 ± 6.0%; P = 0.57 and P = 0.06, respectively) not participating in the exercise training program served as controls. In the trained group, the Mch-induced reduction in IVC from baseline was 22 ± 10% at week 0, 13 ± 11% at week 5 (P = 0.03), and 11 ± 8% at week 10 (P = 0.028). The Mch-induced reduction in FEV(1) did not change with exercise (P = 0.69). The reduction in responsiveness induced by exercise was of the same magnitude of that previously obtained in healthy subjects (50% with respect to pretraining). Conversely, Mch-induced reduction in IVC in controls remained unchanged after 10 wk (%reduction IVC at baseline: 21 ± 20%; after 10 wk: 29 ± 14%; P = 0.28). This study indicates that a short course of physical training is capable of reducing airway responsiveness in mild asthmatics.     

Exercise-induced bronchoconstriction alters airway nitric oxide exchange in a pattern distinct from spirometry

Exhaled nitric oxide (NO) is altered in asthmatic subjects with exercise-induced bronchoconstriction (EIB). However, the physiological interpretation of exhaled NO is limited because of its dependence on exhalation flow and the inability to distinguish completely proximal (large airway) from peripheral (small airway and alveolar) contributions. We estimated flow-independent NO exchange parameters that partition exhaled NO into proximal and peripheral contributions at baseline, postexercise challenge, and postbronchodilator administration in steroid-naive mild-intermittent asthmatic subjects with EIB (24-43 yr old, n = 9) and healthy controls (20-31 yr old, n = 9). The mean +/- SD maximum airway wall flux and airway diffusing capacity were elevated and forced expiratory flow, midexpiratory phase (FEF(25-75)), forced expiratory volume in 1 s (FEV(1)), and FEV(1)/forced vital capacity (FVC) were reduced at baseline in subjects with EIB compared with healthy controls, whereas the steady-state alveolar concentration of NO and FVC were not different. Compared with the response of healthy controls, exercise challenge significantly reduced FEV(1) (-23 +/- 15%), FEF(25-75) (-37 +/- 18%), FVC (-12 +/- 12%), FEV(1)/FVC (-13 +/- 8%), and maximum airway wall flux (-35 +/- 11%) relative to baseline in subjects with EIB, whereas bronchodilator administration only increased FEV(1) (+20 +/- 21%), FEF(25-75) (+56 +/- 41%), and FEV(1)/FVC (+13 +/- 9%). We conclude that mild-intermittent steroid-naive asthmatic subjects with EIB have altered airway NO exchange dynamics at baseline and after exercise challenge but that these changes occur by distinct mechanisms and are not correlated with alterations in spirometry.     

Relationship between respiratory muscle function and age, sex, and other factors

To investigate the effects of gender and age on respiratory muscle function, 160 healthy volunteers (80 males, 80 females) were divided into four age groups. Twenty-eight of the male subjects were smokers. After the subjects were familiarized with the experimental procedure, respiratory muscle strength, inspiratory muscle endurance, and spirometric function, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, tidal volume, breathing rate, and duty cycle, were measured. The respiratory muscle strength was indicated by the maximal static inspiratory and expiratory pressures (PImmax and PEmmax). Inspiratory muscle endurance was determined by the time the subject was able to sustain breathing against an inspiratory pressure load on a modified Nickerson-Keens device. The results showed that 1) except for inspiratory muscle endurance and FEV1/FVC, men had greater respiratory muscle and pulmonary functions than women, 2) respiratory muscle function and pulmonary function decreased with age, 3) smoking tended to lower duty cycle and FEV1/FVC and to enhance PE,mmax, and 4) inspiratory muscle endurance was greater in men who were physically active than in those who were sedentary. Therefore we conclude that there are sexual and age differences in respiratory muscle strength and pulmonary function and that smoking or physical activity may affect respiratory muscle function.     

A comparative analysis of biomass and clean fuel exposure on pulmonary function during cooking among rural women in Tamilnadu,India

It is of interest to document data on the comparative analysis of biomass and clean fuel exposure on pulmonary function during cooking among rural women. The study consisted of 100 biomass and 100 LPG fuel using women with no smoking habits and other related illness Parameters such as FVC, FEV1, FEV1/FVC, PEFR, FEF25-75%were obtained using the computerized spirometry to assess the pulmonary function in these subjects. The collected data were analyzed using the Student t-test method and Pearson correlation. The exposure index for biomass fuel users is 69.78±27.25 showing high exposure duration during cooking. The parameters for pulmonary functions significantly declined in FVC (42.34±13.6), FEV1 (45.55±15.98), PEFR (34.11±14.78) and FEF25-75% (45.56±23.00) for biomass fuel user. However, this is not true for FEV1/FVC ratio (107.56±16.9). The increase in PFT suggests the restrictive and obstructive patterns of pulmonary diseases. There was a negative correlation between increased duration of cooking and the value of FEV1/FVC (r = -0.2961), FEF25-75% (r = -0.3519) and PEFR (r = -0.2868). Thus, the deformation of pulmonary function due to extended exposure of biomass fuel for cooking women in rural Tamilnadu is shown using parameter features such as high exposure index, overcrowded area and improper ventilated houses.     

Lung function decline in relation to diagnostic criteria for airflow obstruction in respiratory symptomatic subjects

Background

Current COPD guidelines advocate a fixed < 0.70 FEV1/FVC cutpoint to define airflow obstruction. We compared rate of lung function decline in respiratory symptomatic 40+ subjects who were 'obstructive' or 'non-obstructive' according to the fixed and/or age and gender specific lower limit of normal (LLN) FEV1/FVC cutpoints.

Methods

We studied 3,324 respiratory symptomatic subjects referred to primary care diagnostic centres for spirometry. The cohort was subdivided into four categories based on presence or absence of obstruction according to the fixed and LLN FEV1/FVC cutpoints. Postbronchodilator FEV1 decline served as primary outcome to compare subjects between the respective categories.

Results

918 subjects were obstructive according to the fixed FEV1/FVC cutpoint; 389 (42%) of them were non-obstructive according to the LLN cutpoint. In smokers, postbronchodilator FEV1 decline was 21 (SE 3) ml/year in those non-obstructive according to both cutpoints, 21 (7) ml/year in those obstructive according to the fixed but not according to the LLN cutpoint, and 50 (5) ml/year in those obstructive according to both cutpoints (p = 0.004).

Conclusion

This study showed that respiratory symptomatic 40+ smokers and non-smokers who show FEV1/FVC values below the fixed 0.70 cutpoint but above their age/gender specific LLN value did not show accelerated FEV1 decline, in contrast with those showing FEV1/FVC values below their LLN cutpoint.     

Combined effects of ozone exposure and ambient heat on exercising females

Ten aerobically trained young adult females exercised continuously at 66% of maximum O2 uptake for 1 h while exposed orally to filtered air and 0.15 and 0.30 parts per million (ppm) ozone (O3) in both moderate (24 degrees C) and hot (35 degrees C) ambient conditions. Exposure to 0.30 ppm O3 induced significant impairment in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), and other pulmonary function variables. Exercise respiratory frequency (fR) increased, whereas tidal volume and alveolar volume (VA) decreased with 0.30 ppm O3 exposure. Significant interactions of O3 and ambient heat were obtained for fR and VA, whereas FVC and FEV1.0 displayed a trend toward an O3-temperature interaction. Although expired ventilation increased, the interactions could not be ascribed to a greater O3 effective dose in the 35 degrees C exposures. However, subjective discomfort increased with both O3 and heat exposure such that three subjects ceased exercise prematurely when O3 and ambient heat were combined. We conclude that accentuation of subjective limitations and certain physiological alterations by ambient heat coinciding with photochemical oxidant episodes is likely to result in more severe impairment of exercise performance, although the mechanisms remain unclear.     

Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation.

Five to ten percent of asthma cases are poorly controlled chronically and refractory to treatment, and these severe cases account for disproportionate asthma-associated morbidity, mortality, and health care utilization. While persons with severe asthma tend to have more airway obstruction, it is not known whether they represent the severe tail of a unimodal asthma population, or a severe asthma phenotype. We hypothesized that severe asthma has a characteristic physiology of airway obstruction, and we evaluated spirometry, lung volumes, and reversibility during a stable interval in 287 severe and 382 nonsevere asthma subjects from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. We partitioned airway obstruction into components of air trapping [indicated by forced vital capacity (FVC)] and airflow limitation [indicated by forced expiratory volume in 1 s (FEV(1))/FVC]. Severe asthma had prominent air trapping, evident as reduced FVC over the entire range of FEV(1)/FVC. This pattern was confirmed with measures of residual lung volume/total lung capacity (TLC) in a subgroup. In contrast, nonsevere asthma did not exhibit prominent air trapping, even at FEV(1)/FVC <75% predicted. Air trapping also was associated with increases in TLC and functional reserve capacity. After maximal bronchodilation, FEV(1) reversed similarly from baseline in severe and nonsevere asthma, but the severe asthma classification was an independent predictor of residual reduction in FEV(1) after maximal bronchodilation. An increase in FVC accounted for most of the reversal of FEV(1) when baseline FEV(1) was <60% predicted. We conclude that air trapping is a characteristic feature of the severe asthma population, suggesting that there is a pathological process associated with severe asthma that makes airways more vulnerable to this component.     

Pulmonary response to threshold levels of sulfur dioxide (1.0 ppm) and ozone (0.3 ppm)

We exposed 22 healthy adult nonsmoking male subjects for 2 h to filtered air, 1.0 ppm sulfur dioxide (SO2), 0.3 ppm ozone (O3), or the combination of 1.0 ppm SO2 + 0.3 ppm O3. We hypothesized that exposure to near-threshold concentrations of these pollutants would allow us to observe any interaction between the two pollutants that might have been masked by the more obvious response to the higher concentrations of O3 used in previous studies. Each subject alternated 30-min treadmill exercise with 10-min rest periods for the 2 h. The average exercise ventilation measured during the last 5 min of exercise was 38 1/min (BTPS). Forced expiratory maneuvers were performed before exposure and 5 min after each of the three exercise periods. Maximum voluntary ventilation, He dilution functional residual capacity, thoracic gas volume, and airway resistance were measured before and after the exposure. After O3 exposure alone, forced expiratory measurements (FVC, FEV1.0, and FEF25-75%) were significantly decreased. The combined exposure to SO2 + O3 produced similar but smaller decreases in these measures. There were small but significant differences between the O3 and the O3 + SO2 exposure for FVC, FEV1.0, FEV2.0, FEV3.0, and FEF25-75% at the end of the 2-h exposure. We conclude that, with these pollutant concentrations, there is no additive or synergistic effect of the two pollutants on pulmonary function.     

Lung function in Canadian Inuit: a follow-up study.

To assess the impact of acculturation on lung function, the forced vital capacity (FVC) and the 1-second forced expiratory volume (FEV1) of 341 Inuit at Igloolik, NWT were measured. The same observers had used the same equipment to test 196 subjects in 1970-71. Cross-sectional analysis suggested that, relative to the previous decade, younger subjects had larger lung volumes (with gains of about 10% in FVC and 5% in FEV1), while the elderly had smaller volumes (with losses of about 22% in FVC and 25% in FEV1). Longitudinal analysis confirmed an accelerating loss of lung function in the older subjects: from age 25 to 35 years men and women had a loss in FVC of 13 and 11 mL/yr respectively, whereas from age 45 to 55 years the corresponding figures were 70 and 38 mL/yr. Cigarette smoking had increased substantially among the Inuit over the decade: the proportion of males and females smoking rose from 64% to 81% and from 85% to 93% respectively. Daily cigarette consumption per smoker increased from 11.8 to 20.2 and from 7.4 to 12.0 among men and women respectively. Nevertheless, the main explanation for the shape of the ageing curve is the survival of a small cohort of elderly Inuit with advanced tuberculosis. With control of this disease future cohorts of the elderly will have better lung function.     

慢性阻塞性肺疾病急性加重期患者血清PCT、hs-CRP、D-D和FIB与肺功能和预后的关系研究

目的:探究慢性阻塞性肺疾病急性加重期(AECOPD)患者血清降钙素原(PCT)、超敏C反应蛋白(hs-CRP)、D-二聚体(D-D)和纤维蛋白原(FIB)与肺功能和预后的关系。方法:选择2017年8月至2019年8月期间我院诊治的88例AECOPD患者作为观察组,根据患者生存情况将患者进一步分为85例存活组和3例死亡组。同时选择同期在我院进行健康体检的50名志愿者作为对照组。检测各组患者的血清PCT、hs-CRP、D-D和FIB水平,采用肺功能检测仪检测第一秒用力呼气容积(FEV1)%、第一秒用力呼气容积占用力肺活量比值(FEV1/FVC)和最大通气量(MVV)肺功能指标,采用Pearson相关性分析进行各指标的相关性分析。结果:与对照组相比,观察组的血清PCT、hs-CRP、D-D和FIB水平均明显升高(P0.05)。与存活组相比,死亡组的血清PCT、hs-CRP、D-D和FIB水平均明显升高(P0.05),FEV1%、FEV1/FVC和MVV指标均明显下降(P0.05)。Pearson相关性分析显示,血清PCT、hs-CRP、D-D和FIB水平均与FEV1%、FEV1/FVC和MVV肺功能指标呈负相关(P0.05)。结论:AECOPD患者肺功能下降和不良预后与血清PCT、hs-CRP、D-D和FIB水平升高密切相关,在AECOPD患者的预后预测中具有一定临床价值。     

Small airway morphology and lung function in the transition from normality to chronic airway obstruction.

This study investigated the relationships between pathological changes in small airways (<6 mm perimeter) and lung function in 22 nonasthmatic subjects (20 smokers) undergoing lung resection for peripheral lesions. Preoperative pulmonary function tests revealed airway obstruction [ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) < 70%] in 12 subjects and normal lung function in 10. When all subjects were considered together, total airway wall thickness was significantly correlated with FEV1/FVC (r2 = 0.25), reactivity to methacholine (r2 = 0.26), and slope of linear regression of FVC against FEV1 values recorded during the methacholine challenge (r2 = 0.56). Loss of peribronchiolar alveolar attachments was significantly associated (r2 = 0.25) with a bronchoconstrictor effect of deep inhalation, as assessed from a maximal-to-partial expiratory flow ratio <1, but not with airway responses to methacholine. No significant correlation was found between airway smooth muscle thickness and lung function measurements. In conclusion, this study suggests that thickening of the airway wall is a major mechanism for airway closure, whereas loss of airway-to-lung interdependence may contribute to the bronchoconstrictor effect of deep inhalation in the transition from normal lung function to airway obstruction in nonasthmatic smokers.     

Multiple exposures to swine barn air induce lung inflammation and airway hyper-responsiveness

Background

Swine farmers repeatedly exposed to the barn air suffer from respiratory diseases. However the mechanisms of lung dysfunction following repeated exposures to the barn air are still largely unknown. Therefore, we tested a hypothesis in a rat model that multiple interrupted exposures to the barn air will cause chronic lung inflammation and decline in lung function.

Methods

Rats were exposed either to swine barn (8 hours/day for either one or five or 20 days) or ambient air. After the exposure periods, airway hyper-responsiveness (AHR) to methacholine (Mch) was measured and rats were euthanized to collect bronchoalveolar lavage fluid (BALF), blood and lung tissues. Barn air was sampled to determine endotoxin levels and microbial load.

Results

The air in the barn used in this study had a very high concentration of endotoxin (15361.75 ± 7712.16 EU/m³). Rats exposed to barn air for one and five days showed increase in AHR compared to the 20-day exposed and controls. Lungs from the exposed groups were inflamed as indicated by recruitment of neutrophils in all three exposed groups and eosinophils and an increase in numbers of airway epithelial goblet cells in 5- and 20-day exposure groups. Rats exposed to the barn air for one day or 20 days had more total leukocytes in the BALF and 20-day exposed rats had more airway epithelial goblet cells compared to the controls and those subjected to 1 and 5 exposures (P < 0.05). Bronchus-associated lymphoid tissue (BALT) in the lungs of rats exposed for 20 days contained germinal centers and mitotic cells suggesting activation. There were no differences in the airway smooth muscle cell volume or septal macrophage recruitment among the groups.

Conclusion

We conclude that multiple exposures to endotoxin-containing swine barn air induce AHR, increase in mucus-containing airway epithelial cells and lung inflammation. The data also show that prolonged multiple exposures may also induce adaptation in AHR response in the exposed subjects.     

肺通气功能程度与慢性阻塞性肺疾病患者夜间低氧发生的相关性分析

目的:研究肺通气功能程度与慢性阻塞性肺疾病患者夜间低氧发生的相关性。方法:选取2012年1月至2013年6月我院治疗的60例稳定期慢性阻塞性肺疾病患者,按肺通气功能分为轻度、中度、重度、极重度4组,每组15例,监测记录研究对象肺通气功能指标及夜间血氧指标,比较各组监测指标的差异,并分析其相关性。结果:不同病情程度COPD患者FEV1/FVC、FEV1、FVC、PEF、RV、RV/TLC、MsaO2、ODI、WsaO2、LsaO2、SIT90%有差异(P0.05);极重度和重度比较FEV1/FVC、FEV1、RV、MsaO2、ODI、WsaO2、LsaO2、SIT90%有差异(P0.05);极重度和中度比较FEV1/FVC、FEV1、FVC、PEF、RV、RV/TLC、MsaO2、ODI、WsaO2、LsaO2、SIT90%有差异(P0.05);极重度和轻度比较FEV1/FVC、FEV1、FVC、PEF、RV、RV/TLC、MsaO2、ODI、WsaO2、LsaO2、SIT90%有差异(P0.05);重度和中度比较FEV1/FVC、FEV1、FVC、PEF、RV/TLC、MsaO2有差异(P0.05);重度和轻度比较FEV1/FVC、FEV1、FVC、PEF、RV/TLC、MsaO2、ODI、LsaO2有差异(P0.05);中度和轻度比较FEV1/FVC、FEV1、FVC、PEF、ODI有差异(P0.05)。COPD患者的肺通气功能FEV1与MsaO2呈正相关(r=0.683,P0.05)。结论:肺通气功能程度与慢性阻塞性肺疾病患者夜间低氧发生具有相关性。