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Limits of human lung function at high altitude.

This paper will review the function of the lung at high altitude in humans. As the first interface between the environment and the body, the lung serves a vital role in the transfer of oxygen from the air to the blood. I will describe the limits of response and adaptation of the lung to this hypoxic stress, both at rest and during exercise when oxygen and carbon dioxide flux from the tissues is greater. First, ventilation will be described in terms of the hypoxic stimulus that causes an increase in breathing (ventilatory drives) and the metabolic cost from the respiratory muscles incurred by this increase. Individuals at high altitude also have a substantial sense of dyspnea which, in and of itself, may limit exercise tolerance. The final function of the lung is to exchange oxygen and carbon dioxide, which it does at the alveolar-capillary interface. Here, important limitations are encountered because the driving pressure for oxygen from the air to the blood is lower and the more rapid transit time of blood across the pulmonary capillary allows less time for equilibration of oxygen with the blood. Both these phenomena lead to a limitation of diffusion of oxygen across the alveolar-capillary membrane and, thus, more accentuated hypoxemia. In spite of these restrictions, humans still do remarkably well in times of great stress from the hypoxic environment.

Adaptation, Physiological↗

Lung function and clinical findings in a cross-sectional study of arc welders. An epidemiological study.

An epidemiological, cross-sectional study was conducted in order to assess non-neoplasic effects on the lung due to chronic exposure to arc welding fumes and gases. The study involved 346 arc welders and 214 control workers from a factory producing industrial vehicles. These workers (welders and controls) had never been exposed to asbestos. Respiratory impairments were evaluated by using a standardized questionnaire, a clinical examination, chest radiophotography and several lung function tests (spirometry, bronchial challenge test to acetylcholine, CO transfer tests according to the breath-holding and the steady-state methods, N2 washout test). The only significant differences between the welders overall compared to the controls were a slightly higher bronchial hyper-reactivity to acetylcholine and a lower lung diffusing capacity for CO in the welders. However, non-specific, radiologic abnormalities (reticulation, micronodulation) and obstructive signs were more frequent in the most exposed welders (welding inside tanks) than in welders working in well ventilated workplaces. The nature of the metal welded (mild-steel, stainless steel, aluminium) did not seem to have an influence on respiratory impairments. In the mild-steel welders, respiratory symptoms (dyspnoea, recurrent bronchitis) and obstructive signs were more frequent in the welders using a manual process than in the welders involved with the semi-automatic process (MIG). For all the workers (welders and controls), smoking had a markedly adverse effect on respiratory symptoms and lung function. Moreover, smoking seemed to interact with welding since CO lung transfer was more impaired in smoking welders than in smoking controls.

Adult↗

Decline of lung function and development of chronic airflow limitation: a longitudinal study of non-smokers and smokers in Busselton, Western Australia.

Data collected during seven population health surveys over 18 years in Busselton, Western Australia, were examined to determine the effect of smoking on lung function and to investigate the development of chronic airflow limitation. Lung function was measured and details of respiratory illness and smoking histories were collected from subjects attending surveys at three year intervals from 1966 to 1984. Data from ex-smokers and asthmatic patients (diagnosis based on answer to questionnaire) were excluded. Regression of height adjusted forced expiratory volume in one second (FEV1) on age was calculated individually for 759 non-smokers and 225 regular smokers with four or more observations. Decline in height adjusted FEV1 was similar for men and women. In smokers the rate of decline in FEV1 was greater than in non-smokers and was related to the amount smoked, to the extent that a smoker could expect a 20-30% greater rate of decline than a non-smoker of the same age. Chronic airflow limitation (defined as FEV1/FEV less than 65% or FEV1 less than 65% predicted on at least two occasions) was common, occurring in 24% of men and 18% of women who were regular smokers and in 5% of male and 8% of female non-smokers. These figures are higher than those reported in other populations, especially for women and for non-smokers. Not all chronic airflow limitation was associated with respiratory symptoms, confirming that the condition may be unrecognised until it is advanced.

Adult↗

The effect of exogenous surfactant replacement therapy on lung function.

Exogenous surfactant replacement therapy, regardless of type, reduces mortality and morbidity. We have reviewed the existing data to determine the effect this form of treatment has on lung function. Several studies have demonstrated that surfactant replacement therapy improves compliance, but the timing and magnitude of the effect is variable. The effect is dependent firstly on the type of surfactant used, natural surfactant being associated with a more rapid effect than artificial surfactant; secondly whether the surfactant is given as rescue or therapy as prophylaxis and thirdly the gestational age of the infant treated. Preliminary evidence also suggests that surfactant replacement therapy may influence lung function in the long term, since infants treated with surfactant rather than a placebo have lower airways resistance and higher specific conductance at follow-up. These preliminary reports are encouraging because they suggest that exogenous surfactant replacement therapy may have the additional benefit of reducing chronic respiratory morbidity associated with premature birth.

Humans↗

Phase-resolved functional lung MRI detects single-dose and sustained bronchodilator responses in COPD in a randomized crossover trial.

OBJECTIVES: To evaluate the effects of tiotropium/olodaterol (T/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized 129Xe MRI measures. MATERIALS AND METHODS: Retrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5&#x2009;&#xb1;&#x2009;7.7 years; 17 men); 30 completed the MRI extension at 1.5&#x2009;T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman's rank and bootstrap 95% confidence intervals (95% CIs). RESULTS: PREFUL parameters improved after T/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) (p&#x2009;<&#x2009;0.05). PWV decreased after multiple doses (-0.87&#x2009;m/s, 95% CI: -1.26 to -0.48&#x2009;m/s). PREFUL MRI baseline values showed significant correlations with pulmonary function tests, cardiac, dynamic contrast-enhanced and 129Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume (&#x3c1;&#x2009;=&#x2009;0.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and &#xb9;&#xb2;&#x2079;Xe-derived VDP, apparent diffusion coefficient, and compartment ratios. CONCLUSION: PREFUL MRI sensitively captured immediate SD T/O-induced improvements in V/Q parameters and dose-dependent PWV responses after sustained bronchodilation. KEY POINTS: Question Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium/olodaterol on ventilation-perfusion and vascular function in COPD patients? Findings Tiotropium/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing. Clinical relevance PREFUL MRI detected immediate and sustained functional improvements after tiotropium/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized &#xb9;&#xb2;&#x2079;Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response.

Humans↗

Lung function screening in industry.

Regression equations for forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) for 518 black factory workers on the Transvaal highveld were calculated from data obtained during routine lung function testing at an asbestos-cement factory. Only those subjects with clinically and radiologically normal lungs were accepted for the study. The lung capacities of the 60% who were light smokers were not significantly affected. Years of dust exposure were included as a separate independent variable and its contributory effect, after age had been allowed for, was insignificant. The final combined regression equations are considered to be representative of healthy black men on the Transvaal highveld. The values of FVC calculated from these equations were compared with values derived by other authors and, in view of the differences found, it was concluded that predicted values for black workers derived from regression equations for white subjects should not be used for industrial screening purposes. Group-specific equations should be followed when using lung function testing for definitive clinical diagnosis or academic research. The equations suggested for black South African men are FVC = 0.055 (height in cm) - 0.016 (age in years) - 4.502 and FEV1 = 0.043 (height) - 00023 (age) - 3.006.

Adolescent↗

Occupational exposure to water-based paints and self-reported asthma, lower airway symptoms, bronchial hyperresponsiveness, and lung function.

The associations between occupational exposure to water-based paints and the prevalence of self-reported asthma, other lower airway symptoms, bronchial hyperresponsiveness (BHR), and lung function were studied in house painters. Symptom prevalences were obtained from a self-administered questionnaire sent to 415 male painters during 1989-1992. Clinical investigations were carried out in three selected groups: 23 painters with asthmatic symptoms, nine painters with other lower airway symptoms, and 12 painters without airway symptoms. The clinical studies included lung function test, methacholine provocation test, and occurrence of atopy, confirmed by skin prick test to common allergens. In addition, a group of 18 young male painters with no occupational exposure to solvent-based paints were followed with dynamic spirometry before and after a workshift, when only water-based paints were used. The prevalence of self-reported asthma (7%) was somewhat, but not statistically, increased compared to an industrial population without exposure to water-based paints or other airway irritants. A decrease in FEV1 and FVC during the workday was observed in the young painters. In the clinical studies the painters exhibited increased BHR compared to the referents and a decreased FEV1. The number of years working as a painter was related to a decrease in FEV1, which was most pronounced in subjects with atopy who also reported lower airway symptoms in relation to the degree of work with water-based paints, but not to the degree of use of solvent-based paints. Our results indicate that house painters have an increased risk of airway problems.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Measurement of regional lung function in rats using hyperpolarized 3helium dynamic MRI.

Dynamic regional lung function was investigated in rats using a radial acquisition cine (RA-CINE) pulse sequence together with hyperpolarized (HP) (3)He gas delivered by a constant flow ventilator. Based on regional differences in the behavior of inspired air, the lung was conceptually divided into two regions (the major airways and the peripheral airspace) for purposes of functional analysis. To measure regional function in the major airways, a large RF flip angle (24 degrees) was applied to reduce (3)He magnetization in the peripheral airspace, and signal intensity (SI) was normalized with the projected airway diameter to estimate local airflow. Higher normalized signal intensity was observed in the left branch airway as compared to the right branch airway. To determine regional function in the peripheral airspace, a small RF flip angle (6 degrees) was used. Incremental increases of peripheral SI in successive lung images were consistent with the increase in lung volume. A new "skipping" scanning strategy using dummy frames allows a trade-off between the number of frames acquired for dynamic information, the RF flip angle, and the penetration depth of (3)He magnetization into the lung. This work provides a novel approach to simultaneously assess dynamic regional function and morphology.

Animals↗

The effect of insecticide aerosols on lung function, airway responsiveness and symptoms in asthmatic subjects.

The object of this study was to compare the effect of standard and "low irritant" insecticide aerosols on lung function, airway hyperresponsiveness (AHR) and symptoms in asthmatic subjects. A double blind randomized, crossover study was conducted in 25 asthmatic subjects who reported sensitivity to insecticide aerosols. All subjects were exposed for 30 min, on separate occasions, to two standard insecticide formulations (A and B), one low irritant formulation (C) and a negative control aerosol. Spirometric function and chest, nose and eye symptoms were recorded during, and for 90 min after, the exposure. AHR to methacholine was measured 90 min after the exposure. Compared to the negative control, the maximum fall in forced expiratory volume in one second (FEV1) was slightly greater after standard insecticides (mean differences from control +/-95% confidence interval: aerosol A, 3.3+/-3.6%, p=0.08; aerosol B, 5.1+/-4.7%, p=0.04), AHR was significantly more severe (mean difference from control: aerosol A, 0.35+/-0.29 doubling doses, p=0.028; aerosol B, 0.52+/-0.43 doubling doses, p=0.028), and symptoms were more severe. The low irritant test aerosol (C) did not differ significantly from the negative control with respect to FEV1, AHR or symptoms. It is concluded that some insecticide aerosols trigger symptoms and falls in lung function in some people with asthma. Furthermore, these aerosols may also increase airway hyperresponsiveness, although the mechanism of this effect has not been determined. The low irritant formulation did not appear to have the same effects.

Adult↗

Surfactant protein-B and lung function in surfactant-treated preterm lambs.

We asked if the amount of SP-B (range 37-410 micrograms/ml) in surfactants used to treat preterm lambs at 123 days of gestation correlated with postnatal lung function or the SP-B content of surfactant recovered by alveolar washes after 10 h ventilation. Ventilation was initiated using a low tidal volume strategy to minimize early lung injury. There were small increases in compliance for the lambs treated with surfactants containing more than 37 micrograms/ml SP-B and an increased lung volume for lambs treated with a surfactant containing 385 micrograms/ml/ml relative to the surfactant containing 37 micrograms/ml SP-B. The amount of SP-B in the surfactant used for treatment correlated linearly with the amount of SP-B in the surfactant recovered from the lambs (r = 0.95, p < 0.001). Albumin leak from the vasculature to the airspace was low as was total protein in alveolar washes, indicating minimal lung injury. The SP-B content of surfactant (from 37 to 410 micrograms/ml) had minimal effects on postnatal lung function over a 10-hour study period in lambs ventilated in a manner to minimize lung injury.

Biological Products↗

Selective recruitment maneuvers for lobar atelectasis: effects on lung function and central hemodynamics: an experimental study in pigs.

We investigated whether selective lung recruitment of a lobar collapse would improve oxygenation and lung volume as well as a general (global) lung recruitment maneuver, with fewer circulatory side effects. In 10 ventilated, anesthetized pigs, a bronchial blocker was inserted in the right lower lobe, which was selectively lavaged to create a dense lobar collapse. The pigs were randomized into two orders of lung recruitment maneuvers (40 cm H2O airway pressure for 30 s): either a selective lung recruitment maneuver (using the inner lumen of the bronchial blocker) followed by a general lung recruitment maneuver, or vice versa. Median end-expiratory lung volume and median Pao2 increased significantly by approximately 100 mL and 16 kPa, respectively, with no significant differences between the two recruitment methods. There were no circulatory changes during the selective lung recruitment maneuver, but during the general lung recruitment maneuver, mean arterial blood pressure decreased significantly by 36 (21, 41) mm Hg (median, 25th and 75th percentiles), cardiac output by 2.1 (1.6, 2.5) L/min and left ventricular end-diastolic area by 4.4 (3.5, 4.5) cm2. In conclusion, a selective recruitment maneuver improved lung function similar to a general lung recruitment maneuver but without any circulatory side effects.

Animals↗

Respiratory symptoms, lung function and use of health services among unemployed young adults in Spain. Spanish Group of the European Community Respiratory Health Survey.

The association of respiratory symptoms, lung function and use of health services with employment status was examined in Spain, a country with a high rate of unemployment. A population sample comprising 179 unemployed and 1,868 employed subjects aged 20-44 yrs in 1993, was randomly selected from a base population of about 170,000 people in five urban and rural areas of Spain. Subjects completed a questionnaire on respiratory symptoms, sociodemographic and lifestyle factors, occupational exposure and use of health services, and performed a forced spirometry, a methacholine challenge test and blood tests. Unemployed subjects had a higher risk of simple chronic bronchitis (odds ratio=2.06, 95% confidence interval 1.30-3.24) and of bronchitis-type symptoms, than those who were employed. These risks were, in part, due to the higher prevalence of smoking, poorer housing and prior occupational exposures among unemployed than among employed people. Smaller differences were found between employed and unemployed subjects for asthma-type symptoms, atopia and lung function tests. Use of health services among subjects with respiratory symptoms was similar among employed and unemployed subjects, except that the latter consistently reported less frequent contact with specialized practitioners. Unemployed subjects had a higher risk of bronchitis-type symptoms than employed subjects. In Spain's national, free-access healthcare system, the differential use of specialized health services by employment status is likely to imply differences in the characteristics of the healthcare provided.

Adult↗

Lung function and morphology after hemorrhagic shock, soft tissue trauma and regional ischemia in dogs.

Among 40 dogs submitted to 1 of 3 experimental shock procedures: hemorrhagic shock, soft tissue trauma or regional ischemia, 24 dogs fulfilled the criteria of irreversible shock, based on survival or characteristic hemodynamic and metabolic changes. The 24 dogs were studied by measurements of lung function and hemodynamics. During the shock period no impairment of lung function was observed. The pulmonary shunting ratio fell and pulmonary vascular resistance increased. The macroscopical aspect of the lungs did not differ from that of 10 control dogs. The microscopical examination of the lungs, performed after infusion fixation, revealed only a higher granulocyte infiltration in traumatic shock and more severe congestion in hemorrhagic shock.

Animals↗

Levels of soluble IL-2 receptor in plasma from asthmatics. Correlations with blood eosinophilia, lung function, and corticosteroid therapy.

Evidence now suggests that eosinophils and T lymphocytes infiltrating bronchial tissues may play a key role in the pathophysiology of asthma. Circulating eosinophils, lung function, and plasma soluble IL-2 receptor (sIL-2R) were measured in 42 asthmatic patients referred for symptomatic asthma. The patients were divided into two groups based on the presence or absence of atopy. The group of non-atopic asthmatics was further divided according to the patients' requirement for long term oral corticosteroids. The mean sIL-2R +/- s.d. was 36.3 +/- 9.9 pM in the control group, 28.9 +/- 9.2 pM in the atopic asthmatics, 43.3 +/- 18.07 pM in the non-atopic asthmatics without oral steroid therapy, but was increased in the steroid-treated group (62.2 +/- 19.3 pM, P less than 0.01). A significant correlation was found between FEV1 and circulating eosinophils in atopic asthmatics and in non-atopic asthmatics without oral corticosteroid therapy, but not in the steroid-treated group. Furthermore, significant correlations were found between sIL-2R and FEV1, and between sIL-2R and blood eosinophils, in the group of non-atopic asthmatics not on oral steroid therapy. No such correlations were evidenced in the other groups of asthmatics. Similar results were obtained during the clinical course of three non-atopic patients followed for more than 1 year. These data suggest that T cell activation appears more prominent in non-atopic asthma than in atopic asthma. Moreover, it appears that T cell activation can occur in severe forms of asthma despite steroid treatment. Finally, the results suggest a possible link between T cell activation, eosinophils, and lung function, which may reflect a particular pathogenetic mechanism involved in non-atopic asthma.

Adrenal Cortex Hormones↗

Corticosteroids and surfactant change lung function and protein leaks in the lungs of ventilated premature rabbits.

Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 d gestational age. The treated and control rabbits were placed on ventilator-plethysmographs so that ventilation could be adjusted by regulation of tidal volumes to 10-13 ml/kg body wt. [125I]albumin was mixed with fetal lung fluid at birth, alternate rabbits from each litter were treated with Surfactant-TA, and [131I]albumin was injected intravascularly. The movement of the labeled albumins into and out of the alveolar wash and lung tissue was measured after 30 min of ventilation. Corticosteroid treatment (total dose, 0.2 mg/kg betamethasone) significantly decreased the protein leak across the endothelium (P less than 0.001) but increased the protein leak across the epithelium (P less than 0.001). Surfactant treatment decreased both the endothelial and epithelial leaks, and the combination of surfactant and corticosteroid treatments decreased endothelial leaks to 29% of control values and increased compliance more than either treatment alone. The 48-h corticosteroid treatment did not increase alveolar surfactant pool sizes. Corticosteroids significantly changed lung protein leaks independently of surfactant, and improved the response of the preterm lung to surfactant treatments.

Adrenal Cortex Hormones↗