Delta FEV1 Research Articles

Total lung capacity does not change during methacholine-stimulated airway narrowing

The accurate measurement of changes in flow rates from partial flow-volume curves depends on their measurement at the same lung volume. This lung volume can be standardized from total lung capacity (TLC) if this does not change at the same time. We examined the effect of methacholine-stimulated maximal airway narrowing [change in mean forced expiratory volume in 1 s (delta FEV1) = 26.4%] on TLC, measured by whole-body plethysmography, in 10 normal subjects and of moderate airway narrowing (mean delta FEV1 = 34.9%) in 10 asthmatics. The TLC changed from 5.88 to 6.03 liters in normal subjects (P greater than 0.05) and from 6.92 to 6.95 liters (P greater than 0.5) in asthmatics. The results of this study suggest that TLC does not change significantly after methacholine-stimulated maximal airway narrowing in normal subjects and after moderate narrowing in asthmatics.

Longitudinal changes in forced expiratory volume in one second in adults. Methodologic considerations and findings in healthy nonsmokers.

Longitudinal changes in FEV1 (delta FEV1) have been examined in a sample of the general population of Tucson, Arizona. Adults with satisfactory spirometric tests in all 7 surveys performed over a period of 11 yr showed some between-survey differences in mean FEV1. Although small in absolute magnitude, such survey biases (which would be impossible to detect unless multiple spirometric tests were carried out on a relatively large group of subjects) could have a marked effect on calculated changes in FEV1 and may explain the widely divergent delta FEV1 values reported in the literature. After adjusting for survey biases, the relationships of delta FEV1 to age, sex, and body size were examined in "healthy" nonsmokers in the population who were followed for an average of 9.6 yr. The FEV1 showed an accelerating decline with age, and delta FEV1 was best explained by a model of proportional change in which it is a function of Age X Height3. Longitudinally determined delta FEV1 showed much less decline in function and a later apparent age of onset of decline than suggested by cross-sectional analyses. While small "learning effects" in longitudinal calculations cannot be excluded, most of the cross-sectional versus longitudinal differences are probably ascribable to past events that have adversely affected the FEV1 in older adults, thereby increasing cross-sectional age effects. Present findings also suggest that generally applicable "prediction equations" for delta FEV1 probably cannot be developed and that delta FEV1 values should only be compared between groups studied in an identical manner within a given study.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory disease in cotton textile workers in the People's Republic of China. II. Pulmonary function results.

Pulmonary function tests were performed pre and post workshift on 887 textile workers with at least two years of employment in two cotton mills and one silk mill in Shanghai, the People's Republic of China. Environmental sampling was performed with vertical elutriators, and pulmonary function was performed with standardized techniques. Cotton textile workers were found to have greater across-shift decrements in forced expiratory volume in 1 s (FEV1.0) than silk workers. Increasing duration of exposure resulted in increasing acute decrements in FEV1.0, although significant acute decrements were found in workers with less than five years of exposure. The acute changes in FEV 1.0 were noted in both symptomatic and asymptomatic cotton workers, though the difference between the across-shift change in FEV1.0 (delta FEV1.0%) of the byssinotics and nonbyssinotics increased as work duration increased. There was no difference in preshift FEV1.0 between the cotton and silk workers, but several selection factors likely influenced the observations.

How many spirograms for a histamine challenge?

Several reports have shown that a prior deep inspiration exerts a blunting effect on pharmacologically induced bronchoconstriction. Inspiration to total lung capacity is a mandatory requirement for valid determination of the FEV1, and thus, the FEV1 may underestimate the magnitude of induced airway obstruction. The present study was designed to assess the effect that the performance and separate analysis of 2 consecutive FEV1 maneuvers (FEV(1)1, FEV(1)2), obtained at different levels of histamine-induced bronchoconstriction, may have on the final interpretation of a histamine challenge. Eight asymptomatic nonsmoking asthmatics (mean age, 24 yr; range, 19 to 27 yr) underwent a total of 16 histamine challenges. Paired FEV1 measurements (FEV(1)1, FEV(1)2) were obtained after inhalation of buffer solution (control) and 3 min after inhalation of aerosolized, serially diluted, histamine diphosphate solutions. A significant airways response (FEV1 decreasing by 20% or more from the control value) was observed in all subjects after inhalation of 5 mg/ml of histamine or less, indicating histamine airway hypersensitivity. At lower doses of histamine the mean values for FEV(1)1 and FEV(1)2 were similar to the control value. At higher histamine doses FEV(1)2 was consistently higher than FEV(1)1 (p = 0.007) and exceeded FEV1 1 by a mean of 9% after inhalation of the provocational histamine concentration; delta FEV1(FEV(1)2-FEV(1)1) was correlated with the log10 of cumulative inhaled histamine dose units (p = 0.040). Assuming that the difference between corresponding FEV1 determinations at a given level of induced bronchoconstriction is a direct consequence of changes in lung mechanics induced by deep inspiration, we are led to conclude that during histamine inhalation challenges, only 1 spirogram should be performed at each level of induced bronchoconstriction.

Airway reactivity and lung function in triiodothyronine-induced thyrotoxicosis

To evaluate the possible relationship between asthma and hyperthyroidism, airway reactivity and lung function were prospectively compared in healthy volunteers before, during, and after liothyronine (triiodothyronine, T3)-induced hyperthyroidism. Base-line evaluation of the 10 subjects included clinical evaluation, thyroid and pulmonary function tests, and airway reactivity assessed by methacholine inhalational challenge (MIC). All studies were normal. During T3-induced hyperthyroidism, no subject developed respiratory symptoms or changes in pulmonary function or airway reactivity. The mean percent change in forced expiratory volume at 1 s from base line (delta FEV1) of -2.4 +/- 3.0 after MIC was not significantly different from that obtained before T3 administration (-1.4 +/- 1.5, P greater than 0.2). When all serum T3 concentrations and delta FEV1 values before, during and after T3-induced hyperthyroidism were compared, there was no significant correlation. We conclude that T3-induced hyperthyroidism of 3-wk duration has no effect on airway reactivity or lung function in normal volunteers.

Variability of airway responsiveness to histamine aerosol in normal subjects. Role of deposition.

The purpose of this investigation was to determine if the variability of bronchial responsiveness to inhaled histamine in normal subjects is related to the total dose of histamine deposited in the airways. To test this possibility, we used a new method of histamine challenge that permits calculating the histamine mass deposited in the airways in an attempt to correlate it with the magnitude of the response. Using a standardized breath-holding maneuver, 10 healthy nonsmokers and 10 healthy smokers with normal spirometry inhaled an aerosol generated from a solution containing a fixed ratio of histamine and a small quantity of hematoporphyrin serving as a fluorescent tracer. The mass of histamine deposited was calculated from the measured fluorescence of the inspired and expired aerosol. Forced expiratory volume in one second (FEV1) was measured before and 10 min after inhalation challenge. There was a negative correlation between percent decrease in FEV1 (delta FEV1) and histamine mass deposited in the nonsmokers (r = -0.83, p less than 0.005) and smokers (r = -0.82, p less than 0.005) without a difference between the 2 slopes. The range of delta FEV1 was 7 to 33% and of histamine mass deposited, 0.02 to 0.18 mg in the nonsmokers. The respective values in the smokers were 2 to 30% and 0.02 to 0.17 mg. In 6 subjects in whom dose-response curves were obtained, the mean deposited histamine mass required to decrease the FEV1 by 10% was 0.11 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors associated with longitudinal change in pulmonary function.

In a longitudinal study of pulmonary function, we investigated the relationship between loss of forced expiration over time and a series of potential risk factors, as well as 4 other measures of pulmonary function at initial visit. Data on 1,912 adults tested twice, with an average of 4.7 yr between visits, were used. Of the potential risk factors examined, only age and smoking were consistently associated with increased loss of forced expiratory function in both men and women. Statistically significant differences among ABO blood types and among Pi types were also seen in women, although the direction of these differences was unexpected in that non-Z Pi variant phenotypes showed less decline in pulmonary function than did the most common Pi M phenotypes. Similar patterns of differences were seen in men, although these were not statistically significant. Of 4 initial-visit pulmonary function measures examined, only closing capacity at initial visit was consistently associated with subsequent loss of forced expiratory volume in one second (delta FEV1) in both men and women. The final predictive model for delta FEV1 accounted for a modest proportion of the total variation seen in this sample, however, limiting its potential use for predicting decline in pulmonary function over a 5-yr span in individual subjects.

Response to cold air hyperventilation in normal and in asthmatic children

To assess the sensitivity of isocapnic hyperventilation with cold air in detecting airway hyperreactivity in asthmatic children, we studied 13 asthmatic patients (mean age 11.1 years) and 10 normal children. Cold air challenge consisted of 4 minutes of moderate hyperventilation plus another 4 minutes of maximal hyperventilation, both with subfreezing air (-16 degrees to -18 degrees C). Exercise and IHCA tests were done within 5 days and in random sequence. Mean (+/- SE) maximal % delta FEV1 after IHCA was 27 +/- 5.1% in the asthmatic children vs 4.5 +/- 1.2% in the normal subjects (P less than 0.01), even though there were no significant differences in the maximal minute ventilation equivalent between the two groups. Mean maximal % delta FEV1 after exercise was 31.7 +/- 5.6 in the asthmatic group. There was no difference in the sensitivity of the exercise and IHCA tests to detect bronchospasm in asthmatic children. Airway obstruction after IHCA was sharp and brief: maximal at 3 minutes after challenge, and back to 10% of baseline after 11 minutes. In seven asthmatic children the refractoriness to cold air and exercise was studied by repeating each test within 30 minutes; all seven showed significant refractoriness to exercise, and six showed no refractoriness to IHCA. We conclude that exercise and cold air-induced bronchospasm have different physiologic mechanisms, and that cold air testing can be used as a routine challenge to identify airway hyperreactivity in children.

Comparison of the tussive effects of histamine and methacholine in humans

The tussive and bronchoconstrictive effects of histamine inhalation in 7 normals, 7 asthmatics, and 24 patients with chronic cough (PCC) were measured by counting coughs during a standard histamine inhalation challenge. All PCC had a tussive response. Fifteen PCC exhibited significant linear correlations between cough count and either the change in forced expiratory volume at 1.0 (delta FEV1) or conductance-volume ratio (sGaw) (delta sGaw). Normals and asthmatics had little or no cough. Metaproterenol pretreatment in seven PCC reduced both the FEV1 and cough response to histamine without changing the relationship between cough and delta FEV1. The tussive and bronchoconstrictive effects of methacholine inhalation were also measured in 7 asthmatics and 16 PCC. One asthmatic coughed. Fifteen PCC coughed. There were significant linear correlations between cough count and delta FEV1 or delta sGaw in 10 PCC. At comparable delta FEV1 and delta sGaw, histamine produced more cough than methacholine. These data indicate that during inhalation of histamine or methacholine by PCC cough is related to, and may be caused by, bronchoconstriction. Histamine also causes cough by an additional mechanism not related to bronchoconstriction.

Refractory period after hyperventilation-induced asthma.

Nine young asthmatic subjects undertook isocapnic hyperventilation while breathing air under different conditions. Each subject undertook 2 pairs of tests. Pair A consisted of 2 hyperventilation challenges performed while breathing cold (2.8 +/- 1.4 degrees C) dry (2.3 +/- 0.05 mg H2O/L) air. Pair B consisted of an initial warm (38.0 +/- 0.9 degrees C) saturated air challenge followed by a cold dry challenge. Tests were closely matched in terms of ventilation and respiratory heat loss in the cold dry tests. The subjects were rendered refractory by the first cold dry hyperventilation challenge, the fall in forced expiratory volume in one second (FEV1) after hyperventilation in the first test (delta FEV1 = 39 +/- 5%) being significantly greater than that after the second challenge of Pair A (delta FEV1 = 21 +/- 5%, p less than 0.005). In test Pair B, the warm humid hyperventilation challenge neither caused significant asthma (delta FEV1 6 +/- 3%) nor rendered the subjects refractory to the subsequent cold dry test (delta FEV1 38 +/- 4%). Because in a previous study it was shown that exercise while breathing warm humid air could induce a refractory period without itself causing asthma, we conclude that hyperventilation-induced asthma is not the same as exercise-induced asthma in most subjects.

The Addition of An Aerosol Anticholinergic to An Oral Beta Agonist Plus Theophylline in Asthma and Bronchitis: A Double-blind Single Dose Study

In two groups of patients, 15 with asthma and 15 with chronic bronchitis, the bronchodilator effects of ipratropium bromide, of fenoterol plus theophylline, and of the combination of the three drugs, were compared using a double-blind, single-dose, placebo-controlled format. Ipratropium bromide caused rapid bronchodilatation which was not significantly different in asthmatic patients and patients with bronchitis (delta FEV1 = .29 L in one hour in asthmatic patients, .18 L in patients with bronchitis). In contrast, fenoterol plus theophylline induced a considerably greater effect in asthmatic patients (delta FEV1 = .41 L in one hour) than in those with bronchitis (delta FEV1 = .07 in one hour). The use of the three drugs in combination compared with ipratropium bromide alone, or fenoterol plus theophylline alone, resulted in a significant additional bronchodilatation in asthmatic patients. In the patients with bronchitis, the triple combination was clearly superior to fenoterol plus theophylline. A similar trend was present in comparing the triple combination to ipratropium bromide, but the difference did not reach statistical significance. There was no evidence of synergism when ipratropium bromide was combined with fenoterol plus theophylline in that the total bronchodilator effect was approximately additive. Asthmatic patients and the physician were able to distinguish the triple combination from placebo. No such ability was demonstrated with respect to those with bronchitis. All three drugs were well tolerated. Side effects were mostly mild, and none was related to the use of ipratropium.

Refractory period after exercise-induced asthma unexplained by respiratory heat loss.

Fifteen asthmatic children and young adults each exercised for 6 min by cycling on a cycle ergometer while breathing either cold (4.1 degrees C +/- 0.5 SEM) and dry (2.05 mg/L +/- 0.05) air or warm (37.2 degrees C +/- 0.3) fully saturated air. Each subject performed 4 tests arranged in pairs. Test pair A consisted of cold dry exercise followed by another cold dry exercise and test pair B consisted of a warm humid exercise followed by a cold dry exercise. Ventilation, heart rate, and gas exchange were closely matched in all 4 tests in each subject with a mean oxygen consumption of 34.8 +/- 0.8 ml/min/kg. In test pair A, all subjects were rendered refractory by the first cold dry exercise as manifested by a significant attenuation of their exercise-induced asthma (EIA) after the second cold dry test (per cent decrease in FEV1, delta FEV1 = 16 +/- 4 compared with 38 +/- 4). In 3 subjects, the warm humid exercise did not cause EIA and did not render them refractory to the second cold dry exercise. The 12 remaining subjects exhibited a refractory period similar to that shown in test pair A. They did not develop EIA after the warm humid test (delta FEV1 = 1 +/- 2), but after the subsequent cold dry exercise the per cent decrease in FEV1 was 19 +/- 3, similar to that in the second of the 2 cold dry exercise tests. These experiments suggest that in the majority of subjects exercise per se appears to be the cause for refractoriness and not airway cooling or bronchoconstriction.

Differences between swimming and running as stimuli for exercise-induced asthma.

Thirteen children each exercised for 6 min by running on a treadmill and by tethered swimming, breathing air at room temperature and either 8% or 99% relative humidity continuously. Ventilation, gas exchange and heart rate were closely matched in all four tests in each child, with a mean oxygen consumption of 32.3 +/- 1.7 ml x min-1 x kg-1. The post-exercise fall in FEV1 expressed as a percentage of the baseline FEV1 (delta FEV1) was significantly greater after running compared with swimming breathing either humid or dry air. The delta FEV1 was also related to respiratory heat loss (RHL) calculated from measurements of inspired and expired gas temperature and humidity. At a standardised RHL, the difference between running and swimming was highly significant [delta FEV1 (%) +/- SE = 39 +/- 5 and 28 +/- 4 respectively, p less than 0.01]. These experiments suggest that the type of exercise influences the severity of exercise-induced asthma even under conditions of the same metabolic stress and respiratory heat loss.

Effect of an H1 Blocker, Chlorpheniramine, on Inhalation Tests with Histamine and Allergen in Allergic Asthma

In 15 asthmatic subjects, flow volume loops were recorded before and after quantitative nebulization of increasing concentration of histamine and allergen, until a threshold response (-delta FEV1 > 10%) was obtained. Nine subjects with reproducible threshold doses to these two agents were included in the study. After pretreatment with 10 mg of intravenously administered chlorpheniramine, the threshold dose of histamine increased fourfold in eight subjects and eightfold in one subject, whereas the threshold doses to allergen doubled in seven and remained unaffected in two. One of these two subjects required 15 mg chlorpheniramine intravenously for comparable protection. In three subjects, the threshold dose to inhaled acetylcholine was determined with a similar procedure and found reproducible. Pretreatment with 10 to 15 mg chlorpheniramine increased this threshold dose two to four times, similarly to the effect produced by 0.4 mg of subcutaneously administered atropine. However, 0.4 mg atropine sc. did not alter the airway responses to allergen. The results suggest that intravenously administered chlorpheniramine provided it has a dose ratio of at least four against inhaled histamine, can prevent attacks of allergen-induced asthma. The effect is probably mediated through the H1 rather than the acetylcholine receptor.

Effects of atropine on respiratory heat loss in asthma.

We have previously observed that although atropine does not alter the magnitude of the response to exercise while breathing cold air, it does cause the predominant site of obstruction to move into the lung periphery. To determine if this effect was due to changes in the conditioning of inspired air, we measured respiratory heat loss (RHL) and retrotracheal (Trt) and retrocardiac esophageal temperature in eight asthmatics while they performed eucapnic hyperventilation with cold air before and after the inhalation of atropine. Multiple aspects of pulmonary mechanics were also recorded. Significant and equivalent airway obstruction developed with and without atropine (control delta FEV1 = 1.0 +/- 0.2 (SE) liter; postatropine = 0.9 +/- 0.3 liter). Despite this, RHL was 17.1% greater and Trt fell 16% more after atropine. These data demonstrate that atropine can influence heat transfer within the lung and alter the sites of conditioning.

Bacterial contamination of cotton as an indicator of respiratory effects among card room workers.

The influence of the bacterial contamination of cotton dust on the development of pulmonary symptoms has been investigated. The pulmonary function of card room workers in 23 US cotton mills was tested before and after the Monday working shift. A significant relation was found between the delta FEV1.0 decrement and the vertical elutriator dust level in the different mills. An improved correlation was obtained when the number of Gram-negative bacteria cultured from the bale cotton used in the different mills was employed in the exposure description. The results support earlier epidemiological and experimental studies, which demonstrate the importance of the Gram-negative bacteria in the development of pulmonary symptoms among workers in cotton mills.

Paradoxic Bronchospasm after Inhalation of Isoproterenol

Paradoxic bronchospasm induced by adrenergic aerosols, especially isoproterenol, is a well-known clinical entity. It normally occurs in patients who abuse the use of isoproterenol, but has also been reported in a small group of other patients. This study attempted to identify patients who exhibit paradoxic bronchospasm after administration of aerosolized isoproterenol. Forty-one stable, ambulant asthmatics, whose FEV 1.0 was less than 70 percent of predicted normal were studied. None of the asthmatics had taken isoproterenol for one year prior to evaluation. Baseline pulmonary function tests (FVC,FEV 1.09 MMEFR), blood pressure and ECG rhythm strips were recorded, and repeated at 15, 30, 60 and 120 min after administration of isoproterenol. Twenty-nine of the asthmatic patients had the expected normal response ( delta FEV 1.09 15 min: + 579; 30 min: + 464; 60 min: + 372; 120 min: + 307 ml: + 44, + 36, + 23 and + 24 percent) (delta MMEFR, 15 min: + 37; 60 min: + 29; 120 min: + 18L/Min: + 75, + 69, + 47 and + 37 percent). Twelve asthmatic patients (29 percent) had paradoxic bronchospasm (delta FEV 1.09 15 min: - 38; 30 min: - 60; 60 min: - 175; 120 min: - 27 ml; -1, -4, - 10 and - 4 percent) (delta MMEFR - 15 min: - .5; 30 min: - 3; 60 min: - 9; 120 min: - 2L/min; + 4, - 3, - 6 and - 5 percent, P less than 0.001).