Interaction of inhaled LTC4 with histamine and PGD2 on airway caliber in asthma

1989 ◽  
Vol 66 (1) ◽  
pp. 304-312 ◽  
Author(s):  
G. D. Phillips ◽  
S. T. Holgate

To investigate possible mediator interaction in asthma, the effect of inhaled leukotriene (LT) C4 on bronchoconstriction provoked by histamine and prostaglandin (PG) D2 was studied in nine asthmatic subjects. The provocation doses of histamine, PGD2, and LTC4 required to produce a 12.5% decrease in baseline forced expiratory volume in 1 s (FEV1, PD12.5) and to further this fall to 25% (PD25–12.5) were determined. On three subsequent occasions, subjects inhaled either the PD12.5 LTC4 plus vehicle or vehicle plus the PD25–12.5 of either histamine or PGD2, and FEV1 and maximal flow at 70% of vital capacity below total lung capacity after a forced partial expiratory maneuver (Vp30) followed for 45 min. From these results, predicted time-course curves for LTC4 with histamine and LTC4 with PGD2 were calculated. On two final occasions, airway caliber was followed for 45 min after inhalation of the PD12.5 LTC4 followed by the PD25–12.5 of either histamine or PGD2. During the first 9 min after LTC4-histamine and LTC4-PGD2, the decreases in airway caliber were greater than the calculated predicted response. This interaction, although small, was significant with LTC4-PGD2 for both FEV1 (P = 0.01) and Vp30 (P less than 0.05) and with LTC4-histamine for Vp30 (P less than 0.05) but not for FEV1 (P less than 0.05). We conclude that inhaled LTC4 interacts synergistically with histamine and PGD2 and that this effect, although small, may be a relevant interaction in asthma.

1977 ◽  
Vol 42 (4) ◽  
pp. 508-513 ◽  
Author(s):  
N. E. Brown ◽  
E. R. McFadden ◽  
R. H. Ingram

Bronchia reactivity to inhaled histamine was assessed in asymptomatic cigarette smokers and in nonsmoking atopic and nonatopic subjects. The only prechallenge between-group difference was the ratio of maximal flow on 80% helium-20% oxygen (Vmax HeO2) to maximal flow on air (Vmax air) from partial expiratory flow volume curves at 25% vital capacity (25% VC PEFV): Mean +/- SEM for smokers 1.18 /+- 0.06, atopics 1.45 +/- 0.08, nonatopics 1.51 +/- 0.03. This suggests that prior to inhalation to total lung capacity, the predominant site of resistance at flow limitation was in smaller airways of the smokers and in larger airways of both groups of nonsmokers. Following inhalation of histamine, smokers and nonatopics had similar changes in lung volumes and Vmax air which were less than in atopics. The Vmax HeO2/Vmax air ratios at 25% VC PEFV increased in smokers and decreased in nonsmokers: smokers 1.48 +/- 0.08, atopics 1.22 +/- 0.10, nontopics 1.16 +/- 0.06. This suggests a predominant large airway response in smokers and a prominent small airway response in nonsmokers. These responses may reflect differences in the predominant site of aerosol deposition rather than in airway reactivity.


2018 ◽  
Vol 125 (5) ◽  
pp. 1378-1383 ◽  
Author(s):  
Christopher Htun ◽  
Alun Pope ◽  
Samir Lahzami ◽  
Darren Luo ◽  
Robin E. Schoeffel ◽  
...  

Multiple breath nitrogen washout (MBNW) indices provide insight into ventilation heterogeneity globally [lung clearance index (LCI)] and within acinar (Sacin) and conducting (Scond) airways. Normal aging leads to an accelerated deterioration of Sacin in older adults, but little is known about the contribution of peripheral airway function to changes in pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] with aging. We aimed to examine associations between MBNW and FEV1/FVC as well as RV/TLC in healthy adults, and to determine if these relationships differ in older (≥50 yr) versus younger subjects (<50 yr). Seventy-nine healthy adult volunteers aged 23–89 yr with no cardiac or respiratory disease and a smoking history of <5 pack-years underwent spirometry, plethysmography, and MBNW. After adjustment for sex, height, and body mass index, the following relationships were present across the entire cohort: Sacin was inversely related to FEV1/FVC (R2 = 0.22, P < 0.001); Sacin and Scond were positively related to RV/TLC (R2 = 0.53, P < 0.001); on separate analyses, the relationship between Sacin and FEV1/FVC was strongest in the older group (R2 = 0.20, P = 0.003) but markedly weaker in the younger group (R2 = 0.09, P = 0.04); and Sacin and Scond were related to RV/TLC in older (R2 = 0.20, P = 0.003) but not younger subgroups. No relationships were observed between LCI and FEV1/FVC or RV/TLC. Changes in FEV1/FVC and RV/TLC are at least in part due to changes in peripheral airway function with aging. Further studies of the relationships between MBNW and standard pulmonary function indices may prove useful for their combined application and interpretation in obstructive airways disease. NEW & NOTEWORTHY This study explores associations between multiple breath nitrogen washout (MBNW) and standard pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] in healthy adults across a wide range of ages. We have demonstrated statistically significant relationships between MBNW and FEV1/FVC as well as RV/TLC. These findings provide novel evidence of the contribution of peripheral airway function to changes in standard pulmonary function indices with aging.


1993 ◽  
Vol 75 (3) ◽  
pp. 1155-1159 ◽  
Author(s):  
E. D'Angelo ◽  
E. Prandi ◽  
J. Milic-Emili

Thirteen normal subjects, sitting in a body plethysmograph and breathing through a pneumotachograph, performed forced vital capacity maneuvers after a rapid inspiration without or with an end-inspiratory pause (maneuvers 1 and 2) and after a slow inspiration without or with an end-inspiratory pause (maneuvers 3 and 4), the pause lasting 4–6 s. Inspirations were initiated close to functional residual capacity. At all lung volumes, expiratory flow was larger with maneuver 1 than with any other maneuver and, over the upper volume range, larger with maneuver 3 than with maneuver 4, whereas it was similar for maneuvers 2 and 4. Relative to corresponding values with maneuver 4, peak expiratory flow was approximately 16 and approximately 4% larger with maneuvers 1 and 3, respectively, whereas forced expiratory volume in 1 s increased by approximately 5% only with maneuver 1. The time dependence of maximal flow-volume curves is consistent with the presence of viscoelastic elements within the respiratory system (D'Angelo et al. J. Appl. Physiol. 70: 2602–2610, 1991).


2008 ◽  
Vol 31 (2) ◽  
pp. 391-395 ◽  
Author(s):  
J. Vandevoorde ◽  
S. Verbanck ◽  
D. Schuermans ◽  
L. Broekaert ◽  
D. Devroey ◽  
...  

2014 ◽  
Vol 12 (1) ◽  
pp. 120-125 ◽  
Author(s):  
Luciana Costa Melo ◽  
Maria Alayde Mendonça da Silva ◽  
Ana Carolina do Nascimento Calles

Obesity is a chronic disease characterized by the excessive accumulation of body fat that is harmful to the individuals. Respiratory disorders are among the comorbidities associated with obesity. This study had the objective of investigating the alterations in respiratory function that affect obese individuals. A systematic review was performed, by selecting publications in the science databases MEDLINE and LILACS, using PubMed and SciELO. The articles that assessed pulmonary function by plethysmography and/or spirometry in obese individuals aged under 18 years were included. The results demonstrated that the obese individuals presented with a reduction in lung volume and capacity as compared to healthy individuals. Reduction of total lung capacity and reduction of forced vital capacity, accompanied by reduction of the forced expiratory volume after one second were the most representative findings in the samples. The articles analyzed proved the presence of a restrictive respiratory pattern associated with obesity.


PEDIATRICS ◽  
1959 ◽  
Vol 24 (2) ◽  
pp. 181-193
Author(s):  
C. D. Cook ◽  
P. J. Helliesen ◽  
L. Kulczycki ◽  
H. Barrie ◽  
L. Friedlander ◽  
...  

Tidal volume, respiratory rate and lung volumes have been measured in 64 patients with cystic fibrosis of the pancreas while lung compliance and resistance were measured in 42 of these. Serial studies of lung volumes were done in 43. Tidal volume was reduced and the respiratory rate increased only in the most severely ill patients. Excluding the three patients with lobectomies, residual volume and functional residual capacity were found to be significantly increased in 46 and 21%, respectively. These changes correlated well with the roentgenographic evaluation of emphysema. Vital capacity was significantly reduced in 34% while total lung capacity was, on the average, relatively unchanged. Seventy per cent of the 61 patients had a signficantly elevated RV/TLC ratio. Lung compliance was significantly reduced in only the most severely ill patients but resistance was significantly increased in 35% of the patients studied. The serial studies of lung volumes showed no consistent trends among the groups of patients in the period between studies. However, 10% of the surviving patients showed evidence of significant improvement while 15% deteriorated. [See Fig. 8. in Source Pdf.] Although there were individual discrepancies, there was a definite correlation between the clinical evaluation and tests of respiratory function, especially the changes in residual volume, the vital capacity, RV/ TLC ratio and the lung compliance and resistance.


1987 ◽  
Vol 62 (3) ◽  
pp. 1179-1185 ◽  
Author(s):  
R. B. Filuk ◽  
N. R. Anthonisen

Twelve stable adult asthmatics slowly inhaled boluses of He at 20, 40, or 60% vital capacity (VC); these volumes were achieved either by expiring from total lung capacity (TLC) or by inspiring from residual volume (RV). Inspirations were continued to TLC and then were followed by slow expirations to RV while expired He was measured as a function of expired volume. At 20% VC slopes of alveolar plateaus (phase III) were positive, at 40% VC they were flat, and at 60% VC they were negative; at 20 and 60% VC the slopes were steeper than those in normals. When boluses were administered at 40 and 60% VC, He washout curves were independent of lung volume history. However at 20% VC the slope of phase III was significantly less positive when boluses were given after inspiration from RV than after expiration from TLC. In eight subjects, who were given inhaled beta-agonists, slopes of all He washouts decreased and became independent of volume history at 20% VC. We conclude that in asthmatics at low lung volumes the airways that determine ventilation distribution behave as though they have less hysteresis than the lung parenchyma probably due to increased airway tone.


1993 ◽  
Vol 74 (6) ◽  
pp. 3034-3039 ◽  
Author(s):  
O. P. Twentyman ◽  
S. V. Hood ◽  
S. T. Holgate

Considerable controversy exists over the influence of baseline airway caliber on indexes of bronchial responsiveness in asthma. To directly investigate this, we used inhaled methacholine to alter baseline airway caliber to determine whether this altered the airway response to subsequent bronchoprovocation with inhaled histamine. Seventeen stable asthmatic subjects were studied; their median age was 22 yr, baseline forced expiratory volume in 1 s (FEV1) was 101.5 +/- 3.7% (SE) predicted, and geometric mean provocative concentration of inhaled methacholine causing a 20% fall in FEV1 (PC20) was 0.87 mg/ml. Initially the time course of bronchoconstriction to inhaled methacholine was determined. Subsequently the airway response to inhaled histamine administered as a single concentration was determined, both before and after reductions in baseline FEV1 by saline or methacholine of 0, 15, 25, and 35%, on 4 separate days. Altering baseline airway caliber had no effect on the subsequent response of the airways to inhaled histamine when calculated as percent fall from the new baseline. The power of the study to detect an effect of altering baseline FEV1 on the measured PC20 histamine of 0.5 doubling dilutions was > 55%, and the power to detect an effect of 1.0 doubling dilutions was > 98%.


2006 ◽  
Vol 101 (3) ◽  
pp. 799-801 ◽  
Author(s):  
Leigh M. Seccombe ◽  
Peter G. Rogers ◽  
Nghi Mai ◽  
Chris K. Wong ◽  
Leonard Kritharides ◽  
...  

One technique employed by competitive breath-hold divers to increase diving depth is to hyperinflate the lungs with glossopharyngeal breathing (GPB). Our aim was to assess the relationship between measured volume and pressure changes due to GPB. Seven healthy male breath-hold divers, age 33 ( 8 ) [mean (SD)] years were recruited. Subjects performed baseline body plethysmography (TLCPRE). Plethysmography and mouth relaxation pressure were recorded immediately following a maximal GPB maneuver at total lung capacity (TLC) (TLCGPB) and within 5 min after the final GPB maneuver (TLCPOST). Mean TLC increased from TLCPRE to TLCGPB by 1.95 (0.66) liters and vital capacity (VC) by 1.92 (0.56) liters ( P < 0.0001), with no change in residual volume. There was an increase in TLCPOST compared with TLCPRE of 0.16 liters (0.14) ( P < 0.02). Mean mouth relaxation pressure at TLCGPB was 65 (19) cmH2O and was highly correlated with the percent increase in TLC ( R = 0.96). Breath-hold divers achieve substantial increases in measured lung volumes using GPB primarily from increasing VC. Approximately one-third of the additional air was accommodated by air compression.


1987 ◽  
Vol 73 (4) ◽  
pp. 401-405 ◽  
Author(s):  
George B. Rhind ◽  
Grahame A. Gould ◽  
David J. Ewing ◽  
Basil F. Clarke ◽  
Neil J. Douglas

1. Twelve male diabetic patients inhaled nebulized histamine in doubling concentrations from 0.03 mg/ml to 32 mg/ml until they reached the maximum concentration or until their forced expiratory volume in 1 s (FEV1.0) fell by at least 20%. Six had evidence of severe autonomic neuropathy (DAN), while the other six did not. 2. More of the DAN group decreased their FEV1.0 on histamine inhalation by at least 20% (P < 0.02) and more of them decreased their maximal flow at 50% vital capacity by at least 20% than those in the group without DAN (P < 0.05). 3. The fall in FEV1.0 and in maximal flow at 50% of vital capacity was greater (P < 0.05) in the DAN group than in the group without DAN. 4. This suggests that diabetic patients with autonomic neuropathy have increased bronchial reactivity to histamine. This could either be due to differential damage of the respiratory autonomic nerves or, alternatively, to denervation hypersensitivity.


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