scholarly journals Plasma P-Selectin Is Inversely Associated with Lung Function and Corticosteroid Responsiveness in Asthma

2020 ◽  
Vol 181 (11) ◽  
pp. 879-887
Author(s):  
Mats W. Johansson ◽  
Brandon M. Grill ◽  
Karina T. Barretto ◽  
Molly C. Favour ◽  
Hazel M. Schira ◽  
...  

<b><i>Background:</i></b> Severe asthma has multiple phenotypes for which biomarkers are still being defined. Plasma P-selectin reports endothelial and/or platelet activation. <b><i>Objective:</i></b> To determine if P-selectin is associated with features of asthma in a longitudinal study. <b><i>Methods:</i></b> Plasmas from 70 adult patients enrolled in the Severe Asthma Research Program (SARP) III at the University of Wisconsin-Madison were analyzed for concentration of P-selectin at several points over the course of 3 years, namely, at baseline (BPS), after intramuscular triamcinolone acetonide (TA) injection, and at 36 months after baseline. Thirty-four participants also came in during acute exacerbation and 6 weeks after exacerbation. <b><i>Results:</i></b> BPS correlated inversely with forced expiratory volume in 1 s (FEV<sub>1</sub>) and with residual volume/total lung capacity, an indicator of air trapping. BPS was inversely associated with FEV<sub>1</sub> change after TA, by regression analysis. FEV<sub>1</sub> did not change significantly after TA if BPS was above the median, whereas patients with BPS below the median had significantly increased FEV<sub>1</sub> after TA. BPS was higher in and predicted assignment to SARP phenotype cluster 5 (“severe fixed-airflow asthma”). P-selectin was modestly but significantly increased at exacerbation but returned to baseline within 3 years. <b><i>Conclusions:</i></b> High BPS is associated with airway obstruction, air trapping, the “severe fixed-airflow” cluster, and lack of FEV<sub>1</sub> improvement in response to TA injection. P-selectin concentration, which is a stable trait with only modest elevation during exacerbation, may be a useful biomarker for a severe asthma pheno- or endotype characterized by low pulmonary function and lack of corticosteroid responsiveness.

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.


2015 ◽  
Vol 14 (2) ◽  
pp. 187-194 ◽  
Author(s):  
Raíssa De Oliveira Borja ◽  
Tania Fernandes Campos ◽  
Diana Amélia de Freitas ◽  
Thalita Medeiros Fernandes de Macêdo ◽  
Waléria Cristina Miranda de Mendonça ◽  
...  

Introduction: Reference equations are used to predict normal values for maximal respiratory pressures. Objectives: To develop predictive equations for maximal respiratory pressure in children. Methods: A total of 144 healthy children, aged between 7 and 11 years, were assessed. Maximal inspiratory and expiratory pressures were assessed with a digital manovacuometer on top of residual volume and total lung capacity, respectively. Results: The variables sex, age and weight showed association with maximal inspiratory pressure, while maximal expiratory pressure, in addition to the aforementioned variables, also showed association with height. After regression analysis, only sex and age had an influence on the variability of inspiratory and expiratory pressures. Conclusions: The present study provides reference values and proposes two equation models that predict maximal respiratory pressure values among children aged between 7 and 11 years.


2003 ◽  
Vol 44 (5) ◽  
pp. 517-524 ◽  
Author(s):  
J. Vikgren ◽  
B. Bake ◽  
A. Ekberg-Jansson ◽  
S. Larsson ◽  
U. Tylén

Purpose: To test the hypothesis that diffuse and/or focal air trapping are sensitive indicators of airflow obstruction in smoker's small airways disease, when age, gender and presence of emphysematous lesions were allowed for. Material and Methods: Fifty-eight smokers and 34 never smokers, recruited from a randomized population study of men born in 1933, were investigated by HRCT and by extended pulmonary function tests, including a sensitive test for small airways disease (N2 slope). Diffuse air trapping was evaluated by calculating a quotient of mean lung density at expiration and inspiration. Focal air trapping was scored visually by consensus. Results: Diffuse air trapping did not differ between non-emphysematous smokers and never smokers. Furthermore, diffuse air trapping correlated well to the quotient between the residual volume and total lung capacity (RV/TLC, p = 0.01) and was consequently higher in emphysematous smokers than in never smokers. Focal air trapping was found as frequently in smokers without emphysema as in never smokers. Smokers with emphysema showed significantly less focal air trapping. Neither the N2 slope nor any of the other lung function variables differed between those with and without focal air trapping among non-emphysematous smokers. Conclusion: Neither diffuse nor focal air trapping are sensitive indicators of smoker's small airways disease.


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.


2017 ◽  
Vol 123 (4) ◽  
pp. 876-883 ◽  
Author(s):  
Robert H. Brown ◽  
Robert J. Henderson ◽  
Elizabeth A. Sugar ◽  
Janet T. Holbrook ◽  
Robert A. Wise

Brown RH, Henderson RJ, Sugar EA, Holbrook JT, Wise RA, on behalf of the American Lung Association Airways Clinical Research Centers. Reproducibility of airway luminal size in asthma measured by HRCT. J Appl Physiol 123: 876–883, 2017. First published July 13, 2017; doi:10.1152/japplphysiol.00307.2017.—High-resolution CT (HRCT) is a well-established imaging technology used to measure lung and airway morphology in vivo. However, there is a surprising lack of studies examining HRCT reproducibility. The CPAP Trial was a multicenter, randomized, three-parallel-arm, sham-controlled 12-wk clinical trial to assess the use of a nocturnal continuous positive airway pressure (CPAP) device on airway reactivity to methacholine. The lack of a treatment effect of CPAP on clinical or HRCT measures provided an opportunity for the current analysis. We assessed the reproducibility of HRCT imaging over 12 wk. Intraclass correlation coefficients (ICCs) were calculated for individual airway segments, individual lung lobes, both lungs, and air trapping. The ICC [95% confidence interval (CI)] for airway luminal size at total lung capacity ranged from 0.95 (0.91, 0.97) to 0.47 (0.27, 0.69). The ICC (95% CI) for airway luminal size at functional residual capacity ranged from 0.91 (0.85, 0.95) to 0.32 (0.11, 0.65). The ICC measurements for airway distensibility index and wall thickness were lower, ranging from poor (0.08) to moderate (0.63) agreement. The ICC for air trapping at functional residual capacity was 0.89 (0.81, 0.94) and varied only modestly by lobe from 0.76 (0.61, 0.87) to 0.95 (0.92, 0.97). In stable well-controlled asthmatic subjects, it is possible to reproducibly image unstimulated airway luminal areas over time, by region, and by size at total lung capacity throughout the lungs. Therefore, any changes in luminal size on repeat CT imaging are more likely due to changes in disease state and less likely due to normal variability. NEW & NOTEWORTHY There is a surprising lack of studies examining the reproducibility of high-resolution CT in asthma. The current study examined reproducibility of airway measurements. In stable well-controlled asthmatic subjects, it is possible to reproducibly image airway luminal areas over time, by region, and by size at total lung capacity throughout the lungs. Therefore, any changes in luminal size on repeat CT imaging are more likely due to changes in disease state and less likely due to normal variability.


1984 ◽  
Vol 56 (1) ◽  
pp. 52-56 ◽  
Author(s):  
T. S. Hurst ◽  
B. L. Graham ◽  
D. J. Cotton

We studied 10 symptom-free lifetime non-smokers and 17 smokers all with normal pulmonary function studies. All subjects performed single-breath N2 washout tests by either exhaling slowly (“slow maneuver”) from end inspiration (EI) to residual volume (RV) or exhaling maximally (“fast maneuver”) from EI to RV. After either maneuver, subjects then slowly inhaled 100% O2 to total lung capacity (TLC) and without breath holding, exhaled slowly back to RV. In the nonsmokers seated upright phase III slope of single-breath N2 test (delta N2/l) was lower (P less than 0.01) for the fast vs. the slow maneuver, but this difference disappeared when the subjects repeated the maneuvers in the supine position. In contrast, delta N2/l was higher for the fast vs. the slow maneuver (P less than 0.01) in smokers seated upright. For the slow maneuver, delta N2/l was similar between smokers and nonsmokers but for the fast maneuvers delta N2/l was higher in smokers than nonsmokers (P less than 0.01). We suggest that the fast exhalation to RV decreases delta N2/l in normal subjects by decreasing apex-to-base differences in regional ratio of RV to TLC (RV/TLC) but increases delta N2/l in smokers, because regional RV/TLC increases distal to sites of small airways obstruction when the expiratory flow rate is increased.


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.


2020 ◽  
Vol 9 (11) ◽  
pp. 3761
Author(s):  
Takato Ikeda ◽  
Yoshiaki Kinoshita ◽  
Yusuke Ueda ◽  
Tomoya Sasaki ◽  
Hisako Kushima ◽  
...  

Background: Diagnostic criteria of idiopathic pleuroparenchymal fibroelastosis (IPPFE) were recently proposed, including physiological criteria of the body mass index (BMI) and percentage of the predicted values of residual volume (RV)/total lung capacity (TLC) (RV/TLC %pred.). The aim of this study was to evaluate (i) whether the physiologic criteria are useful for the diagnosis and (ii) whether the flat chest index, defined as the ratio of the anteroposterior diameter to the transverse diameter of the thoracic cage, could be an alternative parameter to RV/TLC %pred. Methods: We selected consecutive IPPFE patients and idiopathic pulmonary fibrosis (IPF) patients. We examined the diagnostic sensitivity and specificity of the physiological criteria and flat chest index for differentiating IPPFE patients from IPF patients. Results: This study included 37 IPPFE patients and 89 IPF patients. The physiological criteria distinguished IPPFE patients from IPF patients with a sensitivity of 78.6% and specificity of 88.0%. The combination of the flat chest index and BMI was also effective for differentiation (sensitivity of 82.1% and specificity of 89.3%). Conclusion: We verified the good performance of the physiologic criteria in a different cohort. When the RV/TLC is not measured, using the flat chest index instead of RV/TLC %pred. may be reasonable.


1992 ◽  
Vol 73 (1) ◽  
pp. 151-159 ◽  
Author(s):  
D. C. Poole ◽  
O. Mathieu-Costello

To determine the potential range of diaphragm sarcomere lengths in situ and the effect of changes in sarcomere length on capillary and fiber geometry, rat diaphragms were perfusion fixed in situ with glutaraldehyde at different airway pressures and during electrical stimulation. The lengths of thick (1.517 +/- 0.007 microns) and thin (1.194 +/- 0.048 microns) filaments were not different from those established for rat limb muscle. Morphometric techniques were used to determine fiber cross-sectional area, sarcomere length, capillary orientation, and capillary length and surface area per fiber volume. All measurements were referenced to sarcomere length, which averaged 2.88 +/- 0.08 microns at -20 to -25 cmH2O airway pressure (residual volume) and 2.32 +/- 0.05 microns at +20 to +26 cmH2O airway pressure (total lung capacity). The contribution of capillary tortuosity and branching to total capillary length was dependent on sarcomere length and varied from 5 to 22%, consistent with that shown previously for mammalian limb muscles over this range of sarcomere lengths. Capillary length per fiber volume [Jv(c,f)] was significantly greater at residual volume (3,761 +/- 193 mm-2) than at total lung capacity (3,142 +/- 118 mm-2) and correlated with sarcomere length [l; r = 0.628, Jv(c,f) = 876l + 1,156, P less than 0.01; n = 18]. We conclude that the diaphragm is unusual in that the apparent in situ minimal sarcomere length is greater than 2.0 microns.(ABSTRACT TRUNCATED AT 250 WORDS)


2011 ◽  
Vol 83 (3) ◽  
pp. 967-972 ◽  
Author(s):  
Viviane Soares ◽  
Fábio B. Rodrigues ◽  
Marcus F. Vieira ◽  
Maria Sebastiana Silva

The respiratory muscles can present fatigue and even chronic inability to generate force. So, reliable devices are necessary to their evaluation. The aim of this study is to evaluate the MEP (Maximal Expiratory Pressure) values of individuals between 20 and 25 years old and to validate a protocol using a pressure transducer and a signal conditioner comparing it with the digital manometer. We evaluated the MEP of 10 participants. They remained seated and made six respiratory maneuvers from Total Lung Capacity (TLC) to Residual Volume (RV). The results in the study showed no statistically significant differences when compared to values reported in the literature, and that the pressure transducer provides reliable values for MEP.


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