Respiratory impedance and multibreath N2 washout in healthy, asthmatic, and cystic fibrosis subjects

1990 ◽  
Vol 68 (5) ◽  
pp. 2139-2149 ◽  
Author(s):  
K. R. Lutchen ◽  
R. H. Habib ◽  
H. L. Dorkin ◽  
M. A. Wall
Keyword(s):  
Cystic Fibrosis ◽  
Normal Subjects ◽  
Forced Expiratory Volume ◽  
The Other ◽  
Poor Correlation ◽  
Base Line ◽  
Respiratory Impedance ◽  
Ventilation Distribution ◽  
Peripheral Airway ◽  
Lung Periphery

We measured forced expiratory volume in 1 s (FEV1), respiratory impedance (Zrs) from 4 to 60 Hz, and a multibreath N2 washout (MBNW) in 6 normal, 10 asthmatic, and 5 cystic fibrosis (CF) subjects. The MBNW were characterized by the mean dilution number (MDN) derived by a moment analysis. The Zrs spectra were characterized by the minimum resistance (Rmin), the drop in resistance (Rdrop) from 4 Hz to Rmin, and the first resonance frequency (Fr1). Measurements were repeated after bronchodilation in three normal and all asthmatic subjects. Before bronchodilation, six of the asthmatic subjects showed close to normal FEV1. The Zrs in the normal subjects showed low Rmin (1.9 +/- 0.7 cmH2O.l-1.s), Rdrop (0.4 +/- 0.4), and Fr1 (10 +/- 2 Hz). Four of the mildly obstructed asthmatic subjects had normal Zrs but elevated MDNs (i.e., abnormal ventilation distribution). The other six asthmatic subjects had significantly elevated Rmin (4.1 +/- 0.8), Rdrop (6.3 +/- 5.8), and Fr1 (34 +/- 0.4 Hz) and elevated MDNs. The CF patients had elevated Zrs features and MDNs. After bronchodilation, no changes in FEV1, MDN, or Zrs occurred in the normal subjects. All asthmatic subjects showed increased FEV1 and decreased MDN, but the Zrs was unaltered in the four asthmatic subjects whose base-line Zrs was normal. For the other six asthmatic subjects, there were large decreases in the Rmin, Rdrop, and Fr1. Finally, there was a poor correlation between the MDN and the Zrs features but high correlation between the Zrs features alone. These results imply that significant nonuniform peripheral airway obstruction can exist such that ventilation distribution is abnormal but Zrs from 4 to 60 Hz is not. Abnormalities in Zrs from 4 to 60 Hz occur only after significant overall obstruction in the peripheral and more central airways. Combining Zrs and the MBNW may permit us to infer whether the disease is predominantly in the lung periphery or in the more central airways.

The Severity of Bleeding Tendency in 5 Patients with Factor V Deficiency Due to Distinct Kinds of Factor V Mutations.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1764-1764
Author(s):  
Keiko Shinozawa ◽  
Kagehiro Amano ◽  
Takashi Suzuki ◽  
Hiroshi Inaba ◽  
Katsuyuki Fukutake
Keyword(s):  
Coagulation Factor ◽  
Normal Subjects ◽  
Japanese Patients ◽  
The Other ◽  
Hek293 Cells ◽  
Poor Correlation ◽  
Factor V ◽  
Bleeding Tendency ◽  
Wild Type ◽  
Mammalian Expression

Abstract Coagulation factor V (FV) deficiency is a rare autosomal recessive bleeding disorder. It is poor correlation between FV levels in plasma and the severity of bleeding tendency. In the present study, we identified 5 mutations in the FV gene (F5) in 5 unrelated Japanese patients with reduced plasma FV activities associated with inherited FV deficiency. Their bleeding tendencies varied in severity from asymptomatic to severe. We hypothesized that the severity of bleeding symptoms with severe FV deficiency is correlated with FV levels in platelets, and performed recombinant mutant proteins expression experiments and analyzed of platelet FV. The data concerning 5 patient’s FV levels in plasma and the bleeding symptoms are given in Table. The F5 mutations in 5 Japanese patients were identified by direct sequencing. One of the 5 patients was a compound heterozygote for FV mutations and carried a 5-base pair (bp) deletion in exon 22 (del.ACCCT) and V1813M. The other 4 patients were homozygous for a D68H, N468S, V1813M, and R2174L mutations, respectively. Four mutations except V1813M are newly identified mutations. These mutations were introduced independently by site-directed mutagenesis into a pMT2/FV mammalian expression plasmid containing the full-length FV cDNA, and the wild-type and mutant FV proteins were expressed in HEK293 cells. In the conditioned media, FV specific activities of the FV-D68H, FV-N468S, FV-V1813M, FV-R2174L, and 5bp del. mutants were an approximately 22%, 81%, 28%, 40%, and 19% of wild-type, respectively. On the other hand, analysis of platelet from patient by using RT-PCR showed that platelet F5 mRNA of FV-R2174L and FV-N468S was equal amount to that of normal subjects, although the amount of FV-V1813M platelet F5 mRNA was reduced. Platelet FV protein from patients was analyzed by western blotting and ELISA. Although the amount of platelet FV-R2174L protein was equal to that of normal platelets, platelet FV-V1813M protein was considerably reduced. In addition, the amount of FV-N468S protein in platelet was observed between that of normal subjects and FV-V1813M. These results indicate that the fact that sufficient amounts of FV are stored in platelet is required for local hemostasis. The results of FV-R2174L suggest that both functionality and amount of FV-R2174L in platelet is enough to cope with local bleeding, resulting very mild bleeding tendency. On the basis of present findings, we conclude that the severity of bleeding due to severe FV deficiency is correlated with not only plasma FV level, but also platelet FV. Five patient’s FV levels in plasma and the bleeding symptoms Patient No. Mutation FV activity (%) FV antigen (%) Bleeding symptoms 1 D68H 4 4 asymptomatic 2 N468S 3 3 asymptomatic 3 V1813M & 5-bp deletion <1 9 severe 4 V1813M <1 4 moderate 5 R2174L 1 5 very mild

Adenosine 5′-monophosphate challenge elicits a more peripheral airway response than methacholine challenge

2011 ◽  
Vol 110 (5) ◽  
pp. 1241-1247 ◽  
Author(s):  
Alain Michils ◽  
Yvon Elkrim ◽  
Amaryllis Haccuria ◽  
Alain Van Muylem
Keyword(s):  
Airway Hyperreactivity ◽  
Phase Iii ◽  
Ventilation Distribution ◽  
Methacholine Challenge ◽  
Single Breath ◽  
Before And After ◽  
Asthma Patients ◽  
Peripheral Airway ◽  
Airway Response ◽  
Lung Periphery

Adenosine 5′-monophosphate (AMP) and methacholine are commonly used to assess airway hyperreactivity. However, it is not fully known whether the site of airway constriction primarily involved during challenges with either agent is similar. Using a ventilation distribution test, we investigated whether the constriction induced by each agent involves the lung periphery in a similar fashion. Ventilation distribution was evaluated by the phase III slope (S) of the single-breath washout, using gases with different diffusivities like helium (He) and hexafluorosulfur (SF6). A greater postchallenge increase in SHe reflects alterations at the level of terminal and respiratory bronchioles, while a greater increase in SSF6 reflects alterations in alveolar ducts, increases to an equal extent reflecting alterations in more proximal airways where gas transport is still convective for both gases. SSF6 and SHe were measured in 15 asthma patients before and after airway challenges (20% forced expired volume in 1-s fall) with AMP and methacholine. SHe increased to a greater extent than SSF6 after AMP challenge (5.7 vs. 3.7%/l; P = 0.002), with both slopes increasing to an equal extent after methacholine challenge (3.1%/l; P = 0.959). The larger increase in SHe following AMP challenge suggests distal ventilation impairment up to the level of terminal and respiratory bronchioles. With methacholine, the similar increases in SHe and SSF6 suggest a less distal impairment. AMP, therefore, seems to affect more extensively the very peripheral airways, whereas methacholine seems to have an effect on less distal airways.

scholarly journals Role of noninvasive methods for assessing stable non-cystic fibrosis bronchiectasis

2020 ◽  
Author(s):  
Feng-jia Chen ◽  
Geng-peng Lin ◽  
Hui Yi ◽  
Xin-yan Huang ◽  
Yang-li Liu ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Airflow Obstruction ◽  
Stable State ◽  
Patient Characteristics ◽  
Forced Expiratory Volume ◽  
The Other ◽  
European Respiratory Society ◽  
High Resolution Computed Tomography ◽  
Noninvasive Methods ◽  
Clinical Phenotypes

Abstract Background: Bronchiectasis is characterized by the abnormal dilation of lung airways. Only some patients with bronchiectasis may clinically benefit from the treatment recommended in the guidelines of the European Respiratory Society. The value of noninvasive methods for assessing the clinical phenotypes of stable-state non-cystic fibrosis (non-CF) bronchiectasis for treatable characteristics has not been adequately studied.Methods: Eighty-nine patients with stable non-CF bronchiectasis were retrospectively enrolled. Patient characteristics, fractional exhaled nitric oxide (FeNO) values, and the results of blood tests for inflammatory markers, pulmonary function test, high-resolution computed tomography (HRCT), and bronchial hyper-responsiveness test or bronchodilator reversibility test were obtained. These data were used to assess the factors associated with the clinical phenotype of bronchiectasis.Results: The majority of the patients were female (60.67%) and have an average age of 59.08±15.09 years old. The predicted percentages of forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 and forced vital capacity were 56.17%±23.16% and 65.58%±15.26%, respectively. Eighteen (20.22%) of the patients with bronchiectasis had emphysema. The presence of emphysema in bronchiectasis was associated with a high airflow obstruction level. Seventeen (10.10%) of the patients with bronchiectasis had asthma. FeNO was significantly higher in the group of patients with bronchiectasis and asthma than in the other two groups (p < 0.01). The erythrocyte sedimentation rate (ESR) of the bronchiectasis alone group was higher than those of the other two groups. Significant negative correlations were found between ERS and FeNO levels (p = 0.02, r = −0.338), between HRCT score and FeNO levels (p = 0.04, r = −0.229), and between FEV1 (% predicted) and HRCT scores (p = 0.0007, r = −0.3629). A significant positive correlation was found between ERS and HRCT scores (p = 0.0001, r = 6326).Conclusion: A remarkable proportion of patients with bronchiectasis have emphysema or asthma. Biomarkers, such as FeNO, and conventional lung function tests should be routinely used for phenotyping bronchiectasis for potential targeted therapy. ESR can be used as a biomarker to reflect the level of systemic inflammation and the severity of bronchiectasis. These approaches will provide a better understanding of patients with bronchiectasis and their clinical phenotypes and lead to a more individualized and effective therapy.

Effect of bronchomotor tone on static mechanical properties of lung and ventilation distribution

1987 ◽  
Vol 63 (6) ◽  
pp. 2278-2285 ◽  
Author(s):  
A. B. Crawford ◽  
M. Makowska ◽  
L. A. Engel
Keyword(s):  
Mechanical Properties ◽  
Normal Subjects ◽  
Elastic Recoil ◽  
Ventilation Distribution ◽  
Ventilation Inhomogeneity ◽  
Before And After ◽  
Static Mechanical ◽  
Lung Periphery ◽  
Static Mechanical Properties ◽  
Bronchomotor Tone

To study the relationship between bronchomotor tone, static mechanical properties of the lung, and ventilation distribution, we measured the pressure-volume (P-V) curve of the lung and several ventilatory indexes before and after intravenous atropine in eight normal subjects. The indexes of ventilation distribution were derived from multiple breath N2 washouts by a recently developed analysis (7,8). The latter not only provides a sensitive measure of overall ventilation inhomogeneity but distinguishes between the convection-dependent inhomogeneity (CDI) among larger lung units and that due to the interaction of convection and diffusion (DCDI) within the lung periphery. Atropine decreased lung elastic recoil but distensibility, as defined by the exponent (K) in the monoexponential analysis of the P-V data, was unchanged. The overall ventilation inhomogeneity increased by 37% after atropine (P less than 0.02) due to an increase in the CDI component. More importantly, there was a significant correlation between the loss of lung recoil (but not K) and each of the indexes of CDI among the subjects. There was no correlation between the changes in lung recoil and in DCDI. Our findings indicate that normal bronchomotor tone contributes to the elastic recoil of the lung. Furthermore, the tone is distributed in a way that enhances the uniformity of ventilation distribution among diffusion-independent lung units. Presumably this is achieved by minimizing interacinar intrinsic inequalities in static mechanical properties.

Methacholine versus histamine: paradoxical response of spirometry and ventilation distribution

2001 ◽  
Vol 91 (6) ◽  
pp. 2587-2594 ◽  
Author(s):  
Sylvia Verbanck ◽  
Daniël Schuermans ◽  
Marc Noppen ◽  
Walter Vincken ◽  
Manuel Paiva
Keyword(s):  
Dose Group ◽  
Normal Subjects ◽  
Forced Expiratory Volume ◽  
Double Dose ◽  
Ventilation Distribution ◽  
Paradoxical Response ◽  
Airway Narrowing ◽  
Equal Dose ◽  
Ventilation Heterogeneity ◽  
Group A

We investigated the differential effect of histamine and methacholine on spirometry and ventilation distribution (where indexes S cond and S acin represent conductive and acinar ventilation heterogeneity; Verbanck S, Schuermans D, Van Muylem A, Noppen M, Paiva M, and Vincken W. J Appl Physiol 83: 1807–1816, 1997). Thirty normal subjects were challenged with cumulative doses of 6.52 μmol histamine and, on a separate day, with either 6.67 μmol methacholine (equal-dose group; n = 15) or 13.3 μmol methacholine (double-dose group; n = 15). Largest average forced expiratory volume in 1 s (FEV1) decreases or S cond increases obtained in either group were −9% and +286%, respectively; S acin remained unaffected at all times. In the equal-dose group, a smaller FEV1 decline ( P= 0.002) after methacholine was paralleled by a smaller S cond increase ( P = 0.041) than with histamine. However, in the double-dose group, methacholine maintained a smaller FEV1 decline ( P = 0.009) while inducing a larger S cond increase ( P = 0.006) than did histamine. The differential action of histamine and methacholine is confined to the conductive airways, where histamine likely causes the greatest overall airway narrowing and methacholine induces the largest parallel heterogeneity in airway narrowing, probably at the level of the large and small conductive airways, respectively. The observed ventilation heterogeneities predict a risk for dissociation between ventilation-perfusion mismatch and spirometry, particularly after methacholine challenge.

Effect of airway closure on ventilation distribution

1989 ◽  
Vol 66 (6) ◽  
pp. 2511-2515 ◽  
Author(s):  
A. B. Crawford ◽  
D. J. Cotton ◽  
M. Paiva ◽  
L. A. Engel
Keyword(s):  
Normal Subjects ◽  
Phase Iii ◽  
Mixing Efficiency ◽  
Breath Holding ◽  
Airway Closure ◽  
Ventilation Distribution ◽  
Residual Capacity ◽  
Lung Periphery ◽  
Phase Iii Slope ◽  
Volume Range

We examined the effect of airway closure on ventilation distribution during tidal breathing in six normal subjects. Each subject performed multiple-breath N2 washouts (MBNW) at tidal volumes of 1 liter over a range of preinspiratory lung volumes (PILV) from functional residual capacity (FRC) to just above residual volume. All subjects performed washouts at PILV below their measured closing capacity. In addition five of the subjects performed MBNW at PILV below closing capacity with end-inspiratory breath holds of 2 or 5 s. We measured the following two independent indexes of ventilation maldistribution: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency of those breaths of the washout where 80–90% of the initial N2 had been cleared. Between a mean PILV of 0.28 liter above closing capacity and that 0.31 liter below closing capacity, mean Snf increased by 132% (P less than 0.005). Over the same volume range, mean alveolar mixing efficiency decreased by 3.3% (P less than 0.05). Breath holding at PILV below closing capacity resulted in marked and consistent decreases in Snf and increases in alveolar mixing efficiency. Whereas inhomogeneity of ventilation decreases with lung volume when all airways are patent (J. Appl. Physiol. 66: 2502–2510, 1989), airway closure increases ventilation inequality, and this is substantially reduced by short end-inspiratory breath holds. These findings suggest that the predominant determinant of ventilation distribution below closing capacity is the inhomogeneous closure of airways subtending regions in the lung periphery that are close together.

Inhaled PAF fails to induce airway hyperresponsiveness to methacholine in normal human subjects

1990 ◽  
Vol 68 (3) ◽  
pp. 919-926 ◽  
Author(s):  
C. K. Lai ◽  
J. R. Jenkins ◽  
R. Polosa ◽  
S. T. Holgate
Keyword(s):  
Human Subjects ◽  
Control Period ◽  
Platelet Activating Factor ◽  
Normal Subjects ◽  
Forced Expiratory Volume ◽  
High Dose ◽  
Base Line ◽  
Airway Caliber ◽  
Significant Difference ◽  
Dose Dependent

The effects of three increasing doses of platelet-activating factor (PAF) on airway caliber and methacholine bronchial responsiveness were studied. On separate occasions nine normal subjects inhaled a single cumulative provocation concentration of methacholine (control) causing a 40% fall (PC40 Vp30) in maximum expiratory flow rate at 70% of base-line vital capacity below total lung capacity during a partial forced expiratory maneuver or 100 or 200 micrograms PAF, and seven subjects inhaled a further dose of 400 micrograms PAF. Methacholine responsiveness was measured before, at 3 and 7 h, then on days 1, 2, 3, 4, 7, 10, and 14 after each challenge. The maximum falls in Vp30 appeared dose dependent, but a significant difference between the magnitude of the responses was only observed between the 400- and 100-micrograms PAF dose (P less than 0.05). During the control period repeated methacholine challenges resulted in a progressive increase in cumulative provocation concentration of an agonist causing a 20% fall in forced expiratory volume in 1 s from base line, reaching significance on days 1 and 2 (2.44- and 2.4-fold of base line, respectively, P less than 0.01) before returning to base line on day 7. No difference was seen in methacholine responsiveness after any of the three doses of PAF compared with that after the control. We conclude that PAF causes dose-dependent bronchoconstriction but does not change airways responsiveness to methacholine and that repeated high-dose methacholine challenge leads to loss of responsiveness to this agonist.

Blood gas changes during and after nonspecific airway challenge in asthmatic and normal subjects

1989 ◽  
Vol 67 (6) ◽  
pp. 2627-2630 ◽  
Author(s):  
R. Dal Negro ◽  
L. Allegra
Keyword(s):  
Healthy Volunteers ◽  
Normal Subjects ◽  
Forced Expiratory Volume ◽  
Base Line ◽  
Gas Composition ◽  
Flow Volume ◽  
Blood Gas ◽  
Arterial Blood Gas ◽  
Arterial Blood ◽  
Gas Measurements

Twenty-eight asymptomatic asthmatics and 28 healthy volunteers were challenged with ultrasonically nebulized distilled water (UNDW). Blood gas composition was monitored transcutaneously (PtCO2 and PtcCO2) over 42 min (20 min for electrode stability, 3 min base line, 5 min during UNDW, and 14 min after UNDW). Flow-volume curves were recorded before and 15 min after UNDW. Forced expiratory volume in 1 s and expiratory flows decreased in asthmatics but not in normal subjects after UNDW. Mean base-line PtCO2 and PtcCO2 were comparable in the two groups. UNDW in normal subjects produced no significant changes in mean PtcCO2 and PtCO2. In asthmatics, the UNDW-induced decrease in mean PtcCO2 was greater and longer lasting, accompanied by a prolonged decrease in mean PtCO2. PtcCO2 and PtCO2 trends showed highly significant differences compared with healthy volunteers (P less than 0.001). Arterial blood gas measurements validated these changes. UNDW in asymptomatic asthmatics gives rise to a greater and more prolonged hyperventilation than in normal subjects and to gas-exchange abnormalities presumably reflecting a ventilation-perfusion mismatching.

Rectum has abnormal ion transport but normal cAMP-binding proteins in cystic fibrosis

1988 ◽  
Vol 254 (5) ◽  
pp. C719-C724 ◽  
Author(s):  
J. L. Goldstein ◽  
N. T. Nash ◽  
F. al-Bazzaz ◽  
T. J. Layden ◽  
M. C. Rao
Keyword(s):  
Cystic Fibrosis ◽  
Binding Proteins ◽  
Rectal Biopsy ◽  
Normal Subjects ◽  
Base Line ◽  
Free Solution ◽  
Camp Content ◽  
Biopsy Specimens ◽  
Human Rectum

The luminal membranes of involved tissues in cystic fibrosis (CF) are relatively impermeable to Cl and the regulation of Cl transport by adenosine 3',5'-cyclic monophosphate (cAMP)-mediated hormones is abnormal. We investigated the human rectum as a putative model for CF. We compared in vivo transrectal potential difference (PD) in CF and in normal subjects in response to sequential perfusions with various test solutions. The base-line PD was different in normal (-35.5 +/- 4.0 mV; lumen negative; mean +/- SE; n = 9) and CF subjects (-23.4 +/- 3.1 mV; n = 6; P less than 0.025) and was eliminated by amiloride (10(-4) M) perfusion in both groups by 3 min. However, in response to a Cl-free solution with amiloride, all six CF subjects exhibit less of a change in PD (PD, -2.2 +/- 1.2 mV vs. -11.7 +/- 1.5 mV in 6 controls; P less than 0.01). Furthermore, normal subjects (n = 7) respond to a 5 mM theophylline + amiloride perfusion with an increase in lumen-negative PD, whereas, CF subjects (n = 6) show no increase in lumen-negative PD. Rectal biopsy specimens from four normal and four CF subjects exhibit similar (2- to 3-fold) increases in theophylline-induced cAMP content and have similar cAMP-binding proteins (CF, n = 3; control, n = 3). We conclude that the rectum is an involved epithelium in CF in which the aberration may lie at a point beyond the binding of cAMP to its protein kinase.

Responsiveness, inflammation, and effects of deep breaths on obstruction in mild asthma

1989 ◽  
Vol 66 (5) ◽  
pp. 2298-2304 ◽  
Author(s):  
L. B. Pliss ◽  
E. P. Ingenito ◽  
R. H. Ingram
Keyword(s):  
Airway Inflammation ◽  
Total Protein ◽  
Airway Hyperresponsiveness ◽  
Normal Subjects ◽  
Base Line ◽  
Airway Caliber ◽  
Significant Difference ◽  
Peripheral Airway ◽  
Line Level ◽  
Airway Conductance

Using cellular and biochemical characteristics of bronchoalveolar lavage (BAL) liquid as an index of inflammation, we examined the relationships between change of airway caliber after a deep inhalation (DI), degree of base-line airway hyperresponsiveness, and peripheral airway inflammation in a group of 16 atopic asymptomatic mild asthmatics and 6 normal subjects. Compared with normal subjects, asthmatics demonstrated 1) significantly higher BAL concentrations of histamine, total protein, the sulfidopeptide leukotrienes (SRS-A), and leukotiene B4; 2) a decrease in specific airway conductance (sGaw) with a DI at base line vs. an increase in normal subjects (before vs. after percent change in sGaw, -10 vs. 12, P less than 0.05); and 3) no significant difference in BAL total cell count or leukocyte differential. Significant correlations were demonstrated between 1) percent of BAL eosinophils vs. degree of airway hyperresponsiveness; 2) base-line level of airway obstruction vs. degree of hyperresponsiveness; 3) effects of a DI vs. BAL concentrations of eosinophils, total protein, and histamine; 4) base-line forced expired volume in 1 s vs. BAL concentrations of total protein and histamine; and 5) BAL concentrations of the various mediators with each other. These data support the notion that 1) the response to a DI in mild, stable asthmatics represents a physiological indicator of peripheral obstruction because of inflammation and 2) this inflammation is associated with increases in several known mediators of airway inflammation and hyperreactivity.

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