Rate of nitric oxide production by lower alveolar airways  of human lungs

This report describes methods for measuring nitric oxide production by the lungs’ lower alveolar airways (V˙no), defined as those alveoli and bronchioles well perfused by the pulmonary circulation. Breath holding or vigorous rebreathing for 15–20 s minimizes removal of NO from the lower airways and results in a constant partial pressure of NO in the lower airways (Pl). Then the amount of NO diffusing into the perfusing blood will be the pulmonary diffusing capacity for NO (Dno) multiplied by Pl and by mass balance equalsV˙no, or V˙no = Dno(Pl). To measure Pl, 10 normal subjects breath held for 20 s followed by exhalation at a constant flow rate of 0.83 ± 0.14 (SD) l/s or rebreathed at 59 ± 15 l/min for 20 s while NO was continuously measured at the mouth. Dno was estimated to equal five times the single-breath carbon monoxide diffusing capacity. By using breath holding, Pl equaled 2.9 ± 0.8 mmHg × 10−6and V˙noequaled 0.39 ± 0.12 μl/min. During rebreathing Pl equaled 2.3 ± 0.6 mmHg × 10−6 andV˙no equaled 0.29 ± 0.11 μl/min. Measurements of NO at the mouth during rapid, constant exhalation after breath holding for 20 s or during rebreathing provide reproducible methods for measuringV˙no in humans.

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Pulmonary diffusing capacities for oxygen-labeled CO2 and nitric oxide in rabbits

Journal of Applied Physiology ◽

10.1152/jappl.1998.84.2.606 ◽

1998 ◽

Vol 84 (2) ◽

pp. 606-611 ◽

Cited By ~ 4

Author(s):

Hartmut Heller ◽

Gabi Fuchs ◽

Klaus-Dieter Schuster

Keyword(s):

Nitric Oxide ◽

Mass Spectrometry ◽

Mean Value ◽

Breath Holding ◽

Breath Hold ◽

Diffusing Capacity ◽

Membrane Component ◽

Single Breath ◽

Partial Pressures

Heller, Hartmut, Gabi Fuchs, and Klaus-Dieter Schuster. Pulmonary diffusing capacities for oxygen-labeled CO2 and nitric oxide in rabbits. J. Appl. Physiol. 84(2): 606–611, 1998.—We determined the pulmonary diffusing capacity (Dl) for18O-labeled CO2(C18O2) and nitric oxide (NO) to estimate the membrane component of the respective gas conductances. Six anesthetized paralyzed rabbits were ventilated by a computerized ventilatory servo system. Single-breath maneuvers were automatically performed by inflating the lungs with gas mixtures containing 0.9% C18O2or 0.05% NO in nitrogen, with breath-holding periods ranging from 0 to 1 s for C18O2and from 2 to 8 s for NO. The alveolar partial pressures of C18O2and NO were determined by using respiratory mass spectrometry. Dl was calculated from gas exchange during inflation, breath hold, and deflation. We obtained values of 14.0 ± 1.1 and 2.2 ± 0.1 (mean value ± SD) ml ⋅ mmHg−1 ⋅ min−1for[Formula: see text]and Dl NO, respectively. The measured[Formula: see text]/Dl NOratio was one-half that of the theoretically predicted value according to Graham’s law (6.3 ± 0.5 vs. 12, respectively). Analyses of the several mechanisms influencing the determination of[Formula: see text]and Dl NOand their ratio are discussed. An underestimation of the membrane diffusing component for CO2 is considered the likely reason for the low[Formula: see text]/Dl NOratio obtained.

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Improved accuracy and precision of single-breath CO diffusing capacity measurements

Journal of Applied Physiology ◽

10.1152/jappl.1981.51.5.1306 ◽

1981 ◽

Vol 51 (5) ◽

pp. 1306-1313 ◽

Cited By ~ 25

Author(s):

B. L. Graham ◽

J. T. Mink ◽

D. J. Cotton

Keyword(s):

Normal Subjects ◽

Single Equation ◽

Lung Model ◽

New Method ◽

Breath Holding ◽

Diffusing Capacity ◽

Single Breath ◽

Accuracy And Precision ◽

Conventional Methods ◽

The Way

Using three conventional methods and a new method we measured the single-breath diffusing capacity for carbon monoxide [DLCO(SB)] in a group of normal subjects. Whereas the conventional methods calculated DLCO(SB) from a single equation valid only for breath holding, the new method used three equations, one for each phase of the single-breath maneuver, i.e., inhalation, breath holding, and exhalation. We found that while the conventional methods of calculating DLCO(SB) were greatly affected by variations in the way in which the single-breath maneuver was performed and/or the way in which the alveolar gas sample was collected, these variations had little effect on the calculations of DLCO(SB) using the new method. These results were in close agreement with results from a computerized mathematical lung model in which the diffusing capacity did not change with lung volume. We concluded that the new method significantly improves the accuracy and precision of DLCO(SB) measurements while reducing the effects of maneuver variability. For these reasons comparisons of DLCO(SB) values between patients and normal subjects or between two groups with different pulmonary function may be more valid using the new method than using conventional methods.

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Modeling Axial Distribution of Nitric Oxide Production in Normal Subjects.

10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a6025 ◽

2009 ◽

Author(s):

Y Kerckx ◽

A Van Muylem

Keyword(s):

Nitric Oxide ◽

Normal Subjects ◽

Nitric Oxide Production ◽

Axial Distribution ◽

Oxide Production

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Standardisation and application of the single-breath determination of nitric oxide uptake in the lung

European Respiratory Journal ◽

10.1183/13993003.00962-2016 ◽

2017 ◽

Vol 49 (2) ◽

pp. 1600962 ◽

Cited By ~ 58

Author(s):

Gerald S. Zavorsky ◽

Connie C.W. Hsia ◽

J. Michael B. Hughes ◽

Colin D.R. Borland ◽

Hervé Guénard ◽

...

Keyword(s):

Nitric Oxide ◽

Hold Time ◽

Haemoglobin Concentration ◽

Specific Conductance ◽

Breath Holding ◽

Breath Hold ◽

Diffusing Capacity ◽

Detection Range ◽

Single Breath ◽

Alveolar Oxygen

Diffusing capacity of the lung for nitric oxide (DLNO), otherwise known as the transfer factor, was first measured in 1983. This document standardises the technique and application of single-breathDLNO. This panel agrees that 1) pulmonary function systems should allow for mixing and measurement of both nitric oxide (NO) and carbon monoxide (CO) gases directly from an inspiratory reservoir just before use, with expired concentrations measured from an alveolar “collection” or continuously sampledviarapid gas analysers; 2) breath-hold time should be 10 s with chemiluminescence NO analysers, or 4–6 s to accommodate the smaller detection range of the NO electrochemical cell; 3) inspired NO and oxygen concentrations should be 40–60 ppm and close to 21%, respectively; 4) the alveolar oxygen tension (PAO2) should be measured by sampling the expired gas; 5) a finite specific conductance in the blood for NO (θNO) should be assumed as 4.5 mL·min-1·mmHg-1·mL-1of blood; 6) the equation for 1/θCO should be (0.0062·PAO2+1.16)·(ideal haemoglobin/measured haemoglobin) based on breath-holdingPAO2and adjusted to an average haemoglobin concentration (male 14.6 g·dL−1, female 13.4 g·dL−1); 7) a membrane diffusing capacity ratio (DMNO/DMCO) should be 1.97, based on tissue diffusivity.

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Chemiluminescent measurements of nitric oxide pulmonary diffusing capacity and alveolar production in humans

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.5.1931 ◽

2001 ◽

Vol 91 (5) ◽

pp. 1931-1940 ◽

Cited By ~ 19

Author(s):

Irene B. Perillo ◽

Richard W. Hyde ◽

Albert J. Olszowka ◽

Anthony P. Pietropaoli ◽

Lauren M. Frasier ◽

...

Keyword(s):

Nitric Oxide ◽

Breath Holding ◽

No Production ◽

Diffusing Capacity ◽

Volume Changes ◽

Pulmonary Diffusing Capacity ◽

Single Breath ◽

Coefficients Of Variation ◽

Oxygen Tensions ◽

Single Constant

Measurements of nitric oxide (NO) pulmonary diffusing capacity (Dl NO) multiplied by alveolar NO partial pressure (Pa NO) provide values for alveolar NO production (V˙a NO). We evaluated applying a rapidly responding chemiluminescent NO analyzer to measure Dl NO during a single, constant exhalation (DexNO) or by rebreathing (DrbNO). With the use of an initial inspiration of 5–10 parts/million of NO with a correction for the measured NO back pressure, DexNO in nine healthy subjects equaled 125 ± 29 (SD) ml · min−1 · mmHg−1 and DrbNO equaled 122 ± 26 ml · min−1 · mmHg−1. These values were 4.7 ± 0.6 and 4.6 ± 0.6 times greater, respectively, than the subject's single-breath carbon monoxide diffusing capacity (DsbCO). Coefficients of variation were similar to previously reported breath-holding, single-breath measurements of DsbCO. Pa NOmeasured in seven of the subjects equaled 1.8 ± 0.7 mmHg × 10−6 and resulted in V˙a NO of 0.21 ± 0.06 μl/min using DexNO and 0.20 ± 0.6 μl/min with DrbNO. DexNO remained constant at end-expiratory oxygen tensions varied from 42 to 682 Torr. Decreases in lung volume resulted in falls of DexNO and DrbNO similar to the reported effect of volume changes on DsbCO. These data show that rapidly responding chemiluminescent NO analyzers provide reproducible measurements of Dl NO using single exhalations or rebreathing suitable for measuring V˙a NO.

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