Determination of lung capillary blood volume and membrane diffusing capacity in man by the measurements of NO and CO transfer

doi:10.1016/S0034-5687(87)80036-1

Respiration Physiology

Volume 70, Issue 1, 1987, Pages 113-120

Respiration Physiolo...

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Abstract

NO and CO lung transfer values (Tl) were measured separately in 14 healthy subjects (7 men, 7 women), using the single breath technique. Five repetitive maneuvers were performed by each subject for Tl_NO and Tl_CO determinations. The inspired mixture contained either 8 ppm NO or 0.25% CO, with 2% He, 21% O₂ in N₂. In order to measure an appreciable fraction of NO in the alveolar gas it was necessary to shorten the breath holding time to 3 sec. Tl_NO was about five times greater than Tl_CO. This result suggests that the specific conductance of blood (ϑ) for NO is very high and that the second term of the second member of the equation 1/Tl_NO = 1/Dm_NO + 1/(ϑ_NO · Qc) is therefore negligible. Dm_CO and Qc values can thus be computed from Tl_NO and Tl_CO measurements. The results obtained with this method are very close to those reported in the literature; for men Dm_CO = 79.0 ± 14.3 ml · min⁻¹ · Torr⁻¹, Qc = 78.0 ± 13.2 ml and for women Dm_CO = 59.0 ± 10.1 ml · min⁻¹ · Torr⁻¹, Qc = 59.5 ± 11.6 ml.

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Forced vital capacity and lung diffusing capacity for carbon monoxide (DL_CO) are traditionally used to assess lung involvement in systemic sclerosis (SSc) whereas total lung capacity is less frequently measured as marker for progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Oscillometry has been recently proposed to disentangle the complexity of lung mechanical abnormalities in SSc-ILD, but the findings were inconsistent possibly due to device-related discrepancies. In the last three decades, the lung diffusing capacity for nitric oxide (DL_NO) has been introduced because is more sensitive to membrane diffusion limitation than DL_CO. Thus, DL_NO may be abnormal even in the absence of lung restriction or fibrosis at computed tomography suggesting that it may reveal gas exchange alterations in SSc-ILD not detectable by other measurements. Finally, exercise studies have shown that higher slopes of expiratory minute ventilation versus carbon dioxide output relationship may predict mortality from SSc-ILD or pulmonary vasculopathy.
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Alveolar-capillary membrane diffusing capacity for carbon monoxide (DMCO) and pulmonary capillary volume (Vcap) can be estimated by the multi-step Roughton and Foster (RF, original method from 1957) or the single-step NO–CO double diffusion technique (developed in the 1980s). The latter method implies inherent assumptions. We sought to determine which combination of the alveolar membrane diffusing capacity for nitric oxide (DMNO) to DMCO ratio, an specific conductance of the blood for NO (θ_NO) and CO (θ_CO) gave the lowest week-to-week variability in patients with heart failure.
44 heart failure patients underwent DMCO and Vcap measurements on three occasions over a ten-week period using both RF and double dilution NO-CO techniques.
When using the double diffusing method and applying θ_NO = infinity, the smallest week-to-week coefficient of variation for DMCO was 10 %. Conversely, the RF method derived DMCO had a much greater week-to-week variability (2x higher coefficient of variation) than the DMCO derived via the NO-CO double dilution technique. The DMCO derived from the double diffusion technique most closely matched the DMCO from the RF method when θ_NO = infinity and DMCO = DLNO/2.42. The Vcap measured week-to-week was unreliable regardless of the method or constants used.
In heart failure patients, the week-to-week DMCO variability was lowest when using the single-step NO-CO technique. DMCO obtained from double diffusion most closely matched the RF DMCO when DMCO/2.42 and θ_NO = infinity. Vcap estimation was unreliable with either method.
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In people recovering from COVID-19, there is concern regarding potential long-term pulmonary sequelae and associated impairment of functional capacity. Data published thus far indicate that spirometric indices appear to be generally well preserved, but that a defect in diffusing capacity (DLco) is a prevalent abnormality identified on follow-up lung function; present in 20–30% of those with mild to moderate disease and 60% in those with severe disease. Reductions in total lung capacity were commonly reported. Functional capacity is also often impaired, with data now starting to emerge detailing walk test and cardiopulmonary exercise test outcome at follow-up. In this review, we evaluate the published evidence in this area, to summarise the impact of COVID-19 infection on pulmonary function and relate this to the clinico-radiological findings and disease severity.
Can DL<inf>NO</inf>/DL<inf>CO</inf> ratio offset prejudicial effects of functional heterogeneities in acinar regions?
2020, Respiratory Physiology and Neurobiology
(1) To establish the general equation that describes relationship of DM_CO/Vc versus DL_NO/DL_CO under conditions with no functional heterogeneities. (2) To examine the effects of functional heterogeneities, including parallel and series (stratified) heterogeneities, on DL_NO/DL_CO.
Results and discussions: (1) Given that “true” θ_NO in pulmonary capillaries is represented by surface absorption-related θ_NO, relationship between DM_CO/Vc and DL_NO/DL_CO does not differ significantly from that obtained on premise of infinite θ_NO. DL_NO/DL_CO decided physiologically may mirror morphometric DM_CO/Vc actually working for gas exchange but not “total” morphometric ratio of DM_CO/Vc. (2) There are three parallel heterogeneities that affect diffusing capacity (D)-related parameters. Of them, only the heterogeneity of D/V_A, where V_A is alveolar volume, underestimates DL_CO and DL_NO. DL_NO/DL_CO does not alleviate negative impact of D/V_A heterogeneity, indicating that DM_CO/Vc estimated from DL_NO/DL_CO does not mirror “true” morphometric DM_CO/Vc in diseased lungs with D/V_A maldistribution. (3) Stratified heterogeneity underrates morphometric DM_CO, DM_NO, and DM_NO/DM_CO maximally by 1.4 %, 2.8 %, and 1.4 %, respectively, under conditions similar to single-breath D measurements, suggesting that effect of stratified heterogeneity on D measures is no longer needed to be considered in normal subjects but may be in patients having lung diseases with destructive lesions of acinar structures.
Variability in pulmonary diffusing capacity in heart failure
2020, Respiratory Physiology and Neurobiology
As pulmonary diffusing capacity is related to mortality risk and prognosis in patients with heart failure (HF), it is measured frequently. As such, it would be essential to know the week-to-week variability (reproducibility) of pulmonary diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO). This variability would let clinicians understand what a clinically measurable change in DLCO and DLNO would be in these patients.
On three different days spanning over ten weeks, 40 H F patients underwent testing for DLCO and DLNO. DLCO was determined after a 4 s and 10 s breath-hold maneuver, while DLNO was determined after a 4 s breath-hold maneuver.
Forty heart failure patients (66 ± 10 years; BMI = 28.4 ± 4.6 kg∙m⁻²; 28 males), that were referred to our clinic were able to complete the protocol. DLCO (4 s breath-hold) and DLNO (4 s breath-hold) were 79 ± 19 % and 59 ± 14 % predicted, respectively. Fifty percent of patients (n = 20) were below the lower limit of normal (LLN, below the 5th percentile) for predicted DLCO (4 s), while 78 % of patients (n = 31) were below the LLN for predicted DLNO. All 16 patients that were below the LLN for DLCO were also below the LLN for DLNO. Over a ten week period, the reproducibility of DLNO (4 s) DLCO (4 s) and DLCO (10 s) was 18.9, 8.2, and 5.9 mL min mmHg^-1, respectively.
The week-to-week fluctuation in DLNO (4 s), as a percentage, is less than DLCO (4 s) in patients with HF. The reproducibility of DLNO in patients with HF is like that of healthy subjects.

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Determination of lung capillary blood volume and membrane diffusing capacity in man by the measurements of NO and CO transfer

Abstract

J. Inorg. Biochem.

J. Biol. Chem.

Nitric oxide effects on lung structure and blood oxygen affinity in rats

Bull. Eur. Physiopathol. Respir.

The fate in inhaled nitric oxide

Clin. Sci.

Membrane diffusion: comparison between dithionite DO2 and DlCO

The rate of uptake of carbon monoxide and of nitric oxide by normal erythrocytes and experimentally produced spherocytes

J. Gen. Physiol.

Critical evaluation of Saltzman technique for NOx analysis in the 0–100 ppm range

Environ. Sci. Technol.

The kinetics and equilibrium of the reactions of nitric oxide with sheep haemoglobin

J. Physiol. (London)

The atmospheric thermal oxidation of nitric oxide

J. Am. Chem. Soc.

Membrane diffusion: comparison between dithionite D_O₂ and Dl_{C_O}

Critical evaluation of Saltzman technique for NO_x analysis in the 0–100 ppm range