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Pulmonary diffusing capacity for carbon monoxide (DLCO) has been an important pulmonary function test used since the 1950's. It measures the uptake of CO from the alveolar space into pulmonary capillary blood, following the same path as oxygen. It's used to evaluate/follow the progress of various lung diseases. In the eighties, a new test was developed similar to the DLCO test: pulmonary diffusing capacity for nitric oxide (DLNO). About 81-90% of the variance in DLNO is shared by DLCO in patients with cardiopulmonary disease and in healthy subjects. When DLNO is abnormally low, so is DLCO, and when DLNO is normal, so is DLCO (Kappa Statistic=0.69, n=251). The probability that DLNO and DLCO will be abnormally low when a cardiopulmonary disease is present (sensitivity) is 79% and 68%, respectively. The DLNO test avoids many technical issues associated with the measurement of DLCO: (1) DLNO is relatively unaffected by inspired oxygen concentration or ambient pressure, (2) DLNO is unaffected by carboxyhemoglobin, (3) DLNO is minimally affected by hemoglobin (Hb) concentration, thus correcting for Hb is not needed. (4) DLNO is more affected by lung volume compared to DLCO, thus DLNO divided by alveolar volume (KNO) is a better measure than KCO in those with restrictive lung disease, and (5) DLNO is a more stable measure over time compared to DLCO. Therefore, DLNO has several advantages over DLCO in the management of patients and could replace the DLCO test in most cases moving forward.

Pulmonary diffusing capacity for nitric oxide (DL,NO) and carbon monoxide (DL,CO) measured at rest (mL/min/mmHg) is strongly associated with aerobic capacity (cardiorespiratory fitness or peak oxygen uptake, VO2peak) measured in L/min. Data from healthy, non-obese individuals from various studies (n = 121 males and 81 females) were combined to examine this association. Subjects that were above the upper limit of normal (ULN, 97.5th percentile for age and sex and height) for DL,NO and DLCO had a higher median VO2peak compared to subjects below the ULN (Above the ULN = 4.2–4.5 L/min or 54–56 mL/kg/min; below the ULN = 3.0–3.2 L/min, 45–46 mL/kg/min, p

Background 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 (θNO) and CO (θCO) gave the lowest week-to-week variability in patients with heart failure. Methods 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. Results When using the double diffusing method and applying θNO = 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 θNO = infinity and DMCO = DLNO/2.42. The Vcap measured week-to-week was unreliable regardless of the method or constants used. Conclusions 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 θNO = infinity. Vcap estimation was unreliable with either method.

This paper reviews the scientific evidence for the safety of carbon monoxide (CO) and nitric oxide (NO) inhalation to measure pulmonary diffusing capacity (DL(CO) and DL(NO)) in pregnant women and their fetuses. In eight earlier studies, 650 pregnant women had DL(CO) measurements performed at various times during pregnancy, with a minimum of two to four tests per session. Both pregnant subjects that were healthy and those with medical complications were tested. No study reported adverse maternal, fetal, or neonatal outcomes from the CO inhalation in association with measuring DL(CO). Eleven pregnant women, chiefly with pulmonary hypertension, and 1105 pre-term neonates, mostly with respiratory failure, were administered various dosages of NO (5-80ppm for 4 weeks continuously in pregnant women, and 1-20ppm for 15min to 3 weeks for the neonates). NO treatment was found to be an effective therapy for pregnant women with pulmonary hypertension. In neonates with respiratory failure and pulmonary hypertension, NO therapy improved oxygenation and survival and has been associated with only minor, transient adverse effects. In conclusion, maternal carboxyhemoglobin ([Hb(CO)]) levels can safely increase to 5% per testing session when the dose-exposure limit is 0.3% CO inhalation for

This study was designed to compare differences in pulmonary gas exchange at rest and at peak exercise in two groups of women: (1) physically active, non-obese women and (2) women with morbid obesity. Fourteen morbidly obese women (body mass index or BMI = 49 ± 7 kg/m2; peak oxygen consumption or V ˙ O 2 peak = 14 ± 2 ml/ ( kg min ) ) and 14 physically active non-obese women (BMI = 22 ± 2 kg/m2; V ˙ O 2 peak = 50 ± 6 ml/ ( kg min ) ) performed an incremental, ramped exercise test to exhaustion on a cycle ergometer. Arterial blood was sampled at rest and at peak exercise. At rest, the alveolar to arterial oxygen partial pressure difference was 3× higher in the obese women (14 ± 10 mmHg) compared to non-obese women (5 ± 4 mmHg). Arterial carbon dioxide pressure ( P a C O 2 ) was identical in both groups at rest (37 ± 4 mmHg). Only the non-obese women showed a decrease in P a C O 2 rest to peak exercise (−5 ± 3 mmHg). The slope between heart rate and V ˙ O 2 during exercise was higher in the morbidly obese compared to non-obese women indicating that for the same absolute increase in V ˙ O 2 a larger increase in heart rate is needed, demonstrating poorer cardiac efficiency in obese women. In conclusion, morbidly obese women have poorer exercise capacity, cardiac efficiency, and compensatory hyperventilation at peak exercise, and poorer gas exchange at rest compared to physically active, non-obese women.

When monitoring nitric oxide diffusing capacity (DL NO ) in patients, it is necessary to distinguish natural biological variation from a real change in alveolar-membrane conductance. The short-term variability of single-breath DL NO has not been established. The aim was to determine the short-term variability DL NO in healthy subjects. Twelve healthy subjects performed single-breath hold diffusing capacity tests at rest over a 2-month period (eight separate sessions with 8 ± 3 days between each session). Each subject inhaled 41 ± 4 ppm NO and a standard diffusion mixture. DL NO , which is a multiple of the membrane diffusing capacity for carbon monoxide (Dm CO ), as well as carbon monoxide diffusing capacity (DL CO ) and pulmonary capillary blood volume ( V c ) remained unaltered over the 2-month period ( P > 0.05). Reproducibility (calculated as 2.77 multiplied by the within-subject standard deviation) over eight sessions was 20, 5 and 8 mL min −1 mmHg −1 for DL NO , DL CO and Dm CO , respectively, and 19 mL for V c (when Dm CO = DL NO /2.42). DL NO , DL CO , Dm CO and V c remain unchanged over a period of 2 months. Since the inter-session variability is 20, 5 and 8 mL min −1 mmHg −1 for DL NO , DL CO and Dm CO , and 19 mL for V c , a meaningful change should equal or exceed those values. While there is a small chance that week-to-week variation can also be partly due to mild pathophysiological changes, any differences that are below the reproducibility values are likely to be natural biological variation or technical variation of the equipment, rather than true physiological change.

The purpose was to determine if acute plasma volume expansion (PVE) changed red-cell pulmonary transit time (PTT) during severe exercise. Twelve endurance athletes performed 6.5 min of severe cycling exercise on different days. Pentaspan [(500 ml, infusion condition, I] or placebo [(60 ml saline), non-infusion condition, N] were infused prior to exercise. Blood gas tensions, PTT, multigated acquisition (MUGA) derived cardiac output, and oxygen uptake were measured during exercise. PTT was measured during minute 3 of exercise by radionuclide cardiography. Arterial P(O(2)) (Pa(O(2))), and alveolar-arterial oxygen pressure difference (AaD(O(2))) at minute 3 of exercise did not differ between conditions. Mean PTT at minute 3 of exercise was 0.3 sec longer in the I condition (P=0.002). However, the change in PTT between conditions was not correlated to the change in either Pa(O(2)) or AaD(O(2)). We conclude that PVE slows (lengthens) PTT without affecting pulmonary gas exchange. Therefore, rapid PTT may not be related to hypoxemia during exercise.

The purpose of this study was to compare the repeatability (2.77 multiplied by the within-subject SD) between two different rebreathing protocols on cardiac output ( Q ˙ ), pulmonary diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO), and pulmonary capillary blood volume (Vc). This study compared two bag volume protocols [Fixed Bag Volume (FBV) = bag volume fixed at 60% of forced vital capacity; Dynamic Bag Volume (DBV) = bag volume matched to tidal volume at each stage of exercise]. Ten females (age = 27 ± 8 yrs; V ˙ O 2 , peak = 2.5 ± 0.6 L / min had measurements at rest (12%), 52%, 88%, and 100% of V ˙ O 2 , peak on two study days. Neither the slope nor intercept of Q ˙ vs. V ˙ O 2 were different between either bag volume protocols. The slope of DLCO vs. Q ˙ was the same but the intercept was higher for the FBV protocol. The bag volume affected the slope and the intercept between DLNO vs. Q ˙ (p Q ˙ (2.0 vs. 2.3 L/min) and DLCO (3.8 vs. 5.9 mL/min/mmHg), regardless of exercise intensity. Increasing exercise intensity made the measurement error worse for Vc and DLNO (p ≤ 0.06). Measurement error was lower for Vc when using the FBV protocol (p = 0.02). Also, the pattern of bag volume used during rebreathing maneuvers affected the relation between DLNO vs. Q ˙ more than it affected DLCO vs. Q ˙ , or Vc vs. Q ˙ . Additionally, the FBV protocol provided less measurement error for Vc compared to the DBV protocol.