Diffusing Capacity For Nitric Oxide Research Articles

Pulmonary diffusing capacity for carbon monoxide and nitric oxide after COVID-19: A prospective cohort study (the SECURe study).

Many patients exhibit persistently reduced pulmonary diffusing capacity after coronavirus disease 2019 (COVID-19). In this study, dual test gas diffusing capacity for carbon monoxide and nitric oxide (DL,CO,NO) metrics and their relationship to disease severity and physical performance were examined in patients who previously had COVID-19. An initial cohort of 148 patients diagnosed with COVID-19 of all severities between March 2020 and March 2021 had a DL,CO,NO measurement performed using the single-breath method at 5.7months follow-up. All patients with at least one abnormal DL,CO,NO metric (n=87) were revaluated at 12.5months follow-up. The DL,CO,NO was used to provide the pulmonary diffusing capacity for nitric oxide (DL,NO), the pulmonary diffusing capacity for carbon monoxide (DL,CO,5s), the alveolar-capillary membrane diffusing capacity and the pulmonary capillary blood volume. At both 5.7 and 12.5months, physical performance was assessed using a 30 s sit-to-stand test and the 6min walk test. Approximately 60% of patients exhibited a severity-dependent decline in at least one DL,CO,NO metric at 5.7months follow-up. At 12.5months, both DL,NO and DL,CO,5s had returned towards normal but still remained abnormal in two-thirds of the patients. Concurrently, improvements in physical performance were observed, but with no apparent relationship to any DL,CO,NO metric. The severity-dependent decline in DL,NO and DL,CO observed at 5.7months after COVID-19 appears to be reduced consistently at 12.5months follow-up in the majority of patients, despite marked improvements in physical performance.

Lung diffusing capacity for nitric oxide in space: microgravity gas density interactions.

Introduction: During manned space exploration lung health is threatened by toxic planetary dust and radiation. Thus, tests such as lung diffusing capacity (DL) are likely be used in planetary habitats to monitor lung health. During a DL maneuver the rate of uptake of an inspired blood-soluble gas such as nitric oxide (NO) is determined (DLNO). The aim of this study was to investigate the influence of altered gravity and reduced atmospheric pressure on the test results, since the atmospheric pressure in a habitat on the moon or on Mars is planned to be lower than on Earth. Changes of gravity are known to alter the blood filling of the lungs which in turn may modify the rate of gas uptake into the blood, and changes of atmospheric pressure may alter the speed of gas transport in the gas phase. Methods: DLNO was determined in 11 subjects on the ground and in microgravity on the International Space Station. Experiments were performed at both normal (1.0atm absolute, ata) and reduced (0.7 ata) atmospheric pressures. Results: On the ground, DLNO did not differ between pressures, but in microgravity DLNO was increased by 9.8% (9.5) (mean [SD]) and 18.3% (15.8) at 1.0 and 0.7 ata respectively, compared to normal gravity, 1.0 ata. There was a significant interaction between pressure and gravity (p = 0.0135). Discussion: Estimates of the membrane (DmNO) and gas phase (DgNO) components of DLNO suggested that at normal gravity a reduced pressure led to opposing effects in convective and diffusive transport in the gas phase, with no net effect of pressure. In contrast, a DLNO increase with reduced pressure at microgravity is compatible with a substantial increase of DmNO partially offset by reduced DgNO, the latter being compatible with interstitial edema. In microgravity therefore, DmNO would be proportionally underestimated from DLNO. We also conclude that normal values for DL in anticipation of planetary exploration should be determined not only on the ground but also at the gravity and pressure conditions of a future planetary habitat.

Respiratory function in uncomplicated type 1 diabetes: Blunted during exercise even though normal at rest!

Type 1 diabetes is associated with a substantially increased risk of impaired lung function, which may impair aerobic fitness. We therefore aimed to examine the ventilatory response during maximal exercise and the pulmonary diffusion capacity function at rest in individuals with uncomplicated type 1 diabetes. In all, 17 adults with type 1 diabetes free from micro-macrovascular complications (glycated haemoglobin: 8.0 ± 1.3%), and 17 non-diabetic adults, carefully matched to the type 1 diabetes group according to gender, age, level of physical activity and body composition, participated in our study. Lung function was assessed by spirometry and measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) at rest. Subjects performed a maximal exercise test during which the respiratory parameters were measured. At rest, DLCO (30.4 ± 6.1ml min-1 mmHg-1 vs. 31.4 ± 5.7ml min-1 mmHg-1 , respectively, p=0.2), its determinants Dm (membrane diffusion capacity) and Vc (pulmonary capillary volume) were comparable among type 1 diabetes and control groups, respectively. Nevertheless, spirometry parameters (forced vital capacity=4.9 ± 1.0L vs. 5.5 ± 1.0L, p < 0.05; forced expiratory volume 1=4.0 ± 0.7L vs. 4.3 ± 0.7L, p < 0.05) were lower in individuals with type 1 diabetes, although in the predicted normal range. During exercise, ventilatory response to exercise was different between the two groups: tidal volume was lower in type 1 diabetes vs. individuals without diabetes (p < 0.05). Type 1 diabetes showed a reduced VO2max (34.7 ± 6.8 vs. 37.9 ± 6.3, respectively, p=0.04) in comparison to healthy subjects. Individuals with uncomplicated type 1 diabetes display normal alveolar-capillary diffusion capacity and at rest, while their forced vital capacity, tidal volumes and VO2 are reduced during maximal exercise.

Effects of Endurance Training Intensity on Pulmonary Diffusing Capacity at Rest and after Maximal Aerobic Exercise in Young Athletes.

This study compared the effects of varying aerobic training programs on pulmonary diffusing capacity (TLCO), pulmonary diffusing capacity for nitric oxide (TLNO), lung capillary blood volume (Vc) and alveolar–capillary membrane diffusing capacity (DM) of gases at rest and just after maximal exercise in young athletes. Sixteen healthy young runners (16–18 years) were randomly assigned to an intense endurance training program (IET, n = 8) or to a moderate endurance training program (MET, n = 8). The training volume was similar in IET and MET but with different work intensities, and each lasted for 8 weeks. Participants performed a maximal graded cycle bicycle ergometer test to measure maximal oxygen consumption (VO2max) and maximal aerobic power (MAP) before and after the training programs. Moreover, TLCO, TLNO and Vc were measured during a single breath maneuver. After eight weeks of training, all pulmonary parameters with the exception of alveolar volume (VA) and inspiratory volume (VI) (0.104 < p < 0889; 0.001 < ES < 0.091), measured at rest and at the end of maximal exercise, showed significant group × time interactions (p < 0.05, 0.2 < ES < 4.0). Post hoc analyses revealed significant pre-to-post decreases for maximal heart rates (p < 0.0001, ES = 3.1) and improvements for VO2max (p = 0.006, ES = 2.22) in the IET group. Moreover, post hoc analyses revealed significant pre-to-post improvements in the IET for DM, TLNO, TLCO and Vc (0.001 < p < 0.0022; 2.68 < ES < 6.45). In addition, there were increases in Vc at rest, VO2max, TLNO and DM in the IET but not in the MET participants after eight weeks of training with varying exercise intensities. Our findings suggest that the intensity of training may represent the most important factor in increasing pulmonary vascular function in young athletes.

The need for race-specific reference equations for pulmonary diffusing capacity for nitric oxide

BackgroundFew reference equations exist for healthy adults of various races for pulmonary diffusing capacity for nitric oxide (DLNO). The purpose of this study was to collect pilot data to demonstrate that race-specific reference equations are needed for DLNO.MethodsAfrican Americans (blacks) were chosen as the comparative racial group. In 2016, a total of 59 healthy black subjects (27 males and 32 females) were recruited to perform a full battery of pulmonary function tests. In the development of DLNO reference equations, a white reference sample (randomly drawn from a population) matched to the black sample for sex, age, and height was used. Multiple linear regression equations for DLNO, alveolar volume (VA), and pulmonary diffusing capacity for carbon monoxide (DLCO) using a 5–6 s breath-hold were developed.ResultsOur models demonstrated that sex, age2, race, and height explained 71% of the variance in DLNO and DLCO, with race accounting for approximately 5–10% of the total variance. After normalizing for sex, age2, and height, blacks had a 12.4 and 3.9 mL/min/mmHg lower DLNO and DLCO, respectively, compared to whites. The lower diffusing capacity values in blacks are due, in part, to their 0.6 L lower VA (controlling for sex and height).ConclusionThe results of this pilot data reveal small but important and statistically significant racial differences in DLNO and DLCO in adults. Future reference equations should account for racial differences. If these differences are not accounted for, then the risk of falsely diagnosing lung disease increase in blacks when using reference equations for whites.

Lung diffusing capacity for nitric oxide measured by two commercial devices: a randomised crossover comparison in healthy adults.

In Europe, two commercial devices are available to measure combined single-breath diffusing capacity of the lung for nitric oxide (DLNO) and carbon monoxide (DLCO) in one manoeuvre. Reference values were derived by pooling datasets from both devices, but agreement between devices has not been established.We conducted a randomised crossover trial in 35 healthy adults (age 40.0±15.5 years, 51% female) to compare DLNO (primary end-point) between MasterScreen™ (Vyaire Medical, Mettawa, IL, USA) and HypAir (Medisoft, Dinant, Belgium) devices during a single visit under controlled conditions. Linear mixed models were used adjusting for device and period as fixed effects and random intercept for each participant.Difference in DLNO between HypAir and MasterScreen was 24.0 mL·min−1·mmHg−1 (95% CI 21.7–26.3). There was no difference in DLCO (−0.03 mL·min−1·mmHg−1, 95% CI −0.57–0.12) between devices while alveolar volume (VA) was higher on HypAir compared to MasterScreen™ (0.48 L, 95% CI 0.45–0.52). Disparity in the estimation of VA and the rate of NO uptake (KNO=DLNO/VA) could explain the discrepancy in DLNO between devices. Disparity in the estimation of VA and the rate of CO uptake (KCO=DLCO/VA) per unit of VA offset each other resulting in negligible discrepancy in DLCO between devices. Differences in methods of expiratory gas sampling and sensor specifications between devices likely explain these observations.These findings have important implications for derivation of DLNO reference values and comparison of results across studies. Until this issue is resolved, reference values, established on the respective devices, should be used for test interpretation.

Lung diffusing capacity for nitric oxide and carbon monoxide following mild-to-severe COVID-19.

A decreased lung diffusing capacity for carbon monoxide (DLCO) has been reported in a variable proportion of subjects over the first 3 months of recovery from severe coronavirus disease 2019 (COVID‐19). In this study, we investigated whether measurement of lung diffusing capacity for nitric oxide (DLNO) offers additional insights on the presence and mechanisms of gas transport abnormalities. In 94 subjects, recovering from mild‐to‐severe COVID‐19 pneumonia, we measured DLNO and DLCO between 10 and 266 days after each patient was tested negative for severe acute respiratory syndrome coronavirus 2. In 38 subjects, a chest computed tomography (CT) was available for semiquantitative analysis at six axial levels and automatic quantitative analysis of entire lungs. DLNO was abnormal in 57% of subjects, independent of time of lung function testing and severity of COVID‐19, whereas standard DLCO was reduced in only 20% and mostly within the first 3 months. These differences were not associated with changes of simultaneous DLNO/DLCO ratio, while DLCO/VA and DLNO/VA were within normal range or slightly decreased. DLCO but not DLNO positively correlated with recovery time and DLCO was within the normal range in about 90% of cases after 3 months, while DLNO was reduced in more than half of subjects. Both DLNO and DLCO inversely correlated with persisting CT ground glass opacities and mean lung attenuation, but these were more frequently associated with DLNO than DLCO decrease. These data show that an impairment of DLNO exceeding standard DLCO may be present during the recovery from COVID‐19, possibly due to loss of alveolar units with alveolar membrane damage, but relatively preserved capillary volume. Alterations of gas transport may be present even in subjects who had mild COVID‐19 pneumonia and no or minimal persisting CT abnormalities.Trial registryClinicalTrials.gov PRS: No.: NCT04610554 Unique Protocol ID: SARS‐CoV‐2_DLNO 2020.

Effects of exercise on thoracic blood volumes, lung fluid accumulation, and pulmonary diffusing capacity in heart failure with preserved ejection fraction.

Patients with heart failure with preserved ejection fraction (HFpEF) experience symptoms of exertional dyspnea that may be related to lung fluid accumulation during exercise. A computed tomography (CT)-based method was used to measure exercise-induced changes in extravascular lung fluid content and thoracic blood volumes and to determine the effect of lung fluid on lung diffusing capacity for carbon monoxide (DLCO) in stable subjects with HFpEF and healthy controls. Nine subjects with HFpEF (age = 68 ± 8 yr; body mass index = 32.1 ± 2.6 kg/m2) and eight healthy controls (62 ± 9 yr, 23.8 ± 2.4 kg/m2) performed triplicate rebreathe DLCO/DLNO (lung diffusing capacity for nitric oxide) tests in a supine position at rest and duplicate measurements during two 5-min submaximal exercise stages (15W and 35W) and recovery. Subjects subsequently performed a 5-min exercise bout (35W) inside a CT scanner, and extravascular lung fluid content and thoracic blood volumes were quantified at rest and immediately following exercise from thoracic and contrast perfusion scans, respectively. Subjects with HFpEF had a higher lung fluid content at rest compared with controls (means ± SD, HFpEF: 14.4 ± 1.7%, control: 12.8 ± 1.7%, P = 0.043) and a higher lung fluid content following exercise (15.2 ± 2.0% vs. 12.6 ± 1.5%, P = 0.009). Higher lung fluid content was associated with a lower DLCO and alveolar-capillary membrane conductance (Dm) in subjects with HFpEF (DLCO: R = -0.57, P = 0.022, Dm: R = -0.61, P = 0.012) but not in controls. Pulmonary blood volume was not altered by exercise and was similar between groups. Submaximal exercise elicited a greater accumulation of lung fluid in subjects with HFpEF compared with in controls, and lung fluid content was negatively correlated with lung diffusing capacity and alveolar-capillary membrane conductance in subjects with HFpEF.

Acute effects of hypertonic saline inhalation on nitric oxide pulmonary diffusing capacity in healthy adults

We investigated acute effects of inhalation of hypertonic saline solution (HSS) and oxygen (O2, control exposure) on pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO). In a randomized crossover study, 20 healthy, non-smoking subjects were allocated to short-term inhalation of HSS or O2. Spirometry [(forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] and combined single-breath DLNO-DLCO measurements were performed before and immediately after inhalation of either HSS or O2. Percent changes were presented as median values (interquartile range). After HSS inhalation, DLNO, FEV1 and FVC were decreased by −3.0% (−7.3, 0.5), −3.1% (−4.2, −1.6) and −1.2% (−3.3, 0.6), respectively (all P < 0.05), without significant effect on DLCO. No changes in spirometry and diffusing capacity were observed following O2 inhalation. Acute inhalation of HSS causes a slight decrease in membrane conductance, probably as a result of fluid imbalance at the alveolar surface and interstitial fluid accumulation, both of which could impair gas exchange.

Combined diffusing capacity for nitric oxide and carbon monoxide as predictor of bronchiolitis obliterans syndrome following lung transplantation

BackgroundThere is a need for non-invasive parameters that are sensitive to the development of the bronchiolitis obliterans syndrome (BOS) in lung transplantation (LTx) patients. We studied whether the pulmonary diffusing capacity for inhaled nitric oxide is capable of detecting BOS stages.MethodsSixty-one LTx patients were included into this cross-sectional study (19/29/7/3/3 in BOS stages 0/0-p/1/2/3). For analysis stages 0/0-p versus 1/2/3 (“BOS binary-early”), and stages 0/0-p/1 versus 2/3 (“BOS binary-late”) were summarized. Measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) were compared with spirometry and bodyplethysmography, and their relative importance was evaluated by discriminant analysis.ResultsRegarding the recognition of “BOS binary-early”, among spirometric parameters forced expiratory volume in 1 s (FEV1) was best, among bodyplethysmographic parameters airway resistance, and among diffusing parameters DLNO. Regarding “BOS binary-late”, DLNO was inferior to bodyplethysmographic parameters.ConclusionAlthough the study comprised only measurements at a single time point and no follow-up, DLNO outperformed FEV1, the time course of which is used in detecting BOS. Together with its pathophysiological plausibility, this result suggests that the measurement of DLNO, possibly over time, could be an easily applicable tool for the monitoring of LTx patients and should be evaluated in larger studies.

Acute effects of combined exercise and oscillatory positive expiratory pressure therapy on sputum properties and lung diffusing capacity in cystic fibrosis: a randomized, controlled, crossover trial

BackgroundRegular airway clearance by chest physiotherapy and/or exercise is critical to lung health in cystic fibrosis (CF). Combination of cycling exercise and chest physiotherapy using the Flutter® device on sputum properties has not yet been investigated.MethodsThis prospective, randomized crossover study compared a single bout of continuous cycling exercise at moderate intensity (experiment A, control condition) vs a combination of interval cycling exercise plus Flutter® (experiment B). Sputum properties (viscoelasticity, yield stress, solids content, spinnability, and ease of sputum expectoration), pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) were assessed at rest, directly and 45 min post-exercise (recovery) at 2 consecutive visits. Primary outcome was change in sputum viscoelasticity (G’, storage modulus; G”, loss modulus) over a broad frequency range (0.1–100 rad.s− 1).Results15 adults with CF (FEV1range 24–94% predicted) completed all experiments. No consistent differences between experiments were observed for G’ and G” and other sputum properties, except for ease of sputum expectoration during recovery favoring experiment A. DLNO, DLCO, alveolar volume (VA) and pulmonary capillary blood volume (Vcap) increased during experiment A, while DLCO and Vcap increased during experiment B (all P < 0.05). We found no differences in absolute changes in pulmonary diffusing capacity and its components between experiments, except a higher VA immediately post-exercise favoring experiment A (P = 0.032).ConclusionsThe additional use of the Flutter® to moderate intensity interval cycling exercise has no measurable effect on the viscoelastic properties of sputum compared to moderate intensity continuous cycling alone. Elevations in diffusing capacity represent an acute exercise-induced effect not sustained post-exercise.Trial registrationClinicalTrials.gov; No.: NCT02750722; URL: clinical.trials.gov; Registration date: April 25th, 2016.

The association between cardiorespiratory fitness and pulmonary diffusing capacity

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=4.2–4.5L/min or 54–56mL/kg/min; below the ULN=3.0–3.2L/min, 45–46mL/kg/min, p<0.001). Those that were classified as Superior or Excellent in cardiorespiratory fitness (≥80th percentile in VO2peak for the person’s age and sex) increased their odds of being above the ULN for DL,NO and DL,CO by about 6-fold and 8-fold, respectively, compared to those not classified as being Superior or Excellent in cardiorespiratory fitness. Approximately 65–68% of the variance in DL,NO and DL,CO, respectively, was shared by VO2peak (L/min) (p<0.001). However, after controlling for alveolar volume, sex, height, body mass, and age, the shared variance between pulmonary diffusing capacity and VO2peak decreased to 16–20% (95% CI=8–30%), and yet, remained statistically significant (p<0.001). The reasons for the shared variance between pulmonary diffusing capacity and VO2peak are discussed.

Can the measurement of pulmonary diffusing capacity for nitric oxide replace the measurement of pulmonary diffusing capacity for carbon monoxide?

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.

The Role of Flow-Independent Exhaled Nitric Oxide Parameters in the Assessment of Airway Diseases.

Nitric oxide (NO), the first gas known to act as a biological messenger, is one of the most widely studied free radical/gas in medicine, both for its biological function and therapeutic applications. The measurement of endogenous NO in exhaled air is widely used in the evaluation of lung disorders. Partitioning of exhaled nitric oxide (eNO) is of increasing interest because of the additional information about lung pathology and distal lung inflammation that can be obtained. Specifically, measuring exhaled NO at multiple flow rates allows assessment of the flow-independent NO parameters: alveolar NO concentration (CalvNO), bronchial NO flux (JNO), bronchial wall NO concentration (CWNO), and bronchial diffusing capacity of NO (DNO). Several studies have reported that there were different patterns of those parameters in different airway diseases and/or in different severities of the same disease, mostly in asthma. Specifically, while JNO seems to provide the same information as FeNO50, alveolar NO concentration appears to be an independent parameter that is putatively associated with increased distal lung inflammation and more severe disease. However, despite much research interest in partitioning exhaled NO, clinical usefulness has yet to be established.

Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias.

Lung diffusing capacity for carbon monoxide (DLCO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DLCO to changes in alveolar membrane diffusive conductance (DMCO). The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DLNO) better reflects fibrotic changes than DLCO DLNO-DLCO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP. Eighty-one matched healthy subjects served as a control group. The amount of pulmonary fibrosis was estimated by CT volumetric analysis of visually bounded areas showing reticular opacities and honeycombing. DMCO and pulmonary capillary volume (VC) were calculated. DLNO was below the lower limit of normal in all patients irrespective of extent and nature of disease, whereas DLCO was within the normal range in a nonnegligible number of patients. Both DLNO and DLCO were significantly correlated with visual assessment of fibrosis but DLNO more closely than DLCO DMCO was also below the lower limit of normal in all UIP-IPF and NSIP patients and significantly correlated with fibrosis extent in both diseases, whereas VC was weakly correlated with fibrosis in UIP-IPF and uncorrelated in NSIP, with normal values in half of patients. In conclusion, measurement of DLNO may provide a more sensitive evaluation of fibrotic changes than DLCO in either UIP-IPF or NSIP, because it better reflects DMCO.

Pulmonary capillary reserve and exercise capacity at high altitude in healthy humans.

PurposeWe determined whether well-acclimatized humans have a reserve to recruit pulmonary capillaries in response to exercise at high altitude.MethodsAt sea level, lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO), and pulmonary capillary blood volume (Vc) were measured at rest before maximal oxygen consumption (dot{V}{text{O}}_{2hbox{max} }) was determined in seven adults. Then, DLCO, DmCO and Vc were measured pre- and post-exhaustive incremental exercise at 5150 m after ~40 days of acclimatization.ResultsImmediately after exercise at high altitude, there was an increase in group mean DmCO (14 ± 10 %, P = 0.040) with no pre- to post-exercise change in group mean DLCO (46.9 ± 5.8 vs. 50.6 ± 9.6 ml/min/mmHg, P = 0.213) or Vc (151 ± 28 vs. 158 ± 37 ml, P = 0.693). There was, however, a ~20 % increase in DLCO from pre- to post-exercise at high altitude (51.2 ± 0.2 vs. 61.1 ± 0.2 ml/min/mmHg) with a concomitant increase in DmCO (123 ± 2 vs. 156 ± 4 ml/min/mmHg) and Vc (157 ± 3 vs. 180 ± 8 ml) in 2 of the 7 participants. There was a significant positive relationship between the decrease in dot{V}{text{O}}_{2hbox{max} } from sea level to high altitude and the change in DLCO and lung diffusing capacity for nitric oxide (DLNO) from rest to end-exercise at high altitude.ConclusionThese data suggest that recruitment of the pulmonary capillaries in response to exercise at high altitude is limited in most well-acclimatized humans but that any such a reserve may be associated with better exercise capacity.

Confusion in reporting pulmonary diffusing capacity for nitric oxide and the alveolar-capillary membrane conductance for nitric oxide

We read with interest the paper by Magini and col- leagues on the measurement of pulmonary diffusing capacity for nitric oxide in patients with heart failure (ejection fraction<40%). 1 In their study they report pulmonary diffusing capacity and the individual com- ponents of pulmonary diffusing capacity in 50 patients with heart failure (65 years of age), and 50 control sub- jects (61 years of age). We feel that there are two prob- lems with this paper that warrant discussion. First, the mean values for pulmonary diffusing capacity for nitric oxide (DLNO) for the healthy subjects are too low, and second, both their alveolar-membrane conductances (DmNO and DmCO) and pulmonary capillary blood volume (Vc) calculations, and hence conclusions, are incorrect. First, the values for DLNO for the healthy volunteers appear too low. If we assume that the women's and men's mean height in the healthy volunteers was 163 and 173 cm, respectively, then the mean DLNO values should be 96-113 and 140-154 ml/min/mm Hg, for women and men, respectively. 2,3 The combined average for DLNO should be then 118-133 ml/min/mm Hg. The author's mean values of 89 ml/min/mm Hg for the healthy volunteers are 25-33% lower than predicted. However, their values for pulmonary diffusing capacity for carbon monoxide (DLCO) were correct and the healthy volunteers was close to 100% of that pre- dicted. 2,3 Thus, if the mean DLNO in the control group is under-predicted by at least 25%, then the DLNO values in the heart failure patients could be under predicted by � 25% too. Since DLNO and DLCO are measured simultaneously, and DLCO values were appropriate (close to 100% of those predicted), there must be some mathematical error in the calcula- tion of DLNO and/or their breath-hold time was

The effect of increased physical activity on pulmonary diffusing capacity in unfit women

The purpose of the study was to determine whether short-term high-intensity aerobic interval training improves resting pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO). Twenty-eight sedentary women [mean (SD) age 32(11)years, body mass index 24.3(5.7)kgm(-2)] were randomly assigned to either a self-directed moderate-intensity physical activity (n=14) group or a supervised high-intensity aerobic interval training group (n=14). The moderate physical activity group and the aerobic interval training group increased weekly physical activity energy expenditure by 800 and 1600kcalweek(-1), respectively. After 6weeks, aerobic capacity increased to a similar exent in both groups (mean improvement8%, effect size0.39). The DLNO, but not DLCO, increased to a similar extent in both groups, by 4% or 3.0(5.7) [95% confidence interval 0.8, 5.2]mlmin(-1)mmHg(-1)m(-2) from pre- to post-training (effect size0.27). There was no correlation between the change in aerobic capacity and the change in DLNO (P>0.05) or between the change in aerobic capacity and the change in total weekly physical activity energy expenditure (P>0.05). Interval training does not provide additional improvements in DLNO or aerobic capacity compared with self-directed moderate-intensity physical activity (4-6metabolic equivalent tasks, 800kcalweek(-1), for 6weeks) in unfit women. Despite the slight improvement in both DLNO and aerobic capacity, true meaningful physiological changes in these parameters remain questionable.

Lung diffusing capacity for nitric oxide at lowered and raised ambient pressures

Lung diffusing capacity for NO (DLNO) was determined in eight subjects at ambient pressures of 505, 1015, and 4053hPa (379, 761 and 3040mmHg) as they breathed normoxic gases. Mean values were 116.9±11.1 (SEM), 113.4±11.1 and 99.3±10.1mlmin−1hPa−1at 505, 1015, and 4053hPa, with a 13% difference between the two higher pressures (P=0.017). The data were applied to a model with two serially coupled conductances; the gas phase (DgNO, variable with pressure), and the alveolo-capillary membrane (DmNO, constant). The data fitted the model well and we conclude that diffusive transport of NO in the peripheral lung is inversely related to gas density. At normal pressure DmNO was approximately 5% larger than DLNO, suggesting that the Dg factor then is not negligible. We also conclude that the density of the breathing gas is likely to impact the backdiffusion of naturally formed NO from conducting airways to the alveoli.

The rise in carboxyhemoglobin from repeated pulmonary diffusing capacity tests

The purpose of this study determined the rise in carboxyhemoglobin percentage (COHb) from repeated pulmonary diffusing capacity tests using 5 or 10s single breath-hold maneuvers. Five male and four female non-smokers [baseline COHb=1.2 (SD 0.5%)] performed repeated pulmonary diffusing capacity testing on two separate days. The days were randomized to either repeated 10s (0.28% CO), or 5s (0.28% CO, 55ppm NO) breath-hold maneuvers. Twenty-two 5s breath-hold maneuvers, each separated by 4min rest, raised COHb to 11.1 (1.4)% and minimally raised the methemoglobin percentage (METHb) by 0.3 (0.2)% to a value of 0.8 (0.2)%. After the 22nd test, pulmonary diffusing capacity for carbon monoxide (DLCO) was reduced by about 4mL/min/mmHg, equating to a 0.44% increase in COHb per 5s breath-hold maneuver and a concomitant 0.35mL/min/mmHg decrease in DLCO. Pulmonary diffusing capacity for nitric oxide (DLNO) was not altered after 22 tests. On another day, the 10s single breath-hold maneuver increased COHb by 0.64% per test, and reduced DLCO by 0.44mL/min/mmHg per test. In conclusion, 5s breath-hold maneuvers do not appreciably raise METHb or DLNO, and DLCO is only significantly reduced when COHb is at least 6%.