Pulmonary Capillary Blood Volume Research Articles

The Impact of Sickle Cell Disease on Exercise Capacity in Children

Little is known about pulmonary vascular complications in children with sickle cell disease (SCD). We hypothesized that transfer factor (diffusing capacity of the lung for carbon monoxide [D(LCO)] ) may be used as a surrogate for the size of the pulmonary vascular bed and that pulmonary vascular abnormalities in children with SCD may limit exercise capacity. Fifty stable patients with SCD aged 10 to 18 years and 50 healthy control subjects matched for race and age were recruited. Incremental ergometer cardiopulmonary exercise testing was performed using respiratory mass spectrometry for exhaled gas analysis. A rebreathing maneuver was used to measure functional residual capacity, effective pulmonary blood fl ow (Qpeff), and D(LCO), and helium dilution was used to calculate minute ventilation, oxygen consumption, and CO 2 production. In the 89 evaluable subjects, there were no ventilatory differences between SCD and control subjects. Qpeff was consistently 15% to 20% greater in subjects with SCD than control subjects at all stages, but D(LCO) corrected for both surface area and hemoglobin was only about 7% to 10% greater in subjects with SCD at all stages. As a result, the D(LCO)/Qpeff ratio was considerably lower in SCD at all stages. Arteriovenous oxygen content difference was about one-third less in SCD at all stages. Contrary to our hypothesis, failure to maintain a sufficient Qpeff to compensate for anemia led to exercise limitation. The ratio of pulmonary capillary blood volume to fl ow is reduced throughout, implying subtle pulmonary vascular disease; however, this was not a factor limiting exercise.

Loss of alveolar membrane diffusing capacity and pulmonary capillary blood volume in pulmonary arterial hypertension

BackgroundReduced gas transfer in patients with pulmonary arterial hypertension (PAH) is traditionally attributed to remodeling and progressive loss of pulmonary arterial vasculature that results in decreased capillary blood volume available for gas exchange.MethodsWe tested this hypothesis by determination of lung diffusing capacity (DL) and its components, the alveolar capillary membrane diffusing capacity (Dm) and lung capillary blood volume (Vc) in 28 individuals with PAH in comparison to 41 healthy individuals, and in 19 PAH patients over time. Using single breath simultaneous measure of diffusion of carbon monoxide (DLCO) and nitric oxide (DLNO), DL and Dm were respectively determined, and Vc calculated. Dm and Vc were evaluated over time in relation to standard clinical indicators of disease severity, including brain natriuretic peptide (BNP), 6-minute walk distance (6MWD) and right ventricular systolic pressure (RVSP) by echocardiography.ResultsBoth DLCO and DLNO were reduced in PAH as compared to controls and the lower DL in PAH was due to loss of both Dm and Vc (all p < 0.01). While DLCO of PAH patients did not change over time, DLNO decreased by 24 ml/min/mmHg/year (p = 0.01). Consequently, Dm decreased and Vc tended to increase over time, which led to deterioration of the Dm/Vc ratio, a measure of alveolar-capillary membrane functional efficiency without changes in clinical markers.ConclusionsThe findings indicate that lower than normal gas transfer in PAH is due to loss of both Dm and Vc, but that deterioration of Dm/Vc over time is related to worsening membrane diffusion.

Exhaled Breath Condensate Detects Baseline Reductions in Chloride and Increases in Response to Albuterol in Cystic Fibrosis Patients

Impaired ion regulation and dehydration is the primary pathophysiology in cystic fibrosis (CF) lung disease. A potential application of exhaled breath condensate (EBC) collection is to assess airway surface liquid ionic composition at baseline and in response to pharmacological therapy in CF. Our aims were to determine if EBC could detect differences in ion regulation between CF and healthy and measure the effect of the albuterol on EBC ions in these populations. Baseline EBC Cl−, DLCO and SpO2 were lower in CF (n = 16) compared to healthy participants (n = 16). EBC Cl− increased in CF subjects, while there was no change in DLCO or membrane conductance, but a decrease in pulmonary-capillary blood volume in both groups following albuterol. This resulted in an improvement in diffusion at the alveolar-capillary unit, and removal of the baseline difference in SpO2 by 90-minutes in CF subjects. These results demonstrate that EBC detects differences in ion regulation between healthy and CF individuals, and that albuterol mediates increases in Cl− in CF, suggesting that the benefits of albuterol extend beyond simple bronchodilation.

Genetic Variation of SCNN1A Influences Lung Diffusing Capacity in Cystic Fibrosis

Epithelial Na channels (ENaCs) play a crucial role in ion and fluid regulation in the lung. In cystic fibrosis (CF), Na hyperabsorption results from ENaC overactivity, leading to airway dehydration. Previous work has demonstrated functional genetic variation of SCNN1A (the gene encoding the ENaC α-subunit), manifesting as an alanine (A) to threonine (T) substitution at amino acid 663, with the αT663 variant resulting in a more active channel. We assessed the influence of genetic variation of SCNN1A on the diffusing capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO), together with alveolar-capillary membrane conductance (DM), pulmonary capillary blood volume, and alveolar volume (VA) at rest and during peak exercise in 18 patients with CF (10 homozygous for αA663 (AA group) and 8 with at least one T663 allele (AT/TT group)). Because of the more active channel, we hypothesized that the AT/TT group would show a greater increase in DLCO, DLNO, and DM with exercise because of exercise-mediated ENaC inhibition and subsequent attenuation of Na hyperabsorption. The AT/TT group had significantly lower pulmonary function, weight, and body mass index than the AA group. Both groups had similar peak workloads, relative peak oxygen consumptions, and cardiopulmonary responses to exercise. The AT/TT group demonstrated a greater increase in DLNO, DLNO/VA, and DM in response to exercise (% increases: DLNO = 18 ± 11 vs 41 ± 38; DLNO/VA = 14 ± 21 vs 40 ± 37; DM = 15 ± 11 vs 41 ± 38, AA vs AT/TT, respectively). There were no differences between groups in absolute diffusing capacity measures at peak exercise. These results suggest that genetic variation of the α-subunit of ENaC differentially affects the diffusing capacity response to exercise in patients with CF.

TheTL,NO/TL,COratio in pulmonary function test interpretation

The transfer factor of the lung for nitric oxide (T(L,NO)) is a new test for pulmonary gas exchange. The procedure is similar to the already well-established transfer factor of the lung for carbon monoxide (T(L,CO)). Physiologically, T(L,NO) predominantly measures the diffusion pathway from the alveoli to capillary plasma. In the Roughton-Forster equation, T(L,NO) acts as a surrogate for the membrane diffusing capacity (D(M)). The red blood cell resistance to carbon monoxide uptake accounts for ~50% of the total resistance from gas to blood, but it is much less for nitric oxide. T(L,NO) and T(L,CO) can be measured simultaneously with the single breath technique, and D(M) and pulmonary capillary blood volume (V(c)) can be estimated. T(L,NO), unlike T(L,CO), is independent of oxygen tension and haematocrit. The T(L,NO)/T(L,CO) ratio is weighted towards the D(M)/V(c) ratio and to α; where α is the ratio of physical diffusivities of NO to CO (α=1.97). The T(L,NO)/T(L,CO) ratio is increased in heavy smokers, with and without computed tomography evidence of emphysema, and reduced in the voluntary restriction of lung expansion; it is expected to be reduced in chronic heart failure. The T(L,NO)/T(L,CO) ratio is a new index of gas exchange that may, more than derivations from them of D(M) and V(c) with their in-built assumptions, give additional insights into pulmonary pathology.

Pulmonary vascular distensibility predicts aerobic capacity in healthy individuals

It has been suggested that shallow slopes of mean pulmonary artery pressure (MPPA)–cardiac output (Q) relationships and pulmonary transit of agitated contrast during exercise may be associated with a higher maximal aerobic capacity V(O(2)max). If so, individuals with a higher V(O(2)max) could also exhibit a higher pulmonary vascular distensibility and increased pulmonary capillary blood volume during exercise. Exercise stress echocardiography was performed with repetitive injections of agitated contrast and measurements of MPPA, Q and lung diffusing capacities for carbon monoxide (D(L,CO)) and nitric oxide (D(L,CO)) in 24 healthy individuals. A pulmonary vascular distensibility coefficient α was mathematically determined from the slight natural curvilinearity of multipoint MPPA–Q plots. Membrane (D(m)) and capillary blood volume (V(c)) components of lung diffusing capacity were calculated. Maximal exercise increased MPPA, cardiac index (CI), D(L,CO) and (D(L,NO). The slope of the linear best fit of MPPA–CI was 3.2 ± 0.5 mmHg min l(-1) m(2) and α was 1.1 ± 0.3% mmHg(-1). A multivariable analysis showed that higher α and greater V(c) independently predicted V(O(2)max). All individuals had markedly positive pulmonary transit of agitated contrast at maximal exercise, with increases proportional to increases in pulmonary capillary pressure and V(c). Pulmonary transit of agitated contrast was not related to pulse oximetry arterial oxygen saturation. Therefore, a more distensible pulmonary circulation and a greater pulmonary capillary blood volume are associated with a higher V(O(2)max) in healthy individuals. Agitated contrast commonly transits through the pulmonary circulation at exercise, in proportion to increased pulmonary capillary pressures.

Hypoxia induced changes in lung fluid balance in humans is associated with beta-2 adrenergic receptor density on lymphocytes

BackgroundPrevious studies have demonstrated an important role for beta-2 adrenergic receptors (β2AR) in lung fluid clearance. The purpose of this investigation was to examine the relationship between β2AR density on lymphocytes and indices of lung water in healthy humans exposed to ∼17h of hypoxia (FIO2=12.5% in a hypoxia tent). MethodsThirteen adults (mean±SEM; age=31±3 years, BMI=24±1kg/m2, VO2 Peak=40±2 ml/kg/min) participated. Pulmonary function, CT derived lung tissue volume (Vtis-tissue, blood and water), lung diffusing capacity for carbon monoxide (DCO) and nitric oxide (DNO), alveolar-capillary conductance (DM), pulmonary capillary blood volume (Vc) and lung water (CT Vtis−Vc) were assessed before and after ∼17h normobaric hypoxia (FIO2=12.5%). β2AR density on lymphocytes was measured via radioligand binding. Arterial oxygen saturation (SaO2), cardiac output (Q), right ventricular systolic pressure (RVSP) and blood pressure (BP) were also assessed. ResultsAfter 17h hypoxia, SaO2 decreased from 97±1 (normoxia) to 82±4% and RVSP increased from 14±3 (normoxia) to 29±2mmHg (p<0.05) with little change in Q or BP. Vc and DM both increased with hypoxia with a small increase in DM/Vc ratio (p>0.05). CT Vtis decreased and lung water was estimated to decline 7±13%, respectively. β2AR density averaged 1497±187 receptors/lymphocyte and increased 21±34% with hypoxia (range −31 to +86%). The post-hypoxia increase in β2AR density was significantly related to the reduction in lung water (r=−0.64, p<0.05), with the subjects with the greatest increase in density demonstrating the largest decline in lung water. ConclusionsLung water decreases with 17h normobaric hypoxia are associated with changes in beta adrenergic receptor density on lymphocytes in healthy adults.

The effect of β2 adrenergic‐receptor stimulation on lung fluid balance in heart failure

BackgroundIncreased pulmonary capillary pressure and a possible desensitization of lung β2 adrenergic receptors (β2AR) involved in fluid removal mechanisms may increase extravascular lung water (ELW) in stable heart failure (HF) patients. Whether these patients exhibit increased ELW remains controversial.PurposeTo determine if HF patients have elevated ELW versus controls (CTL) and if acute β2AR agonist inhalation stimulates fluid removal.Methods/Results14 stable HF patients and 19 healthy age/gender matched CTL were studied. Lung tissue volume (Vtis) (includes tissue, blood and water) and pulmonary capillary blood volume (Vc) were assessed pre and post nebulized albuterol via CT and rebreathe, respectively. ELW was derived as Vtis – Vc. Pre albuterol, ELW was greater in HF vs. CTL (861±241 vs. 739±143 ml, P&lt;0.01), with no difference in Vtis (938±246 vs. 830±151 ml, P=0.08). Albuterol decreased Vtis (–4±2%, P=0.02) but did not change ELW (739±143 vs. 724±132 ml) (P&gt;0.05) in CTL. In HF, albuterol decreased both Vtis (–5±3%) and ELW (– 4±2%) (P&lt;0.05). There was a negative relationship between baseline values and the pre to post albuterol change for Vtis (r2=0.38) and ELW (r2=0.42) (P&lt;0.01) in HF.ConclusionLung fluid is elevated in stable HF patients relative to healthy subjects. Stimulation of β2ARs appears to enhance fluid removal in HF, especially in patients with elevated lung water at rest.

Erratum to: Impaired diffusing capacity for carbon monoxide in children with type 1 diabetes: is this the first sign of long-term complications?

We assessed the presence of lung dysfunction in children with type 1 diabetes, evaluated as reduced diffusing capacity of the lung for carbon monoxide (DLCO), and its components: membrane diffusing capacity (DM) and pulmonary capillary blood volume (Vc). A total of 42 children, aged 15.6 ± 3.8 years, with type 1 diabetes for 8.3 ± 5.5 years, and 30 healthy age and sex-matched peers were recruited for the study. Lung volumes and spirometric dynamic parameters were assessed by plethysmography. Single-breath DLCO was measured according to international recommendation. DM and Vc volume were calculated. Lung volumes were significantly reduced in young patients with type 1 diabetes when compared to controls. Moreover, DLCO was reduced in patients compared to controls (78% ± 16% vs. 120% ± 1%, P = 0.0001). However, when differentiating DM and Vc compartments, we observed a significant impairment only about Vc (34 ± 20 ml vs. 88 ± 18 ml; P = 0.0001), while no difference was observed about DM compartment (23 ± 4 vs. 26 ± 3 ml/min/mmHg, P = 0.798). Whether this might be seen as the “first” sign of microangiopathic involvement in patients with type 1 diabetes has to be confirmed on larger groups but is still fascinating. Meanwhile, we suggest to screen DLCO in all patients with type 1 diabetes.

Lung capillary blood volume and membrane diffusion in idiopathic interstitial pneumonia

Diffusing capacity of the lung for carbon monoxide (DLCO) is a good marker of disease severity in patients with idiopathic interstitial pneumonia (IIP). The combined diffusing capacity of nitric oxide (DLNO) and DLCO determines the two components of diffusion: membrane conductance (Dm, CO) and pulmonary capillary blood volume (Vc). The aim of this study was to evaluate Vc and Dm, CO in patients with fibrosing IIP in order to determine the relative contribution of membrane resistance and vascular resistance to the loss of DLCO. 32 patients with IIP (IPF: n=22, NSIP: n=10) were evaluated using MRC dyspnea scale, plethysmography, combined DLNO/DLCO, 6-min walk test (6MWT), echocardiography and chest computed tomography (chest CT). DLCO (41.8±11.9%pred), Dm, CO (40.5±12.7%pred) and Vc (41.9±18%pred) were severely and equally reduced. Dm, CO and Vc were related to MRC scale, FVC, maximal desaturation during 6MWT, and systolic pulmonary artery pressure (sPAP). There was no correlation with the extent of fibrotic changes on chest CT. Our main results indicate that Dm, CO and Vc contribute almost equally to DLCO reduction in IIP. Dm, CO and Vc are related to functional indicators of disease severity and to sPAP in agreement with the concept of vascular involvement in IIP.

Impaired diffusing capacity for carbon monoxide in children with type 1 diabetes: is this the first sign of long-term complications?

We assessed the presence of lung dysfunction in children with type 1 diabetes, evaluated as reduced diffusing capacity of the lung for carbon monoxide (DLCO), and its components: membrane diffusing capacity (DM) and pulmonary capillary blood volume (Vc). A total of 42 children, aged 15.6±3.8 years, with type 1 diabetes for 8.3±5.5 years, and 30 healthy age and sex-matched peers were recruited for the study. Lung volumes and spirometric dynamic parameters were assessed by plethysmography. Single-breath DLCO was measured according to international recommendation. DM and Vc volume were calculated. Lung volumes were significantly reduced in young patients with type 1 diabetes when compared to controls. Moreover, DLCO was reduced in patients compared to controls (78%±16% vs. 120%±1%, P=0.0001). However, when differentiating DM and Vc compartments, we observed a significant impairment only about Vc (34±20ml vs. 88±18ml; P=0.0001), while no difference was observed about DM compartment (23±4 vs. 26±3ml/min/mmHg, P=0.798). Whether this might be seen as the "first" sign of microangiopathic involvement in patients with type 1 diabetes has to be confirmed on larger groups but is still fascinating. Meanwhile, we suggest to screen DLCO in all patients with type 1 diabetes.

Corrigendum to ‘Dynamic vs. fixed bag filling: impact on cardiac output rebreathing protocol’ [Respir. Physiol. Neurobiol. 171 (2010) 22–30

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 < 0.05). The mean repeatability was similar between both protocols for 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.

Influence of Genetic variation of the β 2-Adrenergic receptor on lung diffusion in patients with cystic fibrosis

Rationale Cystic fibrosis (CF) is a disease that adversely affects the lung resulting in a reduction in lung diffusion. Stimulation of the β 2-adrenergic receptors mediates mucociliary clearance and bronchodilation. We sought to determine the influence of an inhaled β-agonist on the diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar-capillary membrane conductance ( D M), pulmonary capillary blood volume ( Vc), and peripheral oxygen saturation (SaO 2) in subjects with CF, when compared to matched healthy subjects, according to genetic variation of the β 2-adrenergic receptor (ADRB2). Methods To determine this we recruited 18 subjects with CF and 20 healthy subjects (age = 23 ± 7 vs. 24±4years; ht = 168 ± 8 vs. 174 ± 12 cm; wt = 64 ± 16 vs. 70 ± 13 kg; BMI = 23 ± 4 vs. 23±3 kg/m 2; FEV 1 = 72 ± 27 vs. 92 ± 12%pred; VO 2peak = 45 ± 25 vs. 99 ± 24%pred, p < 0.05 for FEV 1 and VO 2peak, mean ± SD, for CF and healthy, respectively). The study involved measurement of DLCO, D M, V C and SaO 2 before and 30, 60, and 90 min following the administration of inhaled albuterol. Subjects were stratified according to genetic variation of ADRB2, Gln 27Gln vs. Glu 27Glu/Gln 27Glu. Results Within the healthy group, there were no differences in DLCO, D M, V C, D M/ V C at baseline or in response to albuterol according to genetic variation of the ADRB2 at amino acid 27. Within the CF group, the Glu 27Glu/Gln 27Glu group had higher D M/ V C and SaO 2 when compared to the Gln 27Gln group at baseline ( p < 0.05). Both genotype groups demonstrated a significant decline in V C and an improvement in D M/ V C and SaO 2 in response to albuterol. Subjects with the Glu 27 genotype experienced a greater improvement in D M/ V C with albuterol when compared to subjects homozygous for Gln at amino acid 27. Conclusion These results suggest that there are differences in lung diffusion and peripheral SaO 2 according to genetic variation of the ADRB2 at position 27 which could play a potential role in dosing options or adjustments that may be required according to genotype.

Pulmonary capillary recruitment in response to hypoxia in healthy humans: a possible role for hypoxic pulmonary venoconstriction?

We examined mechanisms by which hypoxia may elicit pulmonary capillary recruitment in humans. On separate occasions, twenty-five healthy adults underwent exposure to intravenous saline infusion (30 ml/kg ∼ 15 min) or 17-h normobaric hypoxia ( [FIO2 = 12.5%). Cardiac output (Q) and pulmonary capillary blood volume (Vc) were measured before and after saline infusion and hypoxic-exposure by a rebreathing method. Pulmonary artery systolic pressure (sPpa) and left ventricular (LV) diastolic function were assessed before and after hypoxic-exposure via echocardiography. Saline infusion increased Q and Vc (P < 0.05) with no change in Vc/Q (P = 0.97). Hypoxic-exposure increased Vc (P < 0.01) despite no change in Q (P = 0.25), increased sPpa (P < 0.01), and impaired LV relaxation. Multiple regression suggested that ∼ 37% of the hypoxia-mediated increase in Vc was attributable to alterations in Q, sPpa and LV diastolic function. In conclusion, hypoxia-induced pulmonary capillary recruitment in humans is only partly accounted for by changes in Q, sPpa and LV diastolic function. We speculate that hypoxic pulmonary venoconstriction may play a role in such recruitment.

Lung fluid balance in patients with heart failure: effect of beta‐2 adrenergic‐receptor stimulation

Background β2-adrenergic receptor (β2AR) stimulation promotes lung fluid removal in animals and healthy humans. It is possible that lung fluid accumulation in heart failure (HF) patients is caused by impairment in lung fluid regulation via desensitization of the lung β2ARs. Purpose To determine the effect of an acute inhaled β2AR agonist on lung fluid in HF. Methods/Results 22 stable HF patients and 22 healthy age and gender matched subjects were studied. Lung fluid was estimated at baseline (BL) and up to 30 min after administration of nebulized albuterol by measuring lung diffusing capacity for CO (DLCO), alveolar-capillary conductance (Dm) and pulmonary capillary blood volume (Vc) using a rebreathe method. Pre-inhalation, DLCO was not different in HF vs. healthy subjects (16±5 vs. 19±4 ml/min/mmHg, P=0.06). By contrast, Dm/Vc was greater in HF vs. healthy subjects (0.42 ± 0.14 vs. 0.33 ± 0.15, P=0.04). In HF, group mean DLCO, Dm and Dm/Vc were not different pre- vs. post-albuterol. However, patients who had an increase in DLCO and Dm/Vc with albuterol administration had significantly lower BL values compared to patients who had no improvement (P<0.05). That is, β2AR stimulation improved DLCO and Dm/Vc only in subjects who had evidence for increased lung fluid at BL. Conclusion Stimulation of β2AR may stimulate fluid removal in stable HF patients who exhibit evidence for elevated lung water at rest. HL71478.

High-altitude exposure of three weeks duration increases lung diffusing capacity in humans

high-altitude adaptation leads to progressive increase in arterial Pa(O2). In addition to increased ventilation, better arterial oxygenation may reflect improvements in lung gas exchange. Previous investigations reveal alterations at the alveolar-capillary barrier indicative of decreased resistance to gas exchange with prolonged hypoxia adaptation, but how quickly this occurs is unknown. Carbon monoxide lung diffusing capacity and its major determinants, hemoglobin, alveolar volume, pulmonary capillary blood volume, and alveolar-capillary membrane diffusion, have never been examined with early high-altitude adaptation. lung diffusion was measured in 33 healthy lowlanders at sea level (Milan, Italy) and at Mount Everest South Base Camp (5,400 m) after a 9-day trek and 2-wk residence at 5,400 m. Measurements were adjusted for hemoglobin and inspired oxygen. Subjects with mountain sickness were excluded. After 2 wk at 5,400 m, hemoglobin oxygen saturation increased from 77.2 ± 6.0 to 85.3 ± 3.6%. Compared with sea level, there were increases in hemoglobin, lung diffusing capacity, membrane diffusion, and alveolar volume from 14.2 ± 1.2 to 17.2 ± 1.8 g/dl (P < 0.01), from 23.6 ± 4.4 to 25.1 ± 5.3 ml·min(-1)·mmHg(-1) (P < 0.0303), 63 ± 34 to 102 ± 65 ml·min(-1)·mmHg(-1) (P < 0.01), and 5.6 ± 1.0 to 6.3 ± 1.1 liters (P < 0.01), respectively. Pulmonary capillary blood volume was unchanged. Membrane diffusion normalized for alveolar volume was 10.9 ± 5.2 at sea level rising to 16.0 ± 9.2 ml·min(-1)·mmHg(-1)·l(-1) (P < 0.01) at 5,400 m. at high altitude, lung diffusing capacity improves with acclimatization due to increases of hemoglobin, alveolar volume, and membrane diffusion. Reduction in alveolar-capillary barrier resistance is possibly mediated by an increase of sympathetic tone and can develop in 3 wk.

Reduction in membrane component of diffusing capacity is associated with the extent of acute pulmonary embolism.

Acute pulmonary embolism (PE) often decreases pulmonary diffusing capacity for carbon monoxide (DL,CO), but data on the mechanisms involved are inconsistent. We wanted to investigate whether reduction in diffusing capacity of alveolo-capillary membrane (DM) and pulmonary capillary blood volume (Vc) is associated with the extent of PE or the presence and severity of right ventricular dysfunction (RVD) induced by PE and how the possible changes are corrected after 7-month follow-up. Forty-seven patients with acute non-massive PE in spiral computed tomography (CT) were included. The extent of PE was assessed by scoring mass of embolism. DL,CO, Vc, DM and alveolar volume (VA) were measured by using a single breath method with carbon monoxide and oxygen both at the acute phase and 7 months later. RVD was evaluated with transthoracic echocardiography and electrocardiogram. Fifteen healthy subjects were included as controls. DL,CO, DL, CO/VA, DM, vital capacity (VC) and VA were significantly lower in the patients with acute PE than in healthy controls (P<0·001). DM/Vc relation was significantly lower in patients with RVD than in healthy controls (P = 0·004). DM correlated inversely with central mass of embolism (r = −0·312; P = 0·047) whereas Vc did not. DM, DL,CO, VC and VA improved significantly within 7 months. In all patients (P = 0·001, P = 0·001) and persistent RVD (P = 0·020, P = 0·012), DM and DL,CO remained significantly lower than in healthy controls in the follow-up. DM was inversely related to central mass of embolism. Reduction in DM mainly explains the sustained decrease in DL,CO in PE after 7 months despite modern treatment of PE.

Glycemic control influences lung membrane diffusion and oxygen saturation in exercise-trained subjects with type 1 diabetes

Lung diffusing capacity (DLCO) is influenced by alveolar-capillary membrane conductance (D (M)) and pulmonary capillary blood volume (V (C)), both of which can be impaired in sedentary type 1 diabetes mellitus (T1DM) subjects due to hyperglycemia. We sought to determine if T1DM, and glycemic control, affected DLNO, DLCO, D (M), V (C) and SaO(2) during maximal exercise in aerobically fit T1DM subjects. We recruited 12 T1DM subjects and 18 non-diabetic subjects measuring DLNO, DLCO, D (M), and V (C) along with SaO(2) and cardiac output (Q) at peak exercise. The T1DM subjects had significantly lower DLCO/Q and D (M)/Q with no difference in Q, DLNO, DLCO, D (M), or V (C) (DLCO/Q = 2.1 ± 0.4 vs. 1.7 ± 0.3, D (M)/Q = 2.8 ± 0.6 vs. 2.4 ± 0.5, non-diabetic and T1DM, p < 0.05). In addition, when considering all subjects there was a relationship between DLCO/Q and SaO(2) at peak exercise (r = 0.46, p = 0.01). Within the T1DM group, the optimal glycemic control group (HbA1c <7%, n = 6) had higher DLNO, DLCO, and D (M)/Q than the poor glycemic control subjects (HbA1c ≥ 7%, n = 6) at peak exercise (DLCO = 38.3 ± 8.0 vs. 28.5 ± 6.9 ml/min/mmHg, DLNO = 120.3 ± 24.3 vs. 89.1 ± 21.0 ml/min/mmHg, D (M)/Q = 3.8 ± 0.8 vs. 2.7 ± 0.2, optimal vs. poor control, p < 0.05). There was a negative correlation between HbA1c with DLCO, D (M) and D (M)/Q at peak exercise (DLCO: r = -0.70, p = 0.01; D (M): r = -0.70, p = 0.01; D (M)/Q: r = -0.68, p = 0.02). These results demonstrate that there is a reduction in lung diffusing capacity in aerobically fit athletes with T1DM at peak exercise, but suggests that maintaining near-normoglycemia potentially averts lung diffusion impairments.

The Pulmonary Circulation and Exercise Responses in the Elderly

Aging is associated with a progressive deterioration in the structure and function of the pulmonary circulation. Remodeling of the pulmonary vasculature occurs from maturity to senescence that is characterized by an increase in pulmonary vascular stiffness, pulmonary vascular pressures, and pulmonary vascular resistance along with increased heterogeneity of alveolar ventilation and pulmonary perfusion and decreased pulmonary capillary blood volume and membrane diffusing capacity that is consistent with a reduction in alveolar-capillary surface area. In theory, the aforementioned age-related changes in the pulmonary circulation may conspire to make elderly individuals more susceptible to gas exchange abnormalities during exercise. However, despite the erosion in ventilatory reserve with aging, the healthy older adult appears able to maintain alveolar ventilation at a level that allows maintenance of arterial blood gases within normal limits, even during heavy exercise. This ability to maintain adequate gas exchange likely occurs because age-related reductions in the maximal metabolic demand of exercise occur at a rate equal to or greater than the rate of deterioration in ventilatory reserve. A more prominent aspect of aging is the loss of lung elastic recoil that is associated with a modest reduction in the expiratory boundary of the maximal flow-volume envelope. This in turn increases the severity of expiratory airflow limitation and induces dynamic lung hyperinflation during exercise. The consequences of this age-associated decrease in elastic recoil on the pulmonary circulation are speculative, but an age-associated decline in elastic recoil may influence pulmonary vascular resistance and cardiac output, in addition to its impact on the work and oxygen cost of breathing.

Fatty diabetic lung: functional impairment in a model of metabolic syndrome

The Zucker diabetic fatty (ZDF fa/fa) rat with genetic leptin insensitivity develops obesity and Type 2 diabetes mellitus (T2DM) with age accompanied by hyperplastic changes in the distal lung (Am J Physiol Lung Cell Mol Physiol 298: L392-L403, 2010). To determine the functional consequences of structural changes, we developed a rebreathing (RB) technique to simultaneously measure lung volume, pulmonary blood flow, lung diffusing capacity (Dl(CO)), membrane diffusing capacity (Dm(CO)), pulmonary capillary blood volume (Vc), and septal tissue volume in anesthetized tracheostomized male ZDF fa/fa and matched lean (+/+) control animals at 4, 8, and 12 mo of age. Results obtained by RB technique were compared with that measured by a single-breath (SB) technique and to that expected in a wide range of species. In fa/fa animals compared with +/+, lung volumes and compliance were 13-35% lower at different ages, and the normal age-related increase in lung compliance was no longer evident. Mean pulmonary blood flow declined with age in fa/fa but not in +/+ animals. Dl(CO) measured at a given pulmonary blood flow was 20-43% lower at different ages due to reductions in both Dm(CO) and Vc. Septal tissue volume was also reduced in older fa/fa rats. We conclude that obese rats with T2DM develop significant restrictive pulmonary defects with diffusion impairment in a pattern similar to that previously reported in obese human subjects with T2DM. Functional impairment became exaggerated with age and duration of T2DM. In both fa/fa and +/+ animals, Dl(CO) measured by RB was systematically higher than by SB technique whereas lung volume was similar, a finding consistent with heterogeneous distribution of ventilation in the rat lung.