Pulmonary Gas Exchange Abnormalities Research Articles

Hyperpolarized 129Xe MRI and spectroscopy of gas-exchange abnormalities in bilateral lung transplant recipients

BACKGROUNDThere is currently no sensitive, non-invasive method of screening for chronic lung allograft dysfunction (CLAD), the primary barrier to long-term survival after lung transplant. Conventional pulmonary function testing is imprecise absent a sustained decline. Hyperpolarized 129Xe MRI is a sensitive tool for 3D imaging of regional pulmonary ventilation and gas exchange abnormalities and may aid in early detection of CLAD. METHODSAdult patients post bilateral lung transplant were screened for CLAD based on the ISHLT criteria. Those with established allografts (n=10) underwent 129Xe gas exchange MRI and spectroscopy and were compared to results from 16 young healthy volunteers and 16 age-matched healthy volunteers. One lung transplant recipient was excluded from final data analysis due to a concurrent lung infection found incidentally after MRI. Imaging provided quantitative maps of the ventilation defect percent (VDP), membrane high percent, and RBC defect percent. Spectroscopy yielded RBC/membrane ratio, oxygenation-dependent RBC shift, and RBC oscillation amplitude. RESULTSThe analysis included nine lung transplant recipients, seven with CLAD and two without. CLAD patients exhibited VDP values consistent with their FEV1 decline (rho=0.79, p=0.048). Hemoglobin-corrected RBC transfer was reduced in all transplant recipients vs. young healthy controls (median [first quartile–third quartile] of 13% [9%-22%] vs 2% [1.75%-3%], P=0.003) as well as vs. age-matched controls (5.5% [2% - 9.25%], p=0.039). Spectroscopy demonstrated reduced RBC/membrane signal (0.26 [0.17-0.31] vs. 0.62 [0.50-0.66], p< 0.001 and vs. 0.48 [0.42-0.55], p = 0.002), reduced RBC chemical shift (217.4 [217.2-217.7]ppm vs 218.2 [218.0-218.5]ppm, p=0.009 and vs. 218.3 [218.2-218.5]ppm, p=0.003), and increased RBC oscillation amplitude vs. the young healthy controls (14.1% [12.2%-16.4%] vs 11.1% [9.9%-11.9%], p=0.003). CONCLUSIONSPatients with CLAD exhibited significant ventilation defects that correlated with FEV1 decline, that, along with RBC transfer defects and other 129Xe gas exchange and hemodynamic abnormalities, could provide a promising means of early detection of physiological changes in patients with CLAD.

Physiological Characterization of Preserved Ratio Impaired Spirometry in the CanCOLD Study: Implications for Exertional Dyspnea and Exercise Intolerance.

Rationale: It is increasingly recognized that adults with preserved ratio impaired spirometry (PRISm) are prone to increased morbidity. However, the underlying pathophysiological mechanisms are unknown. Objectives: Evaluate the mechanisms of increased dyspnea and reduced exercise capacity in PRISm. Methods: We completed a cross-sectional analysis of the CanCOLD (Canadian Cohort Obstructive Lung Disease) population-based study. We compared physiological responses in 59 participants meeting PRISm spirometric criteria (post-bronchodilator FEV1 < 80% predicted and FEV1/FVC ⩾ 0.7), 264 control participants, and 170 ever-smokers with chronic obstructive pulmonary disease (COPD), at rest and during cardiopulmonary exercise testing. Measurements and Main Results: Individuals with PRISm had lower total lung, vital, and inspiratory capacities than healthy controls (all P < 0.05) and minimal small airway, pulmonary gas exchange, and radiographic parenchymal lung abnormalities. Compared with healthy controls, individuals with PRISm had higher dyspnea/[Formula: see text]o2 ratio at peak exercise (4.0 ± 2.2 vs. 2.9 ± 1.9 Borg units/L/min; P < 0.001) and lower [Formula: see text]o2peak (74 ± 22% predicted vs. 96 ± 25% predicted; P < 0.001). At standardized submaximal work rates, individuals with PRISm had greater Vt/inspiratory capacity (Vt%IC; P < 0.001), reflecting inspiratory mechanical constraint. In contrast to participants with PRISm, those with COPD had characteristic small airways dysfunction, dynamic hyperinflation, and pulmonary gas exchange abnormalities. Despite these physiological differences among the three groups, the relationship between increasing dyspnea and Vt%IC during cardiopulmonary exercise testing was similar. Resting IC significantly correlated with [Formula: see text]o2peak (r = 0.65; P < 0.001) in the entire sample, even after adjusting for airflow limitation, gas trapping, and diffusing capacity. Conclusions: In individuals with PRISm, lower exercise capacity and higher exertional dyspnea than healthy controls were mainly explained by lower resting lung volumes and earlier onset of dynamic inspiratory mechanical constraints at relatively low work rates. Clinical trial registered with www.clinicaltrials.gov (NCT00920348).

Changes in pulmonary function in patients with breast cancer before and after radiation therapy

Background: The respiratory system is negatively affected by radiation exposure during the comprehensive treatment of breast cancer (BC), which has an effect on the treatment effectiveness and patients’ quality of life.Objective: To evaluate changes in pulmonary ventilation and diffusion characteristics and ventilation effectiveness in patients with BC before and after radiation therapy (RT).Methods: Our prospective cohort study included 232 women with BC admitted to the Meshalkin National Medical Research Center for an adjuvant RT after surgical treatment. Before and after the RT we conducted pulmonary function tests: body plethysmography, lung diffusion capacity testing, and cardiopulmonary exercise testing with measurement of peak oxygen consumption. We used multivariate regression analysis to determine predictors of pulmonary function decline during RT (decrease in the lung diffusion capacity &gt; 5% compared with baseline).Results: Pulmonary function tests prior to RT demonstrated that 15% of the patients with BC had pulmonary ventilation disorders, and 25% of the patients had pulmonary gas exchange abnormalities (most of them were newly diagnosed). In the general group following RT, we saw a significant decrease in the lung diffusion capacity (P = .044) and an increased incidence of obstructive breathing patterns among the examined patients (P = .036). Other pulmonary ventilation parameters, its effectiveness, and reserve capacity of the respiratory system after RT did not change significantly in the study group and corresponded to the reference values. The postradiation pulmonary function was negatively affected by the reduced level of pulmonary diffusion capacity at baseline (≤ 70% of the reference value) [OR 1.15 (1.03-1.34), P = .004], abnormal breathing pattern prior to RT [OR 1.08 (1.01-1.15), P = .029], involvement of regional lymph nodes (N1-3) [OR 1.10 (1.04-1.26), P = .003].Conclusion: Early postradiation respiratory disorders in patients with BC are marked by a decrease in the lung diffusion capacity and an increased incidence of obstructive patterns of pulmonary ventilation. The factors negatively affecting changes in pulmonary ventilation and diffusion characteristics after RT were the baseline pulmonary gas exchange disorders, obstructive breathing pattern prior to RT, and radiation exposure to lymph nodes. Received 28 December 2022. Revised 26 May 2023. Accepted 30 May 2023. Funding: The study did not have sponsorship. Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: O.V. Kamenskaya, V.V. Lomivorotov Data collection and analysis: S.S. Porotnikova, E.A. Samoilova, V.G. Tihomirov Statistical analysis: I.Yu. Loginova, A.S. Klinkova Drafting the article: I.Yu. Loginova, O.V. Kamenskaya Critical revision of the article: S.E. Krasilnikov, A.M. Chernyavskiy Final approval of the version to be published: O.V. Kamenskaya, I.Yu. Loginova, A.S. Klinkova, S.S. Porotnikova, E.A. Samoilova, V.G. Tihomirov, S.E. Krasilnikov, V.V. Lomivorotov, A.M. Chernyavskiy

Exercise responses and mental health symptoms in COVID-19 survivors with dyspnoea.

Dyspnoea is a common persistent symptom post-coronavirus disease 2019 (COVID-19) illness. However, the mechanisms underlying dyspnoea in the post-COVID-19 syndrome remain unclear. The aim of our study was to examine dyspnoea quality and intensity, burden of mental health symptoms, and differences in exercise responses in people with and without persistent dyspnoea following COVID-19. 49 participants with mild-to-critical COVID-19 were included in this cross-sectional study 4 months after acute illness. Between-group comparisons were made in those with and without persistent dyspnoea (defined as modified Medical Research Council dyspnoea score ≥1). Participants completed standardised dyspnoea and mental health symptom questionnaires, pulmonary function tests, and incremental cardiopulmonary exercise testing. Exertional dyspnoea intensity and unpleasantness were increased in the dyspnoea group. The dyspnoea group described dyspnoea qualities of suffocating and tightness at peak exercise (p<0.05). Ventilatory equivalent for carbon dioxide (V'E/V'CO2) nadir was higher (32±5 versus 28±3, p<0.001) and anaerobic threshold was lower (41±12 versus 49±11% predicted maximum oxygen uptake, p=0.04) in the dyspnoea group, indicating ventilatory inefficiency and deconditioning in this group. The dyspnoea group experienced greater symptoms of anxiety, depression and post-traumatic stress (all p<0.05). A subset of participants demonstrated gas-exchange and breathing pattern abnormalities suggestive of dysfunctional breathing. People with persistent dyspnoea following COVID-19 experience a specific dyspnoea quality phenotype. Dyspnoea post-COVID-19 is related to abnormal pulmonary gas exchange and deconditioning and is linked to increased symptoms of anxiety, depression and post-traumatic stress.

Association of Oxygen Therapy with the Natural Disease Progression of Cystic Fibrosis: A Multi-State Model of the European Cystic Fibrosis Society Patient Registry.

Association between dependence on oxygen therapy (OT) and natural disease progression in people with cystic fibrosis (pwCF) has not been estimated yet. The aim of this study is to understand the prognosis for pwCF on OT, evaluating how the transition probabilities from being alive without lung transplantation (LTx) to LTx and to death, and from being alive after LTx to death change in pwCF with and without OT. We used 2008-2017 data from the 35-country European CF Society Patient Registry. A multi-state model was fitted to assess the effects of individual risk factors on transition probabilities. We considered 48,343 pwCF aged from 6 to 50 years. OT (HR 5.78, 95% CI: 5.32-6.29) and abnormal FEV1 (HR 6.41, 95% CI: 5.28-7.79) were strongly associated with the probability of having LTx; chronic infection with Burkholderia cepacia complex (HR 3.19, 95% CI: 2.78-3.67), abnormal FEV1 (HR 5.00, 95% CI: 4.11-6.08) and the need for OT (HR 4.32, 95% CI: 3.93-4.76) showed the greatest association with the probability of dying without LTx. Once pwCF received LTx, OT (HR 1.75, 95% CI: 1.41-2.16) and abnormal FEV1 (HR 1.63, 95% CI: 1.18-2.25) were the main factors associated with the probability of dying. An association of gross national income with the probability of receiving LTx and with the probability of dying without LTx was also found. Oxygen therapy is associated with poor survival in pwCF with and without LTx; harmonization of CF care throughout European countries and minimization of the onset of pulmonary gas exchange abnormalities using all available means remains of paramount importance.

Exercise Intolerance in Untreated OSA: Role of Pulmonary Gas Exchange and Systemic Vascular Abnormalities

Reduced exercise capacity has been reported previously in patients with OSA hypopnea syndrome (OSAHS), although the underlying mechanisms are unclear. What are the underlying mechanisms of reduced exercise capacity in untreated patients with OSAHS? Is there a role for systemic or pulmonary vascular abnormalities? This was a cross-sectional observational study in which 14 patients with moderate to severe OSAHS and 10 control participants (matched for age, BMI, smoking history, and FEV1) underwent spirometry, incremental cycle cardiopulmonary exercise test (CPET) with arterial line, resting echocardiography, and assessment of arterial stiffness (pulse wave velocity [PWV] and augmentation index [AIx]). Patients (age, 50 ± 11 years; BMI, 30.5 ± 2.7kg/m2; smoking history, 2.4 ± 4.0 pack-years; FEV1 to FVC ratio, 0.78 ± 0.04; FEV1, 85 ± 14%predicted, mean±SD for all) had mean ± SD apnea hypopnea index of 43 ± 19/h. At rest, PWV, AIx, and mean pulmonary artery pressure (PAP) were higher in patients vscontrol participants (P< .05). During CPET, patients showed lower peak work rate (WR) and oxygen uptake and greater dyspnea ratings compared with control participants (P< .05 for all). Minute ventilation (V·E), ventilatory equivalent for CO2 output (V·E/V·CO2), and dead space volume (VD) to tidal volume (VT) ratio were greater in patients vscontrol participants during exercise (P< .05 for all). Reduction in VD to VT ratio from rest to peak exercise was greater in control participants compared with patients (0.24 ± 0.08 vs0.04 ± 0.14, respectively; P= .001). Dyspnea intensity at the highest equivalent WR correlated with corresponding values of V·E/V·CO2 (r= 0.65; P= .002), and dead space ventilation (r= 0.70; P= .001). Age, PWV, and mean PAP explained approximately 70%of the variance in peak WR, whereas predictors of dyspnea during CPET were rest-to-peak change in VD to VT ratio and PWV (R2= 0.50; P< .001). Patients with OSAHS showed evidence of pulmonary gas exchange abnormalities during exercise (in the form of increased dead space) and resting systemic vascular dysfunction that may explain reduced exercise capacity and increased exertional dyspnea intensity.

Exertional dyspnoea in patients with mild‐to‐severe chronic obstructive pulmonary disease: neuromechanical mechanisms

In patients with chronic obstructive pulmonary disease (COPD), exertional dyspnoea generally arises when there is imbalance between ventilatory demand and capacity, but the neurophysiological mechanisms are unclear. We therefore determined if disparity between elevated inspiratory neural drive (IND) and tidal volume (VT ) responses (neuromechanical dissociation) impacted dyspnoea intensity and quality during exercise, across the COPD severity spectrum. In this two-centre, cross-sectional observational study, 89 participants with COPD divided into tertiles of FEV1 %predicted (Tertile 1=FEV1 = 87±9%, Tertile 2=60±9%, Tertile 3=32±8%) and 18 non-smoking controls, completed a symptom-limited cardiopulmonary exercise test (CPET) with measurement of IND by diaphragm electromyography (EMGdi (%max)). The association between increasing dyspnoea intensity and EMGdi (%max) during CPET was strong (r=0.730, P<0.001) and not different between the four groups who showed marked heterogeneity in pulmonary gas exchange and mechanical abnormalities. Significant inspiratory constraints (tidal volume/inspiratory capacity (VT /IC)≥70%) and onset of neuromechanical dissociation (EMGdi (%max):VT /IC>0.75) occurred at progressively lower minute ventilation ( ) from Control to Tertile 3. Lower resting IC meant earlier onset of neuromechanical dissociation, heightened dyspnoea intensity and greater propensity (93% in Tertile 3) to select qualitative descriptors of 'unsatisfied inspiration'. We concluded that, regardless of marked variation in mechanical and pulmonary gas exchange abnormalities in our study sample, exertional dyspnoea intensity was linked to the magnitude of EMGdi (%max). Moreover, onset of critical inspiratory constraints and attendant neuromechanical dissociation amplified dyspnoea intensity at higher exercise intensities. Simple measurements of IC and breathing pattern during CPET provide useful insights into mechanisms of dyspnoea and exercise intolerance in individuals with COPD. KEY POINTS: Dyspnoea during exercise is a common and troublesome symptom reported by patients with chronic obstructive pulmonary disease (COPD) and is linked to an elevated inspiratory neural drive (IND). The precise mechanisms of elevated IND and dyspnoea across the continuum of airflow obstruction severity in COPD remains unclear. The present study sought to determine the mechanisms of elevated IND (by diaphragm EMG, EMGdi (%max)) and dyspnoea during cardiopulmonary exercise testing (CPET) across the continuum of COPD severity. There was a strong association between increasing dyspnoea intensity and EMGdi (%max) during CPET across the COPD continuum despite significant heterogeneity in underlying pulmonary gas exchange and respiratory mechanical impairments. Critical inspiratory constraints occurred at progressively lower ventilation during exercise with worsening severity of COPD. This was associated with the progressively lower resting inspiratory capacity with worsening disease severity. Earlier critical inspiratory constraint was associated with earlier neuromechanical dissociation and greater likelihood of reporting the sensation of 'unsatisfied inspiration'.

Impaired Ventilatory Efficiency, Dyspnea, and Exercise Intolerance in Chronic Obstructive Pulmonary Disease: Results from the CanCOLD Study.

Rationale: Impaired exercise ventilatory efficiency (high ventilatory requirements for CO2 [[Formula: see text]e/[Formula: see text]co2]) provides an indication of pulmonary gas exchange abnormalities in chronic obstructive pulmonary disease (COPD). Objectives: To determine 1) the association between high [Formula: see text]e/[Formula: see text]co2 and clinical outcomes (dyspnea and exercise capacity) and its relationship to lung function and structural radiographic abnormalities; and 2) its prevalence in a large population-based cohort. Methods: Participants were recruited randomly from the population and underwent clinical evaluation, pulmonary function, cardiopulmonary exercise testing, and chest computed tomography. Impaired exercise ventilatory efficiency was defined by a nadir [Formula: see text]e/[Formula: see text]co2 above the upper limit of normal (ULN), using population-based normative values. Measurements and Main Results: Participants included 445 never-smokers, 381 ever-smokers without airflow obstruction, 224 with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 COPD, and 200 with GOLD 2-4 COPD. Participants with [Formula: see text]e/[Formula: see text]co2 above the ULN were more likely to have activity-related dyspnea (Medical Research Council dyspnea scale ⩾ 2; odds ratio [5-95% confidence intervals], 1.77 [1.31 to 2.39]) and abnormally low peak [Formula: see text]o2 ([Formula: see text]o2peak below the lower limit of normal; odds ratio, 4.58 [3.06 to 6.86]). The Kco had a stronger correlation with nadir [Formula: see text]e/[Formula: see text]co2 (r = -0.38; P < 0.001) than other relevant lung function and computed tomography metrics. The prevalence of [Formula: see text]e/[Formula: see text]co2 above the ULN was 24% in COPD (similar in GOLD 1 and 2 through 4), which was greater than in never-smokers (13%) and ever-smokers (12%). Conclusions: [Formula: see text]e/[Formula: see text]co2 above the ULN was associated with greater dyspnea and low [Formula: see text]o2peak and was present in 24% of all participants with COPD, regardless of GOLD stage. The results show the importance of recognizing impaired exercise ventilatory efficiency as a potential contributor to dyspnea and exercise limitation, even in mild COPD.

Liver epigenome changes in patients with hepatopulmonary syndrome: A pilot study.

The hepatopulmonary syndrome (HPS) is defined by the presence of pulmonary gas exchange abnormalities due to intrapulmonary vascular dilatations in patients with chronic liver disease. Changes in DNA methylation reflect the genomic variation. Since liver transplant (LT) reverts HPS we hypothesized that it may be associated with specific liver epigenetic changes. Thus, the aim of this study was to investigate the role of the liver epigenome in patients with HPS. We extracted DNA from paraffin embedded liver tissue samples from 10 patients with HPS and 10 age-, sex- and MELD (Model for End-stage Liver Disease)-matched controls. DNA methylation was determined using the 850K array (Illumina). Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify modules related to defining physiologic characteristics of HPS. Only 12 out of the 20 liver biopsies (7 HPS and 5 controls) had sufficient quality to be analyzed. None of the 802,688 DNA probes analyzed in the case control comparison achieved a significant False Discovery Rate (FDR). WGCNA identified 5 co-methylated gene-modules associated to HPS markers, mainly related to nervous and neuroendocrine system, apoptotic processes, gut bacterial translocation, angiogenesis and vascular remodeling ontologies. To conclude, HPS is associated with nervous/neuroendocrine system and vascular remodeling related liver epigenetic changes.

Exercise Training Improved Pulmonary Gas Exchange Abnormalities in Pulmonary Hypertension due to Heart Failure: A Case Report

Heart failure (HF) is the most common cause of pulmonary hypertension (PH), and reduced exercise capacity and exertional dyspnea are the most frequent concerns in patients with PH-HF. Indeed, carbon dioxide end-tidal partial pressure (PETCO 2 ) during exercise is a well-established noninvasive marker of ventilation/perfusion ratio in PH. We aimed to evaluate the effect of aerobic exercise training on PETCO 2 response during exercise in a 59-year-old woman with PH secondary to idiopathic dilated cardiomyopathy. The patient with [...]

Ventilation-perfusion heterogeneity measured by the multiple inert gas elimination technique is minimally affected by intermittent breathing of 100% O2.

Proton magnetic resonance (MR) imaging to quantify regional ventilation–perfusion ( V˙A/Q˙) ratios combines specific ventilation imaging (SVI) and separate proton density and perfusion measures into a composite map. Specific ventilation imaging exploits the paramagnetic properties of O2, which alters the local MR signal intensity, in an FIO2‐dependent manner. Specific ventilation imaging data are acquired during five wash‐in/wash‐out cycles of breathing 21% O2 alternating with 100% O2 over ~20 min. This technique assumes that alternating FIO2 does not affect V˙A/Q˙ heterogeneity, but this is unproven. We tested the hypothesis that alternating FIO2 exposure increases V˙A/Q˙ mismatch in nine patients with abnormal pulmonary gas exchange and increased V˙A/Q˙ mismatch using the multiple inert gas elimination technique (MIGET).The following data were acquired (a) breathing air (baseline), (b) breathing alternating air/100% O2 during an emulated‐SVI protocol (eSVI), and (c) 20 min after ambient air breathing (recovery). MIGET heterogeneity indices of shunt, deadspace, ventilation versus V˙A/Q˙ ratio, LogSD V˙, and perfusion versus V˙A/Q˙ ratio, LogSD Q˙ were calculated. LogSD V˙ was not different between eSVI and baseline (1.04 ± 0.39 baseline, 1.05 ± 0.38 eSVI, p = .84); but was reduced compared to baseline during recovery (0.97 ± 0.39, p = .04). There was no significant difference in LogSD Q˙ across conditions (0.81 ± 0.30 baseline, 0.79 ± 0.15 eSVI, 0.79 ± 0.20 recovery; p = .54); Deadspace was not significantly different (p = .54) but shunt showed a borderline increase during eSVI (1.0% ± 1.0 baseline, 2.6% ± 2.9 eSVI; p = .052) likely from altered hypoxic pulmonary vasoconstriction and/or absorption atelectasis. Intermittent breathing of 100% O2 does not substantially alter V˙A/Q˙ matching and if SVI measurements are made after perfusion measurements, any potential effects will be minimized.

The interactions between respiratory and cardiovascular systems in systolic heart failure.

Heart failure (HF) is a complex and multifaceted disease. The disease affects multiple organ systems, including the respiratory system. This review provides three unique examples illustrating how the cardiovascular and respiratory systems interrelate because of the pathology of HF. Specifically, these examples outline the impact of HF pathophysiology on 1) respiratory mechanics and the mechanical "cost" of breathing; 2) mechanical interactions of the heart and lungs; and on 3) abnormalities of pulmonary gas exchange during exercise, and how this may be applied to treatment. The goal of this review is to, therefore, raise the awareness that HF, though primarily a disease of the heart, is accompanied by marked pathology of the respiratory system.

Low resting diffusion capacity, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease.

The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (DlCO) to dyspnea and exercise intolerance across the chronic obstructive pulmonary disease (COPD) continuum are poorly understood. COPD progression generally involves both DlCO decline and worsening respiratory mechanics, and their relative contribution to dyspnea has not been determined. In a retrospective analysis of 300 COPD patients who completed symptom-limited incremental cardiopulmonary exercise tests, we tested the association between peak oxygen-uptake (V̇o2), DlCO, and other resting physiological measures. Then, we stratified the sample into tertiles of forced expiratory volume in 1 s (FEV1) and inspiratory capacity (IC) and compared dyspnea ratings, pulmonary gas exchange, and respiratory mechanics during exercise in groups with normal and low DlCO [i.e., <lower limit of normal (LLN)] using Global Lung Function Initiative reference values. DlCO was associated with peak V̇o2 (P = 0.006), peak work-rate (P = 0.005), and dyspnea/V̇o2 slope (P < 0.001) after adjustment for other independent variables (airway obstruction and hyperinflation). Within FEV1 and IC tertiles, peak V̇o2 and work rate were lower (P < 0.05) in low versus normal DlCO groups. Across all tertiles, low DlCO groups had higher dyspnea ratings, greater ventilatory inefficiency and arterial oxygen desaturation, and showed greater mechanical volume constraints at a lower ventilation during exercise than the normal DlCO group (all P < 0.05). After accounting for baseline resting respiratory mechanical abnormalities, DlCO<LLN was consistently associated with greater dyspnea and poorer exercise performance compared with preserved DlCO. The higher dyspnea ratings and earlier exercise termination in low DlCO groups were linked to significantly greater pulmonary gas exchange abnormalities, higher ventilatory demand, and associated accelerated dynamic mechanical constraints.NEW & NOTEWORTHY Our study demonstrated that chronic obstructive pulmonary disease patients with diffusing capacity of the lung for carbon monoxide (DlCO) less than the lower limit of normal had greater pulmonary gas exchange abnormalities, which resulted in higher ventilatory demand and greater dynamic mechanical constraints at lower ventilation during exercise. This, in turn, led to greater exertional dyspnea and exercise intolerance compared with patients with normal DlCO.

Abnormal Exercise Responses in Survivors of Acute Lung Injury During Cardiopulmonary Exercise Testing: AN OBSERVATIONAL STUDY.

This study compared exercise responses in individuals who had recently survived an admission to the intensive care unit for acute lung injury (ALI) with healthy controls. Ten patients with ALI were recruited at 2 Australian hospitals. Six weeks after hospital discharge, participants completed lung function measures and a laboratory-based cardiopulmonary exercise test. Identical measures were collected in 21 healthy participants of similar age and gender distribution. Compared with the healthy participants, the ALI participants were similar in age (51 ± 14 vs 50 ± 16 yr), with a lower peak oxygen uptake ((Equation is included in full-text article.)O2) (median [interquartile range], 31.80 [26.60-41.73] vs 17.80 [14.85-20.85] mL/kg/min; P < .01) and higher ventilatory equivalent for carbon dioxide ((Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2) at anaerobic threshold (mean ± SD, 25.7 ± 2.5 vs 35.2 ± 4.1; P < .01). Analysis of individual ALI participant responses showed that 8 participants had a decreased peak (Equation is included in full-text article.)O2 and anaerobic threshold. All ALI participants were limited by leg fatigue. Abnormalities of pulmonary gas exchange were present in 7 participants. Evidence of cardiac ischemia was present in 2 participants. Compared with healthy controls, ALI participants had reduced exercise capacity, mainly due to profound deconditioning. Exercise training to optimize aerobic capacity would appear to be a rehabilitation priority in this population.

Hepatopulmonary Disorders: Gas Exchange and Vascular Manifestations in Chronic Liver Disease.

This review concentrates on the determinants of gas exchange abnormalities in liver-induced pulmonary vascular disorders, more specifically in the hepatopulmonary syndrome. Increased alveolar-arterial O2 difference, with or without different levels of arterial hypoxemia, and reduced diffusing capacity represent the most characteristic gas exchange disturbances in the absence of cardiac and pulmonary comorbidities. Pulmonary gas exchange abnormalities in the hepatopulmonary syndrome are unique encompassing all three pulmonary factors determining arterial PO2 , that is, ventilation-perfusion imbalance, increased intrapulmonary shunt and oxygen diffusion limitation that, combined, interplay with two relevant nonpulmonary determinants, that is, increased total ventilation and high cardiac output. Behind the complexity of this lung-liver association there is an abnormal pulmonary vascular tone that combines inhibition of hypoxic pulmonary vasoconstriction with a reduced (or blunted) hypoxic vascular response. The pathology and pathobiology include the presence of intrapulmonary vascular dilatations with or without pulmonary vascular remodeling, i.e. angiogenesis. Liver transplantation, the only effective therapeutic approach to successfully improve and resolve the vast majority of complications induced by the hepatopulmonary syndrome, along with a large list of frustrating pharmacologic interventions, are also reviewed. Another liver-induced pulmonary vascular disorder with less gas exchange involvement, such as portopulmonary hypertension, is also considered. © 2018 American Physiological Society. Compr Physiol 8:711-729, 2018.

Frequency of Hepatopulmonary Syndrome (HPS) Among Patients With Liver Cirrhosis: A Letter to Editor.

Dear Editor, Hepatopulmonary syndrome (HPS) is a complication of liver disease. It is most frequently related to portal hypertension (with or without cirrhosis), although chronic liver disease of almost any etiology could be related to HPS (1, 2). Moreover, some acute liver diseases are related to HPS, such as ischemic hepatitis (3). HPS can be diagnosed when the following disorders have been approved (1, 4, 5); liver disorder, impaired oxygenation, intrapulmonary vascular anomalies, referred to as intrapulmonary vascular dilatations (IPVDs) and lack of intrinsic cardiopulmonary problem. HPS patients finally develop dyspnea on exertion, at rest, or both, commonly after years of liver disease. Dyspnea may be accompanied by pulmonary findings that are more specific for HPS (1, 6) such as platypnea and orthodeoxia. The frequency of hepatopulmonary syndrome in patients with chronic liver disease is about 4 to 47% regarding the criteria of diagnosis and used methods (7-12). The current study evaluated the prevalence of this complication in patients with cirrhosis. Thirty eight patients with cirrhosis were included in this study. Chest X-ray, air-contrast echocardiography, ABG in supine and standing positions, Tc99 MAA lung perfusion scan, PFT (pulmonary function test), serum bilirubin, PT and albumin were evaluated in patients. Hepatopulmonary syndrome was diagnosed in patients who had intrapulmonary vascular shunting and pulmonary gas exchange abnormalities. Among 38 patients, 28 persons were male (%73.7) and 10 females (%26.3). The mean age was 46.2 ± 13.6 (ranged 18 - 64 years). The most common cause of cirrhosis was hepatitis B. Among 29 patients (%76.3), hepatitis B and among 3 patients (%7.6) hepatitis C was diagnosed. Six patients (%15.8) had cryptogenic cirrhosis. Eleven patients (%28.9) had significant hypoxemia (pa O2 < 70) and 24 patients (%71.1) had not hypoxemia. Using echocardiography, 9 patients (23.7%) had pulmonary shunt. Also using radio isotope scan, 2 patients (%5.3) had pulmonary shunt. No patients with positive results in scan had contrast echocardiography. Therefore, pulmonary shunt frequency was %23.7. Six patients (15.8%) had HPS. Three patients (9.9%) had pulmonary shunt without hypoxemia or elevated p(A-a)O2 that are introduced subclinical HPS or IPVDs. Fourteen patients (%36.8) had child score A, 19 patients (%50) child score B and 5 (%13.2) child score C. The findings of the present study showed the prevalence of HPS and intrapulmonary vascular dilatation syndrome in patients with cirrhosis. Air-contrast echocardiography was more effective in diagnosis of intrapulmonary vascular shunting compared to Tc99 MAA lung perfusion scan. No significant relation was found between sex, age, duration, severity, and primary reason of cirrhosis with hepatopulmonary syndrome, but intrapulmonary vascular shunting was more usual in women patients. Spider angioma, orthodeoxia, low serum albumin, and ascites were determined to be suitable clinical indicators for hepatopulmonary syndrome.

Ventilation/Perfusion Distribution Abnormalities In Morbidly Obese Subjects Before and After Bariatric Surgery

BACKGROUND:Obesity is a global and growing public health problem. Bariatric surgery (BS) is indicated in patients with morbid obesity. To our knowledge, the effects of morbid obesity and BS on ventilation/perfusion ( V.a/ Q.) ratio distributions using the multiple inert gas elimination technique have never before been explored.METHODS:We compared respiratory and inert gas ( V.a/ Q.ratio distributions) pulmonary gas exchange, breathing both ambient air and 100% oxygen, in 19 morbidly obese women (BMI, 45 kg/m2), both before and 1 year after BS, and in eight normal-weight, never smoker, age-matched, healthy women.RESULTS:Before BS, morbidly obese individuals had reduced arterial Po2(76 ± 2 mm Hg) and an increased alveolar-arterial Po2difference (27 ± 2 mm Hg) caused by small amounts of shunt (4.3% ± 1.1% of cardiac output), along with abnormally broadly unimodal blood flow dispersion (0.83 ± 0.06). During 100% oxygen breathing, shunt increased twofold in parallel with a reduction of blood flow to low V.a/ Q.units, suggesting the development of reabsorption atelectasis without reversion of hypoxic pulmonary vasoconstriction. After BS, body weight was reduced significantly (BMI, 31 kg/m2), and pulmonary gas exchange abnormalities were decreased.CONCLUSIONS:Morbid obesity is associated with mild to moderate shunt and V.a/ Q.imbalance. These abnormalities are reduced after BS.

Pulmonary Gas Exchange Abnormalities in Mild Chronic Obstructive Pulmonary Disease. Implications for Dyspnea and Exercise Intolerance.

Several studies in mild chronic obstructive pulmonary disease (COPD) have shown a higher than normal ventilatory equivalent for carbon dioxide ([Formula: see text]e/[Formula: see text]co2) during exercise. Our objective was to examine pulmonary gas exchange abnormalities and the mechanisms of high [Formula: see text]e/[Formula: see text]co2 in mild COPD and its impact on dyspnea and exercise intolerance. Twenty-two subjects (11 patients with GOLD [Global Initiative for Chronic Obstructive Lung Disease] grade 1B COPD, 11 age-matched healthy control subjects) undertook physiological testing and a symptom-limited incremental cycle exercise test with arterial blood gas collection. Patients (post-bronchodilator FEV1: 94 ± 10% predicted; mean ± SD) had evidence of peripheral airway dysfunction and reduced peak oxygen uptake compared with control subjects (80 ± 18 vs. 113 ± 24% predicted; P<0.05). Arterial blood gases were within the normal range and effective alveolar ventilation was not significantly different from control subjects throughout exercise. The alveolar-arterial O2 tension gradient was elevated at rest and throughout exercise in COPD (P<0.05). [Formula: see text]e/[Formula: see text]co2, dead space to tidal volume ratio (Vd/Vt), and arterial to end-tidal CO2 difference were all higher (P<0.05) in patients with COPD than in control subjects during exercise. In patients with COPD versus control subjects, there was significant dynamic hyperinflation and greater tidal volume constraints (P<0.05). Standardized dyspnea intensity ratings were also higher (P<0.05) in patients with COPD versus control subjects in association with higher ventilatory requirements. Within all subjects, Vd/Vt correlated with the [Formula: see text]e/[Formula: see text]co2 ratio during submaximal exercise (r=0.780, P<0.001). High Vd/Vt was the most consistent gas exchange abnormality in smokers with only mild spirometric abnormalities. Compensatory increases in minute ventilation during exercise maintained alveolar ventilation and arterial blood gas homeostasis but at the expense of earlier dynamic mechanical constraints, greater dyspnea, and exercise intolerance in mild COPD.

Surviving ARDS: A Case of Recurrent “Illicit Drug-Induced” ARDS

Acute respiratory distress syndrome (ARDS) is a severe manifestation of abnormal pulmonary gas exchange. Many patients in whom this clinical syndrome develops are critically ill, and most do not recover. However, the critical care physician is likely to encounter more patients who have survived this clinical syndrome with recent improvements in the treatment related to this clinical entity. We describe a unique case of a patient who survived multiple episodes of ARDS. We illustrate potential etiologies relating to the multiple ARDS episodes and the recognition of illicit drug use as one of the pathophysiologic factors of recurrent ARDS. We highlight certain diagnostic clues in the patient’s history that may alert the intensivist to the diagnosis of ARDS related to illicit drug use. J Med Cases. 2014;5(1):11-14 doi: http://dx.doi.org/10.4021/jmc1571w

Surviving ARDS: A Case of Recurrent “Illicit Drug-Induced” ARDS

Acute respiratory distress syndrome (ARDS) is a severe manifestation of abnormal pulmonary gas exchange. Many patients in whom this clinical syndrome develops are critically ill, and most do not recover. However, the critical care physician is likely to encounter more patients who have survived this clinical syndrome with recent improvements in the treatment related to this clinical entity. We describe a unique case of a patient who survived multiple episodes of ARDS. We illustrate potential etiologies relating to the multiple ARDS episodes and the recognition of illicit drug use as one of the pathophysiologic factors of recurrent ARDS. We highlight certain diagnostic clues in the patient’s history that may alert the intensivist to the diagnosis of ARDS related to illicit drug use. J Med Cases. 2014;5(1):11-14 doi: https://doi.org/10.4021/jmc1571w