Alveolar Diffusing Capacity Research Articles

Female Sex Affects Respiratory Function and Exercise Ability in Patients Recovered from COVID-19 Pneumonia.

Background: Coronavirus-19 Disease (COVID-19) may cause persistent symptoms and functional respiratory impairment, known as long COVID. Determinants of long COVID are unclear. Although males experience more severe acute illness, the impact of sex on the occurrence of long-term sequelae is unknown. The aim of this study was to establish whether sex affects pulmonary function, exercise capacity, and clinical outcomes in patients recovered from COVID-19 pneumonia. Materials and Methods: We performed a retrospective analysis on patients evaluated in our "Post-COVID Clinic" after a median follow-up of 128 days from the acute disease. Tests performed included standard spirometry, diffusion capacity of the lung for carbon monoxide (DLCO), and 6-minute walk test (6-MWT). Results: A total of 157 patients (mean age 59.9 ± 12, 91 males) recovered from mild to severe pneumonia, without previous respiratory disease, were included. No differences in demographic data and in the severity of the acute illness were observed between the two study groups, males and females. Abnormal alveolar diffusion was more common and severe among females (DLCO <80% in 31% of males vs. 53% of females, p < 0.01; DLCO <70%, in 20% of males vs. 40% of females, p < 0.01). Severe reduction in 6-MWT was observed in 20% of males versus 46% of females (p < 0.01). Multiple logistic regression showed that female sex was an independent predictor of abnormal DLCO and 6-MWT. The prevalence of symptoms and radiological abnormalities was similar in the two groups. Conclusions: These data show that at 4 months follow-up women recovered from COVID-19 pneumonia are more likely to exhibit a reduced alveolar diffusion capacity and exercise tolerance than men, although a similar severity of the acute disease.

A Case series on Asthma-COPD overlap (ACO) is independent from other chronic obstructive diseases (COPD and Asthma)

As we know that, Asthma and chronic obstructive pulmonary diseases are well characterized diseases, they can co-exist as asthma-COPD overlap (ACO). The co-existence of asthma-chronic obstructive pulmonary disease overlap (ACO) in chronic obstructive pulmonary disease (COPD) patients is often unrecognized. In patients with a primary diagnosis of COPD or Asthma, the identification of ACO has got implication for better prognosis and treatment. Such patients experience frequent exacerbations, poor quality of life, rapid decline in lung function and high mortality than COPD or Asthma alone. Inhalational steroids provide significant alleviation of symptoms in such patients and some studies suggest that the most severe patients may respond to biological agents indicated for severe asthma. Patients who have asthma with a COPD component tend to present with severe hypoxia because of Irreversible/fixed airway obstruction and impairment of the alveolar diffusion capacity by emphysematous changes. In contrast, patients with COPD who have an asthma component not only have exertional dyspnoea but also develop paroxysmal wheezing or dyspnoea at night or in the early morning. The criteria to diagnose asthma-COPD overlap (ACO) include positive bronchodilator response, sputum eosinophilia or previous diagnosis of asthma, high IgE and/or history of atopy. There is scarcity of literature available in country like India. We highlight the importance of identification of Asthma COPD overlap as different phenotype from COPD or asthma alone as it is challenging to diagnose ACO in India. We report 3 cases having both the features of asthma and COPD, later diagnosed with Asthma-COPD overlap.

Does Cold-Water Endurance Swimming Affect Pulmonary Function in Healthy Adults?

The acute effects of cold-water endurance swimming on the respiratory system have received little attention. We investigated pulmonary responses to cold-water endurance swimming in healthy recreational triathletes. Pulmonary function, alveolar diffusing capacity (DLCO), fractional exhaled nitric oxide (FENO) and arterial oxygen saturation by pulse oximetry (SpO2) were assessed in 19 healthy adults one hour before and 2.5 h after a cold-water (mean ± SD, 10 ± 0.9 °C) swim trial (62 ± 27 min). In addition, 12 out of the 19 participants measured pulmonary function, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) 3, 10, 20 and 45 min post-swim by maximal expiratory flow volume loops and DLCO by the single breath technique. FVC and FEV1 were significantly reduced 3 min post-swim (p = 0.02) (p = 0.04), respectively, and five of 12 participants (42%) experienced exercise-induced bronchoconstriction (EIB), defined as a ≥ 10% drop in FEV1. No significant changes were observed in pulmonary function 2.5 h post-swim. However, mean FENO and DLCO were significantly reduced by 7.1% and 8.1% (p = 0.01) and (p < 0.001), respectively, 2.5 h post-swim, accompanied by a 2.5% drop (p < 0.001) in SpO2. The absolute change in DLCO correlated significantly with the absolute decline in core temperature (r = 0.52; p = 0.02). Conclusion: Cold-water endurance swimming may affect the lungs in healthy recreational triathletes lasting up to 2.5 h post-swim. Some individuals appear to be more susceptible to pulmonary impairments than others, although these mechanisms need to be studied further.

Impact of breath sampling on exhaled carbon monoxide

The influence of breath sampling on exhaled carbon monoxide (eCO) and related pulmonary gas exchange parameters is investigated in a study with 32 healthy non-smokers. Mid-infrared tunable diode laser absorption spectroscopy and well-controlled online sampling is used to precisely measure mouth- and nose-exhaled CO expirograms at exhalation flow rates (EFRs) of 250, 120 and 60 ml s−1, and for 10 s of breath-holding followed by exhalation at 120 ml s−1. A trumpet model with axial diffusion is employed to fit simulated exhalation profiles to the experimental expirograms, which provides equilibrium airway and alveolar CO concentrations and the average lung diffusing capacity in addition to end-tidal concentrations. For all breathing maneuvers, excellent agreement is found between mouth- and nose-exhaled end-tidal CO (ETCO), and the individual values for ETCO and alveolar diffusing capacity are consistent across maneuvers. The eCO parameters clearly show a dependence on EFR, where the lung diffusing capacity increases with EFR, while ETCO slightly decreases. End-tidal CO is largely independent of ambient air CO and alveolar diffusing capacity. While airway CO is slightly higher than, and correlates strongly with, ambient air CO, and there is a weak correlation with ETCO, the results point to negligible endogenous airway CO production in healthy subjects. An EFR of around 120 ml s−1 can be recommended for clinical eCO measurements. The employed method provides means to measure variations in endogenous CO, which can improve the interpretation of exhaled CO concentrations and the diagnostic value of eCO tests in clinical studies. Clinical trial registration number: 2017/306-31

Fitting of single-exhalation profiles using a pulmonary gas exchange model—application to carbon monoxide

Real-time breath gas analysis coupled to gas exchange modeling is emerging as promising strategy to enhance the information gained from breath tests. It is shown for exhaled breath carbon monoxide (eCO), a potential biomarker for oxidative stress and respiratory diseases, that a weighted, nonlinear least-squares fit of simulated to measured expirograms can be used to extract physiological parameters, such as airway and alveolar concentrations and diffusing capacities. Experimental CO exhalation profiles are acquired with high time-resolution and precision using mid-infrared tunable diode laser absorption spectroscopy and online breath sampling. A trumpet model with axial diffusion is employed to generate eCO profiles based on measured exhalation flow rates and volumes. The concept is demonstrated on two healthy non-smokers exhaling at a flow rate of 250 ml s−1 during normal breathing and at 120 ml s−1 after 10 s of breath-holding. The obtained gas exchange parameters of the two subjects are in a similar range, but clearly distinguishable. Over a series of twenty consecutive expirograms, the intra-individual variation in the alveolar parameters is less than 6%. After a 2 h exposure to 10 ± 2 ppm CO, end-tidal and alveolar CO concentrations are significantly increased (by factors of 2.7 and 4.9 for the two subjects) and the airway CO concentration is slightly higher, while the alveolar diffusing capacity is unchanged compared to before exposure. Using model simulations, it is found that a three-fold increase in maximum airway CO flux and a reduction in alveolar diffusing capacity by 60% lead to clearly distinguishable changes in the exhalation profile shape. This suggests that extended breath CO analysis has clinical relevance in assessing airway inflammation and chronic obstructive pulmonary disease. Moreover, the novel methodology contributes to the standardization of real-time breath gas analysis.

Heart Rate Recovery Following Aerobic Exercise Training in Patients with Interstitial Lung Disease

Interstitial lung disease (ILD) is characterized by a progressive decline in alveolar diffusion capacity and pulmonary function, often abetted by capillary destruction and hypoxic vasoconstriction. These abnormalities manifest themselves symptomatically by a severe reduction of exercise capacity and excessive fatigue. Heart rate recovery (HRR) reflects the capability of the autonomic nervous system to adapt and cope with the training load and can predict the accumulation of fatigue. Therefore, HRR can be a physiological measure of the endurance capacity and the ability to resist fatigue-induced changes. PURPOSE: To examine the influence of changes in resting heart rate (HR) following an aerobic exercise training (AET) program on recovery HR in patients with ILD. METHODS: 13 ILD patients (57±9 years) underwent a 10-week treadmill walking program at 70-80% of HR reserve for 30-45 minutes thrice a week. The six minute walk test (6MWT) was performed on an 80-meter oval track prior to and at the end of the AET program in accordance with the American Thoracic Society guidelines. Resting HR was measured by pulse oximetry after 10 minutes of seated rest before starting the 6MWT. Recovery HR was measured after 2 minutes of seated rest following the end of the 6MWT. RESULTS: Paired t-test comparisons of pre- and post-AET resting and recovery HRs revealed two HR change patterns which divided the patients into two cohorts. Subset 1 (n=7) displayed a statistically significant decrease in resting HR (104±11 vs. 88±10, p=0.002) and recovery HR (120±12 vs. 104±10, p=0.001) after the 10-week AET. Subset 2 (n=6) displayed a statistically significant increase in resting HR (86±12 vs. 97±12, p=0.034) and no significant improvements in recovery HR. There was a near identical increase in post-training six minute walk distance in subset 1 and 2 of 49 (p=0.045) and 50 meters (p=0.043) respectively. CONCLUSIONS: Our findings show that a decrease in resting HR following AET may be associated with a faster recovery, perhaps permitting patients to more readily engage in subsequent physical activities. The variations in training adaptations in resting and recovery HR suggest a variable cardiac autonomic modulation to exercise training in patients with ILD, implications of which are yet to be explored. NIH/IRP 1 Z01 CL06006802; http://ClinicalTrials.gov; NCT00678821

Computed Tomography-Based Centrilobular Emphysema Subtypes Relate with Pulmonary Function

Introduction:Centrilobular emphysema (CLE) is recognized as low attenuation areas (LAA) with centrilobular pattern on high-resolution computed tomography (CT). However, several shapes of LAA are observed. Our preliminary study showed three types of LAA in CLE by CT-pathologic correlations. This study was performed to investigate whether the morphological features of LAA affect pulmonary functions.Materials and Methods:A total of 73 Japanese patients with stable CLE (63 males, 10 females) were evaluated visually by CT and classified into three subtypes based on the morphology of LAA including shape and sharpness of border; patients with CLE who shows round or oval LAA with well-defined border (Subtype A), polygonal or irregular-shaped LAA with ill-defined border (Subtype B), and irregular-shaped LAA with ill-defined border coalesced with each other (Subtype C). CT score, pulmonary function test and smoking index were compared among three subtypes.Results:Twenty (27%), 45 (62%) and 8 cases (11%) of the patients were grouped into Subtype A, Subtype B and Subtype C, respectively. In CT score and smoking index, both Subtype B and Subtype C were significantly higher than Subtype A. In FEV1%, Subtype C was significantly lower than both Subtype A and Subtype B. In diffusing capacity of lung for carbon monoxide, Subtype B was significantly lower than Subtype A.Conclusion:The morphological differences of LAA may relate with an airflow limitation and alveolar diffusing capacity. To assess morphological features of LAA may be helpful for the expectation of respiratory function.

Alveolar‐capillary membrane conductance is the best pulmonary function correlate of exercise ventilation efficiency in heart failure patients

In heart failure (HF), changes in lung mechanics and gas diffusion are limiting factors to exercise. Their contribution to an increased exercise ventilation to CO2 production (VE/VCO2) slope is undefined. A total of 67 stable HF patients underwent cardiopulmonary exercise and pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal voluntary ventilation (MVV), total lung capacity (TLC) and alveolar diffusing capacity with its subcomponents (alveolar-capillary membrane conductance (D(m)) and capillary blood volume (V(c))). Patients showed a mild restrictive pattern (FEV1=85+/-15% and FVC=75+/-13% of normal predicted) and a moderate D(m) reduction (32+/-12 ml min(-1) mm Hg(-1)). Average peak VO(2) was 15.6+/-4.0 ml min(-1) kg(-1) and the VE/VCO2 slope was 39.6+/-11.0. At simple Spearman correlation analysis, all variables, but V(c), correlated with peak VO2; only D(m) correlated with VE/VCO2 slope. At partial Spearman correlation, all variables lost the peak VO2 correlation, and D(m) still inversely correlated with VE/VCO2 slope (r=-0.35; p=0.005). In patients with a high VE/VCO2 slope (cutoff value 34), despite comparable lung volumes, D(m) was significantly more depressed (30+/-13 vs. 35+/-10 ml min(-1) mm Hg(-1); p<0.01). Pulmonary function tests and alveolar gas diffusing capacity poorly correlate with peak VO2. D(m) impairment rather than lung volumes correlates with exercise ventilation efficiency. This finding further adds to the pathophysiological relevance of an abnormal gas exchange in HF patients.

Alveolar--capillary membrane gas conductance: a novel prognostic indicator in chronic heart failure.

Lung dysfunction occurring in chronic heart failure worsens clinical status and exercise performance. The prognostic value of airway and alveolar function measurements in chronic heart failure has not been explored. We aimed to evaluate the prognostic value of lung function tests in a population of patients with stable chronic heart failure. One hundred and six stable chronic heart failure patients (whose left ventricular ejection fraction averaged 33 +/- 1%) underwent echocardiography, metabolic stress testing, assessment of pulmonary function at rest (by spirometry), of alveolar diffusing capacity (DLco) (with carbon monoxide technique) and of its membrane (DM) and capillary blood volume (Vc) components. Prognostic relevance of pulmonary variables was assessed by the Kaplan-Meier approach with log-rank testing and by Cox regression analysis. Cut-off values of lung parameters were based on the 33rd and 66th centiles. Seventeen patients died for cardiac reasons. Non-survivors compared to survivors showed lower forced expiratory volume in 1 s (2 X 1 +/- 0 X 1 vs 2 X 4 +/- 0 X 1 l; P<0 X 01), forced vital capacity (2 X 6 +/- 0 X 1 vs 2 X 9 +/- 0 X 1 l; P<0 X 01), maximal voluntary ventilation (80 X 7 +/- 2 X 5 vs 95 X 4 +/- 2 X 7 l; P<0 X 01), DLco (16 X 5 +/- 1 X 1 vs 19 X 3 +/- 0 X 6 ml . min(-1) . mmHg(-1); P<0 X 01) and DM (25 X 1 +/- 1 X 8 vs 31 X 9 +/- 1 X 5 ml . min(-1) . mmHg(-1); P<0 X 01). They also exhibited a smaller peak VO2 (14 X 6 +/- 0 X 7 vs 15 X 9 +/- 0 X 6 ml . min(-1) . kg(-1); P<0 X 05) and a steeper VE/VCO2 slope (45 X 0 +/- 1 X 7 vs 41 X 9 +/- 1 X 5; P<0 X 01). Multivariate analysis revealed that DM was the only independent predictor of cardiac death. Cases at high risk for adverse outcome were identified by a DM<24 X 7 ml . min(-1) . mmHg(-1). Patients receiving ACE-inhibitors presented with a higher DM (32 X 1 +/- 1 X 7 vs 27 X 9 +/- 1 X 7 ml . min(-1) . mmHg(-1), P<0 X 05) as well as a better Cox estimated survival rate. Impaired DM is a powerful independent predictor of worse prognosis in stable chronic heart failure and may be considered an additional index of disease severity, as well as a specific therapeutic target.

Effects of Side Lying on Lung Function in Older Individuals

Body positioning exerts a strong effect on pulmonary function, but its effect on other components of the oxygen transport pathway are less well understood, especially the effects of side-lying positions. This study investigated the interrelationships between side-lying positions and indexes of lung function such as spirometry, alveolar diffusing capacity, and inhomogeneity of ventilation in older individuals. Nineteen nonsmoking subjects (mean age=62.8 years, SD=6.8, range=50-74) with no history of cardiac or pulmonary disease were tested over 2 sessions. The test positions were sitting and left side lying in one session and sitting and right side lying in the other session. In each of the positions, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), single-breath pulmonary diffusing capacity (DLCO/VA), and the slope of phase III (DN2%/L) of the single-breath nitrogen washout test to determine inhomogeneity of ventilation were measured. Compared with measurements obtained in the sitting position, FVC and FEV1 were decreased equally in the side-lying positions, but no change was observed in DLCO/VA or DN2%/L. Side-lying positions resulted in decreases in FVC and FEV1, which is consistent with the well-documented effects of the supine position. These findings further support the need for prescriptive rather than routine body positioning of patients with risks of cardiopulmonary compromise and the need to use upright positions in which lung volumes and capacities are maximized.

Primary biliary cirrhosis: lung involvement

Sub-clinical lung impairment, mostly represented by a reduced diffusion of alveolar gases, is a recognised complication of advanced primary biliary cirrhosis. The aim of the study was to evaluate the prevalence and type of pulmonary involvement in primary biliary cirrhosis and the relationship between lung function abnormalities and selected epidemiological and clinical variables. Sixty-one patients with different stages of primary biliary cirrhosis consecutively seen in our outpatient clinic were evaluated. The advancement of primary biliary cirrhosis was characterised by the histological stage, the presence of signs of portal hypertension and the Mayo Risk Score: a Cox regression model using serum bilirubin and albumin levels, prothrombin time, age and degree of oedema as selected variables. We measured static and dynamic lung volumes, by means of a spirometer, and diffusing capacity for carbon monoxide. Rheumatological disorders were evaluated by an independent rheumatologist. No patient complained of respiratory symptoms. Airway obstruction was present in one patient. In 24 patients (39%) the alveolar diffusion capacity was reduced. We did not find any significant relationship between diffusing capacity and smoking habits, advancement of liver disease and concomitant Sjogren syndrome. Reduced diffusion capacity showed a significant correlation with the presence of complete or incomplete CREST syndrome (p < 0.01) and with the presence of circulating anti-centromere antibodies (p < 0.05). Alveolar diffusion capacity is frequently impaired in patients with primary biliary cirrhosis, usually in the absence of clinical manifestations. These alterations mostly affect patients with concomitant CREST syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Marijuana smoking, pulmonary function, and lung macrophage oxidant release

Pulmonary alveolar macrophages lavaged from tobacco smokers release increased levels of oxidants and have been implicated in the pathophysiology of emphysema. It is unknown whether lung macrophages recovered from marijuana smokers also liberate excessive levels of oxidants. To evaluate this possibility, pulmonary alveolar macrophages were obtained by bronchoalveolar lavage from nonsmokers, smokers of marijuana only, smokers of tobacco only, and smokers of tobacco plus marijuana. Spontaneous and stimulated superoxide anion release was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome c. These findings were correlated with recent lung function tests. Superoxide anion production by macrophages, studies of small airway integrity (closing volume, closing capacity, and the slope of Phase III of the single-breath nitrogen washout curve), and evaluation of alveolar gas exchange (diffusing capacity of carbon monoxide) were similar in both nonsmokers and marijuana smokers. However, tobacco smoking was associated with both significantly higher levels of superoxide anion release by pulmonary alveolar macrophages and significant abnormalities of small airway function and alveolar diffusing capacity. Based on the results of this study, pulmonary alveolar macrophages of marijuana-only smokers do not produce increased amounts of oxidants when compared to macrophages of non-smoking subjects. This observation may account for the absence of abnormalities in small airway function and alveolar diffusing capacity in marijuana-only smokers, in contrast to the presence of such findings in smokers of tobacco, regardless of marijuana use.

Silo filler's disease: Clinical, physiologic and pathologic study of a patient

A case of silo filler's disease is reported, resulting from exposure to silage six weeks after it was stored. Pulmonary function studies and lung biopsy specimens were obtained in the acute stage and during the period of convalescence. Pulmonary function studies showed the acute disturbance to be one of impaired diffusion of oxygen across the alveolar-capillary membrane. The initial lung biopsy showed a bronchiolitis. Following therapy with corticosteroids the alveolar diffusion capacity became normal, but the pulmonary function studies as well as the biopsy indicated that a mild degree of pulmonary hyperinflation resulted.