Lung Elastic Recoil Research Articles

Understanding the pathophysiology of the asthma-chronic obstructive pulmonary disease overlap syndrome.

The review will provide an update on the pathophysiology and studies of inflammation associated with the asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) and the mechanism(s) responsible for persistent expiratory airflow limitation in never-smoked asthma patients who develop loss of lung elastic recoil consistent with an asthma-COPD clinical phenotype (ACOS in nonsmokers). Patients with a clinical diagnosis of ACOS have more frequent respiratory exacerbations and hospitalizations than COPD patients without ACOS. ACOS patients should be treated with inhaled corticosteroids, short and long-acting β2-agonist, and long-acting muscarinic receptor antagonist. Biomarker work suggests that a molecular phenotype of ACOS (e.g., elevated markers of eosinophilic or type 2 inflammation) incompletely corresponds to clinical phenotypes. Recently, we reported sentinel observation of unsuspected mild diffuse centrilobular emphysema in never-smoked asthma patients at autopsy, despite mild changes in lung computed tomography and normal diffusing capacity. Recent studies have shown that subgroups of COPD and asthma patients may have overlapping immune responses. Never-smoked asthma patients may have persistent expiratory airflow limitation because of loss of lung elastic recoil. This may be because of unsuspected centrilobular emphysema detected at autopsy, and not easily diagnosed on lung computed tomography and diffusing capacity.

The clinical relevance of the emphysema-hyperinflated phenotype in COPD

The classification of chronic pulmonary obstructive disease (COPD) into clinical and pathophysiological subsets is not new, but increasing data is available on the relation of these different phenotypes to clinically meaningful outcomes. This review focuses on the “emphysema-hyperinflation” (EH) phenotype, which is characterised by a prominent loss of lung elastic recoil and hyperinflation burden that translates into marked exercise intolerance and a heightened sense of dyspnoea. Although no single genetic profile has been associated with the EH phenotype, recent data have shown that certain single nucleotide polymorphisms, such as DNAH5, appear to have an effect on the preferential development of hyperinflation in smokers. Static and dynamic hyperinflation are hallmarks of the EH phenotype, and abnormal increases in resting lung function indices such as total lung capacity (TLC), functional residual capacity (FRC) and inspiratory to TLC ratio (IC/TLC) seem more associated with the clinical EH phenotype than others markers of gas trapping. An increased level of dyspnoea on exertion and exercise intolerance are also characteristic of the EH presentation and are likely related in part to critical mechanical constraints imposed on tidal volume expansion in situations where ventilatory demands are increased, but also possibly on cardiac and hemodynamic anomalies related to emphysema and hyperinflation. Importantly, the clinical relevance of the EH phenotype is underlined by the finding that indices of hyperinflation such as IC/TLC and residual volume (RV) can be used as independent predictors of mortality in patients with COPD. Treatment of patients with the EH phenotype should primarily focus on smoking cessation and maximal bronchodilator therapy. New long-acting combined bronchodilators options provide clinicians with safe and effective ways to address the hyperinflation issue in this population. Pulmonary rehabilitation also has a positive impact on exercise tolerance, quality of life and hyperinflation, and should be routinely considered in patients with EH presentation that remain symptomatic despite optimal treatment, whereas as lung volume reduction techniques should be reserved for highly selected patients.

Unraveling the Pathophysiology of the Asthma-COPD Overlap Syndrome: Unsuspected Mild Centrilobular Emphysema Is Responsible for Loss of Lung Elastic Recoil in Never Smokers With Asthma With Persistent Expiratory Airflow Limitation

Investigators believe most patients with asthma have reversible airflow obstruction with treatment, despite airway remodeling and hyperresponsiveness. There are smokers with chronic expiratory airflow obstruction despite treatment who have features of both asthma and COPD. Some investigators refer to this conundrum as the asthma-COPD overlap syndrome (ACOS). Furthermore, a subset of treated nonsmokers with moderate to severe asthma have persistent expiratory airflow limitation, despite partial reversibility. This residuum has been assumed to be due to large and especially small airway remodeling. Alternatively, we and others have described reversible loss of lung elastic recoil in acute and persistent loss in patients with moderate to severe chronic asthma who never smoked and its adverse effect on maximal expiratory airflow. The mechanism(s) responsible for loss of lung elastic recoil and persistent expiratory airflow limitation in nonsmokers with chronic asthma consistent with ACOS remain unknown in the absence of structure-function studies. Recently we reported a new pathophysiologic observation in 10 treated never smokers with asthma with persistent expiratory airflow obstruction, despite partial reversibility: All 10 patients with asthma had a significant decrease in lung elastic recoil, and unsuspected, microscopic mild centrilobular emphysema was noted in all three autopsies obtained although it was not easily identified on lung CT scan. These sentinel pathophysiologic observations need to be confirmed to further unravel the epiphenomenon of ACOS. The proinflammatory and proteolytic mechanism(s) leading to lung tissue breakdown need to be further investigated.

Impact of obstructive sleep apnea on lung volumes and mechanical properties of the respiratory system in overweight and obese individuals.

BackgroundEven through narrowing of the upper-airway plays an important role in the generation of obstructive sleep apnea (OSA), the peripheral airways is implicated in pre-obese and obese OSA patients, as a result of decreased lung volume and increased lung elastic recoil pressure, which, in turn, may aggravate upper-airway collapsibility.MethodsA total of 263 male (n = 193) and female (n = 70) subjects who were obese to various degrees without a history of lung diseases and an expiratory flow limitation, but troubled with snoring or suspicion of OSA were included in this cross-sectional study. According to nocturnal-polysomnography the subjects were distributed into OSA and non-OSA groups, and were further sub-grouped by gender because of differences between males and females, in term of, lung volume size, airway resistance, and the prevalence of OSA among genders. Lung volume and respiratory mechanical properties at different-frequencies were evaluated by plethysmograph and an impulse oscillation system, respectively.ResultsFunctional residual capacity (FRC) and expiratory reserve volume were significantly decreased in the OSA group compared to the non-OSA group among males and females. As weight and BMI in males in the OSA group were greater than in the non-OSA group (90 ± 14.8 kg vs. 82 ± 10.4 kg, p < 0.001; 30.5 ± 4.2 kg/m2 vs. 28.0 ± 3.0 kg/m2, p < 0.001), multiple regression analysis was required to adjust for BMI or weight and demonstrated that these lung volumes decreases were independent from BMI and associated with the severity of OSA. This result was further confirmed by the female cohort. Significant increases in total respiratory resistance and decreases in respiratory conductance (Grs) were observed with increasing severity of OSA, as defined by the apnea-hypopnea index (AHI) in both genders. The specific Grs (sGrs) stayed relatively constant between the two groups in woman, and there was only a weak association between AHI and sGrs among man. Multiple-stepwise-regression showed that reactance at 5 Hz was highly correlated with AHI in males and females or hypopnea index in females, independently-highly correlated with peripheral-airway resistance and significantly associated with decreasing FRC.ConclusionsTotal respiratory resistance and peripheral airway resistance significantly increase, and its inverse Grs decrease, in obese patients with OSA in comparison with those without OSA, and are independently associated with OSA severity. These results might be attributed to the abnormally increased lung elasticity recoil pressure on exhalation, due to increase in lung elasticity and decreased lung volume in obese OSA.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-015-0063-6) contains supplementary material, which is available to authorized users.

A comparative study of the mechanical properties in aging alveolar wall.

Alveolar wall from the lung of aging humans shows a progressive decrease in maximal extensibility, which should follow an increase in resting tissue length rather than a reduction in maximal length. An increase in resting tissue length is compatible with the change in lung volumes and reduction in elastic recoil that occurs with time. A model of the lung was used to compare the effects of a change in resting tissue length in diminishing elastic recoil with that of a reduction in the volume density of the elastic elements (emphysema). Such differentiation is important in selecting an animal that may model the aging or emphysematous lung. In the rat, rabbit, and horse, alveolar walls show no decrease in maximal extensibility with age. In the male monkey (M. nemestrina and M. mulatta) between birth and 2.4 years there is a decrease in maximal extensibility that lacks significance for the limited age span examined. On the other hand, the energy loss in length-tension cycling (hysteresis) of alveolar wall increases in aging humans, diminishes in rats and rabbits, and shows little change in horses and monkeys. The breaking force of alveolar wall increases with age in rats and rabbits but does not change significantly in the other species. Of these species, the monkey promises a better model of the age-related changes in maximal extensibility of alveolar wall. A measure of maximal extensibility can distinguish the effects of dilatation of air spaces from those of destruction of alveolar wall in causing loss of lung elastic recoil.

What can impulse oscillometry and pulmonary function testing tell us about obstructive sleep apnea: a case-control observational study?

This study aims to determine whether functional residual capacity (FRC) in obese patients with obstructive sleep apnea (OSA) decreases more than in patients without OSA because of decreased outward recoil from chest wall mass loading as well as increased lung inward recoil. Subjects who were overweight and obese to various degrees with normal spirometric values underwent overnight polysomnography to determine the presence or absence of OSA and were labeled as cases or controls. Lung volume and respiratory mechanical properties were measured by plethysmograph and impulse oscillometry, respectively. A total of 76 men and 31 women were diagnosed with OSA (cases); 64 men and 33 women without OSA were confirmed as controls. Expiratory reserve volume and FRC were significantly decreased in cases compared with controls. Respiratory impedance and resistance at 5 Hz were significantly higher in cases than in controls, although reactance at low frequencies was significantly lower in cases than in controls. Reactance at 5 Hz (Xrs5) was found to be independently highly correlated with the severity of OSA as defined by the Apnea-Hypopnea Index and was significantly correlated with FRC. FRC is significantly decreased in overweight or obese patients with OSA compared with those without OSA, which may be attributed to an increase in lung elastic recoil. The stronger correlation between Xrs5 and OSA severity might indicate upper airway stenosis, and abnormally increased lung elastic recoil may contribute to OSA.

Static Respiratory Mechanics are Unaltered in Mild-to-Moderate Obese Men and Women

Morbid obesity can affect spirometric function and lung volume subdivisions. Additionally, compliance of the lung and chest wall are unfavorably altered. However, in mild-to-moderate obesity, rarely are expiratory flows and lung volumes influenced to an extent that they become less than normal. It is unclear if mild-to-moderate obesity alters the flow-pressure-volume relationship of the respiratory system. PURPOSE: To examine whether the interrelationships of maximal flow-pressure-volume are altered due to mild-to-moderate obesity in men and women METHODS: Obese (30 ≤ BMI ≤ 45) and lean (BMI < 25) men (n = 20) and women (n = 17) completed pulmonary function testing. Maximal expiratory flow, static lung elastic recoil pressure (Pst), and the minimal pressure for maximal flow (Pcrit) were determined in a pressure-compensated, volume-displacement body plethysmograph. Parameters were compared at 25, 50, and 75% of forced vital capacity (FVC). Additionally, dysanapsis, the association between airway size and lung size, was estimated using measured values of maximal expiratory flow at 50% FVC, FVC, and Pst at 50% FVC. Dysanapsis also was estimated using a regression equation for the calculation of Pst at 50% FVC. RESULTS: Obese and lean men had similar maximal expiratory flow, Pst and Pcrit at each lung volume examined. Additionally, obese and lean women displayed similar flow-pressure-volume characteristics. However, men had greater maximal expiratory flows, Pst, and Pcrit at all lung volumes, with the exception of Pcrit at 25% FVC, compared with women (p < 0.05). Dysanapsis was unaffected due to mild-to-moderate obesity in men and in women. Dysanapsis estimated using the predicted value for Pst at 50% FVC was significantly different from that obtained using measured parameters. CONCLUSIONS: Unlike in morbid obesity, mild-to-moderate obesity does not affect flow-pressure-volume relationships in men or in women. Furthermore, due to the inability to accurately predict static lung elastic recoil pressure, the use of prediction equations in the estimation of dysanapsis is cautioned.

Integral activity of intrapulmonary source of mechanical energy in healthy subjects and in patients with obstructive lung diseases

Two functional levels of mechanical energy intrapulmonary source have been viewed in this article for the first time. The first level is located into the perialveolar space. This level provides inspiratory and expiratory activity of the lungs together with respiratory muscles. Due to this, the inspiratory alveolar pressure is lower than the intrapleural pressure and the expiratory alveolar pressure is higher than the intrapleural pressure. This is deter mined by work of breathing measured as negative elastic hysteresis area and allows overcoming some nonelastic resistance of the lungs. The lung activity on overcoming the elastic resistance is estimated by multiplying the total work of breathing by a functional coefficient of lung elasticity (FCLE). The latter is calculated by dividing the total lung compliance by the dynamic lung compliance and reflects change in the elastic lung tension from spontaneous breathing level to the total lung compliance level. FCLE approximates 1 in healthy subjects and in patients with normal lung elastic recoil (LER). LER is lower and the total lung capacity is higher in lung obstructive diseases. Consequently, the total lung compliance could increase and FCLE could grow up to 10 in such cases (for instance, in severe emphysema). This leads to increasing lung activity on overcoming the elastic resistance up to 10 kgf × m / min or higher. Actually, this huge work of breathing is not performed due to the 2nd level of lung mechanical activity that is an active dilation of the large airways on expiration; this mechanism prevents valvular bronchial obstruction.

Chest wall strapping. An old physiology experiment with new relevance to small airways diseases.

Chest wall strapping (CWS) induces breathing at low lung volumes. Mild to moderate obesity can lead to similar changes in lung volumes, due to chest wall and abdominal restriction. Chest wall strapping is also conceptually similar to a mismatch between significantly oversized donor lungs transplanted into a recipient with a smaller chest cavity. Chest wall strapping increases lung elastic recoil, reduces pulmonary compliance, and substantially increases maximal expiratory flows. The interactions between elastic properties of the lung parenchyma and small airways are critical for pulmonary function. Chest wall strapping lowers residual volume and closing volume, likely from the interdependence between increased elastic recoil and airways, leading to greater radial distending forces on small airways and small airway dilation. Chronic obstructive pulmonary disease (COPD) and chronic rejection of the transplanted lung, bronchiolitis obliterans syndrome (BOS), are primarily diseases of the small airways, and are characterized by progressive obstruction and subsequent loss of small airways. In COPD, higher body mass index (BMI) (conceptually like being more tightly strapped) is associated with lower lung volumes, increased airway conductance, and lower risk of progression to emphysema or death. Likewise, in lung transplantation, oversized donor lungs have been linked to higher expiratory airflows, lower risk of bronchiolitis obliterans syndrome, and improved survival. This article reviews the physiology of chest wall strapping and explores how it could enhance the understanding or even the treatment of small airway diseases, such as COPD and bronchiolitis obliterans syndrome.

Reading Pulmonary Vascular Pressure Tracings. How to Handle the Problems of Zero Leveling and Respiratory Swings

The accuracy of pulmonary vascular pressure measurements is of great diagnostic and prognostic relevance. However, there is variability of zero leveling procedures, and the current recommendation of end-expiratory reading may not always be adequate. A review of physiological and anatomical data, supported by recent imaging, leads to the practical recommendation of zero leveling at the cross-section of three transthoracic planes, which are, respectively midchest frontal, transverse through the fourth intercostal space, and midsagittal. As for the inevitable respiratory pressure swings, end-expiratory reading at functional residual capacity allows for minimal influence of elastic lung recoil on pulmonary pressure reading. However, hyperventilation is associated with changes in end-expiratory lung volume and increased intrathoracic pressure, eventually exacerbated by expiratory muscle contraction and dynamic hyperinflation, all increasing pulmonary vascular pressures. This problem is amplified in patients with obstructed airways. With the exception of dynamic hyperinflation states, it is reasonable to assume that negative inspiratory and positive expiratory intrathoracic pressures cancel each other out, so averaging pulmonary vascular pressures over several respiratory cycles is most often preferable. This recommendation may be generalized for the purpose of consistency and makes sense, as pulmonary blood flow measurements are not corrected for phasic inspiratory and expiratory changes in clinical practice.

Ventilation heterogeneity in obesity

Obesity is associated with important decrements in lung volumes. Despite this, ventilation remains normally or near normally distributed at least for moderate decrements in functional residual capacity (FRC). We tested the hypothesis that this is because maximum flow increases presumably as a result of an increased lung elastic recoil. Forced expiratory flows corrected for thoracic gas compression volume, lung volumes, and forced oscillation technique at 5-11-19 Hz were measured in 133 healthy subjects with a body mass index (BMI) ranging from 18 to 50 kg/m(2). Short-term temporal variability of ventilation heterogeneity was estimated from the interquartile range of the frequency distribution of the difference in inspiratory resistance between 5 and 19 Hz (R5-19_IQR). FRC % predicted negatively correlated with BMI (r = -0.72, P < 0.001) and with an increase in slope of either maximal (r = -0.34, P < 0.01) or partial flow-volume curves (r = -0.30, P < 0.01). Together with a slight decrease in residual volume, this suggests an increased lung elastic recoil. Regression analysis of R5-19_IQR against FRC % predicted and expiratory reserve volume (ERV) yielded significantly higher correlation coefficients by nonlinear than linear fitting models (r(2) = 0.40 vs. 0.30 for FRC % predicted and r(2) = 0.28 vs. 0.19 for ERV). In conclusion, temporal variability of ventilation heterogeneities increases in obesity only when FRC falls approximately below 65% of predicted or ERV below 0.6 liters. Above these thresholds distribution is quite well preserved presumably as a result of an increase in lung recoil.

Potential role of pentosidine on susceptibility to small airway closure in elderly and smoking asthma

Small airway closure in asthma is determined by a complex interaction of structural and functional characteristics including lung elastic recoil. Recently, we determined that loss of elastic recoil might be attributable to pentosidine level in the airways. This study was designed to investigate the influences of aging and smoking on small airway closure in asthma. Sixty-one patients with asthma (20 non-smoking young adult, 23 non-smoking elderly, and 18 smoking young adult) and 36 control subjects (12 non-smoking young adult, 11 non-smoking elderly, and 13 smoking young adult) were included. We assessed airway responses during methacholine provocation and calculated the closing index. In addition, we measured pentosidine levels in induced sputum from all study subjects. Pentosidine levels in induced sputum were markedly higher in asthmatic patients than in controls. In control subjects, the intergroup differences in pentosidine level among 3 subgroups were significant. Similarly, pentosidine levels were significantly higher in non-smoking elderly and smoking young adult asthmatics than in non-smoking young adult asthmatics. There was no significant difference in pentosidine levels between non-smoking elderly and smoking young adult asthmatics. The closing index was also significantly higher in non-smoking elderly and smoking young adult asthmatics than in non-smoking young adult asthmatics. Moreover, pentosidine levels in non-smoking elderly and smoking young adult asthmatics were closely correlated with closing index. We determined the correlation of pentosidine level with susceptibility to small airway closure in elderly and smoking asthmatics. Our results might facilitate the understanding of elderly and smoking asthma.

Pathogenesis of hyperinflation in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible. In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease. Development of hyperinflation during the course of COPD is insidious. Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation. Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease. Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD. The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD. We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease.

Respiratory safety pharmacology – Current practice and future directions

Current practice in respiratory safety pharmacology generally follows the guidance provided by the ICH document S7A and, in general, focuses on measures of pulmonary ventilation. Respiratory rate, tidal volume and/or a measure of arterial blood gases are the recommended ventilatory measurement parameters. Although these parameters will provide a measure of ventilation, other ventilatory parameters, which can provide mechanistic insight, should also be considered. Such parameters include inspiratory and expiratory times and flows and apneic time. Stimulation models involving exercise and exposure to elevated CO2 or reduced O2 should also be considered when enhancing measurement sensitivity or quantifying reductions in ventilatory functional reserve are desired. Although ventilatory measurements are capable of assessing the functional status of the respiratory pumping apparatus, such measurements are generally not capable of assessing the status of the other functional component of the respiratory system, namely, the gas exchange unit or lung. To characterize drug-induced effects on the gas exchange unit, measures of airway patency, lung elastic recoil and gas diffusion capacity need to be considered. Thus, a variety of methodologies and measurement endpoints are available for detecting and characterizing drug-induced respiratory dysfunction in animal models and should be considered when designing respiratory safety pharmacology studies.

Expiratory flows and airway inflammation in elderly asthmatic patients

Asthma in the elderly is often underrecognized and suboptimally treated, resulting in an increased morbidity and mortality. The characteristics of asthma-related bronchitis and its optimal treatment remain to be determined in this population. We aimed to compare lung function and airway inflammation in elderly and younger asthmatic subjects. Data from two induced sputum databases were analyzed in three groups of asthmatic subjects (18-30 y, n = 136; 31-59 y, n = 385; 60-72 y, n = 172) and one group of healthy elderly subjects (60-89 y, n = 16). Expiratory flows and induced sputum cell counts were analyzed. Airway obstruction was more marked in elderly asthmatics compared with healthy elderly or younger asthmatic subjects (p < 0.01). An increase in sputum neutrophils and a decrease in macrophages and lymphocytes were observed in elderly asthmatics (p < 0.0001). Neutrophil percentages significantly increased with asthma severity in the young and the middle-aged groups, while they remained similar in elderly asthmatics regardless of asthma severity (p < 0.05). Neutrophil percentages weakly correlated with the dose of ICS in all asthmatics (r = 0.17, p < 0.0001). Age and dose of ICS were independent predictors of neutrophil percentage in asthmatic subjects in a regression model (R(2) = 0.12). Asthma in the elderly is associated with a more marked airway obstruction and sputum neutrophilia. Both age and the dose of corticosteroids need to be considered in the interpretation of the clinical relevance of sputum neutrophil count.

Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry. The REPAIR study: study design, methodology and quality control of study assessments

Emphysema is characterized by the destruction of alveolar wall and enlargement of alveolar airspaces, resulting in a reduction of the total lung gas exchange area, loss of lung elastic recoil and hyperinflation. The REPAIR study (Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry) is the first proof-of-concept study of a new potential disease-modifying drug, Palovarotene©, an orally active, gamma selective retinoid agonist in patients with emphysema secondary to alpha-1-antitrypsin deficiency (AATD) as a model population for the general smoke-induced emphysema population. This article describes the study design as well as the effectiveness of the quality control that was implemented on the key efficacy endpoints, based on data derived from the placebo-treated subjects. In this multicentre, multinational study the implementation of standardized procedures included: careful site selection, use of trained staff, regular monitoring and machine calibration, use of biological controls and regular feedback to sites by an independent quality control centre. All of these procedures resulted in high-quality measurements of lung density, spirometry, static lung volumes and gas transfer. It was also confirmed that CT lung density was the most sensitive endpoint followed by TLco, FEV(1) and RV measured by body box.

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.

Supranormal Expiratory Airflow after Bilateral Lung Transplantation Is Associated with Improved Survival

flow volume loops (FVL) in some bilateral lung transplant (BLT) and heart-lung transplant (HLT) patients suggest variable extrathoracic obstruction in the absence of identifiable causes. These FVLs usually have supranormal expiratory and normal inspiratory flow rates (SUPRA pattern). characterize the relationship of the SUPRA pattern to predicted donor and recipient lung volumes, airway size, and survival. we performed a retrospective review of adult BLT/HLT patients. We defined the SUPRA FVL pattern as: (1) mid-vital capacity expiratory to inspiratory flow ratio (Ve50:Vi50) > 1.0, (2) absence of identifiable causes of extrathoracic obstruction, and (3) Ve50/FVC ≥ 1.5 s(-1). We calculated predicted total lung capacity (pTLC) ratio by dividing the donor pTLC by the recipient pTLC. We measured airway luminal areas on thoracic computer tomographic scans. We compared survival in patients with and without the SUPRA pattern. the SUPRA FVL pattern occurred in 56% of the 89 patients who qualified for the analysis. The pTLC ratio of SUPRA and non-SUPRA patients was 1.11 and 0.99, respectively (P = 0.004). A higher pTLC ratio was correlated with increased probability of the SUPRA pattern (P = 0.0072). Airway luminal areas were larger in SUPRA patients (P = 0.009). Survival was better in the SUPRA cohort (P = 0.009). the SUPRA FVL pattern was frequent in BLT/HLT patients. High expiratory flows in SUPRA patients could result from increased lung elastic recoil or reduced airway resistance, both of which could be caused by the pTLC mismatch. Improved survival in the SUPRA cohort suggests potential therapeutic approaches to improve outcomes in BLT/HLT patients.

PPARγ deficiency results in reduced lung elastic recoil and abnormalities in airspace distribution

BackgroundPeroxisome proliferator-activated receptor (PPAR)-γ is a nuclear hormone receptor that regulates gene expression, cell proliferation and differentiation. We previously described airway epithelial cell PPARγ deficient mice that develop airspace enlargement with decreased tissue resistance and increased lung volumes. We sought to understand the impact of airspace enlargement in conditionally targeted mice upon the physio-mechanical properties of the lung.MethodsWe measured elastic recoil and its determinants, including tissue structure and surface forces. We measured alveolar number using radial alveolar counts, and airspace sizes and their distribution using computer-assisted morphometry.ResultsAir vs. saline-filled pressure volume profiles demonstrated loss of lung elastic recoil in targeted mice that was contributed by both tissue components and surface tension, but was proportional to lung volume. There were no significant differences in surfactant quantity/function nor in elastin and collagen content between targeted animals and littermate controls. Importantly, radial alveolar counts were significantly reduced in the targeted animals and at 8 weeks of age there were 18% fewer alveoli with 32% more alveolar ducts. Additionally, the alveolar ducts were 19% larger in the targeted animals.ConclusionsOur data suggest that the functional abnormalities, including loss of recoil are secondary to altered force transmission due to differences in the structure of alveolar ducts, rather than changes in surfactant function or elastin or collagen content. These data further define the nature of abnormal lung maturation in the absence of airway epithelial cell PPARγ and identify a putative genetic determinant of dysanapsis, which may serve as a precursor to chronic lung disease.

Lighter than air: heliox breathing improves exercise tolerance in COPD

Dyspnoea and reduced exercise tolerance are the hallmarks of chronic obstructive pulmonary disease (COPD). In the advanced phases of the disease the ability to exercise is mainly limited by the combination of a reduced ventilatory capacity, increased ventilatory requirement and lung dynamic hyperinflation. Importantly, the aforementioned respiratory mehanical abnormalities are well recognised causes of exertional dyspnoea in COPD [1]. However, in a substantial number of patients a heightened perception of leg effort may reduce tolerance to cycle-ergometer exercise, while dyspnoea appears to be the main symptom limiting the ability to walk [2]. Regardless of this, there would be little question that, in patients with severe COPD and particularly in those subjects with predominant emphysema, maximal exercise tolerance is markedly reduced because of ventilatory limitation, dynamic hyperinflation and dyspnoea sensation. Figure 1⇓ illustrates the lung mechanical abnormalities that cause dyspnoea and exercise intolerance in COPD. Airflow obstruction could be the result of intrinsic airways narrowing, as observed in chronic bronchitis, or may be the result of airways collapse due to loss of lung elastic recoil, as observed in emphysema. Importantly, both these anatomical alterations cause a reduction in expiratory flow reserve. When this occurs, breathing is usually accommodated to a higher lung volume, to prevent the unpleasant sensation arising from the central airways and to permit adequate ventilation. As a result, dynamic lung hyperinflation develops due to well-refined actions of various neural and mechanical mechanisms, presumably to achieve the best compromise between the minimum amount of expiratory flow limitation and the least load for the inspiratory muscles. Breathing under conditions of expiratory flow limitation is associated with an increased work of breathing (WOB) and could lead to two basic physiological consequences: 1) airways undergoing mechanical collapse trigger neural signals elaborated at the cortical level, i.e. dyspnoea sensation; …