Increased Air Trapping Research Articles

Airflow Obstruction in Adults with Williams Syndrome and Mice with Elastin Insufficiency.

Williams–Beuren syndrome (WS) results from the deletion of 25–27 coding genes, including elastin (ELN), on human chromosome 7q11.23. Elastin provides recoil to tissues; emphysema and chronic obstructive pulmonary disease have been linked to its destruction. Consequently, we hypothesized that elastin insufficiency would predispose to obstructive features. Twenty-two adults with WS (aged 18–55) and controls underwent pulmonary function testing, 6 min walk, and chest computed tomography (CT). Lung and airspace dimensions were assessed in Eln+/− and control mice via microCT and histology. The forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) were lower in adults with WS (p < 0.0001 and p < 0.05, respectively). The FEV1/FVC ratio was more frequently below the lower limit of normal in cases (p < 0.01). The ratio of residual volume to total lung capacity (RV/TLC, percent predicted) was higher in cases (p < 0.01), suggesting air trapping. People with WS showed reduced exercise capacity (p < 0.0001). In Eln+/− mice, ex vivo lung volumes were increased (p < 0.0001), with larger airspaces (p < 0.001). Together these data show that elastin insufficiency impacts lung physiology in the form of increased air trapping and obstruction, suggesting a role for lung function monitoring in adults with WS.

Bronchial inflammation biomarker patterns link humoral immunodeficiency with bronchiectasis-related small airway dysfunction.

The progression of chronic destructive lung disease in patients with humoral immunodeficiency (ID) and concomitant development of bronchiectasis is difficult to prevent. Lung function tests in these patients typically show bronchial obstruction of the small airways in combination with increased air trapping in the distal airways, which is consistent with small airway dysfunction. The objective was to assess the grade of chronic lower airway inflammation and small airway dysfunction from induced sputum and the corresponding local pro-inflammatory mediator pattern to discriminate patients affected by bronchiectasis-related Small Airway Dysfunction (SAD). In a prospective design, 22 patients with ID (14 CVID, 3 XLA, 3hyper-IgM syndrome, 1hyper-IgE syndrome and low IgG levels due to treatment with rituximab and 1 SCID after BMT and persistent humoral defect) and 21healthy controls were examined. Lung function, Fraction Expiratory Nitric Oxide (FeNO) and pro-inflammatory cytokine levels were compared in subsets of patients with (ID+BE) and without bronchiectasis (ID) pre-stratified using high-resolution computed tomography (HRCT) scans and control subjects. Analysis of induced sputum showed significantly increased total cell counts and severe neutrophilic inflammation in ID. The concomitant SAD revealed higher total cell numbers compared to ID. Bronchial inflammation in ID is clearly mirrored by pro-inflammatory mediators IL-1β, IL-6 and CXCL-8, whilst TNF-α revealed a correlation with lung function parameters altered in the context of bronchiectasis-related Small Airway Dysfunction. In spite of immunoglobulin substitution, bronchial inflammation was dominated by neutrophils and was highly increased in patients with ID+BE. Notably, the pro-inflammatory cytokines in patients with ID were significantly increased in induced sputum. The context-dependent cytokine pattern in relation to the presence of concomitant bronchiectasis associated with SAD in ID patients could be helpful in delimiting ID patient subgroups and individualizing therapeutic approaches.

Large lungs may predict increased air trapping in navy divers.

Navy divers tend to have large lungs and low expiratory flow rates in the terminal portion of a spirogram. We examined Finnish Navy divers for the presence of air trapping, airway obstruction, and functional airway compression, and their association with lung volumes. Divers (n = 57) and non‐diving men (n = 10) underwent a variety of pulmonary function tests. The amount of trapped air was calculated as the subtraction of the total lung capacity (TLC) measured in a single‐breath helium dilution test from the TLC in body plethysmography (TLCb). Mean vital capacity (VC) was 6.4 L in the divers versus 5.8 L in the controls (p = 0.006) and TLCb 8.9 L in the divers versus 8.1 L in the controls (p = 0.002). No difference existed between them in the amount of trapped air. However, we found break points in a linear regression model (Davies test) between trapped air and several pulmonary parameters. Those individuals above the break points had lower ratio of forced expiratory volume in first second to forced vital capacity, lower resistance of airways, and higher reactance than those below the break points. In conclusion, navy divers had larger lungs than controls. Large lung volumes (VC >7.31 L or >122% of predicted value) were associated with air trapping. Furthermore, large volumes of air trapping (>1.1 L) were associated with increased residual volume (RV) and RV/TLCb. Despite no concurrent obstruction, functional airway compression, or reduced diffusing capacity, this slowly ventilated trapped air might remain disadvantageous for divers.

Raised sputum extracellular DNA confers lung function impairment and poor symptom control in an exacerbation-susceptible phenotype of neutrophilic asthma

BackgroundExtracellular DNA (e-DNA) and neutrophil extracellular traps (NETs) are linked to asthmatics airway inflammation. However, data demonstrating the characterization of airway inflammation associated with excessive e-DNA production and its impact on asthma outcomes are limited.ObjectiveTo characterize the airway inflammation associated with excessive e-DNA production and its association with asthma control, severe exacerbations and pulmonary function, particularly, air trapping and small airway dysfunction.MethodsWe measured e-DNA concentrations in induced sputum from 134 asthma patients and 28 healthy controls. We studied the correlation of e-DNA concentrations with sputum neutrophils, eosinophils and macrophages and the fractional exhaled nitric oxide (FeNO). Lung function was evaluated using spirometry, body plethysmography, impulse oscillometry and inert gas multiple breath washout. We stratified patients with asthma into low-DNA and high-DNA to compare lung function impairments and asthma outcomes.ResultsPatients with severe asthma had higher e-DNA concentration (54.2 ± 42.4 ng/µl) than patients with mild-moderate asthma (41.0 ± 44.1 ng/µl) or healthy controls (26.1 ± 16.5 ng/µl), (all p values < 0.05). E-DNA concentrations correlated directly with sputum neutrophils (R = 0.49, p < 0.0001) and negatively with sputum macrophages (R = − 0.36, p < 0.0001), but neither with sputum eosinophils (R = 0.10, p = 0.26), nor with FeNO (R = − 0.10, p = 0.22). We found that 29% of asthma patients (n = 39) had high e-DNA concentrations above the upper 95th percentile value in healthy controls (55.6 ng /μl). High-DNA was associated with broad lung function impairments including: airflow obstruction of the large (FEV1) and small airways (FEF50%, FEF25–75), increased air trapping (RV, RV/TLC), increased small airway resistance (R5-20, sReff), decreased lung elasticity (X5Hz) and increased ventilation heterogeneity (LCI), (all P values < 0.05). We also found that high e-DNA was associated with nearly three-fold greater risk of severe exacerbations (OR 2·93 [95% CI 1.2–7.5]; p = 0·012), worse asthma control test (p = 0.03), worse asthma control questionnaire scores (p = 0.01) and higher doses of inhaled corticosteroids (p = 0.026).ConclusionIncreased production of extracellular DNA in the airway characterizes a subset of neutrophilic asthma patients who have broad lung function impairments, poor symptom control and increased risk of severe exacerbations.

The Use of Infant Pulmonary Function Tests in the Diagnosis of Neuroendocrine Cell Hyperplasia of Infancy

Infant pulmonary function tests (iPFTs) in subjects with neuroendocrine cell hyperplasia of infancy (NEHI) have demonstrated substantial expiratory airflow obstruction and air trapping. Can indices from iPFTs be used in the diagnosis of NEHI? This is an observational case-control study evaluating iPFT results from a registry of patients assessed at the Hadassah Hebrew University Medical Center between 2008 and 2018. iPFTs results in infants with NEHI were compared to two disease control infant groups (infants evaluated for recurrent wheezing and infants evaluated due to prematurity) and a spirometry control group of infants with normal expiratory airflow, using the Kruskal-Wallis test. Receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy of iPFT indices. We evaluated iPFT data in 481 infants (15, NEHI; 292, wheezing; 128, premature; and 46, spirometry control group). Infants with NEHI had significantly increased trapped air volumes (median functional residual capacity measured with infant whole-body plethysmography [FRCpleth] was 199%predicted; median ratio of residual volume to total lung capacity was 59%predicted) when compared with results in all evaluated groups of infants (P< .001), including multiple pairwise comparisons. Airflow limitation was demonstrated in infants with NEHI when compared with the infants in the spirometry control group but was similar to the two disease control groups. FRCpleth had the best discriminatory ability for NEHI diagnosis, with an FRCpleth≥ 150%predicted demonstrating a ROC of 0.91 (95%CI, 0.82-1.00), sensitivity of 86.7%(95%CI, 59.5%-98.3%), and specificity of 95.5%(95%CI, 93.2%-97.3%). Findings on iPFTs of markedly increased air trapping, out of proportion to the degree of airflow limitation, are characteristic of infants with NEHI. iPFT results demonstrating an FRCpleth≥ 150%predicted are highly specific for NEHI and may aid in early diagnosis. Further research is required to confirm these findings in a prospective cohort and to understand the pathophysiologic explanation for these findings.

Decapneization as supportive therapy for the treatment of status asthmaticus: a case report

BackgroundAcute severe asthma is a life-threatening medical emergency. Characteristics of asthma include increased airway resistance and dynamic pulmonary hyperinflation that can manifest in dangerous levels of hypercapnia and acidosis, with significant mortality and morbidity. Severe respiratory distress can lead to endotracheal intubation followed by mechanical ventilation, which can cause increased air trapping with dynamic hyperinflation, predisposing the lungs to barotraumas.Case presentationThe present case report describes the use of the minimally invasive ECCO2R ProLUNG® (Estor) with protective low-tidal-volume ventilation, in a Caucasian patient with near-fatal asthma and with no response to conventional therapy.ConclusionsSince hypercarbia rather than hypoxemia is the primary abnormality in status asthmaticus, a rescue therapeutic strategy combining the ECCO2R membrane ProLUNG® (Estor) with ultra-protective low-tidal-volume ventilation can be successfully applied to limit the risk of severe barotrauma during invasive mechanical ventilation. ECCO2R ProLUNG® is a partial respiratory support technique that, based on the use of an extracorporeal circuit with a gas-exchange membrane, achieves relevant CO2 clearance directly from the blood using double-lumen venous-venous vascular access, at blood flow in the range of 0.4–1.0 L/minute.

Metrics of lung tissue heterogeneity depend on BMI but not age.

Altered parenchymal microstructure and complexity have been observed in older age. How to distinguish between healthy, expected changes and early signs of pathology remains poorly understood. An objective quantitative analysis of computed tomography imaging was conducted to compare mean lung density, tissue density distributions, and tissue heterogeneity in 16 subjects, 8 aged >60 yr who were gender and body mass index matched with 8 subjects aged <30 yr. Subjects had never been smokers, with no prior respiratory disease, and no radiologically identified abnormalities on computed tomography. Volume-controlled breath hold imaging acquired at 80% vital capacity (end inspiration) and 55% vital capacity (end expiration) were used for analysis. Mean lung density was not different between the age groups at end inspiration ( P = 0.806) but was larger in the younger group at end expiration (0.26 ± 0.033 vs. 0.22 ± 0.026, P = 0.008), as is expected due to increased air trapping in the older population. However, gravitational gradients of tissue density did not differ with age; the only difference in distribution of tissue density between the two age groups was a lower density in the apices of the older group at end expiration. The heterogeneity of the lung tissue assessed using two metrics showed significant differences between end inspiration and end expiration, no dependence on age, and a significant relationship with body mass index at both lung volumes when heterogeneity was calculated using quadtree decomposition but only at end expiration when using a fractal dimension. NEW & NOTEWORTHY Changes to lung tissue heterogeneity can be a normal part of aging but can also be an early indicator of disease. We use novel techniques, which have previously not been used on thoracic computed tomography imaging, to quantify lung tissue heterogeneity in young and old healthy subjects. Our results show no dependence on age but a significant correlation with body mass index.

Late-onset asthma: current perspectives.

Because the pathophysiology of asthma has diverse characteristics, to manage the disease effectively, it is important for clinicians to distinguish among the clinical phenotypes. Among them, adult-onset asthma, that is, late-onset asthma (LOA), is increasing because of the aging of the population. The phenotype of LOA is largely divided into two types according to the presence or absence of eosinophilic inflammation, T-helper (Th)2- and non–Th2-associated LOA. Especially in Th2 LOA related to rhinosinusitis, as pulmonary function at onset is poor and asthma exacerbations occur frequently, it is important to detect this phenotype in the early phase by using a biomarker of Th2-type inflammation such as fractional exhaled nitric oxide (FENO). As non–Th2-LOA is often resistant to corticosteroids, this phenotype often requires another treatment strategy such as macrolide, diet, or smoking cessation. We often struggle with the management of LOA patients due to a lack of evidence; therefore, the elucidation of the mechanism of LOA contributes to increased efficiency of diagnosis and treatment of LOA. Age-related immune system and structural changes are thought to be associated with the pathophysiology of LOA. In the former case, changes in inflammatory cell function such as variations in the innate immune response and acquisition of autoimmunity or upregulation of oxidative stress are thought to be involved in the mechanism. Meanwhile, the latter can also become triggers or exacerbating factors of LOA via enhancement of airway hyperresponsiveness, decline in lung function, increased air trapping, and reduction in chest wall compliance. Therefore, appropriate individualized management in LOA may be possible through precisely assessing the pathophysiology based on age-related functional changes, including the immune and structural system.

Effects of valve timing, valve lift and exhaust backpressure on performance and gas exchanging of a two-stroke GDI engine with overhead valves

The current demand for fuel efficient and lightweight powertrains, particularly for application in downsized and hybrid electric vehicles, has renewed the interest in two-stroke engines. In this framework, an overhead four-valve spark-ignition gasoline engine was modified to run in the two-stroke cycle. The scavenging process took place during a long valve overlap period around bottom dead centre at each crankshaft revolution. Boosted intake air was externally supplied at a constant pressure and gasoline was directly injected into the cylinder after valve closure. Intake and exhaust valve timings and lifts were independently varied through an electrohydraulic valve train, so their effects on engine performance and gas exchanging were investigated at 800rpm and 2000rpm. Different exhaust backpressures were also evaluated by means of exhaust throttling. Air trapping efficiency, charging efficiency and scavenge ratio were calculated based on air and fuel flow rates, and exhaust oxygen concentration at fuel rich conditions. The results indicated that longer intake and exhaust valve opening durations increased the charge purity and hence torque at higher engine speeds. At lower speeds, although, shorter valve opening durations increased air trapping efficiency and reduced the estimated supercharger power consumption due to lower air short-circuiting. A strong correlation was found between torque and charging efficiency, while air trapping efficiency was more associated to exhaust valve opening duration. The application of exhaust backpressure, as well as lower intake/exhaust valve lifts, made it possible to increase air trapping efficiency at the expense of lower charging efficiency.

Exacerbations in neuroendocrine cell hyperplasia of infancy are characterized by increased air trapping.

Neuroendocrine cell Hyperplasia of Infancy (NEHI) presents with tachypnea, retractions, hypoxemia, and often failure to thrive. The radiologic and physiologic findings in infants with NEHI have been well described with a distinct geographic pattern of ground-glass opacities on chest computerized tomography imaging and profound air-trapping on infant pulmonary function testing. Despite gradual improvement over time, unexplained exacerbation has been observed but not well characterized. We present physiological and radiological changes of increased air-trapping during acute exacerbations in two older children with NEHI who had previously experienced significant clinical improvement. These cases illustrate previously undescribed manifestations of NEHI in older children.

Detrimental effects of secondhand smoke exposure on infants with cystic fibrosis

Secondhand smoke (SHS) has deleterious respiratory, immune, and nutritional effects in children, but there is little data regarding the effects of SHS exposure in infants with cystic fibrosis (CF). A retrospective chart review was undertaken from 2008 to 2012 of 75 infants with CF. Growth, lung function, Chest CT imaging, and microbiologic characteristics were compared between 4 and 12 months for SHS and non-SHS exposed patients. SHS exposed infants with CF had decreased growth between 4 and 12 months compared to non-SHS exposed infants. SHS exposure was associated with increased bronchodilator responsiveness and air trapping, but no other lung function or radiologic differences. SHS exposure was also associated with increased methicillin resistant Staphylococcus aureus (MRSA) and anaerobic growth on respiratory culture. There was no difference in Pseudomonas aeruginosa between groups. There were no differences in antibiotic use or hospitalizations between the groups. SHS exposure in CF infants is associated with diminished growth, increased air trapping and bronchodilator responsiveness, and propensity to culture MRSA and facultative anaerobic bacteria, suggesting the need for early, aggressive parental smoking cessation interventions to prevent SHS exposure complications.

Do small airway abnormalities characterize asthma phenotypes? In search of proof

The role of small airway abnormalities in asthma pathogenesis has been extensively studied and debated for several decades. However, whether or not small airway abnormalities play a relevant role in specific phenotypes of asthmatic patients and contribute to clinical presentation is largely unknown. In the present review, we evaluated available data on the role of small airways in severe asthma, with a further focus on asthma in smokers and asthma in the elderly. These phenotypes are characterized by a poor response to treatment and they can represent a model of greater small airway impairment. In severe asthmatics, small airway involvement has been shown through evidence of both distal inflammation and of increased air trapping. The few available data on asthmatics who smoke, and elderly asthmatics, similarly suggests that small airway abnormalities contribute to the pathogenesis of the disease. In this perspective, there could be a rationale for specifically assessing small airway impairment in these patients and for clinical studies evaluating whether pharmacological approaches targeting the more peripheral airways result in clinical benefits beyond conventional therapy.

Chronic lung disease of prematurity and respiratory outcome at eight years of age

The study aimed to determine the respiratory outcome of children who had chronic lung disease of prematurity (CLD) compared with a preterm control group of children at school age. Fifty-two preterm infants with CLD born between 26 and 33 weeks gestation were assessed regarding respiratory illness with 47 having lung function testing. Information regarding respiratory illness was obtained from 52 children in the birthweight-matched control group of whom 45 had lung function testing. The results were compared between the CLD and control groups. There was no difference in respiratory symptomatology between CLD groups and control preterm infants. On lung function testing, a significantly lower mean forced expiratory flow at 25-75% of vital capacity was identified compared with the preterm controls (P=0.024). This significant difference did not persist after bronchodilator therapy. There was no evidence of increased air trapping or bronchial hyper-reactivity in the CLD children compared with the controls. Lung function in CLD children is largely normal in comparison with preterm controls, apart from some evidence of reversible small airway obstruction. Respiratory symptomatology is not increased in chronic disease children in comparison with control preterm children.

Chronic hyperplastic eosinophilic sinusitis as a predictor of aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease (AERD) is a disease of intense eosinophilic inflammation that can produce fibrosis, hyperplasia, and remodeling. To investigate the usefulness of quantifying severity of chronic hyperplastic eosinophilic sinusitis in predicting the presence of AERD. Data were compared between asthmatic patients who reported exacerbations after aspirin ingestion and those who did not. The primary outcome measure was severity of sinusitis using a validated computed tomography (CT) scan-based scoring system. Indices of lower airway remodeling and other markers of inflammation were also evaluated. Twenty-one patients with AERD were compared with 19 patients with aspirin-tolerant asthma (ATA). Patients were well matched for asthma severity as shown by their similar lung function as measured by postbronchodilator forced expiratory volume in 1 second. Patients with AERD were distinguished by their sinus CT scores (AERD patients: 16.9; 95% confidence interval [CI], 13.4-21.3; ATA patients: 6.2; 95% CI, 4.2-9.1; P < .001), and they were considerably more likely to have nasal polyps (AERD patients: 90%; ATA patients: 26%; P < .001). In addition, AERD patients demonstrated increased total lung capacity (AERD patients: 107.9%; 95% CI, 99.9%-117.6%; ATA patients: 98.0%; 95% CI, 93.7%-102.5%; P = .05), reflecting a trend toward increased air trapping. No significant differences occurred in diffusing capacity, exhaled nitric oxide, eosinophilia, or exhaled breath condensate pH. AERD can be distinguished from ATA by the extent of hyperplasia on CT scan and the presence of nasal polyps. We hypothesize that AERD represents a remodeling process that affects both the upper and lower airways.

Effect of induced oligohydramnios on fetal lung development

To investigate the impact of oligohydramnios on fetal growth, development, and lung function, amniotic fluid was shunted from alternate gestational sacs into the maternal peritoneal cavity at 23 days' gestation in the fetal rabbit. Uninstrumented fetuses served as controls. Oligohydramnios was confirmed at the time of planned cesarean delivery on either day 26 or 28. Fetuses subjected to prolonged oligohydramnios had significantly decreased body weight at 26 (p = 0.002) and 28 days (p = 0.007). Similarly, lung weight was decreased at 26 (p = 0.02) and 28 days (p = 0.005). There was a trend toward decreased maximum lung volume for instrumented fetuses at 28 days (p = 0.07). Deflation limbs of the pressure-volume curves revealed significantly increased air trapping for instrumented fetuses at 28 days. These studies suggest not only a detrimental effect of oligohydramnios on fetal body and lung weight but also a beneficial effect of premature rupture of membranes on fetal lung function. Analysis of phospholipid and histologic changes is currently under way.

Influence of head-dependent positions on lung volume and oxygen saturation in chronic air-flow obstruction.

We investigated the influence of head-dependent positions upon functional residual capacity (FRC) and arterial oxygen saturation in 25 patients with clinically stable chronic air-flow obstruction and 25 normal subjects. Lung volume was measured by gas dilution in normal subjects and by plethysmography in patients with chronic obstructive pulmonary disease (COPD). Arterial oxygen saturation was determined by ear oximetry. In normal subjects, sitting FRC declined by 29.9% when a horizontal-supine posture was assumed, but underwent little further change as the supine subject was tilted head-downward to -25 degrees. Lateral decubitus positions caused declines from sitting FRC of 17.1% at 0 degrees, and 27.4% at -25 degrees. In contrast, patients with COPD experienced negligible changes in lung volume as position was varied. The mean falls from sitting FRC were 3.5% and 1.9% in the 0 degree supine and 0 degree lateral decubitus postures, respectively, and little further volume loss occurred in head-dependency. Eight patients actually increased FRC when recumbent. Positional lung volume changes measured by gas dilution exceeded those measured by plethysmography, suggesting that increased air trapping helped to maintain FRC as position was altered. Patients with COPD did not desaturate in any position tested. We conclude that patients with advanced COPD conserve lung volume and do not desaturate when tipped into head-dependent positions. Reduction of FRC is unlikely to contribute to the hypoxemia or dyspnea previously reported to occur in these patients during chest physiotherapy.