Conventional Lung Function Tests Research Articles

Impulse oscillometry for the evaluation and management of pediatric asthma

Asthma is the most common chronic disease during childhood. While most of characteristic structural changes in asthma have been identified in the large airways, there is a growing recognition of peripheral airway dysfunction as a crucial factor in the development of asthma. This dysfunction is a defining feature in adults with persistent asthma. However, little is known about the contribution of small airway impairment in children with asthma due to the relatively low sensitivity of conventional lung function tests, such as spirometry. Recently, new diagnostic tools that are sensitive to both large and small airway function and inflammation have been introduced in clinical practice. The most widely studied of these tools in preschool and school-aged children is impulse oscillometry (IOS). This review addresses the latest findings on the usefulness of IOS in identifying small airway dysfunction, predicting the risk of uncontrolled asthma, and ultimately improving the diagnosis and management of asthma in children.

Long-term pulmonary outcome of children with congenital diaphragmatic hernia: functional lung MRI using matrix-pencil decomposition enables side-specific assessment of lung function

ObjectivesIn patients with congenital diaphragmatic hernia (CDH) the exact functional outcome of the affected lung side is still unknown, mainly due to the lack of spatially resolved diagnostic tools. Functional matrix-pencil decomposition (MP-) lung MRI fills this gap as it measures side-specific ventilation and perfusion. We aimed to assess the overall and side-specific pulmonary long-term outcomes of patients with CDH using lung function tests and MP-MRI.MethodsThirteen school-aged children with CDH (seven with small and six with large defect-sized CDH, defined as > 50% of the chest wall circumference being devoid of diaphragm tissue) and thirteen healthy matched controls underwent spirometry, multiple-breath washout, and MP-MRI. The main outcomes were forced expiratory volume in 1 second (FEV1), lung clearance index (LCI2.5), ventilation defect percentage (VDP), and perfusion defect percentage (QDP).ResultsPatients with a large CDH showed significantly reduced overall lung function compared to healthy controls (mean difference [95%-CIadjusted]: FEV1 (z-score) −4.26 [−5.61, −2.92], FVC (z-score) −3.97 [−5.68, −2.26], LCI2.5 (TO) 1.12 [0.47, 1.76], VDP (%) 8.59 [3.58, 13.60], QDP (%) 17.22 [13.16, 21.27]) and to patients with a small CDH. Side-specific examination by MP-MRI revealed particularly reduced ipsilateral ventilation and perfusion in patients with a large CDH (mean difference to contralateral side [95%-CIadjusted]: VDP (%) 14.80 [10.50, 19.00], QDP (%) 23.50 [1.75, 45.20]).ConclusionsData indicate impaired overall lung function with particular limitation of the ipsilateral side in patients with a large CDH. MP-MRI is a promising tool to provide valuable side-specific functional information in the follow-up of patients with CDH.Clinical relevance statementIn patients with congenital diaphragmatic hernia, easily applicable MP-MRI allows specific examination of the lung side affected by the hernia and provides valuable information on ventilation and perfusion with implications for clinical practice, making it a promising tool for routine follow-up.Key Points• Functional matrix pencil decomposition (MP) MRI data from a small sample indicate reduced ipsilateral pulmonary ventilation and perfusion in children with large congenital diaphragmatic hernia (CDH).• Easily applicable pencil decomposition MRI provides valuable side-specific diagnostic information on lung ventilation and perfusion. This is a clear advantage over conventional lung function tests, helping to comprehensively follow up patients with congenital diaphragmatic hernia and monitor therapy effects.

Evaluation of lung function in a German single center cohort of young patients with sickle cell disease using EIT and standard techniques.

Sickle cell disease (SCD) is a very common autosomal recessive hemoglobinopathy leading to multiple pulmonary complications that are closely associated with mortality. The pathophysiology of chronic pulmonary involvement is not yet fully understood and no specific therapies are available. The aim of this cross-sectional study was to characterize the lung function of children and young adolescents with SCD in a German single-center cohort and to extend conventional lung function testing by the use of a new imaging method. We performed spirometry and body plethysmography in 35 children and young adults with hemoglobin SS, SC, S/β-thalassemia as well as 50 controls. These data were compared with clinical characteristics and typical laboratory parameters of hemolysis and disease activity in SCD. To identify lung inhomogeneities, for example due to atelectasis, hyperinflation, air trapping or vascular occlusions, we used the promising new method of electrical impedance tomography (EIT) and calculated global inhomogeneity indices. Lung function of patients with SCD was significantly reduced compared to that of healthy controls. When the result was found to be pathological, the most commonly observed type of breathing disorder was classified as restrictive. Laboratory parameters showed typical features of SCD including decreased levels of hemoglobin and hematocrit and elevated levels of leucocytes, platelets, lactate dehydrogenase and total bilirubin. However, there was no correlation between blood values and reduced lung function. Electrical impedance tomography (EIT) revealed no abnormalities in SCD patients compared to healthy controls. In particular, we were unable to demonstrate any regional inhomogeneities in lung ventilation. In our study, SCD patients showed impaired lung function, with a relevant percentage of patients suffering from restrictive breathing disorder. Signs of obstruction could not be detected. Electrical impedance tomography (EIT) measurements revealed no unevenness that would suggest air entrapment, blockage of blood vessels, excessive inflation, obstruction, or other forms of lung disease. Additionally, the reduction in lung function observed in SCD patients was not related to the disease severity or laboratory test results.

Adherence, reliability, and variability of home spirometry telemonitoring in cystic fibrosis.

Forced spirometry is the gold standard to assess lung function, but its accessibility may be limited. By contrast, home spirometry telemonitoring allows a multi-weekly lung function follow-up but its real-life adherence, reliability, and variability according to age have been poorly studied in patients with CF (PwCF). We aimed to compare real-life adherence, reliability and variability of home spirometry between children, teenagers and adults with CF. This real-life observational study included PwCF followed for six months in whom lung function (i.e, forced expiratory volume maximum in 1 s (FEV1), forced vital capacity (FVC), forced mid-expiratory flow (FEF) and FEV1/FVC ratio) was monitored by both conventional and home spirometry between July 2015 and December 2021. The adherence, reliability and variability of home spirometry was assessed in all PwCF and compared between children (<12years old), teenagers (12-18 years old) and adults. 174 PwCF were included (74 children, 43 teenagers and 57 adults). Home spirometry was used at least one time per week by 64.1 ± 4.9% PwCF, more frequently in children and teenagers than in adults (79.4 ± 2.9%, 69.2 ± 5.5% and 40.4 ± 11.5% respectively). The reliability to conventional lung function testing was good for all assessed parameters (e.g., FEV1: r = 0.91, p < 0.01) and the variability over the 6 months of observation was low (FEV1 coefficient of variation = 11.5%). For each parameter, reliability was better, and the variability was lower in adults than in teenagers than in children. Home spirometry telemonitoring appears to be a reliable tool for multi-weekly lung function follow-up of PwCF.

Impulse oscillometry system for assessing small airway dysfunction in pediatric bronchiolitis obliterans; association with conventional pulmonary function tests.

Impulse oscillometry system (IOS) is a simple, and less invasive method for assessing small to total airway resistance in children. We analyzed the correlation between IOS, spirometry, and plethysmographic parameters performed for the diagnosis of pediatric BO patients. A total of 89 IOS assessments of pediatric BO patients or children without lung disease were included, and the relationship between pulmonary function tests (PFTs) and diagnostic performance was analyzed. R5, R5-20, X5, and AX were statistically significantly worse in the BO group. In general linear correlation analysis, R5% (adjusted β [aβ], -0.59; p < 0.001) and AX % (aβ, -0.9; p < 0.001) showed the strongest correlation with conventional PFT parameters. R5% and AX % also showed the highest correlation with FEF25-75% (aβ, -0.48; p < 0.001 and aβ, -0.83; p < 0.001), and sRaw % (aβ, -0.73; p = 0.003 and aβ, -0.59; p = 0.008, respectively). Multivariate logistic regression analysis showed that R5 Z-score showed the highest ORs with FEV1 (OR = 3.94, p = 0.006), FEF25-75% (OR = 5.96, p = 0.005), and sRaw % (OR = 4.85, p = 0.022). Receiver operating curve analysis suggested AX % and R5% as the most optimal IOS parameters for BO diagnostic performance with the area under the curve of 0.915 and 0.882, respectively. In conclusion, R5 and AX are the parameters that can independently identify the severity of airway obstruction in pediatric BO patients without conventional lung function tests. IOS is an easy-to-perform, and reliable diagnostic method capable of detecting pathological obliteration of the small airways in children with BO.

Multiple breath washout: measuring early manifestations of lung pathology.

The multiple breath washout (MBW) test measures the efficiency of gas mixing in the lungs and has gained significant interest over the past 20 years. MBW outcomes detect early lung function impairment and peripheral airway pathology, through its main outcome measure lung clearance index (LCI). LCI measures the number of lung turnovers required to washout an inert tracer gas. MBW is performed during normal (tidal) breathing, making it particularly suitable for young children or those who have trouble performing forced manoeuvres. Additionally, research in chronic respiratory disease populations has shown that MBW can detect acute clinically relevant changes before conventional lung function tests, such as spirometry, thus enabling early intervention. The development of technical standards for MBW and commercial devices have allowed MBW to be implemented in clinical research and potentially routine clinical practice. Although studies have summarised clinimetric properties of MBW indices, additional research is required to establish the clinical utility of MBW and, if possible, shorten testing time. Sensitive, feasible measures of early lung function decline will play an important role in early intervention for people living with respiratory diseases.Educational aimTo describe the multiple breath washout test, its applications to lung pathology and respiratory disease, as well as directions for future research.

Evaluation of cardiopulmonary exercise test in the prediction of disease progression in systemic sclerosis.

Cardiopulmonary exercise test (CPET) is a widely used examination to predict the prognosis of many chronic pulmonary diseases, and it has also been tested in systemic sclerosis (SSc) with a focus on the development of pulmonary hypertension. CPET is a highly informative non-invasive tool that provides a more complex information than conventional lung function tests to predict the course of cardiopulmonary diseases, as it provides a general overview of the aerobic metabolism, influenced by pulmonary, cardiovascular and peripheral muscle function. The purpose of this investigation was to assess if the progression and the development of poor overall disease outcome in SSc can be predicted by this method. Twenty-nine SSc patients were investigated prospectively with standard follow-up plus CPET for a mean of 3.7 years to match the results of conventional evaluation modalities and CPET. A composite end-point of several serious outcomes reflecting SSc-related vascular and cardiopulmonary damage was set up, and the predictive value of and correlations between the CPET parameters and resting lung function and echocardiography variables were assessed. None of the clinical parameters, resting lung function or echocardiographic test results proved to be predictive of the development of the endpoint of poor prognosis in this cohort. In contrast, several CPET parameters were found to discriminate between SSc patients with or without adverse outcome. The detection of desaturation (at any CPET test) was associated with a higher risk of poor prognosis (OR:5.265). VO2 and VE/VCO2 at baseline correlated with the annual decrease in FVC, anaerobic threshold with the development of digital ulcers, and VE/VO2 with the increase in pulmonary arterial pressure. Several CPET parameters obtained at the beginning of follow-up are informative of the appearance of various adverse end-points. CPET is a feasible examination in the care of SSc patients and provides excess information to current standard follow-up examinations.

The role of impulse oscillometry in the management of asthma when forced expiratory maneuvers are contraindicated: case series and literature review

Objectives: The impulse oscillometry system (IOS) provides an alternative method of lung function testing for patients in whom forced expiratory manoeuvres are contraindicated, such as those with inherited vascular connective tissue disorders. Here we examine the role of IOS in the diagnosis and monitoring of asthma in such patients through a clinical case series and literature review. Methods: The clinical case series comprised of data from 12 patients with inherited connective tissue disorders representing 32 clinical encounters. Of these, 11 encounters were for asthma diagnosis and 21 were for asthma monitoring. Symptoms, exhaled nitric oxide (FeNO) and IOS were assessed at each encounter. Results: In the clinical case series, 5 of 6 patients with likely asthma (as determined by physician review and exhaled nitric oxide testing) had abnormal IOS parameters compared with 0 of 5 of those with unlikely asthma. In the monitoring group, 11 encounters resulted in treatment escalation (demonstrating suboptimal control), and 8 resulted in no change to treatment (good control). Six of 11 of those with suboptimal control had abnormalities in ≥3 IOS parameters, with R5 and R5-20 most frequently affected. Only 1 of 8 of those with good control had abnormalities in ≥3 IOS parameters. Conclusions: IOS can be used as an alternative to conventional lung function testing to support the diagnosis and monitoring of asthma when forced expiratory manoeuvres are contraindicated. Larger studies are required to establish severity and treatment escalation thresholds and provide clearer comparisons with spirometry values.

Plasma Fibrinogen as a Biomarker of Stable and Exacerbated Chronic Obstructive Pulmonary Disease

Study Design: An experimental, comparative, cross-sectional study Place and Duration of Study: Department of Physiology, Federal Post Graduate Medical Institute (FPGMI), Sheikh Zayed Medical Complex Lahore, Pakistan from August 2013 to 2014 Background: Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease, but is a partially reversible chronic inflammatory condition characterized by airway obstruction. COPD remains under-diagnosed and under-treated because the only available diagnostic method at present is testing lung functions by spirometry which is not helpful to determine the severity and clinical outcomes of the disease. Circulating biomarkers are under consideration for various diseases worldwide. Plasma fibrinogen is emerging as one of the most promising biomarkers of COPD in smokers. Objective: The objective of this study is to investigate if plasma fibrinogen can serve as a diagnostic biomarker of COPD in smokers, and if its further higher levels are seen in the exacerbated state of the disease in comparison to the stable disease. Materials and Methods: 75 middle-aged to old-age smokers of either gender were selected. Lung functions of every participant were measured to determine Forced Expiratory Volume in the first second (FEV1), Forced Vital Capacity (FVC), and the ratio of FEV1/FVC by spirometry. On the basis of the results of the tests, subjects were divided into three groups; firstly, the control group of chronic smokers without COPD, secondly, smokers with COPD in a stable state, and thirdly, patients in an exacerbated state of COPD. Plasma fibrinogen was quantitatively estimated in every individual of all three groups by the Clauss method using the Hemostat Fibrinogen kit. Results: The average Plasma fibrinogen level was found to be 235.008 mg/dl in healthy smokers (control group), while an average of 440.12mg/dl was measured in patients with stable COPD. The difference in plasma fibrinogen levels was found to be significant, having a p-value of (0.000). In the third group with declined lung function predicting acute exacerbated COPD, fibrinogen was found to be &gt; 453.2 mg/dl, which was significantly higher than in the stable disease group (p-value &gt; 0.0017) Conclusion: Plasma fibrinogen level measurement is a reliable and accessible test in terms of a diagnostic marker of COPD, as compared to conventional lung function testing done in the past.

ROLE OF NONINVASIVE METHODS FOR ASSESSING STABLE NON-CYSTIC FIBROSIS BRONCHIECTASIS

SESSION TITLE: Obstructive Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Bronchiectasis is characterized by the abnormal dilation of lung airways. Only some patients with bronchiectasis may clinically benefit from the treatment recommended in the guidelines of the European Respiratory Society. The value of noninvasive methods for assessing the clinical phenotypes of stable-state non-cystic fibrosis (non-CF) bronchiectasis for treatable characteristics has not been adequately studied. METHODS: Patients with stable non-CF bronchiectasis were retrospectively enrolled. Patient characteristics, fractional exhaled nitric oxide (FeNO) values, and the results of blood tests for inflammatory markers, pulmonary function test, high-resolution computed tomography (HRCT), and bronchial hyper-responsiveness test or bronchodilator reversibility test were obtained. These data were used to assess the factors associated with the clinical phenotype of bronchiectasis. RESULTS: Eighty-nine patients were enrolled. The majority of the patients were female (60.67%) and have an average age of 59.08±15.09 years old. The predicted percentages of forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 and forced vital capacity were 56.17%±23.16% and 65.58%±15.26%, respectively. Eighteen (20.22%) of the patients with bronchiectasis had emphysema. The presence of emphysema in bronchiectasis was associated with a high airflow obstruction level. Seventeen (10.10%) of the patients with bronchiectasis had asthma. FeNO was significantly higher in the group of patients with bronchiectasis and asthma than in the other two groups (p < 0.01). The erythrocyte sedimentation rate (ESR) of the bronchiectasis alone group was higher than those of the other two groups. Significant negative correlations were found between ERS and FeNO levels (P = 0.02, r = −0.338), between HRCT score and FeNO levels (P = 0.04, r = −0.229), and between FEV1 (% predicted) and HRCT scores (P = 0.0007, r = −0.3629). A significant positive correlation was found between ERS and HRCT scores (P = 0.0001, r = 6326). CONCLUSIONS: A remarkable proportion of patients with bronchiectasis have emphysema or asthma. Biomarkers, such as FeNO, and conventional lung function tests should be routinely used for phenotyping bronchiectasis for potential targeted therapy. ESR can be used as a biomarker to reflect the level of systemic infiammation and the severity of bronchiectasis. These approaches will provide a better understanding of patients with bronchiectasis and their clinical phenotypes and lead to a more individualized and effective therapy. CLINICAL IMPLICATIONS: FeNO and conventional lung function tests are useful for phenotyping bronchiectasis for potential targeted therapy. ESR can be used as a biomarker to reflect the level of systemic infiammation and the severity of bronchiectasis. DISCLOSURES: No relevant relationships by Fengjia Chen, source=Web Response No relevant relationships by Aiping Chen, source=Web Response No relevant relationships by Gengpeng Lin, source=Web Response

Altered deposition of inhaled nanoparticles in subjects with chronic obstructive pulmonary disease

BackgroundRespiratory tract deposition of airborne particles is a key link to understand their health impact. Experimental data are limited for vulnerable groups such as individuals with respiratory diseases. The aim of this study is to investigate the differences in lung deposition of nanoparticles in the distal lung for healthy subjects and subjects with respiratory disease.MethodsLung deposition of nanoparticles (50 and 100 nm) was measured after a 10 s breath-hold for three groups: healthy never-smoking subjects (n = 17), asymptomatic (active and former) smokers (n = 15) and subjects with chronic obstructive pulmonary disease (n = 16). Measurements were made at 1300 mL and 1800 mL volumetric lung depth. Each subject also underwent conventional lung function tests, including post bronchodilator FEV1, VC, and diffusing capacity for carbon monoxide, DL,CO. Patients with previously diagnosed respiratory disease underwent a CT-scan of the lungs. Particle lung deposition fraction, was compared between the groups and with conventional lung function tests.ResultsWe found that the deposition fraction was significantly lower for subjects with emphysema compared to the other subjects (p = 0.001–0.01), but no significant differences were found between healthy never-smokers and smokers. Furthermore, the particle deposition correlated with pulmonary function tests, FEV1%Pred (p < 0.05), FEV1/VC%Pred (p < 0.01) and DL,CO (p < 0.0005) when all subjects were included. Furthermore, for subjects with emphysema, deposition fraction correlated strongly with DL,CO (Pearson’s r = 0.80–0.85, p < 0.002) while this correlation was not found within the other groups.ConclusionsLower deposition fraction was observed for emphysematous subjects and this can be explained by enlarged distal airspaces in the lungs. As expected, deposition increases for smaller particles and deeper inhalation. The observed results have implications for exposure assessment of air pollution and dosimetry of aerosol-based drug delivery of nanoparticles.

Multiple breath washout testing in adults with pulmonary disease and healthy controls \u2013 can fewer measurements eventually be more?

BackgroundMultiple breath washout (MBW) became a valuable research tool assessing ventilation heterogeneity. However, routine clinical application still faces several challenges. Deriving MBW parameters from three technically acceptable measurements according to current recommendations prolongs test times. We therefore aimed to evaluate reporting only duplicate measurements in healthy adults and pulmonary disease.MethodsOne hundred and fifty-three subjects prospectively underwent conventional lung function testing and closed-circuit SF6-MBW. Three technically acceptable MBW-measurements were obtained in 103 subjects.ResultsLung clearance index (LCI) differed significantly among 19 controls (7.4 ± 0.8), 19 patients with sarcoidosis (8.1 ± 1.2), 32 with bronchial asthma (9.2 ± 1.9) and 33 with COPD (10.8 ± 2.2, p < 0.001). Within-test repeatability was high (coefficient of variation between 2.5% in controls and 3.6% in COPD) and remained unchanged when only including the first two measurements. Likewise, LCI remained stable with mean absolute changes ranging from 0.9 ± 0.8% in controls to 1.5 ± 0.9% in COPD (p = 0.1). Mean test time reduction differed significantly between groups reaching 200 s in COPD (p = 0.01).ConclusionsDuplicate SF6-MBW-measurements are sufficient in adult patients with pulmonary disease and healthy controls. LCI values and intra-test repeatability are not affected reducing total test time statistically significant. Our findings have the potential to further facilitate application of MBW in research and clinical routine.Trial registrationNCT03176745, June 2, 2017 retrospectively registered.

Inert gas washout: background and application in various lung diseases.

Multiple breath inert gas washout (MBW) is a lung function technique to measure ventilation inhomogeneity. The technique was developed more than 60 years ago, but not much used for many decades. Technical improvements, easy protocols and higher sensitivity compared with standard lung function tests in some disease groups have led to a recent renaissance of MBW. The lung clearance index (LCI) is a common measure derived from MBW tests, and offers information on lung pathology complementary to that from conventional lung function tests such as spirometry. The LCI measures the overall degree of pulmonary ventilation inhomogeneity. There are other MBW-derived parameters, which describe more regional airway ventilation and enable specific information on conductive or acinar ventilation inhomogeneity. How this specific ventilation distribution is exactly related to different disease processes has not entirely been examined yet. MBW measurements are performed during tidal breathing, making this technique attractive for children, even young children and infants. These benefits and the additional physiological information on ventilation inhomogeneity early in the course of lung diseases have led to increasing research activities and clinical application of MBW, especially in paediatric lung diseases such as cystic fibrosis (CF). In these patients, LCI detects early airway damage and enables monitoring of disease progression and treatment response. Guidelines for the standardisation of the MBW technique were recently published. These guidelines will, hopefully, increase comparability of LCI data obtained in different centres or intervention trials in children and adults. In this non-systematic review article, we provide an overview of recent developments in MBW, with a special focus on children. We first explain the physiological and technical background to this technique with a short explanation of several methodological aspects that are important for understanding the principle behind the technique and enable high quality measurements. We then provide examples of MBW application in different lung diseases of children and adults, with regards to both clinical application and research activities. Lastly, we report on ongoing clinical trials using MBW as outcome and give an outlook on possible future developments.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia diagnosed by transbronchial lung cryobiopsy: a case report

BackgroundMicronodular lesions are common findings in lung imaging. As an important differential diagnosis, we describe a case of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia; it is notable that the diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is often delayed. This case provides supporting evidence to establish lung biopsy by cryotechnique as the option of first choice when considering a diagnostic strategy for micronodular lung lesions. Case presentationWe report a case of a 65-year-old white woman who presented with obstructive symptoms of chronic coughing and dyspnea confirmed by conventional lung function tests. A computed tomography scan presented disseminated micronodules in all the lobes of her lungs. With the help of bronchoscopic cryobiopsy it was possible to obtain a high yield sample of lung parenchyma. On histologic examination, the micronodules correlated with a diffuse neuroendocrine cell hyperplasia. In the context of clinical symptoms, radiological aspects, and histomorphological aspects we made the diagnosis of a diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Obstructive symptoms were treated with inhaled steroids and beta-2-mimetics continuously. A comparison between current computed tomography scans of our patient and scans of 2014 revealed no significant changes. Last ambulatory checks occurred in January and May of 2016. The course of disease and the extent of limitation of lung function have remained stable.ConclusionsThe diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is best made in a multidisciplinary review including clinical presentation, lung imaging, and histomorphological aspects. This report and current literature indicate that transbronchial lung cryobiopsy can be used as a safe and practicable tool to obtain high quality biopsies of lung parenchyma in order to diagnose micronodular lesions of the lung.

Visualization of neonatal lung injury associated with mechanical ventilation using x-ray dark-field radiography.

Mechanical ventilation (MV) and supplementation of oxygen-enriched gas, often needed in postnatal resuscitation procedures, are known to be main risk factors for impaired pulmonary development in the preterm and term neonates. Unfortunately, current imaging modalities lack in sensitivity for the detection of early stage lung injury. The present study reports a new imaging approach for diagnosis and staging of early lung injury induced by MV and hyperoxia in neonatal mice. The imaging method is based on the Talbot-Lau x-ray grating interferometry that makes it possible to quantify the x-ray small-angle scattering on the air-tissue interfaces. This so-called dark-field signal revealed increasing loss of x-ray small-angle scattering when comparing images of neonatal mice undergoing hyperoxia and MV-O2 with animals kept at room air. The changes in the dark field correlated well with histologic findings and provided superior differentiation than conventional x-ray imaging and lung function testing. The results suggest that x-ray dark-field radiography is a sensitive tool for assessing structural changes in the developing lung. In the future, with further technical developments x-ray dark-field imaging could be an important tool for earlier diagnosis and sensitive monitoring of lung injury in neonates requiring postnatal oxygen or ventilator therapy.

The reproducibility and responsiveness of the lung clearance index in bronchiectasis.

Lung clearance index (LCI) is a potential clinical outcome marker in bronchiectasis. Its responsiveness to therapeutic intervention has not been determined. This study evaluates its responsiveness to a session of physiotherapy and intravenous antibiotic treatment of an exacerbation.32 stable and 32 exacerbating bronchiectasis patients and 26 healthy controls were recruited. Patients had LCI and lung function performed before and after physiotherapy on two separate occasions in the stable patients and at the beginning and end of an intravenous antibiotic course in the exacerbating patients.LCI was reproducible between visits in 25 stable patients, with an intraclass correlation of 0.978 (0.948, 0.991; p<0.001). There was no significant difference in LCI (mean±sd) between stable 11.91±3.39 and exacerbating patients 12.76±3.47, but LCI was significantly higher in both bronchiectasis groups compared with healthy controls (7.36±0.99) (p<0.001). Forced expiratory volume in 1 s improved after physiotherapy, as did alveolar volume after intravenous antibiotics, but LCI did not change significantly.LCI is reproducible in stable bronchiectasis but unlike conventional lung function tests, is unresponsive to two short-term interventions and hence is unlikely to be a useful clinical tool for short-term acute assessment in these patients. Further evaluation is required to establish its role in milder disease and in the evaluation of long-term interventions.

Does quantitative lung SPECT detect lung abnormalities earlier than lung function tests? Results of a pilot study.

BackgroundHeterogeneous ventilation in lungs of individuals with allergies, cigarette smokers, asthmatics and chronic obstructive pulmonary disease (COPD) patients has been demonstrated using imaging modalities such as positron emission tomography (PET), magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). These individuals suffer from narrow and/or closed airways to various extents. By calculating regional heterogeneity in lung ventilation SPECT images as the coefficient of variation (CV) in small elements of the lung, heterogeneity maps and CV-density curves can be generated and used to quantitatively measure heterogeneity. This work explores the potential to use such measurements to detect mild ventilation heterogeneities in lung-healthy subjects.MethodFourteen healthy subjects without documented lung disease or respiratory symptoms, and two patients with documented airway disease, inhaled on average approximately 90 MBq 99mTc-Technegas immediately prior to the 20-min SPECT acquisition. Variation in activity uptake between subjects was compensated for in resulting CV values. The area under the compensated CV density curve (AUC), for CV values greater than a threshold value CVT, AUC(CV > CVT), was used as the measure of ventilation heterogeneity.ResultsPatients with lung function abnormalities, according to lung function tests, generated higher AUC(CV > 20%) values compared to healthy subjects (p = 0.006). Strong linear correlations with the AUC(CV > 20%) values were found for age (p = 0.006) and height (p = 0.001). These demonstrated that ventilation heterogeneities increased with age and that they depend on lung size. Strong linear correlations were found for the lung function value related to indices of airway closure/air trapping, residual volume/total lung capacity (RV/TLC; p = 0.009), and diffusion capacity of the lung for carbon monoxide adjusted for haemoglobin concentration in the blood (DLCOc; p = 0.009), a value partly related to supposed ventilation/perfusion mismatch. These findings support the association between conventional lung function tests and the AUC(CV > 20%) value.ConclusionsAmong the healthy subjects, there is a group with increased AUC(CV > 20%) values, but with normal lung function tests, which implies that it might be possible to differentiate ventilation heterogeneities earlier in a disease process than by lung function tests.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-014-0039-1) contains supplementary material, which is available to authorized users.

Capnovolumetry: a new tool for lung function testing in children with asthma

In capnovolumetry, the expiratory CO2 concentration of exhaled air is plotted against the volume and thereby allows to determine functional dead space volumes. This method might offer additional information in lung function testing in children and adolescents with bronchial asthma. We aimed at determining whether a bronchospasmolysis (BSL) effect in the lower airways could also be detected by capnovolumetry as reflected by changes in the functional threshold dead space volumes (VDT). In 47 patients (aged 4-16 years) with a mild persistent bronchial asthma, VDT were determined before and after bronchodilation prior to starting therapy with inhaled steroids and after 6 months of treatment. Additionally, spirometry and body plethysmography were performed in all patients. There were significantly higher VDT values after BSL before and after 6 months of therapy (P<0.0001). VDT values before BSL were tendatively higher after 6 months of therapy compared with baseline values (P=0.07). VDT values correlated with parameters derived from conventional pulmonary function testing, i.e. vital capacity, forced expiratory volume in 1 s (FEV1), and maximum expiratory flow (MEF50). As VDT values particularly reflect the volumes of the lower bronchi this method may provide supplementary information to conventional lung function tests which are based on breathing mechanics. This seems to be especially helpful in situations where body plethysmography is not available or cooperation in forced expiration manoeuvres is insufficient.

Effect of inhaled corticosteroid treatment on exhaled breath condensate leukotriene E4 in children with mild asthma

Chronic airway inflammation in children with asthma might be present even in the absence of pathological lung function tests and is known to increase the risk of permanent pulmonary damage. Thus, we aimed at investigating to what extent inflammatory markers such as leukotrienes (LTs) in exhaled breath condensate (EBC) or fractional exhaled nitric oxide (FE(NO)) reflect therapeutic effects in these patients. Fifty steroid-naive patients (aged 8.8 +/- 2.7 years) were included in the study. EBC was collected before and 6 months after therapy with inhaled corticosteroids. LTs were determined by using commercially available ELISA. In addition, FE(NO) was measured by means of a chemiluminescence analyzer. Conventional lung function testing was performed revealing vital capacity, forced expiratory volume, maximum expiratory flow, and specific resistance. In EBC, LTE(4) but not LTB(4) levels significantly decreased after steroid therapy from 45.3 +/- 36.0 pg/mL to 17.2 +/- 11.4 pg/mL (p < 0.0001) concomitant with a slight, but significant improvement of lung function parameters. Mean FE(NO) also indicated therapeutic success; however, in 20 of 50 patients, exhaled NO concentrations were higher after therapy. These findings suggest that LTE(4) in breath condensate may be helpful in latent inflammatory activity in the bronchial mucosa in children with asthma.

Generation and Characterization of Diesel Exhaust in a Facility for Controlled Human Exposures

An idling medium-duty diesel truck operated on ultralow sulfur diesel fuel was used as an emission source to generate diesel exhaust for controlled human exposure. Repeat tests were conducted on the Federal Test Procedure using a chassis dynamometer to demonstrate the reproducibility of this vehicle as a source of diesel emissions. Exhaust was supplied to a specially constructed exposure chamber at a target concentration of 100 µg · m-3 diesel particulate matter (DPM). Spatial variability within the chamber was negligible, whereas emission concentrations were stable, reproducible, and similar to concentrations observed on the dynamometer. Measurements of nitric oxide, nitrogen dioxide, carbon monoxide, particulate matter (PM), elemental and organic carbon, carbonyls, trace elements, and polycyclic aromatic hydrocarbons were made during exposures of both healthy and asthmatic volunteers to DPM and control conditions. The effect of the so-called “personal cloud” on total PM mass concentrations was also observed and accounted for. Conventional lung function tests in 11 volunteer subjects (7 stable asthmatic) did not demonstrate a significant change after 2-hr exposures to diesel exhaust. In summary, we demonstrated that this facility can be effectively and safely used to evaluate acute responses to diesel exhaust exposure in human volunteers.