Changes In Lung Structure Research Articles

Exposure Memory and Lung Regeneration.

Many acute and chronic lung diseases could benefit from improved regeneration therapy. In development and throughout life, genetically encoded exposure memory systems allow environmental exposures, diet, and infectious agents to direct subsequent phenotypic adaptation and responses. The impact of such memory systems on lung regeneration is currently unknown. This article provides a brief overview of advances in redox biology and medicine as a framework for elucidating exposure memory and delineating spatiotemporal responses in lung regeneration. New imaging and omics methods enable precise definition to advance knowledge of development and the cumulative changes in lung biochemistry, structure, and cell populations occurring from prior and ongoing exposures. Importantly, conditioning steps may be needed to reverse exposure memory and enable effective regeneration. Thus, to complement developmental biology and regenerative medicine, research programs are needed to gain systematic knowledge of how lifelong exposures impact lung biology and support transition of lung regeneration from hypothetical to practical medicine.

Role of vascular disorders in lung injury in patients with rheumatoid arthritis

Introduction. The incidence of respiratory system involvement in patients with rheumatoid arthritis (RA) has currently increased; thereby new diagnostic methods have been developed actively. Meanwhile role of vascular disorders in pathogenesis of lung injury is almost unknown and single-photon emission computed tomography (SPECT) isn't used as method of lung assessment in RA. The detector of endothelial glycocalyx damage syndecan-1 is little known but potentially perspective serum marker of lung injury in RA. Objective. The purpose of the study was to investigate the role of vascular disorders in lung injury in patients with RA. Materials and methods. 61 patients with RA without comorbid lung diseases were enrolled in the study. Control group consisted of 26 healthy persons. Patients underwent survey and physical examination, high-resolution computed tomography (HRCT) and SPECT of the lungs and pulmonary function tests (PFTs). Also serum levels of rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (ACCP) and syndecan-1 were measured. Results. All patients developed microcirculation impairment on SPECT. Vascular disorders were according to changes of lung structure detected by HRCT (r = 0.434; p = 0.044). Areas of hypoperfusion matched with ground glass opacities, lung fibrosis, branching linear structures and airway obstruction on HRCT-SPECT fusion scans. Syndecan-1 level was higher in patients with RA compared with healthy controls (р = 0.019). Conclusion. Vascular disorders are important in pathogenesis of lung injury in RA, and SPECT has high sensitivity in lung assessment. Perfusion impairment in lungs correlates with syndecan-1 level, thus syndecan-1 could be used as marker of lung injury in RA thereafter.

Tiron ameliorates oxidative stress and inflammation in a murine model of airway remodeling

Airway remodeling includes lung structural changes that have a role in the irreversibility of pulmonary dysfunction shown in chronic bronchial asthmatics. The current experiment investigated the effect of the mitochondrial antioxidant, tiron in comparison with dexamethasone (DEXA) on airway remodeling in chronic asthma. Sensitized BALB/c mice were challenged with ovalbumin (OVA) aerosol for 8weeks, OVA sensitized-challenged mice were treated with either DEXA or tiron, respectively. After that, lung tissue and bronchoaveolar lavage fluid (BALF) were used for measurement of different biological markers. Lungs were examined for histopathological changes and immunohistochemistry. Upon comparing with vehicle treated animals, trion or DEXA treatment significantly reduced eosinophils, lymphocytes, neutrophils and macrophages count in the BALF. Both drugs significantly alleviated chronic OVA-induced oxidative stress as illustrated by decreased pulmonary malondialdenhyde (MDA) and increased glutathione (GSH) and superoxide dismutase (SOD) levels. Asthmatic mice exhibited elevated levels of NOx, IL-13 and TGF-β1 that were reduced by DEXA and tiron. Histopathological changes and increased immunoreactivity of nuclear factor-Kappa B (NF-κ B) in OVA-challenged mice were minimized by tiron and DEXA treatment. In conclusion, in this model of chronic asthma DEXA and tiron ameliorated airway remodeling and inflammation in experimental chronic asthma with no difference between the effect of tiron and DEXA. Tiron has a potential role as adjuvant treatment in chronic asthma.

Impact of Dietary Tomato Juice on Changes in Pulmonary Oxidative Stress, Inflammation and Structure Induced by Neonatal Hyperoxia in Mice (Mus musculus).

Many preterm infants require hyperoxic gas for survival, although it can contribute to lung injury. Experimentally, neonatal hyperoxia leads to persistent alterations in lung structure and increases leukocytes in bronchoalveolar lavage fluid (BALF). These effects of hyperoxia on the lungs are considered to be caused, at least in part, by increased oxidative stress. Our objective was to determine if dietary supplementation with a known source of antioxidants (tomato juice, TJ) could protect the developing lung from injury caused by breathing hyperoxic gas. Neonatal mice (C57BL6/J) breathed either 65% O2 (hyperoxia) or room air from birth until postnatal day 7 (P7d); some underwent necropsy at P7d and others were raised in room air until adulthood (P56d). In subsets of both groups, drinking water was replaced with TJ (diluted 50:50 in water) from late gestation to necropsy. At P7d and P56d, we analyzed total antioxidant capacity (TAC), markers of oxidative stress (nitrotyrosine and heme oxygenase-1 expression), inflammation (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) expression), collagen (COL) and smooth muscle in the lungs; we also assessed lung structure. We quantified macrophages in lung tissue (at P7d) and leukocytes in BALF (at P56d). At P7d, TJ increased pulmonary TAC and COL1α1 expression and attenuated the hyperoxia-induced increase in nitrotyrosine and macrophage influx; however, changes in lung structure were not affected. At P56d, TJ increased TAC, decreased oxidative stress and reversed the hyperoxia-induced increase in bronchiolar smooth muscle. Additionally, TJ alone decreased IL-1β expression, but following hyperoxia TJ increased TNF-α expression and did not alter the hyperoxia-induced increase in leukocyte number. We conclude that TJ supplementation during and after neonatal exposure to hyperoxia protects the lung from some but not all aspects of hyperoxia-induced injury, but may also have adverse side-effects. The effects of TJ are likely due to elevation of circulating antioxidant concentrations.

8-Oxoguanine DNA glycosylase1–driven DNA repair—A paradoxical role in lung aging

Age-associated changes in lung structure and function are some of the most important predictors of overall health, cognitive activities and longevity. Common to all aging cells is an increase in oxidatively modified DNA bases, primarily 8-oxo-7,8-dihydroguanine (8-oxoG). It is repaired via DNA base excision repair pathway driven by 8-oxoguanine DNA glycosylase-1 (OGG1-BER), whose role in aging has been the focus of many studies. This study hypothesizes that signaling and consequent gene expression during cellular response to OGG1-BER “wires” senescence/aging processes. To test OGG1-BER was mimicked by repeatedly exposing diploid lung fibroblasts cells and airways of mice to 8-oxoG base. Results showed that repeated exposures led to G1 cell cycle arrest and pre-matured senescence of cultured cells in which over 1000 genes were differentially expressed −86% of them been identical to those in naturally senesced cells. Gene ontology analysis of gene expression displayed biological processes driven by small GTPases, phosphoinositide 3-kinase and mitogen activated kinase cascades both in cultured cells and lungs. These results together, points to a new paradigm about the role of DNA damage and repair by OGG1 in aging and age-associated disease processes.

CTGF upregulation correlates with MMP-9 level in airway remodeling in amurine model of asthma.

IntroductionConnective tissue growth factor (CTGF) mediates hypertrophy, proliferation, and extracellular matrix synthesis. Matrix metalloproteinase (MMP) plays a role in airway extracellular matrix remodeling. The correlation between CTGF and MMP in airway remodeling of asthma was unknown. This study investigated lung CTGF expression and its correlation with MMP and airway structural changes in a murine model of asthma.Material and methodsFemale BALB/c mice were sensitized and challenged by intraperitoneal injections and intranasal phosphate-buffered saline (PBS) or ovalbumin (OVA). Airway responsiveness and serum OVA-specific IgE were measured. Airway structural changes were quantified by morphometric analysis. Differential cell counts and MMP-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 were evaluated in bronchoalveolar lavage fluid (BALF). Lung CTGF was determined by Western blot.ResultsSerum OVA-specific IgE level and airway responsiveness in enhanced pause (Penh) is significantly higher in sensitized mice challenged with OVA compared to PBS-challenged mice. MMP-2, MMP-9, and TIMP-1 in BALF were significantly higher in OVA mice. Airway structural changes of animals’ lungs with OVA challenge showed increased thickness of the smooth muscle layer and numbers of Goblet cells and inflammatory cells and eosinophils near airways and perivascular areas. Lung CTGF expression significantly increased in OVA-challenged mice. CTGF expressions positively correlated with MMP-9 (r = 0.677, p < 0.05), TIMP-1 (r = 0.574, p < 0.05) and thickness of the smooth muscle layer (r = 0.499, p < 0.05).ConclusionsThis study indicates that CTGF upregulation correlates with MMP-9, probably involved in the pathogenesis of airway remodeling of asthma.

Assessment of lung deposition and analysis of the effect of fluticasone/salmeterol hydrofluoroalkane (HFA) pressurized metered dose inhaler (pMDI) in stable persistent asthma patients using functional respiratory imaging

ABSTRACTBackground: Unambiguously for inhaled products, PK measures are best suited for ensuring that the total systemic exposure is equivalent for two products but cannot provide regional information about lung deposition and structural changes. Functional respiratory imaging (FRI) has been demonstrated to be sensitive for distinguishing small but imperative differences related to a single treatment.Methods: In this study FRI is used in 16 asthmatic patients to assess equivalence in regional deposition for two products (fluticasone/salmeterol, test and reference) by directly measuring regional functional and structural changes within the lungs following its administration.Results: No differences were observed between the lung deposition patterns and the effects on lung structure and function of two products, having the same formulation and manufactured by different organizations using FRI.Conclusions: Results using FRI complement PK assessments. The added value of this approach to the conventional clinical methods could be significant.

Senėjimo sąlygoti astmos patogenezės pokyčiai

Senėjimas - natūralus procesas, prasidedantis vos gimus, kuris apima visą organizmą, įskaitant ir kvėpavimo takus. Amžiniai kvėpavimo sistemos anatominiai, fiziologiniai ir imuniniai pokyčiai gali turėti įtakos plaučių funkcijai bei įvairių kvėpavimo sistemos ligų eigai. Astma - viena labiausiai paplitusių lėtinių kvėpavimo takų ligų visame pasaulyje, todėl organizmo senėjimo poveikis šios ligos patogenezei itin aktualus. Pasaulinės sveikatos organizacijos (PSO) duomenimis, sparčiai auga astmos paplitimas vyresnio amžiaus žmonių grupėje, būdinga sunkensė eiga, mažesnis standartinių gydymo metodų veiksmingumas, blogesnės baigtys. Pastebėti astmos (ypač sunkios) patogenezės ir natūraliai sveikuose plaučiuose žmogui senstant vykstančių procesų panašumai. Norint kuo geriau suprasti astmos patogenezės mechanizmus, pastarąjį dešimtmetį didėjo domėjimasis pagrindinių ligos patogenezėje dalyvaujančių uždegimo ląstelių sąveika su struktūriniais apatinių kvėpavimo takų elementais. Manoma, kad etapinis kvėpavimo takų remodeliacijos procesų blokavimas galėtų pristabdyti struktūrinių pokyčių progresavimą ir sąlygoti geresnį gydymo efektą.

Exercise responses are related to structural lung damage in CF pulmonary disease.

Early detection of lung disease is a primary objective in monitoring patients with Cystic Fibrosis (CF); High-Resolution-Computed-Tomography (HRCT) assesses structural damage. Spirometry and cardiopulmonary exercise testing are used for functional evaluation of CF lung disease. To evaluate the deterioration of exercise testing parameters over a 2-year period compared to the change of spirometry and HRCT parameters among CF patients. Twenty-eight CF patients were evaluated with HRCT, spirometry, and exercise testing; 15 had two assessments with an interval of 2 years. Correlation analyses between Bhalla score parameters and functional measures were performed. Twenty-eight patients with CF (mean age 14.9 years, mean forced expiratory volume in 1 sec [FEV1 ] 83.2%) were evaluated. FEV1 was not found to change significantly in the 2-year period (P = 0.612). Both mean Bhalla score and mean peak oxygen consumption (VO2 peak %) deteriorated significantly (P = 0.014 and P = 0.026, respectively). VO2 peak and respiratory equivalents for O2 and CO2 at peak exercise were found to be significant predictors of Bhalla score (r = -0.477, P = 0.010; r = 0.461, P = 0.018; r = 0.402; P = 0.042, respectively). Anaerobic threshold was associated with changes in Bhalla score over the following 2 years. Exercise testing is more sensitive than spirometry to detect structural changes in CF lungs. Pediatr Pulmonol. 2016; 51:914-920. © 2016 Wiley Periodicals, Inc.

Respiratory Health and Related Quality of Life in Patients with Congenital Agammaglobulinemia in the Northern Region of the UK.

IntroductionPatients with congenital agammaglobulinemia, characterized by a defect in B lymphocyte differentiation causing B alymphocytosis, require life-long IgG replacement. There is scant literature regarding the effectiveness of IgG treatment at preventing mucosal (particularly sinopulmonary tract) infection and whether current management adequately restores “normal” health and quality of life (QoL). We aimed to document infective episodes pre- and post-commencing IgG replacement, determine any change in lung function and structure and assess respiratory status and QoL in a cohort of patients treated in Newcastle.MethodsClinical data were extracted from medical records of 15 patients identified from the immunology database, focusing on infective episodes, serial chest CT and spirometry results. Thirteen patients completed a selection of standardized and validated questionnaires assessing physical health, respiratory health and QoL.ResultsPediatric patients on IgG therapy suffered fewer infections per patient year (0.74) than adults (2.13). 6/14 patients showed deteriorating respiratory status despite adequate therapy. Health questionnaires revealed a significant burden of respiratory disease on a patient’s life.ConclusionClinical data showed patients with congenital agammaglobulinemia receiving immunoglobulin therapy retained a higher than average infection rate, most of which affected mucosal barriers. Most patients self-reported worse respiratory symptoms, a lower respiratory-related QoL and a lower general health QoL relative to a healthy population. Most participants had progressive structural lung damage and decreased lung function. These results suggest that current management is not entirely effective at preventing deterioration of respiratory health or restoring QoL.

Human Placental Extract Ameliorates Structural Lung Changes Iinduced by Amiodarone in Rats.

Amiodarone is used in treatment of cardiac arrhythmias. Therapeutic use of amiodarone is limited by its side effects, including pulmonary toxicity. Human Placenta Extract (HPE) contains a variety of bio-active substances. Thus, the present study aimed to quantitatively evaluate the protective effects of HPE on the structural lung changes induced by amiodarone using stereological methods. Sprague-Dawley male rats were divided into four groups. The first, second, and third groups received no treatment, amiodarone (100 mg/kg, i.p.), and HPE (500 µL/kg, i.p.), respectively. The fourth group was treated with amiodarone + HPE. The animals' lungs were removed after 10 days. The lung volume was estimated using the Cavalieri principle on the embedded and cut tissue and corrected for shrinkage. The volume density of the parenchyma, alveolar space, and septa were estimated using point-counting method. The surface area of the alveoli, the volume-weighted means alveoli volume, and mean septum thickness were also estimated in all groups. The total volume and thickness of the alveolar septum were increased by 40 % and 28 %, respectively. However, the total volume of the alveolar space was decreased by 31 % in the amiodarone treated-rats. The mean alveolar volume was decreased by 64 % on the average in the amiodarone treated group. Yet, these changes were not detected in the amiodarone+HPE group. Moreover, RBC accumulation in the alveolar space and septa was ameliorated after HPE treatment. HPE can protect the lung tissue from the structural changes induced by amiodarone.

Computed Tomography and Magnetic Resonance Imaging for Longitudinal Characterization of Lung Structure Changes in a Yucatan Miniature Pig Silicosis Model

Medical imaging is a rapidly advancing field enabling the repeated, noninvasive assessment of physiological structure and function. These beneficial characteristics can supplement studies in swine by mirroring the clinical functions of detection, diagnosis, and monitoring in humans. In addition, swine may serve as a human surrogate, facilitating the development and comparison of new imaging protocols for translation to humans. This study presents methods for pulmonary imaging developed for monitoring pulmonary disease initiation and progression in a pig exposure model with computed tomography and magnetic resonance imaging. In particular, a focus was placed on systematic processes, including positioning, image acquisition, and structured reporting to monitor longitudinal change. The image-based monitoring procedure was applied to 6 Yucatan miniature pigs. A subset of animals (n= 3) were injected with crystalline silica into the apical bronchial tree to induce silicosis. The methodology provided longitudinal monitoring and evidence of progressive lung disease while simultaneously allowing for a cross-modality comparative study highlighting the practical application of medical image data collection in swine. The integration of multimodality imaging with structured reporting allows for cross comparison of modalities, refinement of CT and MRI protocols, and consistently monitors potential areas of interest for guided biopsy and/or necropsy.

Alteration in Intrapulmonary Pharmacokinetics of Aerosolized Model Compounds Due to Disruption of the Alveolar Epithelial Barriers Following Bleomycin-Induced Pulmonary Fibrosis in Rats

Idiopathic pulmonary fibrosis is a lethal lung disease that is characterized by the accumulation of extracellular matrix and a change in lung structure. In this study, intrapulmonary pharmacokinetics of aerosolized model compounds were evaluated using rats with bleomycin-induced pulmonary fibrosis. Aerosol formulations of indocyanine green, 6-carboxyfluorescein (6-CF), and fluorescein isothiocyanate dextrans (FD; 4.4, 10, 70, and 250 kDa) were administered to rat lungs using a MicroSprayer. Indocyanine green fluorescence signals were significantly weaker in fibrotic lungs than in control lungs and 6-CF and FD concentrations in the plasma of pulmonary fibrotic animals were markedly higher than in the plasma of control animals. Moreover, disrupted epithelial tight junctions, including claudins-1, -3, and -5, were observed in pulmonary fibrotic lesions using immunofluorescence microscopy. In addition, destruction of tight junctions on model alveolar epithelial cells (NCI-H441) by transforming growth factor-β1 treatment enhanced the permeability of 6-CF and FDs through NCI-H441 cell monolayers. These results indicate that aerosolized drugs are easily distributed into the plasma after leakage through damaged tight junctions of alveolar epithelium. Therefore, the development of delivery systems for anti-fibrotic agents to improve intrapulmonary pharmacokinetics may be necessary for effective idiopathic pulmonary fibrosis therapy.

Experimental evidence of age-related adaptive changes in human acinar airways.

The progressive decline of lung function with aging is associated with changes in lung structure at all levels, from conducting airways to acinar airways (alveolar ducts and sacs). While information on conducting airways is becoming available from computed tomography, in vivo information on the acinar airways is not conventionally available, even though acini occupy 95% of lung volume and serve as major gas exchange units of the lung. The objectives of this study are to measure morphometric parameters of lung acinar airways in living adult humans over a broad range of ages by using an innovative MRI-based technique, in vivo lung morphometry with hyperpolarized (3)He gas, and to determine the influence of age-related differences in acinar airway morphometry on lung function. Pulmonary function tests and MRI with hyperpolarized (3)He gas were performed on 24 healthy nonsmokers aged 19-71 years. The most significant age-related difference across this population was a 27% loss of alveolar depth, h, leading to a 46% increased acinar airway lumen radius, hence, decreased resistance to acinar air transport. Importantly, the data show a negative correlation between h and the pulmonary function measures forced expiratory volume in 1 s and forced vital capacity. In vivo lung morphometry provides unique information on age-related changes in lung microstructure and their influence on lung function. We hypothesize that the observed reduction of alveolar depth in subjects with advanced aging represents a remodeling process that might be a compensatory mechanism, without which the pulmonary functional decline due to other biological factors with advancing age would be significantly larger.

Sound transmission in porcine thorax through airway insonification.

Many pulmonary injuries and pathologies may lead to structural and functional changes in the lungs resulting in measurable sound transmission changes on the chest surface. Additionally, noninvasive imaging of externally driven mechanical wave motion in the chest (e.g., using magnetic resonance elastography) can provide information about lung structural property changes and, hence, may be of diagnostic value. In the present study, a comprehensive computational simulation (in silico) model was developed to simulate sound wave propagation in the airways, lung, and chest wall under normal and pneumothorax conditions. Experiments were carried out to validate the model. Here, sound waves with frequency content from 50 to 700Hz were introduced into airways of five porcine subjects via an endotracheal tube, and transmitted waves were measured by scanning laser Doppler vibrometry at the chest wall surface. The computational model predictions of decreased sound transmission with pneumothorax were consistent with experimental measurements. The in silico model can also be used to visualize wave propagation inside and on the chest wall surface for other pulmonary pathologies, which may help in developing and interpreting diagnostic procedures that utilize sound and vibration.

Using the same cut-off for sulfur hexafluoride and nitrogen multiple-breath washout may not be appropriate.

Recent evidence suggests that results from multiple-breath washout (MBW) using nitrogen (N 2 ) as washout gas are different to those obtained by using sulfur hexafluoride (SF 6 ). Explanations were mainly related to different MBW equipment and gas properties. We aim to mention a new aspect, namely using the same cut-off in both techniques to determine lung clearance index (usually 2.5% of initial tracer concentration) irrespective of additional contribution of tissue-nitrogen in N 2 -MBW. In a simple model calculation we subtracted 1% tissue-N 2 from the N 2 -MBW in real washout traces from two children, one with cystic fibrosis (CF) and one healthy. This "SF 6 -washout simulation" decreased LCI differently in the children. In the healthy subject 1/40 th (2.5%) was achieved two breaths earlier compared to the original signal and changed LCI from 6.7 to 5.9 (12%), while in CF 1/40 th was achieved 19 breaths earlier leading to a LCI decrease from 13.7 to 10.0 (27%). It would have been required to wash out SF6 until 1/66 th (1.5%) to be comparable to N 2 washout at 1/40th (2.5%), or to stop N2-MBW already at 3.5% of the starting concentration to make both techniques comparable. We show that a basic physiological-mathematical difference between both techniques additionally accounts for different sensitivities and poor agreement between SF 6 - and N 2 -MBW. The best way of adjusting for the contribution of tissue-N 2 needs to be examined in future studies. Thus, despite increasing use in different disease groups, the books on MBW technology are obviously not closed yet.

Linking clinical phenotypes of chronic lung allograft dysfunction to changes in lung structure.

Chronic lung allograft dysfunction (CLAD) remains the major barrier to long-term success after lung transplantation. This report compares gross and microscopic features of lungs removed from patients receiving a redo-transplant as treatment for CLAD. Lungs donated by patients with either the bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) phenotype of CLAD and appropriate control lungs (eight per group) were air-inflated, frozen solid and kept frozen while a multi-detector computed tomography (MDCT) was obtained. The lung was then cut into 2-cm thick transverse slices and sampled for micro-CT and histopathology. The MDCT showed reduced lung volume with increased lung weight and density in RAS versus BOS and control (p<0.05). Although pre-terminal bronchioles were obstructed in both phenotypes, RAS lungs showed a reduction of pre-terminal bronchioles (p<0.01). Micro-CT and matched histopathology showed that RAS was associated with reduced numbers of terminal bronchioles/lung compared to BOS and controls (p<0.01), with expansion of the interstitial compartment and obliteration of the alveolar airspaces by fibrous connective tissue. RAS is associated with greater destruction of both pre-terminal and terminal bronchioles. Additionally, the interstitial compartments are expanded and alveolar airspaces are obliterated by accumulation of fibrous connective tissue.

Phase-contrast computed tomography for quantification of structural changes in lungs of asthma mouse models of different severity.

Lung imaging in mouse disease models is crucial for the assessment of the severity of airway disease but remains challenging due to the small size and the high porosity of the organ. Synchrotron inline free-propagation phase-contrast computed tomography (CT) with its intrinsic high soft-tissue contrast provides the necessary sensitivity and spatial resolution to analyse the mouse lung structure in great detail. Here, this technique has been applied in combination with single-distance phase retrieval to quantify alterations of the lung structure in experimental asthma mouse models of different severity. In order to mimic an in vivo situation as close as possible, the lungs were inflated with air at a constant physiological pressure. Entire mice were embedded in agarose gel and imaged using inline free-propagation phase-contrast CT at the SYRMEP beamline (Synchrotron Light Source, `Elettra', Trieste, Italy). The quantification of the obtained phase-contrast CT data sets revealed an increasing lung soft-tissue content in mice correlating with the degree of the severity of experimental allergic airways disease. In this way, it was possible to successfully discriminate between healthy controls and mice with either mild or severe allergic airway disease. It is believed that this approach may have the potential to evaluate the efficacy of novel therapeutic strategies that target airway remodelling processes in asthma.

Peak weight velocity in infancy is negatively associated with lung function in adolescence.

Rapid weight gain during infancy increases childhood asthma risk, which might be related to impaired lung function. This study investigated associations between peak weight velocity (PWV) during the first two years of life and spirometric lung function indices at 15 years of age. Data from 1842 children participating in the GINIplus German birth cohort who underwent spirometry at age 15 were analysed. PWV was calculated from weight measurements obtained between birth and two years of age. Generalised additive models were fitted after adjustment for potential confounding factors (birth weight, height, and age at lung function testing). Results are presented per interquartile range increase (3.5 kg/year) in PWV. PWV was negatively associated with pre-bronchodilation flow rates after extensive adjustment for potential confounders including asthma: forced expiratory flow at 50% of forced vital capacity (FEF50 ) decreased by 141 ml/s (95%CI = [-225;-57]), FEF75 by 84 ml/s [-144;-24] and FEF25-75 by 118 ml/s [-192;-44]. FEV1 /FVC was also negatively associated with PWV (-0.750% [-1.273;-0.226]) whereas forced expiratory volume in 1s (FEV1 ) and forced vital capacity (FVC) were not. Similar results were found for measurements post-bronchodilation. Early life weight gain was negatively associated with flow indices in adolescence, suggesting structural changes in peripheral lungs.

78 Differences in infection, inflammation and structural abnormalities between the right and left lung

Background Previous studies, albeit small sample sizes have shown early infection in young children with cystic fibrosis (CF) can be detected in bronchoalveolar lavage (BAL) samples on one side despite inflammation being present on both sides of the lung. Aim To investigate differences between the right and left lung in terms of infection, inflammation and lung structure using microbiological culture taken from the right and left lobes of BAL samples of children. Methods Microbiological culture data were collected from BAL samples of the right and left lobes from children with CF. Samples were analysed using routine microbiological processing procedures at The Royal Children's Hospital, Melbourne. Respective Chest Computed Tomography (CT) images were analysed using the Brody scoring system and all lung lobes were assessed. Results Data from 527 BAL samples from 124 children were analysed. Neutrophil elastase (ne) was detected and reported in 163 (31%) of samples and interleukin-8 (IL-8) measured in 519 (98%). Mean (SD) ne reported was 2654.08 (7249.51) mg/ml, and mean (SD) IL8 measured 3.24 (7.65)ng/ml. A difference between presence of infection in the right and left lung existed (p 2 (1) = 188.72; p 2 (1) = 56.23; p Pseudomonas aeruginosa infection was not present on the left side [χ 2 (1) = 4.72; p Conclusion Lower respiratory infection and early lung structural changes appeared to be more common in the left lung in infants and young children with CF.