Background: Lung clearance index (LCI), obtained by multiple breath washout testing (MBW), is a sensitive measure of lung disease in infants. It has been identified as a particularly suitable endpoint for clinical trials in cystic fibrosis (CF), but has potential applications in many other conditions. However, MBW in infants presents a number of technical challenges. Conventional MBW is based on simultaneous measurement of flow and gas. These two signals are then aligned and combined to derive expired gas volumes and measures of ventilation inhomogeneity: this process becomes increasingly vulnerable to errors in gas signal alignment at rapid respiratory rates. At present, no existing system for infant MBW meets all the criteria set out in international guidelines, and there is no simple method of assessing lung function outside research laboratories in this population. This thesis describes an alternative method of performing MBW in infants. In this method, expired gas is collected and analysed to derive functional residual capacity (FRC) and LCI. There is no need to simultaneously measure flow, and therefore no need for the complicated step of integrating flow and gas signals. Dead space is also significantly reduced by removing the flowmeter. Methods: In the first phase of testing, an existing lung model was modified to generate realistic infant breathing parameters with high accuracy. The prototype system was modified to improve accuracy and subsequently tested at FRC of 100-250mls with respiratory rates of 20-60min-1. In the second phase, testing proceeded to an in vivo pilot study of the novel method in children with cystic fibrosis and healthy controls. Practical applicability of the system was determined by the number of successful duplicate tests, and within-subject repeatability. Comparison was made with LCI measurements obtained using a respiratory mass spectrometer, currently considered the gold standard for infant LCI. Results: In a total of 103 tests performed in the lung model, overall mean error (standard deviation) of FRC measurement was -1.0(3.3)%, with 90% of tests falling within +/-5%. 13 patients were excluded from the clinical study due to being unsedated or inadequately sedated and therefore failing to tolerate the test. A total of 25 patients (7 children with CF, 18 healthy control children) were deemed to be adequately sedated at the start of the test, of these 20 patients (7 with CF) successfully underwent duplicate testing (80% success rate). Mean FRC for healthy controls was 19.5ml/kg, and mean LCI 6.45. For children with CF, mean FRC was 21.8ml/kg and mean LCI 6.98. Mean within-subject coefficient of variation for FRC was 7.18% and for LCI 5.94%. Of 4 infants assessed with both the novel method and the respiratory mass spectrometer, there was good correlation in FRC measurement (mean difference -8.1%). Comparison of LCI with the mass spectrometer was affected by technical difficulties with the test; in those patients who underwent technically adequate tests with both methods, mean difference in LCI between the two methods was 1.65%. Discussion: FRC measurement using the novel method has superior accuracy in vitro than previously described systems. Data from the pilot study suggest that this is a feasible and reproducible method of performing LCI in infants and young children, as long as they are adequately sedated. Results in both children with CF and controls fall within the expected range, and well within accuracy limits set by international guidelines. However, the system and testing protocol could be further improved to reduce the number of technically inadequate tests having to be excluded. This could provide a more accessible alternative to previously described systems for infant MBW.

Pasture-associated severe equine asthma (EPA) is a progressive condition affecting horses in the southeastern United States. Pulmonary function testing with methacholine challenge (MC) provides a definitive diagnosis by eliciting airway hyper-responsiveness. Most horses require extensive conditioning to accept the instrumentation. Our hypothesis was that MC protocols designed to elicit airway hyper-responsiveness would yield equivalent results in the presence and absence of sedation. Sedated and unsedated MCs were performed on 8 EPA-affected horses, with each horse acting as its own control. Acepromazine was superior to xylazine/butorphanol, resulting in sedation and data collection. Based on American Thoracic Society guidelines, an acceptable ability to detect differences in lung resistance is less than a twofold difference in the provocative concentration of methacholine that elicited a 40% increase in lung resistance (PC40RL). Significant differences in PC40RL were not detected. Validation of a sedation protocol for use in MC will expand the application of this diagnostic.

Objective - evaluate horses with acute airway obstruction using three treatment regimens: tapering doses of dexamethasone (DEX), environmental modification (ENV), and a combination of both treatments (DEX + ENV) by analyzing clinical parameters, pulmonary function testing, bronchoalveolar lavage fluid (BALF) cytology and BALF cell expression of the cytokines IFN-? and IL-4 Animals - 6 horses with recurrent airway obstruction (RAO) Procedures - Clinical examination, pulmonary function test, and collection of BALF prior to treatment and during 22 day treatment period Hypothesis - Alterations in clinical parameters, pulmonary function and airway inflammation in acute equine RAO will return to remission values by treating with DEX, ENV or DEX + ENV Results - All horses demonstrated clinical disease, reduced pulmonary dynamic compliance (Cdyn) and an increased maximum change in pleural pressures (?Pplmax) when in a challenge environment. All treatments improved clinical parameters, ?Pplmax and Cdyn. BALF cytology during an RAO crisis demonstrated neutrophilic inflammation. ENV or DEX + ENV resulted in a significant decrease in airway neutrophilia that was maintained throughout the treatment period. In contrast, treatment with DEX caused a reduction in airway neutrophilia initially followed by a rebound neutrophilia as the period between administrations of dexamethasone (0.05mg/kg) was increased to 72 hours. The rebound neutrophilia was not accompanied by equivalent deterioration in clinical parameters or pulmonary function. Conclusions - Environmental modification is important in the management of RAO horses. Treatment of clinical RAO with a decreasing dosage protocol of corticosteroids in the absence of environmental modification results in the persistence of airway inflammation without recrudescence of clinical disease. / Master of Science

of the dissertation Impact of minimally invasive approach on pulmonary function in patients undergoing aortic valve replacement MUDr. Ján Gofus The most common minimally invasive approach to aortic valve replacement is upper hemisternotomy, which has been implemented at our department, as well. Preserving the lower half of thoracic cage could lead to lower postoperative drop of pulmonary function, apart from other benefits. Nevertheless, publications on this topic are insufficient and controversial. Our aim was to perform a prospective randomized trial comparing upper hemisternotomy with standard (median) sternotomy in terms of pulmonary function changes perioperatively. We also added a novel exercise tolerance test, one-minute sit-to-stand test, and a quality of life evaluation to the study. We included patients indicated for elective isolated aortic valve replacement with bioprosthesis who were older than 65 years, signed informed consent, and in which both surgical approaches were technically feasible. Exclusion criteria were re-do surgery and concomitant cardiac surgery. Patients were randomized to minimally invasive and standard group in 1:1 ratio. On the day of admission, on the 7th postoperative day and 3 months postoperatively, the patients underwent pulmonary function testing and one-minute...

Detection of early pathophysiological changes of breathing in children with chronic respiratory disease MD. Vaclav Koucky - Ph.D. thesis Abstract Introduction: Currently, there are different methods for infant pulmonary function testing (iPFT) and morphological assessment of microscopic changes in endobronchial biopsy samples (EBB). In research setting, they allow detection of early pathophysiological changes of breathing in small children with chronic respiratory disease, respectively in risk of its development. Their clinical significance, however, is not fully acknowledged. The aim of this thesis is to evaluate the safety, feasibility and clinical significance of iPFT and EBB in infants younger than 2 years of age. In addition, the relationship between functional and morphological changes of respiratory tract and the function of peripheral chemoreceptors was studied in selected patients' subgroups. Methods: Fifty-five infants with cystic fibrosis (CF), 35 physician-confirmed recurrent wheezers (AB), 9 infants with congenital diaphragmatic hernia, 7 with interstitial lung disease (chILD) and 3 with primary ciliary dyskinesia (PCD) were enrolled. All infants underwent iPFT and relevant clinical history data were recorded. Based on patients' age, CF group was divided into CFmalí (< 6 months) and CFvelcí (>...