OSCILLOMETRY IN EQUINE ASTHMA

The present project investigated the use of oscillometry as a mean for the diagnosis of equine asthma, evaluating two different Techniques: the impulse oscillometry system (IOS) and the Forced Oscillation Technique (FOT). The aim of the first study was to evaluate whether the IOS could be sensitive enough to discriminate amongst healthy and asthmatic horses in different clinical conditions. Seven severely asthmatic (SEA) horses in disease exacerbation, 7 asthmatic horses in clinical remission and 7 control horses from a cohort of experimental age-matched animals underwent IOS testing. Only data at 3, 5 and 7Hz with coherence >0.85 at 3Hz and >0.9 at 5 and 7Hz were considered in the study. Mean, inspiratory and expiratory resistance (R) and reactance (X) and the difference between inspiratory and expiratory X (\u394X) were calculated at each frequency. The three groups were compared using one-way ANOVA and Dunnett\u2019s multiple comparison test or Kruskal-Wallis test and Dunn\u2019s multiple comparison test. Significant differences were found between SEA horses in exacerbation and control horses for all R parameters at 3Hz. For X, significant differences were present between exacerbation horses and control horses at each frequency for mean, inspiratory and expiratory parameters. Between controls and remission horses differences were present for X7 and for inspiratory X3, X5 and X7. Regarding Delta X, values in exacerbation horses were significantly higher than remission or control horses. Results indicate that, as reported in humans during tidal expiratory flow limitation (EFL), X during the expiratory phase is more negative than during inspiration in exacerbated horses. Difference in inspiratory X appears to be promising to discriminate between healthy horse and SEA horses in clinical remission. The aim of the second study was to evaluate the application of a FOT device specially designed for horses and his ability in discriminate between healthy subjects, SEA horses in exacerbation and moderate asthmatic horses (MEA). 4 SEA horses, 4 MEA horses and 4 controls from a clinical population were selected, age-matched. Data of FOT measurement at 2, 3, 4, 5 and 6 Hz were considered in the study. Mean, inspiratory and expiratory resistance (R) and reactance (X) and the difference between inspiratory and expiratory X (\u394X) were calculated at each frequency. The three groups were compared using Kruskal-Wallis test and Dunn\u2019s multiple comparison test. Statistical comparison showed significant differences between SEA and control group for R at 3Hz and for R at 2 Hz in expiration phase. Regarding X, several differences were found between controls and SEA horse at frequencies ranging from 2 to 6 Hz in all the phases of the breath. Finally, comparison for \u394X showed that values in SEA horses were significantly higher than MEA or control horses, indicating that in SEA horses in exacerbation the reactance during expiratory phase is worse than during inspiration. No differences were found between controls and MEA horses. Results showed that the new FOT device was able to discriminate between healthy and SEA horses. EFL in SEA horses was identified also by this system. Further studies are required in order to increase the sensitivity in discriminate between healthy and MEA horses

Equine clinics

The present final report concluding the degree of the Integrated Master in Veterinary Medicine at the University of Évora is based on the curricular externship in an outpatient clinic with Dr. An Sleeckx in the Greater Lisbon / Ribatejo area. This report is divided into two parts. The first part presents the casuistic of the externship and describes clinical cases like abdominal pain, lameness, pre-purchase exam, intoxication with monensin, insect bite hypersensitivity and castration which were followed during the externship. As painful events like lameness and colic are very common in equine clinics, a literature research on pain assessment in horses was made and presented in the second part as a monography. The focus was on new composite pain scales including behavior and facial expressions which seem to be the most reliable to detect pain according to the newest publications; Resumo: Clínica e Cirurgia de Equinos O presente relatório de conclusão do curso de Mestrado Integrado em Medicina Veterinária da Universidade de Évora é baseado no estágio curricular realizado em clínica ambulatória com a Dra. An Sleeckx na zona da Grande Lisboa/ Ribatejo. O relatório é dividido em duas partes. A primeira parte apresenta a casuística do estágio e descreve casos clínicos como dor abdominal, claudicações, acto de compra, intoxicação com monensina, hipersensibilidade à picada de insectos e castração, que foram acompanhados durante o estágio. Uma vez que eventos dolorosos como as claudicações e as cólicas são muito comuns nas clínicas equinas, foi feita uma pesquisa bibliográfica sobre avaliação da dor em cavalos, que foi apresentada na segunda parte como uma monografia. O foco foi em novas escalas composta de dor, incluindo comportamento e expressões faciais que parecem ser as mais fiáveis para detectar a dor de acordo com as mais recentes publicações

Multi-Nuclear Magnetic Resonance Imaging of Obstructive Lung Disease

Obstructive lung diseases such as chronic-obstructive-lung-disease (COPD), bronchiectasis, and asthma are characterized by airflow obstruction. They affect over six million Canadians costing the economy $12 billion/year. Despite decades of research, therapies that modify obstructive-lung-disease progression and control are lacking because patient diagnosis, monitoring, and response to therapy are currently made using airflow measurements that may conceal the independent contributions of underlying pathologies. One goal of obstructive-lung-disease research is to develop ways to identify patients with specific underlying pathological phenotypes to improve patient care and outcomes. Thoracic computed-tomography (CT) and magnetic-resonance-imaging (MRI) provide ways to regionally identify the underlying pathologies associated with obstructive-lung-disease, and offer quantitative biomarkers of obstructive-lung-disease (e.g. lung-density, airway dimensions, ventilation abnormalities, and lung microstructure). As the first step to identify patients with specific underlying pathological phenotypes, it is important to understand the physiological and clinical consequences of these imaging derived measurements. Accordingly, our objective was to evaluate lung structure and function using multi-nuclear pulmonary MRI in aging and obstructive-lung-disease to provide a better understanding of MR-derived biomarkers. In older never-smokers, the majority of subjects had 3He MR ventilation abnormalities that were not responsive to bronchodilation. 3He ventilation abnormalities were related to airflow obstruction and airways resistance, but not occupational exposure or exercise limitation. We then developed and evaluated ultra-short-echo-time MRI in COPD subjects with and without bronchiectasis. This work demonstrated that ultra-short-echo-time MR-derived measurements were reproducible and significantly related to CT tissue-density measurements. In the COPD subjects with bronchiectasis, ultra-short-echo-time signal-intensity was related to airway measurements. In COPD subjects without bronchiectasis, ultra-short-echo-time signal-intensity was related to the severity of emphysema. Finally, based on the ultra-short-echo-time MR biomarkers developed in patients with COPD and bronchiectasis, patients that share some of the airway and inflammatory features common in asthmatics, we produced ultra-short-echo-time MR measurements in asthma. These measurements not only provided similar information as CT, but also information about regional ventilation deficits. These results demonstrated that ultra-short-echo-time MR biomarkers may reflect ventilation heterogeneity and/or gas-trapping in asthma. These important findings indicate that multi-nuclear pulmonary MRI has the potential to quantitatively evaluate the different pathologies of obstructive-lung-disease

Hyperpolarized 3He Magnetic Resonance Imaging Phenotypes of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the world. Identifying clinically relevant COPD phenotypes has the potential to reduce the global burden of COPD by helping to alleviate symptoms, slow disease progression and prevent exacerbation by stratifying patient cohorts and forming targeted treatment plans. In this regard, quantitative pulmonary imaging with hyperpolarized 3He magnetic resonance imaging (MRI) and thoracic computed tomography (CT) have emerged as ways to identify and measure biomarkers of lung structure and function. 3He MRI may be used as a tool to probe both functional and structural properties of the lung whereby static-ventilation maps allow the direct visualization of ventilated lung regions and 3He apparent diffusion coefficient maps show the lung microstructure at alveolar scales. At the same time, thoracic CT provides quantitative measurements of lung density and airway wall and lumen dimensions. Together, MRI and CT may be used to characterize the relative contributions of airways disease and emphysema on overall lung function, providing a way to phenotype underlying disease processes in a way that conventional measurements of airflow, taken at the mouth, cannot. Importantly, structure-function measurements obtained from 3He MRI and CT can be extracted from the whole-lung or from individual lung lobes, providing direct information on specific lung regions. In this thesis, my goal was to identify pulmonary imaging phenotypes to provide a better understanding of COPD pathophysiology in ex-smokers with and without airflow limitation. This thesis showed: 1) ex-smokers without airflow limitation had imaging evidence of subclinical lung and vascular disease, 2) pulmonary abnormalities in ex- smokers without airflow limitation were spatially related to airways disease and very mild emphysema, and, 3) in ex-smokers with COPD, there were distinct apical-basal lung phenotypes associated with disease severity. Collectively, these findings provide strong evidence that quantitative pulmonary imaging phenotypes may be used to characterize the underlying pathophysiology of very mild or early COPD and in patients with severe disease

Interventional Pulmonology and Pulmonary Hypertension

This book, published by IntechOpen, focuses on interesting aspects of pulmonary medicine. The first section of the book is dedicated to interventional pulmonology, and includes updates on bronchial thermoplasty, virtual bronchoscopy, and endobronchial ultrasound. The second section highlights special aspects of pulmonary circulation and pulmonary hypertension. Throughout the book, the authors offer us not only a "vigorous" review of the current literature but also a research path to further advancement

A clinical study on Swasakasam (Bronchial Asthma) with the evaluation of siddha drug Sombu Theeneer

The clinical study on Swasakasam was carried out on Post graduate department of Maruthuvam, Government Siddha Medical College, Arignar Anna Hospital, Chennai-106 during the period of 2015 -2017. A total of 40 patients were treated in the Outpatient department. The clinical and pathological assessment was carried out on the basis of Siddha and Modern aspects. All patients were treated with SOMBU THEENEER (15ml bid with equal amount of warm water) for duration of 30 days. The peak incidence of Swasakasam was found to be in 31-40 years of age group of both sexes. The prevalence of the disease was high among Lower class populations 57.5% followed by Middle class 22.5% and High class population 20%. Out of 40 patients, 9 patient (22.5%) was tailor, 14 patient (35%) were office people, 5patient (12.5%) was traffic policeman, 3 patients (7.5%) were business man, 6 patients (15%) were housewife, 3 patient (7.5%) were student. Regarding personal habits 11 patients were smokers, 4 patients were alcoholic, 3 patients were both smoking and alcoholic, 1 patient was a snuff user. Remaining 21 patients were tee tootlers. Among the dietary patterns, 82.5% consume mixed diet and 17.5% are purely vegetarian. Out of 40 patients, 37.5% comes under Vatha kaalam, 62.5% comes under Azhal kaalam. From selected 40 patients,16 patients(40%) comes under Kaarkaalam, 9 patients (22.5%) comes under Koothirkaalam,7 patients(17.5%) comes under Munpani, 5 patients (12.5%) comes under Pinpani, 2 patients(5%) comes under Elavenil, 1patient (2.5%) comes under Mudhuvenil. Out of 40 patients, 33 patients (82.5%) comes under Neidhal, 7 patients (17.5%) comes under Marudham. From the selected 40 patients, Pranan was affected in 40 patients (100%), Abanan was affected in 5 patients (12.5%), Viyanan was affected in 35 patients (87.5%), Samanan was affected in 14 patients (35%), Koorman was affected in3 patients (7.5%), Kirugaran was affected in 30 patients (75%), Devathan was affected in 40 patients (100%). Out of 40 patients, Analagam was affected in1 4 patients (35%), Ranjagam was affected in 9 patients (22.5%), Saathagam was affected in 40 patients (100%), Aalosagam was affected in 3 patients (7.5%). Out of 40 patients, Avalambagam was affected in 40 patients (100%), Klethagam was affected in 14 patients (35%), Santhigam was affected in 5 patients (12.5%). Out of 40 cases, Saaram was affected in 40 patients (100%), Seneer was affected in 9 patients (22.5%), Enbu was affected in 5 patients(12.5%). Regarding Envagaithervu, Naa was affected in 9 patients (22.5%), Mozhi was affected in 1 patients(2.5%), Vizhi was affected in 9 patients (22.5%), Malam was affected in 5 patients (12.5%), Naadi was affected in 40 patients (100%). Out of 40 patients, 31 patients had Kabhavatha naadi and 9 patients had Vathakabh anaadi. Out of 40 patients, 9 patients (22.5%) had Vatha neer, 31 patients (77.5%) had Kabhaneer. Regarding peak expiratory flow rate (75%) got good results and 10 patients (25%) got moderate results. The ingredient Sombu has the property kaarpu suvai of neutralizing the deranged iyya kutram. The toxicity studies revealed no toxicity in Sombu Theeneer. The pharmacological activity of Sombu Theeneer shows Bronchodilator activity. The Biostatsistical report of the clinical trial significant p value P<0.01 and concluded that the treatment was effective and significant. Thus out of 40 patients before treatment, after treatment 75% of cases showed good result, 25% of the cases showed Moderate result. CONCLUSION: Swasakasam is primarily due to the derangement of Iyyam and Vatha kutram. The ingredients of the trial medicine have the properties of neutralizing the deranged kutrams. From the preclinical toxicity studies, the trial medicine revealed no toxicity and proved to be safe. From the preclinical pharmacological studies, it is evident that SOMBU THEENEER have Bronchodilator activity. No contraindication was reported during the course of the treatment. The SOMBU THEENEER gave maximum relief from the symptoms of Swasa kasam. The reduces SOMBU THEENEER the frequency of wheeze attacks. The SOMBU THEENEER is economical and easily palatable. Therefore I conclude that, can give a SOMBU THEENEER will be the best remedie for asthma sufferers both curative and preventive

Work of breathing in exercise and disease

This thesis is focussed on developing new methods and outcomes to assess respiratory function that require little or no volitional effort on behalf of the participants being tested. Specifically to attempt to detach the behaviour of the patient from the accuracy of the test of respiratory function, resulting in techniques that are simpler and easier to administer and undertake for both assessor and participant. It aims to develop methods that reduce the involvement of the participant during assessment of respiratory function. The human body’s way of controlling respiration has evolved into a sophisticated system that optimises breathing pattern to maintain the most efficient homeostatic action of the respiratory system. Eliciting and assessing this automatic response is the key to removing the action of participation from respiratory functiontesting. The focus must therefore be on developing non-invasive, sub-maximal techniques that allow participants to enter into a steady state of respiration and how this can be assessed. Two techniques were investigated; Respiratory Endurance (as the inspiratory work of breathing) and Tidal Breathing Flow Profile, and these were successfully applied in 99 adult participants (68 healthy controls and 31 COPD patients) and 75 children (48 clinical group and 27 healthy controls) who completed 467 respiratory endurance trials whilst seated and exercising, and 249 relaxed tidal breathing trials. The difficulties with lung function assessment are well established and have been described in this thesis. Much recent emphasis has been put on developing existing devices and protocols rather than developing new techniques and approaching these difficulties from alternative viewpoints. This thesis has described the development of innovative techniques to assess the function of the respiratory systems that aim to overcome the issues associated with maximal testing. It was shown that these techniques are easy to undertake for a range of participants, simple to analyse and are able to reliably differentiate between health and disease, suggesting that they could become a useful adjunct to existing methods of respiratory assessment

Tidal breathing parameters in extremely premature infants. Feasibility and clinical utility of electromagnetic inductance plethysmography

Background: Extremely preterm (EP) birth is associated with adverse lung growth, due to disturbance of programmed and fine-tuned sequences of normal intrauterine development, as well as the trauma inflicted by life-saving treatments. Moreover, EP-born neonates are probably born with variable susceptibilities or predispositions for lung injury. The pulmonary consequences of EP birth are heterogeneous and insufficiently mapped and understood. Particularly, our understanding of the detailed lung mechanics in EP-born infants is limited, largely due to the fact that lung function measurements in neonates and infants are complex and not readily available. Electromagnetic inductance plethysmography (EIP) is a novel non-invasive system that provides tidal breathing parameters in the form of tidal flow volume loops. With these studies, we aimed to: (1) Study feasibility and validity of the EIP method in preterm and term-born infants, (2) use the EIP method to compare lung function in EP and term-born infants at term-equivalent age, and test if lung function measurements obtained at this stage in EP-born infants were associated with respiratory health during their first year of life, and (3) study if tidal breathing parameters, obtained from a mechanical ventilator during the few first hours of life in EP-born neonates, could predict bronchopulmonary dysplasia (BPD). Methods: In study #1, we tested repeatability of the EIP method in a total of 30 preterm born infants who were at various stages of their development. A nurse experienced with the system measured all patients before and after meals, and these measurements were repeated by nurses new to the system. In study #2, the EIP-method was validated against a ‘gold standard method’ (mask-based ultrasonic flowmeter) in 30 infants at postmenstrual ages between 36 to 43 weeks and weights from 2.3 to 4.8 kg, applying both methods simultaneously. In study #3, within a population-based design, 52 EP-born infants recruited at Haukeland and Stavanger University Hospitals had their lung function measured at term-equivalent age using the EIP method, and the results were compared with 45 term-born controls. The EP-born infants were followed during their first year of life, including clinical examinations and questionnaires addressing respiratory symptoms and treatments. In study #4, using custom made software, we calculated tidal breathing parameters from the flow signals of 33 ventilator treated EP born neonates during their first hours of life, and the data were compared between those who later developed moderate/severe versus no/mild BPD. Results: We found in studies #1 and #2 that the EIP method was well tolerated by the infants and also feasible in a busy NICU setting. The repeatability was better for term-born than preterm-born infants, but comparable to what has been reported for “maskbased” infant spirometry. The experience of the personnel and the relationship to meals influenced the reproducibility. Tidal breathing parameters obtained by the EIP method corresponded well with those obtained by the “mask-based” system when applied simultaneously in infants at term-equivalent age. In study #3, we found that lung function measured by EIP was strikingly abnormal in EP compared to healthy term-born infants at term-equivalent age, characterized by obstructive pulmonary abnormalities, and by increased tidal volumes and minute ventilation. Abnormalities were most pronounced for the group of infants with BPD, but significantly present also in infants without BPD. The tidal breathing parameter TEF50/PTEF predicted respiratory morbidity in the first year of life in infants born EP. In study #4, we found that flow data easily obtained from a ventilator during the first 48 hours of life could be used to compute breathing parameters that discriminated between neonates who went on to develop the severe forms of BPD and those who did not. Conclusions and implications: EIP emerges as a feasible method of infant lung function testing. Its major strengths are the relative simplicity by which it can be put to use, and the avoidance of a facemask. This thesis has demonstrated that EIP can provide tidal breathing measurements that can aid the characterization of lung disease after EP birth, and that tidal breathing parameters obtained shortly after birth may identify neonates with predisposition for a difficult clinical respiratory course. If subsequent evaluations were to confirm the findings of this thesis, EIP and tidal breathing parameters have the potential of early recognition of neonates at risk of the severe forms of lung disease of prematurity and of later respiratory morbidity, which may pave the way for lifelong targeted surveillance and guidance of clinical management and intervention studies

Inflammatory Diseases

"Inflammatory Diseases - A Modern Perspective" represents an extended and thoroughly revised collection of papers on inflammation. This book explores a wide range of topics relevant to inflammation and inflammatory diseases while its main objective is to help in understanding the molecular mechanism and a concrete review of inflammation. One of the interesting things about this book is its diversity in topics which include pharmacology, medicine, rational drug design, microbiology and biochemistry. Each topic focuses on inflammation and its related disease thus giving a unique platform which integrates all the useful information regarding inflammation

The role of inhaled endotoxin in the aetiopathogenesis of equine heaves

Soluble lipopolysaccharide (LPS) inhalation challenge induced a dose-dependent bronchoalveolar lavage fluid (BALF) neutrophilia in both heaves-susceptible and control horses, and significant lung dysfunction in the heaves group. The response thresholds were lower for the heaves group, yet were markedly greater than airborne endotoxin exposure during the 5h dusty hay/straw challenge. In addition, there was no significant difference in BALF neutrophil numbers between the 2 groups following challenge with the middle and high LPS dose. There was a significant difference in the airway inflammatory response of the heaves group to 2 separate hay/straw exposures. This response was not related to the level of airborne endotoxin exposure. These findings indicated that inhaled endotoxin is not solely responsible for the induction of naturally occurring heaves.Inhalation challenge of the heaves group with 3 incremental doses of soluble A. fumigatus extract resulted in an increase in a BALF neutrophilia and lung dysfunction, which plateaued following inhalation of the middle dose. Inhalation challenge with LPS-depleted A. fumigatus extract resulted in a significant reduction in airway neutrophil numbers, of a magnitude that was greater than predicted by extrapolation from soluble LPS dose response inhalation experiments. These findings indicated that inhaled endotoxin may act synergistically with mould antigens, and contribute to the pulmonary inflammation observed in heavesInhalation challenge with hay dust suspensions (FIDS), prepared from fine hay dust particles, induced an airway neutrophilia, airway dysfunction and mucus hyper¬ secretion in the heaves group only. Inhalation challenge of the heaves group with the soluble fraction of HDS (SUP) failed to induce the magnitude of response measured following HDS challenge, despite containing almost all of the endotoxin activity of the HDS. These findings supported the involvement of HDS components, other than endotoxin, in the aetiopathogenesis of heaves. Inhalation challenge of the heaves group with the particulate fraction of FIDS (WP) induced only a mild BALF neutrophilia, however a combined challenge with SUP and WP induced a neutrophilic response approaching the magnitude of that following HDS challenge. These findings indicated a synergistic action between the soluble and particulate fractions of HDS.Inhalation challenge of the heaves group with LPS-depleted HDS resulted in a significant reduction in BALF neutrophil numbers, of a magnitude that was greater than predicted by extrapolation from soluble LPS dose response inhalation experiments. Replacement of the depleted LPS resulted in the re-establishment of the original level of BALF neutrophilia. Inhalation challenge of the heaves group with WP reconstituted in LPS solution (containing an equivalent LPS activity to SUP) resulted in a BALF neutrophilia that was not significantly different from that following challenge with combination of WP and SUP. These findings indicated that the endotoxin content of HDS acts synergistically with other HDS components, most notably the particulate fraction